ГЕТЕРОЦИКЛИЧЕСКОЕ СОЕДИНЕНИЕ, СПОСОБ ЕГО ПОЛУЧЕНИЯ И ЕГО ПРИМЕНЕНИЕ В ФАРМАЦЕВТИКЕ

Abstract

The present disclosure relates to a heterocyclic compound, a method for preparing same, and pharmaceutical use thereof. Specifically, the present disclosure relates to a heterocyclic compound represented by general formula (I), a method for preparing same, a pharmaceutical composition comprising same, and use thereof as a therapeutic agent, particularly, use thereof as an Nav inhibitor and use thereof in preparing a medicament for treating and / or alleviating pain and a pain-related disease. Groups in general formula (I) are as defined in the description.

Description

Heterocyclic compounds, preparation methods thereof and their applications in medicine Technical Field

[0001] The present disclosure relates to the field of medicine and relates to a heterocyclic compound, a method for preparing the same, and its use in medicine. In particular, the present disclosure relates to a heterocyclic compound represented by general formula (I), a method for preparing the same, and a pharmaceutical composition containing the same, as well as its use as a Nav inhibitor and its use in the preparation of a medicament for treating and / or alleviating pain and pain-related diseases. Background Art

[0002] Pain is a complex physiological and psychological process and one of the most common clinical symptoms. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience, accompanied by actual or potential tissue damage, which is a subjective feeling." Pain can serve as a warning signal, alerting the body to potential dangers and playing an indispensable protective role in the body's normal life activities. At the same time, pain is also a common clinical symptom. After the external stimulus that causes pain disappears, intense or persistent pain can cause physiological dysfunction and seriously affect the quality of life. Statistics show that approximately one in five people worldwide suffers from moderate to severe chronic pain.

[0003] Pain originates from nociceptors in the peripheral nervous system. These are free nerve endings that are widely distributed throughout the skin, muscles, joints, and visceral tissues of the body. They can convert perceived thermal, mechanical, or chemical stimuli into nerve impulses (action potentials) and transmit them via afferent nerve fibers to their cell bodies located in the dorsal root ganglia (DRG), ultimately transmitting them to higher nerve centers, causing pain. The generation and conduction of action potentials in neurons, in turn, rely on voltage-gated sodium channels (Nav) on the cell membrane. When the cell membrane depolarizes, sodium ion channels activate and open, causing an influx of sodium ions, further depolarizing the cell membrane and leading to the generation of action potentials. Therefore, inhibiting abnormal sodium ion channel activity can help treat and relieve pain.

[0004] Nav is a class of transmembrane ion channel proteins. These proteins are composed of a 260 kDa α subunit and a 30-40 kDa β subunit. Based on the differences in the α subunit, they can be divided into nine subtypes, Nav1.1 to Nav1.9. Different subtypes exhibit distinct tissue distributions and electrophysiological and pharmacological characteristics. Based on whether they can be effectively inhibited by nanomolar tetrodotoxin (TTX), sodium ion channels are classified as TTX-sensitive (TTX-S) and TTX-insensitive (TTX-R). Nav1.1, Nav1.2, Nav1.3, and Nav1.7 are TTX-S subtypes, with their encoding genes located on human chromosomes 2q23-24. They are abundantly expressed in neurons. Nav1.5, Nav1.8, and Nav1.9 are TTX-R subtypes, with their encoding genes located on human chromosomes 3p21-24. Among them, Nav1.5 is primarily found in cardiomyocytes, while Nav1.8 and Nav1.9 are found in the peripheral nervous system. Nav1.4 and Nav1.6 are both TTX-S types, abundant in skeletal muscle and the central nervous system, respectively. The local anesthetic lidocaine relieves pain by inhibiting Nav. Non-selective Nav inhibitors, such as lamotrigine, lacosamide, and mexiletine, have been successfully used to treat chronic pain.

[0005] Nav1.8 is a TTX-R type protein encoded by the gene SCN10A. It is primarily found in trigeminal ganglion and DRG neurons and exhibits the electrophysiological characteristics of slow inactivation and rapid recovery. In neurons expressing Nav1.8, the rise of the action potential is primarily composed of Nav1.8 currents. In some models of neuropathic pain, nerve injury increases Nav1.8 expression in axons and neuronal cell bodies. The use of Nav1.8 antisense oligonucleotides can significantly alleviate pain while simultaneously reducing Nav1.8 expression. Intra-paw injection of carrageenan in rats increases Nav1.8 expression in DRG neurons. Nav1.8 knockout mice fail to exhibit normal visceral inflammatory pain. Gain-of-function mutations in the human Nav1.8 gene cause peripheral neuropathic pain. Based on a series of animal studies and human genetic evidence, selective inhibition of Nav1.8 has the potential to become a novel analgesic therapy for a variety of pain types, including inflammatory pain, neuralgia, postoperative pain, and cancer pain.

[0006] Nav inhibitors used in clinical practice lack subtype selectivity and can only inhibit sodium channels expressed in the heart and central nervous system. Consequently, their therapeutic window is narrow and their scope of application is limited. Nav1.8 is primarily distributed in the peripheral nervous system, so selective inhibition of Nav1.8 can effectively reduce side effects. Therefore, it is necessary to develop Nav1.8 inhibitors with higher activity, better selectivity, improved pharmacokinetic properties, and fewer side effects.

[0007] Published patent applications for Nav1.8 inhibitor compounds include WO2021113627A1, WO2022256622A1, WO2022256676A1, WO2022256679A1, WO2022256842A1, and WO2022256702A1.

[0008] Summary of the Invention

[0009] The purpose of the present disclosure is to provide a compound represented by general formula (I) or a pharmaceutically acceptable salt thereof:

[0010] in:

[0011] Ring A is phenyl or 6-membered heteroaryl;

[0012] Each R A are the same or different and are each independently selected from a deuterium atom, a halogen, a hydroxyl group, a cyano group, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a hydroxyalkoxy group, an alkoxyalkyl group, an alkenyl group, an alkynyl group, -NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 、-P(O)R7 R 8 、-C(O)NR 5 -NR 3 R 4 、-C(=NR 5 )NR 5 -OR 6 、-C(O)NR 5 -alkylene-Cy, -C(=NR 5 )NR 3 R 4 、-C(O)-C(O)-NR 3 R 4 、-S(=NR 5 )NR 3 R 4 、-S(=NR 5 )R 6 、-S(=NR 5 )(O)NR 3 R 4 、-Si(O)NR 3 R 4 、-Si(R 6 )3. -OR 6 , cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, -C(O)-cycloalkyl, -C(O)-heterocyclyl, -alkylene-O-alkylene-cycloalkyl, -alkylene-O-cycloalkyl, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl, wherein the alkyl, alkoxy, alkoxyalkyl, alkenyl, alkynyl, alkylene, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl and heterocyclylalkyl are each independently optionally replaced by one or more R 01 replaced by;

[0013] Cy is a cycloalkyl group or a heterocyclic group, wherein the cycloalkyl group and the heterocyclic group are each independently optionally substituted by one or more substituents selected from the group consisting of a deuterium atom, a halogen, a hydroxyl group, a cyano group, an oxo group, an amino group, an -NH alkyl group, an -N(alkyl) 2 , an acetyl group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, an aryl group, and a heteroaryl group;

[0014] Each R 3 、R 4 and R 5 are the same or different and are each independently selected from hydrogen, alkyl, deuterated alkyl, alkoxy, deuterated alkoxy, alkenyl, alkynyl, NR 20 R 21 、C(O)NR 20 R 21 NR 22 C(O)R23 、C(O)R 23 、C(O)OR 23 、OC(O)R 23 、S(O) v R 23 、S(O) v OR 23 、OS(O) v R 23 、S(O) v NR 20 R 21 , OR 23 , cycloalkyl, heterocyclic, aryl and heteroaryl; wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl are each independently optionally substituted by one or more R 01 replaced by;

[0015] or R 3 、R 4 Together with the nitrogen atom to which it is attached, a heterocyclic group is formed; the heterocyclic group is optionally substituted by one or more R 01 replaced by;

[0016] Each R 6 、R 7 and R 8 are the same or different and are each independently selected from hydrogen, alkyl, alkoxy, haloalkyl, deuterated alkyl, haloalkoxy, deuterated alkoxy, hydroxyalkyl, alkenyl, alkynyl, NR 20 R 21 、C(O)NR 20 R 21 NR 22 C(O)R 23 、C(O)R 23 、C(O)OR 23 、OC(O)R 23 、S(O) v R 23 、S(O) v OR 23 、OS(O) v R 23 、S(O) v NR 20 R 21 , OR 23 , cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl and heteroaryl; the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl and heteroaryl are each independently optionally selected from one or more R 01 replaced by;

[0017] Each R01 are the same or different and are each independently selected from a deuterium atom, a halogen, a hydroxyl group, a cyano group, an oxo group, an amino group, -NH alkyl, -N(alkyl) 2, an acetyl group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, an aryl group, a heteroaryl group, a =CR 7a R 8a 、-NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 、-P(O)R 7 R 8 、-C(O)NR 5 -NR 3 R 4 、-C(=NR 5 )NR 5 -OR 6 、-C(O)NR 5 -alkylene-Cy, -C(=NR 5 )NR 3 R 4 、-C(O)-C(O)-NR 3 R 4 、-S(=NR 5 )NR 3 R 4 、-S(=NR 5 )R 6 、-S(=NR 5 )(O)NR 3 R 4 、-Si(O)NR 3 R 4 、-OR6 、-Si(R 6a )3, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl; the alkyl, alkenyl, alkynyl, alkoxy, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl groups are each independently optionally substituted by one or more substituents selected from deuterium atoms, halogen, hydroxyl, cyano, oxo, amino, -NH alkyl, -N(alkyl)2, acetyl, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl groups;

[0018] Each R 6a 、R 7a and R 8a are the same or different and are each independently selected from a hydrogen atom, a deuterium atom, a halogen, a hydroxyl group, a cyano group, an amino group, an -NH alkyl group, an -N(alkyl) 2 , an acetyl group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group;

[0019] R' is selected from the group consisting of a hydrogen atom, an alkyl group, a haloalkyl group, a deuterated alkyl group, an alkoxy group, a deuterated alkoxy group, a hydroxyalkyl group, a cycloalkyl group, and a heterocyclic group;

[0020] X is O or S;

[0021] R a and R b are the same or different and are each independently selected from a hydrogen atom, a deuterium atom, a halogen, a hydroxyl group, a cyano group, an amino group, an alkyl group, a deuterated alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a deuterated alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, a cycloalkyloxy group and a heterocyclic groupoxy group; the alkyl group, alkoxy group, alkenyl group, alkynyl group, cycloalkyl group, heterocyclic group, cycloalkyloxy group and heterocyclic groupoxy group are optionally replaced by one or more R 02 replaced by;

[0022] The condition is that R a and R b Not simultaneously hydrogen;

[0023] R c and R d are the same or different and are each independently selected from a hydrogen atom, a deuterium atom, a halogen, a hydroxyl group, a cyano group, an amino group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a deuterated alkyl group, a haloalkoxy group, a deuterated alkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, a cycloalkyloxy group and a heterocyclic groupoxy group; the alkyl group, alkoxy group, alkenyl group, alkynyl group, cycloalkyl group, heterocyclic group, cycloalkyloxy group and heterocyclic groupoxy group are optionally replaced by one or more R 02 replaced by;

[0024] or, R a 、R bTogether with the carbon atom to which it is attached, it forms a cycloalkyl or heterocyclic group; or, R c 、R d Together with the carbon atom to which it is connected, it forms a cycloalkyl or heterocyclic group; wherein the cycloalkyl or heterocyclic group is independently optionally substituted by one or more R 02 replaced by;

[0025] R e is selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, a hydroxyl group, a cyano group, an amino group, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a deuterated alkyl group, a deuterated alkoxy group, and a hydroxyalkyl group;

[0026] Each R 02 are the same or different and are each independently selected from a deuterium atom, a halogen, a hydroxyl group, a cyano group, an oxo group, an amino group, an amide group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group;

[0027] Each R 20 、R 21 and R 22 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, a deuterated alkyl group, an alkoxy group, a deuterated alkoxy group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclic group, an aryl group, and a heteroaryl group; the alkyl group, alkoxy group, alkenyl group, alkynyl group, cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are each independently optionally substituted with one or more groups selected from a deuterium atom, a halogen group, a hydroxyl group, a cyano group, an amino group, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, and a hydroxyalkyl group;

[0028] Each R 23 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, a deuterated alkyl group, an alkoxy group, a deuterated alkoxy group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclic group, an aryl group, and a heteroaryl group; the alkyl group, alkoxy group, alkenyl group, alkynyl group, cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are each independently optionally substituted with one or more groups selected from a deuterium atom, a halogen group, a hydroxyl group, a cyano group, an amino group, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, and a hydroxyalkyl group;

[0029] X 1 CR X1 or N;

[0030] X 2 CR X2 or N;

[0031] X 3 CR X3 or N;

[0032] X 4 CR X4 or N;

[0033] X5 CR X5 or N;

[0034] X 1 、X 2 、X 3 、X 4 and X 5 Not all N at the same time;

[0035] R X1 、R X2 、R X3 、R X4 and R X5 are the same or different and are each independently selected from a hydrogen atom, a deuterium atom, a halogen, a hydroxyl group, a cyano group, an amino group, an amide group, a nitro group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a deuterated alkyl group, a haloalkoxy group, a deuterated alkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, -O-(CH2) n -cycloalkyl, -O-(CH2) s -heterocyclic, aryl and heteroaryl; wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl are each independently optionally substituted by one or more R 03 replaced by;

[0036] Each R 03 are the same or different and are each independently selected from a deuterium atom, a halogen, a hydroxyl group, a cyano group, an oxo group, an amino group, an amide group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group;

[0037] Each v is the same or different and is independently selected from 0, 1 and 2;

[0038] n is selected from 0, 1, 2, 3, 4 and 5;

[0039] s is selected from 0, 1, 2, 3, 4, and 5; and,

[0040] r is selected from 0, 1, 2, 3, 4 and 5;

[0041] The condition is, Not for

[0042] The purpose of the present disclosure is to provide a compound represented by general formula (I) or a pharmaceutically acceptable salt thereof:

[0043] in:

[0044] Ring A is phenyl or a 6-membered heteroaryl group;

[0045] Each R Aare the same or different and are each independently selected from a deuterium atom, a halogen, a hydroxyl group, a cyano group, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a hydroxyalkoxy group, an alkoxyalkyl group, an alkenyl group, an alkynyl group, -NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 、-P(O)R 7 R 8 、-C(O)NR 5 -NR 3 R 4 、-C(=NR 5 )NR 5 -OR 6 、-C(O)NR 5 -alkylene-Cy, -C(=NR 5 )NR 3 R 4 、-C(O)-C(O)-NR 3 R 4 、-S(=NR 5 )NR 3 R 4 、-S(=NR 5 )R 6 、-S(=NR 5 )(O)NR 3 R 4 、-Si(O)NR 3 R 4 、-Si(R 6 )3. -OR 6, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, -C(O)-cycloalkyl, -C(O)-heterocyclyl, -alkylene-O-alkylene-cycloalkyl, -alkylene-O-cycloalkyl, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl, wherein the alkyl, alkoxy, alkoxyalkyl, alkenyl, alkynyl, alkylene, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl and heterocyclylalkyl are each independently optionally replaced by one or more R 01 replaced by;

[0046] Cy is a cycloalkyl group or a heterocyclic group, wherein the cycloalkyl group and the heterocyclic group are each independently optionally substituted by one or more substituents selected from the group consisting of a deuterium atom, a halogen, a hydroxyl group, a cyano group, an oxo group, an amino group, an -NH alkyl group, an -N(alkyl) 2 , an acetyl group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, an aryl group, and a heteroaryl group;

[0047] Each R 3 、R 4 and R 5 are the same or different and are independently selected from hydrogen atom, alkyl, alkenyl, alkynyl, NR 20 R 21 、C(O)NR 20 R 21 NR 22 C(O)R 23 、C(O)R 23 、C(O)OR 23 、OC(O)R 23 、S(O) v R 23 、S(O) v OR 23 、OS(O) v R 23 、S(O) v NR 20 R 21 , OR 23 , cycloalkyl, heterocyclic, aryl and heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl are each independently optionally replaced by one or more R 01 replaced by;

[0048] or R 3 、R 4 Together with the nitrogen atom to which it is attached, a heterocyclic group is formed; the heterocyclic group is optionally substituted by one or more R 01 replaced by;

[0049] Each R 6 、R 7 and R 8are the same or different and are each independently selected from hydrogen, alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, alkenyl, alkynyl, NR 20 R 21 、C(O)NR 20 R 21 NR 22 C(O)R 23 、C(O)R 23 、C(O)OR 23 、OC(O)R 23 、S(O) v R 23 、S(O) v OR 23 、OS(O) v R 23 、S(O) v NR 20 R 21 , OR 23 , cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl and heteroaryl; the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl and heteroaryl are each independently optionally selected from one or more R 01 replaced by;

[0050] Each R 01 are the same or different and are each independently selected from a deuterium atom, a halogen, a hydroxyl group, a cyano group, an oxo group, an amino group, -NH alkyl, -N(alkyl) 2, an acetyl group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, an aryl group, a heteroaryl group, a =CR 7a R 8a 、-NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-NR 5 C(O)R 6 、-NR 5 C(O)NR3 R 4 、-C(O)NR 5 -OR 6 、-P(O)R 7 R 8 、-C(O)NR 5 -NR 3 R 4 、-C(=NR 5 )NR 5 -OR 6 、-C(O)NR 5 -alkylene-Cy, -C(=NR 5 )NR 3 R 4 、-C(O)-C(O)-NR 3 R 4 、-S(=NR 5 )NR 3 R 4 、-S(=NR 5 )R 6 、-S(=NR 5 )(O)NR 3 R 4 、-Si(O)NR 3 R 4 、-OR 6 、-Si(R 6a )3, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl; the alkyl, alkenyl, alkynyl, alkoxy, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl groups are each independently optionally substituted with one or more substituents selected from deuterium atoms, halogen, hydroxyl, cyano, oxo, amino, -NH alkyl, -N(alkyl)2, acetyl, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl groups;

[0051] Each R 6a 、R 7a and R 8a are the same or different and are each independently selected from a hydrogen atom, a deuterium atom, a halogen, a hydroxyl group, a cyano group, an amino group, an -NH alkyl group, an -N(alkyl) 2 , an acetyl group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group;

[0052] R' is selected from the group consisting of a hydrogen atom, an alkyl group, a haloalkyl group, a hydroxyalkyl group, a cycloalkyl group, and a heterocyclic group;

[0053] X is O or S;

[0054] R a and R bare the same or different and are each independently selected from a hydrogen atom, a deuterium atom, a halogen, a hydroxyl group, a cyano group, an amino group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, a cycloalkyloxy group and a heterocyclic groupoxy group; the cycloalkyl group, the heterocyclic group, the cycloalkyloxy group and the heterocyclic groupoxy group are optionally replaced by one or more R 02 replaced by;

[0055] The condition is that R a and R b Not simultaneously hydrogen;

[0056] R c and R d are the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, amino, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy; the cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy groups are optionally replaced by one or more R 02 replaced by;

[0057] or, R a 、R b Together with the carbon atom to which it is attached, it forms a cycloalkyl or heterocyclic group; or, R c 、R d Together with the carbon atom to which it is connected, it forms a cycloalkyl or heterocyclic group; wherein the cycloalkyl or heterocyclic group is independently optionally substituted by one or more R 02 replaced by;

[0058] R e is selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, a hydroxyl group, a cyano group, an amino group, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, and a hydroxyalkyl group;

[0059] Each R 02 are the same or different and are each independently selected from a deuterium atom, a halogen, a hydroxyl group, a cyano group, an oxo group, an amino group, an amide group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group;

[0060] Each R 20 、R 21 and R 22 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclic group, an aryl group and a heteroaryl group; the alkyl group, alkoxy group, alkenyl group, alkynyl group, cycloalkyl group, heterocyclic group, aryl group and heteroaryl group are each independently optionally substituted with one or more groups selected from halogen, hydroxyl, cyano, amino, alkyl group, alkoxy group, haloalkyl group, haloalkoxy group and hydroxyalkyl group;

[0061] Each R 23are the same or different and are each independently selected from a hydrogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclic group, an aryl group and a heteroaryl group; the alkyl group, alkoxy group, alkenyl group, alkynyl group, cycloalkyl group, heterocyclic group, aryl group and heteroaryl group are each independently optionally substituted with one or more groups selected from halogen, hydroxyl, cyano, amino, alkyl group, alkoxy group, haloalkyl group, haloalkoxy group and hydroxyalkyl group;

[0062] X 1 CR X1 or N;

[0063] X 2 CR X2 or N;

[0064] X 3 CR X3 or N;

[0065] X 4 CR X4 or N;

[0066] X 5 CR X5 or N;

[0067] X 1 、X 2 、X 3 、X 4 and X 5 Not all N at the same time;

[0068] R X1 、R X2 、R X3 、R X4 and R X5 are the same or different and are each independently selected from a hydrogen atom, a deuterium atom, a halogen, a hydroxyl group, a cyano group, an amino group, an amide group, a nitro group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, -O-(CH2) n -cycloalkyl, -O-(CH2) s -heterocyclic, aryl and heteroaryl; wherein the cycloalkyl, heterocyclic, aryl and heteroaryl are each independently optionally substituted by one or more R 03 replaced by;

[0069] Each R 03 are the same or different and are each independently selected from a deuterium atom, a halogen, a hydroxyl group, a cyano group, an oxo group, an amino group, an amide group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group;

[0070] Each v is the same or different and is independently selected from 0, 1 and 2;

[0071] n is selected from 0, 1, 2, 3, 4 and 5;

[0072] s is selected from 0, 1, 2, 3, 4, and 5; and,

[0073] r is selected from 0, 1, 2, 3, 4 and 5;

[0074] The condition is, Not for

[0075] The purpose of the present disclosure is to provide a compound represented by general formula (I) or a pharmaceutically acceptable salt thereof:

[0076] in:

[0077] Ring A is phenyl or 6-membered heteroaryl;

[0078] Each R A are the same or different and are each independently selected from a deuterium atom, a halogen, a hydroxyl group, a cyano group, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a hydroxyalkoxy group, an alkenyl group, an alkynyl group, -NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 、-P(O)R 7 R 8 、-C(O)NR 5 -NR 3 R 4 、-C(=NR 5 )NR 5 -OR 6 、-C(O)NR5 -alkylene-Cy, -C(=NR 5 )NR 3 R 4 、-C(O)-C(O)-NR 3 R 4 、-S(=NR 5 )NR 3 R 4 , cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl, wherein the alkenyl, alkynyl, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted by one or more R 01 replaced by;

[0079] Cy is a cycloalkyl group or a 3- to 4-membered heterocyclic group, each of which is independently optionally substituted by one or more substituents selected from the group consisting of a deuterium atom, a halogen, a hydroxyl group, a cyano group, an oxo group, an amino group, an -NH alkyl group, an -N(alkyl) 2 , an acetyl group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, an aryl group, and a heteroaryl group;

[0080] Each R 3 、R 4 and R 5 are the same or different and are independently selected from hydrogen atom, alkyl, alkenyl, alkynyl, NR 20 R 21 、C(O)NR 20 R 21 NR 22 C(O)R 23 、C(O)R 23 、C(O)OR 23 、OC(O)R 23 、S(O) v R 23 、S(O) v OR 23 、OS(O) v R 23 、S(O) v NR 20 R 21 NR 22 S(O) v R 23 , OR 23 , cycloalkyl, heterocyclic, aryl and heteroaryl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl are each independently optionally replaced by one or more R 01 replaced by;

[0081] or R 3 、R4 Together with the nitrogen atom to which it is attached, a heterocyclic group is formed; the heterocyclic group is optionally substituted by one or more R 01 replaced by;

[0082] Each R 6 、R 7 and R 8 are the same or different and are each independently selected from hydrogen, alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, alkenyl, alkynyl, NR 20 R 21 、C(O)NR 20 R 21 NR 22 C(O)R 23 、C(O)R 23 、C(O)OR 23 、OC(O)R 23 、S(O) v R 23 、S(O) v OR 23 、OS(O) v R 23 、S(O) v NR 20 R 21 NR 22 S(O) v R 23 , OR 23 , cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl and heteroaryl; the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl and heteroaryl are each independently optionally substituted with one or more substituents selected from deuterium atoms, halogen, hydroxyl, cyano, oxo, amino, -NH alkyl, -N (alkyl) 2, acetyl, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;

[0083] Each R 01 are the same or different and are each independently selected from a deuterium atom, a halogen, a hydroxyl group, a cyano group, an oxo group, an amino group, an -NH alkyl group, an -N(alkyl) 2 , an acetyl group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group;

[0084] R' is selected from the group consisting of a hydrogen atom, an alkyl group, a haloalkyl group, a hydroxyalkyl group, a cycloalkyl group, and a heterocyclic group;

[0085] X is O or S;

[0086] R a and R bare the same or different and are each independently selected from hydrogen, deuterium, halogen, hydroxy, cyano, amino, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy; the cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy groups are optionally replaced by one or more R 02 replaced by;

[0087] The condition is that R a and R b Not simultaneously hydrogen;

[0088] R c and R d are the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, amino, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy; the cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy groups are optionally replaced by one or more R 02 replaced by;

[0089] or, R a 、R b Together with the carbon atom to which it is attached, it forms a cycloalkyl or heterocyclic group; or, R c 、R d Together with the carbon atom to which it is connected, it forms a cycloalkyl or heterocyclic group; wherein the cycloalkyl or heterocyclic group is independently optionally substituted by one or more R 02 replaced by;

[0090] R e is selected from the group consisting of a hydrogen atom, a deuterium atom, a halogen, a hydroxyl group, a cyano group, an amino group, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, and a hydroxyalkyl group;

[0091] Each R 02 are the same or different and are each independently selected from a deuterium atom, a halogen, a hydroxyl group, a cyano group, an oxo group, an amino group, an amide group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group;

[0092] Each R 20 、R 21 and R 22 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclic group, an aryl group and a heteroaryl group; the alkyl group, alkoxy group, alkenyl group, alkynyl group, cycloalkyl group, heterocyclic group, aryl group and heteroaryl group are each independently optionally substituted with one or more groups selected from halogen, hydroxyl, cyano, amino, alkyl group, alkoxy group, haloalkyl group, haloalkoxy group and hydroxyalkyl group;

[0093] Each R 23are the same or different and are each independently selected from a hydrogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclic group, an aryl group, and a heteroaryl group; the alkyl group, alkoxy group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclic group, an aryl group, and a heteroaryl group are each independently optionally substituted with one or more groups selected from a halogen group, a hydroxyl group, a cyano group, an amino group, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, and a hydroxyalkyl group;

[0094] X 1 CR X1 or N;

[0095] X 2 CR X2 or N;

[0096] X 3 CR X3 or N;

[0097] X 4 CR X4 or N;

[0098] X 5 CR X5 or N;

[0099] X 1 、X 2 、X 3 、X 4 and X 5 Not all N at the same time;

[0100] R X1 、R X2 、R X3 、R X4 and R X5 are the same or different and are each independently selected from a hydrogen atom, a deuterium atom, a halogen, a hydroxyl group, a cyano group, an amino group, an amide group, a nitro group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, -O-(CH2) n -cycloalkyl, -O-(CH2) s -heterocyclic, aryl and heteroaryl; wherein the cycloalkyl, heterocyclic, aryl and heteroaryl are each independently optionally substituted by one or more R 03 replaced by;

[0101] Each R 03 are the same or different and are each independently selected from a deuterium atom, a halogen, a hydroxyl group, a cyano group, an oxo group, an amino group, an amide group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group;

[0102] Each v is the same or different and is independently selected from 0, 1 and 2;

[0103] n is selected from 0, 1, 2, 3, 4 and 5;

[0104] s is selected from 0, 1, 2, 3, 4, and 5; and,

[0105] r is selected from 0, 1, 2, 3, 4 and 5;

[0106] The condition is, Not for

[0107] The purpose of the present disclosure is to provide a compound represented by general formula (I) or a pharmaceutically acceptable salt thereof:

[0108] in:

[0109] Ring A is phenyl or a 6-membered heteroaryl group;

[0110] Each R A are the same or different and are each independently selected from halogen, hydroxy, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, alkenyl, -NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 、-P(O)R 7 R 8 、-C(O)NR 5 -NR 3 R 4 、-C(=NR 5 )NR 5 -OR 6 、-C(O)NR 5-alkylene-Cy, -C(=NR 5 )NR 3 R 4 、-C(O)-C(O)-NR 3 R 4 , cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl, wherein the alkenyl, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally replaced by one or more R 01 replaced by;

[0111] Cy is a cycloalkyl group or a 3- to 4-membered heterocyclic group, wherein the cycloalkyl group or the 3- to 4-membered heterocyclic group is each independently optionally substituted by one or more substituents selected from halogen, hydroxyl, cyano, oxo, amino, -NH alkyl, -N(alkyl) 2, acetyl, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclic, aryl and heteroaryl;

[0112] R 3 、R 4 and R 5 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group, a heterocyclic group, an aryl group and a heteroaryl group; wherein the alkyl group, the cycloalkyl group, the heterocyclic group, the aryl group and the heteroaryl group are each independently optionally replaced by one or more R 01 replaced by;

[0113] or R 3 、R 4 Together with the nitrogen atom to which it is attached, a heterocyclic group is formed; the heterocyclic group is optionally substituted by one or more R 01 replaced by;

[0114] R 6 、R 7 and R 8 are the same or different and are each independently selected from hydrogen, alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl and heteroaryl; the alkyl, alkoxy, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl and heteroaryl are each independently optionally substituted with one or more substituents selected from halogen, hydroxyl, cyano, oxo, amino, -NHalkyl, -N(alkyl), acetyl, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;

[0115] R 01each independently selected from halogen, hydroxy, cyano, oxo, amino, -NHalkyl, -N(alkyl), acetyl, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;

[0116] R' is selected from the group consisting of a hydrogen atom, an alkyl group, a haloalkyl group, a hydroxyalkyl group, a cycloalkyl group, and a heterocyclic group;

[0117] X is O or S;

[0118] R a and R b are the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, amino, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy; the cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy groups are optionally replaced by one or more R 02 replaced by;

[0119] The condition is that R a and R b Not simultaneously hydrogen;

[0120] R c and R d are the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, amino, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy; the cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy groups are optionally replaced by one or more R 02 replaced by;

[0121] or, R a 、R b Together with the carbon atom to which it is attached, it forms a cycloalkyl or heterocyclic group; or, R c 、R d Together with the carbon atom to which it is connected, it forms a cycloalkyl or heterocyclic group; wherein the cycloalkyl or heterocyclic group is independently optionally substituted by one or more R 02 replaced by;

[0122] R e is selected from the group consisting of hydrogen, halogen, hydroxy, cyano, amino, alkyl, alkoxy, haloalkyl, haloalkoxy and hydroxyalkyl;

[0123] R 02 each independently selected from halogen, hydroxy, cyano, oxo, amino, amido, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;

[0124] X 1CR X1 or N;

[0125] X 2 CR X2 or N;

[0126] X 3 CR X3 or N;

[0127] X 4 CR X4 or N;

[0128] X 5 CR X5 or N;

[0129] X 1 、X 2 、X 3 、X 4 and X 5 Not all N at the same time;

[0130] R X1 、R X2 、R X3 、R X4 and R X5 are the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, amino, amide, nitro, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclic, -O-(CH2) n -cycloalkyl, -O-(CH2) s -heterocyclic, aryl and heteroaryl; wherein the cycloalkyl, heterocyclic, aryl and heteroaryl are each independently optionally substituted by one or more R 03 replaced by;

[0131] R 03 each independently selected from halogen, hydroxy, cyano, oxo, amino, amido, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;

[0132] v is selected from 0, 1 and 2;

[0133] n is selected from 0, 1, 2, 3, 4 and 5;

[0134] s is selected from 0, 1, 2, 3, 4, and 5; and,

[0135] r is selected from 0, 1, 2, 3, 4 and 5;

[0136] The condition is, Not for

[0137] The purpose of the present disclosure is to provide a compound represented by general formula (I) or a pharmaceutically acceptable salt thereof:

[0138] in:

[0139] Ring A is phenyl or a 6-membered heteroaryl group;

[0140] Each R A are the same or different and are each independently selected from halogen, hydroxy, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, alkenyl, -NR 3 R 4 、-alkylene-NR 3 R 4 、-O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 、-P(O)R 7 R 8 , cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl, wherein the alkenyl, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted by one or more R 01 replaced by;

[0141] R 3 、R 4 and R 5 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group, a heterocyclic group, an aryl group and a heteroaryl group; wherein the alkyl group, the cycloalkyl group, the heterocyclic group, the aryl group and the heteroaryl group are each independently optionally replaced by one or more R 01 replaced by;

[0142] or R 3 、R 4Together with the nitrogen atom to which it is attached, a heterocyclic group is formed; the heterocyclic group is optionally substituted by one or more R 01 replaced by;

[0143] R 6 、R 7 and R 8 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, an aryl group, and a heteroaryl group;

[0144] R 01 each independently selected from halogen, hydroxy, cyano, oxo, amino, -NHalkyl, -N(alkyl), acetyl, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;

[0145] R' is selected from the group consisting of a hydrogen atom, an alkyl group, a haloalkyl group, a hydroxyalkyl group, a cycloalkyl group, and a heterocyclic group;

[0146] X is O or S;

[0147] R a and R b are the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, amino, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy; the cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy groups are optionally replaced by one or more R 02 replaced by;

[0148] The condition is that R a and R b Not simultaneously hydrogen;

[0149] R c and R d are the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, amino, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy; the cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy groups are optionally replaced by one or more R 02 replaced by;

[0150] or, R a 、R b Together with the carbon atom to which it is attached, it forms a cycloalkyl or heterocyclic group; or, R c 、R d Together with the carbon atom to which it is connected, it forms a cycloalkyl or heterocyclic group; wherein the cycloalkyl or heterocyclic group is independently optionally substituted by one or more R 02 replaced by;

[0151] R e is selected from the group consisting of hydrogen, halogen, hydroxy, cyano, amino, alkyl, alkoxy, haloalkyl, haloalkoxy and hydroxyalkyl;

[0152] R 02 each independently selected from halogen, hydroxy, cyano, oxo, amino, amido, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;

[0153] X 1 CR X1 or N;

[0154] X 2 CR X2 or N;

[0155] X 3 CR X3 or N;

[0156] X 4 CR X4 or N;

[0157] X 5 CR X5 or N;

[0158] X 1 、X 2 、X 3 、X 4 and X 5 Not all N at the same time;

[0159] R X1 、R X2 、R X3 、R X4 and R X5 are the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, amino, amide, nitro, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclic, -O-(CH2) n -cycloalkyl, -O-(CH2) s -heterocyclic, aryl and heteroaryl; wherein the cycloalkyl, heterocyclic, aryl and heteroaryl are each independently optionally substituted by one or more R 03 replaced by;

[0160] R 03 each independently selected from halogen, hydroxy, cyano, oxo, amino, amido, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;

[0161] v is selected from 0, 1 and 2;

[0162] n is selected from 0, 1, 2, 3, 4 and 5;

[0163] s is selected from 0, 1, 2, 3, 4, and 5; and,

[0164] r is selected from 0, 1, 2, 3, 4 and 5;

[0165] The condition is, Not for

[0166] The purpose of the present disclosure is to provide a compound represented by general formula (I) or a pharmaceutically acceptable salt thereof:

[0167] in:

[0168] Ring A is phenyl or a 6-membered heteroaryl group;

[0169] Each R A are the same or different and are each independently selected from halogen, hydroxy, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, alkenyl, -NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-P(O)R 7 R 8 , cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl, wherein the alkenyl, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted by one or more R 01 replaced by;

[0170] R 3 、R 4 and R 5are the same or different and are each independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group, a heterocyclic group, an aryl group and a heteroaryl group; wherein the alkyl group, the cycloalkyl group, the heterocyclic group, the aryl group and the heteroaryl group are each independently optionally replaced by one or more R 01 replaced by;

[0171] or R 3 、R 4 Together with the nitrogen atom to which it is attached, a heterocyclic group is formed; the heterocyclic group is optionally substituted by one or more R 01 replaced by;

[0172] R 6 、R 7 and R 8 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, an aryl group, and a heteroaryl group;

[0173] R 01 Each is independently selected from halogen, hydroxyl, cyano, oxo, amino, -NH alkyl, -N(alkyl), acetyl, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclic, aryl and heteroaryl; R' is selected from hydrogen, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl and heterocyclic;

[0174] X is O or S;

[0175] R a and R b are the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, amino, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy; the cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy groups are optionally replaced by one or more R 02 replaced by;

[0176] The condition is that R a and R b Not simultaneously hydrogen;

[0177] R c and R d are the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, amino, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy; the cycloalkyl, heterocyclyl, cycloalkyloxy and heterocyclyloxy groups are optionally replaced by one or more R 02 replaced by;

[0178] or, R a 、R bTogether with the carbon atom to which it is attached, it forms a cycloalkyl or heterocyclic group; or, R c 、R d Together with the carbon atom to which it is connected, it forms a cycloalkyl or heterocyclic group; wherein the cycloalkyl or heterocyclic group is independently optionally substituted by one or more R 02 replaced by;

[0179] R e is selected from the group consisting of hydrogen, halogen, hydroxy, cyano, amino, alkyl, alkoxy, haloalkyl, haloalkoxy and hydroxyalkyl;

[0180] R 02 each independently selected from halogen, hydroxy, cyano, oxo, amino, amido, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;

[0181] X 1 CR X1 or N;

[0182] X 2 CR X2 or N;

[0183] X 3 CR X3 or N;

[0184] X 4 CR X4 or N;

[0185] X 5 CR X5 or N;

[0186] X 1 、X 2 、X 3 、X 4 and X 5 Not all N at the same time;

[0187] R X1 、R X2 、R X3 、R X4 and R X5 are the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, amino, amide, nitro, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclic, -O-(CH2) n -cycloalkyl, -O-(CH2) s -heterocyclic, aryl and heteroaryl; wherein the cycloalkyl, heterocyclic, aryl and heteroaryl are each independently optionally substituted by one or more R 03 replaced by;

[0188] R 03 each independently selected from halogen, hydroxy, cyano, oxo, amino, amido, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;

[0189] v is selected from 0, 1 and 2;

[0190] n is selected from 0, 1, 2, 3, 4 and 5;

[0191] s is selected from 0, 1, 2, 3, 4, and 5; and,

[0192] r is selected from 0, 1, 2, 3, 4 and 5;

[0193] The condition is, Not for

[0194] In some embodiments of the present disclosure, the compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof, wherein R e Selected from hydrogen atoms, halogen, hydroxyl, cyano and C 1-6 Alkyl; preferably, R e A hydrogen atom.

[0195] In some embodiments of the present disclosure, the compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof, wherein X 1 N, X 2 CR X2 , X 3 CR X3 , X 4 CR X4 , X 5 CR X5 ; or X 2 N, X 1 CR X1 , X 3 CR X3 , X 4 CR X4 , X 5 CR X5 ; or X 3 N, X 1 CR X1 , X 2 CR X2 , X 4 CR X4 , X 5 CR X5 ; or X 1 N, X 3 N, X 2 CR X2, X 4 CR X4 , X 5 CR X5 ; or X 2 N, X 4 N, X 1 CR X1 , X 3 CR X3 , X 5 CR X5 ; or X 1 CR X1 , X 2 CR X2 , X 3 CR X3 , X 4 CR X4 , X 5 CR X5 ; R X1 、R X2 、R X3 、R X4 and R X5 As defined in general formula (I); preferably, X 1 CR X1 , X 2 CR X2 , X 3 CR X3 , X 4 CR X4 , X 5 CR X5 ; R X1 、R X2 、R X3 、R X4 and R X5 As defined in general formula (I); more preferably, X 1 CR X1 , X 2 CR X2 , X 3 CR X3 , X 4 CH, X 5 CH; R X1 、R X2 and R X3 are the same or different and are each independently selected from hydrogen atom, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6hydroxyalkyl, 3 to 8-membered cycloalkyl, 4 to 7-membered heterocyclyl, 3 to 8-membered cycloalkyloxy and 4 to 7-membered heterocyclyloxy; the 3 to 8-membered cycloalkyl, 4 to 7-membered heterocyclyl, 3 to 8-membered cycloalkyloxy and 4 to 7-membered heterocyclyloxy are each independently optionally substituted by one or more R 03 Replaced by; R 03 Each independently selected from halogen, hydroxy, cyano, oxo, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3 to 10 membered cycloalkyl, 3 to 10 membered heterocyclyl, 6 to 10 membered aryl and 5 to 14 membered heteroaryl; most preferably, X 1 CR X1 , X 2 CR X2 , X 3 CR X3 , X 4 CH, X 5 CH; R X1 、R X2 and R X3 are the same or different and are each independently selected from hydrogen atom, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl and halogenated C 1-6 Alkoxy.

[0196] In some embodiments of the present disclosure, the compound represented by general formula (I) or a pharmaceutically acceptable salt thereof, wherein Selected from R a 、R b 、 R c 、R d and X are as defined in general formula (I); preferably, Selected from X is O or S, R a and R b Different, and each independently selected from hydrogen atom, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy and 3 to 10-membered cycloalkyl, R c and R d Different, and each independently selected from hydrogen atom, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6Alkoxy and 3 to 10-membered cycloalkyl; further preferably, for R a and R b Different, and each independently selected from hydrogen atom, C 1-6 Alkyl and C 1-6 Haloalkyl, R c and R d Different, and each independently selected from hydrogen atom, C 1-6 Alkyl and C 1-6 Halogenated alkyl.

[0197] In some embodiments of the present disclosure, the compound represented by general formula (I) or a pharmaceutically acceptable salt thereof, wherein for R a and R b are the same or different and are each independently selected from hydrogen atom, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl and 3 to 10 membered cycloalkyl; R c and R d Different, and each independently selected from hydrogen atom, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl and 3- to 10-membered cycloalkyl;

[0198] In some embodiments, the compound represented by general formula (I) or a pharmaceutically acceptable salt thereof, wherein for R a and R b Different, and each independently selected from hydrogen atom, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl and 3 to 10 membered cycloalkyl; R c and R d are the same or different and are each independently selected from hydrogen atom, halogen, C 1-6 Alkyl, halogenated C 1-6 alkyl and 3- to 10-membered cycloalkyl.

[0199] In some embodiments of the present disclosure, the compound represented by general formula (I) or a pharmaceutically acceptable salt thereof is a compound represented by general formula (II) or a pharmaceutically acceptable salt thereof:

[0200] in:

[0201] R a and R b Different, and each independently selected from hydrogen atom, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3 to 10-membered cycloalkyl, 3 to 10-membered heterocyclyl, 3 to 10-membered cycloalkyloxy and 3 to 10-membered heterocyclyloxy; said 3 to 10-membered cycloalkyl, 3 to 10-membered heterocyclyl, 3 to 10-membered cycloalkyloxy and 3 to 10-membered heterocyclyloxy are optionally substituted by one or more R 02 replaced by;

[0202] R c and R d Different, and each independently selected from hydrogen atom, halogen, hydroxyl, cyano, amino, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3 to 10-membered cycloalkyl, 3 to 10-membered heterocyclyl, 3 to 10-membered cycloalkyloxy and 3 to 10-membered heterocyclyloxy; said 3 to 10-membered cycloalkyl, 3 to 10-membered heterocyclyl, 3 to 10-membered cycloalkyloxy and 3 to 10-membered heterocyclyloxy are optionally substituted by one or more R 02 replaced by;

[0203] Ring A, R A , R', X, R X1 、R X2 、R X3 、R 02 and r are as defined in the general formula (I).

[0204] In some embodiments of the present disclosure, the compound represented by the general formula (I) or the general formula (II) or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (II') or a pharmaceutically acceptable salt thereof:

[0205] Among them, R 3a Selected from hydrogen atom, alkyl, haloalkyl, hydroxyalkyl, OR 6 , cycloalkyl and heterocyclyl; the alkyl, cycloalkyl and heterocyclyl are each independently optionally substituted by one or more substituents selected from halogen, hydroxy, cyano, oxo, amino, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl and heterocyclyl;

[0206] r-1 is 0, 1, 2, 3 or 4;

[0207] Ring A, R A, R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 4 、R 5 and R 6 As defined in general formula (II).

[0208] In some embodiments of the present disclosure, the compound represented by the general formula (I) or the general formula (II) or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (II-1) or a pharmaceutically acceptable salt thereof:

[0209] Wherein, r-1 is 0, 1, 2, 3 or 4;

[0210] Ring A, R A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 and R 5 As defined in general formula (II).

[0211] In some embodiments of the present disclosure, the compound represented by the general formula (I) or the general formula (II) or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (III) or a pharmaceutically acceptable salt thereof:

[0212] wherein t is selected from 0, 1, 2, 3 and 4;

[0213] Ring A, R', R a 、R b 、R c 、R d , X, R X1 、R X2 and R X3 As defined in general formula (II).

[0214] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II) or (III) or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (III-1) or a pharmaceutically acceptable salt thereof:

[0215] wherein t is selected from 0, 1, 2, 3 and 4;

[0216] Ring A, R', R a 、R b 、R c 、R d , X, R X1 、R X2 and R X3 As defined in general formula (II).

[0217] In some embodiments of the present disclosure, the compound represented by the general formula (I) or (II) or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (IV) or a pharmaceutically acceptable salt thereof:

[0218] Among them, R 1A With R 2A are the same or different and are each independently a hydrogen atom or R A ;

[0219] R 3A R A ;

[0220] R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 , R' and R A As defined in general formula (II).

[0221] In some embodiments of the present disclosure, the compound represented by the general formula (I) or (II) or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (IV) or a pharmaceutically acceptable salt thereof:

[0222] Among them, R 1A With R 2A are the same or different and are each independently a hydrogen atom or R A ;

[0223] R 3A Selected from F, Cl, hydroxy, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, alkenyl, alkynyl, -NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 、-P(O)R 7 R 8 、-C(O)NR 5 -NR 3 R 4 、-C(=NR 5 )NR 5 -OR 6 、-C(O)NR 5 -alkylene-Cy, -C(=NR 5 )NR 3 R 4 、-C(O)-C(O)-NR 3 R 4 、-S(=NR 5 )NR 3 R 4 , cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl, wherein the alkenyl, alkynyl, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted by one or more R 01 replaced by;

[0224] R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 , R', R A 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 01 and v are as defined in general formula (II).

[0225] In some embodiments of the present disclosure, the compound represented by the general formula (I) or (II) or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (IV) or a pharmaceutically acceptable salt thereof:

[0226] Among them, R 1A With R 2A are the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, alkenyl, -NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4 、-P(O)R 7 R 8 , cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl, wherein the alkenyl, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted by one or more R 01 replaced by;

[0227] R 3A Selected from halogen, hydroxy, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, alkenyl, -NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR5 )(O)R 6 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 、-P(O)R 7 R 8 、-C(O)NR 5 -NR 3 R 4 、-C(=NR 5 )NR 5 -OR 6 、-C(O)NR 5 -alkylene-Cy, -C(=NR 5 )NR 3 R 4 、-C(O)-C(O)-NR 3 R 4 , cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl, wherein the alkenyl, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted by one or more R 01 replaced by;

[0228] R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 , R', R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 01 and v are as defined in general formula (I); preferably, R a 、R b 、R c 、R d As defined in general formula (II).

[0229] In some embodiments of the present disclosure, the compound represented by the general formula (I) or (II) or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (IV) or a pharmaceutically acceptable salt thereof:

[0230] Among them, R 1A With R 2Aare the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, alkenyl, -NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4 、-P(O)R 7 R 8 , cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl, wherein the alkenyl, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted by one or more R 01 replaced by;

[0231] R 3A Selected from halogen, hydroxy, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, alkenyl, -NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-NR 5 C(O)R 6 、-NR5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 、-P(O)R 7 R 8 , cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl, wherein the alkenyl, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted by one or more R 01 replaced by;

[0232] R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 , R', R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 01 and v are as defined in general formula (I); preferably, R a 、R b 、R c 、R d As defined in general formula (II).

[0233] In some embodiments of the present disclosure, the compound represented by the general formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 3A Selected from hydroxyl, amino, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, -C 1-6 Alkylene -NH2, -OC 1-6 Alkylene -NH2, -NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 , 3 to 8 membered cycloalkyl, 3 to 8 membered heterocyclyl, phenyl, 5 or 6 membered heteroaryl and -OC 1-6 Alkylene-5 or 6 membered heteroaryl, said C 1-6 Alkylene, 3 to 8 membered cycloalkyl, 3 to 8 membered heterocyclyl, phenyl and 5 or 6 membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by; R 01Each independently selected from halogen, hydroxy, cyano, oxo, amino, -NH C 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, and 5- to 14-membered heteroaryl, R 3 、R 4 、R 5 and R 6 As defined in formula (I);

[0234] In some embodiments, R 3A Selected from amino, C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, -C 1-6 Alkylene -NH2, -NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 , 3 to 8 membered cycloalkyl and 5 or 6 membered heteroaryl, said C 1-6 Alkylene, 3 to 8 membered cycloalkyl and 5 or 6 membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by R 01 Each independently selected from halogen, hydroxy, cyano, oxo, amino, -NH C 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, and 5- to 14-membered heteroaryl, R 3 、R 4 、R 5 and R 6 As defined in formula (I);

[0235] In some embodiments, R 3A Selected from amino, C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, -C 1-6Alkylene -NH2, -NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 , 3 to 6 membered cycloalkyl and 5 or 6 membered heteroaryl, said C 1-6 Alkylene, 3 to 6 membered cycloalkyl and 5 or 6 membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by R 01 Each independently selected from hydroxyl, cyano, amino, C 1-6 Alkyl and C 1-6 Hydroxyalkyl, R 3 、R 4 、R 5 and R 6 The same or different, and each independently a hydrogen atom or a C 1-6 Alkyl; in some embodiments, R 3A Selected from amino, C 1-6 Hydroxyalkyl, NR 5 C(O)NR 3 R 4 、 Among them, G 1 is a nitrogen atom or CR G , G 2 is a nitrogen atom or CR G , R A4 Selected from hydrogen atoms, hydroxyl groups, C 1-6 Alkyl and C 1-6 Hydroxyalkyl, R 3 、R 4 、R 5 and R 6 The same or different, and each independently a hydrogen atom or a C 1-6 Alkyl, R 01 Selected from hydroxyl, cyano, amino and C 1-6 Hydroxyalkyl, each R G and R N The same or different, and each independently a hydrogen atom or a C 1-6 Alkyl, t is selected from the group consisting of 0, 1, 2, and 3, u1 is selected from the group consisting of 0, 1, and 2, u2 is selected from the group consisting of 0, 1, 2, and 3, and u3 is selected from the group consisting of 1, 2, and 3;

[0236] In some embodiments, R 3A Selected from amino, In some embodiments, R 3A Selected from

[0237] In an embodiment, R 3A Selected from amino,

[0238] In some embodiments of the present disclosure, the compound represented by the general formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 3A Selected from C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, -NR 3 R 4 、-C 1-6 Alkylene-NR 3 R 4 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 , 3 to 10-membered cycloalkyl, 3 to 10-membered heterocyclyl and 5 or 6-membered heteroaryl, the C 1-6 Alkylene, 3 to 10 membered cycloalkyl, 3 to 10 membered heterocyclyl and 5 or 6 membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by R 01 Each independently selected from hydroxyl, cyano, C 1-6 Alkyl and C 1-6 Hydroxyalkyl, R 3 and R 4 are the same or different and are each independently a hydrogen atom or a C 1-6 Alkyl; R 5 and R 6 are the same or different and are each independently a hydrogen atom or a C 1-6 alkyl;

[0239] In some embodiments, R 3A Selected from C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, -C 1-6 Alkylene-NH2, -C(O)NR 5 -OR 6 , 3 to 6 membered cycloalkyl and 5 or 6 membered heteroaryl, said C 1-6 Alkylene, 3 to 6 membered cycloalkyl and 5 or 6 membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by R 01 Each independently selected from hydroxyl, cyano, C 1-6 Alkyl and C 1-6 Hydroxyalkyl, R5 and R 6 are the same or different and are each independently a hydrogen atom or a C 1-6 Alkyl; in some embodiments, R 3A -C 1-6 Alkylene-NH2 or -C(O)NR 5 -OR 6 , the C 1-6 The alkylene group is optionally replaced by one or more R 01 Replaced by R 01 Each independently selected from hydroxyl and C 1-6 Hydroxyalkyl, R 5 and R 6 are the same or different and are each independently a hydrogen atom or a C 1-6 alkyl.

[0240] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II) or (IV) or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (V) or a pharmaceutically acceptable salt thereof:

[0241] in,

[0242] R 1A With R 2A are the same or different and are each independently selected from hydrogen, halogen, hydroxy, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, alkenyl, -NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-P(O)R 7 R 8 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4, cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl, wherein the alkenyl, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted by one or more R 01 replaced by;

[0243] R A4 is selected from the group consisting of hydrogen, hydroxy, alkyl and hydroxyalkyl; u1 is selected from the group consisting of 0, 1, 2 and 3, and u2 is selected from the group consisting of 0, 1, 2 and 3;

[0244] R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 , R', R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 01 and v are as defined in general formula (I); preferably, R a 、R b 、R c 、R d As defined in general formula (II).

[0245] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II), (IV) or (V) or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (V-1) or (V-2) or a pharmaceutically acceptable salt thereof:

[0246] Among them, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 , R', R 1A 、R 2A 、R A4 , u1 and u2 are as defined in the general formula (V).

[0247] In some embodiments of the present disclosure, the compound represented by the general formula (V), (V-1) or (V-2) or a pharmaceutically acceptable salt thereof, wherein R A4 Selected from hydrogen atoms, C 1-6 Alkyl and C 1-6 A hydroxyalkyl group; preferably a hydrogen atom.

[0248] In some embodiments of the present disclosure, the compound represented by the general formula (V), (V-1) or (V-2) or a pharmaceutically acceptable salt thereof, wherein u1 is selected from 0, 1 and 2, and u2 is selected from 0, 1 and 2; preferably, u1 is 0 or 1, and u2 is 0 or 1; more preferably, u1 is 0, and u2 is 1.

[0249] In some embodiments of the present disclosure, the compound represented by the general formula (V), (V-1) or (V-2) or a pharmaceutically acceptable salt thereof, wherein R A4 is a hydrogen atom, u1 is selected from 0, 1 and 2, and u2 is selected from 0, 1 and 2.

[0250] In some embodiments of the present disclosure, the compound represented by the general formula (I) or (II) or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (VI') or a pharmaceutically acceptable salt thereof:

[0251] Among them, Q is selected from CR 5A , N and N + -O - ;

[0252] R 5A R 1A ;

[0253] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 and R 5 As defined in formula (IV).

[0254] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II), or (VI') or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (VI'-1) or a pharmaceutically acceptable salt thereof:

[0255] in,

[0256] Q is selected from CR 5A , N and N + -O - ;

[0257] R 5A R 1A ;

[0258] R C R23 OR 23 ;

[0259] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 5 and R 23 As defined in formula (IV).

[0260] In some embodiments of the present disclosure, the compound represented by the general formula (VI'-1) or a pharmaceutically acceptable salt thereof, wherein R C Selected from C 1-8 Alkyl, C 1-8 alkoxy and 3 to 10 membered cycloalkyloxy; in some embodiments, R C C 1-8 Alkoxy; in some embodiments, R C is isopropoxy or n-hexyloxy.

[0261] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II), (II'), (IV), (VI') or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (VI) or a pharmaceutically acceptable salt thereof:

[0262] Among them, R 3a Selected from hydrogen atom, alkyl, haloalkyl, hydroxyalkyl, OR 6 , cycloalkyl and heterocyclyl; the alkyl, cycloalkyl and heterocyclyl are each independently optionally substituted by one or more substituents selected from halogen, hydroxy, cyano, oxo, amino, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, cycloalkyl and heterocyclyl;

[0263] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 4 、R 5 and R 6 As defined in formula (IV).

[0264] In some embodiments of the present disclosure, the compound represented by the general formula (II') or (VI) or a pharmaceutically acceptable salt thereof, wherein R 3a Selected from hydrogen atoms, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Hydroxyalkyl, OR 6 , 3 to 6 membered cycloalkyl and 3 to 6 membered cycloalkyl C 1-6 Alkyl, R 6 Selected from hydrogen atoms, C 1-6 Alkyl, 3 to 6 membered cycloalkyl and 3 to 6 membered cycloalkyl C 1-6 alkyl;

[0265] In some embodiments, R 3a Selected from hydrogen atoms, C 1-6 Alkyl, C 1-6 alkoxy and 3 to 6 membered cycloalkyl; in some embodiments, R 3a Selected from hydrogen atoms, C 1-6 Alkyl and C 1-6 Alkoxy; in some embodiments, R 3a Selected from hydrogen atoms, C 1-6 alkyl and 3 to 6 membered cycloalkyl; in some embodiments, R 3a A hydrogen atom or C 1-6 alkyl;

[0266] In some embodiments, R 3a is selected from hydrogen, methyl, ethyl, methoxy and cyclopropyl; in some embodiments, R 3a is selected from hydrogen, methyl, ethyl and cyclopropyl; in some embodiments, R 3a is a hydrogen atom; in some embodiments, R 3a Selected from hydrogen atom, methyl, ethyl, hydroxyl, methoxy, deuterated methoxy, cyclopropyl,

[0267] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II), (II-1) or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (VII') or a pharmaceutically acceptable salt thereof:

[0268] Among them, Q is selected from CR 5A , N and N + -O - ;

[0269] R 5A R 1A ;

[0270] R 1A 、R 2A, R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 and R 5 As defined in formula (IV).

[0271] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II), (II-1), (IV) or (VII') or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (VII) or a pharmaceutically acceptable salt thereof:

[0272] Among them, R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 and R 5 As defined in formula (IV).

[0273] In some embodiments of the present disclosure, the compound represented by the general formula (I) or (II) or a pharmaceutically acceptable salt thereof is a compound represented by the general formula (VIII) or a pharmaceutically acceptable salt thereof:

[0274] Among them, Q is selected from CR 5A , N and N + -O - ;

[0275] R 5A R 1A ;

[0276] R 1A 、R 2A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 and R 4 As defined in formula (IV).

[0277] In some embodiments of the present disclosure, the compound represented by the general formula (VI'), (VI'-1), (VII'), (VIII) or a pharmaceutically acceptable salt thereof, wherein Q is N or CR 5A , R 5A R 1A , R 1A As defined in formula (IV); in some embodiments, Q is N; in some embodiments, Q is CR 5A , R 5A R 1A , R 1A As defined in formula (IV); in some embodiments, Q is N or CF.

[0278] In some embodiments of the present disclosure, the compound represented by the general formula (VI'), (VI'-1), (VII'), (VIII) or a pharmaceutically acceptable salt thereof, wherein R 5A Selected from hydrogen atoms, halogens, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3 to 6 membered cycloalkyl and 3 to 6 membered heterocyclyl; in some embodiments, R 5A Selected from hydrogen atoms, halogens, C 1-6 Alkyl and halogenated C 1-6 Alkyl; in some embodiments, R 5A is halogen; in some embodiments, R 5A For F.

[0279] In some embodiments of the present disclosure, the compound represented by the general formula (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or a pharmaceutically acceptable salt thereof, wherein R 1A and R 2A are the same or different and are independently selected from hydrogen, halogen, hydroxyl, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Hydroxyalkoxy; preferably, R 1A and R 2A are the same or different and are each independently selected from hydrogen atom, halogen, C 1-6 Alkyl and C 1-6 More preferably, R 1A and R 2A All are hydrogen atoms.

[0280] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R a Selected from hydrogen atoms, halogens, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3 to 10 membered cycloalkyl, and 3 to 10 membered heterocyclyl; in some embodiments, R a Selected from hydrogen atoms, halogens, C 1-6 Alkyl and halogenated C 1-6 Alkyl; in some embodiments, R a C 1-6 Alkyl or halogenated C 1-6 Alkyl; in some embodiments, R a is CH3 or CF3;

[0281] In some embodiments, R a C 1-6 Alkyl; in some embodiments, R a is selected from CH3, deuterated methyl and CF3; in some embodiments, R a is CH3 or deuterated methyl; in some embodiments, R a For CH3.

[0282] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R b Selected from hydrogen atoms, halogens, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3 to 10 membered cycloalkyl, and 3 to 10 membered heterocyclyl; in some embodiments, R b Selected from hydrogen atoms, halogens, C 1-6 Alkyl and halogenated C 1-6 Alkyl; in some embodiments, R b C1-6 Alkyl or halogenated C 1-6 Alkyl; in some embodiments, R b is selected from CH3, deuterated methyl and CF3; in some embodiments, R b is CH3 or CF3; in some embodiments, R b Halogenated C 1-6 Alkyl; in some embodiments, R b It is CF3.

[0283] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R c Selected from hydrogen atoms, halogens, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3 to 10-membered cycloalkyl and 3 to 10-membered heterocyclic group; preferably, R c Selected from hydrogen atoms, halogens, C 1-6 Alkyl and halogenated C 1-6 Alkyl; More preferably, R c A hydrogen atom or C 1-6 Alkyl; most preferably, R c is a hydrogen atom or CH3; in some embodiments, R c Selected from hydrogen atom, CH3, deuterated methyl and CF3.

[0284] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R d Selected from hydrogen atoms, halogens, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3 to 10-membered cycloalkyl and 3 to 10-membered heterocyclic group; preferably, R d Selected from hydrogen atoms, halogens, C 1-6 Alkyl and halogenated C 1-6 Alkyl; More preferably, Rd A hydrogen atom or C 1-6 Alkyl; further preferably, R d is a hydrogen atom or CH3; in some embodiments, R d is selected from hydrogen atoms, CH3, deuterated methyl and CF3; in some embodiments, R d Selected from hydrogen atom, CH3 and CD3.

[0285] In some embodiments of the present disclosure, the compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof, wherein R a and R b are the same or different and are each independently selected from hydrogen atom, C 1-6 Alkyl and halogenated C 1-6 Alkyl; in some embodiments, R a and R b The same or different, and each independently is C 1-6 Alkyl or halogenated C 1-6 Alkyl; in some embodiments, R a C 1-6 Alkyl, and R b Halogenated C 1-6 Alkyl; in some embodiments, R a is CH3, and R b is CF3;

[0286] In some embodiments, R a and R b are the same or different and are each independently selected from hydrogen, CH3, deuterated methyl and CF3; in some embodiments, R a and R b are the same or different and are each independently selected from hydrogen, CH3 and CF3;

[0287] In some embodiments, R a and R b The same or different, and each independently is C 1-6 Alkyl; in some embodiments, R a and R b The same or different, and each independently is a halogenated C 1-6 alkyl.

[0288] In some embodiments of the present disclosure, the compounds represented by the general formula (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R a and Rb Different, and each independently selected from hydrogen atom, C 1-6 Alkyl and halogenated C 1-6 Alkyl; preferably, R a and R b Different, and each independently C 1-6 Alkyl or halogenated C 1-6 Alkyl; further preferably, R a C 1-6 Alkyl, and R b Halogenated C 1-6 Alkyl, most preferably, R a is CH3, and R b is CF3;

[0289] In some embodiments, R a and R b are different and are each independently selected from hydrogen, CH3, deuterated methyl and CF3; in some embodiments, R a and R b different, and each independently selected from hydrogen, CH3, and CF3;

[0290] In some embodiments, R a and R b Different, and each independently C 1-6 Alkyl; in some embodiments, R a and R b Different, and each independently is a halogenated C 1-6 alkyl.

[0291] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R a Halogenated C 1-6 Alkyl, R b is a hydrogen atom; in some embodiments, R a Halogenated C 1-6 Alkyl, and R b C 1-6 Alkyl; in some embodiments, R a is CF3, and R b is CH3;

[0292] In some embodiments, R a is a hydrogen atom, R b Halogenated C 1-6 Alkyl; in some embodiments, Ra is a hydrogen atom, R b C 1-6 Alkyl; in some embodiments, R a C 1-6 Alkyl, R b A hydrogen atom.

[0293] In some embodiments of the present disclosure, the compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof, wherein R c and R d are the same or different and are each independently selected from hydrogen atom, C 1-6 alkyl and 3 to 6 membered cycloalkyl; in some embodiments, R c and R d The same or different, and each independently a hydrogen atom or a C 1-6 Alkyl; in some embodiments, R c is a hydrogen atom, and R d C 1-6 Alkyl; in some embodiments, R c is a hydrogen atom, and R d is CH3;

[0294] In some embodiments, R c and R d are the same or different and are each independently selected from a hydrogen atom, CH3 and a deuterated methyl group; in some embodiments, R c and R d are the same or different and are each independently a hydrogen atom or CH3; in some embodiments, R c and R d All are hydrogen atoms.

[0295] In some embodiments of the present disclosure, the compounds represented by the general formula (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R c and R d Different, and each independently selected from hydrogen atom, C 1-6 alkyl and 3 to 6 membered cycloalkyl; in some embodiments, R c and R d Different, and each independently a hydrogen atom or a C 1-6 Alkyl; in some embodiments, R c is a hydrogen atom, and R d C 1-6 Alkyl; in some embodiments, R c is a hydrogen atom, and Rd is CH3;

[0296] In some embodiments, R c and R d are different and are each independently selected from a hydrogen atom, CH3 and a deuterated methyl group; in some embodiments, R c and R d are different and are each independently a hydrogen atom or CH3.

[0297] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R c C 1-6 Alkyl, and R d is a hydrogen atom; in some embodiments, R c is CH3, and R d is a hydrogen atom; in some embodiments, R c is a 3- to 10-membered cycloalkyl group (preferably a cyclopropyl group), R d is a hydrogen atom; in some embodiments, R c is a hydrogen atom, R d is a 3- to 10-membered cycloalkyl group (preferably a cyclopropyl group).

[0298] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R a C 1-6 Alkyl, and / or R b Halogenated C 1-6 Alkyl, and / or R c is a hydrogen atom, and / or R d C 1-6 Alkyl; in some embodiments, R a is CH3, and / or R b CF3, and / or R c is a hydrogen atom, and / or R d For CH3.

[0299] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (VIII) or a pharmaceutically acceptable salt thereof, wherein X is O.

[0300] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII), or pharmaceutically acceptable salts thereof, wherein R' is a hydrogen atom or C 1-6 Alkyl; preferably, R' is a hydrogen atom.

[0301] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein X is O, and / or R' is a hydrogen atom.

[0302] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II), (II'), (II-1), (III) or (III-1) or a pharmaceutically acceptable salt thereof, wherein ring A is a 6-membered heteroaryl group; preferably, ring A is selected from pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl and triazinyl; further preferably, ring A is pyridyl or pyrimidinyl; more preferably, ring A is Most preferably The * end is connected to -NR', End and R A connect;

[0303] In some embodiments, ring A is selected from phenyl, pyridinyl, and pyrimidinyl; in some embodiments, ring A is selected from In some embodiments, Ring A is selected from In some embodiments, Ring A is selected from In some embodiments, Ring A is selected from In some embodiments, Ring A is In some embodiments, Ring A is The * end is connected to -NR', End and R A Connection; In some embodiments, ring A is selected from * end is connected to -NR', End with an RA connect.

[0304] In some embodiments of the present disclosure, the compound represented by general formula (I) or (II) or a pharmaceutically acceptable salt thereof, Selected from R A and r are as defined in general formula (I); preferably, Selected from R A and r are as defined in general formula (I); further preferably, Selected from R A As defined in general formula (I); more preferably, for R A As defined in general formula (I); most preferably, for R A As defined in general formula (I).

[0305] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II), (II'), (II-1), (IV) or a pharmaceutically acceptable salt thereof, wherein R A Selected from C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, -NR 3 R 4 、-C 1-6 Alkylene-NR 3 R 4 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 , 3 to 10-membered cycloalkyl, 3 to 10-membered heterocyclyl and 5 or 6-membered heteroaryl, the C 1-6 Alkylene, 3 to 10 membered cycloalkyl, 3 to 10 membered heterocyclyl and 5 or 6 membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by R 01 Each independently selected from halogen, hydroxy, cyano, oxo, amino, -NH C 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, and 5- to 14-membered heteroaryl, R 3 、R 4 、R 5 and R 6 As defined in formula (I); in some embodiments, R A Selected from amino,

[0306] In some embodiments, R A Selected from F, Cl, amino, cyano,

[0307] In some embodiments, R A Selected from F, Cl, amino, cyano,

[0308] In some embodiments, R A Selected from F, Cl, amino,

[0309] In some embodiments, R A Selected from amino,

[0310] In some embodiments, R A Selected from amino,

[0311] In some embodiments, R A Selected from

[0312] In some embodiments, R A Selected from

[0313] In some embodiments, R A Selected from In some embodiments, R A Selected from

[0314] In some embodiments, RA Selected from

[0315] In some embodiments, R A Selected from

[0316] In some embodiments, R A Selected from In some embodiments, R A Selected from In some embodiments, R A for In some embodiments, R A for In some embodiments, R A for In some embodiments, R A for In some embodiments, R A for

[0317] In some embodiments, R A Selected from In some embodiments, R A for In some embodiments, R A for In some embodiments, R A for In some embodiments, R A for

[0318] In some embodiments, R A Selected from -C(O)NR 5 -OR 6 、-C(O)NR 5 -NR 3 R 4 、-C(=NR 5 )NR 5 -OR 6 、-C(O)NR 5 -alkylene-Cy, -C(=NR 5 )NR 3 R 4 and -C(O)-C(O)-NR3 R 4 The alkylene group is optionally replaced by one or more R 01 Replaced by Cy, R 3 、R 4 、R 5 、R 6 and R 01 As defined in formula (I); in some embodiments, R A Selected from -C(O)NR 5 -NR 3 R 4 、-C(=NR 5 )NR 5 -OR 6 、-C(O)NR 5 -alkylene-Cy, -C(O)NR 5 -O-alkylene-cycloalkyl, -C(=NR 5 )NR 3 R 4 and -C(O)-C(O)-NR 3 R 4 , the alkylene and cycloalkyl groups are optionally substituted by one or more R 01 Replaced by Cy, R 3 、R 4 、R 5 、R 6 and R 01 As defined in formula (I); in some embodiments, R A -C(O)NR 5 -NR 3 R 4 or -C(=NR 5 )NR 3 -OR 6 , R 3 、R 4 、R 5 and R 6 As defined in formula (I); in some embodiments, R A -C(O)NR 5 -NR 3 R 4 , R 3 、R 4 and R 5 As defined in formula (I); in some embodiments, R A -C(=NR 5 )NR 3 -OR 6 , R 3 、R 5 and R 6As defined in formula (I); in some embodiments, R A -C(=NR 5 )NR 3 R 4 , R 3 、R 4 and R 5 As defined in formula (I); in some embodiments, R A -C(=NR 5 )NR 3 R 4 , R 3 、R 4 and R 5 are the same or different and are each independently selected from hydrogen atom, C 1-6 Alkyl and 3- to 6-membered cycloalkyl;

[0319] In some embodiments, R A -C(O)-C(O)-NR 3 R 4 , R 3 and R 4 As defined in formula (I); in some embodiments, R A -C(O)-C(O)-NR 3 R 4 , R 3 and R 4 The same or different, and each independently a hydrogen atom or a C 1-6 alkyl;

[0320] In some embodiments, R A -C(O)NR 5 -NR 3 R 4 or -C(=NR 5 )NR 3 -OR 6 , R 3 、R 4 、R 5 and R 6 The same or different, and each independently a hydrogen atom or a C 1-6 alkyl.

[0321] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II), (II') or (II-1) or a pharmaceutically acceptable salt thereof, wherein R A Selected from amino, C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, -C 1-6 Alkylene -NH2, -NR 5 C(O)NR 3 R4 、-C(O)NR 5 -OR 6 , 3 to 8 membered cycloalkyl and 5 or 6 membered heteroaryl, said C 1-6 Alkylene, 3 to 8 membered cycloalkyl and 5 or 6 membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by R 01 Each independently selected from halogen, hydroxy, cyano, oxo, amino, -NH C 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, and 5- to 14-membered heteroaryl, R 3 、R 4 、R 5 and R 6 As defined in formula (I);

[0322] In some embodiments, R A Selected from amino, C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, -C 1-6 Alkylene -NH2, -NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 , 3 to 6 membered cycloalkyl and 5 or 6 membered heteroaryl, said C 1-6 Alkylene, 3 to 6 membered cycloalkyl and 5 or 6 membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by R 01 Each independently selected from hydroxyl, cyano, amino, C 1-6 Alkyl and C 1-6 Hydroxyalkyl, R 3 、R 4 、R 5 and R 6 The same or different, and each independently a hydrogen atom or a C 1-6 alkyl;

[0323] In some embodiments, R A Selected from amino, C 1-6 Hydroxyalkyl, NR 5C(O)NR 3 R 4 、 Among them, G 1 is a nitrogen atom or CR G , G 2 is a nitrogen atom or CR G , R A4 For hydrogen atoms, hydroxyl groups, C 1-6 Alkyl and C 1-6 Hydroxyalkyl, R 3 、R 4 、R 5 and R 6 The same or different, and each independently a hydrogen atom or a C 1-6 Alkyl, R 01 Each independently selected from hydroxyl, cyano, amino and C 1-6 Hydroxyalkyl, each R G and R N The same or different, and each independently a hydrogen atom or a C 1-6 Alkyl, t is selected from the group consisting of 0, 1, 2, and 3, u1 is selected from the group consisting of 0, 1, 2, and 3, u2 is selected from the group consisting of 0, 1, 2, and 3, and u3 is selected from the group consisting of 1, 2, and 3;

[0324] In some embodiments, R A Selected from amino, In some embodiments, R A Selected from

[0325] In some embodiments, R A Selected from C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, -C 1-6 Alkylene-NH2, -C(O)NR 5 -OR 6 , 3 to 6 membered cycloalkyl and 5 or 6 membered heteroaryl, said C 1-6 Alkylene, 3 to 6 membered cycloalkyl and 5 or 6 membered heteroaryl are optionally substituted by one or more R 01 Replaced by R 01 Each independently selected from hydroxyl, cyano, C 1-6 Alkyl and C 1-6 Hydroxyalkyl, R 5 and R 6 The same or different, and each independently a hydrogen atom or a C 1-6 Alkyl; in some embodiments, R A -C 1-6 Alkylene-NH2 or -C(O)NR 5 -OR6 , the C 1-6 The alkylene group is optionally replaced by one or more R 01 Replaced by R 01 Each independently selected from hydroxyl and C 1-6 Hydroxyalkyl, R 5 and R 6 The same or different, and each independently a hydrogen atom or a C 1-6 Alkyl; in some embodiments, R A Selected from

[0326] In some embodiments, R A is a 3- to 6-membered cycloalkyl group or a 5- or 6-membered heteroaryl group, wherein the 3- to 6-membered cycloalkyl group and the 5- or 6-membered heteroaryl group are each independently optionally substituted by one or more R 01 Replaced by R 01 Each independently selected from hydroxyl, cyano, amino, C 1-6 Alkyl and C 1-6 Hydroxyalkyl; in some embodiments, R A is a 3- to 6-membered cycloalkyl group or a 5-membered heteroaryl group, wherein the 3- to 6-membered cycloalkyl group and the 5-membered heteroaryl group are each independently optionally substituted by one or more R 01 Replaced by R 01 Each independently selected from hydroxyl, cyano, amino, C 1-6 Alkyl and C 1-6 Hydroxyalkyl; in some embodiments, R A Selected from G 1 is a nitrogen atom or CR G , G 2 is a nitrogen atom or CR G , R 01 Selected from hydroxyl, cyano, amino and C 1-6 Hydroxyalkyl, each R G and R N The same or different, and each independently a hydrogen atom or a C 1-6 Alkyl; u3 is 1 or 2;

[0327] In some embodiments, each R A are the same or different and are independently selected from fluorine atoms, chlorine atoms, hydroxyl groups, cyano groups, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, -NR 3 R 4 、-C 1-6 Alkylene-NR3 R 4 、-OC 1-6 Alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(=NR 5 )(O)R 6 , 3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, 5- to 14-membered heteroaryl, -OC 1-6 Alkylene-5 to 14 heteroaryl and -OC 1-6 Alkylene-3 to 10-membered heterocyclic group, wherein the C 1-6 Alkylene, 3 to 10-membered cycloalkyl, 3 to 10-membered heterocyclyl, 6 to 10-membered aryl and 5 to 14-membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by; R 01 Each independently selected from halogen, hydroxy, cyano, oxo, amino, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, acetyl, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, and 5- to 14-membered heteroaryl; R 3 、R 4 、R 5 、R 6 and v are as defined in formula (I);

[0328] In some embodiments, R A are the same or different and are independently selected from hydroxyl, amino, -C 1-6 Alkylene -NH2, -OC 1-6 Alkylene-NH2, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, 3- to 8-membered cycloalkyl, 4- to 7-membered heterocyclyl, phenyl, 5- or 6-membered heteroaryl, and -OC 1-6 Alkylene-5 or 6 membered heteroaryl, wherein said C 1-6Alkylene, 3 to 8 membered cycloalkyl, 4 to 7 membered heterocyclyl, phenyl and 5 or 6 membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by; R 01 Each independently selected from halogen, hydroxy, cyano, oxo, amino, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, and 5- to 14-membered heteroaryl;

[0329] In some embodiments, R A are the same or different and are each independently selected from amino, C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, phenyl and 5 or 6-membered heteroaryl, said phenyl and 5 or 6-membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by; R 01 Each independently selected from halogen, hydroxy, cyano, oxo, amino, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3 to 10 membered cycloalkyl, 3 to 10 membered heterocyclyl, 6 to 10 membered aryl, and 5 to 14 membered heteroaryl; in some embodiments, R A are the same or different and are each independently selected from amino, In some embodiments, R A for

[0330] In some embodiments of the present disclosure, the compound represented by the general formula (I) or (II) or a pharmaceutically acceptable salt thereof, wherein for Each R Bare the same or different and are each independently selected from halogen, hydroxy, cyano, amino, alkyl, alkoxy, haloalkyl, haloalkoxy, cycloalkyl and heterocyclyl; the alkyl, alkoxy, cycloalkyl and heterocyclyl are each independently optionally substituted by one or more selected from halogen, hydroxy, cyano, amino, alkyl, alkoxy, haloalkyl, haloalkoxy, cycloalkyl and heterocyclyl; p is 0, 1, 2, 3 or 4; Ring A and R A As defined in formula (I);

[0331] Preferably, for R B Selected from halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl and halogenated C 1-6 Alkoxy; p is selected from 0, 1 and 2, and ring A is selected from phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl and R A As defined in general formula (I); more preferably, for R B Selected from halogen, hydroxyl, C 1-6 Alkyl and halogenated C 1-6 Alkyl; p is 0 or 1, and ring A is selected from phenyl, pyridyl and pyrimidinyl; R A Selected from amino, C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, phenyl and 5 or 6-membered heteroaryl, said phenyl and 5 or 6-membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by R 01 As defined in general formula (I).

[0332] In some embodiments of the present disclosure, each R B are the same or different and are each independently halogen; in some embodiments, R B For F.

[0333] In some embodiments of the present disclosure, each R B are the same or different and are each independently selected from halogen, C 1-6 Alkyl and C 1-6 alkoxy; and / or p is 0 or 1; in some embodiments, each R B are the same or different and are each independently halogen, and / or p is 0 or 1.

[0334] In some embodiments of the present disclosure, p is 0 or 1; in some embodiments, p is 0; in some embodiments, p is 1.

[0335] In some embodiments of the present disclosure, the compound represented by the general formula (I) or (II) or a pharmaceutically acceptable salt thereof, wherein for R 1A 、R 2A and R 3A are the same or different and are each independently selected from hydrogen atoms, fluorine atoms, chlorine atoms, hydroxyl groups, cyano groups, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, -NR 3 R 4 、-C 1-6 Alkylene-NR 3 R 4 、-OC 1-6 Alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 , 3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, 5- to 14-membered heteroaryl, -OC 1-6 Alkylene-5 to 14 heteroaryl and -OC 1-6 Alkylene-3 to 10-membered heterocyclic group, wherein the C 1-6 Alkylene, 3 to 10-membered cycloalkyl, 3 to 10-membered heterocyclyl, 6 to 10-membered aryl and 5 to 14-membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by; R 01 、R 3 、R 4 、R 5 、R 6 and v are as defined in general formula (I).

[0336] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II), (II'), (II-1) or a pharmaceutically acceptable salt thereof, wherein R A Selected from halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C1-6 Alkyl and halogenated C 1-6 Alkoxy.

[0337] In some embodiments of the present disclosure, the compound represented by the general formula (II') or (II-1) or a pharmaceutically acceptable salt thereof, wherein r-1 is 0, 1 or 2; in some embodiments, r-1 is 0; in some embodiments, r-1 is 1.

[0338] In some embodiments of the present disclosure, the compound represented by the general formula (I) or (II) or a pharmaceutically acceptable salt thereof, wherein for R 1A and R 2A are the same or different and are independently selected from hydrogen, halogen, hydroxyl, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Hydroxyalkoxy; R 3A Selected from halogen, hydroxy, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, alkenyl, -NR 3 R 4 、-alkylene-NR 3 R 4 , -O-alkylene-NR 3 R 4 、-C(=NR 5 )R 6 、-S(O) v NR 3 R 4 、-NR 5 S(O) v R 6 、-S(O) v R 6 、-S(=NR 5 )(O)R 6 、-NR 5 C(O)R 6 、-NR 5 C(O)NR 3 R 4 、-C(O)NR 5 -OR 6 、-P(O)R 7 R 8 、-C(O)NR 5 -NR 3 R 4 、-C(=NR 5 )NR5 -OR 6 、-C(O)NR 5 -alkylene-Cy, -C(=NR 5 )NR 3 R 4 、-C(O)-C(O)-NR 3 R 4 , cycloalkyl, heterocyclyl, aryl, heteroaryl, -O-alkylene-heteroaryl and -O-alkylene-heterocyclyl, wherein the alkenyl, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted by one or more R 01 Replaced by; R 01 、R 3 、R 4 、R 5 、R 6 and v are as defined in formula (I);

[0339] In some embodiments, R 1A and R 2A are the same or different and are independently selected from hydrogen, halogen, hydroxyl, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl and C 1-6 Hydroxyalkoxy; R 3A Selected from hydroxyl, amino, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, -C 1-6 Alkylene -NH2, -OC 1-6 Alkylene-NH2, phenyl, 5- or 6-membered heteroaryl and -OC 1-6 Alkylene-5 or 6 membered heteroaryl, said C 1-6 Alkylene, phenyl and 5 or 6 membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by; R 01 Each independently selected from halogen, hydroxy, cyano, oxo, amino, -NH C 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6hydroxyalkyl, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, and 5- to 14-membered heteroaryl;

[0340] Preferably, R 1A and R 2A are the same or different and are each independently selected from hydrogen atom, halogen, C 1-6 Alkyl and halogenated C 1-6 Alkyl; R 3A Selected from hydroxyl, amino, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 1-6 Hydroxyalkoxy, -C 1-6 Alkylene -NH2, -OC 1-6 Alkylene-NH2, phenyl, 5- or 6-membered heteroaryl and -OC 1-6 Alkylene-5 or 6 membered heteroaryl, said C 1-6 Alkylene, phenyl and 5 or 6 membered heteroaryl are each independently optionally substituted by one or more R 01 Replaced by; R 01 Each independently selected from halogen, hydroxy, cyano, oxo, amino, -NH C 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, C 1-6 hydroxyalkyl, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, and 5- to 14-membered heteroaryl.

[0341] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II) or (IV) or a pharmaceutically acceptable salt thereof, wherein R 3A Selected from F, Cl, amino,

[0342] In some embodiments, R 3A Selected from amino,

[0343] In some embodiments, R 3A Selected from amino,

[0344] In some embodiments, R 3A Selected from

[0345] In some embodiments, R 3A Selected from

[0346] In some embodiments, R 3A Selected from

[0347] In some embodiments, R 3A Selected from

[0348] In some embodiments, R 3A Selected from

[0349] In some embodiments, R 3A Selected from In some embodiments, R 3A for In some embodiments, R 3A for In some embodiments, R 3A for In some embodiments, R 3A for

[0350] In some embodiments, R 3A Selected from -C(O)NR 5 -OR 6 、-C(O)NR 5 -NR 3 R 4 、-C(=NR 5 )NR 5 -OR 6 、-C(O)NR 5 -alkylene-Cy, -C(=NR 5 )NR 3 R 4 and -C(O)-C(O)-NR 3 R 4 , the alkylene group is optionally replaced by one or more R 01 Replaced by Cy, R 3 、R 4 、R 5 、R 6 and R 01 As defined in formula (I); in some embodiments, R 3A Selected from -C(O)NR 5 -NR3 R 4 、-C(=NR 5 )NR 5 -OR 6 、 -C(O)NR 5 -alkylene-Cy, -C(O)NR 5 -O-alkylene-cycloalkyl, -C(=NR 5 )NR 3 R 4 and -C(O)-C(O)-NR 3 R 4 , the alkylene group is optionally replaced by one or more R 01 Replaced by Cy, R 3 、R 4 、R 5 、R 6 and R 01 As defined in formula (I); in some embodiments, R 3A -C(O)NR 5 -NR 3 R 4 or -C(=NR 5 )NR 3 -OR 6 , R 3 、R 4 、R 5 and R 6 As defined in formula (I); in some embodiments, R 3A -C(O)NR 5 -NR 3 R 4 , R 3 、R 4 and R 5 As defined in formula (I); in some embodiments, R 3A -C(=NR 5 )NR 3 -OR 6 , R 3 、R 5 and R 6 As defined in formula (I);

[0351] In some embodiments, R 3A -C(=NR 5 )NR 3 R 4 , R 3 、R 4 and R 5 As defined in formula (I); in some embodiments, R 3A -C(=NR5 )NR 3 R 4 , R 3 、R 4 and R 5 are the same or different and are each independently selected from hydrogen atom, C 1-6 Alkyl and 3- to 6-membered cycloalkyl;

[0352] In some embodiments, R 3A -C(O)-C(O)-NR 3 R 4 , R 3 and R 4 As defined in formula (I); in some embodiments, R 3A -C(O)-C(O)-NR 3 R 4 , R 3 and R 4 The same or different, and each independently a hydrogen atom or a C 1-6 alkyl;

[0353] In some embodiments, R 3A -C(O)NR 5 -NR 3 R 4 or -C(=NR 5 )NR 3 -OR 6 , R 3 、R 4 、R 5 and R 6 The same or different, and each independently a hydrogen atom or a C 1-6 alkyl.

[0354] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II), (II'), (II-1) or (IV) or a pharmaceutically acceptable salt thereof, wherein Cy is a 3- to 6-membered cycloalkyl group, and the 3- to 6-membered cycloalkyl group is optionally selected from halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 substituted with one or more substituents selected from alkoxy, hydroxy, amino, cyano and 3 to 6 membered cycloalkyl; in some embodiments, Cy is cyclopropyl, which is optionally substituted with one or more substituents selected from halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 substituted with one or more substituents selected from alkoxy, hydroxy, cyano, and 3- to 6-membered cycloalkyl; in some embodiments, Cy is In some embodiments, Cy is selected from cyclopropyl, cyclobutyl and cyclopentyl, wherein the cyclopropyl, cyclobutyl and cyclopentyl are optionally selected from halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 The alkoxy group and the hydroxy group are substituted by one or more substituents.

[0355] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R 3 and R 4 are the same or different and are each independently selected from hydrogen atom, C 1-6 Alkyl, halogenated C 1-6 Alkyl and C 1-6 Hydroxyalkyl; preferably, R 3 and R 4 The same or different, and each independently a hydrogen atom or a C 1-6 Alkyl; further preferably, R 3 and R 4 All are hydrogen atoms.

[0356] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R 3 Selected from hydrogen atoms, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Hydroxyalkyl, 3 to 6 membered cycloalkyl and 3 to 6 membered cycloalkyl C 1-6 Alkyl; the C 1-6 Alkyl and 3 to 6 membered cycloalkyl are each independently optionally selected from halogen, hydroxy, oxo, C 1-6 Alkyl and C 1-6 substituted by one or more alkoxy groups;

[0357] In some embodiments, R 3 Selected from hydrogen atoms, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Hydroxyalkyl, 3 to 6 membered cycloalkyl and 3 to 6 membered cycloalkyl C 1-6 Alkyl; in some embodiments, R 3 Selected from hydrogen atoms, C1-6 alkyl and 3 to 6 membered cycloalkyl; in some embodiments, R 3 is selected from hydrogen, methyl, ethyl and cyclopropyl; in some embodiments, R 3 is ethyl or cyclopropyl;

[0358] In some embodiments, R 3 is a 3- to 6-membered cycloalkyl group; in some embodiments, R 3 A hydrogen atom or C 1-6 Alkyl; in some embodiments, R 3 Selected from hydrogen atoms, C 1-6 Alkyl, OR 23 , 3 to 6 membered cycloalkyl and C(O)OR 23 , R 23 As defined in formula (I); in some embodiments, R 3 Selected from hydrogen atoms, C 1-6 Alkyl, OR 23 , 3 to 6 membered cycloalkyl and C(O)OR 23 , R 23 A hydrogen atom or C 1-8 alkyl;

[0359] In some embodiments, R 3 Selected from hydrogen atoms, C 1-6 Alkyl, C 1-6 Alkoxy, 3- to 6-membered cycloalkyl and C(O)OR 23 , R 23 As defined in formula (I);

[0360] In some embodiments, R 3 Selected from hydrogen atoms, C 1-6 Alkyl, C 1-6 Alkoxy, 3- to 6-membered cycloalkyl and C(O)OR 23 , R 23 A hydrogen atom or C 1-8 alkyl;

[0361] In some embodiments, R 3 Selected from hydrogen atom, methyl, ethyl, hydroxyl, methoxy, cyclopropyl, In some embodiments, R 3 Selected from hydrogen atom, methyl, ethyl, methoxy, cyclopropyl, In some embodiments, R 3 Selected from hydrogen atom, methyl, ethyl, hydroxyl, methoxy, deuterated methoxy, cyclopropyl,

[0362] In some embodiments, R3 is a hydrogen atom; in some embodiments, R 3 is methyl; in some embodiments, R 3 is ethyl; in some embodiments, R 3 is hydroxyl; in some embodiments, R 3 is methoxy; in some embodiments, R 3 is cyclopropyl; in some embodiments, R 3 C(O)OR 23 , R 23 C 1-8 alkyl.

[0363] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R 4 A hydrogen atom or C 1-6 Alkyl, in some embodiments, R 4 is a hydrogen atom or a methyl group; in some embodiments, R 4 is a hydrogen atom; in some embodiments, R 4 C 1-6 Alkyl; in some embodiments, R 4 It is methyl or ethyl.

[0364] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R 3 Selected from hydrogen atoms, C 1-6 Alkyl, OR 23 and C(O)OR 23 , R 23 As defined in formula (I); and / or R 4 is a hydrogen atom; in some embodiments, R 3 Selected from hydrogen atoms, hydroxyl groups, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, -O-3 to 6-membered cycloalkyl and C(O)OR 23 , R 23 C 1-8 Alkyl; and / or R 4 is a hydrogen atom; in some embodiments, R 3Selected from hydrogen atom, methyl, ethyl, hydroxyl, methoxy, cyclopropyl, and / or R 4 A hydrogen atom.

[0365] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R 20 and R 21 are the same or different and are each independently selected from hydrogen atom, C 1-8 Alkyl, halogenated C 1-8 Alkyl and C 1-8 Hydroxyalkyl; in some embodiments, R 20 and R 21 The same or different, and each independently a hydrogen atom or a C 1-8 Alkyl; in some embodiments, R 20 is a hydrogen atom, R 21 C 1-8 Alkyl; in some embodiments, R 20 is a hydrogen atom, R 21 It is n-hexyl.

[0366] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R 23 Selected from hydrogen atoms, C 1-8 Alkyl, deuterated C 1-6 Alkyl, halogenated C 1-8 Alkyl and C 1-8 Hydroxyalkyl; in some embodiments, R 23 Selected from hydrogen atoms, C 1-8 Alkyl, halogenated C 1-8 Alkyl and C 1-8 Hydroxyalkyl; in some embodiments, R 23 Selected from hydrogen atoms, C 1-8 Alkyl and deuterated C 1-6 Alkyl; in some embodiments, R 23 is selected from hydrogen, methyl, deuterated methyl, cyclopropyl, isopropyl and n-hexyl; in some embodiments, R 23 C 1-8 Alkyl; in some embodiments, R 23 is a hydrogen atom or a methyl group; in some embodiments, R23 is selected from a hydrogen atom, a methyl group, and a deuterated methyl group; in some embodiments, R 23 is isopropyl or n-hexyl.

[0367] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R 22 A hydrogen atom or C 1-6 Alkyl; in some embodiments, R 22 A hydrogen atom.

[0368] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R 5 Selected from hydrogen atoms, C 1-6 Alkyl, halogenated C 1-6 Alkyl and C 1-6 Hydroxyalkyl; preferably, R 5 A hydrogen atom or C 1-6 Alkyl; in some embodiments, R 5 is a hydrogen atom;

[0369] In some embodiments, R 5 Selected from hydrogen atoms, C 1-6 Alkyl, OR 23 , 3 to 6 membered cycloalkyl and C(O)OR 23 , R 23 As defined in formula (I);

[0370] In some embodiments, R 5 Selected from hydrogen atoms, deuterium atoms, C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, 3 to 6 membered cycloalkyl, -O-3 to 6 membered cycloalkyl and C(O)OR 23 , R 23 A hydrogen atom or C 1-8 Alkyl; in some embodiments, R 5 Selected from hydrogen atoms, hydroxyl groups, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6Alkoxy, -O-3 to 6-membered cycloalkyl and C(O)OR 23 , R 23 C 1-8 Alkyl; in some embodiments, R 5 Selected from hydrogen atoms, C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, -O-3 to 6-membered cycloalkyl and C(O)OR 23 , R 23 C 1-8 Alkyl; in some embodiments, R 5 Hydroxyl or C 1-6 alkoxy;

[0371] In some embodiments, R 5 is selected from hydrogen atom, deuterium atom, methyl, deuterated methyl, hydroxyl, methoxy, deuterated methoxy, cyclopropyl, -O-cyclopropyl, In some embodiments, R 5 Selected from hydrogen atom, methyl, hydroxyl, methoxy, OCD3, In some embodiments, R 5 Selected from hydrogen atom, methyl, hydroxyl, methoxy, deuterated methoxy, -O-cyclopropyl, In some embodiments, R 5 is a hydroxyl group or a methoxy group;

[0372] In some embodiments, R 5 is methyl; in some embodiments, R 5 is deuterated methyl; in some embodiments, R 5 is hydroxyl; in some embodiments, R 5 is methoxy; in some embodiments, R 5 is deuterated methoxy; in some embodiments, R 5 is OCD3; in some embodiments, R 5 is cyclopropyl or -O-cyclopropyl; in some embodiments, R 5 for In some embodiments, R 5 is selected from hydrogen, methyl, hydroxy, methoxy, deuterated methoxy, and -O-cyclopropyl; in some embodiments, R 5 is selected from the group consisting of a hydrogen atom, a methyl group, a hydroxyl group and a methoxy group.

[0373] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II), (II'), (II-1), (IV), (VI), (VII), (VI'), (VI'-1), (VII') or a pharmaceutically acceptable salt thereof, wherein R3 and R 4 are all hydrogen atoms, R 5 is selected from hydrogen atom, deuterium atom, methyl, deuterated methyl, hydroxyl, methoxy, deuterated methoxy, cyclopropyl, -O-cyclopropyl, or R 5 is a hydrogen atom, R 4 is a hydrogen atom, R 3 Selected from hydrogen atom, methyl, ethyl, hydroxyl, methoxy, deuterated methoxy, cyclopropyl, In some embodiments, R 3 and R 4 are all hydrogen atoms, R 5 is selected from hydrogen atom, deuterium atom, methyl, deuterated methyl, hydroxyl, methoxy, deuterated methoxy, cyclopropyl, -O-cyclopropyl,

[0374] In some embodiments of the present disclosure, the compound represented by the general formula (I), (II), (II'), (IV), (VI) or a pharmaceutically acceptable salt thereof, wherein R 3a and R 4 are all hydrogen atoms, R 5 is selected from hydrogen atom, deuterium atom, methyl, deuterated methyl, hydroxyl, methoxy, deuterated methoxy, cyclopropyl, -O-cyclopropyl, or R 5 is a hydrogen atom, R 4 is a hydrogen atom, R 3a Selected from hydrogen atom, methyl, ethyl, hydroxyl, methoxy, deuterated methoxy, cyclopropyl, In some embodiments, R 3a and R 4 are all hydrogen atoms, R 5 is selected from hydrogen atom, deuterium atom, methyl, deuterated methyl, hydroxyl, methoxy, deuterated methoxy, cyclopropyl, -O-cyclopropyl,

[0375] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R 6 Selected from hydrogen atoms, C 1-6 Alkyl, halogenated C 1-6 Alkyl and C 1-6 Hydroxyalkyl; preferably, R 6 A hydrogen atom or C 1-6 Alkyl; further preferably, R 6 C1-6 Alkyl; most preferably, R 6 is CH3;

[0376] In some embodiments, R 6 Selected from hydrogen atoms, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, 3 to 6 membered cycloalkyl and 3 to 6 membered cycloalkyl C 1-6 Alkyl; in some embodiments, R 6 Selected from C 1-6 Alkyl, 3 to 6 membered cycloalkyl and 3 to 6 membered cycloalkyl C 1-6 Alkyl; in some embodiments, R 6 C 1-6 Alkyl or 3 to 6 membered cycloalkyl C 1-6 Alkyl; in some embodiments, R 6 CH3 or In some embodiments, R 6 is a hydrogen atom;

[0377] In some embodiments, R 6 Selected from hydrogen atoms, C 1-6 Alkyl, deuterated C 1-6 alkyl and 3 to 6 membered cycloalkyl; in some embodiments, R 6 is selected from hydrogen, methyl, deuterated methyl and cyclopropyl; in some embodiments, R 6 is selected from a hydrogen atom, a methyl group, and a deuterated methyl group; in some embodiments, R 6 is a hydrogen atom or a methyl group.

[0378] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R 7 and R 8 are the same or different and are each independently selected from hydrogen atom, C 1-6 Alkyl, halogenated C 1-6 Alkyl and C 1-6 Hydroxyalkyl; preferably, R 7 and R 8 are each independently a hydrogen atom or a C 1-6 Alkyl; further preferably, R 7 and R 8 Each independently is C 1-6 Alkyl; most preferably, R7 and R 8 are CH3; in some embodiments, R 7 and R 8 The same or different, and each independently is C 1-6 alkyl or amino; in some embodiments, R 7 and R 8 are the same or different and are each independently methyl or amino; in some embodiments, R 7 is methyl, R 8 It is an amino group.

[0379] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R 01 Each is independently selected from halogen, hydroxy, cyano, oxo, amino, -NH alkyl, -N (alkyl) 2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl, C 1-6 Halogenated alkoxy, C 1-6 hydroxyalkyl, 3 to 6 membered cycloalkyl and 3 to 6 membered heterocyclyl; in some embodiments, R 01 Each independently selected from halogen, hydroxy, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl and C 1-6 haloalkoxy; in some embodiments, R 01 Each independently selected from halogen, hydroxy, oxo, C 1-6 Alkyl and C 1-6 Alkoxy; in some embodiments, R 01 A deuterium atom.

[0380] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R X1 Selected from hydrogen atoms, halogens, hydroxyl groups, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6alkoxy, 3 to 6-membered cycloalkyl, 4 to 7-membered heterocyclyl, 3 to 6-membered cycloalkyloxy and 4 to 7-membered heterocyclyloxy, wherein the 3 to 6-membered cycloalkyl, 4 to 7-membered heterocyclyl, 3 to 6-membered cycloalkyloxy and 4 to 7-membered heterocyclyloxy are each independently optionally substituted by one or more R 03 Replaced by R 03 are each independently selected from halogen, C 1-6 Alkyl and halogenated C 1-6 Alkyl; preferably, R X1 Selected from hydroxyl, C 1-6 Alkoxy and halogenated C 1-6 Alkoxy; further preferably, R X1 C 1-6 Alkoxy; most preferably, R X1 is methoxy;

[0381] In some embodiments, R X1 Selected from hydroxyl, C 1-6 alkoxy and 3 to 6 membered cycloalkyloxy; in some embodiments, R X1 Selected from hydroxyl, methoxy and In some embodiments, R X1 is hydroxyl; in some embodiments, R X1 for In some embodiments, R X1 Selected from hydroxy, methoxy, deuterated methoxy and In some embodiments, R X1 Selected from hydroxyl, methoxy, OCD3 and In some embodiments, R X1 is deuterated methoxy; in some embodiments, R X1 It is OCD3.

[0382] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R X2 Selected from hydrogen atoms, halogens, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 alkoxy, 3 to 6 membered cycloalkyl and 4 to 7 membered heterocyclic group; preferably, R X2 Selected from hydrogen atoms, halogens, C 1-6 Alkyl and halogenated C 1-6 Alkyl; further preferably, R X2is halogen; most preferably, R X2 is a fluorine atom.

[0383] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R X3 Selected from hydrogen atoms, halogens, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 alkoxy, 3 to 6 membered cycloalkyl and 4 to 7 membered heterocyclic group; preferably, R X3 Selected from hydrogen atoms, halogens, C 1-6 Alkyl and halogenated C 1-6 Alkyl; further preferably, R X3 is halogen; most preferably, R X3 is a fluorine atom.

[0384] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R X1 、R X2 and R X3 are the same or different and are independently selected from hydrogen, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, halogenated C 1-6 alkoxy, 3 to 6 membered cycloalkyloxy and 3 to 6 membered heterocyclyloxy; in some embodiments, R X1 、R X2 and R X3 The same or different, and each independently selected from halogen, hydroxyl, C 1-6 alkoxy and 3 to 6 membered cycloalkyloxy; in some embodiments, R X1 、R X2 and R X3 are the same or different and are each independently selected from F, hydroxy, methoxy and

[0385] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R X1 Selected from hydroxyl, C 1-6 Alkoxy and 3 to 6-membered cycloalkyloxy, and / or R X2 is halogen, and / or R X3 is halogen; in some embodiments, R X1 Selected from hydroxyl, methoxy and and / or R X2 F, and / or R X3 For F.

[0386] In some embodiments of the present disclosure, the compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof, wherein R X4 and R X5 are independently selected from hydrogen atoms, halogens, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl and halogenated C 1-6 Alkoxy; preferably, R X4 and R X5 All are hydrogen atoms.

[0387] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein R 7a and R 8a are the same or different and are each independently selected from hydrogen atom, C 1-6 Alkyl and halogen; in some embodiments, R 7a and R 8a are the same or different and are each independently a hydrogen atom or F.

[0388] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein n is selected from 0, 1, 2 and 3; preferably, n is 0 or 1, and further preferably, n is 0.

[0389] In some embodiments of the present disclosure, the compounds represented by the general formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, wherein s is selected from 0, 1, 2 and 3; preferably, s is 0 or 1, and further preferably, s is 0.

[0390] In some embodiments of the present disclosure, the compound represented by the general formula (I) or (II) or a pharmaceutically acceptable salt thereof, wherein r is selected from 0, 1 and 2; preferably, r is 1; in some embodiments, r is 2.

[0391] In some embodiments of the present disclosure, for the compounds represented by the general formula (I), (II), (II'), (II-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or pharmaceutically acceptable salts thereof, v is 1 or 2; preferably, v is 2.

[0392] In some embodiments of the present disclosure, the compound represented by the general formula (II) or a pharmaceutically acceptable salt thereof, wherein R a and R b Different, and each independently C 1-6 Alkyl or halogenated C 1-6 Alkyl; R c and R d Different, and each independently a hydrogen atom or a C 1-6 Alkyl; X is O; R' is a hydrogen atom or C 1-6 Alkyl; Ring A is pyridyl or pyrimidinyl; R A Selected from amino, R X1 C 1-6 Alkoxy; R X2 is halogen; R X3 is halogen; and r is 1.

[0393] In some embodiments of the present disclosure, the compound represented by the general formula (II) or a pharmaceutically acceptable salt thereof, wherein R a C 1-6 Alkyl, R b Halogenated C 1-6 Alkyl, R c is a hydrogen atom, and R d C 1-6 Alkyl, R' is a hydrogen atom, X is O; for R A Selected from amino, R X1 C 1-6 Alkoxy; R X2 is halogen; R X3 It is a halogen.

[0394] In some embodiments of the present disclosure, the compound represented by the general formula (II') or a pharmaceutically acceptable salt thereof, wherein R a C 1-6 Alkyl, R b Halogenated C 1-6 Alkyl, R c is a hydrogen atom, and R d C 1-6 Alkyl, R' is a hydrogen atom, X is O; Ring A is a pyridyl or pyrimidyl group; r-1 is 0; R 5 is a hydrogen atom; R 3a Selected from hydrogen atoms, C 1-6 Alkyl and C 1-6 Alkoxy; R 4 is a hydrogen atom or a methyl group; R X1 C 1-6 Alkoxy; R X2 is halogen; R X3 It is a halogen.

[0395] In some embodiments of the present disclosure, the compound represented by the general formula (II-1) or a pharmaceutically acceptable salt thereof, wherein R a C 1-6 Alkyl, R b Halogenated C 1-6 Alkyl, R c is a hydrogen atom, and R d C 1-6 Alkyl, R' is a hydrogen atom, X is O; Ring A is a pyridyl or pyrimidyl group; r-1 is 0; R 5 is a hydrogen atom; R 3 Selected from hydrogen atoms, C 1-6 Alkyl and 3 to 6 membered cycloalkyl; R 4 is a hydrogen atom or a methyl group; R X1 C 1-6 Alkoxy; R X2 is halogen; R X3 It is a halogen.

[0396] In some embodiments of the present disclosure, the compound represented by the general formula (IV) or a pharmaceutically acceptable salt thereof, wherein R a CH3, R b CF3, R c is a hydrogen atom, and Rd is CH3, R' is a hydrogen atom, R 1A and R 2A are all hydrogen atoms; R 3A Selected from R X1 is methoxy; R X2 is a fluorine atom; R X3 is a fluorine atom.

[0397] In some embodiments of the present disclosure, the compound represented by the general formula (IV) or a pharmaceutically acceptable salt thereof, wherein R a C 1-6 Alkyl, R b Halogenated C 1-6 Alkyl, R c is a hydrogen atom, and R d C 1-6 Alkyl, R' is a hydrogen atom, R 1A and R 2A are all hydrogen atoms; R 3A Selected from R X1 C 1-6 Alkoxy; R X2 is halogen; R X3 It is a halogen.

[0398] In some embodiments of the present disclosure, the compound represented by the general formula (IV) or a pharmaceutically acceptable salt thereof, wherein R a C 1-6 Alkyl, R b Halogenated C 1-6 Alkyl, R c is a hydrogen atom, and R d C 1-6 Alkyl, R' is a hydrogen atom, R 1A and R 2A are all hydrogen atoms; R 3A -C(O)NR 5 -NR 3 R 4 or -C(=NR 5 )NR 3 -OR 6 , R 3 、R 4 、R 5 and R 6 The same or different, and each independently a hydrogen atom or a C 1-6 Alkyl; R X1 C 1-6 Alkoxy; R X2 is halogen; RX3 It is a halogen.

[0399] In some embodiments of the present disclosure, the compound represented by the general formula (IV) or a pharmaceutically acceptable salt thereof, wherein R a C 1-6 Alkyl, R b Halogenated C 1-6 Alkyl, R c is a hydrogen atom, and R d C 1-6 Alkyl, R' is a hydrogen atom, R 1A and R 2A are all hydrogen atoms; R 3A -C(=NR 5 )NR 3 R 4 , R 3 、R 4 and R 5 are the same or different and are each independently selected from hydrogen atom, C 1-6 Alkyl and 3 to 6 membered cycloalkyl; R X1 C 1-6 Alkoxy; R X2 is halogen; R X3 It is a halogen.

[0400] In some embodiments of the present disclosure, the compound represented by the general formula (IV) or a pharmaceutically acceptable salt thereof, wherein R a C 1-6 Alkyl, R b Halogenated C 1-6 Alkyl, R c is a hydrogen atom, and R d C 1-6 Alkyl, R' is a hydrogen atom, R 1A and R 2A are all hydrogen atoms; R 3A Selected from R X1 C 1-6 Alkoxy; R X2 is halogen; R X3 It is a halogen.

[0401] In some embodiments of the present disclosure, the compound represented by the general formula (VI) or a pharmaceutically acceptable salt thereof, wherein R a C 1-6 Alkyl, R b Halogenated C 1-6 Alkyl, R c is a hydrogen atom, and R d C 1-6 Alkyl, R' is a hydrogen atom, R 1Aand R 2A are all hydrogen atoms; R 5 is a hydrogen atom; R 3a Selected from hydrogen atoms, C 1-6 Alkyl and C 1-6 Alkoxy; R 4 is a hydrogen atom or a methyl group; R X1 C 1-6 Alkoxy; R X2 is halogen; R X3 It is a halogen.

[0402] In some embodiments of the present disclosure, the compound represented by the general formula (VII) or a pharmaceutically acceptable salt thereof, wherein R a C 1-6 Alkyl, R b Halogenated C 1-6 Alkyl, R c is a hydrogen atom, and R d C 1-6 Alkyl, R' is a hydrogen atom, R 1A and R 2A are all hydrogen atoms; R 5 is a hydrogen atom; R 3 Selected from hydrogen atoms, C 1-6 Alkyl and 3 to 6 membered cycloalkyl; R 4 is a hydrogen atom or a methyl group; R X1 C 1-6 Alkoxy; R X2 is halogen; R X3 It is a halogen.

[0403] In some embodiments of the present disclosure, the compound represented by the general formula (VI') or a pharmaceutically acceptable salt thereof, wherein R a C 1-6 Alkyl, R b Halogenated C 1-6 Alkyl, R c is a hydrogen atom, and R d C 1-6 Alkyl, R' is a hydrogen atom, R X1 C 1-6 Alkoxy; R X2 is halogen; R X3 is halogen; R 1A and R 2A are all hydrogen atoms; Q is selected from CR 5A , N and N + -O - ; R 5A is halogen; R 3 Selected from hydrogen atom, methyl, ethyl, methoxy, cyclopropyl, R 4 is a hydrogen atom or a methyl group; R5 A hydrogen atom.

[0404] In some embodiments of the present disclosure, the compound represented by the general formula (VIII) or a pharmaceutically acceptable salt thereof, wherein X is O; R a C 1-6 Alkyl, R b Halogenated C 1-6 Alkyl, R c is a hydrogen atom, and R d C 1-6 Alkyl, R' is a hydrogen atom, R X1 C 1-6 Alkoxy; R X2 is halogen; R X3 is halogen; R 1A and R 2A are all hydrogen atoms; Q is selected from CR 5A , N and N + -O - ; R 5A is halogen; R 3 Selected from hydrogen atom, methyl, ethyl, methoxy, cyclopropyl, R 4 is a hydrogen atom or a methyl group.

[0405] In some embodiments of the present disclosure, the compound represented by the general formula (II) or a pharmaceutically acceptable salt thereof, wherein R a CH3, R b CF3, R c is a hydrogen atom, R d CH3; R X1 Selected from hydroxyl, methoxy and R X2 F, R X3 is F; X is O, and R' is a hydrogen atom; for Each R B are the same or different and are each independently halogen, p is 0 or 1; Ring A is selected from The * end is connected to -NR', End and R A connect;

[0406] R A Selected from F, Cl, amino, cyano,

[0407] In some embodiments of the present disclosure, the compound represented by the general formula (II) or a pharmaceutically acceptable salt thereof, wherein R a CH3, R bCF3, R c is a hydrogen atom, R d CH3; R X1 Selected from hydroxy, methoxy, deuterated methoxy and R X2 F, R X3 is F; X is O, and R' is a hydrogen atom; for R B is F, p is 0 or 1; Ring A is The * end is connected to -NR', End and R A Connect; R A Selected from

[0408] In some embodiments of the present disclosure, the compound represented by the general formula (VI') or a pharmaceutically acceptable salt thereof, wherein R a CH3, R b CF3, R c is a hydrogen atom, R d CH3; R X1 Selected from hydroxyl, methoxy and R X2 F, R X3 is F; R' is a hydrogen atom; R 1A and R 2A are all hydrogen atoms; Q is selected from CR 5A , N and N + -O - ; R 5A is halogen; R 3 Selected from hydrogen atom, methyl, ethyl, hydroxyl, methoxy, cyclopropyl, R 4 is a hydrogen atom or a methyl group; R 5 A hydrogen atom.

[0409] In some embodiments of the present disclosure, the compound represented by the general formula (VI') or a pharmaceutically acceptable salt thereof, wherein R a CH3, R b CF3, R c is a hydrogen atom, R d CH3; R X1 Selected from hydroxy, methoxy, deuterated methoxy and R X2 F, R X3 is F; R' is a hydrogen atom; R 1A and R 2A are all hydrogen atoms; Q is N or CR 5A ; R5A F; R 3 is a hydrogen atom, R 4 is a hydrogen atom; R 5 is selected from hydrogen atom, deuterium atom, methyl, deuterated methyl, hydroxyl, methoxy, deuterated methoxy, cyclopropyl, -O-cyclopropyl,

[0410] In some embodiments of the present disclosure, the compound represented by the general formula (VI') or a pharmaceutically acceptable salt thereof, wherein R a CH3, R b CF3, R c is a hydrogen atom, R d CH3; R X1 Selected from hydroxyl, methoxy and R X2 F, R X3 is F; R' is a hydrogen atom; R 1A and R 2A are all hydrogen atoms; Q is selected from CR 5A , N and N + -O - ; R 5A F; R 3 is a hydrogen atom, R 4 is a hydrogen atom; R 5 Selected from hydrogen atom, methyl, hydroxyl, methoxy, deuterated methoxy, -O-cyclopropyl,

[0411] In some embodiments of the present disclosure, the compound represented by the general formula (IV) or a pharmaceutically acceptable salt thereof, wherein R a CH3, R b CF3, R c is a hydrogen atom, R d CH3; R X1 Selected from hydroxyl, methoxy and R X2 F, R X3 is F; R' is a hydrogen atom; R 1A and R 2A are all hydrogen atoms; R 3A for

[0412] In some embodiments of the present disclosure, the compound represented by the general formula (IV) or a pharmaceutically acceptable salt thereof, wherein R a CH3, R b CF3, R c is a hydrogen atom, R d CH3; R X1 Selected from hydroxyl, methoxy and R X2 F, R X3 is F; R' is a hydrogen atom; R 1A and R 2A are all hydrogen atoms; R A for

[0413] Table A Typical compounds of the present disclosure include, but are not limited to:

[0414] Another aspect of the present disclosure relates to a compound represented by general formula (IIA') or a salt thereof,

[0415] Among them, ring A, R A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 and r-1 are as defined in the general formula (II').

[0416] Another aspect of the present disclosure relates to a compound represented by general formula (IIa') or a salt thereof,

[0417] wherein R* is selected from hydroxy, alkoxy and halogen;

[0418] Ring A, R A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 and r-1 are as defined in the general formula (II').

[0419] Another aspect of the present disclosure relates to a compound represented by general formula (IIIA) or a salt thereof,

[0420] wherein t is selected from 0, 1, 2, 3 and 4;

[0421] R 12 and R 13 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group and a phenyl group; preferably, R 12 and R 13 are the same or different and are each independently selected from hydrogen atom, C 1-6 alkyl and 5 or 6 membered cycloalkyl; most preferably, R 12 and R 13 All are CH3;

[0422] Ring A, R', R a 、R b 、R c 、R d , X, R X1 、R X2 and R X3 As defined in general formula (III).

[0423] Another aspect of the present disclosure relates to a compound represented by general formula (IIIA-1) or a salt thereof,

[0424] wherein t is selected from 0, 1, 2, 3 and 4;

[0425] R 12 and R 13 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group and a phenyl group; preferably, R 12 and R 13 are the same or different and are each independently selected from hydrogen atom, C 1-6 alkyl and 5 or 6 membered cycloalkyl; most preferably, R 12 and R 13 All are CH3;

[0426] Ring A, R', R a 、R b 、R c 、R d , X, R X1 、R X2 and R X3 As defined in general formula (III-1).

[0427] Another aspect of the present disclosure relates to a compound represented by general formula (IVA') or a salt thereof,

[0428] Among them, R1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 and R X3 As defined in formula (IV).

[0429] Another aspect of the present disclosure relates to a compound represented by general formula (IVa') or a salt thereof,

[0430] wherein R* is selected from hydroxy, alkoxy and halogen;

[0431] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 and R X3 As defined in formula (IV).

[0432] Another aspect of the present disclosure relates to a compound represented by general formula (VI'A) or a salt thereof,

[0433] Among them, Q, R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 and R X3 As defined in formula (VI').

[0434] Another aspect of the present disclosure relates to a compound represented by general formula (VII'A) or a salt thereof,

[0435] wherein R* is selected from hydroxy, alkoxy and halogen;

[0436] Q, R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 and R X3 As defined in general formula (VII').

[0437] Another aspect of the present disclosure relates to a compound represented by general formula (VIIIA) or a salt thereof,

[0438] Among them, R L is selected from halogen, hydroxy and alkoxy;

[0439] Q, R 1A 、R 2A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 and R X3 As defined in general formula (VIII).

[0440] Table B Typical intermediate compounds disclosed herein include, but are not limited to:

[0441] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above general formula (I) or a pharmaceutically acceptable salt thereof, the method comprising:

[0442] The compound represented by general formula (Ia) or its salt is subjected to condensation reaction with the compound represented by general formula (Ib) or its salt to obtain the compound represented by general formula (I) or its pharmaceutically acceptable salt, wherein:

[0443] R 10 is a halogen (preferably a chlorine atom) or OH;

[0444] Ring A, R A , R', R a 、R b 、R c 、R d 、R e ,X,X 1 、X 2 、X 3 、X 4 、X 5 and r are as defined in the general formula (I).

[0445] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above general formula (I) or a pharmaceutically acceptable salt thereof, the method comprising:

[0446] The compound represented by the general formula (IA') or its salt is reacted with the compound represented by the general formula (IB') or its salt (preferably hydrochloride) to obtain the compound represented by the general formula (I) or its pharmaceutically acceptable salt, wherein:

[0447] In the general formula (I), at least one R A -C(=NH)NR 5 -OR 6 or -C(=NH)NR 3 R 4 ;

[0448] r is 1, 2, 3, 4 or 5; r-1 is 0, 1, 2, 3 or 4;

[0449] The remaining R A As defined in the general formula (I); Ring A, R', R a 、R b 、R c 、R d 、R e ,X,X 1 、X 2 、X 3 、X 4 、X 5 、R 3 、R 4 、R 5 and R 6 As defined in general formula (I).

[0450] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above general formula (II) or a pharmaceutically acceptable salt thereof, the method comprising:

[0451] The compound represented by general formula (IIa) or its salt is subjected to condensation reaction with the compound represented by general formula (Ib) or its salt to obtain the compound represented by general formula (II) or its pharmaceutically acceptable salt, wherein:

[0452] R 10 is a halogen (preferably a chlorine atom) or OH;

[0453] Ring A, R A , R', R a 、R b 、R c 、R d , X, R X1 、R X2 、R X3 and r are as defined in general formula (II).

[0454] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above general formula (II) or a pharmaceutically acceptable salt thereof, the method comprising:

[0455] The compound represented by the general formula (IIA') or its salt and NH2-R 5 or its salt (preferably hydrochloride) to obtain a compound represented by general formula (II) or a pharmaceutically acceptable salt thereof, wherein:

[0456] In the general formula (II), at least one R A -C(=NR 5 )NR 3 R 4 ;

[0457] r is 1, 2, 3, 4 or 5; r-1 is 0, 1, 2, 3 or 4;

[0458] R 3 and R 4 are all hydrogen atoms; the remaining R A As defined in formula (II);

[0459] Ring A, R', R a 、R b 、R c 、R d , X, R X1 、R X2 、R X3 and R 5 As defined in general formula (II).

[0460] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above general formula (II) or a pharmaceutically acceptable salt thereof, the method comprising:

[0461] The compound represented by general formula (IIA') or its salt is reacted with the compound represented by general formula (IB') or its salt (preferably hydrochloride) to obtain the compound represented by general formula (II) or its pharmaceutically acceptable salt, wherein:

[0462] In the general formula (II), at least one R A -C(=NH)NR 5 -OR 6 or -C(=NH)NR 3 R 4 ;

[0463] r is 1, 2, 3, 4 or 5; r-1 is 0, 1, 2, 3 or 4;

[0464] The remaining R A As defined in formula (II);

[0465] Ring A, R', R a 、R b 、Rc 、R d , X, R X1 、R X2 、R X3 、R 3 、R 4 、R 5 and R 6 As defined in general formula (II).

[0466] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above general formula (II) or a pharmaceutically acceptable salt thereof, the method comprising:

[0467] The compound represented by general formula (IIa') or its salt undergoes amidation reaction with an amine or its salt (preferably hydrochloride) to obtain the compound represented by general formula (II) or its pharmaceutically acceptable salt, wherein:

[0468] The above-mentioned amine is selected from HNR 5 -OR 6 、HNR 5 -NR 3 R 4 and HNR 5 -alkylene-Cy;

[0469] R* is selected from hydroxy, alkoxy and halogen;

[0470] In the general formula (II), at least one R A Selected from -C(O)NR 5 -OR 6 、-C(O)NR 5 -NR 3 R 4 and -C(O)NR 5 -alkylene-Cy; the remaining R A As defined in formula (II);

[0471] r is 1, 2, 3, 4 or 5; r-1 is 0, 1, 2, 3 or 4;

[0472] When the amino group contains a protecting group, the method further comprises the step of removing the protecting group; the amino protecting group is preferably Boc;

[0473] Ring A, R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 、R 5 、R6 and Cy are as defined in general formula (II).

[0474] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (II') or a pharmaceutically acceptable salt thereof, the method comprising:

[0475] The compound represented by the general formula (IIA') or its salt and NH2-R 5 or its salt (preferably hydrochloride) to obtain a compound represented by general formula (II') or a pharmaceutically acceptable salt thereof, wherein:

[0476] R 3a and R 4 All are hydrogen atoms;

[0477] Ring A, R A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 5 and r-1 are as defined in the general formula (II').

[0478] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (II') or a pharmaceutically acceptable salt thereof, the method comprising:

[0479] The compound represented by general formula (IIA') or its salt is reacted with the compound represented by general formula (II'B) or its salt (preferably hydrochloride) to obtain the compound represented by general formula (II') or its pharmaceutically acceptable salt, wherein:

[0480] R 5 is a hydrogen atom;

[0481] Ring A, R A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3a 、R 4 and r-1 are as defined in the general formula (II').

[0482] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (II') or a pharmaceutically acceptable salt thereof, the method comprising:

[0483] The compound represented by general formula (IIa) or its salt undergoes condensation reaction with the compound represented by general formula (II'b) or its salt (preferably hydrochloride) to obtain the compound represented by general formula (II') or its pharmaceutically acceptable salt, wherein,

[0484] R 10 is a halogen (preferably a chlorine atom) or OH;

[0485] Ring A, R A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3a 、R 4 、R 5 and r-1 are as defined in the general formula (II').

[0486] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (II-1) or a pharmaceutically acceptable salt thereof, the method comprising:

[0487] The compound represented by general formula (IIa') or its salt is reacted with the compound represented by general formula (II-1B) or its salt (preferably hydrochloride) to obtain the compound represented by general formula (II-1) or its pharmaceutically acceptable salt, wherein:

[0488] R* is selected from hydroxy, alkoxy and halogen;

[0489] When the amino group contains a protecting group, the method further comprises the step of removing the protecting group; the amino protecting group is preferably Boc;

[0490] Ring A, R A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 、R 5 and r-1 are as defined in the general formula (II-1).

[0491] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (II-1) or a pharmaceutically acceptable salt thereof, the method comprising:

[0492] The compound represented by general formula (IIa) or its salt undergoes condensation reaction with the compound represented by general formula (II-1b) or its salt (preferably hydrochloride) to obtain the compound represented by general formula (II-1) or its pharmaceutically acceptable salt, wherein:

[0493] R 10 is a halogen (preferably a chlorine atom) or OH;

[0494] Ring A, R A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 、R 5 and r-1 are as defined in the general formula (II-1).

[0495] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above general formula (III) or a pharmaceutically acceptable salt thereof, the method comprising:

[0496] The compound represented by general formula (IIIA) or its salt undergoes hydrolysis reaction to obtain the compound represented by general formula (III) or its pharmaceutically acceptable salt, wherein:

[0497] R 12 and R 13 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group and a phenyl group; preferably, R 12 and R 13 are the same or different and are each independently selected from hydrogen atom, C 1-6 alkyl and 5 or 6 membered cycloalkyl; most preferably, R 12 and R 13 All are CH3;

[0498] Ring A, R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 and t are as defined in general formula (III).

[0499] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above general formula (III-1) or a pharmaceutically acceptable salt thereof, the method comprising:

[0500] The compound represented by the general formula (IIIA-1) or its salt undergoes hydrolysis reaction to obtain the compound represented by the general formula (III-1) or its pharmaceutically acceptable salt, wherein:

[0501] R 12 and R 13 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group and a phenyl group; preferably, R 12 and R 13 are the same or different and are each independently selected from hydrogen atom, C 1-6 alkyl and 5 or 6 membered cycloalkyl; most preferably, R 12 and R 13 All are CH3;

[0502] Ring A, R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 and t are as defined in the general formula (III-1).

[0503] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (IV) or a pharmaceutically acceptable salt thereof, the method comprising:

[0504] The compound represented by general formula (IVa) or its salt undergoes a condensation reaction with the compound represented by general formula (IVb) or its salt to obtain the compound represented by general formula (IV) or its pharmaceutically acceptable salt, wherein:

[0505] R 10 is a halogen (preferably a chlorine atom) or OH;

[0506] R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 , R', R 1A 、R 2A and R 3A As defined in formula (IV).

[0507] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (IV) or a pharmaceutically acceptable salt thereof, the method comprising:

[0508] The compound represented by the general formula (IVA') or its salt and NH2-R 5or its salt (preferably hydrochloride) to obtain a compound represented by general formula (IV) or a pharmaceutically acceptable salt thereof, wherein:

[0509] R 3A -C(=NR 5 )NR 3 R 4 ;

[0510] R 3 and R 4 All are hydrogen atoms;

[0511] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 and R 5 As defined in formula (IV).

[0512] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (IV) or a pharmaceutically acceptable salt thereof, the method comprising:

[0513] The compound represented by the general formula (IVA') or its salt is reacted with the compound represented by the general formula (IB') or its salt (preferably hydrochloride) to obtain the compound represented by the general formula (IV) or its pharmaceutically acceptable salt, wherein:

[0514] R 3A -C(=NH)NR 5 -OR 6 or -C(=NH)NR 3 R 4 ;

[0515] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 、R 5 and R 6 As defined in formula (IV).

[0516] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (IV) or a pharmaceutically acceptable salt thereof, the method comprising:

[0517] The compound represented by the general formula (IVa') or its salt undergoes an amidation reaction with an amine or its salt (preferably hydrochloride) to obtain the compound represented by the general formula (IV) or its pharmaceutically acceptable salt, wherein:

[0518] The above-mentioned amine is selected from HNR 5 -OR 6 、HNR 5 -NR 3 R 4 and HNR 5 -alkylene-Cy;

[0519] R* is selected from hydroxy, alkoxy and halogen;

[0520] R 3A Selected from -C(O)NR 5 -OR 6 、-C(O)NR 5 -NR 3 R 4 and -C(O)NR 5 -alkylene-Cy;

[0521] When the amino group contains a protecting group, the method further comprises the step of removing the protecting group; the amino protecting group is preferably Boc;

[0522] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 、R 5 、R 6 and Cy are as defined in general formula (IV).

[0523] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above general formula (V) or a pharmaceutically acceptable salt thereof, the method comprising:

[0524] The compound represented by the general formula (IVa) or its salt undergoes a condensation reaction with the compound represented by the general formula (Vb) or its salt to obtain the compound represented by the general formula (V) or its pharmaceutically acceptable salt, wherein:

[0525] R W1 is a hydrogen atom or an amino protecting group (preferably tert-butylsulfinyl), R W2 is a hydrogen atom or a hydroxyl protecting group (preferably TBS);

[0526] When R W1 is an amino protecting group and / or R W2 When it is a hydroxyl protecting group, the preparation method further comprises the step of removing the protecting group;

[0527] R 10 is a halogen (preferably a chlorine atom) or OH;

[0528] R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 , R', R 1A 、R 2A 、R A4 , u1 and u2 are as defined in the general formula (V).

[0529] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (V-1) or (V-2) or a pharmaceutically acceptable salt thereof, the method comprising:

[0530] The compound represented by the general formula (IVa) or its salt undergoes a condensation reaction with the compound represented by the general formula (V-1b) or its salt to obtain the compound represented by the general formula (V-1) or its pharmaceutically acceptable salt, or,

[0531] The compound represented by the general formula (IVa) or its salt undergoes a condensation reaction with the compound represented by the general formula (V-2b) or its salt to obtain the compound represented by the general formula (V-2) or its pharmaceutically acceptable salt, wherein:

[0532] R W1 is a hydrogen atom or an amino protecting group (preferably tert-butylsulfinyl), R W2 is a hydrogen atom or a hydroxyl protecting group (preferably TBS);

[0533] When R W1 is an amino protecting group and / or R W2 When it is a hydroxyl protecting group, the preparation method further comprises the step of removing the protecting group;

[0534] R 10 is a halogen (preferably a chlorine atom) or OH;

[0535] R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 , R', R 1A 、R2A 、R A4 , u1 and u2 are as defined in the general formula (V-1).

[0536] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (V-1) or (V-2) or a pharmaceutically acceptable salt thereof, the method comprising:

[0537] The compound represented by the general formula (V-1A) or its salt undergoes a deprotection reaction to obtain the compound represented by the general formula (V-1) or its pharmaceutically acceptable salt,

[0538] The compound represented by the general formula (V-2A) or its salt undergoes a deprotection reaction to obtain the compound represented by the general formula (V-2) or its pharmaceutically acceptable salt, wherein:

[0539] R W1 is an amino protecting group, and the amino protecting group is preferably Boc;

[0540] R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 , R', R 1A 、R 2A 、R A4 , u1 and u2 are as defined in the general formula (V-1).

[0541] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (VI') or a pharmaceutically acceptable salt thereof, the method comprising:

[0542] The compound represented by the general formula (IVa) or its salt undergoes a condensation reaction with the compound represented by the general formula (VI'B) or its salt (preferably hydrochloride) to obtain the compound represented by the general formula (VI') or its pharmaceutically acceptable salt, wherein:

[0543] R 10 is a halogen (preferably a chlorine atom) or OH;

[0544] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 、R 4 and R 5As defined in formula (VI').

[0545] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (VI') or a pharmaceutically acceptable salt thereof, the method comprising:

[0546] The compound represented by the general formula (VI'A) or its salt and NH2-R 5 or its salt (preferably hydrochloride) to obtain a compound represented by general formula (VI') or a pharmaceutically acceptable salt thereof, wherein:

[0547] R 3 and R 4 All are hydrogen atoms;

[0548] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A , Q and R 5 As defined in formula (VI').

[0549] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (VI') or a pharmaceutically acceptable salt thereof, the method comprising:

[0550] The compound represented by the general formula (VI'A) or a salt thereof is reacted with the compound represented by the general formula (IB') or a salt thereof (preferably a hydrochloride) to obtain the compound represented by the general formula (VI') or a pharmaceutically acceptable salt thereof, wherein:

[0551] R 5 is a hydrogen atom;

[0552] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 and R 4 As defined in formula (VI').

[0553] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (VI'-1) or a pharmaceutically acceptable salt thereof, the method comprising:

[0554] The compound represented by the general formula (IVa) or its salt undergoes a condensation reaction with the compound represented by the general formula (VI'-1B) or its salt (preferably hydrochloride) to obtain the compound represented by the general formula (VI'-1) or its pharmaceutically acceptable salt, wherein:

[0555] R 10 is a halogen (preferably a chlorine atom) or OH;

[0556] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 、R 5 and R C As defined in general formula (VI'-1).

[0557] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (VI'-1) or a pharmaceutically acceptable salt thereof, the method comprising:

[0558] The compound represented by the general formula (VI'A) or its salt is reacted with the compound represented by the general formula (VI-1B') or its salt (preferably hydrochloride) to obtain the compound represented by the general formula (VI'-1) or its pharmaceutically acceptable salt, wherein:

[0559] R 5 is a hydrogen atom;

[0560] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 and R C As defined in general formula (VI'-1).

[0561] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (VI'-1) or a pharmaceutically acceptable salt thereof, the method comprising:

[0562] The compound represented by the general formula (VI') or its salt (preferably trifluoroacetate) undergoes an amidation reaction with the compound represented by the general formula (VI'-1b) or its salt to obtain the compound represented by the general formula (VI'-1) or its pharmaceutically acceptable salt, wherein:

[0563] R 4 is a hydrogen atom;

[0564] R 10 is halogen (preferably chlorine) or OH;

[0565] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 、R 5 and R C As defined in general formula (VI'-1).

[0566] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (VI) or a pharmaceutically acceptable salt thereof, the method comprising:

[0567] The compound represented by the general formula (IVA') or its salt and NH2-R 5 or its salt (preferably hydrochloride) to obtain a compound represented by general formula (VI) or a pharmaceutically acceptable salt thereof, wherein:

[0568] R 3a and R 4 All are hydrogen atoms;

[0569] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 and R 5 As defined in formula (VI).

[0570] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (VI) or a pharmaceutically acceptable salt thereof, the method comprising:

[0571] The compound represented by general formula (IVA') or its salt is reacted with the compound represented by general formula (II'B) or its salt (preferably hydrochloride) to obtain the compound represented by general formula (VI) or its pharmaceutically acceptable salt, wherein:

[0572] R 5 is a hydrogen atom;

[0573] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3a and R 4 As defined in formula (VI).

[0574] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (VI) or a pharmaceutically acceptable salt thereof, the method comprising:

[0575] The compound represented by general formula (IVa) or its salt undergoes a condensation reaction with the compound represented by general formula (VIb) or its salt (preferably hydrochloride) to obtain the compound represented by general formula (VI) or its pharmaceutically acceptable salt, wherein:

[0576] R 10 is a halogen (preferably a chlorine atom) or OH;

[0577] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A 、R 3a 、R 4 and R 5 As defined in formula (VI).

[0578] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (VII') or a pharmaceutically acceptable salt thereof, the method comprising:

[0579] The compound represented by the general formula (IVa) or its salt undergoes a condensation reaction with the compound represented by the general formula (VII'B) or its salt (preferably hydrochloride) to obtain the compound represented by the general formula (VII') or its pharmaceutically acceptable salt, wherein:

[0580] R 10 is a halogen (preferably a chlorine atom) or OH;

[0581] R'、R a 、R b 、R c 、R d 、R X1 、RX2 、R X3 、R 1A 、R 2A ,Q,R 3 、R 4 and R 5 As defined in general formula (VII').

[0582] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above-mentioned general formula (VII') or a pharmaceutically acceptable salt thereof, the method comprising:

[0583] The compound represented by the general formula (VII') or its salt undergoes an amidation reaction with the compound represented by the general formula (II-1B) or its salt (preferably hydrochloride) to obtain the compound represented by the general formula (VII') or its pharmaceutically acceptable salt, wherein:

[0584] R* is selected from hydroxy, alkoxy and halogen;

[0585] When the amino group contains a protecting group, the method further comprises the step of removing the protecting group; the amino protecting group is preferably Boc;

[0586] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 、R 4 and R 5 As defined in general formula (VII').

[0587] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above general formula (VII) or a pharmaceutically acceptable salt thereof, the method comprising:

[0588] The compound represented by the general formula (IVa') or its salt undergoes an amidation reaction with the compound represented by the general formula (II-1B) or its salt (preferably hydrochloride) to obtain the compound represented by the general formula (VII) or its pharmaceutically acceptable salt,

[0589] R* is selected from hydroxy, alkoxy and halogen;

[0590] When the amino group contains a protecting group, the method further comprises the step of removing the protecting group; the amino protecting group is preferably Boc;

[0591] Among them, R 1A 、R 2A , R', R a、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 and R 5 As defined in general formula (VII).

[0592] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above general formula (VII) or a pharmaceutically acceptable salt thereof, the method comprising:

[0593] The compound represented by general formula (IVa) or its salt undergoes condensation reaction with the compound represented by general formula (VIIb) or its salt (preferably hydrochloride) to obtain the compound represented by general formula (VII) or its pharmaceutically acceptable salt, wherein:

[0594] R 10 is a halogen (preferably a chlorine atom) or OH;

[0595] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A 、R 3 、R 4 and R 5 As defined in general formula (VII).

[0596] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above general formula (VIII) or a pharmaceutically acceptable salt thereof, the method comprising:

[0597] The compound represented by general formula (IIa) or its salt undergoes condensation reaction with the compound represented by general formula (VIIIB) or its salt (preferably hydrochloride) to obtain the compound represented by general formula (VIII) or its pharmaceutically acceptable salt, wherein:

[0598] R 10 is a halogen (preferably a chlorine atom) or OH;

[0599] R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R1A 、R 2A ,Q,R 3 and R 4 As defined in general formula (VIII).

[0600] Another aspect of the present disclosure relates to a method for preparing the compound represented by the above general formula (VIII) or a pharmaceutically acceptable salt thereof, the method comprising:

[0601] The compound represented by the general formula (VIIIA) or its salt undergoes an ester exchange reaction with the compound represented by the general formula (IB') or its salt (preferably hydrochloride) to obtain the compound represented by the general formula (VIII) or its pharmaceutically acceptable salt, wherein:

[0602] R L is an alkoxy group;

[0603] R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 and R 4 As defined in formula (VIII).

[0604] In some embodiments of the present disclosure, the method for preparing the compound represented by the general formula (VIII) or a pharmaceutically acceptable salt thereof, wherein R L C 1-6 Alkoxy; preferably methoxy or ethoxy.

[0605] In some embodiments of the present disclosure, the method for preparing the compound represented by the general formula (II), (II-1), (IV) or (VII) or a pharmaceutically acceptable salt thereof, wherein R* is selected from hydroxyl, C 1-6 alkoxy and halogen; in some embodiments, R* is selected from hydroxy, methoxy, ethoxy, and chloro; in some embodiments, R* is hydroxy.

[0606] In some embodiments of the present disclosure, the method for preparing the compound represented by the general formula (II), (II-1), (IV) or (VII) or a pharmaceutically acceptable salt thereof, wherein R 4 Selected from hydrogen atoms, C 1-6 Alkyl and amino protecting groups, when R 4 When it is an amino protecting group, the amidation reaction further includes a step of removing the amino protecting group.

[0607] Another aspect of the present disclosure relates to a method for preparing a compound represented by the above-mentioned general formula (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII') or (VIII) or a pharmaceutically acceptable salt thereof, the method comprising: X1 A compound represented by the general formula (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII') or (VIII) or a pharmaceutically acceptable salt thereof, wherein R is an alkoxy or cycloalkoxy group, undergoes a dealkylation reaction or a decycloalkylation reaction to obtain R X1 A compound represented by the general formula (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII') or (VIII) wherein -OH is -OH, or a pharmaceutically acceptable salt thereof.

[0608] The present invention discloses a method for preparing a compound represented by the above-mentioned general formula (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII') or (VIII) or a pharmaceutically acceptable salt thereof, wherein R X1 Selected from methoxy, deuterated methoxy and In some embodiments, R X1 Methoxy or

[0609] Another aspect of the present disclosure relates to a pharmaceutical composition comprising a compound of the present disclosure of formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or shown in Table A, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents or excipients.

[0610] The present disclosure further relates to the use of a compound of formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or as shown in Table A, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, in the preparation of a medicament for inhibiting voltage-gated sodium channels; preferably, the voltage-gated sodium channel is Nav1.8.

[0611] The present disclosure further relates to the use of a compound of formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or a compound shown in Table A or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, in the preparation of a medicament for treating and / or preventing a disease or condition mediated by a voltage-gated sodium channel, preferably, the voltage-gated sodium channel is Nav1.8.

[0612] The present disclosure further relates to the use of a compound of formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or as shown in Table A, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, in the preparation of a medicament for treating and / or alleviating pain and pain-related diseases, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough or arrhythmia; preferably, the pain is selected from chronic pain, acute pain, inflammatory pain, cancer pain, postoperative pain, neuropathic pain, musculoskeletal pain, primary pain, intestinal pain, idiopathic pain; the postoperative pain is preferably selected from bunionectomy pain, hernia repair pain and abdominoplasty pain.

[0613] The present disclosure further relates to a method for inhibiting voltage-gated sodium channels, comprising administering to a patient in need thereof a compound of Formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or as shown in Table A, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same; preferably, the voltage-gated sodium channel is Nav1.8.

[0614] The present disclosure further relates to a method for treating and / or preventing a disease or condition mediated by a voltage-gated sodium channel, comprising administering to a patient in need thereof a compound of Formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or a compound shown in Table A, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same; preferably, the voltage-gated sodium channel is Nav1.8.

[0615] The present disclosure further relates to a method for treating and / or preventing pain and pain-related diseases, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough or arrhythmia, which comprises administering to a patient in need thereof a compound of formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or a compound shown in Table A or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same; preferably, the pain is selected from chronic pain, acute pain, inflammatory pain, cancer pain, postoperative pain, neuropathic pain, musculoskeletal pain, primary pain, intestinal pain and idiopathic pain; and the postoperative pain is preferably selected from bunionectomy pain, hernia repair pain and abdominoplasty pain.

[0616] The present disclosure further relates to a compound of formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or shown in Table A, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, for use as a drug; preferably, for use as a drug for inhibiting the activity of voltage-gated sodium channels.

[0617] The present disclosure further relates to a compound of formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or shown in Table A, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, for inhibiting voltage-gated sodium channels; preferably, the voltage-gated sodium channel is Nav1.8.

[0618] The present disclosure further relates to a compound of Formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or as shown in Table A, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, for use as a voltage-gated sodium channel inhibitor.

[0619] The present disclosure further relates to a compound of formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or shown in Table A, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, for use as a drug for treating and / or preventing diseases or conditions mediated by voltage-gated sodium channels.

[0620] The present disclosure further relates to a compound of formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or shown in Table A, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, for use in treating and / or preventing a disease or condition mediated by a voltage-gated sodium channel; preferably, the voltage-gated sodium channel is Nav1.8.

[0621] The present disclosure further relates to a compound of formula (I), (II), (II'), (II-1), (III), (III-1), (IV), (V), (V-1), (V-2), (VI), (VII), (VI'), (VI'-1), (VII'), (VIII) or shown in Table A, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, for treating and / or preventing pain and pain-related diseases, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough or arrhythmia; preferably, the pain is selected from chronic pain, acute pain, inflammatory pain, cancer pain, neuropathic pain, musculoskeletal pain, primary pain, intestinal pain and idiopathic pain; and the postoperative pain is preferably selected from bunionectomy pain, hernia repair pain and abdominoplasty pain.

[0622] The diseases or conditions described in the present disclosure are diseases or conditions that are treated and / or prevented by inhibiting voltage-gated sodium channels; preferably, the voltage-gated sodium channel is Nav1.8.

[0623] Preferably, the disease or condition mediated by voltage-gated sodium channels described in the present disclosure is pain and pain-related diseases, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence or arrhythmia; preferably, the pain is selected from chronic pain, acute pain, inflammatory pain, cancer pain, neuropathic pain, musculoskeletal pain, primary pain, intestinal pain and idiopathic pain.

[0624] The neuropathic pain described in the present disclosure is preferably selected from trigeminal neuralgia, postherpetic neuralgia, diabetic neuropathy, painful HIV-related sensory neuralgia, burning syndrome, post-amputation pain, pain after spinal cord injury, phantom pain, painful neuroma, traumatic neuroma, Morton's neuroma, nerve crush injury, spinal stenosis, carpal tunnel syndrome, radicular pain, sciatica, nerve avulsion, brachial plexus avulsion, complex regional pain syndrome, drug-induced neuralgia, cancer chemotherapy-induced neuralgia, antiretroviral therapy-induced neuralgia, primary small fiber neuropathy, primary sensory neuralgia and trigeminal autonomic cephalalgia; preferably, the neuropathic pain is selected from postherpetic neuralgia, small fiber neuralgia, diabetic neuropathy or idiopathic small fiber neuralgia.

[0625] The musculoskeletal pain described in the present disclosure is preferably selected from osteoarthritis pain, back pain, cold pain, burning pain and toothache.

[0626] The intestinal pain described in the present disclosure is preferably selected from inflammatory bowel disease pain, Crohn's disease pain or interstitial cystitis pain.

[0627] The inflammatory pain described in the present disclosure is preferably selected from rheumatoid arthritis pain and vulvar pain.

[0628] Idiopathic pain as described in this disclosure includes fibromyalgia.

[0629] Acute pain as used in the present disclosure includes acute postoperative pain.

[0630] The postoperative pain in the present disclosure includes joint replacement pain, soft tissue surgery pain, bunionectomy pain, hernia repair pain and abdominoplasty pain; preferably selected from bunionectomy pain, hernia repair pain and abdominoplasty pain.

[0631] The disease or disorder of the present disclosure is selected from acute pain, chronic pain, neuropathic pain, inflammatory pain, arthritis, migraine, cluster headache, trigeminal neuralgia, herpetic neuralgia, general neuralgia, epilepsy, epileptic disorders, neurodegenerative disorders, psychiatric disorders, anxiety disorders, depression, bipolar disorder, myotonia, arrhythmias, movement disorders, neuroendocrine disorders, ataxia, multiple sclerosis, irritable bowel syndrome, incontinence, pathological cough, visceral pain, osteoarthritis pain, postherpetic neuralgia, diabetic neuropathy, radicular pain, sciatica, back pain, headache, neck pain, severe pain, intractable pain, nociceptive pain, breakthrough pain, postoperative pain, cancer pain, stroke, cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, stress-induced angina, exercise-induced angina, palpitations, hypertension, or abnormal gastrointestinal motility.

[0632] The pain and pain-related diseases of the present disclosure are selected from the group consisting of femoral cancer pain, non-malignant chronic bone pain, rheumatoid arthritis, osteoarthritis, spinal stenosis, neuropathic low back pain, myofascial pain syndrome, muscle fiber pain, temporomandibular joint pain, chronic visceral pain, abdominal pain, pancreatic pain, IBS pain, chronic and acute headaches, migraines, tension headaches, cluster headaches, chronic and acute neuropathic pain, post-herpetic neuralgia, diabetic neuropathy, HIV-related neuropathy, trigeminal neuralgia, Chuck-Mare-Duchesne neuropathy, hereditary sensory neuropathies, peripheral nerve injury, painful neuromas, ectopic proximal and distal discharges, radiculopathy, chemotherapy-induced neuropathic pain, radiation therapy-induced neuropathic pain, post-mastectomy pain, central pain, spinal cord injury pain, Post-stroke pain, thalamic pain, complex regional pain syndrome, phantom pain, phantom limb pain, intractable pain, acute pain, acute postoperative pain, acute musculoskeletal pain, joint pain, mechanical low back pain, neck pain, tendonitis, injury pain, movement pain, acute visceral pain, pyelonephritis, appendicitis, cholecystitis, intestinal obstruction, hernia, chest pain, cardiac pain, pelvic pain, renal colic, acute labor pain, labor pain, cesarean section pain, acute inflammatory pain, burn pain, traumatic pain, acute intermittent pain, endometriosis, acute herpes zoster pain, sickle cell anemia, acute pancreatitis, breakthrough pain, orofacial pain, sinusitis pain, dental pain, multiple sclerosis (MS) pain, pain in depression, leprosy pain, Behcet's disease disease pain, adiposity dolorosa, phlebitis pain, Guillain-Barre pain, leg pain and dyskinesia, Haglund syndrome, erythromelalgia, Fabry's disease pain, bladder and genitourinary disorders, urinary incontinence, pathological cough, hyperresponsive bladder, painful bladder syndrome, interstitial cystitis (IC), prostatitis, complex regional pain syndrome (CRPS) type I, complex regional pain syndrome (CRPS) type II, widespread pain, paroxysmal severe pain, pruritus, tinnitus, or colic-induced pain.

[0633] The diseases or conditions of the present disclosure are selected from acute pain, subacute and chronic pain, nociceptive pain, neuropathic pain, inflammatory pain, nociceptive pain, arthritis, migraine, cluster headache, trigeminal neuralgia, herpetic neuralgia, general neuralgia, epilepsy, epileptic disorders, neurodegenerative disorders, psychiatric disorders, anxiety, depression, bipolar disorder, myotonia, arrhythmias, movement disorders, neurodegenerative diseases, endocrine disorders, ataxia, central neuropathic pain of multiple sclerosis and irritable bowel syndrome, incontinence, pathological cough, visceral pain, osteoarthritis pain, postherpetic neuralgia, diabetic neuropathy, radicular pain, sciatica, back pain, nonspecific chronic back pain, head pain, neck pain, moderate pain, severe pain, intractable pain, nociceptive pain, breakthrough pain, postoperative pain, cancer pain (including chronic cancer pain and breakthrough cancer pain), stroke (e.g., central neuropathic pain after stroke), cervical sprain related diseases, fragility fractures, spinal fractures, ankylosis Spondylitis, pemphigus, Raynaud's disease, scleroderma, systemic lupus erythematosus, epidermolysis bullosa, gout, juvenile idiopathic arthritis, polymyalgia rheumatica, pyoderma gangrenosum, chronic widespread pain, diffuse idiopathic skeletal hyperostosis, pain from disc degeneration / herniation, radiculopathy, facet joint syndrome, failed back surgery syndrome, burns, carpal tunnel syndrome, Paget's disease pain, spinal stenosis, spondylitis, transverse myelitis, Ehlers-Danlos syndrome, Fabry disease, mast cell hyperplasia The present invention also provides the present invention for the treatment of various diseases, such as polymyalgia, neurofibromatosis, ocular neuropathic pain, sarcoidosis, spondylolisthesis, spondylolisthesis, oral mucositis caused by chemotherapy, Charcot neuroarthropathy, temporomandibular joint disorder, arthroplasty pain, non-cardiac chest pain, pudendal pain, renal colic, biliary tract disease, vascular leg ulcers, Parkinson's disease pain, Alzheimer's disease pain, cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, stress-induced angina, exercise-induced angina, palpitations, hypertension or gastrointestinal motility disorders. The active compound can be prepared into a form suitable for administration by any appropriate route, and the composition of the present invention can be prepared using one or more pharmaceutically acceptable carriers by conventional methods. Therefore, the active compound of the present invention can be formulated into various dosage forms for oral administration, injection (e.g., intravenous, intramuscular or subcutaneous) administration, inhalation or insufflation administration. The compounds of the present disclosure may also be formulated into dosage forms such as tablets, hard or soft capsules, aqueous or oily suspensions, emulsions, injectable solutions, dispersible powders or granules, suppositories, lozenges, or syrups.

[0634] As a general guide, the active compounds of the present disclosure are preferably presented in unit dosage form, or in a form that a patient can self-administer as a single dose. A unit dosage form of a compound or composition of the present disclosure may be a tablet, capsule, cachet, bottled solution, powder, granule, lozenge, suppository, reconstituted powder, or liquid formulation. Suitable unit dosage forms may range from 0.1 to 1000 mg.

[0635] The pharmaceutical composition of the present disclosure may contain one or more excipients in addition to the active compound, selected from the following ingredients: fillers (diluents), binders, wetting agents, disintegrants or excipients, etc. Depending on the administration method, the composition may contain 0.1 to 99% by weight of the active compound.

[0636] In some embodiments, the unit dose of the pharmaceutical composition is 0.001 mg-1000 mg.

[0637] In certain embodiments, the pharmaceutical composition contains 0.01-99.99% of the aforementioned compound or its pharmaceutically acceptable salt or its isotopic substitution, based on the total weight of the composition. In certain embodiments, the pharmaceutical composition contains 0.1-99.9% of the aforementioned compound or its pharmaceutically acceptable salt or its isotopic substitution. In certain embodiments, the pharmaceutical composition contains 0.5%-99.5% of the aforementioned compound or its pharmaceutically acceptable salt or its isotopic substitution. In certain embodiments, the pharmaceutical composition contains 1%-99% of the aforementioned compound or its pharmaceutically acceptable salt or its isotopic substitution. In certain embodiments, the pharmaceutical composition contains 2%-98% of the aforementioned compound or its pharmaceutically acceptable salt or its isotopic substitution.

[0638] In certain embodiments, the pharmaceutical composition comprises 0.01% to 99.99% of a pharmaceutically acceptable excipient, based on the total weight of the composition. In certain embodiments, the pharmaceutical composition comprises 0.1% to 99.9% of a pharmaceutically acceptable excipient. In certain embodiments, the pharmaceutical composition comprises 0.5% to 99.5% of a pharmaceutically acceptable excipient. In certain embodiments, the pharmaceutical composition comprises 1% to 99% of a pharmaceutically acceptable excipient. In certain embodiments, the pharmaceutical composition comprises 2% to 98% of a pharmaceutically acceptable excipient.

[0639] The pharmaceutically acceptable salts of the compounds described in the present disclosure may be selected from inorganic salts or organic salts.

[0640] Tablets contain the active ingredient in admixture with nontoxic, pharmaceutically acceptable excipients suitable for tablet preparation. These excipients may include inert excipients, granulating agents, disintegrants, binders, and lubricants. Tablets may be uncoated or coated using known techniques that mask the taste of the drug or delay disintegration and absorption in the gastrointestinal tract, thereby providing a sustained-release effect over a longer period of time.

[0641] Oral formulations may also be provided in soft gelatin capsules wherein the active ingredient is mixed with an inert solid diluent or with a water-soluble carrier or oil-soluble vehicle.

[0642] Aqueous suspensions contain the active substance in admixture with excipients suitable for the preparation of aqueous suspensions. Such excipients are suspending agents, dispersing agents, or wetting agents. Aqueous suspensions may also contain one or more preservatives, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents.

[0643] Oil suspensions can be prepared by suspending the active ingredient in a vegetable oil or mineral oil. The oil suspension may contain a thickener. The above-mentioned sweeteners and flavoring agents may be added to provide a palatable preparation. These compositions may be preserved by adding antioxidants.

[0644] The pharmaceutical compositions of the present disclosure may also be in the form of oil-in-water emulsions. The oil phase may be a vegetable oil, a mineral oil, or a mixture thereof. Suitable emulsifiers may be naturally occurring phospholipids, and the emulsion may also contain sweeteners, flavorings, preservatives, and antioxidants. Such formulations may also contain demulcents, preservatives, colorants, and antioxidants.

[0645] The pharmaceutical compositions disclosed herein may be in the form of sterile injectable aqueous solutions. Acceptable vehicles or solvents that may be used include water, Ringer's solution, and isotonic sodium chloride solution. Sterile injectable formulations may be sterile injectable oil-in-water microemulsions in which the active ingredient is dissolved in an oil phase. The injectable solution or microemulsion may be administered into the patient's bloodstream via local, bolus injection. Alternatively, the solution or microemulsion may be administered in a manner that maintains a constant circulating concentration of the disclosed compound. To maintain this constant concentration, a continuous intravenous drug delivery device may be used. An example of such a device is the Deltec CADD-PLUS™ 5400 intravenous pump.

[0646] Pharmaceutical compositions of the present disclosure may be in the form of sterile water for injection or oil suspensions for intramuscular and subcutaneous administration. The suspensions may be prepared using suitable dispersants or wetting agents and suspending agents as described above according to known techniques. Sterile injectable formulations may also be sterile injectable solutions or suspensions prepared in parenteral, nontoxic diluents or solvents. In addition, sterile fixed oils may be conveniently used as solvents or suspension media. For this purpose, any blended fixed oil may be used. In addition, fatty acids may also be used to prepare injections.

[0647] The disclosed compounds can be administered in the form of suppositories for rectal administration. These pharmaceutical compositions can be prepared by mixing the drug with a suitable non-irritating excipient that is solid at ordinary temperatures but liquid in the rectum and will therefore melt in the rectum to release the drug.

[0648] The compounds of the present disclosure can be administered by preparing water-suspended dispersible powders and granules by adding water. These pharmaceutical compositions can be prepared by mixing the active ingredient with a dispersing or wetting agent, a suspending agent, or one or more preservatives.

[0649] As is well known to those skilled in the art, the dosage of a drug depends on a variety of factors, including but not limited to the following: the activity of the specific compound used, the severity of the disease, the age of the patient, the weight of the patient, the health status of the patient, the behavior of the patient, the diet of the patient, the time of administration, the mode of administration, the rate of excretion, the combination of drugs, etc.; in addition, the optimal treatment method such as the mode of treatment, the daily dose of the compound or the type of pharmaceutically acceptable salt can be verified according to traditional treatment regimens.

[0650] Terminology

[0651] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[0652] The term "alkyl" refers to a saturated straight-chain or branched aliphatic hydrocarbon group having 1 to 20 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20) carbon atoms (i.e., C 1-20 The alkyl group is preferably an alkyl group having 1 to 12 carbon atoms (i.e., C 1-12 alkyl), more preferably an alkyl group having 1 to 6 carbon atoms (i.e., C 1-6Non-limiting examples include: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2 ,3-dimethylpentyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl, and various branched-chain isomers thereof. The alkyl group may be substituted or unsubstituted. When substituted, it may be substituted at any available point of attachment, and the substituents are preferably selected from one or more of a D atom, a halogen, an alkoxy group, a haloalkyl group, a haloalkoxy group, a cycloalkyloxy group, a heterocyclyloxy group, a hydroxyl group, a hydroxyalkyl group, a cyano group, an amino group, a nitro group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group.

[0653] The term "alkylene" refers to a divalent alkyl group, wherein alkyl is as defined above, having from 1 to 20 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) carbon atoms (i.e., C 1-20 The alkylene group is preferably an alkylene group having 1 to 12 carbon atoms (i.e., C 1-12 alkylene), more preferably an alkylene group having 1 to 6 carbon atoms (i.e., C 1-6Alkylene). Non-limiting examples include: -CH2-, -CH(CH3)-, -C(CH3)2-, -CH2CH2-, -CH(CH2CH3)-, -CH2CH(CH3)-, -CH2C(CH3)2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, etc. Alkylene can be substituted or unsubstituted. When substituted, it can be substituted at any available point of attachment. The substituents are preferably selected from one or more of D atoms, halogen, alkoxy, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclyloxy, hydroxyl, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl.

[0654] The term "alkenyl" refers to an alkyl group containing at least one carbon-carbon double bond in the molecule, wherein alkyl is as defined above and has 2 to 12 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12) carbon atoms (i.e., C 2-12 The alkenyl group is preferably an alkenyl group having 2 to 6 carbon atoms (i.e., C 2-6 Alkenyl). Non-limiting examples include: ethenyl, propenyl, isopropenyl, butenyl, etc. Alkenyl can be substituted or unsubstituted. When substituted, it can be substituted at any available point of attachment, and the substituent is preferably selected from one or more of D atoms, alkoxy, halogen, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclyloxy, hydroxyl, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl, and heteroaryl.

[0655] The term "alkynyl" refers to an alkyl group containing at least one carbon-carbon triple bond in the molecule, wherein alkyl is as defined above and has 2 to 12 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12) carbon atoms (i.e., C 2-12 The alkynyl group is preferably an alkynyl group having 2 to 6 carbon atoms (i.e., C 2-6 Alkynyl). Non-limiting examples include: ethynyl, propynyl, butynyl, pentynyl, hexynyl, etc. Alkynyl can be substituted or unsubstituted. When substituted, it can be substituted at any available point of attachment, and the substituent is preferably selected from one or more of D atoms, alkoxy, halogen, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclyloxy, hydroxyl, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl, and heteroaryl.

[0656] The term "alkoxy" refers to -O-(alkyl), wherein alkyl is as defined above. Non-limiting examples include methoxy, ethoxy, propoxy, and butoxy. Alkoxy groups may be substituted or unsubstituted. When substituted, they may be substituted at any available point of attachment, with the substituent preferably being selected from one or more of a D atom, halogen, alkoxy, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclyloxy, hydroxyl, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl, and heteroaryl.

[0657] The term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic all-carbon ring (i.e., monocyclic cycloalkyl) or a polycyclic ring system (i.e., polycyclic cycloalkyl) having 3 to 20 (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., 3 to 20-membered cycloalkyl). The cycloalkyl group is preferably a cycloalkyl group having 3 to 12 ring atoms (i.e., 3 to 12-membered cycloalkyl) and a cycloalkyl group having 3 to 10 ring atoms (i.e., 3 to 10-membered cycloalkyl), more preferably a cycloalkyl group having 3 to 8 ring atoms (i.e., 3 to 8-membered cycloalkyl), and most preferably a cycloalkyl group having 3 to 6 ring atoms (i.e., 3 to 6-membered cycloalkyl).

[0658] Non-limiting examples of the monocyclic cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl and cyclooctyl.

[0659] The polycyclic cycloalkyl group includes: spirocycloalkyl group, fused cycloalkyl group and bridged cycloalkyl group.

[0660] The term "spiroalkyl" refers to a polycyclic ring system having a common carbon atom (called a spiro atom) between the rings, which may contain one or more double bonds within the ring, or one or more heteroatoms selected from nitrogen, oxygen and sulfur (the nitrogen may be optionally oxidized to form nitrogen oxides; the sulfur may be optionally oxoed to form sulfoxides or sulfones, but does not include -OO-, -OS- or -SS-), provided that it contains at least one all-carbon ring and the point of attachment is on the all-carbon ring, and has 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20) ring atoms (i.e., a 5- to 20-membered spiroalkyl). The spiroalkyl preferably has 6 to 14 ring atoms (i.e., a 6- to 14-membered spiroalkyl), and more preferably has 7 to 10 ring atoms (i.e., a 7- to 10-membered spiroalkyl). The spirocycloalkyl group includes a monospirocycloalkyl group and a polyspirocycloalkyl group (such as a bispirocycloalkyl group, etc.), preferably a monospirocycloalkyl group or a bispirocycloalkyl group, more preferably a 3-membered / 4-membered, 3-membered / 5-membered, 3-membered / 6-membered, 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 3-membered, 5-membered / 4-membered, 5-membered / 5-membered, 5-membered / 6-membered, 5-membered / 7-membered, 6-membered / 3-membered, 6-membered / 4-membered, 6-membered / 5-membered, 6-membered / 6-membered, 6-membered / 7-membered, 7-membered / 5-membered or 7-membered / 6-membered monospirocycloalkyl group. Non-limiting examples include:

[0661] Its connection point can be at any position;

[0662] wait.

[0663] The term "fused cycloalkyl" refers to a polycyclic ring system in which two adjacent carbon atoms are shared between the rings, which is a monocyclic cycloalkyl fused to one or more monocyclic cycloalkyls, or a monocyclic cycloalkyl fused to one or more heterocyclyls, aryls, or heteroaryls, wherein the point of attachment is on the monocyclic cycloalkyl, which may contain one or more double bonds within the ring, and has 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., a 5- to 20-membered fused cycloalkyl). The fused cycloalkyl is preferably a fused cycloalkyl having 6 to 14 ring atoms (i.e., a 6- to 14-membered fused cycloalkyl), more preferably a fused cycloalkyl having 7 to 10 ring atoms (i.e., a 7- to 10-membered fused cycloalkyl). The fused cycloalkyl group includes bicyclic fused cycloalkyl groups and polycyclic fused cycloalkyl groups (such as tricyclic fused cycloalkyl groups, tetracyclic fused cycloalkyl groups, etc.), preferably bicyclic fused cycloalkyl groups or tricyclic fused cycloalkyl groups, more preferably 3-membered / 4-membered, 3-membered / 5-membered, 3-membered / 6-membered, 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 3-membered, 5-membered / 4-membered, 5-membered / 5-membered, 5-membered / 6-membered, 5-membered / 7-membered, 6-membered / 3-membered, 6-membered / 4-membered, 6-membered / 5-membered, 6-membered / 6-membered, 6-membered / 7-membered, 7-membered / 5-membered or 7-membered / 6-membered bicyclic fused cycloalkyl groups. Non-limiting examples include:

[0664] Its connection point can be at any position;

[0665] wait.

[0666] The term "bridged cycloalkyl" refers to a full carbon polycyclic ring system that shares two carbon atoms that are not directly connected between the rings, which may contain one or more double bonds within the ring and has 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20) carbon atoms (i.e., a 5 to 20-membered bridged cycloalkyl). The bridged cycloalkyl preferably has a bridged cycloalkyl of 6 to 14 carbon atoms (i.e., a 6 to 14-membered bridged cycloalkyl), more preferably a bridged cycloalkyl of 7 to 10 carbon atoms (i.e., a 7 to 10-membered bridged cycloalkyl). The bridged cycloalkyl includes bicyclic bridged cycloalkyl and polycyclic bridged cycloalkyl (e.g., tricyclic bridged cycloalkyl, tetracyclic bridged cycloalkyl, etc.), preferably bicyclic bridged cycloalkyl or tricyclic bridged cycloalkyl. Non-limiting examples include:

[0667] Its connection point can be at any position.

[0668] The cycloalkyl group may be substituted or unsubstituted. When substituted, it may be substituted at any available point of attachment, and the substituents are preferably selected from one or more of a D atom, a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a cycloalkyloxy group, a heterocyclyloxy group, a hydroxyl group, a hydroxyalkyl group, an oxo group, a cyano group, an amino group, a nitro group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group.

[0669] The term "heterocyclyl" refers to a saturated or partially unsaturated monocyclic heterocycle (i.e., a monocyclic heterocyclyl) or a polycyclic heterocyclic ring system (i.e., a polycyclic heterocyclyl) containing at least one (e.g., 1, 2, 3, or 4) heteroatoms selected from nitrogen, oxygen, and sulfur (the nitrogen may be optionally oxidized, i.e., to form nitrogen oxides; the sulfur may be optionally oxoed, i.e., to form sulfoxides or sulfones, but excluding -OO-, -OS-, or -SS-) in the ring, and having 3 to 20 (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., a 3- to 20-membered heterocyclyl). The heterocyclic group is preferably a heterocyclic group having 3 to 12 ring atoms (i.e., a 3- to 12-membered heterocyclic group); further preferably a heterocyclic group having 3 to 10 ring atoms (i.e., a 3- to 10-membered heterocyclic group) and a heterocyclic group having 3 to 8 ring atoms (i.e., a 3- to 8-membered heterocyclic group); more preferably a heterocyclic group having 4 to 7 ring atoms (i.e., a 4- to 7-membered heterocyclic group); more preferably a heterocyclic group having 3 to 6 ring atoms (i.e., a 3- to 6-membered heterocyclic group); most preferably a heterocyclic group having 5 or 6 ring atoms (i.e., a 5- or 6-membered heterocyclic group) or a heterocyclic group having 3 to 4 ring atoms (i.e., a 3- to 4-membered heterocyclic group).

[0670] Non-limiting examples of the monocyclic heterocyclic group include pyrrolidinyl, tetrahydropyranyl, 1,2,3,6-tetrahydropyridinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl and homopiperazinyl.

[0671] The polycyclic heterocyclic group includes a spiro heterocyclic group, a fused heterocyclic group and a bridged heterocyclic group.

[0672] The term "spiroheterocyclyl" refers to a polycyclic heterocyclic ring system in which the rings share one atom (called a spiro atom), which may contain one or more double bonds in the ring and at least one (e.g., 1, 2, 3 or 4) heteroatom selected from nitrogen, oxygen and sulfur (the nitrogen may be optionally oxidized, i.e., to form a nitrogen oxide; the sulfur may be optionally oxidized, i.e., to form a sulfoxide or sulfone, but excluding -OO-, -OS- or -SS-), provided that it contains at least one monocyclic heterocyclic group and the point of attachment is on the monocyclic heterocyclic group, which has 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20) ring atoms (i.e., a 5- to 20-membered spiroheterocyclyl). The spiro heterocyclic radical preferably has a spiro heterocyclic radical (i.e., a 6 to 14 yuan spiro heterocyclic radical) of 6 to 14 ring atoms, more preferably a spiro heterocyclic radical (i.e., a 7 to 10 yuan spiro heterocyclic radical) with 7 to 10 ring atoms. The spiro heterocyclic radical includes monospiro heterocyclic radical and polyspiro heterocyclic radical (such as dispiro heterocyclic radical etc.), preferably monospiro heterocyclic radical or dispiro heterocyclic radical, more preferably 3 yuan / 4 yuan, 3 yuan / 5 yuan, 3 yuan / 6 yuan, 4 yuan / 4 yuan, 4 yuan / 5 yuan, 4 yuan / 6 yuan, 5 yuan / 3 yuan, 5 yuan / 4 yuan, 5 yuan / 5 yuan, 5 yuan / 6 yuan, 5 yuan / 7 yuan, 6 yuan / 3 yuan, 6 yuan / 4 yuan, 6 yuan / 5 yuan, 6 yuan / 6 yuan, 6 yuan / 7 yuan, 7 yuan / 5 yuan or 7 yuan / 6 yuan monospiro heterocyclic radical. Non-limiting examples include:

[0673] wait.

[0674] The term "fused heterocyclyl" refers to a polycyclic heterocyclic ring system that shares two adjacent atoms between the rings, which may contain one or more double bonds within the ring and at least one (e.g., 1, 2, 3, or 4) heteroatom selected from nitrogen, oxygen, and sulfur (the nitrogen may be optionally oxidized, i.e., to form a nitrogen oxide; the sulfur may be optionally oxoed, i.e., to form a sulfoxide or sulfone, but excluding -OO-, -OS-, or -SS-), which is a monocyclic heterocyclyl fused to one or more monocyclic heterocyclyls, or a monocyclic heterocyclyl fused to one or more cycloalkyl, aryl, or heteroaryl groups, wherein the point of attachment is on the monocyclic heterocyclyl, and has 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., a 5- to 20-membered fused heterocyclyl). The fused heterocyclic radical preferably has a fused heterocyclic radical of 6 to 14 ring atoms (i.e., a 6 to 14-membered fused heterocyclic radical), more preferably a fused heterocyclic radical of 7 to 10 ring atoms (i.e., a 7 to 10-membered fused heterocyclic radical). The fused heterocyclic radical includes bicyclic and polycyclic fused heterocyclic radicals (such as tricyclic fused heterocyclic radicals, tetracyclic fused heterocyclic radicals, etc.), preferably bicyclic fused heterocyclic radicals or tricyclic fused heterocyclic radicals, more preferably 3 yuan / 4 yuan, 3 yuan / 5 yuan, 3 yuan / 6 yuan, 4 yuan / 4 yuan, 4 yuan / 5 yuan, 4 yuan / 6 yuan, 5 yuan / 3 yuan, 5 yuan / 4 yuan, 5 yuan / 5 yuan, 5 yuan / 6 yuan, 5 yuan / 7 yuan, 6 yuan / 3 yuan, 6 yuan / 4 yuan, 6 yuan / 5 yuan, 6 yuan / 6 yuan, 6 yuan / 7 yuan, 7 yuan / 5 yuan or 7 yuan / 6 yuan bicyclic fused heterocyclic radicals. Non-limiting examples include:

[0675] wait.

[0676] The term "bridged heterocyclic group" refers to a polycyclic heterocyclic ring system that shares two atoms that are not directly connected between the rings, which may contain one or more double bonds within the ring and at least one (e.g., 1, 2, 3, or 4) heteroatom selected from nitrogen, oxygen, and sulfur (the nitrogen may be optionally oxidized, i.e., to form a nitrogen oxide; the sulfur may be optionally oxidized, i.e., to form a sulfoxide or sulfone, but excluding -OO-, -OS-, or -SS-), and has 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., a 5- to 20-membered bridged heterocyclic group). The bridged heterocyclic group is preferably a bridged heterocyclic group having 6 to 14 ring atoms (i.e., a 6- to 14-membered bridged heterocyclic group), and more preferably a bridged heterocyclic group having 7 to 10 ring atoms (i.e., a 7- to 10-membered bridged heterocyclic group). According to the number of constituent rings, heterocyclic groups can be divided into bicyclic bridged heterocyclic groups and polycyclic bridged heterocyclic groups (such as tricyclic bridged heterocyclic groups, tetracyclic bridged heterocyclic groups, etc.), preferably bicyclic bridged heterocyclic groups or tricyclic bridged heterocyclic groups. Non-limiting examples include:

[0677] wait.

[0678] The heterocyclic group may be substituted or unsubstituted. When substituted, it may be substituted at any available point of attachment. The substituents are preferably selected from one or more of a D atom, a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a cycloalkyloxy group, a heterocyclic group, a hydroxyl group, a hydroxyalkyl group, an oxo group, a cyano group, an amino group, a nitro group, a cycloalkyl group, a heterocyclic group, an aryl group, and a heteroaryl group.

[0679] The term "aryl" refers to a monocyclic all-carbon aromatic ring (i.e., a monocyclic aromatic group) or a polycyclic aromatic ring system (i.e., a polycyclic aromatic group) having a conjugated π electron system, which has 6 to 14 (e.g., 6, 7, 8, 9, 10, 11, 12, 13 or 14) ring atoms (i.e., a 6- to 14-membered aromatic group). The aryl group is preferably an aromatic group having 6 to 10 ring atoms (i.e., a 6- to 10-membered aromatic group). The monocyclic aromatic group is, for example, a phenyl group. Non-limiting examples of the polycyclic aromatic group include: naphthyl, anthracenyl, phenanthrenyl, etc. The polycyclic aromatic group also includes a phenyl group fused with one or more heterocyclic groups or cycloalkyl groups, or a naphthyl group fused with one or more heterocyclic groups or cycloalkyl groups, wherein the connection point is on the phenyl group or naphthyl group, and in this case, the number of ring atoms continues to represent the number of ring atoms in the polycyclic aromatic ring system, non-limiting examples include:

[0680] wait.

[0681] The aryl group may be substituted or unsubstituted. When substituted, it may be substituted at any available point of attachment, and the substituents are preferably selected from one or more of a D atom, a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a cycloalkyloxy group, a heterocyclyloxy group, a hydroxyl group, a hydroxyalkyl group, an oxo group, a cyano group, an amino group, a nitro group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group.

[0682] The term "heteroaryl" refers to a monocyclic heteroaromatic ring (i.e., a monocyclic heteroaryl) or a polycyclic heteroaromatic ring system (i.e., a polycyclic heteroaryl) having a conjugated π electron system, which contains at least one (e.g., 1, 2, 3, or 4) heteroatoms selected from nitrogen, oxygen, and sulfur (the nitrogen may be optionally oxidized, i.e., to form a nitrogen oxide; the sulfur may be optionally oxidized, i.e., to form a sulfoxide or sulfone, but excluding -OO-, -OS-, or -SS-), and has 5 to 14 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14) ring atoms (i.e., a 5- to 14-membered heteroaryl). The heteroaryl is preferably a heteroaryl having 5 to 10 ring atoms (i.e., a 5- to 10-membered heteroaryl), more preferably a heteroaryl having 5 or 6 ring atoms (i.e., a 5- or 6-membered heteroaryl).

[0683] The monocyclic heteroaryl groups include, but are not limited to, furyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furazanyl, pyrrolyl, N-alkylpyrrolyl, pyridyl, pyrimidinyl, pyridonyl, N-alkylpyridone (e.g. etc.), pyrazinyl, pyridazinyl, etc.

[0684] The polycyclic heteroaryl groups include, but are not limited to, indolyl, indazolyl, quinolyl, isoquinolyl, quinoxalinyl, phthalazinyl, benzimidazolyl, benzothiophenyl, quinazolinyl, benzothiazolyl, carbazolyl, and the like. The polycyclic heteroaryl groups also include monocyclic heteroaryl groups fused to one or more aromatic groups, wherein the point of attachment is on the aromatic ring, and in this case, the number of ring atoms continues to represent the number of ring atoms in the polycyclic heteroaromatic ring system. The polycyclic heteroaryl groups also include monocyclic heteroaryl groups fused to one or more cycloalkyl or heterocyclic groups, wherein the point of attachment is on the monocyclic heteroaromatic ring, and in this case, the number of ring atoms continues to represent the number of ring atoms in the polycyclic heteroaromatic ring system. Non-limiting examples include:

[0685] wait.

[0686] The heteroaryl group may be substituted or unsubstituted. When substituted, it may be substituted at any available point of attachment, and the substituents are preferably selected from one or more of a D atom, a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a cycloalkyloxy group, a heterocyclyloxy group, a hydroxyl group, a hydroxyalkyl group, a cyano group, an amino group, a nitro group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group.

[0687] The term "amino protecting group" refers to a group that is easily removed and introduced onto an amino group in order to keep the amino group unchanged while reacting other parts of the molecule. Non-limiting examples include: (trimethylsilyl)ethoxymethyl, tetrahydropyranyl, tert-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), methyloxycarbonyl (Fmoc), allyloxycarbonyl (Alloc), trimethylsilylethoxycarbonyl (Teoc), methoxycarbonyl, ethoxycarbonyl, phthaloyl (Pht), p-toluenesulfonyl (Tos), tert-butylsulfinyl, trifluoroacetyl (Tfa), trichloroacetyl, trityl (Trt), 2,4-dimethoxybenzyl (DMB), p-methoxybenzyl (PMB), acetyl, benzyl, allyl, p-methoxybenzyl, and the like.

[0688] The term "hydroxy protecting group" refers to a group that is introduced on a hydroxy group and is easily removed, and is used to block or protect the hydroxy group while reacting on other functional groups of the compound. Non-limiting examples include: trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), tert-butyldimethylsilyl (TBS), tert-butyldimethylsilyl (TBDMS), tert-butyldiphenylsilyl (TBDPS), methyl, tert-butyl, allyl, benzyl, methoxymethyl (MOM), ethoxyethyl, 2-tetrahydropyranyl (THP), formyl, acetyl, benzoyl, p-nitrobenzoyl, etc.

[0689] The term "cycloalkylalkyl" refers to an alkyl group substituted with one or more cycloalkyl groups, wherein cycloalkyl and alkyl are as defined above.

[0690] The term "heterocyclylalkyl" refers to an alkyl group substituted by one or more heterocyclyl groups, wherein heterocyclyl and alkyl are as defined above.

[0691] The term "alkoxyalkyl" refers to an alkyl group substituted by one or more alkoxy groups, wherein alkoxy and alkyl are as defined above.

[0692] The term "cycloalkyloxy" refers to a cycloalkyl-O- group in which cycloalkyl is as defined above.

[0693] The term "heterocyclyloxy" refers to a heterocyclyl-O- group in which heterocyclyl is as defined above.

[0694] The term "aryloxy" refers to an aryl-O- group in which the aryl group is as defined above.

[0695] The term "heteroaryloxy" refers to a heteroaryl-O- group in which heteroaryl is as defined above.

[0696] The term "alkylthio" refers to an alkyl-S- group in which alkyl is as defined above.

[0697] The term "haloalkyl" refers to an alkyl group substituted with one or more halogens, wherein alkyl is as defined above.

[0698] The term "haloalkoxy" refers to an alkoxy group substituted with one or more halogens, wherein alkoxy is as defined above.

[0699] The term "deuterated alkyl" refers to an alkyl group substituted with one or more deuterium atoms, wherein alkyl is as defined above.

[0700] The term "hydroxyalkyl" refers to an alkyl group substituted with one or more hydroxy groups, wherein alkyl is as defined above.

[0701] The term "hydroxyalkoxy" refers to an alkoxy group substituted with one or more hydroxy groups, wherein alkoxy is as defined above.

[0702] The term "methylidene" refers to =CH2.

[0703] The term "deuterated methyl" refers to a methyl group substituted with one or more deuterium atoms, such as CHD2, CH2D and CD3; preferably CD3.

[0704] The term "deuterated methoxy" refers to -O-deuterated methyl, where deuterated methyl is as defined above, such as OCD3.

[0705] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0706] The term "hydroxy" refers to -OH.

[0707] The term "mercapto" refers to -SH.

[0708] The term "amino" refers to -NH2.

[0709] The term "cyano" refers to -CN.

[0710] The term "nitro" refers to -NO2.

[0711] The term "oxo" or "oxo" refers to "=0".

[0712] The term "carbonyl" refers to C=O.

[0713] The term "acetyl" refers to -C(O)CH3.

[0714] The term "amido" refers to -C(O)NH2.

[0715] The term "carboxy" refers to -C(O)OH.

[0716] The term "carboxylate" refers to -C(O)O(alkyl), -C(O)O(cycloalkyl), (alkyl)C(O)O-, or (cycloalkyl)C(O)O-, where alkyl and cycloalkyl are as defined above.

[0717] The compounds of the present disclosure may exist in specific stereoisomeric forms. The term "stereoisomer" refers to isomers that have the same structure but different arrangements of atoms in space. This includes cis and trans (or Z and E) isomers, (-)- and (+)-isomers, - and (S)-enantiomers, diastereomers, (D)- and (L)-isomers, tautomers, atropisomers, conformers and mixtures thereof (e.g., racemates, mixtures of diastereomers). The substituents in the compounds disclosed herein may have additional asymmetric atoms. All of these stereoisomers and mixtures thereof are included within the scope of the present disclosure. Optically active (-)- and (+)-isomers, (R)- and (S)-enantiomers, and (D)- and (L)-isomers can be prepared by chiral synthesis, chiral reagents or other conventional techniques. An isomer of a compound disclosed herein can be prepared by asymmetric synthesis or chiral auxiliary agents, or, when the molecule contains a basic functional group (e.g., amino) or an acidic functional group (e.g., carboxyl), it can be formed into diastereomeric salts with an appropriate optically active acid or base, and then diastereomeric separation can be performed by conventional methods known in the art to obtain pure isomers. Furthermore, separation of enantiomers and diastereomers is often accomplished by chromatography.

[0718] In the chemical structures of the compounds disclosed herein, the bond Indicates that the configuration is not specified, that is, if chiral isomers exist in the chemical structure, the bond Can be or include both Two configurations. In the chemical structure of the compound disclosed in the present invention, the bond The configuration is not specified, that is, it can be Z or E, or both. For all carbon-carbon double bonds, even if only one configuration is named, both Z and E are included; The configuration is not specified, that is, it can be Z configuration or E configuration, or contain both configurations.

[0719] In the chemical structures of the compounds disclosed herein, the bond to the stereogenic center of the compound is or like In the formula (a), represents the relative configuration of the stereogenic center; wherein, compound 1a of Example 1 is a mixture of 1b-1 and 1b-2.

[0720] The compounds of the present disclosure may exist in different tautomeric forms, and all such forms are included within the scope of the present disclosure. The term "tautomer" or "tautomeric form" refers to a structural isomer that exists in equilibrium and is readily converted from one isomeric form to another. This includes all possible tautomers, i.e., existing as a single isomer or as a mixture of any proportions of the tautomers. Non-limiting examples include: keto-enol, imine-enamine, lactam-lactim, etc. An example of an enamine-imine equilibrium is shown below:

[0721] "Amidines", also known as iminoamides, are compounds in which the carbonyl oxygen atom in the amide molecule is replaced by an imino group. The imino and amino groups of the amidines can convert into each other to form tautomers. The tautomerism of amidines is shown below:

[0722] For example, when referring to pyrazolyl, it is understood to include either of the following two structures or a mixture of two tautomers:

[0723] All tautomeric forms are within the scope of the present disclosure, and the naming of compounds does not exclude any tautomer.

[0724] The compounds of the present disclosure include all suitable isotopic derivatives of the compounds thereof. The term "isotopic derivative" refers to a compound in which at least one atom is replaced by an atom having the same atomic number but a different atomic mass. Examples of isotopes that can be introduced into the compounds of the present disclosure include stable and radioactive isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine, and iodine, for example, 2 H (deuterium, D), 3 H (tritium, T), 11 C. 13 C. 14 C. 15 N. 17 O. 18 O. 32 p、 33 p、 33 S. 34 S. 35 S. 36 S. 18 F. 36 Cl, 82 Br, 123 I. 124 I. 125 I. 129 I and 131 I, etc., preferably deuterium.

[0725] Compared to non-deuterated drugs, deuterated drugs have advantages such as reduced toxic side effects, increased drug stability, enhanced efficacy, and prolonged biological half-life. All isotopic variations of the compounds disclosed herein, whether radioactive or not, are encompassed by the present disclosure. Each available hydrogen atom attached to a carbon atom can be independently replaced with a deuterium atom, where the deuterium replacement can be partial or complete. Partial deuterium replacement refers to the replacement of at least one hydrogen atom with at least one deuterium atom.

[0726] Compounds of the present disclosure, when a position is specifically designated as "deuterium" or "D," are understood to have an abundance of deuterium at that position that is at least 1000 times greater than the natural abundance of deuterium (which is 0.015%) (i.e., at least 15% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 1000 times greater than the natural abundance of deuterium (i.e., at least 15% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 2000 times greater than the natural abundance of deuterium (i.e., at least 30% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 3000 times greater than the natural abundance of deuterium (i.e., at least 45% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 3340 times greater than the natural abundance of deuterium (i.e., at least 50.1% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 3500 times greater than the natural abundance of deuterium (i.e., at least 52.5% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 4000 times greater than the natural abundance of deuterium (i.e., at least 60% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 4500 times greater than the natural abundance of deuterium (i.e., at least 67.5% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 5000 times greater than the natural abundance of deuterium (i.e., at least 75% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 5500 times greater than the natural abundance of deuterium (i.e., at least 82.5% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 6000 times greater than the natural abundance of deuterium (i.e., at least 90% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 6333.3 times greater than the natural abundance of deuterium (i.e., at least 95% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 6466.7 times greater than the natural abundance of deuterium (i.e., at least 97% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 6600 times greater than the natural abundance of deuterium (i.e., at least 99% deuterium incorporation). In some embodiments, the abundance of deuterium for each designated deuterium atom is at least 6633.3 times greater than the natural abundance of deuterium (ie, at least 99.5% deuterium incorporation).

[0727] "Optional" or "optionally" means that the event or circumstances described subsequently may but need not occur, and includes both situations in which the event or circumstances occur and do not occur. For example, "alkyl optionally (optionally) substituted with halogen or cyano" includes both situations in which the alkyl is substituted with halogen or cyano and situations in which the alkyl is not substituted with halogen and cyano.

[0728] "Substitution" or "substituted" means that one or more hydrogen atoms, preferably 1 to 6, more preferably 1 to 3 hydrogen atoms, in a group are independently replaced by a corresponding number of substituents. Those skilled in the art can determine (by experiment or theory) whether substitution is possible or not without undue effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom with an unsaturated bond (such as an alkene).

[0729] A "pharmaceutical composition" refers to a mixture containing one or more compounds described herein, or pharmaceutically acceptable salts thereof, and other chemical components, as well as other components such as pharmaceutically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to an organism, facilitating absorption of the active ingredients and thereby exerting their biological activity.

[0730] "Pharmaceutically acceptable salts" refer to salts of the compounds of the present disclosure, which may be selected from inorganic or organic salts. Such salts are safe and effective for use in mammals and possess the desired biological activity. They can be prepared during the final isolation and purification of the compound, or separately by reacting a suitable group with a suitable base or acid. Bases commonly used to form pharmaceutically acceptable salts include inorganic bases, such as sodium hydroxide and potassium hydroxide, and organic bases, such as ammonia. Acids commonly used to form pharmaceutically acceptable salts include inorganic acids and organic acids.

[0731] The term "pharmaceutically acceptable" as used herein refers to compounds, materials, compositions and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with patient tissues without excessive toxicity, irritation, allergic response or other problems or complications, commensurate with a reasonable benefit / risk ratio, and effective for the intended use.

[0732] As used herein, the singular form "a," "an," and "the" include plural references and vice versa unless the context clearly dictates otherwise.

[0733] When the term "about" is applied to a parameter such as pH, concentration, temperature, etc., it indicates that the parameter can vary by ±10%, and sometimes more preferably within ±5%. As will be understood by those skilled in the art, when a parameter is not critical, numbers are generally given for illustrative purposes only and are not limiting.

[0734] Synthesis method of the disclosed compound

[0735] In order to achieve the purpose of this disclosure, the present disclosure adopts the following technical solutions:

[0736] Option 1

[0737] The present disclosure provides a method for preparing a compound represented by general formula (I) or a pharmaceutically acceptable salt thereof, the method comprising:

[0738] The compound represented by general formula (Ia) or its salt is subjected to condensation reaction with the compound represented by general formula (Ib) or its salt under alkaline conditions to obtain the compound represented by general formula (I) or its pharmaceutically acceptable salt.

[0739] R 10 is a halogen (preferably a chlorine atom) or OH;

[0740] Among them, when R 10 When it is OH, the reaction occurs in the presence of a condensing agent;

[0741] Ring A, R A , R', R a 、R b 、R c 、R d 、R e ,X,X 1 、X 2 、X 3 、X 4 、X 5 and r are as defined in the general formula (I).

[0742] Plan 1-1

[0743] The present disclosure provides a method for preparing a compound represented by general formula (I) or a pharmaceutically acceptable salt thereof, the method comprising:

[0744] The compound represented by the general formula (IA') or its salt and the compound represented by the general formula (IB') or its salt (preferably hydrochloride) undergo a Pinner reaction in the presence of a catalyst to obtain the compound represented by the general formula (I) or its pharmaceutically acceptable salt.

[0745] Preferably, the compound represented by the general formula (IA') or its salt is reacted with the compound represented by the general formula (IB') or its salt (preferably hydrochloride) in the presence of thioglycolic acid and a base to obtain the compound represented by the general formula (I) or its pharmaceutically acceptable salt, wherein:

[0746] In the general formula (I), at least one R A -C(=NH)NR 5 -OR 6 or -C(=NH)NR 3 R 4 ;

[0747] r is 1, 2, 3, 4 or 5; r-1 is 0, 1, 2, 3 or 4;

[0748] The remaining R A As defined in formula (I);

[0749] Ring A, R', R a、R b 、R c 、R d 、R e ,X,X 1 、X 2 、X 3 、X 4 、X 5 、R 3 、R 4 、R 5 and R 6 As defined in general formula (I).

[0750] Option 2

[0751] The present disclosure provides a method for preparing a compound represented by general formula (II) or a pharmaceutically acceptable salt thereof, the method comprising:

[0752] The compound represented by general formula (IIa) or its salt is subjected to a condensation reaction with the compound represented by general formula (Ib) or its salt under alkaline conditions to obtain the compound represented by general formula (II) or its pharmaceutically acceptable salt, wherein:

[0753] R 10 is a halogen (preferably a chlorine atom) or OH;

[0754] Among them, when R 10 When is OH, the reaction occurs in the presence of a condensing agent or oxalyl chloride, preferably in the presence of a condensing agent;

[0755] Ring A, R A , R', R a 、R b 、R c 、R d , X, R X1 、R X2 、R X3 and r are as defined in general formula (II).

[0756] Option 2-1

[0757] The present disclosure provides a method for preparing a compound represented by general formula (II) or a pharmaceutically acceptable salt thereof, the method comprising:

[0758] The compound represented by the general formula (IIA') or its salt and the compound represented by the general formula (IB') or its salt (preferably hydrochloride) undergo a Pinner reaction in the presence of a catalyst to obtain the compound represented by the general formula (II) or its pharmaceutically acceptable salt.

[0759] Preferably, the compound represented by the general formula (IIA') or its salt is reacted with the compound represented by the general formula (IB') or its salt (preferably hydrochloride) in the presence of thioglycolic acid and a base to obtain the compound represented by the general formula (II) or its pharmaceutically acceptable salt, wherein:

[0760] In the general formula (II), at least one R A -C(=NH)NR 5 -OR 6 or -C(=NH)NR 3 R 4 ;

[0761] r is 1, 2, 3, 4 or 5; r-1 is 0, 1, 2, 3 or 4;

[0762] The remaining R A As defined in formula (II);

[0763] Ring A, R', R a 、R b 、R c 、R d , X, R X1 、R X2 、R X3 、R 3 、R 4 、R 5 and R 6 As defined in general formula (II).

[0764] Option 2-2

[0765] The present disclosure provides a method for preparing a compound represented by general formula (II) or a pharmaceutically acceptable salt thereof, the method comprising:

[0766] The compound represented by general formula (IIa') or its salt undergoes amidation reaction with an amine or its salt (preferably hydrochloride) to obtain the compound represented by general formula (II) or its pharmaceutically acceptable salt, wherein:

[0767] The above-mentioned amine is selected from HNR 5 -OR 6 、HNR 5 -NR 3 R 4 and HNR 5 -alkylene-Cy;

[0768] R* is selected from hydroxy, alkoxy and halogen;

[0769] In the general formula (II), at least one R A Selected from -C(O)NR 5 -OR 6 、-C(O)NR5 -NR 3 R 4 and -C(O)NR 5 -alkylene-Cy;

[0770] The remaining R A As defined in formula (II);

[0771] r is 1, 2, 3, 4 or 5; r-1 is 0, 1, 2, 3 or 4;

[0772] When the amino group contains a protecting group, the method further comprises the step of removing the protecting group; the amino protecting group is preferably Boc;

[0773] Ring A, R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 、R 5 、R 6 and Cy are as defined in general formula (II).

[0774] Option 2-3

[0775] The present disclosure provides a method for preparing a compound represented by general formula (II) or a pharmaceutically acceptable salt thereof, the method comprising: X1 The compound represented by the general formula (II) or its pharmaceutically acceptable salt which is an alkoxy or cycloalkoxy group undergoes dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 A compound represented by the general formula (II) wherein -OH is -OH, or a pharmaceutically acceptable salt thereof.

[0776] Option 2-4

[0777] The present disclosure provides a method for preparing a compound represented by general formula (II) or a pharmaceutically acceptable salt thereof, the method comprising:

[0778] The compound represented by the general formula (IIA') or its salt and NH2-R 5 or its salt (preferably hydrochloride) in the presence of a catalyst to undergo a Pinner reaction to obtain a compound represented by general formula (II) or a pharmaceutically acceptable salt thereof,

[0779] In the general formula (II), at least one R A -C(=NR 5 )NR 3 R 4 ;

[0780] r is 1, 2, 3, 4 or 5; r-1 is 0, 1, 2, 3 or 4;

[0781] R 3 and R 4 All are hydrogen atoms;

[0782] The remaining R A As defined in formula (II);

[0783] Ring A, R', R a 、R b 、R c 、R d , X, R X1 、R X2 、R X3 and R 5 As defined in general formula (II).

[0784] Option 2-A

[0785] The present disclosure provides a method for preparing a compound represented by general formula (II') or a pharmaceutically acceptable salt thereof, the method comprising:

[0786] The compound represented by the general formula (IIA') or its salt and the compound represented by the general formula (II'B) or its salt (preferably hydrochloride) undergo a pinner reaction in the presence of a catalyst to obtain the compound represented by the general formula (II') or its pharmaceutically acceptable salt, wherein:

[0787] R 5 is a hydrogen atom;

[0788] Ring A, R A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3a 、R 4 and r-1 are as defined in the general formula (II').

[0789] Option 2-A1

[0790] The present disclosure provides a method for preparing a compound represented by general formula (II') or a pharmaceutically acceptable salt thereof, the method comprising:

[0791] The compound represented by general formula (IIa) or its salt and the compound represented by general formula (II'b) or its salt (preferably hydrochloride) undergo condensation reaction under alkaline conditions to obtain the compound represented by general formula (II') or its pharmaceutically acceptable salt, wherein,

[0792] R 10 is a halogen (preferably a chlorine atom) or OH; when R 10 When is OH, the reaction occurs in the presence of a condensing agent or oxalyl chloride, preferably in the presence of a condensing agent;

[0793] Ring A, R A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3a 、R 4 、R 5 and r-1 are as defined in the general formula (II').

[0794] Option 2-A2

[0795] The present disclosure provides a method for preparing a compound represented by general formula (II') or a pharmaceutically acceptable salt thereof, the method comprising: X1 The compound represented by the general formula (II') or its pharmaceutically acceptable salt which is an alkoxy or cycloalkoxy group undergoes dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 The compound represented by the general formula (II') or a pharmaceutically acceptable salt thereof is -OH.

[0796] Option 2-A3

[0797] The present disclosure provides a method for preparing a compound represented by general formula (II') or a pharmaceutically acceptable salt thereof, the method comprising:

[0798] The compound represented by the general formula (IIA') or its salt and NH2-R 5 or its salt (preferably hydrochloride) in the presence of a catalyst to undergo a Pinner reaction to obtain a compound represented by general formula (II') or a pharmaceutically acceptable salt thereof, wherein:

[0799] R 3a and R 4 All are hydrogen atoms;

[0800] Ring A, R A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 5 and r-1 are as defined in the general formula (II').

[0801] Option 2-B

[0802] The present disclosure provides a method for preparing a compound represented by general formula (II-1) or a pharmaceutically acceptable salt thereof, the method comprising:

[0803] The compound represented by the general formula (IIa') or its salt undergoes an amidation reaction with the compound represented by the general formula (II-1B) or its salt (preferably hydrochloride) under alkaline conditions to obtain the compound represented by the general formula (II-1) or its pharmaceutically acceptable salt, wherein:

[0804] R* is selected from hydroxy, alkoxy and halogen;

[0805] When the amino group contains a protecting group, the method further comprises the step of removing the protecting group; the amino protecting group is preferably Boc;

[0806] Ring A, R A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 、R 5 and r-1 are as defined in the general formula (II-1).

[0807] Option 2-B1

[0808] The present disclosure provides a method for preparing a compound represented by general formula (II-1) or a pharmaceutically acceptable salt thereof, the method comprising:

[0809] The compound represented by general formula (IIa) or its salt and the compound represented by general formula (II-1b) or its salt (preferably hydrochloride) undergo condensation reaction under alkaline conditions to obtain the compound represented by general formula (II-1) or its pharmaceutically acceptable salt, wherein,

[0810] R 10 is a halogen (preferably a chlorine atom) or OH; when R 10 When is OH, the reaction occurs in the presence of a condensing agent or oxalyl chloride, preferably in the presence of a condensing agent;

[0811] Ring A, R A , R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R3 、R 4 、R 5 and r-1 are as defined in the general formula (II-1).

[0812] Option 2-B2

[0813] The present disclosure provides a method for preparing a compound represented by general formula (II-1) or a pharmaceutically acceptable salt thereof, the method comprising: X1 The compound represented by the general formula (II-1) or its pharmaceutically acceptable salt which is an alkoxy or cycloalkoxy group undergoes dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 A compound represented by the general formula (II-1) wherein -OH is -OH, or a pharmaceutically acceptable salt thereof.

[0814] Option 3

[0815] The present disclosure provides a method for preparing a compound represented by general formula (III) or a pharmaceutically acceptable salt thereof, the method comprising:

[0816] The compound represented by general formula (IIIA) or its salt is hydrolyzed under acidic conditions to obtain the compound represented by general formula (III) or its pharmaceutically acceptable salt, wherein:

[0817] R 12 and R 13 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group and a phenyl group; preferably, R 12 and R 13 are the same or different and are each independently selected from hydrogen atom, C 1-6 alkyl and 5 or 6 membered cycloalkyl; most preferably, R 12 and R 13 All are CH3;

[0818] Ring A, R', R a 、R b 、R c 、R d , X, R X1 、R X2 、R X3 and t are as defined in general formula (III).

[0819] Plan 3-1

[0820] The present disclosure provides a method for preparing a compound represented by general formula (III) or a pharmaceutically acceptable salt thereof, the method comprising: X1 The compound represented by the general formula (III) or its pharmaceutically acceptable salt which is an alkoxy or cycloalkoxy group undergoes dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 A compound represented by the general formula (III) wherein -OH is -OH, or a pharmaceutically acceptable salt thereof.

[0821] Option 4

[0822] The present disclosure provides a method for preparing a compound represented by general formula (III-1) or a pharmaceutically acceptable salt thereof, the method comprising:

[0823] The compound represented by the general formula (IIIA-1) or a salt thereof is hydrolyzed under acidic conditions to obtain the compound represented by the general formula (III-1) or a pharmaceutically acceptable salt thereof, wherein:

[0824] R 12 and R 13 are the same or different and are each independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group and a phenyl group; preferably, R 12 and R 13 are the same or different and are each independently selected from hydrogen atom, C 1-6 alkyl and 5 or 6 membered cycloalkyl; most preferably, R 12 and R 13 All are CH3;

[0825] Ring A, R', R a 、R b 、R c 、R d , X, R X1 、R X2 、R X3 and t are as defined in the general formula (III-1).

[0826] Plan 4-1

[0827] The present disclosure provides a method for preparing a compound represented by general formula (III-1) or a pharmaceutically acceptable salt thereof, the method comprising: X1 The compound represented by the general formula (III-1) or a pharmaceutically acceptable salt thereof, which is an alkoxy or cycloalkoxy group, undergoes a dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 A compound represented by the general formula (III-1) wherein -OH is -OH, or a pharmaceutically acceptable salt thereof.

[0828] Plan 5

[0829] The present disclosure provides a method for providing a compound represented by general formula (IV) or a pharmaceutically acceptable salt thereof, the method comprising:

[0830] The compound represented by general formula (IVa) or its salt undergoes a condensation reaction with the compound represented by general formula (IVb) or its salt under alkaline conditions to obtain the compound represented by general formula (IV) or its pharmaceutically acceptable salt, wherein:

[0831] R 10 is a halogen (preferably a chlorine atom) or OH;

[0832] Among them, when R 10 When is OH, the reaction occurs in the presence of a condensing agent or oxalyl chloride, preferably in the presence of a condensing agent;

[0833] R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 , R', R 1A 、R 2A and R 3A As defined in formula (IV).

[0834] Plan 5-1

[0835] The present disclosure provides a method for providing a compound represented by general formula (IV) or a pharmaceutically acceptable salt thereof, the method comprising:

[0836] The compound represented by the general formula (IVA') or its salt reacts with the compound represented by the general formula (IB') or its salt (preferably hydrochloride) in the presence of a catalyst to obtain the compound represented by the general formula (IV) or its pharmaceutically acceptable salt.

[0837] Preferably, the compound represented by the general formula (IVA') or its salt is reacted with the compound represented by the general formula (IB') or its salt (preferably hydrochloride) in the presence of thioglycolic acid and a base to obtain the compound represented by the general formula (IV) or its pharmaceutically acceptable salt, wherein:

[0838] R 3A -C(=NH)NR 5 -OR 6 or -C(=NH)NR 3 R 4 ;

[0839] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 、R 5 and R 6 As defined in formula (IV).

[0840] Plan 5-2

[0841] The present disclosure provides a method for providing a compound represented by general formula (IV) or a pharmaceutically acceptable salt thereof, the method comprising:

[0842] The compound represented by the general formula (IVa') or its salt undergoes an amidation reaction with an amine or its salt (preferably hydrochloride) under alkaline conditions to obtain the compound represented by the general formula (IV) or its pharmaceutically acceptable salt, wherein:

[0843] The above-mentioned amine is selected from HNR 5 -OR 6 、HNR 5 -NR 3 R 4 and HNR 5 -alkylene-Cy;

[0844] R* is selected from hydroxy, alkoxy and halogen;

[0845] R 3A Selected from -C(O)NR 5 -OR 6 、-C(O)NR 5 -NR 3 R 4 and -C(O)NR 5 -alkylene-Cy;

[0846] When the amino group contains a protecting group, the method further comprises the step of removing the protecting group; the amino protecting group is preferably Boc;

[0847] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 、R 5 、R 6 and Cy are as defined in general formula (IV).

[0848] Plan 5-3

[0849] The present disclosure provides a method for providing a compound represented by general formula (IV) or a pharmaceutically acceptable salt thereof, the method comprising: R X1 The compound represented by the general formula (IV) or its pharmaceutically acceptable salt which is an alkoxy or cycloalkoxy group undergoes dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 A compound represented by the general formula (IV) wherein -OH is -OH, or a pharmaceutically acceptable salt thereof.

[0850] Plan 5-4

[0851] The present disclosure provides a method for providing a compound represented by general formula (IV) or a pharmaceutically acceptable salt thereof, the method comprising:

[0852] The compound represented by the general formula (IVA') or its salt and NH2-R 5 or its salt (preferably hydrochloride) in the presence of a catalyst to obtain a compound represented by general formula (IV) or a pharmaceutically acceptable salt thereof,

[0853] R 3A -C(=NR 5 )NR 3 R 4 ;

[0854] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 and R 5 As defined in formula (IV).

[0855] Plan 6

[0856] The present disclosure provides a method for preparing a compound represented by general formula (V) or a pharmaceutically acceptable salt thereof, the method comprising:

[0857] The compound represented by the general formula (IVa) or its salt undergoes a condensation reaction with the compound represented by the general formula (Vb) or its salt to obtain the compound represented by the general formula (V) or its pharmaceutically acceptable salt, wherein:

[0858] R W1 is a hydrogen atom or an amino protecting group (preferably tert-butylsulfinyl), R W2 is a hydrogen atom or a hydroxyl protecting group (preferably TBS);

[0859] When R W1 is an amino protecting group and / or R W2 When the protecting group is a hydroxyl group, the preparation method further comprises the step of removing the protecting group under acidic conditions after the condensation reaction;

[0860] R 10 is a halogen (preferably a chlorine atom) or OH; when R 10 When is OH, the reaction occurs in the presence of a condensing agent or oxalyl chloride, preferably in the presence of a condensing agent;

[0861] R a、R b 、R c 、R d 、R X1 、R X2 、R X3 , R', R 1A 、R 2A 、R A4 , u1 and u2 are as defined in the general formula (V).

[0862] Plan 6-1

[0863] The present disclosure provides a method for preparing a compound represented by general formula (V) or a pharmaceutically acceptable salt thereof, the method comprising: R X1 The compound represented by the general formula (V) or a pharmaceutically acceptable salt thereof, which is an alkoxy or cycloalkoxy group, undergoes dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 A compound represented by the general formula (V) wherein -OH is -OH, or a pharmaceutically acceptable salt thereof.

[0864] Plan 7

[0865] The present disclosure provides a method for producing a compound represented by formula (V-1) or (V-2) or a pharmaceutically acceptable salt thereof, the method comprising:

[0866] The compound represented by the general formula (IVa) or its salt undergoes a condensation reaction with the compound represented by the general formula (V-1b) or its salt under alkaline conditions to obtain the compound represented by the general formula (V-1) or its pharmaceutically acceptable salt, or,

[0867] The compound represented by the general formula (IVa) or its salt undergoes a condensation reaction with the compound represented by the general formula (V-2b) or its salt under alkaline conditions to obtain the compound represented by the general formula (V-2) or its pharmaceutically acceptable salt, wherein:

[0868] R W1 is a hydrogen atom or an amino protecting group (preferably tert-butylsulfinyl), R W2 is a hydrogen atom or a hydroxyl protecting group (preferably TBS);

[0869] When R W1 is an amino protecting group and / or R W2 When the protecting group is a hydroxyl group, the preparation method further comprises the step of removing the protecting group under acidic conditions after the condensation reaction;

[0870] R 10 is a halogen (preferably a chlorine atom) or OH; when R 10 When is OH, the reaction occurs in the presence of a condensing agent or oxalyl chloride, preferably in the presence of a condensing agent;

[0871] R a 、Rb 、R c 、R d 、R X1 、R X2 、R X3 , R', R 1A 、R 2A 、R A4 , u1 and u2 are as defined in the general formula (V-1).

[0872] Plan 7-1

[0873] The present disclosure provides a method for preparing a compound represented by formula (V-1) or (V-2) or a pharmaceutically acceptable salt thereof, the method comprising: X1 The compound represented by the general formula (V-1) or (V-2) or a pharmaceutically acceptable salt thereof, which is an alkoxy or cycloalkoxy group, undergoes a dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 A compound represented by the general formula (V-1) or (V-2) or a pharmaceutically acceptable salt thereof, wherein -OH is

[0874] Plan 8

[0875] The present disclosure provides a method for producing a compound represented by formula (V-1) or (V-2) or a pharmaceutically acceptable salt thereof, the method comprising:

[0876] The compound represented by the general formula (V-1A) or its salt undergoes a deprotection reaction under acidic conditions to obtain the compound represented by the general formula (V-1) or its pharmaceutically acceptable salt.

[0877] The compound represented by the general formula (V-2A) or its salt undergoes a deprotection reaction under acidic conditions to obtain the compound represented by the general formula (V-2) or its pharmaceutically acceptable salt, wherein:

[0878] R W1 is an amino protecting group, and the amino protecting group is preferably Boc;

[0879] R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 , R', R 1A 、R 2A 、R A4 , u1 and u2 are as defined in the general formula (V-1).

[0880] Plan 9-A1

[0881] The present disclosure provides a method for preparing a compound represented by general formula (VI') or a pharmaceutically acceptable salt thereof, the method comprising:

[0882] The compound represented by the general formula (IVa) or its salt undergoes a condensation reaction with the compound represented by the general formula (VI'B) or its salt (preferably hydrochloride) under alkaline conditions to obtain the compound represented by the general formula (VI') or its pharmaceutically acceptable salt, wherein:

[0883] R 10 is a halogen (preferably a chlorine atom) or OH; when R 10 When is OH, the reaction occurs in the presence of a condensing agent or oxalyl chloride, preferably in the presence of a condensing agent;

[0884] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 、R 4 and R 5 As defined in formula (VI').

[0885] Plan 9-A2

[0886] The present disclosure provides a method for preparing a compound represented by general formula (VI') or a pharmaceutically acceptable salt thereof, the method comprising:

[0887] The compound represented by the general formula (VI'A) or its salt undergoes a Pinner reaction with the compound represented by the general formula (IB') or its salt (preferably hydrochloride) to obtain the compound represented by the general formula (VI') or its pharmaceutically acceptable salt, wherein:

[0888] R 5 is a hydrogen atom;

[0889] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 and R 4 As defined in formula (VI').

[0890] Plan 9-A3

[0891] The present disclosure provides a method for preparing a compound represented by general formula (VI') or a pharmaceutically acceptable salt thereof, the method comprising:X1 The compound represented by the general formula (VI') or a pharmaceutically acceptable salt thereof, which is an alkoxy or cycloalkoxy group, undergoes a dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 A compound represented by the general formula (VI') wherein -OH is -OH, or a pharmaceutically acceptable salt thereof.

[0892] Plan 9-A4

[0893] The present disclosure provides a method for preparing a compound represented by general formula (VI') or a pharmaceutically acceptable salt thereof, the method comprising:

[0894] The compound represented by the general formula (VI'A) or its salt and NH2-R 5 or its salt (preferably hydrochloride) undergoes Pinner reaction to obtain a compound represented by general formula (VI') or a pharmaceutically acceptable salt thereof, wherein:

[0895] R 3 and R 4 All are hydrogen atoms;

[0896] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A , Q and R 5 As defined in formula (VI').

[0897] Plan 9-A-A1

[0898] The present disclosure provides a method for preparing a compound represented by general formula (VI'-1) or a pharmaceutically acceptable salt thereof, the method comprising:

[0899] The compound represented by the general formula (IVa) or its salt and the compound represented by the general formula (VI'-1B) or its salt (preferably hydrochloride) undergo condensation reaction under alkaline conditions to obtain the compound represented by the general formula (VI'-1) or its pharmaceutically acceptable salt, wherein:

[0900] R 10 is a halogen (preferably a chlorine atom) or OH; when R 10 When is OH, the reaction occurs in the presence of a condensing agent or oxalyl chloride, preferably in the presence of a condensing agent;

[0901] R'、R a 、R b 、R c 、R d 、R X1、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 、R 5 and R C As defined in general formula (VI'-1).

[0902] Plan 9-A-A2

[0903] The present disclosure provides a method for preparing a compound represented by general formula (VI'-1) or a pharmaceutically acceptable salt thereof, the method comprising:

[0904] The compound represented by the general formula (VI'A) or its salt undergoes a pinner reaction with the compound represented by the general formula (VI-1B') or its salt (preferably hydrochloride) to obtain the compound represented by the general formula (VI'-1) or its pharmaceutically acceptable salt, wherein:

[0905] R 5 is a hydrogen atom;

[0906] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 and R C As defined in general formula (VI'-1).

[0907] Plan 9-A-A3

[0908] The present disclosure provides a method for preparing a compound represented by general formula (VI'-1) or a pharmaceutically acceptable salt thereof, the method comprising:

[0909] The compound represented by the general formula (VI') or its salt (preferably trifluoroacetate) and the compound represented by the general formula (VI'-1b) or its salt (preferably hydrochloride) undergo amidation reaction under alkaline conditions to obtain the compound represented by the general formula (VI'-1) or its pharmaceutically acceptable salt, wherein:

[0910] R 4 is a hydrogen atom;

[0911] R 10 is halogen (preferably chlorine) or OH; when R 10 When is OH, the reaction occurs in the presence of a condensing agent or oxalyl chloride, preferably in the presence of a condensing agent;

[0912] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 、R 5 and R C As defined in general formula (VI'-1).

[0913] Plan 9-A-A4

[0914] The present disclosure provides a method for preparing a compound represented by the general formula (VI'-1) or a pharmaceutically acceptable salt thereof, the method comprising: X1 The compound represented by the general formula (VI'-1) or its pharmaceutically acceptable salt, which is an alkoxy or cycloalkoxy group, undergoes dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 The compound represented by the general formula (VI'-1) or a pharmaceutically acceptable salt thereof is -OH.

[0915] Plan 9

[0916] The present disclosure provides a method for preparing a compound represented by formula (VI) or a pharmaceutically acceptable salt thereof, the method comprising:

[0917] The compound represented by the general formula (IVA') or its salt and the compound represented by the general formula (II'B) or its salt (preferably hydrochloride) undergo a pinner reaction in the presence of a catalyst to obtain the compound represented by the general formula (VI) or its pharmaceutically acceptable salt, wherein:

[0918] R 5 is a hydrogen atom;

[0919] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3a and R 4 As defined in formula (VI).

[0920] Plan 9-1

[0921] The present disclosure provides a method for preparing a compound represented by formula (VI) or a pharmaceutically acceptable salt thereof, the method comprising:

[0922] The compound represented by general formula (IVa) or its salt and the compound represented by general formula (VIb) or its salt (preferably hydrochloride) undergo condensation reaction under alkaline conditions to obtain the compound represented by general formula (VI) or its pharmaceutically acceptable salt, wherein:

[0923] R 10 is a halogen (preferably a chlorine atom) or OH; when R 10 When is OH, the reaction occurs in the presence of a condensing agent or oxalyl chloride, preferably in the presence of a condensing agent;

[0924] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A 、R 3a 、R 4 and R 5 As defined in formula (VI).

[0925] Plan 9-2

[0926] The present disclosure provides a method for preparing a compound represented by general formula (VI) or a pharmaceutically acceptable salt thereof, the method comprising: X1 The compound represented by the general formula (VI) or a pharmaceutically acceptable salt thereof, which is an alkoxy or cycloalkoxy group, undergoes a dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 A compound represented by the general formula (VI) wherein -OH is -OH, or a pharmaceutically acceptable salt thereof.

[0927] Plan 9-3

[0928] The present disclosure provides a method for preparing a compound represented by formula (VI) or a pharmaceutically acceptable salt thereof, the method comprising:

[0929] The compound represented by the general formula (IVA') or its salt and NH2-R 5 or its salt (preferably hydrochloride) in the presence of a catalyst to undergo a Pinner reaction to obtain a compound represented by general formula (VI) or a pharmaceutically acceptable salt thereof, wherein:

[0930] R 3a and R 4 All are hydrogen atoms;

[0931] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、RX1 、R X2 、R X3 and R 5 As defined in formula (VI).

[0932] Plan 10-A1

[0933] The present disclosure provides a method for preparing a compound represented by general formula (VII') or a pharmaceutically acceptable salt thereof, the method comprising:

[0934] The compound represented by the general formula (IVa) or its salt and the compound represented by the general formula (VII'B) or its salt (preferably hydrochloride) undergo condensation reaction under alkaline conditions to obtain the compound represented by the general formula (VII') or its pharmaceutically acceptable salt, wherein:

[0935] R 10 is a halogen (preferably a chlorine atom) or OH; when R 10 When is OH, the reaction occurs in the presence of a condensing agent or oxalyl chloride, preferably in the presence of a condensing agent;

[0936] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A 、R 3 、R 4 and R 5 As defined in general formula (VII').

[0937] Plan 10-A2

[0938] The present disclosure provides a method for preparing a compound represented by general formula (VII') or a pharmaceutically acceptable salt thereof, the method comprising:

[0939] The compound represented by general formula (VII') or its salt undergoes a condensation reaction with the compound represented by general formula (II-1B) or its salt (preferably hydrochloride) under alkaline conditions to obtain the compound represented by general formula (VII') or its pharmaceutically acceptable salt, wherein,

[0940] R* is selected from hydroxy, alkoxy and halogen;

[0941] When the amino group contains a protecting group, the method further comprises the step of removing the protecting group; the amino protecting group is preferably Boc;

[0942] R'、R a 、R b 、Rc 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 、R 4 and R 5 As defined in general formula (VII').

[0943] Plan 10-A3

[0944] The present disclosure provides a method for preparing a compound represented by general formula (VII') or a pharmaceutically acceptable salt thereof, the method comprising: X1 The compound represented by the general formula (VII') or a pharmaceutically acceptable salt thereof, which is an alkoxy or cycloalkoxy group, undergoes dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 The compound represented by the general formula (VII') or a pharmaceutically acceptable salt thereof is -OH.

[0945] Plan 10

[0946] The present disclosure provides a method for preparing a compound represented by formula (VII) or a pharmaceutically acceptable salt thereof, comprising:

[0947] The compound represented by the general formula (IVa') or its salt undergoes an amidation reaction with the compound represented by the general formula (II-1B) or its salt (preferably hydrochloride) under alkaline conditions to obtain the compound represented by the general formula (VII) or its pharmaceutically acceptable salt.

[0948] wherein R* is selected from hydroxy, alkoxy and halogen;

[0949] When the amino group contains a protecting group, the method further comprises the step of removing the protecting group; the amino protecting group is preferably Boc;

[0950] R 1A 、R 2A , R', R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 3 、R 4 and R 5 As defined in general formula (VII).

[0951] Plan 10-1

[0952] The present disclosure provides a method for preparing a compound represented by formula (VII) or a pharmaceutically acceptable salt thereof, comprising:

[0953] The compound represented by general formula (IVa) or its salt and the compound represented by general formula (VIIb) or its salt (preferably hydrochloride) undergo condensation reaction under alkaline conditions to obtain the compound represented by general formula (VII) or its pharmaceutically acceptable salt, wherein:

[0954] R 10 is a halogen (preferably a chlorine atom) or OH; when R 10 When is OH, the reaction occurs in the presence of a condensing agent or oxalyl chloride, preferably in the presence of a condensing agent;

[0955] R'、R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A 、R 3 、R 4 and R 5 As defined in general formula (VII).

[0956] Plan 10-2

[0957] The present disclosure provides a method for preparing a compound represented by formula (VII) or a pharmaceutically acceptable salt thereof, the method comprising: X1 The compound represented by the general formula (VII) or a pharmaceutically acceptable salt thereof, which is an alkoxy or cycloalkoxy group, undergoes dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 A compound represented by the general formula (VII) wherein -OH is -OH, or a pharmaceutically acceptable salt thereof.

[0958] Plan 11-1

[0959] The present disclosure provides a method for preparing a compound represented by general formula (VIII) or a pharmaceutically acceptable salt thereof, the method comprising:

[0960] The compound represented by general formula (IIa) or its salt undergoes a condensation reaction with the compound represented by general formula (VIIIB) or its salt (preferably hydrochloride) under alkaline conditions to obtain the compound represented by general formula (VIII) or its pharmaceutically acceptable salt, wherein:

[0961] R 10 is a halogen (preferably a chlorine atom) or OH; when R 10 When is OH, the reaction occurs in the presence of a condensing agent or oxalyl chloride, preferably in the presence of a condensing agent;

[0962] R', X, Ra 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 and R 4 As defined in general formula (VIII).

[0963] Plan 11-2

[0964] The present disclosure provides a method for preparing a compound represented by general formula (VIII) or a pharmaceutically acceptable salt thereof, the method comprising:

[0965] The compound represented by the general formula (VIIIA) or its salt undergoes an ester exchange reaction with the compound represented by the general formula (IB') or its salt (preferably hydrochloride) to obtain the compound represented by the general formula (VIII) or its pharmaceutically acceptable salt, wherein:

[0966] R L is an alkoxy group;

[0967] R', X, R a 、R b 、R c 、R d 、R X1 、R X2 、R X3 、R 1A 、R 2A ,Q,R 3 and R 4 As defined in general formula (VIII).

[0968] Plan 11-3

[0969] The present disclosure provides a method for preparing a compound represented by general formula (VIII) or a pharmaceutically acceptable salt thereof, the method comprising: X1 The compound represented by the general formula (VIII) or a pharmaceutically acceptable salt thereof, which is an alkoxy or cycloalkoxy group, undergoes a dealkylation or decycloalkylation reaction under acidic conditions to obtain R X1 A compound represented by the general formula (VIII) wherein -OH is -OH, or a pharmaceutically acceptable salt thereof.

[0970] The Pinner reaction is based on the Pinner amidine synthesis method, and its specific mechanism is as follows: the raw material cyano compound undergoes alcoholysis reaction with an alcohol solvent under the catalysis of a catalyst to form an imine ester, which then undergoes aminolysis or ammonolysis reaction with an amine or ammonia to form an amidine.

[0971] The catalyst described in the above-mentioned Pinner reaction can be an acid catalyst or a base catalyst. The acid catalyst is an organic acid or an inorganic acid, including but not limited to hydrochloric acid, hydrogen chloride gas, thioglycolic acid and N-acetylcysteine, etc., preferably thioglycolic acid; the base catalyst is an organic base or an inorganic base, including but not limited to sodium methoxide, sodium ethoxide, triethylamine, N,N-diisopropylethylamine, N,N-diisopropylethylenediamine, etc., preferably N,N-diisopropylethylamine or sodium methoxide, more preferably sodium methoxide.

[0972] The ammonia used in the above-mentioned aminolysis reaction is liquid ammonia, ammonia water or ammonium salt, preferably ammonium chloride; the amine used in the aminolysis reaction is an organic amine.

[0973] The above-mentioned alcohol solvents include but are not limited to methanol, ethanol, isopropanol and n-butanol.

[0974] The reagents providing acidic conditions in the above synthesis scheme include organic acids and inorganic acids, and the organic acids include but are not limited to trifluoroacetic acid, formic acid, acetic acid, methanesulfonic acid, p-toluenesulfonic acid, Me3SiCl and TMSOTf; the inorganic acids include but are not limited to hydrogen chloride, HCl·dioxane solution, hydrochloric acid-dioxane solution, hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid; preferably HCl·dioxane solution or hydrochloric acid-dioxane solution; the reagent providing acidic conditions in the dealkylation or decycloalkylation reaction in the above synthesis scheme is preferably a Lewis acid, such as BBr3, ALCl3, etc., preferably BBr3.

[0975] The reagents providing alkaline conditions in the above synthesis scheme include organic bases and inorganic bases, wherein the organic bases include but are not limited to triethylamine, N,N-diisopropylethylamine, N,N-diisopropylethylenediamine, n-butyllithium, lithium diisopropylamide, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, tetrabutylammonium fluoride, tetrabutylammonium fluoride in tetrahydrofuran or 1,8-diazabicycloundec-7-ene, and the inorganic bases include but are not limited to sodium hydride, potassium phosphate, sodium carbonate, sodium acetate, potassium acetate, potassium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, cesium fluoride and potassium hydroxide; preferably triethylamine or N,N-diisopropylethylamine; when R 10 When R is halogen, the reagent providing alkaline conditions is preferably triethylamine. 10 When it is OH, the reagent providing alkaline conditions is preferably N,N-diisopropylethylamine. The condensation reaction is preferably carried out in the presence of a condensing agent, which is defined as follows; the base in the above synthetic schemes 1-1, 2-1 and 5-1 is preferably N,N-diisopropylethylamine.

[0976] The condensing agent described in the above reaction includes but is not limited to 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazole-N,N,N',N'-tetramethyluronium tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazole, O-benzotriazole-N,N,N',N'-tetramethyluronium tetrafluoroborate, Methyluronium hexafluorophosphate, O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), 2-(7-benzotriazole oxide)-N,N,N',N'-tetramethyluronium hexafluorophosphate, benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate or benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate; preferably HATU.

[0977] In the condensation reaction in the above synthesis scheme, when R 10 When is halogen, the condensation reaction is optionally carried out in the presence of a catalyst, and the catalyst is preferably 4-dimethylaminopyridine.

[0978] In the above synthesis scheme, when R* is a hydroxyl group, the amidation reaction is optionally carried out in the presence of a condensing agent; the condensing agent is as defined above.

[0979] The reaction in the above steps is preferably carried out in a solvent, and the solvent used includes but is not limited to: pyridine, ethylene glycol dimethyl ether, acetic acid, methanol, ethanol, acetonitrile, n-butanol, toluene, tetrahydrofuran, dichloromethane, petroleum ether, ethyl acetate, n-hexane, dimethyl sulfoxide, 1,4-dioxane, water, N,N-dimethylformamide, N,N-dimethylacetamide, 1,2-dibromoethane and mixtures thereof. BRIEF DESCRIPTION OF THE DRAWINGS

[0980] Figure 1 HN HSQC spectrum of the compound of Example 16;

[0981] FIG2 HN HMBC spectrum of the compound of Example 16;

[0982] FIG3 shows the analgesic efficacy of the compound of Example 16 in a rat incisional pain model;

[0983] FIG4 shows the effect of the compound of Example 16 on body weight in a rat incisional pain model;

[0984] FIG5 shows the analgesic efficacy of the compound of Example 32 in a rat incisional pain model;

[0985] Figure 6 shows the effect of the compound of Example 32 on body weight in the rat incisional pain model. DETAILED DESCRIPTION

[0986] The present disclosure is further described below with reference to the following embodiments, but these embodiments are not intended to limit the scope of the present disclosure.

[0987] Example

[0988] The structures of the compounds were determined by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS). -6 The unit of ppm is given. NMR measurements were performed using a Bruker AVANCE-400 NMR spectrometer or a Bruker AVANCE NEO 500M NMR spectrometer. The solvents used were deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3), or deuterated methanol (CD3OD), and tetramethylsilane (TMS) was used as the internal standard.

[0989] MS was measured using an Agilent 1200 / 1290 DAD-6110 / 6120 Quadrupole MS liquid spectrometer-mass spectrometer (manufacturer: Agilent, MS model: 6110 / 6120 Quadrupole MS).

[0990] waters ACQuity UPLC-QD / SQD (Manufacturer: waters, MS model: waters ACQuity Qda Detector / waters SQ Detector)

[0991] THERMO Ultimate 3000-Q Exactive (Manufacturer: THERMO, MS model: THERMO Q Exactive)

[0992] High performance liquid chromatography (HPLC) analysis was performed using Agilent HPLC 1200DAD, Agilent HPLC 1200VWD and Waters HPLC e2695-2489 high performance liquid chromatographs.

[0993] Chiral HPLC analysis was performed using an Agilent 1260 DAD high performance liquid chromatograph.

[0994] High performance liquid chromatography (HPLC) was performed using Waters 2545-2767, Waters 2767-SQ Detecor2, Shimadzu LC-20AP, and Gilson GX-281 preparative chromatographs.

[0995] Chiral preparations were performed using a Shimadzu LC-20AP preparative chromatograph.

[0996] The CombiFlash rapid preparation instrument used was Combiflash Rf200 (TELEDYNE ISCO).

[0997] The thin layer chromatography silica gel plate uses Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plate. The specification of the silica gel plate used in thin layer chromatography (TLC) is 0.15mm~0.2mm, and the specification used for thin layer chromatography separation and purification products is 0.4mm~0.5mm.

[0998] Silica gel column chromatography generally uses Yantai Huanghai Silica Gel 200-300 mesh silica gel as the carrier.

[0999] Average kinase inhibition rate and IC 50 The values ​​were determined using a NovoStar microplate reader (BMG, Germany).

[1000] The known starting materials of the present invention can be synthesized by methods known in the art, or can be purchased from ABCR GmbH & Co. KG, Acros Organics, Aldrich Chemical Company, Accela ChemBio Inc, Darui Chemicals, and other companies.

[1001] Unless otherwise specified in the examples, all reactions can be carried out under an argon atmosphere or a nitrogen atmosphere.

[1002] Argon atmosphere or nitrogen atmosphere means that the reaction bottle is connected to an argon or nitrogen balloon with a capacity of about 1 L.

[1003] Hydrogen atmosphere means that the reaction bottle is connected to a hydrogen balloon with a capacity of about 1L.

[1004] The pressurized hydrogenation reaction uses a Parr 3916EKX hydrogenator and a Qinglan QL-500 hydrogen generator or an HC2-SS hydrogenator.

[1005] The hydrogenation reaction is usually carried out by evacuating the chamber and filling it with hydrogen, and the operation is repeated three times.

[1006] A CEM Discover-S 908860 microwave reactor was used for the microwave reaction.

[1007] Unless otherwise specified in the examples, the solution refers to an aqueous solution.

[1008] Unless otherwise specified in the examples, the reaction temperature is room temperature, 20°C to 30°C.

[1009] The reaction progress in the examples was monitored by thin layer chromatography (TLC). The developing solvent used in the reaction, the eluent system for column chromatography used to purify the compound, and the developing solvent system for thin layer chromatography included: A: dichloromethane / methanol system, B: n-hexane / ethyl acetate system, and C: petroleum ether / ethyl acetate system. The volume ratio of the solvent was adjusted according to the polarity of the compound, and a small amount of alkaline or acidic reagents such as triethylamine and acetic acid could also be added for adjustment.

[1010] Example 1

[1011] (2R,3S,4S,5R)-N-(2-aminopyrimidin-5-yl)-3-(3,4-difluoro-2-methoxyphenyl)-4,5-dimethyl-5-(trifluoromethyl)tetrahydrofuran-2-carboxamide 1

[1012] first step

[1013] (2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)-4,5-dimethyl-5-(trifluoromethyl)tetrahydrofuran-2-carboxylic acid 1b-1

[1014] (2S,3R,4R,5S)-3-(3,4-difluoro-2-methoxyphenyl)-4,5-dimethyl-5-(trifluoromethyl)tetrahydrofuran-2-carboxylic acid 1b-2

[1015] rac-(2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)-4,5-dimethyl-5-(trifluoromethyl)tetrahydrofuran-2-carboxylic acid 1a (12 g, 33.87 mmol, prepared by the method disclosed in Example 3 on page 231 of the specification of patent application "WO2021113627") was separated by chiral column (Waters SFC 150, chromatographic column: DAICEL 40*250mm, 10μm; mobile phase A: supercritical CO2, mobile phase B: IPA), gradient ratio: A:B: 90:10, flow rate: 120mL / min) to obtain the title products 1b-1 (5.5g, yield: 45.8%) and 1b-2 (5.08g, yield: 42.3%).

[1016] MS m / z(ESI):353.2[M-1].

[1017] Single configuration compound (shorter retention time) 1b-1 (5.5 g, yield: 45.8%)

[1018] MS m / z(ESI):353.2[M-1].

[1019] Chiral HPLC analysis: retention time 2.414 minutes, purity: 99% (chromatographic column: DAICEL 100*3mm, 3μm; mobile phase A: supercritical CO2, mobile phase B: IPA (0.1% DEA), gradient ratio: mobile phase A: 60%-95%, flow rate: 1.5mL / min).

[1020] Single configuration compound (longer retention time) 1b-2 (5.08 g, yield: 42.3%).

[1021] MS m / z(ESI):353.2[M-1].

[1022] Chiral HPLC analysis: retention time 2.724 minutes, purity: 99% (chromatographic column: DAICEL 100*3mm, 3μm; mobile phase A: supercritical CO2, mobile phase B: IPA (0.1% DEA), gradient ratio: mobile phase A: 60%-95%, flow rate: 1.5mL / min).

[1023] Step 2

[1024] (2R,3S,4S,5R)-N-(2-aminopyrimidin-5-yl)-3-(3,4-difluoro-2-methoxyphenyl)-4,5-dimethyl-5-(trifluoromethyl)tetrahydrofuran-2-carboxamide 1

[1025] Compound 1b-1 (22 mg, 62 μmol) and 2,5-diaminopyrimidine 1c (10.3 mg, 93 μmol, Shanghai Bidex) were dissolved in 1 mL of N,N-dimethylformamide. N,N-diisopropylethylamine (24 mg, 186 μmol) and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) (28.3 mg, 74 μmol) were added under ice bath. The temperature was maintained for 2 hours. The reaction solution was purified by high performance liquid chromatography (Waters-2545, column: YMC Triart-Exrs C18, 30*150 mm, 5 μm; mobile phase: aqueous phase (10 mmol / L ammonium bicarbonate) and acetonitrile, gradient ratio: acetonitrile 35%-45%, flow rate: 30 mL / min) to give the title compound 1 (8 mg, yield: 28.8%).

[1026] MS m / z(ESI):447.2[M+1].

[1027] 1H NMR (500MHz, CD3OD): δ8.39(s,2H),7.13(ddd,1H),6.98(td,1H),5.05(d,1H ),4.26(dd,1H),3.99(d,3H),2.78(p,1H),1.68-1.64(m,3H),0.80(dq,3H).

[1028] Example 2

[1029] (2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)-N-(2-((R)-2,3-dihydroxypropoxy)pyridin-4-yl)-4,5-dimethyl-5-(trifluoromethyl)tetrahydrofuran-2-carboxamide

[1030] first step

[1031] (S)-(+)-2-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)pyridin-4-amine 2c

[1032] (S)-(+)-(2,2-Dimethyl-1,3-dioxolan-4-yl)methanol 2b (616 mg, 4.66 mmol, Shanghai Shaoyuan) was dissolved in 10 mL of anhydrous N,N-dimethylformamide, and sodium hydride (199 mg, 5 mmol, 60% purity) was added under ice bath. After maintaining the temperature for 1 hour, 2-chloro-4-aminopyridine 2a (200 mg, 1.55 mmol, Shanghai Bid) was added and stirred at 160°C for 10 hours. The reaction solution was cooled to room temperature and quenched with water. The product was extracted with dichloromethane (30 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and concentrated under reduced pressure. The residue was purified by preparative HPLC (Waters-2545, column: YMC Triart-Exrs C18, 30*150mm, 5μm; mobile phase: aqueous phase (10mmol / L ammonium bicarbonate) and acetonitrile, gradient ratio: acetonitrile 35%-45%, flow rate: 30mL / min) to give the title compound 2c (140mg, yield: 40%).

[1033] MS m / z(ESI):225.2[M+1].

[1034] Step 2

[1035] (2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)-N-(2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)pyridin-4-yl)-4,5-dimethyl-5-(trifluoromethyl)tetrahydrofuran-2-carboxamide 2d

[1036] Compound 1b-1 (20 mg, 56.43 μmol) was dissolved in dichloromethane (0.8 mL), and oxalyl chloride (14.3 mg, 112 μmol) and 1 drop of N,N-dimethylformamide were added under ice bath. The reaction was restored to room temperature for 1 hour. The reaction solution was concentrated under reduced pressure. The residue was dissolved in dichloromethane (1 mL), and compound 2c (15.2 mg, 67.7 μmol), triethylamine (22.8 mg, 225.8 μmol) and 4-dimethylaminopyridine (1.4 mg, 11.2 μmol) were added. The reaction was stirred for 1 hour. The reaction solution was concentrated under reduced pressure to obtain the crude title compound 2d (31 mg). The product was used directly in the next step without purification.

[1037] MS m / z(ESI):561.2[M+1].

[1038] Step 3

[1039] (2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)-N-(2-((R)-2,3-dihydroxypropoxy)pyridin-4-yl)-4,5-dimethyl-5-(trifluoromethyl)tetrahydrofuran-2-carboxamide

[1040] The crude compound 2d (30 mg, 53.5 μmol) was dissolved in dichloromethane (1 mL), and a 4 M HCl solution in dioxane (0.5 mL) was added. The reaction mixture was stirred for 1 hour. The reaction solution was concentrated under reduced pressure, and the residue was purified by preparative HPLC (Waters-2545, column: YMC Triart-Exrs C18, 30*150 mm, 5 μm; mobile phase: aqueous phase (10 mmol / L ammonium bicarbonate) and acetonitrile, gradient ratio: acetonitrile 30%-45%, flow rate: 30 mL / min) to give the title compound 2 (2 mg, yield: 7%).

[1041] MS m / z(ESI):521.2[M+1].

[1042] 1 H NMR (500MHz, CD3OD): δ8.00(dd,1H),7.41(d,1H),7.30(d,1H),7.17(dd,1H),7.00(td,1H),5.07(s,1H ),4.25(dd,1H),4.05-3.84(m,5H),3.64(qd,2H),2.80(t,1H),2.21(t,1H),1.66(s,3H),0.83(dt,3H).

[1043] Example 3

[1044] (2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)-N-(2-(2-hydroxypropan-2-yl)pyridin-4-yl)-4,5-dimethyl-5-(trifluoromethyl)tetrahydrofuran-2-carboxamide

[1045] Compound 1b-1 (20 mg, 56 μmol) and 2-(4-aminopyridin-2-yl)propan-2-ol 3a (12.9 mg, 84.6 μmol, Shanghai Shaoyuan) were dissolved in 1 mL of N,N-dimethylformamide. N,N-diisopropylethylamine (22 mg, 169 μmol) and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) (26 mg, 68 μmol) were added under ice bath. The temperature was maintained for 2 hours. The reaction solution was purified by preparative HPLC (Waters-2545, column: YMC Triart-Exrs C18, 30*150mm, 5μm; mobile phase: aqueous phase (10mmol / L ammonium bicarbonate) and acetonitrile, gradient ratio: acetonitrile 35%-45%, flow rate: 30mL / min) to obtain the title compound 3 (4mg, yield: 14.5%).

[1046] MS m / z(ESI):489.2[M+1].

[1047] 1 H NMR (500MHz, CD3OD): δ8.34(d,1H),7.90(d,1H),7.58(dd,1H),7.12(ddd,1H),6.98(td,1H), 5.07(d,1H),4.32(dd,1H),4.00(d,3H),2.79(p,1H),1.66(d,3H),1.51(s,6H),0.81(dt,3H).

[1048] Example 4-1 or Example 4-2

[1049] (2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)-4,5-dimethyl-N-(2-(2-methyl-2H-tetrazol-5-yl)pyridin-4-yl)-5-(trifluoromethyl)tetrahydrofuran-2-carboxamide 4-1 or

[1050] (2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)-4,5-dimethyl-N-(2-(1-methyl-1H-tetrazol-5-yl)pyridin-4-yl)-5-(trifluoromethyl)tetrahydrofuran-2-carboxamide

[1051] first step

[1052] 4-Azido-2-(2H-tetrazol-5-yl)pyridine 4b

[1053] 4-Bromopyridine-2-carbonitrile 4a (1 g, 5.46 mmol, Shanghai Shaoyuan) and sodium azide (535 mg, 8.22 mmol) were dissolved in N,N-dimethylformamide (25 mL), and ammonium chloride (1.0 g, 18.7 mmol) was added. The mixture was stirred at 120°C for 4 hours. The reaction solution was cooled to room temperature, poured into water, and extracted with ethyl acetate (15 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and concentrated under reduced pressure to give the crude title compound 4b (1 g). The product was used directly in the next reaction without purification.

[1054] MS m / z(ESI):189.2[M+1].

[1055] Step 2

[1056] 4-Azido-2-(2-methyl-2H-tetrazol-5-yl)pyridine 4c-1 and

[1057] Mixture of 4-azido-2-(1-methyl-1H-tetrazol-5-yl)pyridine 4c-2

[1058] Compound 4b (1 g, 5.3149 mmol) was dissolved in N,N-dimethylformamide (20 mL), and potassium hydroxide (900 mg, 16 mmol) and iodomethane (1 g, 7 mmol) were added. The mixture was stirred and reacted for 16 hours. The reaction solution was filtered, and water was added to the filtrate. The mixture was extracted with ethyl acetate (15 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and concentrated under reduced pressure to obtain a crude mixture (1 g) of the title compounds 4c-1 and 4c-2. The product was used directly in the next reaction without purification.

[1059] MS m / z(ESI):203.2[M+1].

[1060] Step 3

[1061] 2-(2-Methyl-2H-tetrazol-5-yl)pyridin-4-amine 4d-1

[1062] 2-(1-methyl-1H-tetrazol-5-yl)pyridin-4-amine 4d-2

[1063] A crude mixture of compounds 4c-1 and 4c-2 (400 mg, 1.97 mmol) was dissolved in methanol (20 mL), and 10% palladium carbon catalyst (wet) (100 mg) was added. The reaction was stirred under a hydrogen atmosphere for 14 hours. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by high-performance liquid preparative chromatography (Waters-2545, chromatographic column: YMC Triart-Exrs C18, 30*150 mm, 5 μm; mobile phase: aqueous phase (10 mmol / L ammonium bicarbonate) and acetonitrile, gradient ratio: acetonitrile 30%-45%, flow rate: 30 mL / min) to give the title compound (40 mg, 30 mg, yield: 11.4%, 8.6%).

[1064] MS m / z(ESI):177.2[M+1].

[1065] Single configuration compound (shorter retention time) (30 mg, yield: 8.6%)

[1066] HPLC analysis: retention time 0.54 minutes, purity: 99% (chromatographic column: ACQUITY C18, 1.7 μm, 2.1*50 mm; mobile phase: water (10 mM ammonium bicarbonate), acetonitrile, gradient ratio: acetonitrile 10%-95%).

[1067] Single configuration compound (longer retention time) (40 mg, yield: 11.4%)

[1068] HPLC analysis: retention time 0.81 minutes, purity: 92% (chromatographic column: ACQUITY C18, 1.7 μm, 2.1*50 mm; mobile phase: water (10 mM ammonium bicarbonate), acetonitrile, gradient ratio: acetonitrile 10%-95%).

[1069] Step 4

[1070] (2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)-4,5-dimethyl-N-(2-(2-methyl-2H-tetrazol-5-yl)pyridin-4-yl)-5-(trifluoromethyl)tetrahydrofuran-2-carboxamide 4-1 or

[1071] (2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)-4,5-dimethyl-N-(2-(1-methyl-1H-tetrazol-5-yl)pyridin-4-yl)-5-(trifluoromethyl)tetrahydrofuran-2-carboxamide

[1072] Compound 1b-1 (20 mg, 56.43 μmol) was dissolved in dichloromethane (2 mL), and oxalyl chloride (40 mg, 315 μmol) and 1 drop of N,N-dimethylformamide were added under ice bath. The reaction was restored to room temperature for 1 hour. The reaction solution was concentrated under reduced pressure. The residue was dissolved in dichloromethane (3 mL), and triethylamine (40 mg, 395 μmol) was added. A dichloromethane solution (1 mL) of the compound corresponding to the longer retention time of compounds 4d-1 and 4d-2 (15.2 mg, 67.7 μmol) was added dropwise at -10°C. The reaction was stirred for 1 hour. The reaction solution was concentrated under reduced pressure. The residue was purified by preparative HPLC (Waters-2545, column: YMC Triart-Exrs C18, 30*150mm, 5μm; mobile phase: aqueous phase (10mmol / L ammonium bicarbonate) and acetonitrile, gradient ratio: acetonitrile 30%-45%, flow rate: 30mL / min) to obtain the title compound 4-1 or 4-2 (4mg, yield: 13.8%).

[1073] MS m / z(ESI):513.2[M+1].

[1074] 1 H NMR (500MHz, DMSO-d6): δ10.87(s,1H),8.69-8.67(m,1H),8.58-8.56(m,1H),7.88-7.84(m,1H),7.23-7.15(m,2H), 5.18-5.13(m,1H),4.40(s,3H),4.31-4.23(m,1H),3.96(s,3H),2.83-2.74(m,1H),1.63(s,3H),0.76-0.72(m,3H).

[1075] Example 4-1 or Example 4-2

[1076] (2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)-4,5-dimethyl-N-(2-(2-methyl-2H-tetrazol-5-yl)pyridin-4-yl)-5-(trifluoromethyl)tetrahydrofuran-2-carboxamide 4-1 or

[1077] (2R,3S,4S,5R)-3-(3,4-difluoro-2-methoxyphenyl)-4,5-dimethyl-N-(2-(1-methyl-1H-tetrazol-5-yl)pyridin-4-yl)-5-(trifluoromethyl)tetrahydrofuran-2-carboxamide

[1078] first step

[1079] 4-Azido-2-(2H-tetrazol-5-yl)pyridine 4b

[1080] 4-Bromopyridine-2-carbonitrile 4a (1 g, 5.46 mmol, Shanghai Shaoyuan) and sodium azide (535 mg, 8.22 mmol) were dissolved in N,N-dimethylformamide (25 mL), and ammonium chloride (1.0 g, 18.7 mmol) was added. The mixture was stirred at 120°C for 4 hours. The reaction solution was cooled to room temperature, poured into water, and extracted with ethyl acetate (15 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and concentrated under reduced pressure to give the crude title compound 4b (1 g). The product was used directly in the next reaction without purification.

[1081] MS m / z(ESI):189.2[M+1].

[1082] Step 2

[1083] 4-Azido-2-(2-methyl-2H-tetrazol-5-yl)pyridine 4c-1 and

[1084] Mixture of 4-azido-2-(1-methyl-1H-tetrazol-5-yl)pyridine 4c-2

[1085] Compound 4b (1 g, 5.3149 mmol) was dissolved in N,N-dimethylformamide (20 mL), and potassium hydroxide (900 mg, 16 mmol) and iodomethane (1 g, 7 mmol) were added. The mixture was stirred and reacted for 16 hours. The reaction solution was filtered, and water was added to the filtrate. The mixture was extracted with ethyl acetate (15 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and concentrated under reduced pressure to obtain a crude mixture (1 g) of the title compounds 4c-1 and 4c-2. The product was used directly in the next reaction without purification.

[1086] MS m / z(ESI):203.2[M+1].

[1087] Step 3

[1088] 2-(2-Methyl-2H-tetrazol-5-yl)pyridin-4-amine 4d-1

[1089] 2-(1-methyl-1H-tetrazol-5-yl)pyridin-4-amine 4d-2

[1090] A crude mixture of compounds 4c-1 and 4c-2 (400 mg, 1.97 mmol) was dissolved in methanol (20 mL), and 10% palladium carbon catalyst (wet) (100 mg) was added. The reaction was stirred under a hydrogen atmosphere for 14 hours. The reaction solution was filtered, and the filtrate was concentrated under r...

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