N, N-dimethyltryptamine derivative and pharmaceutical composition, preparation method and application thereof

Abstract

The invention discloses an N, N-dimethyl tryptamine derivative as well as a pharmaceutical composition, a preparation method and application of the N, N-dimethyl tryptamine derivative. The N, N-dimethyl tryptamine derivative is shown as a formula (I), and specific substituent groups and definitions are described in the specification. The N, N-dimethyltryptamine derivative has good binding capacity with 5-HT2A, and the compound or the pharmaceutical composition thereof is used for treating 5-HT2A receptor related central nervous system diseases, disorders or symptoms and / or nerve diseases, disorders or symptoms.

Description

N,N-dimethyltryptamine derivative and pharmaceutical composition, preparation method and use thereof

[0001] This application claims priority to the Chinese patent application filed on November 6, 2023, with application number 202311463634.6, entitled “A N,N-dimethyltryptamine derivative and its pharmaceutical composition, preparation method and use” and the Chinese patent application filed on August 9, 2024, with application number 202411096546.1, entitled “A N,N-dimethyltryptamine derivative and its pharmaceutical composition, preparation method and use”, the contents of which should be understood as being incorporated into this application by reference. Technical Field

[0002] The present invention relates to the field of pharmaceutical chemistry, and specifically relates to an N,N-dimethyltryptamine derivative and its pharmaceutical composition, preparation method and use. Background Art

[0003] N,N-dimethyltryptamine (DMT) is an indolealkylamine alkaloid that is endogenously present in a variety of plant and animal species. DMT is a psychoactive hallucinogenic compound that can cause profound changes in human perception, mood, and cognition (Cameron, ACS Chem Neurosci. 17;9(10):2344-2357, 2018). DMT interacts with a variety of ionotropic and metabotropic receptors, the most well-known of which are serotonin receptors, especially 5-HT 2A (Rickli, Eur Neuropsychopharmacol. 26(8):1327-37. 2016).

[0004] Serotonin receptors are a group of G protein-coupled receptors and ligand-gated ion channels found in the central and peripheral nervous systems that mediate excitatory and inhibitory neurotransmission. Serotonin receptors are activated by the neurotransmitter serotonin (5-hydroxytryptamine). Increased density in the cortex can be detected in autopsies of patients with depression, and long-term use of various antidepressants can downregulate 5-HT. 2A receptor density and exerts antidepressant effects by affecting the forebrain subcortical circuit. 2A 5-HT receptors are important factors in sleep regulation and cognitive function (Eison, Behav Brain Res. 73(1-2): 177-81. 1996; Umbricht, Neuropsychopharmacology. 28(1): 170-81. 2003). 2AReceptors have become a hot topic of extensive research as targets for treating mental disorders such as depression. Major depressive disorder (MDD) is a chronic, recurrent mental disorder characterized by persistent low mood, loss of interest, loss of appetite, and sleep disturbances. The pathogenesis of depression is complex and remains unclear (Chen, Sleep, Vol. 46, Issue Supplement 1, A284-A285, 2023).

[0005] Clinically, it acts on 5-HT 2A SSRIs include ritanserin, lubazodone (YM-992), volinanserin, LY-367265, and nefazodone. 2A The receptors of dapoxetine all have high affinity and show effective efficacy in treating depression. However, as clinical trials progress, their shortcomings have gradually become apparent, including a large number of adverse reactions, such as dry mouth, nausea and vomiting, constipation, diarrhea, and liver failure; a long onset of action, often requiring more than 3 weeks for the drug to fully exert its antidepressant effect; low clinical response values, with no therapeutic effect in some patients; and even symptoms of poisoning (Seo, J Med Chem, Sep 22; 54(18): 6305-1, 2011; Pullar, Eur J Pharmacol, Oct 27; 407(1-2): 39-46, 2000).

[0006] New fast-acting antidepressant psychotherapeutic hallucinogenic compounds, such as psilocybin, lysergic acid diethylamide (LSD), and ketamine, have a rapid onset of action and can effectively relieve anxiety and depression symptoms ( Curr Top Behav Neurosci, 36: 45-73, 2018). However, psilocybin has no significant effect on 5-HT 2B Both LSD and psilocybin exhibit rapid tolerance to serotonin receptors and are poorly suited to repeated dosing regimens.

[0007] From the above reports, we can see that there are limitations in our understanding of the pathogenesis of depression, and existing antidepressants have certain defects and still fail to meet clinical needs. Therefore, it is of great significance to explore more effective and safer antidepressants.

[0008] Summary of the Invention

[0009] The following is an overview of the subject matter described in detail in this application. This overview is not intended to limit the scope of protection of the claims.

[0010] In a first aspect, the present application provides a compound as shown in formula (1), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof:

[0011] in,

[0012] R1 and R2 are each independently selected from the group consisting of hydroxy, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, unsubstituted C3-C6 cycloalkyl, substituted C3-C6 cycloalkyl, unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, and substituted heteroaryl; or

[0013] R1 and R2 form an unsubstituted nitrogen-containing heterocyclic ring or a substituted nitrogen-containing heterocyclic ring with the nitrogen atom to which they are directly attached;

[0014] R3, R4, R5 and R6 are independently selected from hydrogen, deuterium and substituted C1-C6 alkyl; or, R3 and R4 or R5 and R6 and their connecting carbon atoms form a -C(O)- group or a -C(S)- group;

[0015] R7 is one, two, three or four and is each independently selected from hydrogen, deuterium, amino, halogen, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, C1-C6 alkanoyloxy, aryloxy, heteroaryloxy, C1-C6 alkoxy-substituted C1-C6 alkanoyloxy, C1-C6 alkanesulfonyloxy, arylsulfonyloxy, substituted arylsulfonyloxy, phosphoryloxy and hydroxy;

[0016] R8 is hydrogen, deuterium, substituted C1-C6 alkyl, unsubstituted C3-C6 cycloalkyl or substituted C3-C6 cycloalkyl;

[0017] Y is N or CR 11 ; When Y is N, R9 and R 10 Each is independently hydrogen, hydroxyl, thiol; or R9 and its connected carbon atom form a -C(O)- group or a -C(S)- group; when Y is CR 11 When R 10 With R 11 A bond is formed, and R9 is hydrogen, hydroxy, amino, di(C1-C4 alkyl)amino or mercapto.

[0018] In a second aspect, the present application provides a pharmaceutical composition comprising the above-mentioned DMT derivative or its stereoisomer, pharmaceutically acceptable salt, solvate, deuterated substance, metabolite or prodrug, and a pharmaceutically acceptable carrier.

[0019] In a third aspect, the present application provides a method for preparing the above-mentioned DMT derivative or its stereoisomers, pharmaceutically acceptable salts, solvates, deuterated substances, metabolites or prodrugs.

[0020] In a fourth aspect, the present application provides the above-mentioned DMT derivatives or their stereoisomers, pharmaceutically acceptable salts, solvates, deuterated substances, metabolites or prodrugs, or pharmaceutical compositions thereof, for pharmaceutical use.

[0021] In a fifth aspect, the present application provides the above-mentioned DMT derivatives or their stereoisomers, pharmaceutically acceptable salts, solvates, deuterated substances, metabolites or prodrugs, or pharmaceutical compositions thereof, for stimulating 5-HT 2A receptor.

[0022] In a sixth aspect, the present application provides the above-mentioned DMT derivatives or their stereoisomers, pharmaceutically acceptable salts, solvates, deuterated substances, metabolites or prodrugs, or pharmaceutical compositions thereof, for use in treating 5-HT 2A Receptor-associated diseases / disorders.

[0023] In a seventh aspect, the present application provides the above-mentioned DMT derivatives or their stereoisomers, pharmaceutically acceptable salts, solvates, deuterated substances, metabolites or prodrugs, or pharmaceutical compositions thereof for use in the preparation of a method for treating 5-HT. 2A Use in medicine for receptor-related central nervous system diseases, disorders or conditions and / or neurological diseases, disorders or conditions.

[0024] In an eighth aspect, the present application provides a method for treating 5-HT in patients. 2A A method for treating a receptor-related disease / disorder, comprising administering the above-mentioned DMT derivative or its stereoisomer, pharmaceutically acceptable salt, solvate, deuterated substance, metabolite or prodrug, or a pharmaceutical composition thereof to a patient in need thereof.

[0025] Details

[0026] The present application provides a DMT derivative and its preparation method and use, which overcomes the shortcomings of the existing antidepressant drugs such as limited types, adverse reactions, and hallucinogenic side effects. At the same time, the DMT derivative of the present application is combined with 5-HT 2A Has good bonding ability.

[0027] In an embodiment of the first aspect, the present application provides a compound as shown in formula (I), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated substance, metabolite or prodrug thereof,

[0028] in,

[0029] R1 and R2 are each independently selected from the group consisting of hydroxy, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, unsubstituted C3-C6 cycloalkyl, substituted C3-C6 cycloalkyl, unsubstituted aryl, substituted aryl, unsubstituted heteroaryl and substituted heteroaryl; wherein the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, substituted C3-C6 cycloalkyl, substituted aryl or substituted heteroaryl refers to substituted by 1-3 groups independently selected from the group consisting of deuterium, C1-C3 alkyl, C1-C3 alkoxy, hydroxy, halogen, halogenated C1-C3 alkyl, halogenated C1-C3 alkoxy, C3-C6 cycloalkyl, aryl and heteroaryl; or

[0030] R1 and R2 form an unsubstituted nitrogen-containing heterocycle or a substituted nitrogen-containing heterocycle with the nitrogen atom to which they are directly attached; wherein the substituted nitrogen-containing heterocycle is substituted by 1-3 groups independently selected from the following groups: unsubstituted C1-C6 alkyl and substituted C1-C6 alkyl; wherein the substituted C1-C6 alkyl is substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, halogen, halogenated C1-C3 alkyl, C3-C6 cycloalkyl, aryl and heteroaryl;

[0031] R3, R4, R5 and R6 are independently selected from hydrogen, deuterium and substituted C1-C6 alkyl; or, R3 and R4 or R5 and R6 form a -C(O)- group or a -C(S)- group with the carbon atom to which they are attached; herein, the substituted C1-C6 alkyl refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, halogen, halogenated C1-C3 alkyl, C3-C6 cycloalkyl, aryl and heteroaryl;

[0032] R7 is one, two, three or four and is independently selected from hydrogen, deuterium, amino, halogen, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, C1-C6 alkanoyloxy, aromatic acyloxy, heteroaroyloxy, C1-C6 alkoxy substituted C1-C6 alkanoyloxy, C1-C6 alkanesulfonyloxy, aromatic sulfonyloxy, substituted aromatic sulfonyloxy, phosphoryloxy Here, the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, or substituted arylsulfonyloxy refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, phenyl and substituted phenyl, and here, the substituted phenyl refers to substituted by 1-3 groups independently selected from the following groups: halogen, C1-C3 alkyl, C1-C3 alkoxy, hydroxy, phenyl and C1-C6 alkanoyloxy;

[0033] R8 is hydrogen, deuterium, substituted C1-C6 alkyl, unsubstituted C3-C6 cycloalkyl or substituted C3-C6 cycloalkyl, wherein the substituted C3-C6 cycloalkyl is substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, halogen, halogenated C1-C3 alkyl, C3-C6 cycloalkyl, aryl and heteroaryl; the substituted C1-C6 alkyl is substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkoxy, halogen, halogenated C1-C3 alkyl, C3-C6 cycloalkyl, aryl and heteroaryl;

[0034] Y is N or CR 11 ; When Y is N, R9 and R 10 are independently hydrogen, hydroxyl or mercapto, or R9 and R 10 and its connected carbon atom forms a -C(O)- group or a -C(S)- group; when Y is CR 11 When R 10 With R 11 A bond is formed, and R9 is hydrogen, hydroxy, amino, di(C1-C4 alkyl)amino or mercapto.

[0035] The present application provides a compound as shown in formula (I), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein when Y is CR 11 , R 10 With R 11 forming a bond, R8 is hydrogen, R9 is hydrogen, one or both of R3 and R4 are deuterium, R5 and R6 are both hydrogen, and R1 and R2 are not selected from the group consisting of methyl, deuterated methyl, ethyl, propyl, deuterated ethyl and deuterated propyl; and / or

[0036] When Y is CR 11 , R 10 With R 11 forms a bond, R9 is hydrogen, R3, R4, R5 and R6 are all deuterium, R1 and R2 are both deuterated methyl, and R7 is not hydrogen, fluorine, methoxy, deuterated methoxy, benzylphosphoryloxy, phosphoryloxy or hydroxy; and / or

[0037] When Y is CR 11 , R 10 With R 11 forming a bond, R8 is hydrogen, R9 is hydrogen, R3, R4, R5 and R6 are all hydrogen, R1 and R2 cannot both be deuterated methyl, and, when R1 is deuterated methyl, deuterated ethyl or deuterated propyl, R2 is not methyl, ethyl, propyl or deuterated ethyl; and / or

[0038] When Y is CR 11 , R 10 With R11 forming a bond, R8 is hydrogen, R9 is hydrogen, R3, R4, R5 and R6 are all hydrogen, R1 is methyl, ethyl, propyl, isopropyl, allyl or cyclopropyl, R2 is methyl, ethyl, propyl, isopropyl, allyl, isobutyl, cyclopropylmethyl, cyclopropyl, benzyl or phenyl, and R7 is not hydrogen, hydroxy, fluoro, methyl or methoxy; and / or;

[0039] When Y is CR 11 , R 10 With R 11 forms a bond, R8 is hydrogen, R9 is hydrogen, R3, R4, R5 and R6 are all hydrogen, R1 is propylethyl, when R2 is propyl, R7 is not hydroxy, methoxy, acetoxy, phosphoryloxy, p-nitrobenzenesulfonyloxy, p-trifluoromethylbenzoyloxy, p-fluorobenzoyloxy, pivaloyloxy, methanesulfonyloxy, amino, fluorine, chlorine, bromine, iodine, methyl or trifluoromethyl; and / or

[0040] When Y is CR 11 , R 10 With R 11 forms a bond, R8 is hydrogen, R9 is hydrogen, R3, R4, R5 and R6 are all hydrogen, R1 is methyl, R2 is methyl or ethyl, and R7 is not hydroxy, methoxy, acetoxy, phosphoryloxy, amino, fluorine, chlorine, bromine, iodine, methyl or trifluoromethyl; and / or

[0041] When Y is CR 11 , R 10 With R 11 forms a bond, R8 is hydrogen, R9 is hydrogen, at least two of R3, R4, R5 and R6 are deuterium and the rest are hydrogen or all are deuterium, R1 is methyl, when R2 is methyl, R7 is not methoxy; and / or

[0042] When Y is CR 11 , R 10 With R 11 When a bond is formed, R8 is hydrogen, R9 is hydrogen, R3, R4, R5 and R6 are all hydrogen, R1 and R2 form a nitrogen-containing heterocyclic ring with the nitrogen atom to which they are directly attached, and R7 is not hydrogen, hydroxy, methoxy, fluorine, chlorine, bromine or iodine.

[0043] The present application provides a compound as shown in formula (I), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated substance, metabolite or prodrug thereof, wherein the compound does not include the following compounds: 5-hydroxy-N,N-dimethyltryptamine, 5-bromo-N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, Psilocybin, Psilocin, 5-methoxy-N,N-diallyltryptamine, 5-methoxy-N-allyl-N-methyltryptamine, 4-hydroxy-N,N-diethyltryptamine, 4-acetoxy-N,N-dimethyltryptamine, 4-hydroxy-NN-dipropyltryptamine, 5-methoxy-N,N-dipropyltryptamine, 5-methoxy-N-isopropyl-N-methyltryptamine or 4-hydroxy-N-isopropyl-N-methyltryptamine.

[0044] In some embodiments, the present application provides a compound of formula (I), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite, or prodrug thereof, wherein when Y is N, formula (I) is formula (IA):

[0045] In formula (IA), R1-R8 are as defined in formula (I), R9 and R 10 are independently hydrogen, hydroxyl or mercapto, or R9 and R 10 and its attached carbon atom forms a -C(O)- group or a -C(S)- group; or

[0046] Y is CR 11 When, formula (I) is formula (IB):

[0047] In formula (IB), R1-R8 are as defined in formula (I), and R9 is hydrogen, hydroxy, amino, di(C1-C4 alkyl)amino or mercapto.

[0048] In some embodiments, R1 and R2 in Formula (I), Formula (IA) or Formula (IB) are selected from the following groups: hydroxy, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, unsubstituted C3-C6 cycloalkyl, substituted C3-C6 cycloalkyl, unsubstituted aryl and unsubstituted heteroaryl; Here, the substituted C1-C6 alkyl, substituted C1-C6 alkoxy or substituted C3-C6 cycloalkyl refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, hydroxy, halogen, halogenated C1-C3 alkyl, halogenated C1-C3 alkoxy, C3-C6 cycloalkyl, phenyl, substituted phenyl, pyridyl and pyrimidinyl; the substituted phenyl refers to substituted by 1-3 groups independently selected from the following groups: halogen, C1-C3 alkyl, C1-C3 alkoxy, hydroxy, phenyl and C1-C3 alkanoyloxy;

[0049] Preferably, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl or tert-butyl;

[0050] Preferably, the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy or tert-butoxy;

[0051] Preferably, the C3-C6 cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl;

[0052] Preferably, the aryl group is phenyl or naphthyl;

[0053] Preferably, the heteroaryl group is pyridyl or pyrimidinyl;

[0054] Preferably, the substituents of the substituted C1-C6 alkyl are independently selected from the following 1-3 groups: deuterium, hydroxyl, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, fluorine, chlorine, bromine, iodine, trifluoromethyl, trifluoromethoxy, cyclopropyl, phenyl and pyridyl;

[0055] Preferably, the substituents of the substituted C1-C6 alkoxy group are independently selected from the following 1-3 groups: deuterium, fluorine, chlorine, bromine and iodine.

[0056] Preferably, the substituents of the substituted C3-C6 cycloalkyl are independently selected from the following 1-3 groups: deuterium, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, fluorine, chlorine, bromine, iodine, trifluoromethyl, trifluoromethoxy, cyclopropyl, phenyl and pyridyl.

[0057] In some embodiments, R1 and R2 in Formula (I), Formula (IA) or Formula (IB) are selected from the following groups: hydroxyl, methyl, ethyl, n-propyl, isopropyl, substituted isopropyl, n-butyl, tert-butyl, cyclopropyl, substituted cyclopropyl, deuterated methyl, cyclopropylmethyl, pyridine-substituted methyl, phenyl and substituted phenyl; here, the substituted isopropyl refers to substituted by hydroxyl; the substituted cycloalkyl refers to substituted by a group selected from the following groups: deuterium, fluorine, chlorine, bromine and iodine; the substituted phenyl refers to substituted by a substituent selected from the following groups: deuterium, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, cyclopropyl and phenyl.

[0058] In some embodiments, R1 and R2 in Formula (I), Formula (IA) or Formula (IB) are each independently selected from the following groups: hydroxy, methyl, deuterated methyl, ethyl, n-propyl, isopropyl, 2-hydroxyisopropyl, n-butyl, tert-butyl, cyclopropyl, deuterated cyclopropyl, fluorocyclopropyl, deuterated methyl, cyclopropylmethyl, pyridine-substituted methyl, phenyl and substituted phenyl; here, the substituted phenyl refers to substituted by a group selected from the following groups: methoxy and trifluoromethyl.

[0059] In some embodiments, R1 and R2 in Formula (I), Formula (IA) or Formula (IB) are each independently selected from the group consisting of hydroxy, methyl, trideuteromethyl, ethyl, n-propyl, isopropyl, 2-hydroxyisopropyl, n-butyl, tert-butyl, cyclopropyl, 2-fluorocyclopropyl, 2-deuterocyclopropyl, 2,2-dideuterocyclopropyl, 2,2,3,3-tetradeuterocyclopropyl, cyclopropylmethyl, (pyridin-2-yl)methyl, phenyl and (5-trifluoromethyl-2-methoxy)phenyl.

[0060] In some embodiments, R1 and R2 in Formula (I), Formula (IA) or Formula (IB) form an unsubstituted nitrogen-containing heterocycle or a substituted nitrogen-containing heterocycle with the nitrogen atom to which they are directly attached; here, the unsubstituted nitrogen-containing heterocycle is piperidine or piperazine, and the substituted nitrogen-containing heterocycle is a substituted piperazine or piperidine; here, the substituted nitrogen-containing heterocycle is substituted by 1-3 substituents independently selected from the following groups: methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, cyclopropyl, cyclopropylmethyl and phenyl.

[0061] In some embodiments, R1 and R2 in Formula (I), Formula (IA) or Formula (IB) form an unsubstituted nitrogen-containing heterocycle or a substituted nitrogen-containing heterocycle with the nitrogen atom to which they are directly attached; the unsubstituted nitrogen-containing heterocycle is piperidine, or the substituted nitrogen-containing heterocycle is 4-(cyclopropylmethyl)piperazine.

[0062] In some embodiments, R3, R4, R5, and R6 in Formula (I), Formula (IA), or Formula (IB) are independently selected from hydrogen and deuterium; or, R3, R4, or R5, R6 and the carbon atom to which they are attached form a -C(O)- group or a -C(S)- group.

[0063] In some embodiments, R7 in Formula (I), Formula (IA) or Formula (IB) is one, two, three or four, and each is independently selected from the following substituents: hydrogen, deuterium, amino, fluorine, chlorine, bromine, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, C1-C6 alkanoyloxy, benzoyloxy, C1-C6 alkoxy-substituted C1-C6 alkanoyloxy, C1-C6 alkanesulfonyloxy, benzylsulfonyloxy , substituted benzenesulfonyloxy, phosphoryloxy and hydroxyl; here, the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, or substituted benzenesulfonyloxy refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, phenyl and substituted phenyl, here, the substituted phenyl refers to substituted by 1-3 groups independently selected from the following groups: fluorine, chlorine, bromine, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, phenyl and C1-C6 alkanoyloxy.

[0064] In some embodiments, R7 in Formula (I), Formula (IA) or Formula (IB) is one, two, three or four, and each is independently selected from the following groups: hydrogen, deuterium, amino, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, benzyl, methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, benzyloxy, substituted benzyloxy, formyloxy, acetoxy, propionyloxy, benzoyloxy, tert-butoxycarbonyloxy, methoxycarbonyloxy, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, phosphoryloxy and hydroxyl; Here, the substituted benzyloxy refers to that its phenyl ring is substituted by 1-3 groups independently selected from the following groups: fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, hydroxy, phenyl, formyloxy, acetoxy, and propionyloxy;

[0065] In some embodiments, R7 in Formula (I), Formula (IA) or Formula (IB) is one, two, three or four, and each is independently selected from the following groups: hydrogen, deuterium, amino, hydroxyl, fluorine, chlorine, bromine, 1,1-dideuteroethyl, methoxy, (4-acetoxy)benzyloxy, acetoxy, methoxycarbonyloxy, phosphoryloxy, and methylsulfonyloxy.

[0066] In some embodiments, R7 in Formula (I), Formula (IA), or Formula (IB) is at the 4 position (uppermost position), 5 position, 6 position, or 7 position (lowermost position) of the phenyl ring to which it is attached, in counterclockwise order:

[0067] In some embodiments, R8 in Formula (I), Formula (IA) or Formula (IB) is selected from the group consisting of hydrogen, C3-C6 cycloalkyl, and substituted C1-C6 alkyl.

[0068] In some embodiments, R8 in formula (I) is selected from the group consisting of hydrogen, cyclopropylmethyl, and deuterated methyl.

[0069] In some embodiments, the present application provides a compound represented by Formula (I), Formula (IA) or Formula (IB), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R1 and R2 in Formula (I), Formula (IA) or Formula (IB) are each independently selected from the following groups: hydroxy, methyl, ethyl, n-propyl, isopropyl, hydroxyisopropyl, n-butyl, tert-butyl, cyclopropyl, substituted cyclopropyl, deuterated methyl, cyclopropylmethyl, pyridine-substituted methyl, phenyl and substituted phenyl; herein, the substituted cycloalkyl refers to substituted by a group selected from the following groups: deuterium, fluorine, chlorine, bromine and iodine; the substituted phenyl refers to substituted by a substituent selected from the following groups: deuterium, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, cyclopropyl and phenyl;

[0070] Alternatively, R1 and R2 in formula (I), formula (IA) or formula (IB) form an unsubstituted nitrogen-containing heterocycle or a substituted nitrogen-containing heterocycle with the nitrogen atom to which they are directly attached; wherein the nitrogen-containing heterocycle is piperidine or piperazine; and the substituted nitrogen-containing heterocycle is substituted by 1 to 3 groups independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, cyclopropyl, cyclopropylmethyl and phenyl;

[0071] R3, R4, R5 and R6 are independently selected from hydrogen and deuterium; or, R3, R4 or R5, R6 and the carbon atom to which they are attached form a -C(O)- group or a -C(S)- group;

[0072] R7 is one, two, three or four, and each is independently selected from the following substituents: hydrogen, deuterium, amino, fluorine, chlorine, bromine, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, C1-C6 alkanoyloxy, benzoyloxy, C1-C6 alkoxy-substituted C1-C6 alkanoyloxy, C1-C6 alkanesulfonyloxy, benzenesulfonyloxy, substituted benzenesulfonyloxy, phosphoryloxy Here, the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, or substituted phenylsulfonyloxy refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, phenyl and substituted phenyl, and here, the substituted phenyl refers to substituted by 1-3 groups independently selected from the following groups: fluorine, chlorine, bromine, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, phenyl and C1-C6 alkanoyloxy;

[0073] R8 is a substituent selected from the group consisting of hydrogen, cyclopropylmethyl, and deuterated methyl;

[0074] R9 is hydrogen, amino or di(C1-C4 alkyl)amino, or R9 and R 10 and its attached carbon atom to form a -C(O)- group.

[0075] In some embodiments, the present application provides a compound represented by Formula (I), Formula (IA) or Formula (IB), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R1 and R2 in Formula (I), Formula (IA) or Formula (IB) are each independently selected from the following groups: hydroxy, methyl, ethyl, n-propyl, 2-hydroxyisopropyl, isopropyl, n-butyl, tert-butyl, cyclopropyl, deuterated cyclopropyl, fluorocyclopropyl, deuterated methyl, cyclopropylmethyl, pyridine-substituted methyl, phenyl and substituted phenyl; herein, the substituted phenyl refers to substituted by a group selected from the following groups: methoxy and trifluoromethyl;

[0076] Alternatively, R1 and R2 form an unsubstituted nitrogen-containing heterocycle or a substituted nitrogen-containing heterocycle with the nitrogen atom to which they are directly attached; wherein the nitrogen-containing heterocycle is piperidine or piperazine; and the substituted nitrogen-containing heterocycle is substituted by 1 to 3 groups independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, cyclopropyl, cyclopropylmethyl, and phenyl.

[0077] R3, R4, R5 and R6 are all deuterium; or, R3, R4, R5 and R6 are all hydrogen;

[0078] R7 is one, two, three or four, and each is independently selected from the following substituents: hydrogen, deuterium, amino, fluorine, chlorine, bromine, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, C1-C6 alkanoyloxy, benzoyloxy, C1-C6 alkoxy-substituted C1-C6 alkanoyloxy, C1-C6 alkanesulfonyloxy, benzenesulfonyloxy, substituted benzenesulfonyloxy, phosphoryloxy Here, the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, or substituted phenylsulfonyloxy refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, phenyl and substituted phenyl, and here, the substituted phenyl refers to substituted by 1-3 groups independently selected from the following groups: fluorine, chlorine, bromine, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, phenyl and C1-C6 alkanoyloxy;

[0079] R8 is a substituent selected from the group consisting of hydrogen, cyclopropylmethyl, and deuterated methyl;

[0080] R9 is hydrogen, amino or di(C1-C4 alkyl)amino, or R9 and R 10 and its attached carbon atom to form a -C(O)- group.

[0081] In some embodiments, the present application provides a compound represented by Formula (I), Formula (IA) or Formula (IB), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R1 and R2 in Formula (I), Formula (IA) or Formula (IB) are each independently selected from the following groups: hydroxyl, methyl, deuterated methyl, ethyl, n-propyl, isopropyl, 2-hydroxyisopropyl, n-butyl, tert-butyl, cyclopropyl, 2-fluorocyclopropyl, 2-deuterated cyclopropyl, 2,2-dideuterated cyclopropyl, 2,2,3,3-tetradeuterated cyclopropyl, cyclopropylmethyl, (pyridin-2-yl)methyl, phenyl and (5-trifluoromethyl-2-methoxy)phenyl;

[0082] Alternatively, R1 and R2, together with the nitrogen atom to which they are directly attached, form piperidine or 4-(cyclopropylmethyl)piperazine;

[0083] R3, R4, R5 and R6 are all deuterium; or, R3, R4, R5 and R6 are all hydrogen;

[0084] R7 is one, two, three or four and is independently selected from the group consisting of hydrogen, deuterium, amino, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, benzyl, methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, benzyloxy, substituted benzyloxy, formyloxy, acetoxy, propionyloxy, benzoyloxy, tert-butoxycarbonyloxy, methoxycarbonyloxy, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, phosphoryloxy and hydroxy; wherein the substituted benzyloxy group refers to a benzyloxy group whose phenyl ring is substituted by 1 to 3 groups independently selected from the group consisting of fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, hydroxy, phenyl, formyloxy, acetoxy and propionyloxy;

[0085] R8 is a substituent selected from the group consisting of hydrogen, cyclopropylmethyl, and deuterated methyl;

[0086] In formula (I), Y is N or CR 11 , where R 10 With R 11 forming a bond;

[0087] R9 is hydrogen, amino or dimethylamino, or R9 and R 10 and its attached carbon atom to form a -C(O)- group.

[0088] In some embodiments, the present application provides a compound of formula (I), formula (IA) or formula (IB), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R1 and R2 in formula (I), formula (IA) or formula (IB) are each independently selected from the following groups: hydroxy, methyl, trideuteromethyl, ethyl, n-propyl, isopropyl, 2-hydroxyisopropyl, n-butyl, tert-butyl, cyclopropyl, 2-fluorocyclopropyl, 2-deuterocyclopropyl, 2,2-dideuterocyclopropyl, 2,2,3,3-tetradeuterocyclopropyl, cyclopropylmethyl, (pyridin-2-yl)methyl, phenyl and (5-trifluoromethyl-2-methoxy)phenyl;

[0089] Alternatively, R1 and R2, together with the nitrogen atom to which they are directly attached, form piperidine or 4-(cyclopropylmethyl)piperazine;

[0090] R3, R4, R5 and R6 are all deuterium; or, R3, R4, R5 and R6 are all hydrogen;

[0091] R7 is one, two, three or four and is independently selected from the group consisting of hydrogen, deuterium, amino, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, benzyl, methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, benzyloxy, substituted benzyloxy, formyloxy, acetoxy, propionyloxy, benzoyloxy, tert-butoxycarbonyloxy, methoxycarbonyloxy, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, phosphoryloxy and hydroxy; wherein the substituted benzyloxy group refers to a benzyloxy group whose phenyl ring is substituted by 1 to 3 groups independently selected from the group consisting of fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, hydroxy, phenyl, formyloxy, acetoxy and propionyloxy;

[0092] R8 is a substituent selected from the group consisting of hydrogen, cyclopropylmethyl, and deuterated methyl;

[0093] In formula (I), Y is N or CR 11 , where R 10 With R 11 forming a bond;

[0094] R9 is hydrogen, amino or dimethylamino, or R9 and R 10 and its attached carbon atom to form a -C(O)- group.

[0095] In some embodiments, the present application provides a compound of formula (IB), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite, or prodrug thereof, wherein R1 and R2 in formula (IB) are each independently selected from the group consisting of hydroxy, methyl, trideuteromethyl, ethyl, n-propyl, isopropyl, 2-hydroxyisopropyl, n-butyl, tert-butyl, cyclopropyl, 2-fluorocyclopropyl, 2-deuterocyclopropyl, 2,2-dideuterocyclopropyl, 2,2,3,3-tetradeuterocyclopropyl, cyclopropylmethyl, (pyridin-2-yl)methyl, phenyl, and (5-trifluoromethyl-2-methoxy)phenyl;

[0096] R3, R4, R5, and R6 are all deuterium;

[0097] R7 is one, two, three or four and is independently selected from the group consisting of hydrogen, deuterium, amino, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, benzyl, methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, benzyloxy, substituted benzyloxy, formyloxy, acetoxy, propionyloxy, benzoyloxy, tert-butoxycarbonyloxy, methoxycarbonyloxy, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, phosphoryloxy and hydroxy; wherein the substituted benzyloxy group refers to a benzyloxy group whose phenyl ring is substituted by 1 to 3 groups independently selected from the group consisting of fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, hydroxy, phenyl, formyloxy, acetoxy and propionyloxy;

[0098] R8 is a substituent selected from the group consisting of hydrogen, cyclopropylmethyl, and deuterated methyl;

[0099] In formula (I), Y is N or CR 11 , where R 10 With R 11 forming a bond;

[0100] R9 is hydrogen, amino or dimethylamino.

[0101] In some embodiments, the present application provides a compound represented by formula (IB), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated product, metabolite or prodrug thereof, wherein in formula (IB), R1 is -CD3, R2 is cyclopropyl or cyclopropylmethyl;

[0102] R3, R4, R5, and R6 are all deuterium;

[0103] R7 is one, two, three or four and is independently selected from the following groups: hydrogen, amino, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, benzyl, methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, benzyloxy, formyloxy, acetoxy, propionyloxy, benzoyloxy, tert-butoxycarbonyloxy, methoxycarbonyloxy, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, phosphoryloxy and hydroxy:

[0104] R8 is a substituent selected from the group consisting of: hydrogen;

[0105] R9 is hydrogen, amino or dimethylamino.

[0106] In some embodiments, the present application provides a compound represented by formula (IB), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated product, metabolite or prodrug thereof, wherein R1 and R2 in formula (I), formula (IA) or formula (IB) form piperidine or 4-(cyclopropylmethyl)piperazine with the nitrogen atom to which they are directly attached;

[0107] R3, R4, R5 and R6 are all deuterium; or, R3, R4, R5 and R6 are all hydrogen;

[0108] R7 is one, two, three or four and is independently selected from the group consisting of hydrogen, deuterium, amino, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, benzyl, methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, benzyloxy, substituted benzyloxy, formyloxy, acetoxy, propionyloxy, benzoyloxy, tert-butoxycarbonyloxy, methoxycarbonyloxy, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, phosphoryloxy and hydroxy; wherein the substituted benzyloxy group refers to a benzyloxy group whose phenyl ring is substituted by 1 to 3 groups independently selected from the group consisting of fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, hydroxy, phenyl, formyloxy, acetoxy and propionyloxy;

[0109] R8 is a substituent selected from the group consisting of hydrogen, cyclopropylmethyl, and deuterated methyl;

[0110] R9 is hydrogen, amino or dimethylamino.

[0111] In some embodiments, the present application provides a compound represented by formula (IB), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated product, metabolite or prodrug thereof, wherein R1 and R2 in formula (I), formula (IA) or formula (IB) form piperidine or 4-(cyclopropylmethyl)piperazine with the nitrogen atom to which they are directly attached;

[0112] R3, R4, R5 and R6 are all hydrogen;

[0113] R7 is one, two, three or four and is independently selected from the group consisting of hydrogen, deuterium, amino, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, benzyl, methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, benzyloxy, formyloxy, acetoxy, propionyloxy, benzoyloxy, tert-butoxycarbonyloxy, methoxycarbonyloxy, methylsulfonyloxy, ethylsulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, phosphoryloxy and hydroxy;

[0114] R8 is a substituent selected from the group consisting of hydrogen and cyclopropylmethyl;

[0115] R9 is hydrogen.

[0116] In some embodiments, the present application provides a compound represented by formula (IB), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated product, metabolite or prodrug thereof, wherein, in formula (I), formula (IA) or formula (IB), R1 is methyl and R2 is 2-hydroxyisopropyl;

[0117] R3, R4, R5 and R6 are all hydrogen;

[0118] R7 is one, two, three or four and is independently selected from the group consisting of hydrogen, deuterium, amino, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, benzyl, methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, benzyloxy, formyloxy, acetoxy, propionyloxy, benzoyloxy, tert-butoxycarbonyloxy, methoxycarbonyloxy, methylsulfonyloxy, ethylsulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, phosphoryloxy and hydroxy;

[0119] R8 is hydrogen;

[0120] R9 is hydrogen.

[0121] In some embodiments, the present application provides a compound represented by formula (IB), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated product, metabolite or prodrug thereof, wherein, in formula (I), formula (IA) or formula (IB), R1 is methyl and R2 is cyclopropyl;

[0122] R3, R4, R5 and R6 are all hydrogen;

[0123] R7 is one, two, three or four and is independently selected from the group consisting of deuterium, amino, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, benzyl, methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, benzyloxy, formyloxy, acetoxy, propionyloxy, benzoyloxy, tert-butoxycarbonyloxy, methoxycarbonyloxy, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, phosphoryloxy and hydroxy;

[0124] R8 is hydrogen;

[0125] R9 is hydrogen.

[0126] In some embodiments, the compound provided by the present application is represented by formula (I), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein formula (I) is formula (IC):

[0127] Wherein, in formula (IC), n is 0 or 1;

[0128] R1 is an unsubstituted C1-C6 alkyl group or a substituted C1-C6 alkyl group, wherein the substituted C1-C6 alkyl group is substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, hydroxy, halogen, halogenated C1-C3 alkyl, halogenated C1-C3 alkoxy, C3-C6 cycloalkyl, aryl and heteroaryl;

[0129] R7 is one, two, three or four and is independently selected from hydrogen, deuterium, amino, halogen, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, C1-C6 alkanoyloxy, aromatic acyloxy, heteroaroyloxy, C1-C6 alkoxy substituted C1-C6 alkanoyloxy, C1-C6 alkanesulfonyloxy, aromatic sulfonyloxy, substituted aromatic sulfonyloxy, phosphoryloxy Here, the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, or substituted arylsulfonyloxy refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, phenyl and substituted phenyl, and here, the substituted phenyl refers to substituted by 1-3 groups independently selected from the following groups: halogen, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, phenyl and C1-C6 alkanoyloxy.

[0130] In some embodiments, the present application provides a compound of formula (IC), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein n is 0.

[0131] In some embodiments, the present application provides a compound of formula (IC), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein n is 1.

[0132] In some embodiments, the present application provides a compound of formula (IC), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, deuterated n-butyl or deuterated tert-butyl.

[0133] In some embodiments, the present application provides a compound of formula (IC), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R1 is a deuterated methyl group.

[0134] In some embodiments, the present application provides a compound of formula (IC), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R1 is -CD3.

[0135] In some embodiments, the present application provides a compound of formula (IC), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R7 is one, two, three or four, and each is independently selected from hydrogen, deuterium, amino, halogen, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, C1-C6 alkanoyloxy, aroyloxy, heteroaroyloxy, C1-C6 alkoxy substituted C1-C6 alkoxy Acyloxy, C1-C6 alkanesulfonyloxy, aromatic sulfonyloxy, substituted aromatic sulfonyloxy, phosphoryloxy and hydroxyl; Here, the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, or substituted aromatic sulfonyloxy refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, phenyl and substituted phenyl, here, the substituted phenyl refers to substituted by 1-3 groups independently selected from the following groups: halogen, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, phenyl and C1-C6 alkanoyloxy.

[0136] In some embodiments, the present application provides a compound of formula (IC), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R7 is one, two, three or four, and each is independently selected from the following substituents: hydrogen, deuterium, amino, fluorine, chlorine, bromine, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, C1-C6 alkanoyloxy, benzoyloxy, C1-C6 alkoxy substituted C1-C6 alkoxy Acyloxy, C1-C6 alkanesulfonyloxy, benzenesulfonyloxy, substituted benzenesulfonyloxy, phosphoryloxy and hydroxyl; Here, the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, or substituted benzenesulfonyloxy refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, phenyl and substituted phenyl, here, the substituted phenyl refers to substituted by 1-3 groups independently selected from the following groups: fluorine, chlorine, bromine, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, phenyl and C1-C6 alkanoyloxy.

[0137] In some embodiments, the present application provides a compound of formula (IC), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R7 is one, two, three or four, and each is independently selected from the following groups: hydrogen, deuterium, amino, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, benzyl, methoxy, ethoxy, n-propoxy, isopropyloxy, tert-butyl, butoxy, benzyloxy, substituted benzyloxy, formyloxy, acetoxy, propionyloxy, benzoyloxy, tert-butoxycarbonyloxy, methoxycarbonyloxy, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, phosphoryloxy and hydroxy; wherein the substituted benzyloxy group refers to a phenyl ring substituted by 1 to 3 groups independently selected from the following groups: fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, hydroxy, phenyl, formyloxy, acetoxy and propionyloxy;

[0138] In some embodiments, the present application provides a compound of formula (IC), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R7 is one, two, three or four, and each is independently selected from the following groups: hydrogen, deuterium, amino, hydroxyl, fluorine, chlorine, bromine, 1,1-dideuteroethyl, methoxy, (4-acetoxy)benzyloxy, acetoxy, methoxycarbonyloxy, phosphoryloxy, and methylsulfonyloxy.

[0139] In some embodiments, the present application provides a compound of formula (IC), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R7 is one, two, three or four, and each is independently selected from the following groups: hydrogen, amino, fluorine, chlorine, bromine and hydroxyl.

[0140] In some embodiments, the present application provides a compound of formula (IC), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R7 is at position 4, 5, 6 or 7 of the benzene ring to which it is attached (i.e., the position determined by the indole structure).

[0141] In some embodiments, the present application provides a compound of formula (IC), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein n is 0; R1 is -CD3; R7 is one, two, three or four, and each is independently selected from the following groups: hydrogen, amino, fluorine, chlorine, bromine and hydroxyl.

[0142] In some embodiments, the present application provides a compound of formula (IC), or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated product, metabolite or prodrug thereof, wherein n is 1: R1 is -CD3: R7 is one, two, three or four, and each is independently selected from the following groups: hydrogen, amino, fluorine, chlorine, bromine and hydroxyl.

[0143] Furthermore, the compound of formula (I) is selected from the following compounds, and stereoisomers, pharmaceutically acceptable salts, solvates, deuterated compounds, metabolites or prodrugs thereof:

[0144] In an embodiment of the second aspect, the present application provides a pharmaceutical composition comprising the above-mentioned DMT derivative or its stereoisomer, pharmaceutically acceptable salt, solvate, deuterated substance, metabolite or prodrug, and a pharmaceutically acceptable carrier.

[0145] In some embodiments, the present application also discloses a pharmaceutical composition comprising: an effective dose of a DMT derivative represented by formula (I), formula (IA), formula (IB) or formula (IC) described herein, or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated substance, metabolite or prodrug thereof, and a pharmaceutically acceptable carrier or excipient.

[0146] In some embodiments, the pharmaceutical composition further comprises one or more additional therapeutic agents.

[0147] The pharmaceutically acceptable excipient(s) can be, for example, selected from carriers (e.g., solid, liquid or semisolid carriers), adjuvants, diluents (e.g., solid diluents such as fillers or extenders; and liquid diluents such as solvents and co-solvents), granulating agents, binders, glidants, coating agents, release controlling agents (e.g., polymers or waxes that retard or delay release), binders, disintegrants, buffers, lubricants, preservatives, antifungal and antibacterial agents, antioxidants, buffers, tonicity adjusting agents, thickeners, flavor enhancers, sweeteners, pigments, plasticizers, taste-masking agents, stabilizers or any other excipient conventionally used in pharmaceutical compositions.

[0148] As used herein, the term "pharmaceutically acceptable" refers to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of subjects (e.g., human subjects) without excessive toxicity, irritation, allergic response, or other problems or complications commensurate with a reasonable benefit / risk ratio. Each excipient must also be "acceptable" in the sense of being compatible with the other ingredients of the formulation.

[0149] The pharmaceutical composition may be in any form suitable for oral, parenteral, topical, intranasal, intrabronchial, sublingual, ophthalmic, otic, rectal, intravaginal or transdermal administration.

[0150] Suitable pharmaceutical dosage forms for oral administration include tablets (coated or uncoated), capsules (hard or soft shell), caplets, pills, lozenges, syrups, solutions, powders, granules, elixirs and suspensions, sublingual tablets or patches such as buccal patches.

[0151] In an embodiment of the third aspect, the present application provides a method for preparing a DMT derivative represented by the above formula (I), formula (IA), formula (IB) or formula (IC) or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated substance, metabolite or prodrug thereof, the preparation method comprising the following steps:

[0152] (1) Substitution reaction of the compound (I-1) with oxalyl chloride to obtain a compound (I-2);

[0153] (2) Acylation reaction of the compound of formula (I-2) with the compound of formula (I-3) to obtain the compound of formula (I-3);

[0154] (3) The compound of formula (I-4) is subjected to reduction reaction to obtain the compound of formula (I-5);

[0155] Optionally, the compound of formula (I-4) is subjected to a thiocarbonylation reaction to obtain a compound of formula (I-5);

[0156] Alternatively, the method comprises the following steps: performing a substitution reaction between formula (I-6) and formula (I-7) to obtain a compound of formula (I-8);

[0157] Formula (I-8) and formula (I-9) undergo substitution reaction to obtain a compound of formula (I-5);

[0158] (4) Substitution reaction of formula (I-5) with formula (I-10) to obtain a compound of formula (I);

[0159] In the above preparation method, X represents a leaving group such as bromine, etc., and other groups are defined as formula (I).

[0160] In an embodiment of the fourth aspect, the present application provides a DMT derivative represented by formula (I), formula (IA), formula (IB) or formula (IC) described herein, or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated substance, metabolite or prodrug thereof, or a pharmaceutical composition thereof, for pharmaceutical use.

[0161] In the embodiment of the fifth aspect, the present application provides a DMT derivative represented by formula (I), formula (IA), formula (IB) or formula (IC) as described in the present application, and its stereoisomers, pharmaceutically acceptable salts, solvates, deuterated substances, metabolites or prodrugs, or pharmaceutical compositions thereof, for stimulating 5-HT 2A receptor.

[0162] In the embodiment of the sixth aspect, the present application provides a DMT derivative represented by formula (I), formula (IA), formula (IB) or formula (IC) as described in the present application and its stereoisomers, pharmaceutically acceptable salts, solvates, deuterated substances, metabolites or prodrugs, or pharmaceutical compositions thereof for the treatment of 5-HT 2A Receptor-associated diseases / disorders.

[0163] In the embodiment of the seventh aspect, the present application provides a DMT derivative represented by formula (I), formula (IA), formula (IB) or formula (IC) described in the present application, or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated substance, metabolite or prodrug thereof, or a pharmaceutical composition thereof for the preparation of a method for treating 5-HT. 2A Use in medicine for receptor-related central nervous system diseases, disorders or conditions and / or neurological diseases, disorders or conditions.

[0164] In some embodiments, the present application provides the above-mentioned use, wherein the 5-HT 2A The receptor-associated central nervous system disease, disorder or condition and / or neurological disease, disorder or condition may be selected from the group consisting of major depressive disorder, anxiety disorder, attention deficit hyperactivity disorder, post-traumatic stress disorder, cancer-related conditions, loss of drive, burnout, cluster headaches, migraines, Parkinson's disease, schizophrenia, eating disorders, nausea or vomiting, and addictive psychoactive substance abuse.

[0165] In an embodiment of the eighth aspect, the present application provides a method for treating 5-HT in a patient. 2A A method for treating a receptor-related disease / disorder, comprising administering to a patient in need thereof a DMT derivative represented by formula (I), formula (IA), formula (IB) or formula (IC) described herein, or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated substance, metabolite or prodrug thereof, or a pharmaceutical composition thereof.

[0166] In some embodiments, the present application provides a method for treating or preventing a patient's central nervous system disease, disorder or condition and / or neurological disease, disorder or condition, the method comprising administering to a patient in need thereof a DMT derivative of formula (I), formula (IA), formula (IB) or formula (IC) as described herein, or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, or the pharmaceutical composition. The central nervous system disease, disorder or condition and / or neurological disease, disorder or condition can be selected from: major depressive disorder, anxiety disorder, attention deficit hyperactivity disorder, post-traumatic stress disorder, cancer-related illness, decreased drive, burnout, cluster headache, migraine, Parkinson's disease, schizophrenia, eating disorders, nausea or vomiting, and abuse of addictive psychoactive substances.

[0167] In some embodiments, the present application provides a method for treating 5-HT in a patient. 2A A method for treating a receptor-related disease / disorder, comprising administering a DMT derivative represented by formula (I), formula (IA), formula (IB) or formula (IC) described herein, or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated substance, metabolite or prodrug thereof, or the pharmaceutical composition described herein.

[0168] In some embodiments, the present application provides a method for stimulating 5-HT 2A A method for treating or preventing a patient's central nervous system disease, disorder or condition and / or neurological disease, disorder or condition, comprising administering to a patient in need thereof a DMT derivative represented by formula (I), formula (IA), formula (IB) or formula (IC) herein, or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, or a pharmaceutical composition thereof. The central nervous system disease, disorder or condition and / or neurological disease, disorder or condition may be selected from the group consisting of major depressive disorder, anxiety disorder, attention deficit hyperactivity disorder, post-traumatic stress disorder, cancer-related conditions, decreased drive, burnout, cluster headache, migraine, Parkinson's disease, schizophrenia, eating disorders, nausea or vomiting, and abuse of addictive psychoactive substances. Beneficial effects

[0169] The compounds of the present application can react with 5-HT 2A Receptor binding, with good 5-HT 2A It has receptor binding activity, a short half-life, rapid metabolism, is suitable for medicinal use, and has clinical application value.

[0170] Definitions and Explanations of Terms

[0171] Unless otherwise indicated, the definitions of groups and terms in the specification and claims of this application, including those used as examples, illustrative examples, preferred examples, definitions of specific compounds in tables, and definitions of specific compounds in the Examples, may be combined and coupled with each other in any manner. Subsequent group definitions and compound structures shall fall within the scope of those described in the specification.

[0172] The carbon, hydrogen, oxygen, sulfur, nitrogen or halogen involved in the groups and compounds described in this application include their isotopes, and the carbon, hydrogen, oxygen, sulfur, nitrogen or halogen involved in the groups and compounds are optionally further replaced by one or more of their corresponding isotopes, wherein hydrogen isotopes include protium (H), deuterium (D, also known as heavy hydrogen), tritium (T, also known as super tritium), carbon isotopes include 12 C. 13 C and 14 C, nitrogen isotopes include 14 N and 15 N, oxygen isotopes include 16 O. 17 O and 18 O, sulfur isotopes include 32 S. 33 S. 34 S and 36 S, isotope of fluorine 19 F, chlorine isotopes include 35 Cl and 37 Isotopes of Cl, bromine include 79 Br and 81 Br.

[0173] In the present application, "alkyl" refers to a linear and branched monovalent saturated hydrocarbon group with a main chain comprising 1 to 10 carbon atoms. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, n-hexyl, n-heptyl, n-octyl, n-nonyl and n-decyl. The alkyl group may be further substituted by any substituent.

[0174] In this application, "cycloalkyl" refers to a monovalent saturated carbocyclic hydrocarbon group, a single ring, usually having 3 to 10 carbon atoms, non-limiting examples of which include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc. The cycloalkyl group may be optionally further substituted with any substituent.

[0175] In this application, "heterocycloalkane" refers to a saturated cyclic hydrocarbon group containing at least one heteroatom, a monocyclic ring, wherein the heteroatom is N, O, S, P, and oxidized forms thereof. Non-limiting examples include aziridine, oxirane, thiirane, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydrothienyl, and the like. The heterocycloalkane may be optionally further substituted with any substituent.

[0176] In the present application, "aryl" refers to a 6- to 14-membered all-carbon monocyclic or fused polycyclic (i.e., rings sharing adjacent pairs of carbon atoms) group having a conjugated π electron system, preferably 6- to 10-membered, such as phenyl and naphthyl. The aryl ring includes an aryl ring as described above fused to a heteroaryl, heterocyclyl or cycloalkyl ring, wherein the ring connected to the parent structure is the aryl ring. The aryl group can be substituted or unsubstituted, and when substituted, the substituent can be substituted at any available point of attachment, and the substituent is preferably independently optionally selected from one or more substituents of hydrogen, halogen, alkyl, alkoxy, haloalkyl, hydroxyl, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl.

[0177] As used herein, "heteroaryl" refers to a heteroaromatic system containing 1 to 4 heteroatoms and 5 to 14 ring atoms, wherein the heteroatoms are selected from nitrogen, oxygen, and sulfur. The heteroaryl group is preferably 5 to 10-membered (e.g., 5, 6, 7, 8, 9, or 10-membered), more preferably 5- or 6-membered, such as furyl, thienyl, pyridyl, pyrrolyl, N-alkylpyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and the like. The heteroaryl ring includes a heteroaryl group as described above fused to an aryl, heterocyclyl, or cycloalkyl ring, wherein the ring attached to the parent structure is the heteroaryl ring.

[0178] As used herein, "pharmaceutically acceptable salts" refer to salts that retain the biological effectiveness and properties of the free acid or free base and are obtained by reacting the free acid with a non-toxic inorganic base or organic base, or by reacting the free acid with a non-toxic inorganic acid or organic acid.

[0179] As used herein, "carrier" refers to a carrier or diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered compound.

[0180] As used herein, "excipient" refers to an inert substance added to a pharmaceutical composition to further enhance the administration of a compound. Examples of excipients include, but are not limited to, calcium carbonate, calcium phosphate, various sugars and different types of starch, cellulose derivatives (including microcrystalline cellulose), gelatin, vegetable oils, polyethylene glycols, diluents, granulating agents, lubricants, binders, disintegrants, and the like.

[0181] As used herein, a "prodrug" refers to a compound that can be converted under physiological conditions or by solvolysis into a biologically active compound of the present invention. The prodrugs of the present invention are prepared by modifying the phenolic group in the compound. This modification can be removed by conventional procedures or in vivo to yield the parent compound. When the prodrugs of the present invention are administered to a mammalian subject, the prodrugs are cleaved to form free hydroxyl groups. Examples of prodrugs include, but are not limited to, phenolic hydroxyl groups and sodium phosphate derivatives of the compounds of the present invention.

[0182] As used herein, "effective dose" refers to the amount of a compound that elicits the physiological or medical translation of the tissue, system, or subject being treated, and includes an amount of the compound that, when administered to a subject, is sufficient to prevent the occurrence of one or more symptoms of the disorder or condition being treated or to alleviate them to some extent.

[0183] In this application, "solvate" refers to the compound of the present application or its salt, which also includes a stoichiometric or non-stoichiometric solvent bound by intermolecular non-covalent forces. When the solvent is water, it is a hydrate.

[0184] As used herein, "optionally" or "optionally" means that the subsequently described event or circumstance may but need not occur, and the description includes instances where the event or circumstance occurs or does not occur. For example, "alkyl optionally substituted with Cl" means that the alkyl group may but need not be substituted with Cl, and the description includes instances where the alkyl group is substituted with Cl and instances where the alkyl group is not substituted with Cl. DETAILED DESCRIPTION

[0185] The following will further describe in detail the general formula compounds of the present application, their preparation methods, and uses with reference to specific examples. The following examples are merely illustrative and explanatory of the present application and should not be construed as limiting the scope of protection of the present application. All technologies implemented based on the above content of the present application are encompassed within the scope of protection intended by the present application.

[0186] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0187] This application uses the following abbreviations:

[0188] ACN: acetonitrile;

[0189] DCM: dichloromethane

[0190] DMF: N,N-dimethylformamide

[0191] EA: ethyl acetate

[0192] K2CO3: Potassium carbonate

[0193] LiAlD4: ​​lithium aluminum hydride deuterated;

[0194] LiAlH4: lithium aluminum hydride

[0195] MTBE: Methyl tert-butyl ether

[0196] NaBH3CN: sodium cyanoborohydride;

[0197] NaH: sodium hydride

[0198] Na2SO4: sodium sulfate

[0199] PE: petroleum ether;

[0200] THF: tetrahydrofuran;

[0201] TEA: triethylamine

[0202] 2-MTHF: 2-methyltetrahydrofuran

[0203] The compounds were named according to conventional naming conventions in the art; commercial reagents were named according to the supplier's catalogue names.

[0204] 1 H NMR data were collected and recorded using a Bruker Avance Neo 400 MHz / 600 MHz liquid superconducting nuclear magnetic resonance spectrometer at 400 MHz / 600 MHz, using DMSO-d6 as the solvent and TMS (δ = 0) as the internal standard. Chemical shifts (δ) were reported in ppm. Mass spectra were acquired and recorded using a Waters ACQUITY UPLC system, with detection using an ACQUITY UPLC BEH C8 column (50 mm x 2.1 mm, 1.7 μm, 20180306-C8-08). Mobile phase A: 0.01% TFA / H2O; mobile phase B: CH3CN; flow rate: 0.2 mL / min; column temperature: 30°C; detection wavelength: UV-210 nm. High-performance liquid chromatography (HPLC) was performed on a Thermo UltiMate 3000 liquid chromatograph using a Venusil ASB C18 column (4.6 x 250 mm, 5 μm). Mobile phase A: pH 1.5 phosphoric acid aqueous solution; mobile phase B: CH3CN; flow rate: 1.0 mL / min; column temperature: 35°C; detection wavelength: UV-215 nm; injection volume: 2 μL; gradient elution conditions: elution at a flow rate of 1.0 mL / min throughout, initially with 95% A and 5% B for 10 minutes, then with 20% A and 80% B for 5 minutes, and finally with 95% A and 5% B for 5 minutes. Percentages represent the volume percentage of mobile phase to elution solution.

[0205] Example 1: Synthesis of 5-(1,1-dideuteroethyl)-3-[1,1,2,2-tetradeutero-2-(dimethylamino)ethyl]-1H-indole. The route is as follows:

[0206] 5-(Acetyl)indole (200 mg, 1.26 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (240 mg, 1.89 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 5-(acetyl)indole remained. The product was filtered under reduced pressure to obtain 210 mg of intermediate 1a.

[0207] Intermediate 1a (210 mg, 0.84 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Dimethylamine hydrochloride (103 mg, 1.26 mmol, 1.5 eq) and TEA (255 mg, 2.52 mmol, 3.0 eq) were added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 1a, and LC-MS confirmed the molecular weight of 1b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Elution was performed by column chromatography (PE:EA = 10:1) to afford 110 mg of intermediate 1b.

[0208] Intermediate 1b (110 mg, 0.43 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (90 mg, 2.15 mmol, 5.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC confirmed the absence of 1b. LC-MS confirmed the molecular weight of compound 1. The reaction mixture was quenched with 10% aqueous NaOH and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) was used to obtain 20 mg of compound 1 as a yellow oil. HPLC purity: 95.01%; MS m / z (ESI): 223.34 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ1.32 (t, J=8.3Hz, 3H), 2.45 (s, 6H), 6.96-6.94 (m, 1H), 7.02 ( d, J=8.3Hz, 1H), 7.10 (d, J=7.5Hz, 1H), 7.28 (d, J=1.6Hz, 1H), 10.72 (d, J=8.3Hz, 1H).

[0209] Example 2: Synthesis of 3-[1,1,2,2-tetradeuterium-2-(dimethylamino)ethyl]-1H-indole-7-ol. The route is as follows:

[0210] 7-(Acetoxy)indole (200 mg, 1.14 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (217 mg, 1.71 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 7-(acetoxy)indole remained. The product was filtered under reduced pressure to obtain 200 mg of intermediate 2a.

[0211] Intermediate 2a (200 mg, 0.75 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Dimethylamine hydrochloride (92 mg, 1.13 mmol, 1.5 eq) and TEA (228 mg, 2.25 mmol, 3.0 eq) were added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 2a, and LC-MS confirmed the molecular weight of 2b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Elution was performed by column chromatography (PE:EA = 10:1) to afford 100 mg of intermediate 2b.

[0212] Intermediate 2b (100 mg, 0.36 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (30 mg, 0.72 mmol, 2.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC revealed no residue of 2b. LC-MS confirmed the molecular weight of compound 2. The reaction mixture was quenched with 10% aqueous NaOH and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) afforded 22 mg of compound 2 as a yellow oil. HPLC purity: 95.42%; MS m / z (ESI): 209.14 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ2.65 (s, 6H), 6.78-6.73 (m, 1H), 6.89 (d, J = 8.6Hz, 1H), 7.12 (t, J=7.4Hz, 1H), 7.37-7.34 (m, 1H), 8.51 (s, 1H), 10.72 (d, J=8.6Hz, 1H).

[0213] Example 3: Synthesis of 3-[1,1,2,2-tetradeuterium-2-(dimethylamino)ethyl]-1H-indole-5,6-diol. The route is as follows:

[0214] 5,6-(diacetoxy)indole (200 mg, 0.86 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (164 mg, 1.29 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 5,6-(diacetoxy)indole remained. The product was filtered under reduced pressure to obtain 140 mg of intermediate 3a.

[0215] Intermediate 3a (140 mg, 0.43 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Dimethylamine hydrochloride (53 mg, 0.65 mmol, 1.5 eq) and TEA (131 mg, 1.29 mmol, 3.0 eq) were then added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 3a, and LC-MS confirmed the molecular weight of 3b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. 50 mg of intermediate 3b was obtained by column chromatography (PE:EA = 10:1).

[0216] Intermediate 3b (50 mg, 0.15 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (13 mg, 0.30 mmol, 2.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC confirmed the absence of 3b. LC-MS confirmed the molecular weight of compound 3. The reaction mixture was quenched with 10% aqueous NaOH and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) was used to obtain 10 mg of compound 3 as a yellow oil. HPLC purity: 95.42%; MS m / z (ESI): 225.14 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ2.71 (s, 6H), 6.71 (s, 1H), 6.97 (s, 1H), 7.10 (d, J = 8.6Hz, 1H), 8.86. (s, 1H), 9.01 (s, 1H), 10.78 (d, J = 8.6Hz, 1H).

[0217] Example 4: Synthesis of 6-methoxy-3-[1,1,2,2-tetradeuterium-2-(diethylamino)ethyl]-1H-indole. The route is as follows:

[0218] 6-(Methoxy)indole (200 mg, 1.36 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (259 mg, 2.04 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 6-(methoxy)indole remained. The product was filtered under reduced pressure to obtain 160 mg of intermediate 4a.

[0219] Intermediate 4a (160 mg, 0.67 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Diethylamine hydrochloride (111 mg, 1.01 mmol, 1.5 eq) and TEA (203 mg, 2.01 mmol, 3.0 eq) were added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 4a, and LC-MS confirmed the molecular weight of 4b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 10:1) was used to obtain 75 mg of intermediate 4b.

[0220] Intermediate 4b (75 mg, 0.27 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (23 mg, 0.54 mmol, 2.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC revealed no residue of 4b. LC-MS confirmed the molecular weight of compound 4. The reaction mixture was quenched with 10% aqueous NaOH and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 15 mg of compound 4 as a yellow oil. HPLC purity: 95.71%; MS m / z (ESI): 251.38 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ1.12 (t, J = 7.1Hz, 6H), 2.57-2.72 (m, 4H), 3.87 (s, 3H), 6.72-6.74 (m, 1H), 6.90 (d, J = 2.2Hz, 1H), 7.18 (d, J = 2.2Hz, 1H), 7.62 (d, J = 8.6Hz, 1H), 10.58 (s, 1H).

[0221] Example 5: Synthesis of 5-(1,1-dideuteroethyl)-3-[1,1,2,2-tetradeuteroyl-2-(diethylamino)ethyl]-1H-indole. The route is as follows:

[0222] 5-(Acetyl)indole (200 mg, 1.26 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (240 mg, 1.89 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 5-(acetyl)indole remained. The product was filtered under reduced pressure to obtain 150 mg of intermediate 5a.

[0223] Intermediate 5a (150 mg, 0.60 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Diethylamine hydrochloride (99 mg, 0.90 mmol, 1.5 eq) and TEA (182 mg, 1.80 mmol, 3.0 eq) were added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 5a, and LC-MS confirmed the molecular weight of 5b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 10:1) was used to obtain 80 mg of intermediate 5b.

[0224] Intermediate 5b (80 mg, 0.28 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (59 mg, 1.40 mmol, 5.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC revealed no residue of 5b. LC-MS confirmed the molecular weight of compound 5. The reaction mixture was quenched with 10% aqueous NaOH and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 10 mg of compound 5 as a yellow oil. HPLC purity: 95.36%; MS m / z (ESI): 251.04 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ1.07 (t, J=7.2Hz, 6H), 1.22 (s, 3H), 2.55-2.69 (m, 4H), 6.91-6.93 (m, 1H), 7.18 (d, J = 2.4Hz, 1H), 7.21 (d, J = 8.3Hz, 1H), 7.31 (d, J = 1.6Hz, 1H), 10.79 (s, 1H).

[0225] Example 6: Synthesis of 3-[1,1,2,2-tetradeuterium-2-(diethylamino)ethyl]-1H-indole-7-ol. The route is as follows:

[0226] 7-(Acetoxy)indole (200 mg, 1.14 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (217 mg, 1.71 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 7-(acetoxy)indole remained. The product was filtered under reduced pressure to obtain 130 mg of intermediate 6a.

[0227] Intermediate 6a (130 mg, 0.49 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Diethylamine hydrochloride (81 mg, 0.74 mmol, 1.5 eq) and TEA (149 mg, 1.47 mmol, 3.0 eq) were then added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 6a, and LC-MS confirmed the molecular weight of 6b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 10:1) was used to obtain 60 mg of intermediate 6b.

[0228] Intermediate 6b (60 mg, 0.20 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (17 mg, 0.40 mmol, 2.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC detected no residue of 6b. LC-MS confirmed the molecular weight of compound 6. The reaction mixture was quenched with 10% aqueous NaOH and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 12 mg of compound 6 as a yellow oil. HPLC purity: 95.47%; MS m / z (ESI): 237.49 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ1.08 (t, J=8.0Hz, 6H), 2.64-2.60 (m, 4H), 6.68-6.64 (m, 1H), 6.94 ( d, J=7.5Hz, 1H), 7.01-6.97 (m, 1H), 7.54-7.53 (m, 1H), 8.45 (s, 1H), 10.79 (d, J=8.9Hz, 1H).

[0229] Example 7: Synthesis of 3-[1,1,2,2-tetradeuterium-2-(diethylamino)ethyl]-1H-indole-5,6-diol. The route is as follows:

[0230] 5,6-(diacetoxy)indole (200 mg, 0.86 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (164 mg, 1.29 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 5,6-(diacetoxy)indole remained. The product was filtered under reduced pressure to obtain 130 mg of intermediate 7a.

[0231] Intermediate 7a (130 mg, 0.40 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Diethylamine hydrochloride (66 mg, 0.60 mmol, 1.5 eq) and TEA (121 mg, 1.20 mmol, 3.0 eq) were added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 7a, and LC-MS confirmed the molecular weight of 7b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 10:1) was used to obtain 65 mg of intermediate 7b.

[0232] Intermediate 7b (65 mg, 0.18 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (15 mg, 0.36 mmol, 2.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC revealed no residual 7b. LC-MS confirmed the molecular weight of compound 7. The reaction mixture was quenched with 10% aqueous NaOH and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 10 mg of compound 7 as a yellow oil. HPLC purity: 95.38%; MS m / z (ESI): 253.15 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ1.09 (t, J=8.0Hz, 6H), 2.64-2.60 (m, 4H), 6.65 (s, 1H), 7.0 1 (s, 1H), 7.18 (d, J = 8.6Hz, 1H), 8.90 (s, 1H), 8.98 (s, 1H), 10.62 (d, J = 8.6Hz, 1H).

[0233] Example 8: Synthesis of 6-methoxy-3-{1,1,2,2-tetradeuteride-2-[di(propyl-2-yl)amino]ethyl}-1H-indole. The route is as follows:

[0234] 6-(Methoxy)indole (200 mg, 1.36 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (259 mg, 2.04 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 6-(methoxy)indole remained. The product was filtered under reduced pressure to obtain 160 mg of intermediate 8a.

[0235] Intermediate 8a (160 mg, 0.67 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Diisopropylamine (102 mg, 1.01 mmol, 1.5 eq) and TEA (203 mg, 2.01 mmol, 3.0 eq) were added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 8a, and LC-MS confirmed the molecular weight of 8b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 10:1) was used to obtain 90 mg of intermediate 8b.

[0236] Intermediate 8b (90 mg, 0.30 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (25 mg, 0.60 mmol, 2.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC detected no residue of 8b, and LC-MS determined the presence of compound 8. The reaction mixture was quenched with 10% aqueous NaOH, extracted with DCM, and the organic phase dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 18 mg of compound 8 as a pale yellow solid. HPLC purity: 95.71%; MS m / z (ESI): 279.51 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ1.09 (d, J=6.7Hz, 12H), 3.07-3.04 (m, 2H), 3.87 (s, 3H), 6.73-6.69 (m, 1H), 6.90 (s, 1H), 7.18 (d, J = 8.6Hz, 1H), 7.68 (d, J = 7.5Hz, 1H), 10.59 (d, J = 8.6Hz, 1H).

[0237] Example 9: Synthesis of 5-(1,1-dideuteroethyl)-3-{1,1,2,2-tetradeutero-2-[di(propyl-2-yl)amino]ethyl}-1H-indole. The route is as follows:

[0238] 5-(Acetyl)indole (200 mg, 1.26 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (240 mg, 1.89 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 5-(acetyl)indole remained. The product was filtered under reduced pressure to obtain 120 mg of intermediate 9a.

[0239] Intermediate 9a (120 mg, 0.48 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Diisopropylamine (73 mg, 0.72 mmol, 1.5 eq) and TEA (146 mg, 1.44 mmol, 3.0 eq) were then added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 9a, and LC-MS confirmed the molecular weight of 9b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Column chromatography (PE:EA = 10:1) was used to obtain 60 mg of intermediate 9b.

[0240] Intermediate 9b (60 mg, 0.19 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (40 mg, 0.95 mmol, 5.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC detected no residue of 9b. LC-MS confirmed the molecular weight of compound 9. The reaction mixture was quenched with 10% aqueous NaOH and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) afforded 12 mg of compound 9 as a yellow oil. HPLC purity: 95.91%; MS m / z (ESI): 279.25 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ1.19 (t, J=8.6Hz, 3H), 1.41 (d, J=6.7Hz, 12H), 3.51-3.45 (m, 2H), 7.12- 7.07 (m, 1H), 7.15 (d, J = 8.4Hz, 1H), 7.30 (s, 1H), 7.35 (d, J = 1.3Hz, 1H), 10.71 (d, J = 8.6Hz, 1H).

[0241] Example 10: Synthesis of 3-{1,1,2,2-tetradeuterium-2-[di(propyl-2-yl)amino]ethyl}-1H-indole-7-ol. The route is as follows:

[0242] 7-(Acetoxy)indole (200 mg, 1.14 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (217 mg, 1.71 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 7-(acetoxy)indole remained. The product was filtered under reduced pressure to obtain 100 mg of intermediate 10a.

[0243] Intermediate 10a (100 mg, 0.38 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Diisopropylamine (58 mg, 0.57 mmol, 1.5 eq) and TEA (115 mg, 1.14 mmol, 3.0 eq) were then added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 10a, and LC-MS confirmed the molecular weight of 10b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. 55 mg of intermediate 10b was obtained by column chromatography (PE:EA = 10:1).

[0244] Intermediate 10b (55 mg, 0.17 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (14 mg, 0.34 mmol, 2.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC revealed no residue of 10b. LC-MS confirmed the molecular weight of compound 10. The reaction mixture was quenched with 10% aqueous NaOH and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 10 mg of compound 10 as a yellow oil. HPLC purity: 95.67%; MS m / z (ESI): 265.32 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ1.22 (d, J=6.7Hz, 12H), 3.61-3.56 (m, 2H), 6.75-6.70 (m, 1H), 7.05- 6.98 (m, 1H), 7.14 (d, J = 7.5Hz, 1H), 7.41-7.38 (m, 1H), 8.32 (s, 1H), 10.72 (d, J = 8.6Hz, 1H).

[0245] Example 11: Synthesis of 3-{1,1,2,2-tetradeuterium-2-[di(propyl-2-yl)amino]ethyl}-1H-indole-5,6-diol. The route is as follows:

[0246] 5,6-(diacetoxy)indole (200 mg, 0.86 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (164 mg, 1.29 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 5,6-(diacetoxy)indole remained. The product was filtered under reduced pressure to obtain 130 mg of intermediate 11a.

[0247] Intermediate 11a (130 mg, 0.40 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Diisopropylamine (61 mg, 0.60 mmol, 1.5 eq) and TEA (121 mg, 1.20 mmol, 3.0 eq) were added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 11a, and LC-MS confirmed the molecular weight of 11b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Column chromatography (PE:EA = 10:1) was performed to yield 70 mg of intermediate 11b.

[0248] Intermediate 11b (70 mg, 0.18 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (15 mg, 0.36 mmol, 2.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC confirmed the absence of 11b. LC-MS confirmed the molecular weight of compound 11. The reaction mixture was quenched with 10% aqueous NaOH and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 10 mg of compound 11 as a yellow oil. HPLC purity: 95.81%; MS m / z (ESI): 281.10 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ1.09 (d, J=6.7Hz, 12H), 6.77 (s, 1H), 7.01 (s, 1H), 7.18 (d, J=8.6Hz, 1H), 8.85 (s, 1H), 8.98 (s, 1H), 10.66 (d, J=8.6Hz, 1H).

[0249] Example 12: Synthesis of 3-{2-[cyclopropyl(trideuteriomethyl)amino]-1,1,2,2-tetradeuterioethyl}-1H-indole. The route is as follows:

[0250] Indole (200 mg, 1.71 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (326 mg, 2.57 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no indole remained. The product was filtered under reduced pressure to obtain 250 mg of intermediate 12a.

[0251] Intermediate 12a (250 mg, 1.20 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Cyclopropyl(trideuteriomethyl)amine hydrochloride (199 mg, 1.80 mmol, 1.5 eq) and TEA (364 mg, 3.60 mmol, 3.0 eq) were added and the mixture was in an oil bath at 60°C. After 5 h, TLC detected no residue of 12a, and LC-MS determined the molecular weight of 12b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Elution with column chromatography (PE:EA = 10:1) afforded 150 mg of intermediate 12b.

[0252] Intermediate 12b (150 mg, 0.61 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (51 mg, 1.22 mmol, 2.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC confirmed the absence of 12b. LC-MS confirmed the molecular weight of compound 12. The reaction mixture was quenched with 10% aqueous NaOH and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) afforded 40 mg of compound 12 as a yellow oil. HPLC purity: 95.11%; MS m / z (ESI): 222.34 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.29-0.36(m,2H), 0.40-0.48(m,2H), 1.67-1.77(m, 1H), 6.94-7.03(m, 1H) , 7.02-7.10 (m, 1H), 7.13 (d, J = 2.4Hz, 1H), 7.30-7.38 (m, 1H), 7.51 (d, J = 7.8Hz, 1H), 10.75 (s, 1H).

[0253] Example 13: Synthesis of 3-{2-[cyclopropyl(trideuterylmethyl)amino]-1,1,2,2-tetradeuterylethyl}-1H-indole-4-ol. The route is as follows:

[0254] 4-(Acetoxy)indole (200 mg, 1.14 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (217 mg, 1.71 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 4-(acetoxy)indole remained. The product was filtered under reduced pressure to obtain 210 mg of intermediate 13a.

[0255] Intermediate 13a (210 mg, 0.79 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Cyclopropyl(trideuteriomethyl)amine hydrochloride (132 mg, 1.19 mmol, 1.5 eq) and TEA (240 mg, 2.37 mmol, 3.0 eq) were added and the mixture was in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 13a, and LC-MS confirmed the molecular weight of 13b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 10:1) was used to obtain 120 mg of intermediate 13b.

[0256] Intermediate 13b (120 mg, 0.40 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (34 mg, 0.80 mmol, 2.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC confirmed the absence of 13b. LC-MS confirmed the molecular weight of compound 13. The reaction mixture was quenched with 10% aqueous NaOH and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 30 mg of compound 13 as an off-white solid. HPLC purity: 95.91%; MS m / z (ESI): 238.14 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.32-0.38(m,2H), 0.38-0.43(m,2H), 1.64-1.76(m, 1H), 6.52-6.54(m, 1H), 6.78-6.80 (m, 1H), 6.89 (d, J=7.7Hz, 1H), 7.08 (d, J=2.3Hz, 1H), 8.23 ​​(s, 1H), 10.79 (s, 1H).

[0257] Example 14: Synthesis of 3-{2-[cyclopropyl(trideuteriomethyl)amino]-1,1,2,2-tetradeuterioethyl}-1H-indole-5-ol. The route is as follows:

[0258] 5-(Acetoxy)indole (200 mg, 1.14 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (217 mg, 1.71 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 5-(acetoxy)indole remained. The product was filtered under reduced pressure to obtain 150 mg of intermediate 14a.

[0259] Intermediate 14a (150 mg, 0.56 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Cyclopropyl(trideuteriomethyl)amine hydrochloride (93 mg, 0.84 mmol, 1.5 eq) and TEA (170 mg, 1.68 mmol, 3.0 eq) were added and the mixture was in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 14a, and LC-MS confirmed the molecular weight of 14b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 10:1) was used to obtain 60 mg of intermediate 14b.

[0260] Intermediate 14b (60 mg, 0.20 mmol, 1.0 eq) was dissolved in 5 mL of 2-MTHF. LiAlD4 (17 mg, 0.40 mmol, 2.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC confirmed the absence of 14b. LC-MS confirmed the molecular weight of compound 14. The reaction mixture was quenched with 10% aqueous NaOH and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 10 mg of compound 14 as an off-white solid. HPLC purity: 95.21%; MS m / z (ESI): 238.07 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.27-0.39(m,2H), 0.38-0.46(m,2H), 1.62-1.76(m, 1H), 6.75(m, 1H), 7.03 (d, J=2.3Hz, 1H), 7.12 (d, J=2.3Hz, 1H), 7.23 (d, J=8.5Hz, 1H), 8.91 (s, 1H), 10.72 (s, 1H).

[0261] Example 15: Synthesis of 3-{2-[cyclopropyl(trideuteriomethyl)amino]-1,1,2,2-tetradeuterioethyl}-1H-indole-6-ol. The route is as follows:

[0262] 6-(Acetoxy)indole (200 mg, 1.14 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (217 mg, 1.71 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 6-(acetoxy)indole remained. The product was filtered under reduced pressure to obtain 210 mg of intermediate 15a.

[0263] Intermediate 15a (210 mg, 0.79 mmol, 1.0 eq) was added to 10 mL of ACN. Cyclopropyl(trideuteriomethyl)amine hydrochloride (132 mg, 1.19 mmol, 1.5 eq) and TEA (240 mg, 2.37 mmol, 3.0 eq) were then added. The mixture was in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 15a, and LC-MS confirmed the molecular weight of 15b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 10:1) was used to obtain 120 mg of intermediate 15b.

[0264] Intermediate 15b (120 mg, 0.40 mmol, 1.0 eq) was added to 5 mL of 2-MTHF, and LiAlD4 (34 mg, 0.80 mmol, 2.0 eq) was weighed. The mixture was incubated in an oil bath at 60°C. After 8 h, TLC confirmed the absence of 15b, and LC-MS confirmed the molecular weight of compound 15. The reaction mixture was quenched with 10% aqueous NaOH, extracted with DCM, and the organic phase dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 30 mg of compound 15 as an off-white solid. HPLC purity: 95.08%; MS m / z (ESI): 238.22 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.25-0.31 (m, 2H), 0.40-0.51 (m, 2H), 1.65-1.76 (m, 1H), 6.88-7.02 (m, 1H), 7.15 (d, J = 2.1Hz, 1H), 7.30 (d, J=2.1Hz, 1H), 7.43 (d, J=8.4Hz, 1H), 9.23 (s, 1H), 10.79 (s, 1H).

[0265] Example 16: Synthesis of 3-{2-[cyclopropyl(trideuteriomethyl)amino]-1,1,2,2-tetradeuterioethyl}-1H-indole-7-ol. The route is as follows:

[0266] 7-(Acetoxy)indole (200 mg, 1.14 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (217 mg, 1.71 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 7-(acetoxy)indole remained. The product was filtered under reduced pressure to obtain 210 mg of intermediate 16a.

[0267] Intermediate 16a (210 mg, 0.79 mmol, 1.0 eq) was added to 10 mL of ACN. Cyclopropyl(trideuteriomethyl)amine hydrochloride (132 mg, 1.19 mmol, 1.5 eq) and TEA (240 mg, 2.37 mmol, 3.0 eq) were then added. The mixture was in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 16a, and LC-MS confirmed the molecular weight of 16b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 10:1) was used to obtain 120 mg of intermediate 16b.

[0268] Intermediate 16b (120 mg, 0.40 mmol, 1.0 eq) was added to 5 mL of 2-MTHF, and LiAlD4 (34 mg, 0.80 mmol, 2.0 eq) was weighed. The mixture was incubated in an oil bath at 60°C for 8 h. TLC confirmed the absence of 16b, and LC-MS confirmed the molecular weight of compound 16. The reaction mixture was quenched with 10% aqueous NaOH, extracted with DCM, and the organic phase dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) was used to elute the mixture to afford 20 mg of compound 16 as an off-white solid. HPLC purity: 95.34%; MS m / z (ESI): 238.14 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.34-0.40 (m, 2H), 0.46-0.57 (m, 2H), 1.61-1.80 (m, 1H), 6.85 (d, J = 7.5Hz, 1H), 7.10 (d, J=7.7Hz, 1H), 7.20 (d, J=7.9Hz, 1H), 7.43 (d, J=2.4Hz, 1H), 8.33 (s, 1H), 10.79 (s, 1H).

[0269] Example 17: Synthesis of 3-{2-[cyclopropyl(trideuteriomethyl)amino]-1,1,2,2-tetradeuterioethyl}-1H-indole-5,6-diol. The route is as follows:

[0270] 5,6-(diacetoxy)indole (200 mg, 0.86 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (164 mg, 1.29 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 5,6-(diacetoxy)indole remained. The product was filtered under reduced pressure to obtain 150 mg of intermediate 17a.

[0271] Intermediate 17a (150 mg, 0.46 mmol, 1.0 eq) was added to 10 mL of ACN. Cyclopropyl(trideuteriomethyl)amine hydrochloride (76 mg, 0.69 mmol, 1.5 eq) and TEA (140 mg, 1.38 mmol, 3.0 eq) were then added. The mixture was in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 17a, and LC-MS confirmed the molecular weight of 17b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The elution was performed by column chromatography (PE:EA = 10:1) to afford 80 mg of intermediate 17b.

[0272] Intermediate 17b (80 mg, 0.22 mmol, 1.0 eq) was added to 5 mL of 2-MTHF, and LiAlD4 (18 mg, 0.44 mmol, 2.0 eq) was weighed. The mixture was incubated in an oil bath at 60°C for 8 h. TLC confirmed the absence of 17b, and LC-MS confirmed the molecular weight of compound 17. The reaction mixture was quenched with 10% aqueous NaOH, extracted with DCM, and the organic phase dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) was used to elute the mixture to afford 10 mg of compound 17 as an off-white solid. HPLC purity: 95.05%; MS m / z (ESI): 254.14 [M+H] + ; 1 H NMR(400MHz, DMSO-d6)δ 0.31-0.28(m,2H), 0.46-0.34(m,2H), 1.70-1.65(m,1H), 6.95(s,1H), 7.03(s , 1H), 7.12 (d, J=8.4Hz, 1H), 8.83 (s, 1H), 8.99 (s, 1H), 10.79 (d, J=8.6Hz, 1H).

[0273] Example 18: Synthesis of 4-bromo-3-{2-[cyclopropyl(trideuteriomethyl)amino]-1,1,2,2-tetradeuterioethyl}-1H-indole. The route is as follows:

[0274] 4-Bromoindole (200 mg, 1.02 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (194 mg, 1.53 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 4-bromoindole remained. The product was filtered under reduced pressure to obtain 200 mg of intermediate 18a.

[0275] Intermediate 18a (200 mg, 0.70 mmol, 1.0 eq) was added to 10 mL of ACN. Cyclopropyl(trideuteriomethyl)amine hydrochloride (116 mg, 1.05 mmol, 1.5 eq) and TEA (212 mg, 2.10 mmol, 3.0 eq) were then added. The mixture was incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 18a, and LC-MS confirmed the molecular weight of 18b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Elution was performed by column chromatography (PE:EA = 10:1) to afford 100 mg of intermediate 18b.

[0276] Intermediate 18b (100 mg, 0.31 mmol, 1.0 eq) was added to 5 mL of 2-MTHF, and LiAlD4 (26 mg, 0.62 mmol, 2.0 eq) was weighed. The mixture was incubated in an oil bath at 60°C. After 8 h, TLC confirmed the absence of 18b, and LC-MS confirmed the molecular weight of compound 18. The reaction mixture was quenched with 10% aqueous NaOH, extracted with DCM, and the organic phase dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) afforded 20 mg of compound 18 as a yellow oil. HPLC purity: 95.32%; MS m / z (ESI): 300.04 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.35-0.24(m,2H), 0.49-0.35(m,2H), 1.79-1.75(m,1H), 7.16(d, J=8. 6hZ, 1H), 7.23 (d, J = 7.5Hz, 1H), 7.34-7.30 (m, 1H), 7.61-7.58 (m, 1H), 10.68 (d, J = 8.6Hz, 1H).

[0277] Example 19: Synthesis of 5-bromo-3-{2-[cyclopropyl(trideuteriomethyl)amino]-1,1,2,2-tetradeuterioethyl}-1H-indole. The route is as follows:

[0278] 5-Bromoindole (200 mg, 1.02 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (194 mg, 1.53 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 5-bromoindole remained. The product was filtered under reduced pressure to obtain 200 mg of intermediate 19a.

[0279] Intermediate 19a (200 mg, 0.70 mmol, 1.0 eq) was added to 10 mL of ACN. Cyclopropyl(trideuteriomethyl)amine hydrochloride (116 mg, 1.05 mmol, 1.5 eq) and TEA (212 mg, 2.10 mmol, 3.0 eq) were then added. The mixture was incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 19a, and LC-MS confirmed the molecular weight of 19b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Elution was performed by column chromatography (PE:EA = 10:1) to afford 100 mg of intermediate 19b.

[0280] Intermediate 19b (100 mg, 0.31 mmol, 1.0 eq) was added to 5 mL of 2-MTHF, and LiAlD4 (26 mg, 0.62 mmol, 2.0 eq) was weighed. The mixture was incubated in an oil bath at 60°C. After 8 h, TLC detected no residue of 19b, and LC-MS determined the molecular weight of compound 19. The reaction mixture was quenched with 10% aqueous NaOH, extracted with DCM, and the organic phase dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) was used to obtain 20 mg of compound 19 as a yellow oil. HPLC purity: 95.91%; MS m / z (ESI): 300.06 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.27-0.36(m,2H), 0.47-0.57(m,2H), 1.76-1.89(m,1H), 7.11(d, J=7.5Hz, 1H), 7.20-7.30 (m, 1H), 7.30-7.32 (m, 1H), 7.63 (d, J=2.4Hz, 1H), 10.71 (s, 1H).

[0281] Example 20: Synthesis of 6-bromo-3-{2-[cyclopropyl(trideuteriomethyl)amino]-1,1,2,2-tetradeuterioethyl}-1H-indole. The route is as follows:

[0282] 6-Bromoindole (200 mg, 1.02 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (194 mg, 1.53 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 6-bromoindole remained. The product was filtered under reduced pressure to obtain 200 mg of intermediate 20a.

[0283] Intermediate 20a (200 mg, 0.70 mmol, 1.0 eq) was added to 10 mL of ACN. Cyclopropyl(trideuteriomethyl)amine hydrochloride (116 mg, 1.05 mmol, 1.5 eq) and TEA (212 mg, 2.10 mmol, 3.0 eq) were then added. The mixture was incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 20a, and LC-MS confirmed the molecular weight of 20b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Elution was performed by column chromatography (PE:EA = 10:1) to afford 100 mg of intermediate 20b.

[0284] Intermediate 20b (100 mg, 0.31 mmol, 1.0 eq) was added to 5 mL of 2-MTHF, and LiAlD4 (26 mg, 0.62 mmol, 2.0 eq) was weighed. The mixture was incubated in an oil bath at 60°C. After 8 h, TLC confirmed the absence of 20b, and LC-MS confirmed the molecular weight of compound 20. The reaction mixture was quenched with 10% aqueous NaOH, extracted with DCM, and the organic phase dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) was used to obtain 25 mg of compound 20 as a yellow oil. HPLC purity: 95.22%; MS m / z (ESI): 300.01 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.35-0.24(m,2H), 0.49-0.38(m,2H), 1.69-1.57(m,1H), 7.16(d, J=8.6 Hz, 1H), 7.33-7.29 (m, 1H), 7.54 (d, J = 1.5Hz, 1H), 7.61 (d, J = 7.5Hz, 1H), 10.77 (d, J = 8.6Hz, 1H).

[0285] Example 21: Synthesis of 7-bromo-3-{2-[cyclopropyl(trideuteriomethyl)amino]-1,1,2,2-tetradeuterioethyl}-1H-indole. The route is as follows:

[0286] 7-Bromoindole (200 mg, 1.02 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (194 mg, 1.53 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 7-bromoindole remained. The product was filtered under reduced pressure to obtain 200 mg of intermediate 21a.

[0287] Intermediate 21a (200 mg, 0.70 mmol, 1.0 eq) was added to 10 mL of ACN. Cyclopropyl(trideuterylmethyl)amine hydrochloride (116 mg, 1.05 mmol, 1.5 eq) and TEA (212 mg, 2.10 mmol, 3.0 eq) were then added. The mixture was incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 21a, and LC-MS confirmed the molecular weight of 21b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Elution was performed by column chromatography (PE:EA = 10:1) to afford 100 mg of intermediate 21b.

[0288] Intermediate 21b (100 mg, 0.31 mmol, 1.0 eq) was added to 5 mL of 2-MTHF, and LiAlD4 (26 mg, 0.62 mmol, 2.0 eq) was weighed. The mixture was incubated in an oil bath at 60°C. After 8 h, TLC confirmed the absence of 21b, and LC-MS confirmed the molecular weight of compound 21. The reaction mixture was quenched with 10% aqueous NaOH, extracted with DCM, and the organic phase dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) afforded 12 mg of compound 21 as a yellow oil. HPLC purity: 95.31%; MS m / z (ESI): 300.15 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.31-0.24(m,2H), 0.41-0.34(m,2H), 1.74-1.64(m, 1H), 7.11(d, J= 8.0Hz, 1H), 7.31-7.27 (m, 1H), 7.58-7.48 (m, 1H), 7.66-7.64 (m, 1H), 10.79 (d, J=8.0Hz, 1H)

[0289] Example 22: Synthesis of 5,6-dibromo-3-{2-[cyclopropyl(trideuteriomethyl)amino]-1,1,2,2-tetradeuterioethyl}-1H-indole. The route is as follows:

[0290] 5,6-Dibromoindole (200 mg, 0.73 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (140 mg, 1.10 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 5,6-bromoindole remained. The product was filtered under reduced pressure to obtain 200 mg of intermediate 22a.

[0291] Intermediate 22a (200 mg, 0.55 mmol, 1.0 eq) was added to 10 mL of ACN. Cyclopropyl(trideuteriomethyl)amine hydrochloride (92 mg, 0.83 mmol, 1.5 eq) and TEA (167 mg, 1.65 mmol, 3.0 eq) were then added. The mixture was incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 22a, and LC-MS confirmed the molecular weight of 22b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Elution was performed by column chromatography (PE:EA = 10:1) to afford 100 mg of intermediate 22b.

[0292] Intermediate 22b (100 mg, 0.25 mmol, 1.0 eq) was added to 5 mL of 2-MTHF, and LiAlD4 (21 mg, 0.50 mmol, 2.0 eq) was weighed. The mixture was incubated in an oil bath at 60°C. After 8 h, TLC confirmed the absence of 22b, and LC-MS confirmed the molecular weight of compound 22. The reaction mixture was quenched with 10% aqueous NaOH, extracted with DCM, and the organic phase dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) afforded 22 mg of compound 22 as a yellow oil. HPLC purity: 95.83%; MS m / z (ESI): 380.07 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.39-0.25(m,2H), 0.54-0.43(m,2H), 1.81-1.70(m, 1H), 7.11 (d, J=8.6Hz, 1H), 7.44 (s, 1H), 7.62 (s, 1H), 10.70 (d, J=8.6Hz, 1H).

[0293] Example 23: Synthesis of 3-{2-[(cyclopropylmethyl)(methyl)amino]ethyl}-1H-indole. The route is as follows:

[0294] 3-(2-Bromoethyl)indole (200 mg, 0.89 mmol, 1.0 eq) was weighed and dissolved in 10 mL of ACN. Methylamine (42 mg, 1.34 mmol, 1.5 eq) and TEA (270 mg, 2.67 mmol, 3.0 eq) were then added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 3-(2-bromoethyl)indole. LC-MS confirmed the molecular weight of 23a. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Column chromatography (PE:EA = 1:5) was used to obtain 80 mg of intermediate 23a.

[0295] Intermediate 23a (80 mg, 0.46 mmol, 1.0 eq) was dissolved in 3 mL of ACN. Bromomethylcyclopropane (93 mg, 0.69 mmol, 1.5 eq) and TEA (140 mg, 1.38 mmol, 3.0 eq) were then added. After 5 h, TLC detected no residue of 23a, and LC-MS determined the molecular weight of compound 23. The reaction solution was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) was used to obtain 30 mg of compound 23 as a yellow oil. HPLC purity: 95.77%; MS m / z (ESI): 229.34 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.37-0.45(m, 2H), 1.17-1.39(m, 2H), 1.68-1.87(m, H), 2.21(s, 3H), 2.51-2.52(m, 2H), 2.73-2.86(m, 2H), 2.93-3.06(m, 2H), 7.08(d,J=7.4Hz, 1H), 7.08-7.15(m, 1 H), 7.18 (d, J=2.3Hz, 1H), 7.28-7.37 (m, 1H), 7.52 (d, J=7.8Hz, 1H), 10.67 (s, 1H).

[0296] Example 24: Synthesis of 3-{2-[(cyclopropylmethyl)(trideuteriomethyl)amino]ethyl}-1H-indole. The route is as follows:

[0297] 3-(2-bromoethyl)indole (200 mg, 0.89 mmol, 1.0 eq) was weighed and dissolved in 10 mL of ACN. Deuterated methylamine hydrochloride (95 mg, 1.34 mmol, 1.5 eq) and TEA (270 mg, 2.67 mmol, 3.0 eq) were then added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 3-(2-bromoethyl)indole. LC-MS confirmed the molecular weight of 24a. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Column chromatography (PE:EA = 1:5) was used to obtain 70 mg of intermediate 24a.

[0298] Intermediate 24a (70 mg, 0.39 mmol, 1.0 eq) was dissolved in 3 mL of ACN. Bromomethylcyclopropane (80 mg, 0.59 mmol, 1.5 eq) and TEA (118 mg, 1.17 mmol, 3.0 eq) were then added. After 5 h, TLC revealed no residue of 24a. LC-MS confirmed the molecular weight of compound 24. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 20 mg of compound 24 as a yellow oil. HPLC purity: 95.15%; MS m / z (ESI): 232.40 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.42-0.53 (m, 2H), 1.24-1.39 (m, 2H), 1.62-1.75 (m, H), 2.53 (d, J=6.5Hz, 2H), 2.66-2.77 (m, 2H), 2.8 4-2.99(m, 2H), 7.07-7.14(m, 1H), 7.11-7.17(m, 1H), 7.21-7.22(m, 1H), 7.34-7.36(m, 1H), 7.45-7.50(m, 1H), 10.71(s, 1H).

[0299] Example 25: Synthesis of 1-(cyclopropylmethyl)-3-[2-(piperidin-1-yl)ethyl]indole. The route is as follows:

[0300] 3-(2-Bromoethyl)indole (200 mg, 0.89 mmol, 1.0 eq) was weighed and dissolved in 10 mL of DMF. Piperidine (114 mg, 1.34 mmol, 1.5 eq) and KCO (369 mg, 2.67 mmol, 3.0 eq) were then added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 3-(2-bromoethyl)indole. LC-MS confirmed the molecular weight of 25a. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Elution was performed by column chromatography (PE:EA = 10:1) to afford 150 mg of intermediate 25a.

[0301] Intermediate 25a (150 mg, 0.66 mmol, 1.0 eq) was dissolved in 5 mL of DMF. NaH (53 mg, 1.32 mmol, 2.0 eq) was added and stirred for 30 min. Bromomethylcyclopropane (134 mg, 0.99 mmol, 1.5 eq) was then added. After 5 h, TLC analysis revealed no residue of 25a. LC-MS analysis confirmed the molecular weight of compound 25. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 120 mg of compound 25 as a yellow oil. HPLC purity: 95.72%; MS m / z (ESI): 283.35 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.29-0.35(m,2H), 0.38-0.50(m,2H), 1.03-1.21(m ,H), 1.29-1.43(m,2H), 1.41-1.59(m,4H), 2.38-2.40(m,4H), 2.48-2.55(m ,2H), 2.77-2.79(m,2H), 3.87(d, J=6.9Hz, 2H), 6.97(t, J=7.4Hz, 1H), 7.05 (t, J=7.6Hz, 1H), 7.14 (s, 1H), 7.33 (d, J=8.2Hz, 1H), 7.50 (d, J=7.8Hz, 1H).

[0302] Example 26: Synthesis of N-(cyclopropylmethyl)-N-[2-(1H-indol-3-yl)ethyl]hydroxylamine. The route is as follows:

[0303] 3-(2-Bromoethyl)indole (200 mg, 0.89 mmol, 1.0 eq) was weighed and dissolved in 10 mL of DMF. Hydroxylamine hydrochloride (93 mg, 1.34 mmol, 1.5 eq) and KCO (369 mg, 2.67 mmol, 3.0 eq) were then added. The mixture was in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 3-(2-bromoethyl)indole. LC-MS confirmed the molecular weight of 26a. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Column chromatography (PE:EA = 1:5) was used to obtain 50 mg of intermediate 26a.

[0304] Intermediate 26a (50 mg, 0.28 mmol, 1.0 eq) was dissolved in 3 mL of DMF. Bromomethylcyclopropane (57 mg, 0.42 mmol, 1.5 eq) and K2CO3 (116 mg, 0.84 mmol, 3.0 eq) were then added. After 5 h, TLC detected no residue of 26a. LC-MS confirmed the molecular weight of compound 26. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 10 mg of compound 26 as a yellow oil. HPLC purity: 95.01%; MS m / z (ESI): 231.35 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.45-0.36(m,2H), 0.67-0.54(m,2H), 1.22-1.15(m,H), 2.51(d, J=7.0Hz, 2H), 3.05(t, J=7.0Hz, 2H), 3.25(t, J=7.1Hz, 2H), 7.08-7.05(m, 1H), 7.16-7.11(m, 1H), 7.28-7.22(m, 1H), 7.35(d, J =7.3Hz, 1H), 7.42 (d, J = 7.1Hz, 1H), 7.68 (s, 1H), 10.72 (d, J = 8.3Hz, 1H).

[0305] Example 27: Synthesis of 3-{2-[(cyclopropylmethyl)(2-methylpropan-2-yl)amino]ethyl}-1H-indole. The route is as follows:

[0306] 3-(2-Bromoethyl)indole (200 mg, 0.89 mmol, 1.0 eq) was weighed and dissolved in 10 mL of ACN. 2-Methylpropan-2-amine hydrochloride (147 mg, 1.34 mmol, 1.5 eq) and TEA (270 mg, 2.67 mmol, 3.0 eq) were then added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 3-(2-bromoethyl)indole. LC-MS confirmed the molecular weight of 27a. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Column chromatography (PE:EA = 1:5) was used to obtain 60 mg of intermediate 27a.

[0307] Intermediate 27a (60 mg, 0.28 mmol, 1.0 eq) was dissolved in 3 mL of ACN. Bromomethylcyclopropane (57 mg, 0.42 mmol, 1.5 eq) and TEA (85 mg, 0.84 mmol, 3.0 eq) were then added. After 5 h, TLC detected no residue of 27a, and LC-MS confirmed the molecular weight of compound 27. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) afforded 15 mg of compound 27 as a yellow oil. HPLC purity: 95.36%; MS m / z (ESI): 271.46 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ1.35-1.25(m, 2H), 1.39-1.35(m, 2H), 1.44(, 9H) ,1.73-1.58(m,H),2.18-2.07(m,2H),2.49-2.36(m,2H),2.89-278(m,2H) , 2.95-2.90 (m, 2H), 6.85-6.72 (m, 1H), 6.94 (d, J=8.5Hz, 1H), 7.08-7.00 (m, 1H), 7.25-7.12 (m, 1H), 7.45 (d, J=7.0Hz, 1H), 10.61 (d, J=8.6Hz, 1H).

[0308] Example 28: Synthesis of 3-(2-{[2-methoxy-5-(trifluoromethyl)phenyl](methyl)amino}ethyl)-1H-indole. The route is as follows:

[0309] 3-(2-bromoethyl)indole (200 mg, 0.89 mmol, 1.0 eq) was weighed and dissolved in 10 mL of ACN. 2-Methoxy-5-trifluoromethylaniline (256 mg, 1.34 mmol, 1.5 eq) and TEA (270 mg, 2.67 mmol, 3.0 eq) were then added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 3-(2-bromoethyl)indole. LC-MS confirmed the molecular weight of 28a. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Column chromatography (PE:EA = 10:1) was used to obtain 40 mg of intermediate 28a.

[0310] Intermediate 28a (40 mg, 0.12 mmol, 1.0 eq) was dissolved in 3 mL of THF. Formaldehyde (5 mg, 0.18 mmol, 1.5 eq) and acetic acid (7 mg, 0.12 mmol, 1.0 eq) were then added. 8 h later, NaBH3CN (15 mg, 0.24 mmol, 2.0 eq) was added. After 12 h, the molecular weight of compound 28 was determined by LC-MS. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 5:1) was used to obtain 10 mg of compound 28 as a yellow oil. HPLC purity: 95.21%; MS m / z (ESI): 349.21 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ2.43 (t, J=7.1Hz, 2H), 2.81 (t, J=7.0Hz, 2H), 3.04 (s, 3H), 3.85 (s, 3H), 6.84 (d, J=7.5Hz, 1H), 7.03-6.94 (m, 1H ), 7.08-7.04 (m, 1H), 7.12 (d, J = 8.3Hz, 1H), 7.21 (m, 1H), 7.32 (m, 1H), 7.45-7.36 (m, 1H), 7.58 (d, J = 7.3Hz, 1H), 10.69 (d, J = 8.6Hz, 1H).

[0311] Example 29: Synthesis of 3-{2-[methyl(pyridin-2-ylmethyl)amino]ethyl}-1H-indole. The route is as follows:

[0312] 3-(2-bromoethyl)indole (200 mg, 0.89 mmol, 1.0 eq) was weighed and dissolved in 10 mL of ACN. 2-Pyridinemethylamine (145 mg, 1.34 mmol, 1.5 eq) and TEA (270 mg, 2.67 mmol, 3.0 eq) were then added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 3-(2-bromoethyl)indole. LC-MS confirmed the molecular weight of 29a. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Column chromatography (PE:EA = 1:5) was used to obtain 90 mg of intermediate 29a.

[0313] Intermediate 29a (90 mg, 0.36 mmol, 1.0 eq) was dissolved in 3 mL of THF. Formaldehyde (16 mg, 0.54 mmol, 1.5 eq) and acetic acid (22 mg, 0.36 mmol, 1.0 eq) were then added. 8 h later, NaBH3CN (45 mg, 0.72 mmol, 2.0 eq) was added. After 12 h, the molecular weight of compound 29 was determined by LC-MS. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 5:1) was used to obtain 30 mg of compound 29 as a yellow oil. HPLC purity: 95.12%; MS m / z (ESI): 266.32 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ2.47(s,3H), 2.81-2.70(m,2H), 2.97-2.83(m,2H) , 3.72 (s, 2H), 7.11 (d, J = 8.1Hz, 1H), 7.14 (s, 1H), 7.18 (d, J = 8.3Hz, 1H), 7 .33-7.23(m,1H),7.35(d,J=7.1Hz,1H),7.54-7.45(m,1H),7.59(d,J=7.0 Hz, 1H), 7.71-7.64 (m, 1H), 8.58 (d, J = 7.6Hz, 1H), 10.70 (d, J = 8.6Hz, 1H).

[0314] Example 30: Synthesis of 3-{2-[4-(cyclopropylmethyl)piperazin-1-yl]ethyl}-1H-indole. The route is as follows:

[0315] 3-(2-Bromoethyl)indole (200 mg, 0.89 mmol, 1.0 eq) was weighed and dissolved in 10 mL of ACN. 1-Cyclopropylmethylpiperazine (188 mg, 1.34 mmol, 1.5 eq) and TEA (270 mg, 2.67 mmol, 3.0 eq) were then added and incubated in an oil bath at 60°C. After 8 h, TLC confirmed the absence of 3-(2-bromoethyl)indole. LC-MS confirmed the molecular weight of compound 30. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 5:1) was performed to yield 180 mg of compound 30 as a yellow solid. HPLC purity: 95.95%; MS m / z (ESI): 284.35 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ0.29-0.52(m,2H), 0.66-0.84(m,2H), 1.23-1.41(m, 1H), 2.25 (d, J=6.6Hz, 2H), 2.54-2.56 (m, 4H), 2.56-2.58 (m, 4H), 2.90-2.92 ( m, 2H), 2.86-3.04 (m, 2H), 6.91 (d, J = 7.4Hz, 1H), 7.08 (d, J = 7.5Hz, 1H), 7.27 (d, J=2.2Hz, 1H), 7.44 (d, J=8.0Hz, 1H), 7.64 (d, J=7.8Hz, 1H), 10.70 (s, 1H).

[0316] Example 31: Synthesis of 2-{[2-(1H-indol-3-yl)ethyl](methyl)amino}propan-2-ol. The route is as follows:

[0317] 3-(2-Bromoethyl)indole (200 mg, 0.89 mmol, 1.0 eq) was weighed and dissolved in 10 mL of ACN. 2-(Methylamino)propan-2-ol (119 mg, 1.34 mmol, 1.5 eq) and TEA (450 mg, 4.45 mmol, 5.0 eq) were then added and incubated in an oil bath at 60°C for 12 h. The molecular weight of compound 31 was determined by LC-MS. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 5:1) was used to obtain 10 mg of compound 31 as a yellow oil. HPLC purity: 95.21%; MS m / z (ESI): 233.37 [M+H] + ; 1H NMR (600MHz, DMSO-d6) δ1.12 (s, 6H), 2.50 (s, 3H), 3.00-2.91 (m, 4H), 4.75 (s, 1H), 7.03-6.95 (m, 1H), 7.11-7.05 (m, 1H), 7.23 (d, J = 2.4Hz, 1H), 7.35 (d, J = 8.1Hz, 1H), 7.53 (d, J = 7.9Hz, 1H), 10.90 (s, 1H).

[0318] Example 32: Synthesis of 3-{2-[cyclopropyl(methyl)amino]ethyl}-1H-indole-5-amine. The route is as follows:

[0319] 5-Nitroindole (200 mg, 1.23 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (235 mg, 1.85 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected no residual 5-nitroindole. The product was filtered under reduced pressure to obtain 200 mg of intermediate 32a.

[0320] Intermediate 32a (200 mg, 0.79 mmol, 1.0 eq) was added to 10 mL of ACN. Cyclopropyl(methyl)amine hydrochloride (128 mg, 1.19 mmol, 1.5 eq) and TEA (240 mg, 2.37 mmol, 3.0 eq) were then added. The mixture was incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of 32a, and LC-MS confirmed the molecular weight of 32b. The reaction mixture was washed with saturated brine and extracted with EA. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Elution was performed by column chromatography (PE:EA = 10:1) to afford 100 mg of intermediate 32b.

[0321] Intermediate 32b (100 mg, 0.35 mmol, 1.0 eq) was added to 5 mL of 2-MTHF, and LiAlH₄ (27 mg, 0.70 mmol, 2.0 eq) was weighed. The mixture was incubated in an oil bath at 60°C. After 8 h, TLC confirmed the absence of 32b, and LC-MS confirmed the molecular weight of compound 32. The reaction mixture was quenched with 10% aqueous NaOH, extracted with DCM, and the organic phase dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) afforded 15 mg of compound 32 as a yellow oil. HPLC purity: 95.36%; MS m / z (ESI): 230.15 [M+H] + ; 1H NMR (600MHz, DMSO-d6) δ0.34-0.30 (m, 2H), 0.49-0.44 (m, 2H), 1.71-1.66 (m, 1H), 2.34 (s, 3H), 2.73-2.70 (m, 4H), 4.45 (s, 2H), 6.47-6.42 (m, 1H), 6.64 (d, J=2.1Hz, 1H), 6.92 (d, J=2.3Hz, 1H), 7.01 (d, J=8.4Hz, 1H), 10.25 (s, 1H).

[0322] Example 33: Synthesis of 3-{2-[cyclopropyl(methyl)amino]ethyl}-1H-indole. The route is as follows:

[0323] 3-(2-Bromoethyl)indole (200 mg, 0.89 mmol, 1.0 eq) was weighed and dissolved in 10 mL of acetonitrile. N-methylcyclopropylamine hydrochloride (191 mg, 1.78 mmol, 2.0 eq) and TEA (450 mg, 4.45 mmol, 5.0 eq) were then added and incubated in an 80°C oil bath. After 5 h, TLC confirmed the absence of 3-(2-bromoethyl)indole. LC-MS confirmed the molecular weight of compound 33. The reaction mixture was washed with saturated brine and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) was performed to yield 80 mg of compound 33 as a yellow oil. HPLC purity: 95.66%; MS m / z (ESI): 215.37 [M+H] + ; 1 H NMR (600MHz, DMSO-d6) δ10.77 (s, 1H), 7.49 (d, J = 7.9Hz, 1H), 7.32 (d, J = 8.1Hz, 1H), 7.12 (d, J = 2.3Hz, 1H), 7.07-7.02 (m, 1H), 6 .99-6.94(m,1H),2.88-2.81(m,2H),2.80-2.73(m,2H),2.35(s,3H),1.75-1.67(m,1H),0.49-0.38(m,2H),0.35-0.27(m,2H).

[0324] Example 34: Synthesis of 3-{2-[cyclopropyl(methyl)amino]ethyl}-1H-indole-4-ol. The route is as follows:

[0325] 4-(Acetoxy)indole (200 mg, 1.14 mmol, 1.0 eq) was weighed and dissolved in 10 mL of MTBE. Oxalyl chloride (217 mg, 1.71 mmol, 1.5 eq) was slowly added dropwise under ice bath, accompanied by solid precipitation. After 3 h, TLC detected that no 4-(acetoxy)indole remained. The product was filtered under reduced pressure to obtain 210 mg of intermediate 34a.

[0326] Intermediate 34a (210 mg, 0.79 mmol, 1.0 eq) was dissolved in 10 mL of ACN. Cyclopropyl(methyl)amine hydrochloride (128 mg, 1.19 mmol, 1.5 eq) and TEA (400 mg, 3.95 mmol, 5.0 eq) were added and incubated in an oil bath at 60°C. After 5 h, TLC confirmed the absence of intermediate 34a. LC-MS confirmed the molecular weight of intermediate 34b. The reaction mixture was washed with saturated brine and extracted with DCM. The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure. Elution was performed by column chromatography (PE:EA = 10:1) to afford 100 mg of intermediate 34b.

[0327] Intermediate 34b (100 mg, 0.33 mmol, 1.0 eq) was dissolved in 5 mL of 2-methyltetrahydrofuran, and LiAlH4 (63 mg, 1.65 mmol, 5.0 eq) was weighed and incubated in an oil bath at 60°C. After 8 h, TLC detected no residue of intermediate 34b. LC-MS determined the molecular weight of compound 34. The reaction solution was quenched with 10% aqueous NaOH, extracted with DCM, and the organic phase dried over anhydrous Na2SO4 and concentrated under reduced pressure. Column chromatography (PE:EA = 1:1) yielded 30 mg of compound 34 as an off-white solid with HPLC purity of 95.97%; LC-MS (ESI) m / z: 231.29 (M+H). + ; 1 H NMR (600MHz, DMSO-d6) δ10.57 (s, 1H), 9.87 (s, 1H), 6.90 (d, J = 2.2Hz, 1H), 6.78 (d, J = 7.6Hz, 1H), 6.74 (dd, J = 8.1, 1.0Hz, 1H), 6.26 (dd, J =7.4, 1.0Hz, 1H), 2.91 (t, J = 7.2Hz, 2H), 2.80 (d, J = 7.2Hz, 2H), 2.36 (s, 3H), 1.76 (s, 1H), 0.42 (dd, J = 6.6, 2.3Hz, 2H), 0.38-0.23 (m, 2H).

[0328] Biological activity test

[0329] 1. 5-HT 2A Binding affinity assay

[0330] 1. Experimental equipment and reagents

[0331] 5-HT 2A -HEK293 cells were purchased from WuXi AppTec; polyethyleneimine was purchased from Sigma, P3143; 96-well plates were purchased from Agilent, #5042-1385; 3 [H]-Ketanserin was purchased from Sigma, USA, S006; Filtermate collector was purchased from Perkin Elmer, C961961; TopSeal-A sealing membrane was purchased from Perkin Elmer, #6050185; Unifilter-96GF / C filter plate was purchased from Perkin Elmer; Microscint 20 cocktail scintillation fluid was purchased from Perkin Elmer, #6013329.

[0332] 2. Experimental Preparation

[0333] The test compound was dissolved in DMSO to 0.02 mM and serially diluted 4-fold to 8 concentrations; the detection buffer solution was 50 mM Tris-HCl, pH 7.4, and the washing buffer solution was 50 mM Tris-HCl, pH 7.4.

[0334] 3. Experimental Procedure

[0335] 1 μL of the test compound (LC) at different concentrations and 1 μL of DMSO (HC) were added to the 5-HT incubation chamber containing 100 μL of buffer solution. 2a -HEK293 cells in a 96-well plate, and then add 100 μL of radioligand [ 3 H]-Ketanserin (1 μM). Incubate at room temperature at 3000 rpm. Then, soak the Unifilter-96GF / C filter plate with 50 μL of 0.3% polyethyleneimine per well for 0.5 hour at room temperature. Filter the reaction mixture using a Filtermate collector and wash the plate four times with cold wash buffer. Dry the filter plate at 50°C for 1 hour, add 50 μL of Microscint 20 cocktail scintillation fluid, and seal the plate with TopSeal-A sealing film. Let it stand and detect in a Perkin Elmer MicroBeta2 counter. 3 H] content.

[0336] 4. Analysis methods and results

[0337] The inhibition rate was calculated using the formula: % inhibition rate = (1 - (assay well - mean value_LC) / (mean value_HC - mean value_LC)) * 100%.

[0338] Data were analyzed using Prism 5. The data were fit using a "log(inhibitor) vs. response - variable slope" model and are shown in Table 1.

[0339] Table 1 5-HT 2A Receptor binding affinity data *Data from Anna Rickli et al., European Neuropsychopharmacology, 2016

[0340] As can be seen from Table 1, compared with DMT and Psilocin, compounds 13, 14 and 19 have a strong affinity for 5-HT. 2A Higher binding affinity.

[0341] 2. FLIPR Calcium Assays in Whole Cells

[0342] 1. Experimental equipment and reagents

[0343] 384-well plates were purchased from Greiner, #781090; Fluo-4 Direct TM Crystals were purchased from Invitrogen, F10471.

[0344] 2. Experimental Preparation

[0345] The test compound was serially diluted 4-fold to 10 concentrations for later use; probenecid was dissolved in FLIPR assay buffer to prepare a 2.5 mM test solution for later use; 25 mg of poly-L-lysine hydrobromide was added to 500 mL of ddH2O to prepare the coating solution; a vial of Fluo-4 Direct TM Crystals, add 10 mL of FLIPR Assay Buffer to the vial to prepare Fluo-4 Direct TM Loading buffer;

[0346] 3. Experimental Procedure

[0347] 5HT 2A HEK293 cells were trypsinized, centrifuged and the culture medium removed, and the cells were resuspended in growth medium and counted at 10 × 10 5 / mL density was seeded into a 384-well plate treated with coating solution and incubated overnight at 37℃, 5% CO2. The prepared test compound solution was added to the 384-well compound plate. Remove the cell plate and add 20μL of assay buffer and 20μL of 2×Fluo-4 Direct TMThe loading buffer was added to a 384-well plate and incubated at 37°C, 5% CO2 for 50 minutes and at room temperature for 10 minutes. The cell plate and compound plate were then placed in the FLIPR system, 10 μL of compound and test solvent were transferred from the compound plate to the cell plate, and the fluorescence signal was read.

[0348] 4. Analysis methods and results

[0349] The "max-min" values ​​from readings 1 to 90 were calculated to generate the final signal for % effect calculation; data were analyzed using the Prism curve fit equation "log(agonist) vs. response - variable slope." Table 2 shows the results of these assays.

[0350] Table 2 Effects of compounds on FLIPR calcium concentration in cells *Data from Anna Rickli et al., European Neuropsychopharmacology, 2016

[0351] As can be seen from the table, by measuring the changes in calcium ion levels, it was found that compounds 13 and 19 can significantly activate intracellular 5-HT 2A The ability of compounds 24 and 25 to activate intracellular 5-HT2A receptors is not as good as that of DMT, but is stronger than that of compound 23 and Psilocin.

[0352] 3. Experiment on the stability of liver microsomes

[0353] 1. Experimental equipment and reagents

[0354] Male SD rat liver microsomes were purchased from Shanghai Ruide Liver Disease Research Co., Ltd., LM-DS-02M; testosterone was purchased from Shanghai Aladdin Biochemical, L2209423; 7-hydroxycoumarin was purchased from Shanghai Aladdin Biochemical, A2224109; NADPH was purchased from Biyuntian Biotechnology; D-glucarboxylic acid-1,4-lactone-water was purchased from Shanghai Bid Pharmaceutical, GCP490; HPLC-acetonitrile was purchased from Wuhan Futon, FT36F121301; formic acid was purchased from Chengdu Kelong, 2023020601; HPLC instrument was purchased from Thermo, U3000.

[0355] 2. Experimental Preparation

[0356] Samples obtained at various time points in the liver microsome incubation system were precipitated with 3 volumes of acetonitrile, centrifuged, and the supernatant was transferred to a liquid phase sample vial using a pipette; NADPH regeneration system (15 mM NADPH and 3.2 mM magnesium chloride); UGT incubation system (10.8 mM UDPGA, 10.8 mM D-glucaric acid-1,4-lactone, and 83.8 μg / mL alamethicone)

[0357] 3. Experimental Procedure

[0358] Refer to the incubation system recommended by Shanghai Ruizhi Chemical Research Co., Ltd. and Suzhou Huizhi Heyuan Biotechnology Co., Ltd., taking a total volume of 60 μL per incubation system as an example, the system includes 0.1 M buffer, 6 mg / mL rat liver microsomal protein, NADPH regeneration system, UGT incubation system, and the appropriate concentration of the test compound. Incubate at 37°C, 600 rpm, with each sample replicated three times. Testosterone was used as a positive control for Phase I metabolic reaction, 7-hydroxycoumarin was used as a positive control for Phase II metabolic reaction, and the absence of the NADPH regeneration system and UGT system served as a negative control. The reaction was terminated by adding three volumes of acetonitrile (containing 0.5% formic acid) at predetermined reaction time points, such as 0, 5, 15, 30, 60, 90, and 120 min.

[0359] 4. Analysis methods and results

[0360] The HPLC detection of each compound in the liver microsome incubation system at each time point of the liquid chromatography peak area value was statistically analyzed, and the obtained data were imported into Excel software for processing and analysis to obtain the residual percentage of each compound after metabolism in the liver microsome incubation system-time scatter plot and its half-life (T 1 / 2 ) value. The specific data processing method is as follows:

[0361] 1) Compound remaining percentage-time graph:

[0362] The formula for calculating the remaining percentage of the compound (Percent Remaining%) is:

[0363] Percent Remaining%=A0 / At*100%

[0364] A0: Liquid chromatography peak area response value of the compound in the liver microsome incubation system at 0h.

[0365] At:th, the liquid chromatography peak area response value of the compound in the liver microsome incubation system.

[0366] This figure shows the metabolic trends of compounds in the liver microsome incubation system.

[0367] 2)T 1 / 2 :

[0368] T 1 / 2 =ln2 / k

[0369] k: slope of the trend line fitted on the ln(Percent Remaining%)-time graph.

[0370] This test used Microsoft Office Excel to process the data. Based on the obtained data, a scatter plot of the remaining percentage of the compound versus time was drawn, and the half-life of each compound was calculated. The data are shown in Table 3.

[0371] Table 3 Liver microsome stability

[0372] The above test results show that compared with compounds 23, 33 and 34, the half-lives of compounds 24, 12 and 13 with deuteration at specific sites are significantly shortened, the metabolic clearance rate is increased, and the safety of the drug is improved.

Claims

1. A compound as represented by formula (I), or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof; in, R1 and R2 are each independently selected from the following groups: hydroxyl, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, unsubstituted C3-C6 cycloalkyl, substituted C3-C6 cycloalkyl, unsubstituted aryl, substituted aryl, unsubstituted heteroaryl and substituted heteroaryl; Here, the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, substituted C3-C6 cycloalkyl, substituted aryl or substituted heteroaryl refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, halogen, halogenated C1-C3 alkyl, halogenated C1-C3 alkoxy, C3-C6 cycloalkyl, aryl and heteroaryl; or R1 and R2 form an unsubstituted nitrogen-containing heterocycle or a substituted nitrogen-containing heterocycle with the nitrogen atom to which they are directly attached; the substituted nitrogen-containing heterocycle is substituted by 1-3 groups independently selected from the following groups: unsubstituted C1-C6 alkyl and substituted C1-C6 alkyl; the substituted C1-C6 alkyl is substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, halogen, halogenated C1-C3 alkyl, C3-C6 cycloalkyl, aryl and heteroaryl; R3, R4, R5 and R6 are independently selected from hydrogen, deuterium and substituted C1-C6 alkyl; or, R3 and R4 or R5 and R6 form a -C(O)- group or a -C(S)- group with the carbon atom to which they are connected; herein, the substituted C1-C6 alkyl refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, halogen, halogenated C1-C3 alkyl, C3-C6 cycloalkyl, aryl and heteroaryl; R7 is one, two, three or four and is independently selected from hydrogen, deuterium, halogen, amino, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, C1-C6 alkanoyloxy, aromatic acyloxy, heteroaroyloxy, C1-C6 alkoxy substituted C1-C6 alkanoyloxy, C1-C6 alkanesulfonyloxy, aromatic sulfonyloxy, substituted aromatic sulfonyloxy, phosphoryloxy Here, the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, or substituted arylsulfonyloxy refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, phenyl and substituted phenyl, and here, the substituted phenyl refers to substituted by 1-3 groups independently selected from the following groups: halogen, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, phenyl and C1-C6 alkanoyloxy; R8 is hydrogen, deuterium, substituted C1-C6 alkyl, unsubstituted C3-C6 cycloalkyl or substituted C3-C6 cycloalkyl, wherein the substituted C3-C6 cycloalkyl refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, halogen, halogenated C1-C3 alkyl, C3-C6 cycloalkyl, aryl and heteroaryl; the substituted C1-C6 alkyl refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkoxy, halogen, halogenated C1-C3 alkyl, C3-C6 cycloalkyl, aryl and heteroaryl; Y is N or CR 11 ; When Y is N, R9 and R 10 are independently hydrogen, hydroxyl or thiol, or R9 and R 10 and the carbon atom to which it is connected forms a -C(O)- group or a -C(S)- group; when Y is CR 11 When R 10 With R 11 forms a bond, and R9 is hydrogen, hydroxy, amino, di(C1-C4alkyl)amino or mercapto; And it is stipulated that when Y is CR 11 , R 10 With R 11 When forming a bond, R8 is hydrogen, R9 is hydrogen, one or both of R3 and R4 are deuterium, R5 and R6 are both hydrogen, R1 and R2 are not selected from the group consisting of methyl, deuterated methyl, ethyl, propyl, deuterated ethyl and deuterated propyl; and / or When Y is CR 11 , R 10 With R 11 forms a bond, R8 is hydrogen, R9 is hydrogen, R3, R4, R5 and R6 are all deuterium, R1 and R2 are both deuterated methyl, and R7 is not hydrogen, fluorine, methoxy, deuterated methoxy, benzyl ester phosphoryloxy, phosphoryloxy or hydroxy; and / or When Y is CR 11 , R 10 With R 11 forms a bond, R8 is hydrogen, R9 is hydrogen, R3, R4, R5 and R6 are all hydrogen, R1 and R2 cannot be deuterated methyl at the same time, and, when R1 is deuterated methyl, deuterated ethyl or deuterated propyl, R2 is not methyl, ethyl, propyl or deuterated ethyl; and / or When Y is CR 11 , R 10 With R 11 When forming a bond, R8 is hydrogen, R9 is hydrogen, R3, R4, R5 and R6 are all hydrogen, R1 is methyl, ethyl, propyl, isopropyl, allyl or cyclopropyl, R2 is methyl, ethyl, propyl, isopropyl, allyl, isobutyl, cyclopropylmethyl, cyclopropyl, benzyl or phenyl, R7 is not hydrogen, hydroxy, fluoro, methyl or methoxy; and / or; When Y is CR 11 , R 10 With R 11 forms a bond, R8 is hydrogen, R9 is hydrogen, R3, R4, R5 and R6 are all hydrogen, R1 is propyl or ethyl, when R2 is propyl, R7 is not hydroxy, methoxy, acetoxy, phosphoryloxy, p-nitrobenzenesulfonyloxy, p-trifluoromethylbenzoyloxy, p-fluorobenzoyloxy, pivaloyloxy, methanesulfonyloxy, amino, fluorine, chlorine, bromine, iodine, methyl or trifluoromethyl; and / or; When Y is CR 11 , R 10 With R 11 forms a bond, R8 is hydrogen, R9 is hydrogen, R3, R4, R5 and R6 are all hydrogen, R1 is methyl, R2 is methyl or ethyl, and R7 is not hydroxy, methoxy, acetoxy, phosphoryloxy, amino, fluorine, chlorine, bromine, iodine, methyl or trifluoromethyl; and / or When Y is CR 11 , R 10 With R 11 forms a bond, R8 is hydrogen, R9 is hydrogen, at least two of R3, R4, R5 and R6 are deuterium and the others are hydrogen or all are deuterium, R1 is methyl, when R2 is methyl, R7 is not methoxy; and / or When Y is CR 11 , R 10 With R 11 When a bond is formed, R8 is hydrogen, R9 is hydrogen, R3, R4, R5 and R6 are all hydrogen, R1 and R2 form a nitrogen-containing heterocyclic ring with the nitrogen atom to which they are directly connected, and R7 is not hydrogen, hydroxy, methoxy, fluorine, chlorine, bromine or iodine.

2. The compound according to claim 1, or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof, wherein: When Y is N, formula (I) is formula (IA): In formula (IA), R1-R8 are as defined in formula (I), R9 and R 10 are independently hydrogen, hydroxyl or thiol, or R9 and R 10 and its connected carbon atom to form a -C(O)- group or a -C(S)- group; Y is CR 11 When, formula (I) is formula (IB): In formula (IB), R1-R8 are as defined in formula (I), and R9 is hydrogen, hydroxy, amino, di(C1-C4 alkyl)amino or mercapto.

3. The compound according to claim 1 or 2, or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof, wherein: R1 and R2 are each independently selected from the following groups: hydroxyl, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, unsubstituted C3-C6 cycloalkyl, substituted C3-C6 cycloalkyl, unsubstituted aryl and unsubstituted heteroaryl; herein, the substituted C1-C6 alkyl, substituted C1-C6 alkoxy or substituted C3-C6 cycloalkyl refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, halogen, halogenated C1-C3 alkyl, halogenated C1-C3 alkoxy, C3-C6 cycloalkyl, phenyl, substituted phenyl, pyridyl and pyrimidyl; the substituted phenyl refers to substituted by 1-3 groups independently selected from the following groups: halogen, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, phenyl and C1-C3 alkanoyloxy; Preferably, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl or tert-butyl; Preferably, the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy or tert-butoxy; Preferably, the C3-C6 cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; Preferably, the aryl group is phenyl or naphthyl; Preferably, the heteroaryl group is pyridyl or pyrimidinyl; Preferably, the substituents of the substituted C1-C6 alkyl are independently selected from the following 1-3 groups: deuterium, hydroxyl, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, fluorine, chlorine, bromine, iodine, trifluoromethyl, trifluoromethoxy, cyclopropyl, phenyl and pyridyl; Preferably, the substituents of the substituted C1-C6 alkoxy group are independently selected from the following 1-3 groups: deuterium, fluorine, chlorine, bromine and iodine; Preferably, the substituents of the substituted C3-C6 cycloalkyl are independently selected from the following 1-3 groups: deuterium, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, fluorine, chlorine, bromine, iodine, trifluoromethyl, trifluoromethoxy, cyclopropyl, phenyl and pyridyl.

4. A compound according to any one of claims 1 to 3, or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, wherein R1 and R2 are each independently selected from the group consisting of hydroxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, cyclopropyl, substituted cyclopropyl, deuterated methyl, cyclopropylmethyl, pyridine-substituted methyl, phenyl and substituted phenyl; wherein the substituted cycloalkyl refers to substituted with a substituent selected from the group consisting of deuterium, fluorine, chlorine, bromine and iodine; and the substituted phenyl refers to substituted with a substituent selected from the group consisting of deuterium, hydroxy, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, cyclopropyl and phenyl; Preferably, R1 and R2 are each independently selected from the following groups: hydroxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-hydroxyisopropyl, tert-butyl, cyclopropyl, deuterated cyclopropyl, fluorocyclopropyl, deuterated methyl, cyclopropylmethyl Here, the substituted phenyl group refers to a substituted group selected from the following groups: methoxy and trifluoromethyl; Preferably, R1 and R2 are each independently selected from the following groups: hydroxy, methyl, trideuteromethyl, ethyl, n-propyl, isopropyl, n-butyl, 2-hydroxyisopropyl, tert-butyl, cyclopropyl, 2-fluorocyclopropyl, 2-deuterocyclopropyl, 2,2-dideuterocyclopropyl, 2,2,3,3-tetradeuterocyclopropyl, cyclopropylmethyl, (pyridin-2-yl)methyl, phenyl and (5-trifluoromethyl-2-methoxy)phenyl.

5. The compound of claim 1 or 2, or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated product, metabolite or prodrug thereof, wherein R1 and R2 form an unsubstituted nitrogen-containing heterocycle or a substituted nitrogen-containing heterocycle with the nitrogen atom to which they are directly attached; wherein the nitrogen-containing heterocycle is piperidine or piperazine; and the substituted nitrogen-containing heterocycle is substituted by 1 to 3 groups independently selected from the following: methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, cyclopropyl, cyclopropylmethyl and phenyl; Preferably, R1 and R2 together with the nitrogen atom to which they are directly attached form piperidine or 4-(cyclopropylmethyl)piperazine.

6. The compound according to any one of claims 1 to 2 and 5, or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof, wherein: R3, R4, R5 and R6 are independently selected from hydrogen and deuterium; or, R3, R4 or R5, R6 and the carbon atom to which they are connected form a -C(O)- group or a -C(S)- group; Preferably, R3, R4, R5 and R6 are all deuterium; or, R3, R4, R5 and R6 are all hydrogen.

7. The compound according to any one of claims 1 to 6, or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof, wherein: R7 is one, two, three or four, and each is independently selected from the following substituents: hydrogen, deuterium, amino, fluorine, chlorine, bromine, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, C1-C6 alkanoyloxy, benzoyloxy, C1-C6 alkoxy substituted C1-C6 alkanoyloxy, C1-C6 alkanesulfonyloxy, benzenesulfonyloxy, substituted benzenesulfonyloxy, phosphoryloxy Here, the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, or substituted benzenesulfonyloxy refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, phenyl and substituted phenyl, and here, the substituted phenyl refers to substituted by 1-3 groups independently selected from the following groups: fluorine, chlorine, bromine, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, phenyl and C1-C6 alkanoyloxy; Preferably, R7 is one, two, three or four, and each is independently selected from the following groups: hydrogen, deuterium, amino, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, benzyl, methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, benzyloxy, substituted benzyloxy, formyloxy, acetoxy, propionyloxy, benzoyloxy, tert-butoxycarbonyloxy, methoxycarbonyloxy, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, phosphoryloxy and hydroxyl; Here, the substituted benzyloxy means that its phenyl ring is substituted by 1-3 groups independently selected from the following groups: fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, hydroxyl, phenyl, formyloxy, acetoxy and propionyloxy; Preferably, R7 is one, two, three or four, and each is independently selected from the following groups: hydrogen, deuterium, hydroxyl, amino, fluorine, chlorine, bromine, 1,1-dideuteroethyl, methoxy, (4-acetyloxy)benzyloxy, acetoxy, methoxycarbonyloxy, phosphoryloxy, and methanesulfonyloxy.

8. The compound of any one of claims 1 to 7, or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof, wherein R8 is selected from the following substituents: hydrogen, cyclopropylmethyl, deuterated methyl.

9. The compound according to any one of claims 1 to 8, or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof, wherein the formula (I) is the formula (IB), wherein: In formula (IB), R1 and R2 are each independently selected from the group consisting of hydroxy, methyl, trideuteromethyl, ethyl, n-propyl, isopropyl, 2-hydroxyisopropyl, n-butyl, tert-butyl, cyclopropyl, 2-fluorocyclopropyl, 2-deuterocyclopropyl, 2,2-dideuterocyclopropyl, 2,2,3,3-tetradeuterocyclopropyl, cyclopropylmethyl, (pyridin-2-yl)methyl, phenyl and (5-trifluoromethyl-2-methoxy)phenyl; R3, R4, R5 and R6 are all deuterium; R7 is one, two, three or four and is independently selected from the following groups: hydrogen, deuterium, amino, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, benzyl, methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, benzyloxy, substituted benzyloxy, formyloxy, acetoxy, propionyloxy, benzoyloxy, tert-butoxycarbonyloxy, methoxycarbonyloxy, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, phosphoryloxy and hydroxyl; Here, the substituted benzyloxy group refers to a benzyl ring substituted by 1 to 3 groups independently selected from the following groups: fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, hydroxyl, phenyl, formyloxy, acetoxy and propionyloxy; R8 is selected from the following substituents: hydrogen, cyclopropylmethyl, deuterated methyl; In formula (I), Y is N or CR 11 , where R 10 With R 11 Form a bond; R9 is hydrogen, amino or dimethylamino.

10. The compound of claim 9, or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof, wherein: In formula (IB), R1 is -CD3, and R2 is cyclopropyl or cyclopropylmethyl; R3, R4, R5 and R6 are all deuterium; R7 is one, two, three or four and is independently selected from the following groups: hydrogen, amino, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, benzyl, methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, benzyloxy, formyloxy, acetyloxy, propionyloxy, benzoyloxy, tert-butoxycarbonyloxy, methoxycarbonyloxy, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, phosphoryloxy and hydroxyl; R8 is a substituent selected from the following: hydrogen; R9 is hydrogen, amino or dimethylamino.

11. The compound according to claim 1, or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof, wherein: Formula (I) is Formula (IC): Wherein, in formula (IC), n is 0 or 1; R1 is an unsubstituted C1-C6 alkyl group or a substituted C1-C6 alkyl group, wherein the substituted C1-C6 alkyl group refers to a group substituted by 1 to 3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, hydroxy, halogen, halogenated C1-C3 alkyl, halogenated C1-C3 alkoxy, C3-C6 cycloalkyl, aryl and heteroaryl; R7 is one, two, three or four and each is independently selected from hydrogen, deuterium, amino, halogen, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxy, substituted C1-C6 alkoxy, C1-C6 alkanoyloxy, aromatic acyloxy, heteroaroyloxy, C1-C6 alkoxy-substituted C1-C6 alkanoyloxy, C1-C6 alkanesulfonyloxy, aromatic sulfonyloxy, substituted aromatic sulfonyloxy, phosphoryloxy and hydroxyl; herein, the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, or substituted aromatic sulfonyloxy refers to substituted by 1-3 groups independently selected from the following groups: deuterium, C1-C3 alkyl, C1-C3 alkoxy, phenyl and substituted phenyl; herein, the substituted phenyl refers to substituted by 1-3 groups independently selected from the following groups: halogen, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, phenyl and C1-C6 alkanoyloxy.

12. The compound according to claim 11, or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof, wherein: R1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, deuterated methyl, deuterated ethyl, deuterated n-propyl, deuterated isopropyl, deuterated n-butyl or deuterated tert-butyl; preferably, R1 is methyl or deuterated methyl; more preferably, R1 is -CD3.

13. The compound according to claim 11 or 12, or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof, wherein: n is 0; R1 is -CD3; R7 is one, two, three or four, and each is independently selected from the following groups: hydrogen, amino, fluorine, chlorine, bromine and hydroxyl; or, n is 1; R1 is -CD3; R7 is one, two, three or four, and each is independently selected from the following groups: hydrogen, amino, fluorine, chlorine, bromine and hydroxyl.

14. The compound according to claim 1, or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof, selected from any one of the following compounds: or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated substance, a metabolite or a prodrug thereof.

15. A pharmaceutical composition comprising the compound according to any one of claims 1 to 14 or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated substance, a metabolite or a prodrug thereof, and a pharmaceutically acceptable carrier.

16. A compound according to any one of claims 1 to 14 or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, or a pharmaceutical composition according to claim 15 for use in treating a central nervous system disease, disorder or condition and / or a neurological disease, disorder or condition.

17. A compound according to any one of claims 1 to 14 or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof, or a pharmaceutical composition according to claim 15 for use in treating 5-HT 2A Receptor-associated diseases / disorders.

18. The method for treating 5-HT according to claim 17. 2A A compound according to any one of claims 1 to 14 or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated substance, metabolite or prodrug thereof for a receptor-related disease / disorder, or a pharmaceutical composition according to claim 15, wherein: The 5-HT 2A The receptor-related central nervous system disease, disorder or condition and / or neurological disease, disorder or condition can be major depressive disorder, anxiety disorder, attention deficit hyperactivity disorder, post-traumatic stress disorder, cancer-related disorders, loss of drive, burnout, cluster headache, migraine, Parkinson's disease, schizophrenia, eating disorders, nausea or vomiting, and addictive psychoactive substance abuse.

19. A compound according to any one of claims 1 to 14 or a stereoisomer, pharmaceutically acceptable salt, solvate, deuterated compound, metabolite or prodrug thereof, or a pharmaceutical composition according to claim 15 for use in treating 5-HT 2A Receptor-associated central nervous system diseases, disorders or conditions and / or neurological diseases, disorders or conditions.

20. A compound according to any one of claims 1 to 14 or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated compound, a metabolite or a prodrug thereof, or a pharmaceutical composition according to claim 15 for use in the preparation of a drug for treating 5-HT 2A Use in medicine for receptor-related central nervous system diseases, disorders or conditions and / or neurological diseases, disorders or conditions.

21. A method for treating the following diseases, comprising administering to an individual in need thereof a compound according to any one of claims 1 to 14 or a stereoisomer, a pharmaceutically acceptable salt, a solvate, a deuterated substance, a metabolite or a prodrug thereof, or a pharmaceutical composition according to claim 15; the disease being 5-HT 2A Receptor-associated central nervous system diseases, disorders or conditions and / or neurological diseases, disorders or conditions.

Images