CN118834211A - Nitrogen-containing heterocyclic compound, and preparation method and application thereof - Google Patents

Abstract

The present invention discloses a nitrogen-containing heterocyclic compound, a preparation method and application thereof. Specifically, the present invention discloses a compound as shown in formula X, a compound as shown in formula I or a compound as shown in formula V, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof. The compound as shown in formula I or the compound as shown in formula V of the present invention is relatively easy to synthesize, can be used to improve neuronal plasticity, and has good medicinal prospects.

Description

A nitrogen-containing heterocyclic compound, preparation method and application thereof

This application claims the priority of Chinese patent application No. 2023104423038 filed on April 23, 2023. This application cites the entire text of the above Chinese patent application.

Technical Field

The invention relates to a nitrogen-containing heterocyclic compound, a preparation method and application thereof.

Background Art

At present, drugs that regulate the serotonergic system, such as selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, etc., have been widely used in the treatment of mental disorders such as depression, anxiety, schizophrenia, etc. However, the above therapies are slow to take effect, insufficient in efficacy or drug resistance in some patients, and have side effects such as insomnia, drowsiness, blood pressure and weight changes, resulting in poor patient compliance.

Alterations in synaptic connectivity and plasticity have been observed in the brains of individuals with neurological diseases and disorders. In recent years, preclinical and clinical studies have found that hallucinogens such as ketamine, psilocybin, ibogaine, and lysergic acid diethylamide (LSD) have rapid onset of action and long-lasting effects that may stem from their unique receptor affinity and regulation of neuroplasticity. Therefore, the development of drugs that regulate neuroplasticity has broad application prospects in the treatment of neuropsychiatric diseases.

Summary of the invention

The technical problem to be solved by the present invention is to overcome the defects of insufficient efficacy or poor compliance of existing therapeutic drugs for neuropsychiatric diseases, and thus, a nitrogen-containing heterocyclic compound, a preparation method and application thereof are provided. The nitrogen-containing heterocyclic compound provided by the present invention is easy to synthesize, has good activity, and has a relatively broad application prospect.

The present invention solves the above technical problems through the following methods.

The present invention provides a compound as shown in Formula I, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof:

in,

m is 0, 1, 2, 3 or 4;

n is 0, 1, 2, 3, 4 or 5;

_Z1 is N or CH;

X ₁ and X ₂ are each independently a chemical bond or -CH ₂ -;

X ₃ and X ₄ are each independently -CH ₂ -;

each R ¹ is independently cyano, halogen, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^1-1 , C _1-6 alkoxy, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl or C _1-6 alkoxy substituted by 1, 2 or 3 R ^1-2 ;

Each R ^1-1 is independently deuterium or halogen;

Each R ^1-2 is independently deuterium or halogen;

each R ² is independently deuterium, halogen, hydroxyl, C _1-6 alkyl, amino, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, or 3-6 membered heterocycloalkyl substituted with 1, 2 or 3 R ^2-1 ;

Each R ^2-1 is independently halogen, hydroxyl or C _1-6 alkyl;

R ³ is each independently H, C _1-6 alkyl, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 , or 3-6 membered heterocycloalkyl substituted by 1, 2 or 3 R ^3-3 ;

Each R ^3-1 is independently deuterium, halogen, 3-6 membered heterocycloalkyl, or 3-6 membered heterocycloalkyl substituted with one or more ^Ra ;

Each R ^3-2 is independently deuterium, halogen or C _1-6 alkyl;

Each R ^3-3 is independently deuterium, halogen or C _1-6 alkyl;

Each ^Ra is independently deuterium, halogen or _C1-6 alkyl;

The compound shown in formula I satisfies one or both of the following conditions:

IR ³ is each independently C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 , or 3-6 membered heterocycloalkyl substituted by 1, 2 or 3 R ^3-3 ;

II. m is 1, 2, 3 or 4, and each R ¹ is independently a C _2-6 alkoxy group substituted by 1, 2 or 3 R ^1-2 ;

In any of the above 3-6 membered heterocycloalkyl groups, the heteroatoms are 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3.

In a certain embodiment of the present invention, certain groups in the compound as shown in Formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt are defined as follows, and the unmentioned groups are the same as those described in any embodiment of the present invention (referred to as "a certain embodiment").

In one embodiment, in the compound shown in formula I, in R ¹ , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound shown in formula I, in ^R1 , the _C1-6 alkyl group and the _C1-6 alkyl group substituted by 1, 2 or 3 ^R1-1 are _each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

In one embodiment _, in the compound shown in formula I, in ^R1 , the _C1-6 alkoxy group and the _C1-6 alkoxy group substituted by 1, 2 or 3 ^R1-2 are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, for example, methoxy.

In one embodiment, in the compound of formula I, in ^R1 , the _C3-6 cycloalkyl groups are each independently cyclopropane, cyclobutane, cyclopentane or cyclohexane.

In one embodiment, in the compound shown in formula I, in ^R1 , the 3-6 membered heterocycloalkyl groups are each independently 4-6 membered heterocycloalkyl groups, in which the heteroatoms are preferably N and/or O, and in which the heteroatoms are preferably 1 or 2.

In one embodiment, in the compound shown in formula I, in R ^1-1 , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound of formula I, in R ^1-2 , the halogen is independently F, Cl, Br or I, for example, F.

In one embodiment, in the compound shown in formula I, in R ² , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound of formula I, in R ² , the C _1-6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

In one embodiment, in the compound of formula I, in R ² , the C _3-6 cycloalkyl groups are each independently cyclopropane, cyclobutane, cyclopentane or cyclohexane.

In a certain embodiment, in the compound represented by formula I, in R ² , the 3-6 membered heterocycloalkyl group and the 3-6 membered heterocycloalkyl group substituted by 1, 2 or 3 R ^{2 -1} are each independently a 4-6 membered heterocycloalkyl group, in which the heteroatom is preferably N and/or O, and in which the number of heteroatoms is preferably 1 or 2.

In one embodiment, in the compound shown in formula I, in R ^2-1 , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound of formula I, in R ^2-1 , the C _1-6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

In one embodiment, in the compound shown in formula I, in R ³ , the C _1-6 alkyl group and the C _1-6 alkyl group substituted by 1, 2 or 3 R ^3-1 are _each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, for example, methyl, isopropyl or tert-butyl.

In one embodiment, in the compound shown in formula I, in _R ³ , the C _3-6 cycloalkyl group and the C _3-6 cycloalkyl group substituted by 1, 2 or 3 R ^3-2 are each independently cyclopropane, cyclobutane, cyclopentane or cyclohexane, for example cyclopropane.

In one embodiment, in the compound shown in formula I, in _R ³ , the C _3-6 cycloalkyl group and the C _3-6 cycloalkyl group substituted by 1, 2 or 3 R ^3-2 are each independently cyclobutane, cyclopentane or cyclohexane.

In one embodiment, in the compound shown in formula I, in R ³ , the 3-6 membered heterocycloalkyl and the 3-6 membered heterocycloalkyl substituted by 1, 2 or 3 R ^{3 -3} are each independently a 4-6 membered heterocycloalkyl, wherein the heteroatom in the 4-6 membered heterocycloalkyl is preferably N and/or O, and the number of heteroatoms in the 4-6 membered heterocycloalkyl is preferably 1 or 2, for example, the 4-6 membered heterocycloalkyl is an oxetane (for example ).

In one embodiment, in the compound shown in formula I, in R ^3-1 , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound shown in Formula I, the 3-6 membered heterocycloalkyl group has a heteroatom of N, O or S, and the number of heteroatoms is 1, 2 or 3.

In a certain embodiment, in the compound shown in formula I, in R ^3-1 , the 3-6-membered heterocycloalkyl group and the 3-6-membered heterocycloalkyl group substituted by one or more ^Ra are each independently a 4-6-membered heterocycloalkyl group, in which the heteroatom is preferably N and/or O, and in which the heteroatom is preferably 1 or 2, for example, the 4-6-membered heterocycloalkyl group is an oxetane group (for example ).

In one embodiment, in the compound shown in formula I, in R ^3-2 , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound of formula I, in R ^3-2 , the C _1-6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, such as methyl.

In one embodiment, in the compound shown in formula I, in R ^3-3 , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound shown in formula I, in R ^3-3 , the C _1-6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

In one embodiment, in the compound shown in Formula I, in ^Ra , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound of formula I, in ^Ra , the _C1-6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, such as methyl.

In one embodiment, in the compound of formula I (e.g., condition II), in R ¹ , the C _2-6 alkoxy groups substituted by 1, 2 or 3 R ^1-2 are each independently ethoxy, n _- propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, for example, isopropoxy (e.g. ), the C _2-6 alkoxy group substituted by 1, 2 or 3 R ^1-2 is preferably (For example ).

In one embodiment, the compound shown in formula I is not

In one embodiment, in the compound represented by formula I, each R ^1-1 is independently halogen.

In one embodiment, in the compound represented by formula I, each R ^1-2 is independently halogen.

In one embodiment, in the compound shown in formula I, m is 1.

In one embodiment, in the compound represented by formula I, n is 0.

In one embodiment, in the compound represented by formula I, each R ¹ is independently a C _1-6 alkoxy group or a C _1-6 alkoxy group substituted by 1, 2 or 3 R ^1-2 groups.

In a certain embodiment, in the compound shown in formula I, R ³ is each independently C _1-6 alkyl, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , or C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 , in which the heteroatom is N, O or S, and the number of heteroatoms is 1 or 2; for example, it is C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, or C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , or C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 , in which the heteroatom is N, O or S, and the number of heteroatoms is 1 or 2.

In a certain embodiment, in the compound shown in formula I, R ³ is each independently C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, or C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , or C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 , in which the heteroatom is N, O or S, and the number of heteroatoms is 1 or 2.

In one embodiment, in the compound shown in Formula I, each R ^3-1 is independently deuterium or a 3-6 membered heterocycloalkyl substituted by one or more ^Ra , wherein the heteroatom in the 3-6 membered heterocycloalkyl is N, O or S, and the number of heteroatoms is 1 or 2.

In one embodiment, in the compound represented by formula I, each R ^3-2 is independently a C _1-6 alkyl group.

In one embodiment, in the compound represented by formula I, each ^Ra is independently a _C1-6 alkyl group.

In one embodiment, in the compound represented by formula I, _X1 and _X2 are _-CH2- .

In one embodiment, in the compound shown in formula I, Z ₁ is CH.

In one embodiment, in the compound represented by formula I, each R ¹ is independently a C _1-6 alkoxy group.

In one embodiment, in the compound shown in Formula I, R ³ is a C _3-6 cycloalkyl group (e.g., cyclopropane group) or a 3-6 membered heterocycloalkyl group (e.g., oxetane group, preferably ).

In one embodiment, in the compound represented by formula I, the compound represented by formula I satisfies the following conditions: R ³ is C _3-6 cycloalkyl or 3-6 membered heterocycloalkyl, for example, R ³ is

In one embodiment, in the compound shown in formula I,

m is 0, 1, 2, 3 or 4;

n is 0, 1, 2, 3, 4 or 5;

_Z1 is N or CH;

X ₁ and X ₂ are each independently a chemical bond or -CH ₂ -;

X ₃ and X ₄ are each independently -CH ₂ -;

each R ¹ is independently cyano, halogen, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^1-1 , C _1-6 alkoxy, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl or C _1-6 alkoxy substituted by 1, 2 or 3 R ^1-2 ;

Each R ^1-1 is independently deuterium or halogen;

Each R ^1-2 is independently deuterium or halogen;

each R ² is independently deuterium, halogen, hydroxyl, C _1-6 alkyl, amino, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, or 3-6 membered heterocycloalkyl substituted with 1, 2 or 3 R ^2-1 ;

Each R ^2-1 is independently halogen, hydroxyl or C _1-6 alkyl;

R ³ is each independently H, C _1-6 alkyl, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 , or 3-6 membered heterocycloalkyl substituted by 1, 2 or 3 R ^3-3 ;

Each R ^3-1 is independently deuterium, halogen, 3-6 membered heterocycloalkyl, or 3-6 membered heterocycloalkyl substituted with one or more ^Ra ;

Each R ^3-2 is independently deuterium, halogen or C _1-6 alkyl;

Each R ^3-3 is independently deuterium, halogen or C _1-6 alkyl;

Each ^Ra is independently deuterium, halogen or _C1-6 alkyl;

The compound shown in formula I satisfies one or both of the following conditions:

IR ³ is each independently C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 , or 3-6 membered heterocycloalkyl substituted by 1, 2 or 3 R ^3-3 ;

II. m is 1, 2, 3 or 4, and each R ¹ is independently a C _2-6 alkoxy group substituted by 1, 2 or 3 R ^1-2 ;

In any of the above 3-6 membered heterocycloalkyl groups, the heteroatom is N, O or S, and the number of heteroatoms is 1, 2 or 3.

In one embodiment, in the compound shown in formula I,

m is 1;

n is 0;

_Z1 is N or CH;

_X1 and _X2 are each independently a chemical bond or _-CH2-

X ₃ and X ₄ are each independently -CH ₂ -;

Each R ¹ is independently a C _1-6 alkoxy group or a C _1-6 alkoxy group substituted by 1, 2 or 3 R ^{1-2 groups} ;

Each R ^1-2 is independently halogen;

R ³ is each independently C _1-6 alkyl, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , or C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 ;

Each R ^3-1 is independently deuterium or a 3-6 membered heterocycloalkyl substituted with one or more ^Ra ;

Each R ^3-2 is independently a C _1-6 alkyl group;

Each ^Ra is independently _C1-6 alkyl;

The compound represented by formula I satisfies one or both of the following conditions:

IR ³ is each independently C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , or C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 ;

II. each R ¹ is independently a C _2-6 alkoxy group substituted by 1, 2 or 3 R ^1-2 ;

In any of the above 3-6 membered heterocycloalkyl groups, the heteroatom is N, O or S, and the number of heteroatoms is 1 or 2.

In one embodiment, in the compound shown in formula I,

m is 1;

n is 0;

_Z1 is N or CH;

_X1 and _X2 are each independently a chemical bond or _-CH2-

X ₃ and X ₄ are each independently -CH ₂ -;

Each R ¹ is independently a C _1-6 alkoxy group or a C _1-6 alkoxy group substituted by 1, 2 or 3 R ^{1-2 groups} ;

Each R ^1-2 is independently halogen;

R ³ is each independently C _1-6 alkyl, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , or C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 ;

Each R ^3-1 is independently deuterium or a 3-6 membered heterocycloalkyl substituted with one or more ^Ra ;

Each R ^3-2 is independently a C _1-6 alkyl group;

Each ^Ra is independently _C1-6 alkyl;

The compound represented by formula I satisfies one or both of the following conditions:

IR ³ is each independently C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , or C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 ;

II. each R ¹ is independently a C _2-6 alkoxy group substituted by 1, 2 or 3 R ^1-2 ;

In any of the above 3-6 membered heterocycloalkyl groups, the heteroatoms are 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1 or 2.

In one embodiment, in the compound shown in formula I,

m is 1;

n is 0;

Z ₁ is CH;

_X1 and _X2 are _-CH2-

_X3 and _X4 are _-CH2- ;

Each R ¹ is independently a C _1-6 alkoxy group;

R ³ is each independently C _3-6 cycloalkyl (e.g. cyclopropane) or 3-6 membered heterocycloalkyl (e.g. oxetanyl, preferably );

The compound represented by formula I satisfies one or both of the following conditions:

IR ³ is each independently C _3-6 cycloalkyl or 3-6 membered heterocycloalkyl;

Any of the above 3-6 membered heterocycloalkyl groups, wherein the heteroatom is N, O or S, and the number of the heteroatom is 1.

In one embodiment, in the compound shown in Formula I, each R ¹ is independently methoxy or

In one embodiment, in the compound represented by formula I, each R ¹ is independently methoxy.

In one embodiment, in the compound shown in formula I, R ³ is each independently -CD ₃ ,

In one embodiment, in the compound shown in formula I, R ³ is each independently Preferably

In one embodiment, the compound represented by formula I is a compound represented by formula I-1,

wherein n, R ¹ , R ² , R ³ , Z ₁ , X ₁ and X ₂ are as described in any one of the present invention.

In one embodiment, the compound represented by formula I-1 is a compound represented by formula I-1-1,

Preferably, the compound shown in formula 1-1-2

wherein n, R ² , R ³ , Z ₁ , X ₁ and X ₂ are as described in any one of the present invention.

In one embodiment, the compound represented by formula I-1 is a compound represented by formula I-1-3, I-1-4 or I-1-5:

Wherein, in the compounds represented by formula I-1-3, formula I-1-4 and formula I-1-5, ^R1 and ^R3 are as described in any one of the present invention.

In a certain embodiment, the compound as shown in formula I, its pharmaceutically acceptable salt, its solvate, or its pharmaceutically acceptable salt solvate, the compound as shown in formula I is any of the following compounds:

The present invention provides a compound as shown in Formula V, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof:

in,

m is 1, 2, 3 or 4;

n is 0, 1, 2, 3, 4 or 5;

Ring A is C _6-7 cycloalkyl;

_Z1 is N or CH;

each R ¹ is independently cyano, halogen, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^1-1 , C _1-6 alkoxy, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl or C _1-6 alkoxy substituted by 1, 2 or 3 R ^1-2 ;

Each R ^1-1 is independently deuterium or halogen;

Each R ^1-2 is independently deuterium or halogen;

Each R ² is independently deuterium, halogen, hydroxyl, carbonyl, C _1-6 alkyl, amino, C _3-7 cycloalkyl or 3-7 membered heterocycloalkyl, or two R ² and the atoms to which they are attached form a C _3-6 cycloalkyl;

R ^N-1 and R ^N-2 are each independently H, deuterium, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^N-1-1 , C _3-6 cycloalkyl, or, R ^N-1 and R ^N-2 and the N atom to which they are attached form a 3-12 membered heterocycloalkyl, and the 3-12 membered heterocycloalkyl is optionally substituted by 1, 2 or 3 R ^N-1-2 ;

Each R ^N-1-1 is independently deuterium, halogen or hydroxyl;

Each R ^N-1-2 is independently deuterium, halogen or hydroxyl;

In any of the above 3-6 membered heterocycloalkyl, 3-7 membered heterocycloalkyl, 3-12 membered heterocycloalkyl, the heteroatom is 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3.

In a certain embodiment of the present invention, certain groups in the compound of formula V, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt are defined as follows, and the unmentioned groups are the same as those described in any embodiment of the present invention (referred to as "a certain embodiment").

In one embodiment, in the compound represented by formula V, in ring A, the C _6-7 cycloalkyl group is a monocyclic C _6-7 cycloalkyl group (eg, cyclohexyl group or cycloheptyl group).

In one embodiment, in the compound represented by formula V, in R ¹ , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound represented by formula V, in ^R1 , the _C1-6 alkyl group and the _C1-6 alkyl group substituted by 1, 2 or 3 ^R1-1 are _each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

In one embodiment _, in the compound represented by formula V, in ^R1 , the _C1-6 alkoxy group and the _C1-6 alkoxy group substituted by 1, 2 or 3 ^R1-2 are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, for example, methoxy or isopropoxy.

In one embodiment, in the compound represented by formula V, in R ¹ , the C _3-6 cycloalkyl groups are each independently cyclopropane, cyclobutane, cyclopentane or cyclohexane.

In one embodiment, in the compound represented by formula V, in ^R1 , the 3-6 membered heterocycloalkyl is a 4-6 membered heterocycloalkyl, in which the heteroatom is preferably N and/or O, and in which the number of heteroatoms is preferably 1 or 2.

In one embodiment, in the compound represented by formula V, in R ^1-1 , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound represented by formula V, in R ^1-2 , the halogen is independently F, Cl, Br or I, for example, F.

In one embodiment, in the compound represented by formula V, in R ² , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound represented by formula V, in R ² , the C _1-6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

In one embodiment, in the compound represented by formula V, in R ² , the C _3-7 cycloalkyl groups are each independently cyclopropane, cyclobutane, cyclopentane or cyclohexane.

In one embodiment, in the compound represented by formula V, in ^R2 , the 3-7 membered heterocycloalkyl groups are each independently 4-6 membered heterocycloalkyl groups, in which the heteroatoms are preferably N and/or O, and in which the heteroatoms are preferably 1 or 2.

In one embodiment, in the compound shown in formula V, when two R ² and the atoms connected thereto form a C _3-6 cycloalkyl group, the C _3-6 cycloalkyl group is cyclopropane, cyclobutane, cyclopentane or cyclohexane, for example, cyclopropane.

In one embodiment, in the compound represented by formula V, in R ^N-1 and _R ^N-2 , the C _1-6 alkyl group and the C _1-6 alkyl group substituted by 1, 2 or 3 R ^{N -1-1} are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, for example, methyl.

In one embodiment, in the compound represented by formula V, in R ^N-1 and R ^N-2 , the C _3-6 cycloalkyl group is independently cyclopropane, cyclobutane, cyclopentane or cyclohexane, for example cyclopropane.

In a certain embodiment, in the compound shown in formula V, when R ^N-1 and R ^N-2 and the N atom connected thereto form a 3-12-membered heterocycloalkyl group, the 3-12-membered heterocycloalkyl group is a 3-6-membered monocyclic heterocycloalkyl group or a 6-12-membered polycyclic heterocycloalkyl group; the 3-6-membered monocyclic heterocycloalkyl group may be a 4-6-membered monocyclic heterocycloalkyl group, in which the heteroatom in the 3-6-membered monocyclic heterocycloalkyl group is preferably N and/or O, and in which the heteroatom number in the 3-6-membered monocyclic heterocycloalkyl group is preferably 1 or 2; for example, the 3-6-membered monocyclic heterocycloalkyl group is an azetidinyl group (for example );

The 6-12 membered polycyclic heterocycloalkyl may be a 6-12 membered spirocyclic heterocycloalkyl; the 6-12 membered spirocyclic heterocycloalkyl may be a 6-8 membered spirocyclic heterocycloalkyl, in which the heteroatom is preferably N and/or O, and in which the number of heteroatoms is preferably 1 or 2; for example, the 6-8 membered spirocyclic heterocycloalkyl is

In a certain embodiment, in the compound shown in formula V, when R ^N-1 and R ^N-2 and the N atom connected thereto form a 3-12-membered heterocycloalkyl group, the 3-12-membered heterocycloalkyl group is a 3-6-membered monocyclic heterocycloalkyl group, the 3-6-membered monocyclic heterocycloalkyl group may be a 4-6-membered monocyclic heterocycloalkyl group, in which the heteroatom is preferably N and/or O, and in which the heteroatom is preferably 1 or 2; for example, the 3-6-membered monocyclic heterocycloalkyl group is an azetidinyl group (for example ).

In one embodiment, in the compound represented by formula V, in the 3-6 membered heterocycloalkyl, 3-7 membered heterocycloalkyl, 3-12 membered heterocycloalkyl, the heteroatom is N, O or S, and the number of heteroatoms is 1, 2 or 3.

In one embodiment, in the compound represented by formula V, in R ^N-1-1 , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound represented by formula V, in R ^N-1-2 , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound represented by formula V, m is 1.

In one embodiment, in the compound represented by formula V, n is 0 or 2;

In one embodiment, in the compound represented by formula V, each R ¹ is independently a C _1-6 alkoxy group or a C _1-6 alkoxy group substituted by 1, 2 or 3 R ^1-2 groups.

In one embodiment, in the compound represented by formula V, each R ^1-2 is independently halogen.

In one embodiment, in the compound shown in formula V, when n is 2, two R ² and the atoms connected thereto form a C _3-6 cycloalkyl group.

In a certain embodiment, in the compound shown in formula V, R ^N-1 and R ^N-2 are each independently H, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^N-1-1 , C _3-6 cycloalkyl, or, R ^N-1 and R ^N-2 and the N atom connected thereto form a 3-12 membered heterocycloalkyl, and the 3-12 membered heterocycloalkyl is optionally substituted by 1, 2 or 3 R ^N-1-2 , and in the 3-12 membered heterocycloalkyl, the heteroatom is N, O or S, and the number of heteroatoms is 1 or 2.

In one embodiment, in the compound represented by formula V, each R ^N-1-1 is independently deuterium.

In one embodiment, in the compound represented by formula V, m is 1.

In one embodiment, in the compound represented by formula V, n is 0.

In one embodiment, in the compound represented by formula V, _Z2 is CH.

In one embodiment, in the compound represented by formula V, each R ¹ is independently a C _1-6 alkoxy group (eg, a methoxy group).

In a certain embodiment, in the compound shown in formula V, R ^N-1 and R ^N-2 are each independently C _1-6 alkyl or C _3-6 cycloalkyl; or, R ^N-1 and R ^N-2 and the N atom connected thereto form a 3-12-membered heterocycloalkyl (e.g., azetidinyl); preferably, R ^N-1 and R ^N-2 are each independently C _1-6 alkyl; or, R ^N-1 and R ^N-2 and the N atom connected thereto form a 3-12-membered heterocycloalkyl (e.g., azetidinyl); further preferably, the 3-12-membered heterocycloalkyl is a 4-6-membered heterocycloalkyl, the heteroatom is N, and the number of heteroatoms is 1 or 2, such as azetidinyl, preferably

In one embodiment, in the compound shown in formula V,

m is 1, 2, 3 or 4;

n is 0, 1, 2, 3, 4 or 5;

Ring A is C _6-7 cycloalkyl;

_Z1 is N or CH;

each R ¹ is independently cyano, halogen, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^1-1 , C _1-6 alkoxy, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl or C _1-6 alkoxy substituted by 1, 2 or 3 R ^1-2 ;

Each R ^1-1 is independently deuterium or halogen;

Each R ^1-2 is independently deuterium or halogen;

Each R ² is independently deuterium, halogen, hydroxyl, carbonyl, C _1-6 alkyl, amino, C _3-7 cycloalkyl or 3-7 membered heterocycloalkyl, or two R ² and the atoms to which they are attached form a C _3-6 cycloalkyl;

R ^N-1 and R ^N-2 are each independently H, deuterium, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^N-1-1 , C _3-6 cycloalkyl, or, R ^N-1 and R ^N-2 and the N atom to which they are attached form a 3-12 membered heterocycloalkyl, and the 3-12 membered heterocycloalkyl is optionally substituted by 1, 2 or 3 R ^N-1-2 ;

Each R ^N-1-1 is independently deuterium, halogen or hydroxyl;

Each R ^N-1-2 is independently deuterium, halogen or hydroxyl;

In any of the above 3-6 membered heterocycloalkyl, 3-7 membered heterocycloalkyl, 3-12 membered heterocycloalkyl, the heteroatom is N, O or S, and the number of heteroatoms is 1, 2 or 3.

In one embodiment, in the compound shown in formula V,

m is 1;

n is 0 or 2;

Ring A is C _6-7 cycloalkyl;

_Z1 is N or CH;

Each R ¹ is independently a C _1-6 alkoxy group or a C _1-6 alkoxy group substituted by 1, 2 or 3 R ^{1-2 groups} ;

Each R ^1-2 is independently halogen;

When n is 2, two R ² and the atoms to which they are attached form a C _3-6 cycloalkyl group;

R ^N-1 and R ^N-2 are each independently H, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^N-1-1 , C _3-6 cycloalkyl, or R ^N-1 and R ^N-2 and the N atom to which they are attached form a 3-12 membered heterocycloalkyl;

Each R ^N-1-1 is independently deuterium;

In any of the above 3-12 membered heterocycloalkyl groups, the heteroatom is N, O or S, and the number of the heteroatoms is 1 or 2.

In one embodiment, in the compound shown in formula V,

m is 1;

n is 0 or 2;

Ring A is C _6-7 cycloalkyl;

_Z1 is N or CH;

Each R ¹ is independently a C _1-6 alkoxy group or a C _1-6 alkoxy group substituted by 1, 2 or 3 R ^{1-2 groups} ;

Each R ^1-2 is independently halogen;

When n is 2, two R ² and the atoms to which they are attached form a C _3-6 cycloalkyl group;

R ^N-1 and R ^N-2 are each independently H, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^N-1-1 , C _3-6 cycloalkyl, or R ^N-1 and R ^N-2 and the N atom to which they are attached form a 3-12 membered heterocycloalkyl;

Each R ^N-1-1 is independently deuterium;

In any of the above 3-12 membered heterocycloalkyl groups, the heteroatoms are 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1 or 2.

In one embodiment, in the compound shown in formula V,

m is 1;

n is 0;

Ring A is C _6-7 cycloalkyl (e.g. cycloheptyl);

_Z2 is CH;

Each R ¹ is independently a C _1-6 alkoxy group;

R ^N-1 and R ^N-2 are each independently C _1-6 alkyl; or, R ^N-1 and R ^N-2 and the N atom to which they are attached form a 3-12 membered heterocycloalkyl (e.g., azetidinyl, preferably );

In any of the above 3-12 membered heterocycloalkyl groups, the heteroatoms are 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1 or 2.

In one embodiment, in the compound represented by formula V, ring A is cyclohexyl or cycloheptyl.

In one embodiment, in the compound represented by formula V, ring A is cycloheptyl.

In one embodiment, in the compound shown in Formula V, each R ¹ is independently methoxy or

In one embodiment, in the compound represented by formula V, each R ¹ is independently methoxy.

In one embodiment, in the compound shown in formula V, when n is 2, two R ² and the atoms connected thereto form a cyclopropane group.

In one embodiment, in the compound represented by formula V, R ^N-1 and R ^N-2 are each independently H, methyl, -CD ₃ or cyclopropane.

In one embodiment, in the compound represented by formula V, R ^N-1 and R ^N-2 are methyl groups.

In one embodiment, in the compound shown in formula V, R ^N-1 and R ^N-2 and the N atom connected thereto form a 3-12 membered heterocycloalkyl group, wherein the 3-12 membered heterocycloalkyl group is

In one embodiment, in the compound shown in formula V, R ^N-1 and R ^N-2 and the N atom connected thereto form a 3-12 membered heterocycloalkyl group, wherein the 3-12 membered heterocycloalkyl group is

In one embodiment, the compound represented by formula V is a compound represented by formula V-1,

Wherein, X ₁ and X ₂ are each independently -CH ₂ - or a chemical bond;

Z ₂ , R ¹ , R ² , ^RN-1 , ^RN-2 and n are as described in any one of the present invention.

In one embodiment, the compound represented by formula V-1 is a compound represented by formula V-1-1 or a compound represented by formula V-1-2.

Wherein, X ₁ and X ₂ are each independently -CH ₂ - or a chemical bond;

R ¹ , R ² , RN ^-1 , ^RN-2 and n are as described in any one of the present invention.

In one embodiment, the compound represented by formula V-1 is a compound represented by formula V-1-1a or a compound represented by formula V-1-2a.

in,

R ¹ , ^RN-1 and ^RN-2 are as described in any one of the present invention.

In one embodiment, the compound represented by formula V-1 is a compound represented by formula V-1-3, a compound represented by formula V-1-4, or a compound represented by formula V-1-5.

Wherein, R ¹ , ^RN-1 and ^RN-2 are as described in any one of the present invention.

In a certain embodiment, the compound represented by formula V, its pharmaceutically acceptable salt, its solvate or its pharmaceutically acceptable salt solvate, the compound represented by formula V is any of the following compounds:

In one embodiment, the compound represented by formula I is In the embodiment, the compound that elutes first under the following liquid phase conditions, preferably, the retention time of the compound that elutes first is 4.9 min, or the retention time of the compound that elutes later is 5.2 min; further preferably, the liquid phase conditions are: C18 chromatographic column, mobile phase A is acetonitrile, mobile phase B is 10 mmol/L ammonium bicarbonate aqueous solution, gradient elution, acetonitrile gradient is 47-53%, and flow rate is 20 mL/min; the liquid phase conditions are further preferably: chromatographic column: Waters-XBndge-C18-10μm-19*250mm, mobile phase A is acetonitrile, mobile phase B is 10 mmol/L ammonium bicarbonate aqueous solution, gradient elution, acetonitrile gradient is 47-53%, and flow rate is 20 mL/min.

In one embodiment, the compound represented by formula I is In the method, the compound that elutes first under the following conditions, preferably, the retention time of the compound that elutes first is 4.9 min, or the retention time of the compound that elutes later is 5.2 min; further preferably, the liquid phase conditions are: C18 chromatographic column, mobile phase A is acetonitrile, mobile phase B is 10 mmol/L ammonium bicarbonate aqueous solution, gradient elution, acetonitrile gradient is 25-55%, and flow rate is 20 mL/min; the conditions are further preferably: chromatographic column: Waters-Xbridge-C18-10 μm-19*250 mm, mobile phase A is acetonitrile, mobile phase B is 10 mmol/L ammonium bicarbonate aqueous solution, gradient elution, acetonitrile gradient is 25-55%, and flow rate is 20 mL/min.

The present invention provides a compound as shown in formula X, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof:

k is 0, 1, or 2;

Z ₃ is O or S;

Each R ^1a is independently C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^1-1a , C _1-6 alkoxy, or C _1-6 alkoxy substituted by 1, 2 or 3 R ^1-2a ;

Each R ^1-1a and R ^1-2a is independently halogen;

R ^3a is C _1-6 alkyl or C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1a ;

Each R ^3-1a is independently halogen.

In a certain embodiment of the present invention, certain groups in the compound of formula X, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt are defined as follows, and the unmentioned groups are the same as those described in any embodiment of the present invention (referred to as "a certain embodiment").

In one embodiment, in the compound represented by formula X, in _R ^1a , the C _1-6 alkoxy group and the C _1-6 alkoxy group substituted by 1, 2 or 3 R ^1-2a are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, for example, methoxy or isopropoxy.

In one embodiment, in the compound represented by formula X, in _R ^1a , the C _1-6 alkyl group and the C _1-6 alkyl group substituted by 1, 2 or 3 R ^1-1a are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, for example, methyl.

In one embodiment _, in the compound represented by formula X, in R ^3a , the C _1-6 alkyl group and the C _1-6 alkyl group substituted by 1, 2 or 3 R ^3-1a are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, for example, methyl.

In one embodiment, in the compound represented by formula X, in R ^1-1a , R ^1-2a and R ^3-1a , the halogen is independently F, Cl, Br or I.

In one embodiment, in the compound represented by formula X, k is 1 or 0.

In one embodiment, in the compound represented by formula X, Z ₃ is S.

In one embodiment, in the compound represented by formula X, R ^1a is C _1-6 alkyl, such as methyl.

In one embodiment, in the compound represented by formula X, R ^3a is C _1-6 alkyl, such as methyl.

In one embodiment, in the compound shown in formula X,

k is 0 or 1;

Z ₃ is S;

R ^1a is C _1-6 alkyl (e.g. methyl);

R ^3a is C _1-6 alkyl (eg methyl).

In one embodiment, in the compound represented by formula X, R ^1a is H or methyl.

In one embodiment, in the compound represented by formula X, R ^3a is methyl.

In one embodiment, the compound represented by formula X, its pharmaceutically acceptable salt, its solvate or its pharmaceutically acceptable salt solvate, the compound represented by formula X is

In one embodiment, the pharmaceutically acceptable salt of the compound represented by Formula X is a formate salt (e.g., a monoformate salt) of the compound represented by Formula X, for example, a monoformate salt of the compound represented by Formula X, for example The monoformate.

The present invention also provides a pharmaceutical composition, comprising a substance Y and a pharmaceutically acceptable carrier, wherein the substance Y is the above-mentioned compound as shown in formula I, its (referring to the compound as shown in formula I) pharmaceutically acceptable salt, its (referring to the compound as shown in formula I) solvate or its (referring to the compound as shown in formula I) pharmaceutically acceptable salt solvate, the above-mentioned compound as shown in formula V, its (referring to the compound as shown in formula V) pharmaceutically acceptable salt, its (referring to the compound as shown in formula V) solvate, its (referring to the compound as shown in formula V) pharmaceutically acceptable salt solvate, the above-mentioned compound as shown in formula X, its (referring to the compound as shown in formula X) pharmaceutically acceptable salt, its (referring to the compound as shown in formula X) solvate or its (referring to the compound as shown in formula X) pharmaceutically acceptable salt solvate.

The present invention also provides a use of a substance X or the above-mentioned pharmaceutical composition in the preparation of a drug for regulating neuronal plasticity, wherein the substance X is the above-mentioned compound as shown in formula I, its (referring to the compound as shown in formula I) pharmaceutically acceptable salt, its (referring to the compound as shown in formula I) solvate or its (referring to the compound as shown in formula I) solvate of a pharmaceutically acceptable salt or the above-mentioned compound as shown in formula V, its (referring to the compound as shown in formula V) pharmaceutically acceptable salt, its (referring to the compound as shown in formula V) solvate, its (referring to the compound as shown in formula V) solvate of a pharmaceutically acceptable salt, the above-mentioned compound as shown in formula X, its (referring to the compound as shown in formula X) pharmaceutically acceptable salt, its (referring to the compound as shown in formula X) solvate or its (referring to the compound as shown in formula X) solvate of a pharmaceutically acceptable salt.

The present invention also provides a use of a substance X or the above-mentioned pharmaceutical composition in the preparation of a drug for treating and/or preventing depression, schizophrenia, anxiety, and post-traumatic stress disorder, wherein the substance X is the above-mentioned compound as shown in formula I, its (referring to the compound as shown in formula I) pharmaceutically acceptable salt, its (referring to the compound as shown in formula I) solvate, or its (referring to the compound as shown in formula I) solvate of a pharmaceutically acceptable salt, or the above-mentioned compound as shown in formula V, its (referring to the compound as shown in formula V) pharmaceutically acceptable salt, its (referring to the compound as shown in formula V) solvate, its (referring to the compound as shown in formula V) solvate of a pharmaceutically acceptable salt, the above-mentioned compound as shown in formula X, its (referring to the compound as shown in formula X) pharmaceutically acceptable salt, its (referring to the compound as shown in formula X) solvate, or its (referring to the compound as shown in formula X) solvate of a pharmaceutically acceptable salt.

The present invention provides a method for preparing the above compound or a pharmaceutically acceptable salt thereof, which is any of the following schemes:

Option 1:

Scheme 1 comprises the following steps: in an organic solvent (such as a mixed solution of methanol and tetrahydrofuran), coupling reaction is carried out with compound Ib and compound Ia to obtain a compound represented by formula I;

Wherein, W ₁ and W ₂ are each independently -OC _1-6 alkyl or -O-Si-(C _1-6 alkyl) ₃ ;

Alternatively, W ₁ is H, W ₂ is oxo (=O);

n, m, R ¹ , R ² , R ³ , Z ₁ , X ₃ , X ₄ , X ₁ and X ₂ are as described in any one of the present invention;

Scheme 2 comprises the following steps: in a mixture of an organic solvent (such as methanol) and an alkali metal (such as magnesium), compound Va is hydrolyzed (such as hydrolyzed under microwave action) to obtain a compound represented by formula V;

Wherein, W ₃ is an amino protecting group, such as p-toluenesulfonyl;

n, m, R ¹ , R ² , Ring A, R ^N-1 , R ^N-2 and Z ₁ are as described in any one of the present invention;

Scheme 3 comprises the following steps: Compound Xa is subjected to a cyclization reaction with a 1-methylhexahydroazepine-4-one salt (e.g., hydrochloride, preferably a mixture of 1-methylhexahydroazepine-4-one hydrochloride and hydrochloric acid) in an organic solvent (e.g., ethanol) to obtain a compound represented by formula X;

W ₄ is C _1-6 alkyl (e.g. tert-butyl);

k, R ^1a , R ^3a and Z ₃ are as described in any one of the present invention.

The present invention provides a compound Va or a compound Xa;

Wherein, W ₃ , n, m, R ¹ , R ² , Ring A, RN ^-1 , RN ^-2 , Z ₁ , k, R ^1a , W ₄ , R ^3a and Z ₃ are as described in any one of the present invention.

In one embodiment, the compound Va is

In one embodiment, the compound Xa is

In addition to the foregoing, when used in the specification and claims of this application, unless otherwise specifically indicated, the following terms have the following meanings:

The term "pharmaceutically acceptable salt" refers to a salt prepared from a compound of the present invention and a relatively nontoxic, pharmaceutically acceptable acid or base. When the compound of the present invention contains a relatively acidic functional group, a base addition salt can be obtained by contacting a neutral form of such compound with a sufficient amount of a pharmaceutically acceptable base in a pure solution or a suitable inert solvent. When the compound of the present invention contains a relatively basic functional group, an acid addition salt can be obtained by contacting a neutral form of such compound with a sufficient amount of a pharmaceutically acceptable acid in a pure solution or a suitable inert solvent.

The term "halogen" refers to F, Cl, Br, I.

The term "alkyl" refers to a linear or branched, saturated, monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C _1-6 ). Alkyl includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, and the like.

The term "alkoxy" refers to a group _-ORX , wherein _RX is alkyl as defined above.

The term "cycloalkyl" refers to a saturated monocyclic, spirocyclic, bridged or paracyclic cyclic group having a specified number of ring carbon atoms (e.g., C _3-12 or C _3-6 ), wherein the ring atoms consist only of carbon atoms. Cycloalkyl includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.

The term "heterocycloalkyl" refers to a saturated monocyclic, spirocyclic, bridged or paracyclic cyclic group with a specified number of ring atoms (e.g., 3-12, 3-6 or 3-5), a specified number of heteroatoms (e.g., 1, 2 or 3), and a specified heteroatom type (1, 2 or 3 of N, O and S). When it is polycyclic, each ring is saturated. Heterocycloalkyl includes, but is not limited to, azetidinyl, oxetanyl, tetrahydropyrrolyl, tetrahydrofuranyl, piperidinyl, morpholinyl, piperazinyl, 2-azaspiro [3,3] heptane, 2-azaspiro [3,5] nonane, or 2-azabicyclo[2.2.2]octanyl.

The term "one or more" means 1, 2, 3, 4 or more.

It will be understood by those skilled in the art that the structural formulas used in the present invention to describe groups are based on the conventions used in the art. It means that the corresponding group R is connected to other fragments and groups in the compound through this site.

The term "pharmaceutically acceptable carrier" refers to excipients and additives used in the production of drugs and the preparation of prescriptions, and is all substances contained in pharmaceutical preparations in addition to the active ingredients. Please refer to the Pharmacopoeia of the People's Republic of China (2020 Edition) Part IV, or Handbook of Pharmaceutical Excipients (Raymond C Rowe, 2009 Sixth Edition).

Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

The reagents and raw materials used in the present invention are commercially available.

The positive and progressive effect of the present invention is that the nitrogen-containing polycyclic compound provided by the present invention has good effects and good pharmacokinetic properties and can be used for the prevention and treatment of neurological diseases.

DETAILED DESCRIPTION

The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

Example 1

Synthesis route:

first step

Compound 1-1 (5.00 g, 33.4 mmol) was dissolved in ethanol (200 mL), and compound 1-1a (5.84 g, 33.4 mmol) and concentrated hydrochloric acid (16.7 mL, 201 mmol, 12 mol/L) were added, and stirred at 60 ° C for 16 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure to remove ethanol, water (20 mL) was added, and the pH was adjusted to 9 with saturated sodium bicarbonate, and extracted with ethyl acetate (30 mL x 7), and the organic phases were combined. The organic phase was washed with saturated brine (150 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain compound 1-2. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.69 (s, 1H), 7.26 (d, J = 8.64 Hz, 1H), 6.77 (d, J = 2.24 Hz, 1H), 6.61 (dd, J = 8.64, 2.24 Hz, 1H), 3.74 (s, 3H), 3.26-3.16 (m, 4H), 3.06-3.02 (m, 2H), 2.97-2.92 (m, 2H). ESI-MS theoretical calculated value: [M+H] ⁺ = 217.13, found 217.1.

Step 2

Compound 1-2 (100 mg, 0.46 mmol) was dissolved in methanol (2 mL) and tetrahydrofuran (2 mL), and compound 1-2a (66.3 mg, 0.92 mmol), sodium cyanoborohydride (116 mg, 1.84 mmol) and acetic acid (0.2 mL) were added, and the mixture was reacted at 50°C for 16 hours. After the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by high performance liquid chromatography (Waters-Xbridge-C18-10 μm-19*250 mm, mobile phase: acetonitrile-10 mmol/L aqueous ammonium bicarbonate solution, gradient: 24-54%, retention time: 1.5 min) to obtain compound 1. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.76 (s, 1H), 7.23 (d, J = 8.64 Hz, 1H), 6.77 (d, J = 2.24 Hz, 1H), 6.62 (dd, J = 8.64, 2.24 Hz, 1H), 4.74-4.70 (m, 2H), 4.67-4.64 (m, 2H), 3.87-3.82 (m, 1H), 3.78 (s, 3H), 2.97-2.92 (m, 2H), 2.89-2.84 (m, 2H), 2.65-2.61 (m, 4H). ESI-MS theoretical calculated value: [M+H] ⁺ = 257.16, found 257.2.

Examples 2 and 3

Synthesis route:

first step

Compound 2-1 (4.95 g, 35.9 mmol) and 1,4-cyclohexanedione monoethylene glycol acetal (5.14 mL, 35.9 mmol) were dissolved in toluene (100 mL), stirred at 130 ° C for 0.5 hours, the reaction solution was cooled to room temperature, concentrated under reduced pressure, ethylene glycol (100 mL) was added to the residue, and stirred at 180 ° C for 3 hours. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and purified by silica gel column chromatography (petroleum ether/ethyl acetate, 3/1, v/v) to obtain compound 2-2. ESI-MS theoretical calculated value: [M+H] ⁺ = 260.12, measured value 260.2.

Step 2

Compound 2-2 (500 mg, 1.93 mmol) was dissolved in N,N-dimethylformamide (10 mL), sodium hydride (80.0 mg, 2.12 mmol, 60%) was added at 0°C, stirred at 0°C for 0.5 hours, p-toluenesulfonyl chloride (440 mg, 2.31 mmol) was added, and stirred at 25°C for 3 hours. Saturated aqueous ammonium chloride solution (20 mL) was added to quench, and ethyl acetate (100 mL×1) was used for extraction. The organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by silica gel column chromatography (petroleum ether/ethyl acetate, 1/1, v/v) to obtain compound 2-3. ESI-MS theoretical calculated value: [M+H] ⁺ = 414.13, measured value 414.2.

Step 3

Compound 2-3 (300 mg, 0.726 mmol) was dissolved in acetone (1 mL), trifluoroacetic acid (5.0 mL, 0.726 mmol) was added, and the mixture was stirred at 65 °C for 2 hours. The reaction solution was cooled to room temperature, quenched with saturated sodium bicarbonate aqueous solution (30 mL), extracted with dichloromethane (30 mL × 2), the organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by silica gel column chromatography (petroleum ether/ethyl acetate, 1/1, v/v) to obtain compound 2-4. ESI-MS theoretical calculated value: [M+H] ⁺ = 370.10, measured value 370.2.

Step 4

Dissolve trimethylsilylated diazomethane in n-hexane (6.16 mL, 12.3 mmol, 2.0 M) in tetrahydrofuran (25 mL), add butyl lithium in n-hexane (5.31 mL, 13.3 mmol, 2.5 M) dropwise at -70°C, and stir at -78°C for 0.5 hours. Add compound 2-4 (3.50 g, 9.47 mmol) in tetrahydrofuran (50 mL) dropwise to the reaction solution at -78°C, and stir at -78°C for 0.5 hours. Add methanol (0.77 mL, 18.9 mmol) to the reaction solution, and stir at 20°C for 0.5 hours. Water (50 mL) was added to the reaction solution to quench the reaction, and the mixture was extracted with ethyl acetate (30 mL×2). The organic phases were combined, washed with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a crude product containing the target compound. The crude product was purified by silica gel column chromatography (petroleum ether/ethyl acetate, 3/1, v/v) to give a mixture of compounds 2-5 and 3-5. ¹ H NMR (400MHz, DMSO-d ₆ ) δ7.74-7.65(m,2H),7.57(t,J＝2.34Hz,1H),7.47-7.32(m,3H),6.90(dd,J＝8.64,2.34Hz,1H),3.82(s,3H),3.38-3.32(m,1H), 3.24-3.20(m,1H),2.97-2.89(m,1H),2.86-2.80(m,1H),2.70-2.63(m,1H),2.60-2.53(m,2H),2.32(s,3H),2.20-2.13(m,1H). ESI-MS theoretical calculated value: [M+H] ⁺ =384.12, found value 384.0.

Step 5

The mixture of intermediates 2-5 and 3-5 (320 mg, 0.83 mmol) and azetidine (47.7 mg, 0.83 mmol) were dissolved in 1,2-dichloroethane (5 mL), sodium triacetoxyborohydride (264 mg, 1.25 mmol) was added at 25°C, and stirred at 20°C for 18 hours. The reaction solution was quenched by adding saturated sodium bicarbonate aqueous solution (30 mL), extracted with ethyl acetate (30 mL×2), and the organic phases were combined, washed with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by silica gel column chromatography (dichloromethane/methanol, 8/1, v/v) to obtain a mixture of compounds 2-6 and 3-6. ESI-MS theoretical calculated value: [M+H] ⁺ = 425.18, found value 425.2.

Step 6

Magnesium (229 mg, 4.71 mmol) was dissolved in methanol (10 mL), and compounds 2-6 and 3-6 (200 mg, 0.48 mmol) were added, and the mixture was stirred at 20 ° C for 3 hours under microwave reaction. Saturated aqueous ammonium chloride solution (20 mL) was added to the reaction solution to quench, filter, wash the filter cake with methanol (5 mL × 3), and concentrate the filtrate under reduced pressure. The residue was purified by high performance liquid chromatography (Waters-XBndge-C18-10μm-19*250mm, mobile phase: acetonitrile-10mmol/L aqueous ammonium bicarbonate solution, gradient: 47-53%, flow rate 20 mL/min, elution time: 9 min) to obtain compound 2 (retention time: 4.9 min). ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.44 (s, 1H), 7.21 (d, J = 8.50 Hz, 1H), 6.73 (d, J = 2.32 Hz, 1H), 6.58 (dd, J = 8.50, 2.32 Hz, 1H), 3.73 (s, 3H), 3.10 (t, J = 6.80 Hz, 4H), 2.84-2.81 (m, 1H), 2.75-2.66 (m, 2H), 2.31-2.25 (m, 1H), 2.11-2.07 m, 1H), 1.94-1.81 (m, 4H), 1.49-1.35 (m, 2H). ESI-MS theoretical calculated value: [M+H] ⁺ = 271.17, found 271.1. and compound 3 (retention time: 5.2 min). ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.41 (s, 1H), 7.21 (d, J = 8.50 Hz, 1H), 6.72 (d, J = 2.32 Hz, 1H), 6.57 (dd, J = 8.50, 2.32 Hz, 1H), 3.73 (s, 3H), 3.12 (t, J = 6.80 Hz, 4H), 2.90-2.80 (m, 2H), 2.63-2.55 (m, 1H), 2.47-2.40 (m, 1H), 2.33-2.27 (m, 1H), 1.93-1.86 (m, 2H), 1.81-1.75 (m, 2H), 1.39-1.27 (m, 2H). ESI-MS theoretical calculated value: [M+H] ⁺ = 271.17, found value 271.1.

Example 4

Synthesis route:

first step

Compound 1-2 (100 mg, 0.46 mmol) was dissolved in methanol (2 mL), and compound 3-oxetanone (66.3 mg, 0.92 mmol) and sodium cyanoborohydride (116 mg, 1.84 mmol) were added, and the mixture was reacted at 25° C. for 16 hours. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by high performance liquid chromatography (Waters-Xbridge-C18-10 μm-19*250 mm, mobile phase: acetonitrile-10 mmol/L aqueous ammonium bicarbonate solution, gradient: 42-72%, retention time: 9 min) to obtain compound 4. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.45 (s, 1H), 7.21 (d, J = 8.62 Hz, 1H), 6.72 (d, J = 2.32 Hz, 1H), 6.57 (dd, J = 8.62, 2.32 Hz, 1H), 3.72 (s, 3H), 2.95-2.90 (m, 4H), 2.89-2.84 (m, 2H), 2.77-2.74 (m, 2H), 2.14-2.10 (m, 1H), 0.53-0.48 (m, 2H), 0.41-0.38 (m, 2H). ESI-MS theoretical calculated value: [M+H] ⁺ = 273.15, found 273.2.

Examples 5 and 6

Synthesis route:

first step

The mixture of compounds 2-5 and 3-5 (100 mg, 0.26 mmol) and dimethylamine hydrochloride (42.5 mg, 0.52 mmol) were dissolved in methanol (5 mL), triethylamine (52.8 mg, 0.52 mmol) was added, and the mixture was stirred at 20°C for 10 minutes. Acetic acid (23.5 mg, 0.39 mmol) was added to the reaction solution and stirred for 1 hour. Sodium triacetoxyborohydride (110 mg, 0.52 mmol) was added and stirred at 20°C for 16 hours. Water (10 mL) was added to the reaction solution, and the mixture was extracted with dichloromethane (10 mL × 2). The organic phases were combined, washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by silica gel column chromatography (dichloromethane/methanol, 10/1, v/v) to obtain a mixture of compounds 5-1 and 6-1. ESI-MS theoretical calculated value: [M+H] ⁺ = 413.18, found value 413.2.

Step 2

Magnesium (94.3 mg, 1.94 mmol) was dissolved in methanol (2 mL), and compounds 5-1 and 6-1 (40.0 mg, 0.10 mmol) were added, and the reaction was stirred at 25 ° C for 1 hour in a microwave reaction. Saturated aqueous ammonium chloride solution (5 mL) was added to the reaction solution to quench, filter, wash the filter cake with methanol (5 mL × 3), and concentrate the filtrate under reduced pressure. The residue was purified by high performance liquid chromatography (Waters-Xbridge-C18-10μm-19*250mm, mobile phase: acetonitrile-10mmol/L aqueous ammonium bicarbonate solution, gradient: 25-55%, flow rate 20mL/min, elution time: 9min) to obtain compound 5 (retention time: 4.9min) or compound 6 (retention time: 5.2min). ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.42 (s, 1H), 7.24 (d, J = 8.52 Hz, 1H), 6.72 (d, J = 2.26 Hz, 1H), 6.58 (dd, J = 8.52, 2.26 Hz, 1H), 3.72 (s, 3H), 2.95-2.92 (m, 1H), 2.77-2.63 (m, 4H), 2.22 (s, 6H), 1.76-1.65 (m, 2H), 1.57-1.45 (m, 2H). ESI-MS theoretical calculated value: [M+H] ⁺ = 259.17, found 259.1. Compound 5 or Compound 6. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.43 (s, 1H), 7.22 (d, J = 8.52 Hz, 1H), 6.72 (d, J = 2.24 Hz, 1H), 6.57 (dd, J = 8.52, 2.24 Hz, 1H), 3.72 (s, 3H), 2.98-2.85 (m, 2H), 2.64-2.60 (m, 2H), 2.42-2.39 (m, 1H), 2.20 (s, 6H), 1.97-1.94 (m, 2H), 1.59-1.46 (m, 2H). ESI-MS theoretical calculated value: [M+H] ⁺ = 259.17, found 259.1.

Example 7

Synthesis route:

first step

Under nitrogen protection, cuprous iodide (0.91 g, 4.76 mmol) was added to N, N-dimethylformamide (70 mL), and 2-iodothiophene (5.00 g, 23.8 mmol), compound 7-1 (3.78 g, 28.6 mmol), cesium carbonate (15.5 g, 47.6 mmol) and 1,10-phenanthroline (1.03 g, 5.71 mmol) were added. Stir at 70 ° C for 4 hours under nitrogen protection. The reaction solution was cooled to room temperature, and water (100 mL) was added, and ethyl acetate (50 mL x 3) was extracted. The organic phases were combined, washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by silica gel column chromatography (petroleum ether/ethyl acetate, 10/1, v/v) to obtain compound 7-2. ¹ H NMR (400MHz, CDCl ₃ ) δ6.93 (s, 1H), 6.92-6.81 (m, 2H), 4.70 (s, 2H), 1.57 (s, 9H).

Step 2

Compound 7-2 (2.00 g, 9.33 mmol) was dissolved in ethanol (100 mL), and 1-methylhexahydroazepine-4-one hydrochloride (1.53 g, 9.33 mmol) and concentrated hydrochloric acid (5.13 mL, 61.6 mmol) were added. Stir at 100 °C for 6 hours. The reaction solution was cooled to room temperature, and a saturated sodium bicarbonate aqueous solution was added dropwise to adjust the pH to 9, and extracted with ethyl acetate (30 mL x 4). The organic phases were combined, washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. The residue was purified by high performance liquid chromatography (Waters-Xbridge-C18-10 μm-19*250 mm, mobile phase: acetonitrile-10 mmol/L ammonium bicarbonate aqueous solution, gradient: 18-48%, retention time: 9 min) to obtain compound 7. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 10.81 (s, 1H), 6.86 (d, J = 5.20 Hz, 1H), 6.79 (d, J = 5.20 Hz, 1H), 2.82-2.75 (m, 2H), 2.74-2.69 (m, 2H), 2.66-2.62 (m, 4H), 2.44 (s, 3H). ESI-MS theoretical calculated value: [M+H] ⁺ = 207.09, found 207.1.

Example 8

Synthesis route:

first step

Under nitrogen protection, cuprous iodide (1.70 g, 8.93 mmol) was added to N, N-dimethylformamide (100 mL), followed by compound 8-1 (10.0 g, 44.6 mmol), tert-butyl carbazate (8.85 g, 67.0 mmol), cesium carbonate (29.08 g, 89.26 mmol) and 1,10-phenaloline (1.93 g, 10.71 mmol). Stir at 70 °C for 18 hours. The reaction solution was added with aqueous solution (100 mL), extracted with ethyl acetate (150 mL x 3), the organic phases were combined, washed with saturated brine (100 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound, which was purified by silica gel column chromatography (petroleum ether/ethyl acetate, 10/1, v/v) to obtain compound 8-2. ¹ H NMR (400MHz, DMSO-d ₆ ) δ6.57 (d, J = 3.52 Hz, 1H), 6.47 (d, J = 3.08 Hz, 1H), 5.30 (s, 2H), 2.30 (s, 3H), 1.48 (s, 9H).

Step 2

Compound 8-2 (1.00 g, 4.38 mmol) was dissolved in ethanol (20 mL), and 1-methylhexahydroazepine-4-one hydrochloride (720 mg, 4.38 mmol) and concentrated hydrochloric acid (2 mL, 17.9 mmol, 33% purity) were added. The reaction solution was stirred at 60 ° C for 18 hours. After the reaction was completed, it was concentrated under reduced pressure, and saturated sodium bicarbonate aqueous solution (50 mL) was added to the residue, and ethyl acetate (50 mL x 3) was extracted. The organic phases were combined, washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product containing the target compound. The residue was purified by high performance liquid chromatography (Waters-SunFire-C18-10μm-19*250mm, mobile phase: acetonitrile-10mmol/L formic acid aqueous solution, gradient: 18-48%, retention time: 9min) to obtain the monoformate of compound 8. ¹ H NMR (400 MHz, DMSO-d ₆ )δ10.68(s,1H),8.19(s,1H),6.55(s,1H),2.83-2.75(m,2H),2.74-2.66(m,6H),2.37(s,6H).ESI-MS theoretical calculated value: [M+H] ⁺ =221.10, found value 221.0.

Effect Example 1 Evaluation of the calcium flux agonist activity of the compound on 5-HT _2A receptor

Purpose:

The activity of the compounds on 5-HT _2A receptors was determined using a stable transgenic cell line (HEK293 cells) expressing human 5-HT _2A receptors.

Experimental equipment:

Experimental operation:

Day 1: Cell seeding and compound preparation

Test compounds were diluted to 400-fold concentration of stock solution on 384-well LDV plates using DMSO. The compound solution was then transferred to the 384-well plate.

HEK-293/5-HT _2A cells were cultured using DMEM medium (10% FBS), and when the cells reached 80% of the density, the cells were detached using 0.25% Trypsin-EDTA.

The cell density was measured and the cells were diluted using DMEM (10% FBS).

30 μl of cells (25,000 cells per well) were added to each well of a Matrigel-coated 384-well plate using Multidrop and incubated at 37° C., 5% CO 2 for 20-24 hours.

Day 2: Cell-Based Experimental Procedures

The culture medium was removed from the cell plate, and 40 μl of fluorescent dye was added to each well of the cell plate. The cells were incubated at 37°C, 5% CO2 in the dark for 0.5 hours.

Add 20 μl of assay buffer (1X HBSS + 20 mM HEPES + 0.1% BSA) to each well in the compound plate to prepare a 5x concentration of agonist working solution for calcium signal readings. Program to add 10 μl of compound to the cell plate (10 μl + 40 μl) to collect activation data.

10. Read and save the data using the FLIPR at room temperature using the specified settings.

Data Analysis:

Compound dilutions were prepared from 20 mmol dimethyl sulfoxide (DMSO) stock solutions. Compound additions were performed on a fluorescence imaging plate reader and fluorescence changes reflecting calcium ion release were monitored every 1 second for 130 seconds (excitation wavelength = 470-495 nm, emission wavelength = 515-575 nm). Data were exported as the difference between maximum and minimum fluorescence for each well. Results were calculated using nonlinear regression to determine agonist EC ₅₀ and Emax values (using XL-fit and Graphpad Prism software).

Experimental results:

Experimental conclusion:

The experimental samples (compounds) were prepared from the corresponding examples. The results are shown in the table above. The compounds of the present application showed agonist activity on 5-HT _2A receptors in the test system.

Evaluation of the pharmacokinetic properties of the compound in mice

Purpose:

The pharmacokinetic properties of the examples of the present invention were evaluated in CD-1 mice.

Experimental Materials:

Experimental operation:

The pharmacokinetic characteristics of the compounds in rodents after subcutaneous injection and oral gavage were tested by standard protocols. In the experiment, the candidate compounds were prepared into clear solutions or suspensions with the specified solvents and administered to three mice subcutaneously and orally by gavage. The solvents for intravenous injection, subcutaneous injection and oral gavage were all 10% sulfobutyl-β-cyclodextrin aqueous solution. Whole blood samples were collected within 8 hours into commercial EDTA2K anticoagulant tubes, centrifuged to obtain the upper plasma sample, and acetonitrile solution containing internal standard was added to precipitate protein. The supernatant was centrifuged and added with an equal volume of water. After centrifugation, the supernatant was sampled and the blood drug concentration was quantitatively analyzed by LCMS/MS analysis method and the pharmacokinetic parameters were calculated.

Experimental methods:

Experimental results:

Experimental conclusion:

The test samples were prepared from the corresponding examples, and the results showed that the compounds of the examples of the present invention had good pharmacokinetic properties in mice.

Claims (14)

1. A compound as shown in formula X, a compound as shown in formula I or a compound as shown in formula V, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof, characterized in that: Among them, in the compound represented by formula X, k is 0, 1, or 2; Z ₃ is O or S; Each R ^1a is independently C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^1-1a , C _1-6 alkoxy, or C _1-6 alkoxy substituted by 1, 2 or 3 R ^1-2a ; Each R ^1-1a and R ^1-2a is independently halogen; R ^3a is C _1-6 alkyl or C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1a ; Each R ^3-1a is independently halogen; In the compound shown in formula I, m is 0, 1, 2, 3 or 4; n is 0, 1, 2, 3, 4 or 5; _Z1 is N or CH; X ₁ and X ₂ are each independently a chemical bond or -CH ₂ -; X ₃ and X ₄ are each independently -CH ₂ -; each R ¹ is independently cyano, halogen, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^1-1 , C _1-6 alkoxy, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl or C _1-6 alkoxy substituted by 1, 2 or 3 R ^1-2 ; Each R ^1-1 is independently deuterium or halogen; Each R ^1-2 is independently deuterium or halogen; each R ² is independently deuterium, halogen, hydroxyl, C _1-6 alkyl, amino, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, or 3-6 membered heterocycloalkyl substituted with 1, 2 or 3 R ^2-1 ; Each R ^2-1 is independently halogen, hydroxyl or C _1-6 alkyl; R ³ is H, C _1-6 alkyl, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 , or 3-6 membered heterocycloalkyl substituted by 1, 2 or 3 R ^3-3 ; Each R ^3-1 is independently deuterium, halogen, 3-6 membered heterocycloalkyl, or 3-6 membered heterocycloalkyl substituted with one or more ^Ra ; Each R ^3-2 is independently deuterium, halogen or C _1-6 alkyl; Each R ^3-3 is independently deuterium, halogen or C _1-6 alkyl; Each ^Ra is independently deuterium, halogen or _C1-6 alkyl; The compound shown in formula I satisfies one or both of the following conditions: IR ³ is C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2, or 3-6 membered heterocycloalkyl substituted by 1, 2 or 3 R ^3-3 ; II. m is 1, 2, 3 or 4, and each R ¹ is independently a C _2-6 alkoxy group substituted by 1, 2 or 3 R ^1-2 ; Wherein, the 3-6 membered heterocycloalkyl group has one, two or three heteroatoms selected from N, O and S, and the number of heteroatoms is one, two or three; In the compound represented by formula V, m is 1, 2, 3 or 4; n is 0, 1, 2, 3, 4 or 5; Ring A is C _6-7 cycloalkyl; _Z1 is N or CH; each R ¹ is independently cyano, halogen, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^1-1 , C _1-6 alkoxy, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl or C _1-6 alkoxy substituted by 1, 2 or 3 R ^1-2 ; Each R ^1-1 is independently deuterium or halogen; Each R ^1-2 is independently deuterium or halogen; Each R ² is independently deuterium, halogen, hydroxyl, carbonyl, C _1-6 alkyl, amino, C _3-7 cycloalkyl or 3-7 membered heterocycloalkyl, or two R ² and the atoms to which they are attached form a C _3-6 cycloalkyl; R ^N-1 and R ^N-2 are each independently H, deuterium, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^N-1-1 , C _3-6 cycloalkyl, or, R ^N-1 and R ^N-2 and the N atom to which they are attached form a 3-12 membered heterocycloalkyl, and the 3-12 membered heterocycloalkyl is optionally substituted by 1, 2 or 3 R ^N-1-2 ; Each R ^N-1-1 is independently deuterium, halogen or hydroxyl; Each R ^N-1-2 is independently deuterium, halogen or hydroxyl; Among them, in the 3-6 membered heterocycloalkyl, 3-7 membered heterocycloalkyl and 3-12 membered heterocycloalkyl, the heteroatoms are 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3. 2. The compound of formula X, the compound of formula I or the compound of formula V according to claim 1, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof, characterized in that the compound of formula I satisfies one or more of the following conditions: (1) In R ¹ , the halogen is independently F, Cl, Br or I; (2) In R ¹ , the C _1-6 alkyl group and the C _1-6 alkyl group substituted by 1, 2 or ₃ R ^1-1 are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; (3) In R ¹ , the C _1-6 alkoxy group and the C _1-6 alkoxy group substituted by 1, 2 or ₃ R ^1-2 are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, such as methoxy; (4) In R ¹ , the C _3-6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; (5) In ^R1 , the 3-6 membered heterocycloalkyl group is independently a 4-6 membered heterocycloalkyl group, wherein the heteroatom in the 4-6 membered heterocycloalkyl group is preferably N and/or O, and the number of heteroatoms in the 4-6 membered heterocycloalkyl group is preferably 1 or 2; (6) In R ^1-1 , the halogen is independently F, Cl, Br or I; (7) In R ^1-2 , the halogen is independently F, Cl, Br or I, for example, F; (8) In R ² , the halogen is independently F, Cl, Br or I; (9) In R ² , the C _1-6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; (10) In R ² , the C _3-6 cycloalkyl groups are each independently cyclopropane, cyclobutane, cyclopentane or cyclohexane; (11) In R ² , the 3-6-membered heterocycloalkyl group and the 3-6-membered heterocycloalkyl group substituted by 1, 2 or 3 R ^2-1 are each independently a 4-6-membered heterocycloalkyl group, wherein the heteroatom in the 4-6-membered heterocycloalkyl group is preferably N and/or O, and the number of heteroatoms in the 4-6-membered heterocycloalkyl group is preferably 1 or 2; (12) In R ^2-1 , the halogen is independently F, Cl, Br or I; (13) In R ^2-1 , the C _1-6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; (14) In R ³ , the C _1-6 alkyl group and the C _1-6 alkyl group substituted by 1, 2 or 3 _R ^3-1 are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, for example, methyl, isopropyl or tert-butyl; (15) In R ³ , the C _3-6 cycloalkyl group and the C _3-6 cycloalkyl group substituted by 1, ₂ or 3 R ^3-2 are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclopropyl; (16) In R ³ , the 3-6-membered heterocycloalkyl group and the 3-6-membered heterocycloalkyl group substituted by 1, 2 or 3 R ^3-3 are each independently a 4-6-membered heterocycloalkyl group, wherein the heteroatom in the 4-6-membered heterocycloalkyl group is preferably N and/or O, and the number of heteroatoms in the 4-6-membered heterocycloalkyl group is preferably 1 or 2. For example, the 4-6-membered heterocycloalkyl group is an oxetane group, and the oxetane group may be (17) In R ^3-1 , the halogen is independently F, Cl, Br or I; (18) In R ^3-1 , the 3-6-membered heterocycloalkyl group and the 3-6-membered heterocycloalkyl group substituted by one or more ^Ra are each independently a 4-6-membered heterocycloalkyl group, wherein the heteroatom in the 4-6-membered heterocycloalkyl group is preferably N and/or O, and the number of heteroatoms in the 4-6-membered heterocycloalkyl group is preferably 1 or 2. For example, the 4-6-membered heterocycloalkyl group is an oxetane group, and the oxetane group may be (19) In R ^3-2 , the halogen is independently F, Cl, Br or I; (20) In R ^3-2 , the C _1-6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, for example, methyl; (21) In R ^3-3 , the halogen is independently F, Cl, Br or I; (22) In R ^3-3 , the C _1-6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; (23) In ^Ra , the halogen is independently F, Cl, Br or I; (24) In ^Ra , the _C1-6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, for example, methyl; (25) In R ¹ , the C _2-6 alkoxy group substituted by 1, 2 or 3 R ^1-2 is independently ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, such as isopropoxy. The C _2-6 alkoxy group substituted by 1, 2 or ₃ R ^1-2 is preferably For example Alternatively, the compound represented by formula V satisfies one or more of the following conditions: (1) In ring A, the C _6-7 cycloalkyl group is a monocyclic C _6-7 cycloalkyl group; (2) In R ¹ , the halogen is independently F, Cl, Br or I; (3) In R ¹ , the C _1-6 alkyl group and the C _1-6 alkyl group substituted by 1, 2 or ₃ R ^1-1 are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; (4) In R ¹ , the C _1-6 alkoxy group and the C _1-6 alkoxy group substituted by 1, 2 or ₃ R ^1-2 are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, such as methoxy or isopropoxy; (5) In R ¹ , the C _3-6 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; (6) In ^R1 , the 3-6 membered heterocycloalkyl group is a 4-6 membered heterocycloalkyl group, wherein the heteroatom in the 4-6 membered heterocycloalkyl group is preferably N and/or O, and the number of heteroatoms in the 4-6 membered heterocycloalkyl group is preferably 1 or 2; (7) In R ^1-1 , the halogen is independently F, Cl, Br or I; (8) In R ^1-2 , the halogen is independently F, Cl, Br or I, for example, F; (9) In R ² , the halogen is independently F, Cl, Br or I; (10) In R ² , the C _1-6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; (11) In R ² , the C _3-7 cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; (12) In R ² , the 3-7-membered heterocycloalkyl group is each independently a 4-6-membered heterocycloalkyl group, wherein the heteroatom in the 4-6-membered heterocycloalkyl group is preferably N and/or O, and the number of heteroatoms in the 4-6-membered heterocycloalkyl group is preferably 1 or 2; (13) When two R ² and the atoms to which they are attached form a C _3-6 cycloalkyl group, the C _3-6 cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclopropyl; (14) In R ^N-1 and R ^N-2 , the C _1-6 alkyl group and the C _1-6 alkyl group substituted by 1, 2 or 3 R ^N-1-1 are each independently methyl, ethyl, n _- propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, for example methyl; (15) In R ^N-1 and R ^N-2 , the C _3-6 cycloalkyl group is each independently cyclopropane, cyclobutane, cyclopentane or cyclohexane, for example cyclopropane; (16) When R ^N-1 and R ^N-2 form a 3-12-membered heterocycloalkyl group with the N atom connected thereto, the 3-12-membered heterocycloalkyl group is a 3-6-membered monocyclic heterocycloalkyl group or a 6-12-membered polycyclic heterocycloalkyl group; the 3-6-membered monocyclic heterocycloalkyl group may be a 4-6-membered monocyclic heterocycloalkyl group, in which the heteroatom is preferably N and/or O, and in which the heteroatom is preferably 1 or 2; for example, the 3-6-membered monocyclic heterocycloalkyl group is an azetidinyl group, and the azetidinyl group may be The 6-12 membered polycyclic heterocycloalkyl may be a 6-12 membered spirocyclic heterocycloalkyl; the 6-12 membered spirocyclic heterocycloalkyl may be a 6-8 membered spirocyclic heterocycloalkyl, in which the heteroatom is preferably N and/or O, and in which the number of heteroatoms is preferably 1 or 2; for example, the 6-8 membered spirocyclic heterocycloalkyl is (17) In the compound represented by formula V, in R ^N-1-1 , the halogen is independently F, Cl, Br or I; (18) In the compound represented by formula V, in R ^N-1-2 , the halogen is independently F, Cl, Br or I; Alternatively, the compound represented by formula X satisfies one or more of the following conditions: (1) In R ^1a , the C _1-6 alkoxy group and the C _1-6 alkoxy group substituted by 1, 2 or ₃ R ^1-2a are each independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, such as methoxy or isopropoxy; (2) In R ^1a , the C _1-6 alkyl group and the C _1-6 alkyl group substituted by 1, 2 or ₃ R ^1-1a are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, such as methyl; (3) In R ^3a , the C _1-6 alkyl group and the C _1-6 alkyl group substituted by 1, 2 or ₃ R ^3-1a are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, such as methyl; (4) In R ^1-1a , R ^1-2a and R ^3-1a , the halogen is each independently F, Cl, Br or I. 3. The compound of formula X, the compound of formula I or the compound of formula V according to claim 1, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof, characterized in that: The compound as shown in formula I satisfies one or more of the following conditions: (1) m is 1; (2) n is 0; (3) each R ¹ is independently a C _1-6 alkoxy group or a C _1-6 alkoxy group substituted by 1, 2 or 3 R ^{1-2 groups} ; (4) R ³ is each independently C _1-6 alkyl, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , or C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 , wherein the heteroatom in the 3-6 membered heterocycloalkyl is N, O or S, and the number of heteroatoms is 1 or 2; for example, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , or C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 , wherein the heteroatom in the 3-6 membered heterocycloalkyl is N, O or S, and the number of heteroatoms is 1 or 2; (5) Each R ^3-1 is independently deuterated or a 3-6-membered heterocycloalkyl substituted by one or more ^Ra , wherein the heteroatom in the 3-6-membered heterocycloalkyl is N, O or S, and the number of heteroatoms is 1 or 2; (6) Each R ^3-2 is independently a C _1-6 alkyl group; (7) each ^Ra is independently a _C1-6 alkyl group; Alternatively, the compound as shown in formula V satisfies one or more of the following conditions: (1) m is 1; (2) n is 0 or 2; (3) each R ¹ is independently a C _1-6 alkoxy group or a C _1-6 alkoxy group substituted by 1, 2 or 3 R ^{1-2 groups} ; (4) Each R ^1-2 is independently halogen; (5) When n is 2, two R ² and the atoms to which they are attached form a C _3-6 cycloalkyl group; (6) R ^N-1 and R ^N-2 are each independently H, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^N-1-1 , or C _3-6 cycloalkyl; or, R ^N-1 and R ^N-2 and the nitrogen atom to which they are attached form a 3-12 membered heterocycloalkyl, wherein the 3-12 membered heterocycloalkyl is optionally substituted by 1, 2 or 3 R ^N-1-2 , wherein the heteroatom in the 3-12 membered heterocycloalkyl is N, O or S, and the number of heteroatoms is 1 or 2; (7) Each R ^N-1-1 is independently deuterium. 4. The compound of formula X, the compound of formula I or the compound of formula V according to claim 1, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof, characterized in that the compound of formula I satisfies one or more of the following conditions: (1) In _R ³ , the C _3-6 cycloalkyl group and the C _3-6 cycloalkyl group substituted by 1, 2 or 3 R ^3-2 are each independently cyclobutane, cyclopentane or cyclohexane; (2) In the compound represented by formula I, the 3-6 membered heterocycloalkyl group has a heteroatom of N, O or S, and the number of heteroatoms is 1, 2 or 3; (3) The compound shown in formula I is not (4) Each R ^1-1 is independently halogen; (5) Each R ^1-2 is independently halogen; (6) _X1 and _X2 are _-CH2- ; (7) Z ₁ is CH; (8) Each R ¹ is independently a C _1-6 alkoxy group, such as a methoxy group; (9) R ³ is a C _3-6 cycloalkyl group or a 3-6 membered heterocycloalkyl group, such as a cyclopropane group or an oxetane group, wherein the oxetane group is Preferably, in the compound represented by formula I, the compound represented by formula I satisfies the following conditions: R ³ is C _3-6 cycloalkyl or 3-6 membered heterocycloalkyl, for example, R ³ is Alternatively, the compound as shown in formula V satisfies one or more of the following conditions: (1) m is 1; (2) n is 0; (3) Z ₂ is CH; (4) Each R ¹ is independently a C _1-6 alkoxy group, such as a methoxy group; (5) R ^N-1 and R ^N-2 are each independently C _1-6 alkyl or C _3-6 cycloalkyl; or, R ^N-1 and R ^N-2 and the nitrogen atom to which they are attached form a 3-12-membered heterocycloalkyl (e.g., azetidinyl); preferably, R ^N-1 and R ^N-2 are each independently C _1-6 alkyl; or, R ^N-1 and R ^N-2 and the nitrogen atom to which they are attached form a 3-12-membered heterocycloalkyl; Further preferably, when R ^N-1 and R ^N-2 form a 3-12-membered heterocycloalkyl with the N atom connected thereto, the 3-12-membered heterocycloalkyl is a 3-6-membered monocyclic heterocycloalkyl, the 3-6-membered monocyclic heterocycloalkyl may be a 4-6-membered monocyclic heterocycloalkyl, in which the heteroatom is preferably N and/or O, and in which the heteroatom is preferably 1 or 2; for example, the 3-6-membered monocyclic heterocycloalkyl is an azetidinyl, preferably (6) In the 3-6 membered heterocycloalkyl, 3-7 membered heterocycloalkyl, 3-12 membered heterocycloalkyl, the heteroatom is N, O or S, and the number of heteroatoms is 1, 2 or 3; (7) Ring A is cycloheptyl; (8) R ^N-1 and R ^N-2 are methyl groups; Alternatively, the compound represented by formula X satisfies one or more of the following conditions: (1) k is 1 or 0; (2) Z ₃ is S; (3) R ^1a is C _1-6 alkyl, such as methyl; (4) R ^3a is C _1-6 alkyl, such as methyl. 5. The compound of formula X, the compound of formula I or the compound of formula V according to claim 1, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof, characterized in that the compound of formula I is a compound of formula I-1, wherein n, R ¹ , R ² , R ³ , Z ₁ , X ₁ and X ₂ are as described in claim 1; Preferably, the compound represented by formula I-1 is a compound represented by formula I-1-1, wherein n, R ² , R ³ , Z ₁ , X ₁ and X ₂ are as described in claim 1; Further preferably, the compound shown in formula I-1 is a compound shown in formula 1-1-2 wherein n, R ² , R ³ , X ₁ and X ₂ are as described in claim 1; For example, the compound represented by formula I-1 is a compound represented by formula I-1-3, I-1-4 or I-1-5: Wherein, in the compounds represented by formula I-1-3, formula I-1-4, and formula I-1-5, R ¹ and R ³ are as described in claim 1; Alternatively, the compound represented by formula V is a compound represented by formula V-1, Wherein, X ₁ and X ₂ are each independently -CH ₂ - or a chemical bond; Z ₁ , R ¹ , R ² , RN ^-1 , ^RN-2 and n are as described in claim 1; Preferably, the compound represented by formula V-1 is a compound represented by formula V-1-1 or a compound represented by formula V-1-2, Wherein, X ₁ and X ₂ are each independently -CH ₂ - or a chemical bond; R ¹ , R ² , R ^N-1 , R ^N-2 and n are as described in claim 1; Further preferably, the compound represented by formula V-1 is a compound represented by formula V-1-3, a compound represented by formula V-1-4 or a compound represented by formula V-1-5. wherein R ¹ , ^RN-1 and ^RN-2 are as described in claim 1. 6. The compound of formula X, the compound of formula I or the compound of formula V according to claim 5, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof, characterized in that the compound of formula V-1 is a compound of formula V-1-1a or a compound of formula V-1-2a, in, R ¹ , R ^N-1 and R ^N-2 are as described in claim 5. 7. The compound of formula X, the compound of formula I or the compound of formula V according to claim 1, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof, characterized in that the compound of formula I is any of the following: Option 1: m is 1; n is 0; _Z1 is N or CH; _X1 and _X2 are each independently a chemical bond or _-CH2- X ₃ and X ₄ are each independently -CH ₂ -; Each R ¹ is independently a C _1-6 alkoxy group or a C _1-6 alkoxy group substituted by 1, 2 or 3 R ^{1-2 groups} ; Each R ^1-2 is independently halogen; R ³ is each independently C _1-6 alkyl, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , or C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 ; Each R ^3-1 is independently deuterium or a 3-6 membered heterocycloalkyl substituted with one or more ^Ra ; Each R ^3-2 is independently a C _1-6 alkyl group; Each ^Ra is independently _C1-6 alkyl; The compound shown in formula I satisfies one or both of the following conditions: IR ³ is each independently C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , or C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 ; II. each R ¹ is independently a C _2-6 alkoxy group substituted by 1, 2 or 3 R ^1-2 ; Any of the above 3-6 membered heterocycloalkyl groups, wherein the heteroatom is N, O or S, and the number of heteroatoms is 1 or 2; Option 2: In the compound shown in formula I, m is 0, 1, 2, 3 or 4; n is 0, 1, 2, 3, 4 or 5; _Z1 is N or CH; X ₁ and X ₂ are each independently a chemical bond or -CH ₂ -; X ₃ and X ₄ are each independently -CH ₂ -; each R ¹ is independently cyano, halogen, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^1-1 , C _1-6 alkoxy, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl or C _1-6 alkoxy substituted by 1, 2 or 3 R ^1-2 ; Each R ^1-1 is independently deuterium or halogen; Each R ^1-2 is independently deuterium or halogen; each R ² is independently deuterium, halogen, hydroxyl, C _1-6 alkyl, amino, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, or 3-6 membered heterocycloalkyl substituted with 1, 2 or 3 R ^2-1 ; Each R ^2-1 is independently halogen, hydroxyl or C _1-6 alkyl; R ³ is each independently H, C _1-6 alkyl, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 , or 3-6 membered heterocycloalkyl substituted by 1, 2 or 3 R ^3-3 ; Each R ^3-1 is independently deuterium, halogen, 3-6 membered heterocycloalkyl, or 3-6 membered heterocycloalkyl substituted with one or more ^Ra ; Each R ^3-2 is independently deuterium, halogen or C _1-6 alkyl; Each R ^3-3 is independently deuterium, halogen or C _1-6 alkyl; Each ^Ra is independently deuterium, halogen or _C1-6 alkyl; The compound shown in formula I satisfies one or both of the following conditions: IR ³ is each independently C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 , or 3-6 membered heterocycloalkyl substituted by 1, 2 or 3 R ^3-3 ; II. m is 1, 2, 3 or 4, and each R ¹ is independently a C _2-6 alkoxy group substituted by 1, 2 or 3 R ^1-2 ; Any of the above 3-6 membered heterocycloalkyl groups, wherein the heteroatom is N, O or S, and the number of heteroatoms is 1, 2 or 3; Option 3: m is 1; n is 0; _Z1 is N or CH; _X1 and _X2 are each independently a chemical bond or _-CH2- X ₃ and X ₄ are each independently -CH ₂ -; Each R ¹ is independently a C _1-6 alkoxy group or a C _1-6 alkoxy group substituted by 1, 2 or 3 R ^{1-2 groups} ; Each R ^1-2 is independently halogen; R ³ is each independently C _1-6 alkyl, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , or C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 ; Each R ^3-1 is independently deuterium or a 3-6 membered heterocycloalkyl substituted with one or more ^Ra ; Each R ^3-2 is independently a C _1-6 alkyl group; Each ^Ra is independently _C1-6 alkyl; The compound represented by formula I satisfies one or both of the following conditions: IR ³ is each independently C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^3-1 , or C _3-6 cycloalkyl substituted by 1, 2 or 3 R ^3-2 ; II. each R ¹ is independently a C _2-6 alkoxy group substituted by 1, 2 or 3 R ^1-2 ; Any of the above 3-6 membered heterocycloalkyl groups, wherein the heteroatoms are 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1 or 2; Option 4: In the compound shown in formula I, m is 1; n is 0; Z ₁ is CH; _X1 and _X2 are _{-CH2- X3} and _X4 are _-CH2- ; Each R ¹ is independently a C _1-6 alkoxy group; R ³ is each independently C _3-6 cycloalkyl or 3-6 membered heterocycloalkyl; The compound represented by formula I satisfies one or both of the following conditions: IR ³ is each independently C _3-6 cycloalkyl or 3-6 membered heterocycloalkyl; Any of the above 3-6 membered heterocycloalkyl groups, the heteroatom is N, O or S, and the number of heteroatoms is 1; Alternatively, the compound as shown in formula V is any of the following schemes: Option 1: m is 1; n is 0 or 2; Ring A is C _6-7 cycloalkyl; _Z1 is N or CH; Each R ¹ is independently a C _1-6 alkoxy group or a C _1-6 alkoxy group substituted by 1, 2 or 3 R ^{1-2 groups} ; Each R ^1-2 is independently halogen; When n is 2, two R ² and the atoms to which they are attached form a C _3-6 cycloalkyl group; R ^N-1 and R ^N-2 are each independently H, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^N-1-1 , C _3-6 cycloalkyl, or R ^N-1 and R ^N-2 and the N atom to which they are attached form a 3-12 membered heterocycloalkyl; Each R ^N-1-1 is independently deuterium; In any of the above 3-12 membered heterocycloalkyl groups, the heteroatom is N, O or S, and the number of heteroatoms is 1 or 2; Option 2: In the compound shown in formula V, m is 1, 2, 3 or 4; n is 0, 1, 2, 3, 4 or 5; Ring A is C _6-7 cycloalkyl; _Z1 is N or CH; each R ¹ is independently cyano, halogen, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^1-1 , C _1-6 alkoxy, C _3-6 cycloalkyl, 3-6 membered heterocycloalkyl or C _1-6 alkoxy substituted by 1, 2 or 3 R ^1-2 ; Each R ^1-1 is independently deuterium or halogen; Each R ^1-2 is independently deuterium or halogen; Each R ² is independently deuterium, halogen, hydroxyl, carbonyl, C _1-6 alkyl, amino, C _3-7 cycloalkyl or 3-7 membered heterocycloalkyl, or two R ² and the atoms to which they are attached form a C _3-6 cycloalkyl; R ^N-1 and R ^N-2 are each independently H, deuterium, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^N-1-1 , C _3-6 cycloalkyl, or, R ^N-1 and R ^N-2 and the N atom to which they are attached form a 3-12 membered heterocycloalkyl, and the 3-12 membered heterocycloalkyl is optionally substituted by 1, 2 or 3 R ^N-1-2 ; Each R ^N-1-1 is independently deuterium, halogen or hydroxyl; Each R ^N-1-2 is independently deuterium, halogen or hydroxyl; In any of the above 3-6 membered heterocycloalkyl, 3-7 membered heterocycloalkyl, 3-12 membered heterocycloalkyl, the heteroatom is N, O or S, and the number of heteroatoms is 1, 2 or 3; Option 3: In the compound shown in formula V, m is 1; n is 0 or 2; Ring A is C _6-7 cycloalkyl; _Z1 is N or CH; Each R ¹ is independently a C _1-6 alkoxy group or a C _1-6 alkoxy group substituted by 1, 2 or 3 R ^{1-2 groups} ; Each R ^1-2 is independently halogen; When n is 2, two R ² and the atoms connected thereto form a C _3-6 cycloalkyl group; R ^N-1 and R ^N-2 are each independently H, C _1-6 alkyl, C _1-6 alkyl substituted by 1, 2 or 3 R ^N-1-1 , C _3-6 cycloalkyl, or R ^N-1 and R ^N-2 and the N atom to which they are attached form a 3-12 membered heterocycloalkyl; Each R ^N-1-1 is independently deuterium; In any of the above 3-12 membered heterocycloalkyl groups, the heteroatoms are 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1 or 2; Option 4: m is 1; n is 0; Ring A is C _6-7 cycloalkyl; _Z2 is CH; Each R ¹ is independently a C _1-6 alkoxy group; R ^N-1 and R ^N-2 are each independently C _1-6 alkyl; or, R ^N-1 and R ^N-2 and the N atom to which they are attached form a 3-12 membered heterocycloalkyl; In any of the above 3-12 membered heterocycloalkyl groups, the heteroatoms are 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1 or 2; Alternatively, in the compound represented by formula X: k is 0 or 1; Z ₃ is S; R ^1a is C _1-6 alkyl; R ^3a is C _1-6 alkyl. 8. The compound of formula X, the compound of formula I or the compound of formula V according to claim 1, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof, characterized in that the compound of formula I satisfies one or more of the following conditions: (1) Each R ¹ is independently methoxy or (2) R ³ are each independently -CD ₃ , Alternatively, the compound as shown in formula V satisfies one or more of the following conditions: (1) Ring A is cyclohexyl or cycloheptyl; (2) Each R ¹ is independently methoxy or (3) When n is 2, two R ² and the atoms connected thereto form a cyclopropane group; (4) R ^N-1 and R ^N-2 are each independently H, methyl, -CD ₃ or cyclopropane; (5) R ^N-1 and R ^N-2 and the N atom to which they are attached form a 3-12 membered heterocycloalkyl group, wherein the 3-12 membered heterocycloalkyl group is Alternatively, the compound represented by formula X satisfies one or more of the following conditions: (1) R ^1a is H or methyl; (2) R ^3a is methyl. 9. The compound of formula X, the compound of formula I or the compound of formula V as claimed in claim 1, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof, characterized in that: The compound shown in formula I is any of the following compounds: Alternatively, the compound represented by formula V is any of the following compounds: Alternatively, the compound as shown in formula X is Preferably, the pharmaceutically acceptable salt of the compound represented by formula X is a formate salt of the compound represented by formula X, such as a monoformate salt of the compound represented by formula X, preferably Monoformate of; Further preferably, the compound represented by formula I is In the liquid phase, the compound that elutes first, preferably, has a retention time of 4.9 min, or, the compound that elutes later has a retention time of 5.2 min; further preferably, the liquid phase conditions are: C18 chromatographic column, mobile phase A is acetonitrile, mobile phase B is 10 mmol/L ammonium bicarbonate aqueous solution, gradient elution, acetonitrile gradient is 47-53%, flow rate is 20 mL/min; the liquid phase conditions are further preferably: chromatographic column: Waters-XBndge-C18-10 μm-19*250 mm, mobile phase A is acetonitrile, mobile phase B is 10 mmol/L ammonium bicarbonate aqueous solution, gradient elution, acetonitrile gradient is 47-53%, flow rate is 20 mL/min; Further preferably, the compound represented by formula I is The compound that elutes first in the liquid phase, preferably, has a retention time of 4.9 min, or, the compound that elutes later has a retention time of 5.2 min; further preferably, the liquid phase conditions are: C18 chromatographic column, mobile phase A is acetonitrile, mobile phase B is 10 mmol/L ammonium bicarbonate aqueous solution, gradient elution, acetonitrile gradient is 25-55%, and flow rate is 20 mL/min; the conditions are further preferably: chromatographic column: Waters-Xbridge-C18-10 μm-19*250 mm, mobile phase A is acetonitrile, mobile phase B is 10 mmol/L ammonium bicarbonate aqueous solution, gradient elution, acetonitrile gradient is 25-55%, and flow rate is 20 mL/min. 10. A pharmaceutical composition, characterized in that it comprises a substance Y and a pharmaceutically acceptable carrier, wherein the substance Y is a compound as shown in formula X, a compound as shown in formula I, or a compound as shown in formula V as described in any one of claims 1 to 9, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof. 11. Use of a substance Y or a pharmaceutical composition as claimed in claim 10 in the preparation of a drug for regulating neuronal plasticity, wherein the substance Y is a compound as represented by formula X, a compound as represented by formula I, or a compound as represented by formula V as claimed in any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof. 12. Use of a substance Y or a pharmaceutical composition as claimed in claim 10 in the preparation of a medicament for treating and/or preventing depression, schizophrenia, anxiety, or post-traumatic stress disorder, wherein the substance Y is a compound as represented by formula X, a compound as represented by formula I, or a compound as represented by formula V as claimed in any one of claims 1 to 9, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof. 13. A method for preparing a compound of formula X, a compound of formula I or a compound of formula V, or a pharmaceutically acceptable salt thereof as claimed in any one of claims 1 to 9, characterized in that it is any of the following schemes: Option 1: Scheme 1 comprises the following steps: in an organic solvent, coupling reaction is carried out on compound Ib and compound Ia to obtain a compound represented by formula I; Wherein, W ₁ and W ₂ are each independently -OC _1-6 alkyl or -O-Si-(C _1-6 alkyl) ₃ ; Alternatively, _W1 is H, _W2 is oxo; n, m, R ¹ , R ² , R ³ , Z ₁ , X ₃ , X ₄ , X ₁ and X ₂ are as described in any one of claims 1 to 9; Scheme 2 comprises the following steps: in a mixture of an organic solvent and an alkali metal, compound Va is hydrolyzed to obtain a compound represented by formula V; Wherein, W ₃ is an amino protecting group, such as p-toluenesulfonyl; n, m, R ¹ , R ² , Ring A, R ^N-1 , R ^N-2 and Z ₁ are as described in any one of claims 1 to 9; Scheme 3 comprises the following steps: in an organic solvent, compound Xa is subjected to a cyclization reaction with 1-methylhexahydroazepine-4-one salt to obtain a compound represented by formula X; W ₄ is C _1-6 alkyl; k, R ^1a , R ^3a and Z ₃ are as described in any one of claims 1 to 9. 14. A compound Va or a compound Xa; wherein W ₃ , W ₄ , k, R ^1a , R ^3a , Z ₃ , n, m, R ¹ , R ² , Ring A, R ^N-1 , R ^N-2 and Z ₁ are as described in claim 13; Preferably, the compound Va is Preferably, the compound Xa is