Amide derivative, preparation method therefor and use thereof

Abstract

The present invention provides an amide derivative shown as in formula (I) or a tautomer, stereoisomer or pharmaceutically acceptable salt thereof, and a use thereof. In-vitro experimental results show that the compound in the present invention has relatively high MAO-B selective inhibition activity. In-vivo experimental results show that the compound in the present invention can remarkably reduce the weight of a mouse under the condition that the feeding amount is not affected.

Description

Amide derivatives and their preparation methods and uses Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a novel amide derivative, a preparation method thereof, and a pharmaceutical use thereof as a monoamine oxidase-B (MAO-B) inhibitor. Background Art

[0002] Monoamine oxidase (MAO) is an enzyme in the human body that catalyzes the oxidative deamination of monoamines. The products of this oxidative deamination are the corresponding aldehydes, amines, and hydrogen peroxide. For example, hydrogen peroxide can trigger the production of reactive oxygen species (ROS) and induce mitochondrial damage and neuronal apoptosis. Depending on the substrate, MAO is divided into two types: MAO-A and MAO-B. MAO-A has a high affinity for substrates such as tyramine, serotonin, epinephrine, and norepinephrine, while MAO-B shows a preference for dopamine, phenylethylamine, and other trace arylalkylamines. MAO-B is expressed in multiple organs, including the brain, heart, adipose tissue, pancreas, lung, kidney, muscle, and liver.

[0003] MAO-B is abundantly distributed in the basal ganglia of the brain, and its activity increases with age. Because MAO-B metabolizes dopamine (DA), it exacerbates DA deficiency in related brain regions of Parkinson's disease (PD) patients. Furthermore, the aldehydes and hydrogen peroxide produced by MAO-B-catalyzed reactions are both neurotoxic, and the deficiency of aldehyde dehydrogenase in the substantia nigra of PD patients potentiates the neurotoxicity caused by MAO-B-catalyzed reactions. Therefore, inhibiting MAO-B could treat PD by both increasing brain monoamine neurotransmitters such as DA and reducing neurotoxicity. Furthermore, MAO-B-mediated redox damage is a prominent feature of Alzheimer's disease (AD), and evidence of ROS-mediated neuronal damage has been observed in the brains of AD patients. Consequently, MAO-B has been considered a valuable potential target for AD treatment in recent years and has garnered extensive attention and research.

[0004] The complex balance between food intake and energy expenditure is controlled by the hypothalamus in the brain. Astrocytes in the lateral hypothalamus are able to regulate the activity of GABRA5 neurons. Studies have shown that as the number and size of reactive astrocytes increase, they begin to overexpress the MAO-B enzyme, which in turn produces large amounts of gamma-aminobutyric acid (GABA), thereby inhibiting the surrounding GABRA5 neurons, leading to reduced energy expenditure and fat accumulation. Inhibiting the expression of the MAO-B gene in reactive astrocytes can reduce GABA secretion, thereby reversing the adverse inhibitory effects of GABRA5 neurons. At the same time, because appetite-suppressing neurons do not express GABAa receptors outside the synapse, they are not affected by GABA. Therefore, MAO-B inhibitors act on neurons that selectively stimulate energy expenditure, thereby exhibiting a therapeutic effect on obesity.

[0005] Most existing MAO-B inhibitors are irreversible and exhibit a variety of side effects. While some progress has been made in the development of reversible MAO-B inhibitors, there is still a need to develop significantly reversible MAO-B inhibitors that can effectively improve cognitive function, treat neurodegenerative diseases, and treat obesity. Summary of the Invention

[0006] The first aspect of the present invention provides a compound as shown in formula (I), its tautomers, stereoisomers or pharmaceutically acceptable salts thereof,

[0007] in,

[0008] Ring A and Ring B are each independently selected from C 6-10 Aryl or 5-10 membered heteroaryl;

[0009] R 1 and R 2 Each independently selected from deuterium, halogen, cyano, nitro, amino, hydroxyl, mercapto, -SF5, -COOH, -OR 5 、-SR 5 、-NR 5 R 5 、-C(O)R 5 、-C(O)OR 5 、-C(O)NR 5 R 5 、-OC(O)R 5 、-S(O) 1-2 R 5 、-S(O)2NR 5 R 5 、-N(R 5 )S(O)2R 5 、-N(R 5 )C(O)R5 、-N(R 5 )C(O)NR 5 、C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, C 6-10 aryl, 3-10 membered heterocyclyl and 5-10 membered heteroaryl; wherein the C 1-6 Alkyl, C 2- 6 alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, C 6-10 Aryl, 3-10 membered heterocyclyl and 5-10 membered heteroaryl are each optionally substituted with 0-6 identical or different deuterium, cyano, amino, hydroxyl or halogen;

[0010] R 5 are each independently selected from hydrogen, deuterium, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl and 3-10 membered heterocyclic group, wherein the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 The cycloalkyl and 3-10 membered heterocyclyl groups are each optionally substituted with 0-6 identical or different deuterium, cyano, amino, hydroxyl or halogen groups;

[0011] m, n are each independently selected from 0-6;

[0012] Y is independently selected from (CR 6 R 7 ) 1-2 Or a single key;

[0013] R 6 and R 7 are each independently selected from hydrogen, deuterium, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C1-6 alkoxy, C 1-6 C substituted with haloalkoxy or hydroxy 1-6 alkyl;

[0014] Alternatively, when Y is selected from (CR 6 R 7 )2, one of the R 6 or R 7 Together with two carbon atoms, it forms C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, other R6 and R 7 is selected from hydrogen, deuterium or halogen; wherein the heterocyclic group contains 0-2 N, O, C (= O) or S heteroatoms, and the heteroatoms are not 0 at the same time; the C 3-6 The cycloalkyl and 3-6 membered heterocyclyl groups are optionally substituted with 0-6 identical or different deuterium, C 1-6 Alkyl, cyano, amino, hydroxy or halogen substitution;

[0015] Or, R 2 and R 6 The atoms connected to them together form C 5-8 A carbocyclic group or a 5-8 membered heterocyclic group; wherein the heterocyclic group contains 0-2 N, O, C (= O) or S heteroatoms, and the heteroatoms are not 0 at the same time; the C 5-8 The carbocyclyl and 5-8 membered heterocyclyl are optionally substituted by 0-6 identical or different deuterium, cyano, amino, hydroxyl, C 1-6 Alkyl or halogen substituted; R 7 Selected from hydrogen, deuterium, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 C substituted with haloalkoxy or hydroxy 1-6 alkyl;

[0016] R 3 independently selected from hydrogen, deuterium, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 C substituted with halogenated alkoxy or hydroxy 1-6 Alkyl or C 3-8 Cycloalkyl;

[0017] Or, R 2 and R 3 The atoms connected to them together form a 4-8 membered nitrogen-containing heterocyclic group; wherein the 4-8 membered nitrogen-containing heterocyclic group contains 1-2 N heteroatoms, 0-2 O, C (=O) or S heteroatoms; the 4-8 membered nitrogen-containing heterocyclic group is optionally substituted by 0-6 identical or different deuterium, C 1-6 Alkyl, cyano, amino, hydroxy or halogen substitution;

[0018] R 4a 、R 4b are each independently selected from hydrogen, deuterium, halogen, hydroxyl, cyano, amino, thiol, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C2-6 Alkynyl, C 3-10 Cycloalkyl or C 3-10 Cycloalkenyl; the C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl or C 3-10 The cycloalkenyl group is optionally substituted with 0-3 deuterium, halogen, hydroxy, amino, nitro, cyano, mercapto, C 1-6 Alkyl or C 1-6 substituted with alkoxy;

[0019] or R 4a and R 4b The carbon atoms to which they are attached together form C 3-6 A carbocyclic group or a 3-6 membered heterocyclic group; wherein the heterocyclic group contains 0-2 N, O, C (= O) or S heteroatoms, and the heteroatoms are not 0 at the same time; the C 3-6 The carbocyclyl and 3-6 membered heterocyclyl are optionally substituted by 0-6 identical or different deuterium, cyano, amino, hydroxyl, halogen or C 1-6 Alkyl substitution;

[0020] Or, R 3 and R 4a The atoms connected to them together form a 3-8 membered nitrogen-containing heterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1-3 N heteroatoms and 0-2 O, C (=O) or S heteroatoms; the 3-8 membered nitrogen-containing heterocyclic groups are optionally substituted by 0-6 identical or different deuterium, cyano, amino, hydroxyl, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl, C 1-3 Haloalkoxy or halogen substituted; R 4b Selected from hydrogen, deuterium, halogen, hydroxyl, cyano, amino, thiol, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl or C 3-10 Cycloalkenyl; the C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl or C 3-10 The cycloalkenyl group is optionally substituted with 0-3 deuterium, halogen, hydroxy, amino, nitro, cyano, mercapto, C 1-6 Alkyl or C 1-6 Alkoxy substituted.

[0021] In some embodiments of the present invention, rings A and B are each independently selected from phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, thienyl, furanyl, pyrrolyl, thiazolyl, oxazolyl, pyrazolyl or imidazolyl;

[0022] Preferably, ring A and ring B are each independently selected from phenyl, pyridyl, thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, pyrazolyl or imidazolyl;

[0023] More preferably, ring A and ring B are each independently selected from phenyl, pyridyl, thienyl or thiazolyl;

[0024] More preferably, rings A and B are each independently selected from phenyl.

[0025] In some embodiments of the present invention, R 1 and R 2 Each independently selected from deuterium, halogen, -SF5, -OR 5 、-SR 5 、-NR 5 R 5 、-C(O)R 5 、-C(O)OR 5 、-C(O)NR 5 R 5 、-OC(O)R 5 、-S(O) 1- 2R 5 、-S(O)2NR 5 R 5 、-N(R 5 )S(O)2R 5 、-N(R 5 )C(O)R 5 、-N(R 5 )C(O)NR 5 、C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, C 6-10 Aryl, 3-10 membered heterocyclic group and 5-10 membered heteroaryl; wherein, the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3- 10 Cycloalkyl, C 3-10 Cycloalkenyl, C 6-10 Aryl, 3-10 membered heterocyclyl and 5-10 membered heteroaryl are each optionally substituted with 0-6 identical or different deuterium, cyano, amino, hydroxyl or halogen;

[0026] R 5 are each independently selected from hydrogen, deuterium, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl and 3-10 membered heterocyclic group, wherein the C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 The cycloalkyl and 3-10 membered heterocyclyl are each optionally substituted with 0-6 identical or different deuterium, cyano, amino, hydroxy or halogen.

[0027] In some preferred embodiments of the present invention, R 1 and R 2 Each independently selected from deuterium, halogen, -SF5, -OR 5 、-SR 5 、-NR 5 R 5 、-C(O)R 5 、-C(O)OR 5 、-C(O)NR 5 R 5 、-OC(O)R 5 、-S(O) 1-2 R 5 、-S(O)2NR 5 R 5 、-N(R 5 )S(O)2R 5 、-N(R 5 )C(O)R 5 、-N(R 5 )C(O)NR 5 、C 1-6 Alkyl, C 3-10 Cycloalkyl and 3-10 membered heterocyclic group; wherein the C 1-6 Alkyl, C 3-10 The cycloalkyl and 3-10 membered heterocyclyl groups are each optionally substituted with 0-6 identical or different deuterium, cyano, amino, hydroxyl or halogen groups;

[0028] R 5 are each independently selected from hydrogen, deuterium, C 1-6 Alkyl, C 3-10 Cycloalkyl and 3-10 membered heterocyclic group, wherein the C 1-6 Alkyl, C 3-10 The cycloalkyl and 3-10 membered heterocyclyl are each optionally substituted with 0-6 identical or different deuterium, cyano, amino, hydroxy or halogen.

[0029] In some preferred embodiments of the present invention, R1 and R 2 Each independently selected from deuterium, halogen, -SF5, -OR 5 、-SR 5 、-NR 5 R 5 、-C(O)R 5 、-S(O) 1-2 R 5 、C 1-6 Alkyl, C 3-10 Cycloalkyl and 3-10 membered heterocyclic group; wherein the C 1-6 Alkyl, C 3-10 The cycloalkyl and 3-10 membered heterocyclyl groups are each optionally substituted with 0-6 identical or different deuterium, cyano, amino, hydroxyl or halogen groups;

[0030] R 5 are each independently selected from hydrogen, deuterium, C 1-6 Alkyl, C 3-10 Cycloalkyl and 3-10 membered heterocyclic group, wherein the C 1-6 Alkyl, C 3-10 The cycloalkyl and 3-10 membered heterocyclyl are each optionally substituted with 0-6 identical or different deuterium, cyano, amino, hydroxy or halogen.

[0031] In some preferred embodiments of the present invention, R 1 and R 2 Each independently selected from deuterium, halogen, -SF5, -OR 5 、-SR 5 、C 1-6 Alkyl, C 3-10 Cycloalkyl and 3-10 membered heterocyclic group; wherein the C 1-6 Alkyl, C 3-10 The cycloalkyl and 3-10 membered heterocyclyl groups are each optionally substituted with 0-6 identical or different deuterium, cyano, amino, hydroxyl or halogen groups;

[0032] R 5 are each independently selected from hydrogen, deuterium, C 1-6 Alkyl, C 3-10 Cycloalkyl and 3-10 membered heterocyclic group, wherein the C 1-6 Alkyl, C 3-10 The cycloalkyl and 3-10 membered heterocyclyl are each optionally substituted with 0-6 identical or different deuterium, cyano, amino, hydroxy or halogen.

[0033] In some preferred embodiments of the present invention, R 1 and R 2 Each independently selected from deuterium, halogen, -SF5, -OR 5 、-SR 5 、C1-6 Alkyl, C 3-10 Cycloalkyl and 3-10 membered heterocyclic group; wherein the C 1-6 Alkyl, C 3-10 Cycloalkyl and 3-10 membered heterocyclyl are each optionally substituted with 0-6 identical or different deuterium or halogen;

[0034] R 5 are each independently selected from hydrogen, deuterium, C 1-6 Alkyl, C 3-10 Cycloalkyl and 3-10 membered heterocyclic group, wherein the C 1-6 Alkyl, C 3-10 The cycloalkyl and 3-10 membered heterocyclyl are each optionally substituted with 0-6 identical or different deuterium or halogen.

[0035] In some preferred embodiments of the present invention, R 1 and R 2 Each independently selected from deuterium, halogen, -SF5, -OR 5 、-SR 5 、C 1-6 Alkyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic group; wherein said C 1- 6 alkyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclyl are each optionally substituted with 0-6 identical or different deuterium or halogen;

[0036] R 5 are each independently selected from hydrogen, deuterium, C 1-6 Alkyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 3-6 The cycloalkyl and 3-6 membered heterocyclyl are each optionally substituted with 0-6 identical or different deuterium or halogen atoms.

[0037] In some preferred embodiments of the present invention, R 1 and R 2 Each independently selected from deuterium, fluorine, chlorine, bromine, -SF5, -OR 5 、-SR 5 、C 1-6 Alkyl, C 3-6 Cycloalkyl and 3-6 membered heterocyclic group; wherein said C 1-6 Alkyl, C 3-6 The cycloalkyl and 3-6 membered heterocyclyl groups are each optionally substituted with 0-6 identical or different deuterium, fluorine, chlorine or bromine groups;

[0038] R 5 Each independently selected from C 1-6 Alkyl, C 3-6Cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 3-6 The cycloalkyl and 3-6 membered heterocyclyl are each optionally substituted with 0-6 identical or different deuterium, fluorine, chlorine or bromine groups.

[0039] In some preferred embodiments of the present invention, R 1 and R 2 Each is independently selected from fluorine, chlorine, -SF5, -SCF3, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl, tert-butyl, cyclobutyl, methoxy, ethoxy, propoxy, isopropyloxy, cyclopropyloxy, butoxy, isobutyloxy, tert-butoxy or cyclobutyloxy; wherein, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl, tert-butyl, cyclobutyl, methoxy, ethoxy, propoxy, isopropyloxy, cyclopropyloxy, butoxy, isobutyloxy, tert-butoxy or cyclobutyloxy are optionally substituted with 0-6 identical or different deuterium, fluorine, chlorine or bromine.

[0040] In some preferred embodiments of the present invention, R 1 and R 2 Each is independently selected from fluorine, chlorine, -SF5, -SCF3, -OCF3, -CF3, methyl, deuterated methyl or cyclopropyl.

[0041] In some preferred embodiments of the present invention, R 1 Selected from -CF3, R 2 Selected from fluorine.

[0042] In some embodiments of the present invention, m and n are each independently selected from 0 to 5, preferably 0, 1, 2, 3, 4, or 5, and more preferably 0, 1, 2 or 3.

[0043] In some embodiments of the present invention, m is selected from 0 to 3, preferably 1, 2 or 3, more preferably 1; n is selected from 0 or 1.

[0044] In some embodiments of the present invention, Y is independently selected from (CR 6 R 7 ) 1-2 ;

[0045] R 6 and R 7 are each independently selected from hydrogen, deuterium, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C1-6 alkoxy, C 1-6 C substituted with haloalkoxy or hydroxy 1-6 alkyl;

[0046] Alternatively, when Y is selected from (CR 6 R 7)2, one of the R 6 or R 7 Together with two carbon atoms, it forms C 3-6 Cycloalkyl or 3-6 membered heterocyclic group, other R 6 and R 7 is selected from hydrogen, deuterium or halogen; wherein the heterocyclic group contains 0-2 N, O, C (= O) or S heteroatoms, and the number of heteroatoms is not 0 at the same time; the C 3-6 The cycloalkyl and 3-6 membered heterocyclyl groups are each optionally substituted with 0-6 identical or different deuterium, cyano, amino, hydroxyl or halogen groups;

[0047] Or, R 2 and R 6 The atoms connected to them together form C 5-8 A carbocyclic group or a 5-8 membered heterocyclic group; wherein the heterocyclic group contains 0-2 N, O, C (=O) or S heteroatoms, and the number of heteroatoms is not 0 at the same time; the C 5-8 The carbocyclyl and 5-8 membered heterocyclyl are optionally substituted by 0-6 identical or different deuterium, cyano, amino, hydroxyl or halogen groups; R 7 Selected from hydrogen, deuterium, halogen, C1-6 alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 C substituted with haloalkoxy or hydroxy 1-6 alkyl.

[0048] In some preferred embodiments of the present invention, Y is independently selected from (CR 6 R 7 ) 1-2 ;

[0049] R 6 and R 7 are each independently selected from hydrogen, deuterium, methyl or halogen;

[0050] or R 6 and R 7 The carbon atoms to which they are attached together form a three-membered cycloalkyl group; wherein the three-membered cycloalkyl group is optionally substituted by 0-4 identical or different deuterium, cyano, amino, hydroxyl or halogen groups;

[0051] Or, R 2 and R 6 The atoms connected to them together form C 5-6 A carbocyclic group or a 5-6 membered heterocyclic group; wherein the heterocyclic group contains 0-2 N, O, C (=O) or S heteroatoms, and the number of heteroatoms is not 0 at the same time; the C 5-6 The carbocyclyl and 5-6 membered heterocyclyl are each optionally substituted with 0-6 identical or different deuterium or halogen; R7 is selected from hydrogen, deuterium, methyl or halogen.

[0052] In some preferred embodiments of the present invention, Y is independently selected from (CR 6 R 7 ) 1-2 ;

[0053] R 6 and R 7 are each independently selected from hydrogen or methyl;

[0054] Alternatively, when Y is selected from (CR 6 R 7 )2, one of the R 6 or R 7 Together with two carbon atoms, it forms a three-membered cycloalkyl group;

[0055] Or, R 2 and R 6 The atoms connected to them together form a five-membered carbocyclic group; R 7 is selected from hydrogen or methyl.

[0056] In some embodiments of the present invention, R 3 independently selected from hydrogen, deuterium, C 1-6 Alkyl, C 2-6 Alkynyl or C 3-8 Cycloalkyl;

[0057] Or, R 2 and R 3 The atoms to which they are attached together form a 5-6 membered nitrogen-containing heterocyclic group, wherein the 5-6 membered nitrogen-containing heterocyclic group is optionally substituted by 0-3 identical or different deuterium, halogen or C 1-6 Alkyl substitution.

[0058] In some preferred embodiments of the present invention, R 3 independently selected from hydrogen or propynyl;

[0059] Or, R 2 and R 3 The atoms connected to them together form a 5-6 membered nitrogen-containing heterocyclic group, wherein the 5-6 membered nitrogen-containing heterocyclic group is optionally replaced by 0-3 identical or different C 1-6 Alkyl substitution.

[0060] In some embodiments of the present invention, R 4a 、R 4b are independently selected from hydrogen, halogen or C1-6 alkyl, wherein the C 1-6 The alkyl group is optionally substituted with 0-3 identical or different deuterium, amino, hydroxyl, C 1-3 Alkyl, C 1-3 Alkoxy, C1-3 Halogenated alkyl, C 1-3 haloalkoxy or halogen substitution;

[0061] or R 4a and R 4b The carbon atoms to which they are attached form C 3-4 Cycloalkyl or 3-4 membered heterocycloalkyl; wherein the heterocycloalkyl contains one O, N, C(=O) or S heteroatom; the C 3-4 Cycloalkyl and 3-4 membered heterocycloalkyl are each optionally substituted with 0-6 identical or different deuterium or halogen;

[0062] Or, R 3 and R 4a The atoms connected to them together form a 3-7 membered nitrogen-containing heterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1-3 N, and 0-3 O or C (=O) heteroatoms; the 3-7 membered heterocyclic group is optionally substituted by 0-6 identical or different deuterium, amino, hydroxyl, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl, C 1-3 Haloalkoxy or halogen substituted; R 4b is selected from hydrogen, halogen or C1-6 alkyl, wherein the C 1-6 The alkyl group is optionally substituted with 0-3 identical or different deuterium, amino, hydroxyl, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl, C 1-3 Haloalkoxy or halogen substituted.

[0063] In some preferred embodiments of the present invention, R 4a 、R 4b are each independently selected from hydrogen, fluorine or methyl;

[0064] or R 4a and R 4b The carbon atoms to which they are attached together form C 3-4 Cycloalkyl or 3-4 membered heterocycloalkyl; wherein the heterocycloalkyl contains 1 O; the C 3-4 Cycloalkyl and 3-4 membered heterocycloalkyl are each optionally substituted with 0-6 identical or different halogens;

[0065] Or, R 3 and R 4a The atoms connected to them together form a 3-7 membered nitrogen-containing heterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1-3 N, and 0-3 O or C (=O) heteroatoms; the 3-7 membered nitrogen-containing heterocyclic group is optionally substituted by 0-6 identical or different amino, hydroxyl, C 1-3 Alkyl or halogen substituted;

[0066] Or, R 3 and R 4a The atoms connected to them together form a 3-6 membered nitrogen-containing heterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1 N; the 3-6 membered nitrogen-containing heterocyclic group is optionally substituted by 0-3 identical or different amino, hydroxyl, C 1-3 Alkyl or halogen substituted;

[0067] Or, R 3 and R 4a The atoms connected to them together form a 3-5 membered nitrogen-containing heterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1 N; the 3-5 membered nitrogen-containing heterocyclic group is optionally substituted by 0-2 identical or different amino, hydroxyl, C 1-3 Alkyl or halogen substituted;

[0068] Or, R 3 and R 4a The atoms connected to them together form a 4-membered nitrogen-containing heterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1 N; the 4-membered nitrogen-containing heterocyclic group is optionally substituted by 0-2 identical or different amino, hydroxyl, C 1-3 Alkyl or halogen substituted.

[0069] In some preferred embodiments of the present invention, R 4a 、R 4b are each independently selected from hydrogen, fluorine or methyl;

[0070] Or, R 4a and R 4b The carbon atoms connected to them together form a cyclopropyl group, a cyclobutyl group, or an oxygen-containing four-membered ring; wherein the cyclopropyl group, the cyclobutyl group, or the oxygen-containing four-membered ring are optionally substituted with 0-6 fluorine atoms;

[0071] Or, R 3 and R 4a The atoms connected to them together constitute a nitrogen-containing 3-membered monoheterocyclic group, 4-membered monoheterocyclic group, 5-membered monoheterocyclic group, 6-membered monoheterocyclic group, 7-membered monoheterocyclic group, 5-membered spiro heterocyclic group, 5-membered bridged heterocyclic group, 6-membered spiro heterocyclic group, 6-membered bridged heterocyclic group, 6-membered fused heterocyclic group, 7-membered spiro heterocyclic group, 7-membered bridged heterocyclic group or 7-membered fused heterocyclic group, etc.; wherein the nitrogen-containing heterocyclic group contains 1-3 N and 0-3 O or C (=O) heteroatoms; the nitrogen-containing heterocyclic group is optionally substituted with 0-6 identical or different amino, hydroxyl, methyl, ethyl, propyl, isopropyl, fluorine, chlorine or bromine groups; R 4b is selected from hydrogen, fluorine or methyl;

[0072] Or, R 3 and R 4aThe atoms connected to them together constitute a nitrogen-containing 3-membered monoheterocyclic group, 4-membered monoheterocyclic group, 5-membered monoheterocyclic group, 6-membered monoheterocyclic group, or 7-membered monoheterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1-3 N, and 0-3 O or C(=O) heteroatoms; the nitrogen-containing heterocyclic group is optionally substituted with 0-6 identical or different amino, hydroxyl, methyl, ethyl, propyl, isopropyl, fluorine, chlorine, or bromine groups; R 4b is selected from hydrogen, fluorine or methyl;

[0073] Or, R 3 and R 4a The atoms connected to them together constitute a nitrogen-containing 3-membered monoheterocyclic group, a 4-membered monoheterocyclic group, a 5-membered monoheterocyclic group, or a 6-membered monoheterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1-3 N, and 0-3 O or C(=O) heteroatoms; the nitrogen-containing heterocyclic group is optionally substituted with 0-6 identical or different amino, hydroxyl, methyl, ethyl, propyl, isopropyl, fluorine, chlorine or bromine groups; R 4b is selected from hydrogen, fluorine or methyl;

[0074] Or, R 3 and R 4a The atoms connected to them together constitute a nitrogen-containing 3-membered monoheterocyclic group, a 4-membered monoheterocyclic group, a 5-membered monoheterocyclic group, or a 6-membered monoheterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1 N; the nitrogen-containing heterocyclic group is optionally substituted by 0-3 identical or different amino, hydroxyl, methyl, ethyl, propyl, isopropyl, fluorine, chlorine, or bromine groups; R 4b is selected from hydrogen, fluorine or methyl;

[0075] Or, R 3 and R 4a The atoms connected to them together constitute a nitrogen-containing 3-membered monoheterocyclic group, a 4-membered monoheterocyclic group, or a 5-membered monoheterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1 N; the nitrogen-containing heterocyclic group is optionally substituted by 0-2 identical or different amino, hydroxyl, methyl, ethyl, propyl, isopropyl, fluorine, chlorine, or bromine groups; R 4b is selected from hydrogen, fluorine or methyl;

[0076] Or, R 3 and R 4a The atoms connected to them together form a nitrogen-containing 4-membered monoheterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1 N; the nitrogen-containing heterocyclic group is optionally substituted by 0-2 identical or different amino, hydroxyl, methyl, or fluorine groups; R 4b is selected from hydrogen, fluorine or methyl.

[0077] In some preferred embodiments of the present invention, R 4a 、R 4b are each independently selected from hydrogen, fluorine or methyl;

[0078] or R4a and R 4b The carbon atoms connected to them together form a cyclopropyl group, a cyclobutyl group, or an oxygen-containing four-membered ring; wherein the cyclopropyl group, the cyclobutyl group, or the oxygen-containing four-membered ring are optionally substituted with 0-6 fluorine atoms;

[0079] Or, R 3 and R 4a The atoms they are connected to form etc. nitrogen-containing heterocyclic groups; wherein, Indicates connection with the Y terminal, Said nitrogen-containing heterocyclic groups are optionally substituted by 0-6 identical or different amino, hydroxy, methyl, ethyl, propyl, isopropyl, fluorine, chlorine or bromine groups; R 4b is selected from hydrogen, fluorine or methyl.

[0080] In some preferred embodiments of the present invention, R 4a 、R 4b are each independently selected from hydrogen, fluorine or methyl;

[0081] Or, R 4a and R 4b The carbon atoms connected to them together form a cyclopropyl group, a cyclobutyl group, or an oxygen-containing four-membered ring; wherein the cyclopropyl group, the cyclobutyl group, or the oxygen-containing four-membered ring are optionally substituted with 0-6 fluorine atoms;

[0082] Or, R 3 and R 4a The atoms connected to them can be connected together to form etc. nitrogen-containing heterocyclic groups; wherein, Indicates connection with the Y terminal, Said nitrogen-containing heterocyclic groups are optionally substituted by 0-6 identical or different amino, hydroxyl, methyl, ethyl, propyl, isopropyl, fluorine, chlorine or bromine groups; R 4b is selected from hydrogen, fluorine or methyl.

[0083] In some preferred embodiments of the present invention, R 4a 、R 4b are each independently selected from hydrogen, fluorine or methyl;

[0084] Or, R 4a and R 4b The carbon atoms connected thereto together form a cyclopropyl group, a cyclobutyl group, or an oxygen-containing four-membered ring; wherein the cyclopropyl group, the cyclobutyl group, or the oxygen-containing four-membered ring are optionally substituted with 0-6 fluorine atoms;

[0085] Or, R 3 and R 4a The atoms they are connected to together form in, Indicates connection with the Y terminal, Indicates connection with C(O)NH2 terminal; R 4b is selected from hydrogen, fluorine or methyl;

[0086] Or, R 3 and R 4a The atoms they are connected to together form in, Indicates connection with the Y terminal, Indicates connection with C(O)NH2 terminal; R 4b is selected from hydrogen, fluorine or methyl;

[0087] Or, R 3 and R 4a The atoms they are connected to together form in, Indicates connection with the Y terminal, Indicates connection with C(O)NH2 terminal; R 4b is selected from hydrogen, fluorine or methyl;

[0088] Or, R 3 and R 4a The atoms they are connected to together form in, Indicates connection with the Y terminal, Indicates connection with C(O)NH2 terminal; R 4b Selected from hydrogen.

[0089] In the above embodiments of the present invention, except for the defined groups, the definitions of other groups are the same as those in the present invention, and are not described one by one for the sake of space saving.

[0090] The above embodiments of the present invention can be combined arbitrarily, and the embodiments obtained by the combination also belong to the embodiments of the present invention.

[0091] In the above technical solution, the compound of formula (I) does not include the following compounds:

[0092] The following are example structures, including but not limited to compounds of the following structural formulas, their tautomers, stereoisomers, or pharmaceutically acceptable salts thereof:

[0093] In some preferred embodiments of the present invention, the pharmaceutically acceptable salt is selected from: methanesulfonate.

[0094] In a second aspect, the present invention provides a pharmaceutical composition comprising the aforementioned compound, its tautomers, stereoisomers or pharmaceutically acceptable salts thereof, and optionally, a pharmaceutically acceptable carrier.

[0095] The third aspect of the present invention provides the use of the aforementioned compound, its tautomers, stereoisomers or pharmaceutically acceptable salts thereof, or the pharmaceutical composition described in the second aspect of the present invention in the preparation of a drug for diseases or conditions related to monoamine oxidase-B (MAO-B) overexpression.

[0096] In some embodiments of the present invention, the medicament is used to prevent, improve and / or treat diseases or conditions related to memory, cognition, mood, neurodegeneration, obesity, etc.

[0097] In some embodiments of the invention, the disease or condition is selected from Alzheimer's disease, depression, stroke, Parkinson's disease, hypertension, or obesity.

[0098] In a fourth aspect, the present invention provides a method for preventing, ameliorating and / or treating diseases or conditions associated with monoamine oxidase-B (MAO-B) overexpression, comprising administering to a patient a therapeutically effective dose of the aforementioned compound, its tautomers, stereoisomers or pharmaceutically acceptable salts thereof, or the pharmaceutical composition of the present invention; preferably, the disease or condition associated with monoamine oxidase-B (MAO-B) overexpression is a disease or condition related to memory, cognition, mood, neurodegeneration, obesity, etc., preferably: Alzheimer's disease, depression, stroke, Parkinson's disease, hypertension or obesity, etc.

[0099] In a fifth aspect, the present invention provides a drug comprising the aforementioned compound, its tautomers, stereoisomers or pharmaceutically acceptable salts thereof, wherein the drug is used to prevent, improve and / or treat diseases or conditions related to monoamine oxidase-B (MAO-B) overexpression; the diseases or conditions related to monoamine oxidase-B (MAO-B) overexpression are diseases or conditions related to memory, cognition, mood, neurodegeneration and obesity, and are preferably Alzheimer's disease, depression, stroke, Parkinson's disease, hypertension or obesity, etc.

[0100] In a sixth aspect, the present invention provides a method for preparing a compound represented by formula (I), its tautomers, stereoisomers, or pharmaceutically acceptable salts thereof, wherein the compound can be prepared by the following steps:

[0101] Option 1:

[0102] Among them: Ring A, Ring B, R 1 、R 2 、R 3 、R 4a 、R 4b , m, n are defined as described in the present invention;

[0103] X 1 、X 2 、X 3 is a leaving group, preferably halogen, OMs, OTf, OTs, B(OH)2, Bpin or Bneop.

[0104] More preferably, when X 1 When X is Cl, Br, I, OMs, OTf or OTs, 2 is B(OH)2, Bpin or Bneop;

[0105] Or when X 1 When X is B(OH)2, Bpin or Bneop, 2 is Cl, Br, I, OMs, OTf or OTs;

[0106] X 3 is Cl, Br, I, OMs, OTf or OTs.

[0107] in,

[0108] (1) 1A and 1B react with a suitable catalyst to produce 1C;

[0109] (2) 1C and 1D or a salt thereof undergo reductive amination reaction to produce a compound represented by formula (I);

[0110] or,

[0111] (3) 1C generates 1E under reducing conditions;

[0112] (4) 1E is converted to 1F with a leaving group;

[0113] (5) 1F and 1D react under alkaline conditions to produce the compound represented by formula (I);

[0114] in:

[0115] The catalyst in step (1) is preferably a transition metal catalyst, more preferably palladium, nickel, etc.;

[0116] The reducing agent used in steps (2) and (3) is preferably sodium borohydride, sodium cyanoborohydride, etc.;

[0117] The base used in step (5) is an organic base or an inorganic base, such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium phosphate, potassium phosphate, triethylamine, N,N-diisopropylethylamine or 1,8-diazobisspiro[5.4.0]undec-7-ene;

[0118] The above reaction can be carried out in a suitable solvent conventionally used in the art. Preferably, the solvent used is selected from the group consisting of benzene, toluene, methanol, ethanol, isopropanol, water, N,N-dimethylformamide, dimethyl sulfoxide, acetone, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, N-methylpyrrolidone, N,N-dimethylacetamide, and the like, or a mixed solvent thereof.

[0119] The above reaction can be carried out at a suitable temperature. Preferably, the reaction temperature is -20 to 150°C, more preferably -10 to 120°C.

[0120] The intermediate or target product obtained by the reaction can be purified as needed by a purification method conventionally used in the art, such as column chromatography purification, thin layer chromatography purification, etc.

[0121] Option 2:

[0122] Among them: Ring A, Ring B, R 1 、R 2 、R 3 、R 4a 、R 4b , R, Y, m, n are as defined in the present invention;

[0123] X 1 、X 4 、X 5 is a leaving group, preferably halogen, OMs, OTf, OTs, B(OH)2, Bpin or Bneop.

[0124] More preferably, when X 1 When X is Cl, Br, I, OMs, OTf or OTs, 4 is B(OH)2, Bpin or Bneop;

[0125] Or when X 1 When X is B(OH)2, Bpin or Bneop, 4 is Cl, Br, I, OMs, OTf or OTs;

[0126] X 5 is Cl, Br, I, OMs, OTf or OTs.

[0127] in,

[0128] (1) 1A and 2A react in the presence of a suitable catalyst to produce 2B;

[0129] (2) 2B and 2C-1 react under alkaline conditions to produce the compound represented by formula (I);

[0130] or,

[0131] (3) 2B and 2C-2 react under alkaline conditions to produce 2D;

[0132] (4) 2D reacts under alkaline conditions to produce 2E;

[0133] or,

[0134] (5) 2B and 2C-3 react under alkaline conditions to produce 2E;

[0135] (6) 2E undergoes a condensation reaction with ammonia under alkaline conditions to produce the compound represented by formula (I).

[0136] in:

[0137] The catalyst in step (1) is preferably a transition metal catalyst, more preferably palladium, nickel, etc.;

[0138] The base used in steps (2), (3), (5) and (6) is an organic base or an inorganic base, such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium phosphate, potassium phosphate, triethylamine, N,N-diisopropylethylamine or 1,8-diazobisspiro[5.4.0]undec-7-ene;

[0139] The base used in step (4) is lithium hydroxide, sodium hydroxide or potassium hydroxide.

[0140] The ammonia in step (6) is selected from NH3, or ammonium salts, such as ammonium chloride, ammonium nitrate, ammonium bicarbonate, ammonium carbonate, ammonium sulfate and ammonium bisulfate.

[0141] The above reaction can be carried out in a suitable solvent conventionally used in the art. Preferably, the solvent used is selected from the group consisting of benzene, toluene, methanol, ethanol, isopropanol, water, N,N-dimethylformamide, dimethyl sulfoxide, acetone, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, N-methylpyrrolidone, N,N-dimethylacetamide, and the like, or a mixed solvent thereof.

[0142] The above reaction can be carried out at a suitable temperature. Preferably, the reaction temperature is -20 to 150°C, more preferably -10 to 120°C.

[0143] The intermediate or target product obtained by the reaction can be purified as needed by a purification method conventionally used in the art, such as column chromatography purification, thin layer chromatography purification, etc.

[0144] definition

[0145] Unless otherwise specified, D in the present invention represents deuterium ( 2 H).

[0146] Unless otherwise specified, the term "pharmaceutically acceptable salt" or "pharmaceutically acceptable salt" refers to a salt that is suitable for use in contact with mammalian tissues, particularly human tissues, without excessive toxicity, irritation, allergic response, etc., and is commensurate with a reasonable benefit / risk ratio, within the scope of sound medical judgment. For example, pharmaceutically acceptable salts of amines, carboxylic acids, and other types of compounds are well known in the art. The salts can be prepared in situ during the final isolation and purification of the compounds of the present invention, or separately by reacting the free base or free acid with a suitable reagent.

[0147] Unless otherwise specified, pharmaceutically acceptable salts of the compounds of the present invention also include "solvates" thereof. The terms "solvate" and "solvate" refer to the physical association of a salt of a compound of the present invention with one or more solvent molecules (whether organic or inorganic). This physical association includes hydrogen bonding. In certain cases, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid, the solvate will be able to be separated. The solvent molecules in the solvate may exist in a regular and / or disordered arrangement. The solvate may contain stoichiometric or non-stoichiometric amounts of solvent molecules. "Solvate" encompasses solution phases and separable solvates. Exemplary solvates include, but are not limited to, hydrates, ethanolates, methanolates, and isopropanolates. Solvation methods are well known in the art.

[0148] Unless otherwise specified, pharmaceutically acceptable salts of the compounds of the present invention also include "hydrates" thereof. The term "hydrate" refers to a substance formed by water molecules binding to cations or anions in the compound by coordinate bonds or covalent bonds, or refers to a substance formed by water ions not directly binding to cations or anions but existing in a certain proportion at a certain position in the solid crystal lattice.

[0149] Unless otherwise specified, the compounds of the present invention also include their "prodrugs," which refers to drugs that are converted into the parent drug in vivo. Prodrugs are generally useful because they can improve certain, undesirable physical or biological properties. Physical properties are often related to solubility (excessive or insufficient lipid or water solubility) or stability, while problematic biological properties include rapid metabolism or poor bioavailability, which may themselves be related to physicochemical properties. For example, they may be bioavailable by oral administration, whereas the parent drug is not. Prodrugs also have improved solubility in pharmaceutical compositions compared to the parent drug. An example, but not limited to, of a prodrug is any compound of the present invention administered as an ester ("prodrug") to facilitate transport across cell membranes, where water solubility is detrimental to mobility, but once inside the cell, water solubility is beneficial, which is then metabolically hydrolyzed to the carboxylic acid, the active entity. Another example of a prodrug is a short peptide (polyamino acid) conjugated to an acid group, where the peptide is metabolized to reveal the active moiety.

[0150] Unless otherwise specified, the compounds of the present invention also include their "solvates". The terms "solvate" and "solvate" mean the physical association of a compound of the present invention with one or more solvent molecules (whether organic or inorganic). This physical association includes hydrogen bonding. In certain cases, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid, the solvate will be able to be separated. The solvent molecules in the solvate may exist in a regular and / or disordered arrangement. The solvate may contain stoichiometric or non-stoichiometric amounts of solvent molecules. "Solvate" encompasses solution phases and separable solvates. Exemplary solvates include, but are not limited to, hydrates, ethanolates, methanolates, and isopropanolates. Solvation methods are well known in the art.

[0151] Unless otherwise specified, the compounds of the present invention also include their "hydrates". The term "hydrate" refers to a substance formed by water molecules binding to cations or anions in the compound through coordination bonds or covalent bonds, or refers to a substance formed by water ions not directly binding to cations or anions but existing in a certain proportion at a certain position in the solid crystal lattice.

[0152] Unless otherwise specified, the term "stereoisomer" refers to compounds that have the same chemical constitution but differ in the way the atoms or groups are arranged in space. Stereoisomers include enantiomers, diastereomers, conformers (rotamers), geometric isomers (cis / trans) isomers, atropisomers, etc. Any resulting mixture of stereoisomers can be separated into pure or substantially pure geometric isomers, enantiomers, and diastereomers based on the differences in the physicochemical properties of the components, for example, by chromatography and / or fractional crystallization.

[0153] Unless otherwise specified, the term "geometric isomers (cis / trans) isomers" may contain carbon-carbon double bonds or carbon-nitrogen double bonds in the E or Z configuration, wherein the term "E" represents higher-order substituents on opposite sides of the carbon-carbon or carbon-nitrogen double bond, and the term "Z" represents higher-order substituents on the same side of the carbon-carbon or carbon-nitrogen double bond (determined using the Cahn-Ingold Prelog priority rules). The compounds of the present invention may also exist as mixtures of "E" and "Z" isomers.

[0154] Unless otherwise specified, the term "tautomer" refers to structural isomers of different energies that are interconvertible through a low energy barrier. If tautomerism is possible (e.g., in solution), a chemical equilibrium of the tautomers can be achieved. For example, proton tautomers (also known as prototropic tautomers) include interconversions that occur via proton migration, such as keto-enol isomerization and imine-enamine isomerization. Valence tautomers include interconversions that occur via reorganization of some of the bonding electrons.

[0155] Unless otherwise indicated, the structural formulas described herein include all isomeric forms (e.g., enantiomers, diastereomers, and geometric isomers (or conformers)): for example, R and S configurations containing asymmetric centers, (Z) and (E) isomers of double bonds, and (Z) and (E) conformers. Therefore, single stereochemical isomers of the compounds of the present invention or mixtures of their enantiomers, diastereomers, or geometric isomers (or conformers) are within the scope of the present invention.

[0156] Unless otherwise specified, the term "carbocyclyl" refers to a non-aromatic cyclic hydrocarbon group ("C 3-14 In some embodiments, the carbocyclyl group has 3-8 ring carbon atoms ("C 3-8 carbocyclyl”), or 3-6 ring carbon atoms (“C 3-6 carbocyclyl”), or 5 to 8 ring carbon atoms (“C 5-8 In some embodiments, a carbocyclyl group has 5 to 6 ring carbon atoms ("C 5-6 Carbocyclyl”). Exemplary C 3-6 Carbocyclyl groups include, but are not limited to, cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), and the like. 5-8 Carbocyclyl groups include, but are not limited to, the aforementioned C 3-6Carbocyclyl groups and cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), bicyclo [2.2.1] heptyl (C7), bicyclo [2.2.2] octyl (C8), etc. As illustrated in the above examples, in certain embodiments, the carbocyclyl group is monocyclic ("monocyclic carbocyclyl") or a fused (fused cyclyl), bridged (bridged cyclyl) or spiro-fused (spirocyclyl) ring system, such as a bicyclic ring system ("bicyclic carbocyclyl") and can be saturated or partially unsaturated. "Carbocyclyl" also includes ring systems in which the carbocyclyl ring as defined above is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the carbocyclyl ring, and in such cases, the number of members of the carbocyclyl ring system is the number of carbons in the carbocyclyl ring system after fusion. In certain embodiments, each instance of a carbocyclyl group is independently optionally substituted, e.g., unsubstituted (an “unsubstituted carbocyclyl”) or substituted (a “substituted carbocyclyl”) with one or more substituents. In certain embodiments, the carbocyclyl group is an unsubstituted C 5-8 In certain embodiments, the carbocyclyl group is a substituted C 5-8 Carbocyclic group.

[0157] Unless otherwise specified, the term "alkyl" refers to a monovalent saturated aliphatic hydrocarbon group, a straight or branched chain group containing 1 to 20 carbon atoms, preferably containing 1 to 10 carbon atoms (i.e., C 1-10 Alkyl), further preferably containing 1 to 8 carbon atoms (C 1-8 Alkyl), more preferably containing 1-6 carbon atoms (ie C 1-6 Alkyl), such as "C 1-6 "Alkyl" means that the group is an alkyl group and the number of carbon atoms in the carbon chain is between 1 and 6 (specifically 1, 2, 3, 4, 5 or 6). Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, neopentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, n-heptyl, n-octyl, and the like.

[0158] Unless otherwise specified, the term "cycloalkyl" refers to a monocyclic saturated aliphatic hydrocarbon group having the specified number of carbon atoms, preferably containing 3 to 12 carbon atoms (i.e., C 3-12 cycloalkyl), more preferably containing 3 to 10 carbon atoms (C 3-10 cycloalkyl), further preferably 3-8 carbon atoms (C 3-8 Cycloalkyl), 3-6 carbon atoms (C 3-6 Cycloalkyl), 5-6 carbon atoms (C 5-6Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, 2-ethyl-cyclopentyl, dimethylcyclobutyl, and the like.

[0159] Unless otherwise specified, "cycloalkenyl" refers to a group consisting of monocyclic hydrocarbon rings, bicyclic hydrocarbon rings and spiro-hydrocarbon rings, however, the system is unsaturated, i.e., there is at least one C—C double bond but no aromatic system. Preferably, it contains 3 to 12 carbon atoms (i.e., C 3-12 cycloalkenyl), more preferably containing 3 to 10 carbon atoms (C 3-10 cycloalkenyl), further preferably 3-6 carbon atoms (C 3-6 Cycloalkenyl), 4-6 carbon atoms (C 4-6 Cycloalkenyl), 5-6 carbon atoms (C 5-6 cycloalkenyl).

[0160] Unless otherwise specified, the term "alkoxy" refers to an -O-alkyl group, wherein the alkyl group is as defined above, i.e., containing 1-20 carbon atoms, preferably, containing 1-10 carbon atoms, more preferably 1-8 carbon atoms, and more preferably 1-6 carbon atoms (specifically 1, 2, 3, 4, 5 or 6). Representative examples include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, tert-butoxy, pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, and the like.

[0161] Unless otherwise specified, the term "halogen" or "halo" refers to F, Cl, Br, I. The term "haloalkyl" refers to an alkyl group as defined above in which one, two or more hydrogen atoms or all of the hydrogen atoms are replaced by halogen. Representative examples of haloalkyl include CCl3, CF3, CHF2, CH2F, CHCl2, CH2Cl, CH2Br, CH2I, CH2CF3, CF2CF3 and the like.

[0162] Unless otherwise specified, the term "heterocyclyl" or "heterocycle" refers to a saturated or partially unsaturated monocyclic or polycyclic non-aromatic substituent having ring carbon atoms and 1 to 4 ring heteroatoms, containing 3 to 20 ring atoms, of which 1, 2, 3 or more ring atoms are selected from N, O or S, and the remaining ring atoms are C, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may be optionally oxidized, and wherein one or more carbon ring atoms may be optionally oxidized (i.e., to form an oxo group). Preferably, it contains 3 to 10 ring atoms (3-10 membered heterocyclyl), more preferably 3 to 8 ring atoms (3-8 membered heterocyclyl), or 3 to 6 ring atoms (3-6 membered heterocyclyl), or 4 to 6 ring atoms (4-6 membered heterocyclyl), 5 to 8 ring atoms (5-8 membered heterocyclyl) or 5 to 6 ring atoms (5-6 membered heterocyclyl). The number of heteroatoms is preferably 1-4, more preferably 1-3 (i.e., 1, 2, or 3). Examples of monocyclic heterocyclic groups include pyrrolidinyl, imidazolidinyl, tetrahydrofuranyl, dihydropyrrolyl, piperidinyl, piperazinyl, pyranyl, and the like. Polycyclic heterocyclic groups include spiro, fused, and bridged heterocyclic groups. A "heterocyclic group" may be monocyclic ("monocyclic heterocyclic group") or a fused ("fused heterocyclic group" or "heterofused heterocyclic group"), bridged ("heterobridged heterocyclic group" or "bridged heterocyclic group"), or spiro-fused ("heterospirocyclic group" or "spiroheterocyclic group") ring system, such as a bicyclic ring system ("bicyclic heterocyclic group"), and may be saturated or partially unsaturated. A heterocyclic bicyclic ring system may include one or more heteroatoms in one or both rings. "Heterocyclyl" also includes ring systems in which the heterocyclyl ring, as defined above, is fused to one or more carbocyclyl groups, wherein the point of attachment is on the carbocyclyl or heterocyclyl ring, or "heterocyclyl" also includes ring systems in which the heterocyclyl ring, as defined above, is fused to one or more aryl or heteroaryl groups, or a cycloalkyl ring, as defined above, is fused to one or more heteroaryl groups, wherein the point of attachment is on the heterocyclyl or cycloalkyl ring, and in such cases, the number of members of the heterocyclyl ring system is the number of atoms in the ring system after fusion. In certain embodiments, each instance of heterocyclyl is independently optionally substituted, e.g., unsubstituted (an "unsubstituted heterocyclyl") or substituted (a "substituted heterocyclyl") with one or more substituents. Exemplary 3-membered heterocyclyl groups containing 1 heteroatom include, but are not limited to, aziridine, oxiranyl, and thiorenyl. Exemplary 4-membered heterocyclyl groups containing 1 heteroatom include, but are not limited to, azetidinyl, oxetanyl, and thietanyl. Exemplary 5-membered heterocyclyl groups containing 1 heteroatom include, but are not limited to, tetrahydrofuranyl, dihydrofuranyl, tetrahydrophenylthio, dihydrophenylthio, pyrrolidinyl, dihydropyrrolyl, and pyrrolyl-2,5-dione.Exemplary 5-membered heterocyclyl groups containing 2 heteroatoms include, but are not limited to, dioxolanyl, oxathiolanyl, dithiolanyl, and oxazolidin-2-one. Exemplary 5-membered heterocyclyl groups containing 3 heteroatoms include, but are not limited to, triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6-membered heterocyclyl groups containing 1 heteroatom include, but are not limited to, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6-membered heterocyclyl groups containing 2 heteroatoms include, but are not limited to, piperazinyl, morpholinyl, dithiolanyl, and dioxanyl. Exemplary 6-membered heterocyclyl groups containing 3 heteroatoms include, but are not limited to, triazacyclohexanyl, oxadiazinyl, thiadiazinyl, oxathiazinyl, and dioxazacyclohexanyl. Exemplary 7-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azepanyl, oxepanyl, and thiepanyl. Exemplary 8-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azocanyl, oxepanyl, and thiepanyl. Exemplary 5-membered heterocyclyl groups fused to a C6 aryl ring (also referred to herein as a 5,6-bicyclic heterocycle) include, but are not limited to, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, benzoxazolinone, and the like. Exemplary 6-membered heterocyclyl groups fused to an aryl ring (also referred to herein as a 6,6-bicyclic heterocycle) include, but are not limited to, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and the like.

[0163] Unless otherwise specified, "heterocycloalkyl" refers to a monocyclic, saturated "heterocyclyl" or "heterocycle" as defined above, with the ring atoms as defined above, i.e., containing 3 to 20 ring atoms ("3-20 membered heterocycloalkyl"), with 1 to 4 heteroatoms (1, 2, 3 or 4), preferably 1 to 3 (1, 2 or 3), wherein each heteroatom is independently selected from N, O or S. One or more S ring atoms (if present) and / or one or more N ring atoms (if present) may be optionally oxidized, and one or more carbon ring atoms may be optionally oxidized (i.e., to form an oxo group). Preferably, the ring atoms are 3 to 12 ("3-12 membered heterocycloalkyl"), more preferably 3 to 10 ("3-10 membered heterocycloalkyl"), even more preferably 3 to 8 ("3-8 membered heterocycloalkyl"), and even more preferably 3 to 4 ("3-4 membered heterocycloalkyl"). In certain embodiments, each example of heterocycloalkyl is independently optionally substituted, e.g., unsubstituted (an "unsubstituted heterocycloalkyl") or substituted with one or more substituents (a "substituted heterocycloalkyl"). Some exemplary "heterocycloalkyl" groups are given above in the "heterocyclyl" or "heterocycle" section, and also include, but are not limited to, aziridine, oxirane, thiirane, azetidinyl, oxetanyl, thietanyl, tetrahydrofuranyl, oxanyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, oxathiolanyl, oxazolidinyl, dioxanyl, dithiolanyl, thiazolidinyl, pyrrolidinyl, pyrazolidinyl, imidazolinyl, and the like.

[0164] Unless otherwise specified, "heterocyclenyl" refers to an unsaturated alicyclic (non-aromatic) ring radical, including monocyclic as well as bridged, spirocyclic and / or fused ring systems (which may consist of two or three rings; for example, a fused ring system consisting of two or three fused rings), wherein the ring radical contains one or more (e.g., one, two, three or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may be optionally oxidized, wherein one or more carbon ring atoms may be optionally oxidized (i.e., to form an oxo group), and wherein the ring radical further contains at least one double bond between adjacent ring atoms and does not contain any triple bonds between adjacent ring atoms. For example, each heteroatom-containing ring contained in the unsaturated alicyclic ring group may contain one or two O atoms and / or one or two S atoms (which may be optionally oxidized) and / or one, two, three or four N atoms (which may be optionally oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1-4 and there is at least one carbon ring atom (which may be optionally oxidized) in the corresponding heteroatom-containing ring. "Heterocycloalkenyl" may, for example, refer to imidazolinyl (e.g., 2-imidazolinyl (i.e., 4,5-dihydro-1H-imidazolyl), 3-imidazolinyl, or 4-imidazolinyl), tetrahydropyridinyl (e.g., 1,2,3,6-tetrahydropyridinyl), dihydropyridinyl (e.g., 1,2-dihydropyridinyl, or 2,3-dihydropyridinyl), pyranyl (e.g., 2H-pyranyl, or 4H-pyranyl), thiopyranyl (e.g., 2H-thiopyranyl, or 4H-thiopyranyl), dihydropyranyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrazinyl, dihydroisoindolyl, octahydroquinolinyl (e.g., 1,2,3,4,4a,5,6,7-octahydroquinolinyl), or octahydroisoquinolinyl (e.g., 1,2,3,4,5,6,7,8-octahydroisoquinolinyl).Unless otherwise defined, "heterocycloalkenyl" preferably refers to a 3- to 12-membered unsaturated alicyclic radical that is a monocyclic or fused ring system (e.g., a fused ring system consisting of two fused rings), wherein the ring radical contains one or more (e.g., one, two, three, or four) ring heteroatoms independently selected from O, S, and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, wherein one or more carbon ring atoms are optionally oxidized, wherein the ring radical contains at least one double bond between adjacent ring atoms and does not contain any triple bonds between adjacent ring atoms; more preferably, "heterocycloalkenyl" refers to a 5- to 7-membered monocyclic unsaturated non-aromatic ring radical containing one or more (e.g., one, two, or three) ring heteroatoms independently selected from O, S, and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, wherein one or more carbon ring atoms are optionally oxidized, and wherein the ring radical contains at least one double bond between adjacent ring atoms and does not contain any triple bonds between adjacent ring atoms.

[0165] Unless otherwise specified, the term "aryl" or "aromatic ring group" refers to a monocyclic, bicyclic, or tricyclic aromatic carbocyclic ring system containing 6 to 16 carbon atoms, or 6 to 14 carbon atoms, or 6 to 12 carbon atoms, or 6 to 10 carbon atoms, preferably 6 to 10 carbon atoms. The term "aryl" can be used interchangeably with the term "aromatic ring group." Examples of aryl groups include, but are not limited to, phenyl, naphthyl, anthracenyl, phenanthrenyl, or pyrenyl.

[0166] Unless otherwise specified, the term "heteroaryl" or "heteroaromatic ring group" means an aromatic monocyclic or polycyclic ring system containing a 5-14 membered structure, or preferably a 5-10 membered structure, or preferably a 5-8 membered structure, more preferably a 5-6 membered structure, wherein 1, 2, 3 or more ring atoms are heteroatoms and the remaining atoms are carbon, the heteroatoms are independently selected from O, N or S, and the number of heteroatoms is preferably 1, 2 or 3. Examples of heteroaryl groups include, but are not limited to, furyl, thienyl, oxazolyl, thiazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, thiodiazolyl, triazinyl, phthalazinyl, quinolyl, isoquinolyl, pteridinyl, purinyl, indolyl, isoindolyl, indazolyl, benzofuranyl, benzothiophenyl, benzopyridinyl, benzopyrimidinyl, benzo pyrazinyl, benzimidazolyl, benzophthalazinyl, pyrrolo[2,3-b]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-b]pyridazinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, [1,2,4]triazolo[1,5-a]pyrimidinyl, [1,2,4]triazolo[1,5-a]pyridinyl, etc.

[0167] Unless otherwise specified, the term "treat," "treatment," "treatment," or "treating" encompasses any treatment of a disease, disorder, or condition in a patient, including: (a) inhibiting the symptoms of the disease, disorder, or condition, i.e., arresting its development; or (b) relieving the symptoms of the disease, disorder, or condition, i.e., causing regression of the disease or symptoms; or (c) ameliorating or eliminating the disease, disorder, or condition or one or more symptoms associated with the disease.

[0168] The therapeutically effective amount of the present invention refers to the effective dosage considered pharmaceutically, that is, the amount of the active compound is sufficient to significantly improve the condition without causing serious side effects.

[0169] The beneficial effects of the present invention are:

[0170] The present invention provides a novel MAO-B inhibitor. In vitro experimental results show that the compound of the present invention has strong selective MAO-B inhibitory activity. In vivo experimental results show that the compound of the present invention can significantly reduce the body weight of mice without affecting food intake.

[0171] Figures in the specification

[0172] Figure 1 shows the changes in mouse body weight during the DIO mouse weight loss experiment.

[0173] FIG2 is a graph showing changes in weight growth rate of mice in a DIO mouse weight loss experiment.

[0174] Figure 3 shows the changes in food intake of mice during the DIO mouse weight loss experiment. DETAILED DESCRIPTION

[0175] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention only and are not intended to limit the scope of the present invention. Experimental methods in the following examples where specific conditions are not specified are generally performed under conventional conditions or according to the conditions recommended by the manufacturer. Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to professionals in the field. In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention. The preferred embodiments and materials shown herein are for demonstration purposes only.

[0176] The structures of the compounds of the present invention were determined by nuclear magnetic resonance (NMR) and / or liquid chromatography-mass spectrometry (LC-MS) and / or liquid chromatography (HPLC). NMR measurements were performed using a Bruker AVANCE III 600 MHz instrument, LC-MS using an LCMS WATERS ACQUITY UPLC H-Class PLUS or / and SQD2, and HPLC using a WATERS e2695-2998 or / and an Agilent 1100.

[0177] The starting materials in the examples of the present invention are known and can be purchased commercially, or can be synthesized using or according to methods known in the art.

[0178] Explanation of terms or abbreviations:

[0179] OMs: methylsulfonyl

[0180] OTf: trifluoromethanesulfonyl

[0181] OTs: p-Toluenesulfonyl

[0182] B(OH)2: Boric acid group

[0183] Bpin: pinacol borate

[0184] Bneop: neopentyl borate.

[0185] Example 1: Preparation of Compound 1

[0186] (1) Preparation of intermediate 1-1

[0187] 2-Fluoro-4-bromobenzaldehyde (203 mg, 1.00 mmol), 4-trifluoromethylphenylboronic acid (247 mg, 1.30 mmol), sodium carbonate (424 mg, 4.00 mmol), and tetrakistriphenylphosphine palladium (58 mg, 0.05 mmol) were added to toluene / methanol / water (4 mL / 2 mL / 1 mL). The nitrogen atmosphere was replaced three times, and the mixture was heated to 100°C under a nitrogen atmosphere and stirred for 18 h. The mixture was filtered through celite and extracted with ethyl acetate (20 mL × 3). The organic phases were combined, washed with saturated sodium chloride solution (20 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (petroleum ether:ethyl acetate = 50:1) to obtain intermediate 1-1 (231 mg, 86% yield).

[0188] (2) Preparation of Compound 1

[0189] Intermediate 1-1 (231 mg, 0.86 mmol) was added to anhydrous methanol (10 mL), followed by the addition of L-alaninamide hydrochloride (128 mg, 1.03 mmol) and triethylamine (130 mg, 1.29 mmol). The mixture was allowed to react at room temperature for 2 h, then cooled to 0°C, sodium cyanoborohydride (216 mg, 3.44 mmol) was added, and the reaction mixture was gradually returned to room temperature and allowed to react overnight. The mixture was concentrated under reduced pressure and purified by preparative thin-layer chromatography (dichloromethane:methanol=20:1) to obtain compound 1 (228 mg, 78% yield). ESI-MS (m / z): 341.15 [M+H] + . 1 H NMR (600MHz, DMSO-d6) δ7.92(d,J=8.4Hz,2H),7.81(d,J=8.4Hz,2H),7.62-7.56(m,3H),7.33(s,1H),7. 02(s,1H),3.75(d,J=14.4Hz,1H),3.65(d,J=14.4Hz,1H),3.06(q,J=6.6Hz,1H),1.16(d,J=6.6Hz,3H).

[0190] Example 2: Preparation of Compound 2

[0191] Referring to the preparation method of compound 1, 2-fluoro-4-bromobenzaldehyde was replaced with 2-chloro-4-bromobenzaldehyde to prepare compound 2 (222 mg, 2-step yield 62%), ESI-MS (m / z): 357.16 [M+H] + . 1H NMR (600MHz, DMSO-d6) δ7.92(d,J=7.8Hz,2H),7.81-7.79(m,3H),7.71(d,J=8.4Hz,1H),7.68(d,J=7.8Hz,1H),7.35(s,1H ),7.02(s,1H),3.80(d,J=15.0Hz,1H),3.70(d,J=15.0Hz,1H),3.09(q,J=6.6Hz,1H),2.54(s,1H),1.19(d,J=6.6Hz,3H).

[0192] Example 3: Preparation of Compound 3

[0193] Referring to the preparation method of compound 1, 2-fluoro-4-bromobenzaldehyde was replaced with 4-bromobenzaldehyde, and L-alaninamide hydrochloride was replaced with 1-aminocyclopropionamide to prepare compound 3 (191 mg, 2-step yield 57%), ESI-MS (m / z): 335.16 [M+H] + . 1 H NMR (600MHz, DMSO-d6) δ7.88(d,J=8.4Hz,2H),7.80(d,J=8.4Hz,2H),7.68(d,J=7.8Hz,2H),7.48(d,J= 7.8Hz,2H),7.47(s,1H),7.16(s,1H),3.74(s,2H),2.86(s,1H),1.05-1.04(m,2H),0.90-0.87(m,2H).

[0194] Example 4: Preparation of Compound 4

[0195] (1) Preparation of intermediate 4-1

[0196] Referring to the preparation method of compound 3, 1-aminocyclopropionamide was replaced with 3-aminooxetane-3-carboxylic acid to prepare intermediate 4-1 (222 mg, yield 61%).

[0197] (2) Preparation of Compound 4

[0198] Intermediate 4-1 (80 mg, 0.23 mmol) was dissolved in dichloromethane (10 mL), and 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (175 mg, 0.46 mmol), ammonium chloride (37 mg, 0.69 mmol), and triethylamine (70 mg, 0.69 mmol) were added. The mixture was reacted at room temperature for 4 h. The mixture was concentrated under reduced pressure to obtain a crude product, which was then purified by column chromatography (dichloromethane:methanol = 50:1-20:1) to afford compound 4 (40 mg, 50% yield). ESI-MS (m / z): 351.10 [M+H] + . 1 H NMR (600MHz, DMSO-d6) δ7.90(d,J=8.4Hz,2H),7.81(d,J=8.4Hz,2H),7.71(d,J=8.4Hz,2H),7.53(d,J=8.4Hz,2H),7 .37(s,1H),7.28(s,1H),4.72(d,J=6.0Hz,2H),4.43(d,J=6.0Hz,2H),3.59(d,J=7.2Hz,2H),3.37(t,J=7.2Hz,1H).

[0199] Example 5: Preparation of Compound 5

[0200] Referring to the preparation method of compound 1, 4-trifluoromethylphenylboronic acid was replaced with 3,4-dichlorophenylboronic acid, and 2-fluoro-4-bromobenzaldehyde was replaced with 4-bromobenzaldehyde to prepare compound 5 (239 mg, 2-step yield 74%), ESI-MS (m / z): 323.10 [M+H] + . 1 H NMR(600MHz,DMSO-d6)δ7.92(d,J=1.8Hz,1H),7.71-7.66(m,4H),7.44(d,J=8.4Hz,2H),7.34(s,1H),6. 99 (s, 1H), 3.73 (d, J = 13.8Hz, 1H), 3.59 (d, J = 13.8Hz, 1H), 3.03 (q, J = 7.2Hz, 1H), 1.15 (d, J = 6.6Hz, 3H).

[0201] Example 6: Preparation of Compound 6

[0202] (1) Preparation of Intermediate 6-1

[0203] Intermediate 3-1 (250 mg, 1.00 mmol) was dissolved in anhydrous methanol (10 mL), followed by the addition of sodium borohydride (45 mg, 1.20 mmol), and the reaction was stirred at room temperature for 1 h. Water (20 mL) was added to the reaction solution, which was concentrated and extracted with ethyl acetate (20 mL x 3). The organic phases were combined, washed with saturated sodium chloride solution (20 mL x 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Purification by column chromatography (petroleum ether:ethyl acetate = 50:1-10:1) afforded Intermediate 6-1 (250 mg, 99% yield).

[0204] (2) Preparation of intermediate 6-2

[0205] Intermediate 6-1 (250 mg, 0.99 mmol) was dissolved in anhydrous N,N-dimethylformamide (10 mL). Thionyl chloride (118 mg, 1.98 mmol) was added at 0°C, and the reaction was allowed to proceed at room temperature for 2 h. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL × 3). The organic phases were combined, washed with saturated sodium chloride solution (30 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (petroleum ether:ethyl acetate = 50:1) to obtain intermediate 6-2 (267 mg, 99% yield).

[0206] (3) Preparation of Compound 6

[0207] Intermediate 6-2 (267 mg, 0.98 mmol), (S)-azetidine-2-carboxamide (118 mg, 1.18 mmol), and triethylamine (148 mg, 1.47 mmol) were dissolved in N,N-dimethylformamide (10 mL). The reaction mixture was allowed to react overnight at room temperature. Water (20 mL) was added, and extraction with ethyl acetate (20 mL × 3) was performed. The organic phases were combined, washed with saturated sodium chloride solution (20 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (dichloromethane:methanol = 50:1-20:1) to obtain compound 6 (134 mg, 41% yield). ESI-MS (m / z): 335.20 [M+H] + . 1HNMR (600MHz, CDCl3) δ7.70-7.67(m,4H),7.56(d,J=7.2Hz,2H),7.37(d,J=7.2Hz,2H),7.05(s,1H),5.57(s,1H),3.79(d,J=12.6Hz, 1H),3.72(dd,J=8.4,8.4Hz,1H),3.62(d,J=12.6Hz,1H),3.41-3.38(m,1H),3.06-3.02(m,1H),2.47-2.42(m,1H),2.24-2.17(m,1H).

[0208] Example 7: Preparation of Compound 7

[0209] Referring to the preparation method of compound 6, and replacing (S)-azetidine-2-carboxamide with azetidine-3-carboxamide hydrochloride, compound 7 (80 mg, yield 64%) was prepared. ESI-MS (m / z): 335.06 [M+H] + . 1 H NMR (600MHz, DMSO-d6) δ7.89(d,J=7.8Hz,2H),7.80(d,J=8.4Hz,2H),7.69(d,J=8.4Hz,2H),7.41(d,J=7. 8Hz,2H),7.31(s,1H),6.90(s,1H),3.62(s,2H),3.41-3.39(m,2H),3.21-3.19(m,2H),3.17-3.11(m,1H).

[0210] Example 8: Preparation of Compound 8

[0211] Referring to the preparation method of compound 3, 1-aminocyclopropaneamide was replaced with L-prolinamide to prepare compound 8 (153 mg, yield 44%), ESI-MS (m / z): 349.12 [M+H] + . 1HNMR (600MHz, CDCl3) δ7.69-7.68(m,4H),7.56(d,J=7.8Hz,2H),7.39(d,J=7.8Hz,2H),7.24(s,1H),5.45(s,1H),4.00(d,J=13.2Hz,1H), 3.55(d,J=13.2Hz,1H),3.24-3.21(m,1H),3.10-3.08(m,1H),2.41-2.37(m,1H),2.31-2.24(m,1H),1.98-1.93(m,1H),1.86-1.76(m,2H).

[0212] Example 9: Preparation of Compound 9

[0213] Referring to the preparation method of compound 3, L-alaninamide hydrochloride was replaced with (2S,4S)-4-fluoropyrrolidine-2-carboxamide to prepare compound 9 (132 mg, yield 36%), ESI-MS (m / z): 367.16 [M+H] + . 1 HNMR (600MHz, CDCl3) δ7.71-7.68(m,4H),7.58(d,J=7.8Hz,2H),7.40(d,J=7.8Hz,2H),7.25(s,1H),5.37(s,1H),5.37(ddd,J= 53.4,3.6,3.6Hz,1H),4.07(d,J=13.2Hz,1H),3.57(d,J=13.2Hz,1H),3.38-3.30(m,2H),2.67-2.50(m,2H),2.31-2.24(m,1H).

[0214] Example 10: Preparation of Compound 10

[0215] (1) Preparation of Intermediate 10-1

[0216] 5-Bromoisoindoline hydrochloride (1.00 g, 4.26 mmol), (R)-methyl 2-bromopropionate (1.07 g, 6.40 mmol), and N,N-diisopropylethylamine (1.65 g, 12.78 mmol) were dissolved in dichloromethane (30 mL) and allowed to react overnight at room temperature. Water (50 mL) was added, and the mixture was extracted with ethyl acetate (50 mL x 3). The combined organic phases were washed with saturated sodium chloride (50 mL x 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (petroleum ether:ethyl acetate = 20:1 to 5:1) to obtain Intermediate 10-1 (900 mg, 74% yield).

[0217] (2) Preparation of Intermediate 10-2

[0218] Intermediate 10-1 (284 mg, 1.00 mmol), 4-trifluoromethylphenylboronic acid (247 mg, 1.30 mmol), sodium carbonate (424 mg, 4.00 mmol), and tetrakistriphenylphosphine palladium (58 mg, 0.05 mmol) were added to toluene / methanol / water (4 mL / 2 mL / 1 mL). The nitrogen atmosphere was replaced three times, and the mixture was heated to 100°C under a nitrogen atmosphere and stirred for 18 h. The mixture was filtered through celite and extracted with ethyl acetate (20 mL × 3). The organic phases were combined, washed with saturated sodium chloride (20 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (petroleum ether:ethyl acetate = 20:1-5:1) to obtain intermediate 10-2 (241 mg, 69% yield).

[0219] (3) Preparation of Compound 10

[0220] Intermediate 10-2 (241 mg, 0.69 mmol) and sodium hydroxide (42 mg, 1.04 mmol) were dissolved in tetrahydrofuran / methanol / water (10 mL / 2 mL / 2 mL) and reacted at 50°C for 6 h. Water (10 mL) was added and the pH was adjusted to 5-6. The mixture was extracted with dichloromethane (20 mL x 3). The combined organic phases were washed with saturated sodium chloride (20 mL x 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in dichloromethane (10 mL), and 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (394 mg, 1.04 mmol), ammonium chloride (55 mg, 1.04 mmol), and triethylamine (139 mg, 1.38 mmol) were added. The mixture was reacted at room temperature for 4 h, concentrated under reduced pressure, and purified by column chromatography (dichloromethane:methanol = 50:1-20:1) to obtain compound 10 (100 mg, yield 43%). ESI-MS (m / z): 335.16 [M+H] + 。ESI-MS(m / z):357.16[M+H] + . 1 H NMR (600MHz, DMSO-d6) δ7.86(d,J=8.4Hz,2H),7.80(d,J=8.4Hz,2H),7.62(s,1H),7.57-7.56(m,1H),7.38( d,J=7.8Hz,1H),7.32(s,1H),7.02(s,1H),4.02-3.99(m,4H),3.20(q,J=6.6Hz,1H),1.29(d,J=6.6Hz,3H).

[0221] Example 11: Preparation of Compound 11

[0222] (1) Preparation of Intermediate 11-1

[0223] 5-Bromo-1-indanone (1.00 g, 4.74 mmol), 4-trifluoromethylphenylboronic acid (1.15 g, 6.07 mmol), sodium carbonate (2.44 g, 23.04 mmol), and tetrakistriphenylphosphine palladium (0.27 g, 0.24 mmol) were dissolved in toluene / water (21 mL / 3 mL). The nitrogen atmosphere was replaced three times and the mixture was heated to 110°C with stirring for 4 h under a nitrogen atmosphere. The mixture was filtered through celite and extracted with ethyl acetate (20 mL x 3). The organic phases were combined, washed with saturated sodium chloride solution (20 mL x 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (petroleum ether:ethyl acetate = 20:1-5:1) to obtain intermediate 11-1 (1.25 g, 95% yield).

[0224] (2) Preparation of Intermediate 11-2

[0225] Intermediate 11-1 (450 mg, 1.63 mmol), (S)-tert-butylsulfenamide (237 mg, 1.96 mmol), and tetraethyl titanate (1.10 g, 4.89 mmol) were dissolved in tetrahydrofuran (20 mL) and heated to 80°C with stirring for 24 h. Water (20 mL) was added to the reaction solution, and the mixture was filtered through celite. The filter cake was washed with ethyl acetate, and the resulting solution was collected and extracted with ethyl acetate (20 mL x 3). The organic phases were combined, washed with saturated sodium chloride (20 mL x 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (petroleum ether:ethyl acetate = 10:1-2:1) to obtain Intermediate 11-2 (220 mg, 36% yield).

[0226] (3) Preparation of Intermediate 11-3

[0227] Intermediate 11-2 (220 mg, 0.58 mmol) was dissolved in tetrahydrofuran (20 mL), and sodium borohydride (44 mg, 1.16 mmol) was slowly added. The mixture was stirred at room temperature for 3 h. The mixture was concentrated under reduced pressure and purified by column chromatography (petroleum ether:ethyl acetate = 5:1 to 1:1) to obtain Intermediate 11-3 (170 mg, 77% yield).

[0228] (4) Preparation of Intermediate 11-4

[0229] Intermediate 11-3 (170 mg, 0.45 mmol) was dissolved in dioxane hydrochloride (10 mL, 2 M), stirred at room temperature for 2 h, and concentrated under reduced pressure to obtain intermediate 11-4, which was used directly in the next step.

[0230] (5) Preparation of Intermediate 11-5

[0231] Intermediate 11-4, methyl 2-chloropropionate (66 mg, 0.54 mmol), potassium carbonate (186 mg, 1.35 mmol), and potassium iodide (75 mg, 0.45 mmol) were dissolved in N,N-dimethylformamide (15 mL) and stirred at 90°C for 24 h. Water (20 mL) was added, and the mixture was extracted with ethyl acetate (20 mL × 3). The organic phases were combined, washed with saturated sodium chloride solution (20 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (petroleum ether:ethyl acetate = 10:1-3:1) to obtain Intermediate 11-5 (60 mg, 37% yield).

[0232] (6) Preparation of Compound 11

[0233] Intermediate 11-5 (60 mg, 0.17 mmol) and sodium hydroxide (34 mg, 0.85 mmol) were dissolved in tetrahydrofuran / methanol / water (2 mL / 2 mL / 2 mL) and reacted at room temperature for 2 h. Water (5 mL) was added and the pH was adjusted to 5-6. The mixture was extracted with dichloromethane (15 mL x 3). The combined organic phases were washed with saturated sodium chloride solution (15 mL x 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in dichloromethane (10 mL), and 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (129 mg, 0.34 mmol), ammonium chloride (27 mg, 0.51 mmol), and triethylamine (52 mg, 0.51 mmol) were added. The mixture was reacted at room temperature for 4 h, concentrated under reduced pressure, and purified by column chromatography (dichloromethane:methanol=50:1-20:1) to obtain compound 11 (20 mg, yield 35%). ESI-MS (m / z): 349.12 [M+H] + . 1 H NMR (600MHz, DMSO-d6) δ7.87(d,J=8.4Hz,2H),7.80(d,J=8.4Hz,2H),7.58(d,J=3.0Hz,1H),7.55-7.52(m,1H),7.46-7.41(m,2H),7.04(s,1H),4.11 -4.10(m,1H),3.26-3.19(m,1H),3.03-2.99(m,1H),2.82-2.78(m,1H),2. 37-2.34(m,1H),2.32-2.25(m,1H),1.81-1.74(m,1H),1.19-1.17(m,3H).

[0234] Example 12: Preparation of Compound 12

[0235] Referring to the preparation method of compound 1, 4-trifluoromethylphenylboronic acid was replaced with 5-trifluoromethylthiophene-2-boronic acid, and 2-fluoro-4-bromobenzaldehyde was replaced with 4-bromobenzaldehyde to prepare compound 12 (161 mg, 2-step yield 49%), ESI-MS (m / z): 329.12 [M+H] + . 1 H NMR (600MHz, DMSO-d6) δ7.72(d,J=3.0Hz,1H),7.69(d,J=7.8Hz,2H),7.59(d,J=3.0Hz,1H),7.43(d,J=8.4Hz,2H),7. 34(s,1H),6.99(s,1H),3.73(d,J=14.4Hz,1H),3.59(d,J=14.4Hz,1H),3.03(q,J=6.6Hz,1H),1.15(d,J=6.6Hz,3H).

[0236] Example 13: Preparation of Compound 13

[0237] Referring to the preparation method of compound 1, 2-fluoro-4-bromobenzaldehyde was replaced with 3-methyl-5-bromothiophene-2-carboxaldehyde to prepare compound 13 (188 mg, 2-step yield 55%), ESI-MS (m / z): 343.12 [M+H] + . 1 H NMR (600MHz, DMSO-d6) δ7.79(d,J=8.4Hz,2H),7.72(d,J=8.4Hz,2H),7.40(s,1H),7.33(s,1H),7.02(s,1H),3.79 (d,J=14.4Hz,1H),3.68(d,J=14.4Hz,1H),3.12(q,J=6.6Hz,1H),2.60(s,1H),2.14(s,3H),1.15(d,J=7.2Hz,3H).

[0238] Example 14: Preparation of Compound 14

[0239] Referring to the preparation method of compound 1, 2-fluoro-4-bromobenzaldehyde was replaced with 5-bromothiophene-2-carboxaldehyde to prepare compound 11 (204 mg, 2-step yield 62%), ESI-MS (m / z): 329.11 [M+H] + . 1H NMR (600MHz, DMSO-d6) δ7.83(d,J=7.8Hz,2H),7.73(d,J=7.8Hz,2H),7.52(d,J=3.6Hz,1H),7.33(s,1H),7.01-6.9 9(m,2H),3.90(d,J=15.0Hz,1H),3.76(d,J=15.0Hz,1H),3.12(q,J=7.2Hz,1H),2.69(s,1H),1.15(d,J=6.6Hz,3H).

[0240] Example 15: Preparation of Compound 15

[0241] Referring to the preparation method of compound 1, 2-fluoro-4-bromobenzaldehyde was replaced with 5-bromo-2-pyridinecarboxaldehyde to prepare compound 15 (222 mg, 2-step yield 47%), ESI-MS (m / z): 324.13 [M+H] + . 1 H NMR (600MHz, DMSO-d6) δ8.88(d,J=1.8Hz,1H),8.15-8.13(m,1H),7.96(d,J=7.8Hz,2H),7.85(d,J=8.4Hz,2H),7.60(d,J=7.8Hz,1H) ,7.38(s,1H),7.02(s,1H),3.86(d,J=15.0Hz,1H),3.75(d,J=15.0Hz,1H),3.10(q,J=6.6Hz,1H),2.73(s,1H),1.19(d,J=6.6Hz,3H).

[0242] Example 16: Preparation of Compound 16

[0243] (1) Preparation of Intermediate 16-1

[0244] 4-(Thiotrifluoromethyl)bromobenzene (300 mg, 1.17 mmol), 4-formylphenylboronic acid (264 mg, 1.76 mmol), sodium carbonate (248 mg, 2.34 mmol), and tetrakistriphenylphosphine palladium (139 mg, 0.12 mmol) were added to toluene / methanol / water (18 mL / 2 mL / 2 mL). The nitrogen atmosphere was replaced three times, and the mixture was heated to 110°C under a nitrogen atmosphere and stirred for 4 h. The mixture was filtered through celite and extracted with ethyl acetate (20 mL × 3). The organic phases were combined, washed with saturated sodium chloride solution (20 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (petroleum ether:ethyl acetate = 30:1-10:1) to obtain intermediate 16-1 (300 mg, 91% yield).

[0245] (2) Preparation of Compound 16

[0246] Referring to the preparation method of compound 1, intermediate 1-1 was replaced with intermediate 16-1 to prepare compound 16 (20 mg, yield 32%), ESI-MS (m / z): 355.07 [M+H] + . 1 H NMR (600MHz, DMSO-d6) δ7.84(d,J=8.4Hz,2H),7.80(d,J=8.4Hz,2H),7.69(d,J=8.4Hz,2H),7.47(d,J=8.4Hz,2H),7. 35(s,1H),7.01(s,1H),3.75(d,J=13.8Hz,1H),3.61(d,J=13.8Hz,1H),3.05(q,J=6.6Hz,1H),1.16(d,J=6.6Hz,3H).

[0247] Example 17: Preparation of Compound 17

[0248] Referring to the preparation method of compound 16, 4-(thiotrifluoromethyl)bromobenzene was replaced with 4-bromophenyl sulfur pentafluoride to prepare compound 17 (20 mg, 2-step yield 36%), ESI-MS (m / z): 381.06 [M+H] + . 1 H NMR (600MHz, DMSO-d6) δ7.97(d,J=9.0Hz,2H),7.89(d,J=9.0Hz,2H),7.70(d,J=7.8Hz,2H),7.48(d,J=7.8Hz,2H),7. 35(s,1H),7.01(s,1H),3.76(d,J=13.8Hz,1H),3.62(d,J=13.8Hz,1H),3.05(q,J=6.6Hz,1H),1.16(d,J=7.2Hz,3H).

[0249] Example 18-21: Preparation of Compound 18-21

[0250] Referring to the synthesis method of compound 1, the reaction raw materials were replaced with corresponding reagents to prepare compounds 18-21.

[0251] Examples 22-24: Preparation of Compounds 22-24

[0252] Referring to the preparation method of compound 3, the reaction raw materials were replaced with corresponding reagents to prepare compounds 22-24.

[0253] Examples 25-27: Preparation of Compounds 25-27

[0254] Referring to the preparation method of compound 4, the reaction raw materials were replaced with corresponding reagents to prepare compounds 25-27.

[0255] Examples 28-37: Preparation of Compounds 28-37

[0256] Referring to the preparation method of compound 3, the reaction raw materials were replaced with corresponding reagents to prepare compounds 28-37.

[0257] Example 38: Preparation of Compound 38

[0258] (1) Preparation of Intermediate 38-1

[0259] Referring to the preparation method of intermediate 1-1, 2-fluoro-4-bromobenzaldehyde was replaced with (1R,2S)-2-(4-bromophenyl)cyclopropaneamine to prepare intermediate 38-1.

[0260] (2) Preparation of Compound 38

[0261] Referring to the preparation method of intermediate 10-1, 5-bromoisoindoline hydrochloride was replaced with intermediate 38-1, and (R)-2-bromopropionic acid methyl ester was replaced with 2-bromoacetamide to prepare compound 38. ESI-MS (m / z): 335.16 [M+H] + .

[0262] Examples 39-47: Preparation of Compounds 39-47

[0263] Referring to the preparation method of compound 38, the reaction raw materials were replaced with corresponding reagents to prepare compounds 39-47.

[0264] Example 48: Preparation of Compound 48

[0265] Referring to the preparation method of compound 11, (S)-tert-butylsulfenamide was replaced with (R)-tert-butylsulfenamide to prepare compound 48, ESI-MS (m / z): 349.16 [M+H] + .

[0266] Examples 49-50: Preparation of Compounds 49-50

[0267] Referring to the preparation method of compound 48, the reaction raw materials were replaced with corresponding reagents to prepare compounds 49-50.

[0268] Examples 51-52: Preparation of Compounds 51-52

[0269] Referring to the preparation method of compound 11, the reaction raw materials were replaced with corresponding reagents to prepare compounds 51-52.

[0270] Examples 53-63: Preparation of Compounds 53-63

[0271] Referring to the preparation method of compound 16, the reaction raw materials were replaced with corresponding reagents to prepare compounds 53-63.

[0272] Example 64: Preparation of Compound 64

[0273] Compound 1 (0.50 mmol), 3-bromopropyne (1.5 equivalents), potassium carbonate (3.0 equivalents), and potassium iodide (0.2 equivalents) were dissolved in acetonitrile and the system was reacted at room temperature overnight. Water (50 mL) was added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, washed with saturated sodium chloride (50 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography (dichloromethane:methanol = 50:1-20:1) to obtain compound 64 (0.45 mmol, yield 90%). ESI-MS (m / z): 379.12 [M+H] + .

[0274] Example 65: Preparation of Compound 1 Methanesulfonate

[0275] Compound 1 (420 mg, 1.23 mmol) was added to ethyl acetate (10 mL) and heated to 55°C until compound 1 completely dissolved. Methanesulfonic acid (148 mg, 1.54 mmol) was then slowly added dropwise and allowed to react at 55°C for 2 h. The mixture was slowly cooled to room temperature, filtered, and the filter cake was washed with ethyl acetate (20 mL) to obtain the methanesulfonate salt of compound 1 (460 mg, 86% yield). 1HNMR(600MHz,DMSO-d6)δ9.23(s,2H),7.97(d,J=8.4Hz,2H),7.94(s,1H),7.83(d,J=8.4Hz,2H),7.75- 7.69(m,3H),7.66(s,1H),4.22-4.16(m,2H),3.87(q,J=6.6Hz,1H),2.29(s,3H),1.44(d,J=6.6Hz,3H).

[0276] Test example control compound:

[0277] Test Example 1: MAO-B Inhibitory Activity Test of Compounds

[0278] 1.1 Test materials

[0279] 1.2 Test methods

[0280] (1) Sample preparation: The 10 mM compound was diluted 100-fold, and then the high concentration of 0.1 mM (100,000 nM) was diluted 5-fold to prepare 20,000 nM, 4,000 nM, 800 nM, 160 nM, 32 nM, 6.4 nM, and 1.28 nM. Finally, 8 concentrations were prepared, and 0.05 M sodium phosphate (pH = 7.4) buffer was prepared.

[0281] (2) Prepare enzyme buffer by diluting 290 μg / mL human monoamine oxidase B to 1 / 121 with 0.05 M sodium phosphate buffer and mixing with 10 μL of the compound solution at each of the eight concentrations to a final volume of 100 μL. Add the enzyme buffer to a 96-well plate and incubate for 30 minutes.

[0282] (3) Prepare working buffer by adding 20 mM Amplex Red (200 μL), 100 mM benzylamine substrate (200 μL) and 200 U / mL horseradish peroxidase (100 μL) to 0.05 M sodium phosphate (pH = 7.4) buffer (9.5 mL). Mix 100 μL of working buffer with the enzyme buffer of (2) at a ratio of 1:1 and incubate for 30 minutes. Then, read the fluorescence with an excitation wavelength in the range of 530-560 nm and an emission wavelength of 590 nm.

[0283] (4) The enzyme activity inhibition rate data were processed using formula (1) to calculate the inhibition rate corresponding to different concentrations of compounds, where RLU compound is the RLU value detected after compound incubation, RLU blank well is the RLU detected without monoamine oxidase B, and RLU solvent control well is the RLU detected after adding 0.05M sodium phosphate buffer. GraphPad Prism software was used to draw the inhibition rate curve and calculate IC 50 value.

[0284] Inhibition Rate (Inh%) = (1-(RLU compound-RLU blank well) / (RLU solvent control well-RLU blank well)) × 100% (Formula 1)

[0285] Representative compounds in the examples were tested according to the above method and found to have strong inhibitory activity against MAO-B. The activity data of the exemplary compounds are shown in the table below.

[0286] A:IC 50 <50nM, B:50nM≤IC 50 <100nM, C: 100nM≤IC 50 <1000nM,

[0287] D: 1000nM≤IC 50 <2000nM, E: 2000nM≤IC 50 <10000nM, F:IC 50 ≥10000nM

[0288] Test Example 2: Inhibitory activity test of compounds against MAO-A

[0289] 2.1 Test materials

[0290] 2.2 Test methods

[0291] (1) Sample preparation: Dilute the 10 mM compound 50-fold. Then, dilute the high concentration of 0.2 mM (200,000 nM) 5-fold to prepare three concentrations: 40,000 nM, 8,000 nM, and 1,600 nM. For clorpheniramine, prepare eight concentrations: 40,000 nM, 8,000 nM, 1,600 nM, 320 nM, 64 nM, 12.8 nM, 2.56 nM, and 0.5 nM. Also prepare the MAO Reaction Buffer.

[0292] (2) Dilute 270 μg / mL human monoamine oxidase A to 4 μg / mL with MAO Reaction Buffer and add 25 μL to each well of a 96-well plate.

[0293] (3) Add the prepared compounds of different concentrations to the corresponding 96-well plates, add 12.5 μL to each well, mix briefly, and incubate for 30 minutes.

[0294] (4) Dilute 4 mM MAO substrate to 160 μM with MAO Reaction Buffer and add 12.5 μL to each well of a 96-well plate. Continue incubation for 30 minutes.

[0295] (5) Add 50 μL of Reconstituted Luciferin Detection Reagent to each well, mix briefly, incubate in the dark for 20 minutes, and then read the fluorescence.

[0296] (6) The enzyme activity inhibition rate data were processed using formula (1) to calculate the inhibition rate corresponding to different concentrations of compounds, where RLU compound is the RLU value detected after compound incubation, RLU blank well is the RLU detected without adding MAO A, and RLU solvent control well is the RLU detected after adding MAO Reaction Buffer.

[0297] Representative compounds in the examples were tested according to the above method and found to have weak inhibitory activity against MAO-A. The activity data of the exemplary compounds are shown in the table below.

[0298] A:IC 50 <50nM, B:50nM≤IC 50 <100nM, C: 100nM≤IC 50 <1000nM,

[0299] D: 1000nM≤IC 50 <2000nM, E: 2000nM≤IC 50 <10000nM, F:IC 50 ≥10000nM

[0300] The experimental results show that the compound of the present invention has selective inhibitory activity on MAO-B.

[0301] Test Example 3: Weight loss test of compounds on DIO mice

[0302] 3.1 Experimental animals

[0303] DIO mice, SPF grade, male, 45-55 g, were purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd.

[0304] 3.2 Experimental Grouping and Process

[0305] DIO mice were established by feeding C57BL / 6J mice a high-fat diet for several weeks to induce an obese mouse model. After a week of adaptive feeding, when their weight stabilized, the animals were divided into groups (d0) balanced by weight, with six animals per group. Both the solvent group (purified water) and the drug-treated group were gavage-administered once daily at a dose of 10 mg / kg. Mouse weights and food weights were measured daily, and the data were recorded.

[0306] The formula for calculating weight change is: weight change = Wt-W0, Wt is the average weight of the mouse per day, and W0 is the average weight of the mouse on day 0.

[0307] The weight growth rate calculation formula is: weight growth rate = (Wt-W0) / W0*100%, Wt is the average weight of the mouse per day, and W0 is the average weight of the mouse on day 0.

[0308] The formula for calculating food intake is: food intake = F0-Ft, F0 is the weight of basic food, and Ft is the weight of remaining food.

[0309] 3.3 Test results

[0310] The test results show that the compound of the present invention can significantly reduce the body weight of mice without affecting food intake, and is even better than the positive control drug KDS2010. Exemplary test results are shown in the following table and Figures 1, 2 and 3.

[0311] Note: Compound 1 and KDS2010 used in Test Example 3 were in the form of mesylate salts, and the compounds used in other test examples were in free form.

Claims

1. A compound represented by the following formula (I), its tautomer, stereoisomer or pharmaceutically acceptable salt thereof, which has the following structure Wherein, Ring A and B are each independently selected from C 6-10 aryl or 5- to 10-membered heteroaryl; R 1 and R 2 each independently selected from deuterium, halogen, cyano, nitro, amino, hydroxy, mercapto, -SF5, -COOH, -OR 5 , -SR 5 , -NR 5 R 5 , -C(O)R 5 , -C(O)OR 5 , -C(O)NR 5 R 5 , -OC(O)R 5 , -S(O) 1-2 R 5 , -S(O)2NR 5 R 5 , -N(R 5 )S(O)2R 5 , -N(R 5 )C(O)R 5 , -N(R 5 )C(O)NR 5 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 3-10 cycloalkenyl, C 6-10 aryl, 3- to 10-membered heterocyclic group, and 5- to 10-membered heteroaryl; wherein said C 1-6 alkyl, C 2- 6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 3-10 cycloalkenyl, C 6-10 aryl, 3- to 10-membered heterocyclic group, and 5- to 10-membered heteroaryl are each optionally substituted with 0 to 6 identical or different deuterium, cyano, amino, hydroxy, or halogen; R 5 Each independently selected from hydrogen, deuterium, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl and 3- to 10-membered heterocyclic group, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl and 3- to 10-membered heterocyclic group are each optionally substituted with 0 to 6 identical or different deuterium, cyano, amino, hydroxyl or halogen; m and n are each independently selected from 0 - 6; Y is independently selected from (CR 6 R 7 ) 1-2 or is a single bond; R 6 and R 7 each independently selected from hydrogen, deuterium, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1- 6-alkoxy, C 1-6 haloalkoxy or hydroxy-substituted C 1-6 alkyl; Alternatively, when Y is selected from (CR 6 R 7 )2, one of the Rs 6 or R 7 together with two carbon atoms forms a C 3-6 cycloalkyl or a 3- to 6-membered heterocyclic group, and the other Rs 6 and R 7 are selected from hydrogen, deuterium or halogen; wherein the heterocyclic group contains 0 to 2 N, O, C(=O) or S heteroatoms, and the heteroatoms are not simultaneously 0; the C 3-6 cycloalkyl and the 3- to 6-membered heterocyclic group are each optionally substituted with 0 to 6 identical or different deuteriums, C 1-6 alkyl, cyano, amino, hydroxy or halogen; Alternatively, R 2 and R 6 together with the atoms attached thereto form a C 5-8 carbocyclic group or a 5- to 8-membered heterocyclic group; wherein the heterocyclic group contains 0 to 2 N, O, C(=O) or S heteroatoms, and the heteroatoms are not simultaneously 0; the C 5-8 carbocyclic group and the 5- to 8-membered heterocyclic group are each optionally substituted with 0 to 6 identical or different deuterium, cyano, amino, hydroxy, C 1-6 alkyl, or halogen; R 7 is selected from hydrogen, deuterium, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy or hydroxy-substituted C 1-6 alkyl; R 3 independently selected from hydrogen, deuterium, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, hydroxy-substituted C 1-6 alkyl or C 3-8 cycloalkyl; Alternatively, R 2 and R 3 together with the atoms connected thereto form a 4- to 8-membered nitrogen-containing heterocyclic group; wherein the 4- to 8-membered nitrogen-containing heterocyclic group contains 1 to 2 N heteroatoms and 0 to 2 O, C(=O) or S heteroatoms; the 4- to 8-membered nitrogen-containing heterocyclic groups are each optionally substituted with 0 to 6 identical or different deuterium, C 1-6 alkyl, cyano, amino, hydroxy or halogen; R 4a and R 4b are each independently selected from hydrogen, deuterium, halogen, hydroxy, cyano, amino, mercapto, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl or C 3-10 cycloalkenyl; the C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl or C 3-10 cycloalkenyl is optionally substituted by 0 - 3 deuteriums, halogens, hydroxy, amino, nitro, cyano, mercapto, C 1-6 alkyl or C 1-6 alkoxy; or R 4a and R 4b together with the carbon atoms to which they are attached form C 3-6 a carbocyclic group or a 3- to 6-membered heterocyclic group; wherein the heterocyclic group contains 0 to 2 N, O, C(=O) or S heteroatoms, and the heteroatoms are not simultaneously 0; the 3-6 carbocyclic group and the 3- to 6-membered heterocyclic group are each optionally substituted by 0 to 6 identical or different deuterium, cyano, amino, hydroxy, halogen or 1-6 alkyl groups; Alternatively, R 3 and R 4a together with the atoms attached thereto form a 3- to 8-membered nitrogen-containing heterocyclic group; wherein, the nitrogen-containing heterocyclic group contains 1 to 3 N heteroatoms, and 0 to 2 O, C(=O) or S heteroatoms; the 3- to 8-membered nitrogen-containing heterocyclic group is optionally substituted with 0 to 6 identical or different deuterium, cyano, amino, hydroxy, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 haloalkyl, C 1-3 haloalkoxy or halogen; R 4b is selected from hydrogen, deuterium, halogen, hydroxy, cyano, amino, mercapto, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl or C 3-10 cycloalkenyl; the C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl or C 3-10 cycloalkenyl is optionally substituted with 0 to 3 deuterium, halogen, hydroxy, amino, nitro, cyano, mercapto, C 1-6 alkyl or C 1-6 alkoxy, The compound of formula (I) does not include the following compounds:

2. The compound according to claim 1, its tautomer, stereoisomer or pharmaceutically acceptable salt thereof, characterized in that, Ring A and B are each independently selected from phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, pyrazolyl or imidazolyl; Preferably, ring A and B are each independently selected from phenyl, pyridyl, thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, pyrazolyl or imidazolyl; More preferably, ring A and B are each independently selected from phenyl, pyridyl, thienyl or thiazolyl; Even more preferably, ring A and B are each independently selected from phenyl.

3. The compound, tautomer, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-2, characterized in that, R 1 and R 2 are each independently selected from deuterium, halogen, -SF5, -OR 5 , -SR 5 , -NR 5 R 5 , -C(O)R 5 , -C(O)OR 5 , -C(O)NR 5 R 5 , -OC(O)R 5 , -S(O) 1-2 R 5 , -S(O)2NR 5 R 5 , -N(R 5 )S(O)2R 5 , -N(R 5 )C(O)R 5 , -N(R 5 )C(O)NR 5 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 3-10 cycloalkenyl, C 6-10 aryl, 3- to 10-membered heterocyclic group, and 5- to 10-membered heteroaryl; wherein, the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 3-10 cycloalkenyl, C 6-10 aryl, 3- to 10-membered heterocyclic group, and 5- to 10-membered heteroaryl are each optionally substituted with 0 to 6 identical or different deuterium, cyano, amino, hydroxyl, or halogen; R 5 each independently selected from hydrogen, deuterium, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl and 3- to 10-membered heterocyclic group, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl and 3- to 10-membered heterocyclic group are each optionally substituted with 0 to 6 identical or different deuterium, cyano, amino, hydroxy or halogen; Or, R 1 and R 2 are each independently selected from deuterium, halogen, -SF5, -OR 5 , -SR 5 , -NR 5 R 5 , -C(O)R 5 , -C(O)OR 5 , -C(O)NR 5 R 5 , -OC(O)R 5 , -S(O) 1-2 R 5 , -S(O)2NR 5 R 5 , -N(R 5 )S(O)2R 5 , -N(R 5 )C(O)R 5 , -N(R 5 )C(O)NR 5 , C 1-6 alkyl, C 3-10 cycloalkyl, and 3- to 10-membered heterocyclic group; wherein the C 1-6 alkyl, C 3-10 cycloalkyl, and 3- to 10-membered heterocyclic group are each optionally substituted with 0 to 6 identical or different deuterium, cyano, amino, hydroxy, or halogen; R 5 Each independently selected from hydrogen, deuterium, C 1-6 alkyl, C 3-10 cycloalkyl, and 3- to 10-membered heterocyclic groups, wherein the C 1-6 alkyl, C 3-10 cycloalkyl, and 3- to 10-membered heterocyclic groups are each optionally substituted with 0 to 6 identical or different deuterium, cyano, amino, hydroxy, or halogen; Or, R 1 and R 2 are each independently selected from deuterium, halogen, -SF5, -OR 5 , -SR 5 , -NR 5 R 5 , -C(O)R 5 , -S(O) 1-2 R 5 , C 1-6 alkyl, C 3-10 cycloalkyl, and 3- to 10-membered heterocyclic group; wherein the C 1-6 alkyl, C 3-10 cycloalkyl, and 3- to 10-membered heterocyclic group are each optionally substituted with 0 to 6 identical or different deuterium, cyano, amino, hydroxy, or halogen; R 5 Each independently selected from hydrogen, deuterium, C 1-6 alkyl, C 3-10 cycloalkyl, and 3- to 10-membered heterocyclic group, wherein the C 1-6 alkyl, C 3-10 cycloalkyl, and 3- to 10-membered heterocyclic group are each optionally substituted with 0 to 6 identical or different deuterium, cyano, amino, hydroxyl, or halogen; Or, R 1 and R 2 each independently selected from deuterium, halogen, -SF5, -OR 5 , -SR 5 , C 1-6 alkyl, C 3- 10 cycloalkyl, and 3- to 10-membered heterocyclic group; wherein the C 1-6 alkyl, C 3-10 cycloalkyl, and 3- to 10-membered heterocyclic group are each optionally substituted with 0 to 6 identical or different deuterium, cyano, amino, hydroxy, or halogen; R 5 Each independently selected from hydrogen, deuterium, C 1-6 alkyl, C 3-10 cycloalkyl and 3- to 10-membered heterocyclic groups, wherein the C 1-6 alkyl, C 3-10 cycloalkyl and 3- to 10-membered heterocyclic groups are each optionally substituted with 0 to 6 identical or different deuterium, cyano, amino, hydroxy or halogen; Or, R 1 and R 2 are each independently selected from deuterium, halogen, -SF5, -OR 5 , -SR 5 , C 1-6 alkyl, C 3- 10 cycloalkyl, and 3- to 10-membered heterocyclic groups; wherein the C 1-6 alkyl, C 3-10 cycloalkyl, and 3- to 10-membered heterocyclic groups are each optionally substituted with 0 to 6 identical or different deuterium or halogen atoms; R 5 Each independently selected from hydrogen, deuterium, C 1-6 alkyl, C 3-10 cycloalkyl, and 3- to 10-membered heterocyclic group, wherein the C 1-6 alkyl, C 3-10 cycloalkyl, and 3- to 10-membered heterocyclic group are each optionally substituted with 0 to 6 identical or different deuteriums or halogens; Or, R 1 and R 2 each independently selected from deuterium, halogen, -SF5, -OR 5 , -SR 5 , C 1-6 alkyl, C 3- 6 cycloalkyl and 3-6 membered heterocyclic group; wherein, the C 1-6 alkyl, C 3-6 cycloalkyl and 3-6 membered heterocyclic group are each optionally substituted with 0-6 identical or different deuterium or halogen; R 5 each independently selected from hydrogen, deuterium, C 1-6 alkyl, C 3-6 cycloalkyl, and 3- to 6-membered heterocyclic group, wherein the C 1-6 alkyl, C 3-6 cycloalkyl, and 3- to 6-membered heterocyclic group are each optionally substituted with 0 to 6 identical or different deuterium or halogen atoms; Or, R 1 and R 2 are each independently selected from deuterium, fluorine, chlorine, bromine, -SF5, -OR 5 , -SR 5 , C 1-6 alkyl, C 3-6 cycloalkyl, and 3- to 6-membered heterocyclic groups; wherein the C 1-6 alkyl, C 3-6 cycloalkyl, and 3- to 6-membered heterocyclic groups are each optionally substituted with 0 to 6 identical or different deuterium, fluorine, chlorine, or bromine; R 5 Each independently selected from C 1-6 alkyl, C 3-6 cycloalkyl, and 3- to 6-membered heterocyclic group, wherein the C 1-6 alkyl, C 3-6 cycloalkyl, and 3- to 6-membered heterocyclic group are each optionally substituted with 0 to 6 identical or different deuterium, fluorine, chlorine, or bromine; Or, R 1 and R 2 each independently selected from fluorine, chlorine, -SF5, -SCF3, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl, tert-butyl, cyclobutyl, methoxy, ethoxy, propoxy, isopropoxy, cyclopropoxy, butoxy, isobutoxy, tert-butoxy or cyclobutoxy; wherein methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl, tert-butyl, cyclobutyl, methoxy, ethoxy, propoxy, isopropoxy, cyclopropoxy, butoxy, isobutoxy, tert-butoxy or cyclobutoxy are each optionally substituted with 0 - 6 identical or different deuterium, fluorine, chlorine or bromine; Or, R 1 and R 2 are each independently selected from fluorine, chlorine, -SF5, -SCF3, -OCF3, -CF3, methyl, deuterated methyl or cyclopropyl; Alternatively, R 1 is selected from -CF3, R 2 is selected from fluorine.

4. The compound, tautomer, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-3, characterized in that, m and n are each independently selected from 0 - 5, preferably 0, 1, 2, 3, 4, or 5, more preferably 0, 1, 2 or 3; Or, m is selected from 0 - 3, preferably 1, 2 or 3, more preferably 1; n is selected from 0 or 1.

5. The compound, tautomer, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-4, characterized in that, Y is independently selected from (CR 6 R 7 ) 1-2 ; R 6 and R 7 each independently selected from hydrogen, deuterium, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1- 6 alkoxy, C 1-6 haloalkoxy or hydroxy-substituted C 1-6 alkyl; Alternatively, when Y is selected from (CR 6 R 7 )2, one of the Rs 6 or R 7 together with two carbon atoms forms a C 3-6 cycloalkyl or a 3- to 6-membered heterocyclic group, and the other Rs 6 and R 7 are selected from hydrogen, deuterium or a halogen; wherein the heterocyclic group contains 0 to 2 N, O, C(=O) or S heteroatoms, and the number of heteroatoms is not 0 at the same time; the C 3-6 cycloalkyl and the 3- to 6-membered heterocyclic group are each optionally substituted by 0 to 6 identical or different deuteriums, cyano groups, amino groups, hydroxyl groups or halogens; Alternatively, R 2 and R 6 together with the atoms connected thereto form a C 5-8 carbocyclic group or a 5- to 8-membered heterocyclic group; wherein the heterocyclic group contains 0 to 2 N, O, C(=O) or S heteroatoms, and the number of said heteroatoms is not 0 at the same time; the C 5-8 carbocyclic group and the 5- to 8-membered heterocyclic group are each optionally substituted with 0 to 6 identical or different deuterium, cyano, amino, hydroxy or halogen; R 7 is selected from hydrogen, deuterium, halogen, C 1- 6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy or hydroxy-substituted C 1-6 alkyl; Preferably, Y is independently selected from (CR 6 R 7 ) 1-2 ; R 6 and R 7 are each independently selected from hydrogen, deuterium, methyl or halogen; or R 6 and R 7 together with the carbon atom to which they are attached form a three-membered cycloalkyl group; wherein the three-membered cycloalkyl group is optionally substituted with 0-4 identical or different deuterium, cyano, amino, hydroxyl or halogen atoms; Alternatively, R 2 and R 6 together with the atoms connected thereto form C 5-6 a carbocyclic group or a 5- or 6-membered heterocyclic group; wherein the heterocyclic group contains 0-2 N, O, C(=O) or S heteroatoms, and the number of said heteroatoms is not 0 at the same time; the C 5-6 carbocyclic group and the 5- or 6-membered heterocyclic group are each optionally substituted with 0-6 identical or different deuteriums or halogens; R 7 is selected from hydrogen, deuterium, methyl or halogen; More preferably, Y is independently selected from (CR 6 R 7 ) 1-2 ; R 6 and R 7 each independently selected from hydrogen or methyl; Alternatively, when Y is selected from (CR 6 R 7 )2, one of the Rs 6 or Rs 7 together with two carbon atoms forms a tri-cycloalkyl group; Alternatively, R 2 and R 6 together with the atoms attached thereto form a five-membered carbocyclic group; R 7 is selected from hydrogen or methyl.

6. The compound, tautomer, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-5, characterized in that, R 3 independently selected from hydrogen, deuterium, C 1-6 alkyl, C 2-6 alkynyl or C 3-8 cycloalkyl; Alternatively, R 2 and R 3 together with the atoms linked thereto form a 5- or 6-membered nitrogen-containing heterocyclic group, wherein the 5- or 6-membered nitrogen-containing heterocyclic group is optionally substituted with 0 to 3 identical or different deuterium, halogen or C 1-6 alkyl groups; Preferably, R 3 independently selected from hydrogen or propargyl; Alternatively, R 2 and R 3 together with the atoms attached thereto form a 5- or 6-membered nitrogen-containing heterocyclic group, wherein the 5- or 6-membered nitrogen-containing heterocyclic group is optionally substituted with 0 to 3 identical or different C 1-6 alkyl groups.

7. The compound, tautomer, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-6, characterized in that, R 4a and R 4b are each independently selected from hydrogen, halogen or C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with 0 - 3 identical or different deuterium, amino, hydroxy, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 haloalkyl, C 1-3 haloalkoxy or halogen; or R 4a and R 4b The carbon atoms connected to them form C 3-4 cycloalkyl or 3- to 4-membered heterocycloalkyl; wherein, the heterocycloalkyl contains 1 O, N, C(=O) or S heteroatom; the C 3-4 cycloalkyl and 3- to 4-membered heterocycloalkyl are each optionally substituted with 0 to 6 identical or different deuteriums or halogens; Alternatively, R 3 and R 4a together with the atoms to which they are attached form a 3- to 7-membered nitrogen-containing heterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1 to 3 N's, and 0 to 3 O or C(=O) heteroatoms; the 3- to 7-membered heterocyclic group is optionally substituted with 0 to 6 identical or different deuteriums, amino groups, hydroxyl groups, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 haloalkyl, C 1-3 haloalkoxy or halogen; R 4b is selected from hydrogen, halogen or C 1- 6-alkyl, wherein the C 1-6 alkyl is optionally substituted with 0 to 3 identical or different deuteriums, amino groups, hydroxyl groups, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 haloalkyl, C 1-3 haloalkoxy or halogen; Preferably, R 4a 、R 4b each independently selected from hydrogen, fluorine or methyl; or R 4a and R 4b together with the carbon atom to which they are attached form C 3-4 cycloalkyl or 3- to 4-membered heteroalkyl; wherein, the heteroalkyl contains 1 O; the C 3-4 cycloalkyl and 3- to 4-membered heteroalkyl are each optionally substituted with 0 to 6 identical or different halogens; Alternatively, R 3 and R 4a together with the atoms connected thereto form a 3- to 7-membered nitrogen-containing heterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1 to 3 N's, and 0 to 3 O or C(=O) heteroatoms; the 3- to 7-membered nitrogen-containing heterocyclic group is optionally substituted with 0 to 6 identical or different amino groups, hydroxyl groups, C 1-3 alkyl groups or halogens; R 4b is selected from hydrogen, fluorine or methyl; Alternatively, R 3 and R 4a together with the atoms attached thereto form a 3- to 6-membered nitrogen-containing heterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1 N; the 3- to 6-membered nitrogen-containing heterocyclic group is optionally substituted with 0 to 3 identical or different amino groups, hydroxyl groups, C 1-3 alkyl groups or halogens; Alternatively, R 3 and R 4a together with the atoms connected thereto form a 3- to 5-membered nitrogen-containing heterocyclic group; wherein, the nitrogen-containing heterocyclic group contains 1 N; the 3- to 5-membered nitrogen-containing heterocyclic group is optionally substituted with 0 to 2 identical or different amino groups, hydroxyl groups, C 1-3 alkyl groups or halogens; Alternatively, R 3 and R 4a together with the atoms linked thereto form a 4-membered nitrogen-containing heterocyclic group; wherein, the nitrogen-containing heterocyclic group contains 1 N; the 4-membered nitrogen-containing heterocyclic group is optionally substituted with 0-2 identical or different amino groups, hydroxyl groups, C 1-3 alkyl groups or halogens; More preferably, R 4a 、R 4b are each independently selected from hydrogen, fluorine or methyl; Alternatively, R 4a and R 4b together with the carbon atoms to which they are attached form a cyclopropyl, cyclobutyl, or oxetane ring; wherein the cyclopropyl, cyclobutyl, and oxetane rings are each optionally substituted with 0 - 6 fluorine atoms; Alternatively, R 3 and R 4a together with the atoms connected thereto form a nitrogen-containing 3-membered monocyclic heterocyclic group, 4-membered monocyclic heterocyclic group, 5-membered monocyclic heterocyclic group, 6-membered monocyclic heterocyclic group, 7-membered monocyclic heterocyclic group, 5-membered spiro heterocyclic group, 5-membered bridged heterocyclic group, 6-membered spiro heterocyclic group, 6-membered bridged heterocyclic group, 6-membered fused heterocyclic group, 7-membered spiro heterocyclic group, 7-membered bridged heterocyclic group or 7-membered fused heterocyclic group, etc., nitrogen-containing heterocyclic groups; wherein, the nitrogen-containing heterocyclic group contains 1-3 Ns, and 0-3 O or C(=O) heteroatoms; the nitrogen-containing heterocyclic group is optionally substituted with 0-6 identical or different amino groups, hydroxyl groups, methyl groups, ethyl groups, propyl groups, isopropyl groups, fluorine, chlorine or bromine; R 4b is selected from hydrogen, fluorine or methyl; Alternatively, R 3 and R 4a together with the atoms attached thereto form a 3-membered monocyclic heterocyclic group containing nitrogen, a 4-membered monocyclic heterocyclic group containing nitrogen, a 5-membered monocyclic heterocyclic group containing nitrogen, a 6-membered monocyclic heterocyclic group containing nitrogen, or a 7-membered monocyclic heterocyclic group containing nitrogen; wherein the nitrogen-containing heterocyclic group contains 1-3 Ns and 0-3 O or C(=O) heteroatoms; the nitrogen-containing heterocyclic group is optionally substituted with 0-6 identical or different amino groups, hydroxyl groups, methyl groups, ethyl groups, propyl groups, isopropyl groups, fluorine, chlorine or bromine; R 4b is selected from hydrogen, fluorine or methyl; Alternatively, R 3 and R 4a together with the atoms connected thereto form a nitrogen-containing 3-membered monocyclic heterocyclic group, 4-membered monocyclic heterocyclic group, 5-membered monocyclic heterocyclic group, 6-membered monocyclic heterocyclic group; wherein, the nitrogen-containing heterocyclic group contains 1-3 Ns, and 0-3 O or C(=O) heteroatoms; the nitrogen-containing heterocyclic group is optionally substituted with 0-6 identical or different amino groups, hydroxyl groups, methyl groups, ethyl groups, propyl groups, isopropyl groups, fluorine, chlorine or bromine; R 4b is selected from hydrogen, fluorine or methyl; Alternatively, R 3 and R 4a together with the atoms attached thereto form a nitrogen-containing 3-membered monocyclic heterocyclic group, 4-membered monocyclic heterocyclic group, 5-membered monocyclic heterocyclic group, 6-membered monocyclic heterocyclic group; wherein, the nitrogen-containing heterocyclic group contains 1 N; the nitrogen-containing heterocyclic group is optionally substituted with 0-3 identical or different amino groups, hydroxyl groups, methyl groups, ethyl groups, propyl groups, isopropyl groups, fluorine, chlorine or bromine; R 4b is selected from hydrogen, fluorine or methyl; Alternatively, R 3 and R 4a together with the atoms connected thereto form a nitrogen-containing 3-membered monocyclic heterocyclic group, 4-membered monocyclic heterocyclic group, or 5-membered monocyclic heterocyclic group; wherein the nitrogen-containing heterocyclic group contains 1 N; the nitrogen-containing heterocyclic group is optionally substituted with 0-2 identical or different amino groups, hydroxyl groups, methyl groups, ethyl groups, propyl groups, isopropyl groups, fluorine, chlorine, or bromine; R 4b is selected from hydrogen, fluorine, or methyl; Alternatively, R 3 and R 4a together with the atoms connected thereto form a nitrogen-containing 4-membered monocyclic hetero group; wherein, the nitrogen-containing hetero group contains 1 N; the nitrogen-containing hetero group is optionally substituted with 0-2 identical or different amino groups, hydroxyl groups, methyl groups, or fluorine atoms; R 4b is selected from hydrogen, fluorine, or methyl; Even more preferably, R 4a 、R 4b are each independently selected from hydrogen, fluorine or methyl; or R 4a and R 4b Together with the carbon atoms connected thereto, form a cyclopropyl group, a cyclobutyl group, or an oxetane ring; wherein the cyclopropyl group, the cyclobutyl group, and the oxetane ring are each optionally substituted with 0-6 fluorine atoms; Alternatively, R 3 and R 4a together with the atoms connected to them form a nitrogen-containing heterocyclic group; wherein, Indicates connection to the Y terminal, means being connected to C(O)NH2; the nitrogen-containing heterocyclic groups are each optionally substituted with 0-6 identical or different amino groups, hydroxyl groups, methyl groups, ethyl groups, propyl groups, isopropyl groups, fluorine, chlorine or bromine; R 4b is selected from hydrogen, fluorine or methyl; Even further preferably, R 4a 、R 4b are each independently selected from hydrogen, fluorine or methyl; Alternatively, R 4a and R 4b together with the carbon atoms to which they are attached form a cyclopropyl group, a cyclobutyl group, or an oxetane ring; wherein the cyclopropyl group, the cyclobutyl group, and the oxetane ring are each optionally substituted with 0 to 6 fluorine atoms; Alternatively, R 3 and R 4a together with the atoms attached to them may be attached to form a nitrogen-containing heterocyclic group; wherein, Indicates connection to the Y terminal, Indicates connection to the C(O)NH2 terminus; each of the nitrogen-containing heterocyclic groups is optionally substituted with 0 - 6 identical or different amino groups, hydroxyl groups, methyl groups, ethyl groups, propyl groups, isopropyl groups, fluorine, chlorine or bromine; R 4b is selected from hydrogen, fluorine or methyl; Even further preferably, R 4a and R 4b are each independently selected from hydrogen, fluorine or methyl; Alternatively, R 4a and R 4b together with the carbon atom to which it is attached form a cyclopropyl, cyclobutyl, or oxetane ring; wherein the cyclopropyl, cyclobutyl, and oxetane rings are each optionally substituted with 0 - 6 fluorine atoms; Alternatively, R 3 and R 4a together with the atoms connected to them form Among them, Indicates connection to the Y terminal, represents connection to the C(O)NH2 terminus; R 4b is selected from hydrogen, fluorine or methyl; Alternatively, R 3 and R 4a together with the atoms attached to them form Among them, Indicates connection to the Y terminal, denotes connection to the C(O)NH2 terminus; R 4b is selected from hydrogen, fluorine or methyl; Alternatively, R 3 and R 4a together with the atoms connected to them form Among them, Indicates connection to the Y terminal, denotes connection to the C(O)NH2 terminus; R 4b is selected from hydrogen, fluorine or methyl; Alternatively, R 3 and R 4a together with the atoms connected to them form Among them, Indicates connection to the Y terminal, represents connection to the C(O)NH2 terminus; R 4b is selected from hydrogen.

8. A compound of the following structural formula, its tautomer, stereoisomer or its pharmaceutically acceptable salt:

9. The compound, tautomer, stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-8, characterized in that, The pharmaceutically acceptable salt is selected from: mesylate.

10. A pharmaceutical composition comprising the compound according to any one of claims 1 - 9, its tautomer, stereoisomer or its pharmaceutically acceptable salt, and optionally further comprising a pharmaceutically acceptable carrier.

11. Use of the compound according to any one of claims 1 - 9, its tautomer, stereoisomer or its pharmaceutically acceptable salt or the pharmaceutical composition according to claim 10 in the preparation of a medicament for diseases or disorders associated with overexpression of monoamine oxidase - B (MAO - B).

12. The use according to claim 11, wherein The medicament is used for preventing, improving and / or treating diseases or disorders related to memory, cognition, mood, neurodegeneration and obesity, etc.

13. The use according to claim 11 or 12, characterized in that The diseases or disorders are selected from Alzheimer's disease, depression, stroke, Parkinson's disease, hypertension or obesity.

14. A medicament comprising the compound according to any one of claims 1 - 9, its tautomer, stereoisomer or its pharmaceutically acceptable salt, and the medicament is used for preventing, improving and / or treating diseases or disorders associated with overexpression of monoamine oxidase - B (MAO - B); Preferably, the diseases or disorders associated with overexpression of monoamine oxidase - B (MAO - B) are diseases or disorders related to memory, cognition, mood, neurodegeneration and obesity, etc., more preferably: Alzheimer's disease, depression, stroke, Parkinson's disease, hypertension or obesity.

15. A method for preventing, improving and / or treating diseases or disorders associated with overexpression of monoamine oxidase - B (MAO - B), comprising administering to a patient a therapeutically effective dose of the compound according to any one of claims 1 - 9, its tautomer, stereoisomer or its pharmaceutically acceptable salt, or the pharmaceutical composition according to claim 10; preferably, the diseases or disorders associated with overexpression of monoamine oxidase - B (MAO - B) are diseases or disorders related to memory, cognition, mood, neurodegeneration and obesity, etc., preferably: Alzheimer's disease, depression, stroke, Parkinson's disease, hypertension or obesity.

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