Fluorinated tryptamine compounds, analogs thereof, and methods of using same - Patents.com

Abstract

The present disclosure relates to fluorinated tryptamine compounds, or analogs thereof, and compositions comprising same, that can be used to treat, prevent, and / or ameliorate a psychiatric disease or disorder in a subject.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 63 / 195,943, filed June 2, 2021, and U.S. Provisional Application No. 63 / 288,313, filed December 10, 2021, all of which are incorporated by reference in their entireties herein. [Background technology]

[0002] 2. Background of the Invention In the United States, it is estimated that 51.5 million adults aged 18 years or older suffer from at least one mental illness and / or disorder, representing approximately 20.6% of all U.S. adults. The impact of such mental illnesses and / or disorders can range from mild to severe impairment, i.e., severe mental illness that substantially interferes with or limits one or more major life activities. It is estimated that there are 13.1 million U.S. adults (5.2%) with a severe mental illness.

[0003] Thus, there is a need in the art for compositions and methods for treating, preventing, and / or ameliorating psychiatric diseases and / or disorders in a subject. The present disclosure addresses this need. Summary of the Invention

[0004] The present disclosure provides certain compounds of Formula (I), Formula (II), and Formula (III), or salts, prodrugs, solvates, isotopologues, or stereoisomers thereof, where the substituents of (I), (II), and (III) are defined elsewhere herein. TIFF2024523822000002.tif34141

[0005] The present disclosure further provides pharmaceutical compositions comprising at least one compound of the present disclosure and a pharma- ceutically acceptable carrier.

[0006] The present disclosure further provides a method for treating, preventing, and / or ameliorating a psychiatric disease or disorder in a subject in need thereof. In certain embodiments, the method comprises administering to the subject a therapeutically effective amount of at least one compound of the present disclosure and / or at least one pharmaceutical composition of the present disclosure. In certain embodiments, the psychiatric disease or disorder is selected from the group consisting of a depressive disorder, an anxiety disorder, and an eating disorder.

[0007] In certain embodiments, the subject is further administered at least one additional agent useful for treating, preventing, and / or ameliorating a psychiatric disease or disorder. In certain embodiments, the at least one additional agent is a selective serotonin reuptake inhibitor, a triple reuptake inhibitor, a serotonin and norepinephrine reuptake inhibitor, a tricyclic antidepressant, a tetracyclic antidepressant, a dopamine reuptake inhibitor, a mood stabilizer, an anticonvulsant, an antipsychotic, an anxiolytic, a benzodiazepine, a monoamine releasing agent, a dopamine receptor agonist, a cannabinoid, a triptan, a migraine medication, an analgesic, an anti-inflammatory, an immunomodulator, a 5-HT 1A Receptor antagonist, 5-HT 2 Receptor antagonist, 5-HT 3 The therapeutic agent is selected from the group consisting of receptor antagonists, monoamine oxidase inhibitors, and noradrenergic antagonists. [Brief description of the drawings]

[0008] The drawings illustrate generally, by way of example, but not by way of limitation, various embodiments of the present application.

[0009] [Figure 1] 1 shows the head spasm response (HTR) dose response curve for Compound 4. [Diagram 2] 1 shows the head spasm response (HTR) dose response curve for Compound 9. [Diagram 3] FIG. 1 shows the head twitch response (HTR) dose-response curve for the non-hallucinogen 6-fluoro-N,N-diethyltryptamine (6-F-DET). [Figure 4] 1 shows the predicted binding pose of compound 51 to 5-HT2A. [Diagram 5] FIG. 1 shows head-twitch response (HTR) in mice as a function of time following administration of Compound 88 at 2 mg / kg and 6 mg / kg compared to control (vehicle). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Detailed Description of the Invention Reference will now be made in detail to particular embodiments of the disclosed subject matter. While the disclosed subject matter will be described in conjunction with the recited claims, it will be understood that the illustrated subject matter is not intended to limit the claims to the disclosed subject matter.

[0011] Throughout this document, values ​​expressed in range format should be interpreted flexibly to include not only the numerical values ​​explicitly stated as limits of the range, but also all individual numerical values ​​or subranges subsumed within that range, as if each numerical value and subrange were explicitly stated. For example, the range "about 0.1% to about 5%" or "about 0.1% to 5%" should be interpreted to include not only about 0.1% to about 5%, but also the individual values ​​(e.g., 1%, 2%, 3%, and 4%) and subranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the range stated. Unless otherwise indicated, the phrase "about X to Y" has the same meaning as "about X to about Y". Similarly, unless otherwise indicated, the phrase "about X, Y, or about Z" has the same meaning as "about X, about Y, or about Z".

[0012] In this document, the terms "a," "an," or "the" are used to include one or more than one unless the context clearly dictates otherwise. The term "or" is used to refer to a non-exclusive "or" unless otherwise indicated. The phrases "at least one of A and B" or "at least one of A or B" have the same meaning as "A, B, or A and B." In addition, it should be understood that any phrases or terms used herein, unless otherwise defined, are for descriptive purposes only and not for limiting purposes. The use of section headings is intended to aid in the reading of the document and is not to be construed as limiting. Information associated with a section heading may be found within or outside that particular section. All publications, patents, and patent documents referred to in this document are incorporated herein by reference in their entirety, as if each were individually incorporated by reference.

[0013] In the methods described herein, acts may be performed in any order unless a temporal or operational sequence is explicitly recited. Moreover, unless express claim language recites that the specified acts are performed separately, the specified acts may be performed simultaneously. For example, a claimed act of doing X and a claimed act of doing Y may be performed simultaneously in a single operation, and the resulting process would fall within the literal scope of the claimed process.

[0014] explanation 5-HT 1A The stimulatory effects are being explored in many therapeutic areas, including pain, seizures, and depression. 1A Partial agonists are approved for the treatment of anxiety. At the cellular and organismal level, without wishing to be bound by theory, 5-HT 1A The stimulatory effect is 5-HT 2A In opposition to activation, 5-HT 2A The intensity of the signaling and hallucinogenic effects can be reduced. For example, weak partial agonists (e.g., pindolol) can be used to inhibit 5-HT1A Blocking 5-HT has been reported to enhance the psychostimulant effects of dimethyltryptamine (DMT) in human volunteers. 2A 5-HT on signal transduction 1A This effect may or may not be desirable, depending on the therapeutic application.

[0015] 5-HT 1A The stimulatory effect is different from other 5-HT 2A They may also contribute to the subjective experience of psychoactivation of agonists. For example, the potent hallucinogenic tryptamine 5-methoxy-dimethyltryptamine (5-MeO-DMT) has a similar effect to many other hallucinogenic 5-HT agonists, such as DMT. 2A In contrast to agonists, they lack a strong visible component, but often produce intense tactile effects and near-death experiences. 1A It is speculated that irritation effects are responsible for at least some of the aforementioned differences.

[0016] 5-HT 2C Stimulants are known to cause anorexic effects (i.e., loss of appetite) along with effects on mood, including anxiety. With respect to hallucinogenic drug profiles, such effects may or may not be desirable depending on the indication. In some embodiments, 5-HT 2C It is desirable to minimize the stimulant effect, and compared to existing compounds, it may result in a hallucinogenic experience with a reduced or reduced chance of anxiety. In some cases, some anxiety may actually increase the probability of having a transformative experience that may contribute to a desirable therapeutic outcome. Similarly, strong 5-HT 2C The stimulatory effect is 5-HT 2A / 5-HT 2C 5-HT after administration of agonist 2C It may result in long-term (weeks to months) changes in receptor expression that may confer or contribute to sustained anxiolytic and antidepressant effects.

[0017] Possible 5-HT after agonist exposure 2CIt has further been hypothesized that altered expression (e.g., downregulation) may have unique benefits in anorexia. 2C Antagonism or knockdown of 5-HT leads to weight gain in many models. 2C Chronic treatment with the agonist resulted in significant rebound weight gain in animal models.

[0018] The compounds described herein inhibit 5-HT 2A , 5-HT 2B , 5-HT 2C , and 5-HT 1A In certain embodiments, the compounds described herein may agonize one or more receptors selected from the group consisting of 5-HT 2B Beyond 5-HT 2A In certain embodiments, the compounds described herein are selective for 5-HT 2C Beyond 5-HT 2A In certain embodiments, the compounds described herein are selective for 5-HT 1A Beyond 5-HT 2A In certain embodiments, the compounds described herein are selective for 5-HT 2B , 5-HT 2C , and 5-HT 1A Beyond 5-HT 2A In certain embodiments, the compounds of the present disclosure are selective for 5-HT 2B and 5-HT 2C than 5-HT 2A and 5-HT 1A In certain embodiments, the compounds of the present disclosure selectively agonize 5-HT 2B Beyond 5-HT 2A , 5-HT 2C , and 5-HT 1A In certain embodiments, the compounds of the present disclosure selectively agonize 5-HT 2A , 5-HT 2B and 5-HT 2C Beyond 5-HT 1A Selectively agonize.

[0019] In certain embodiments, 5-HT 2B More than 5-HT 2A Selectivity for 5-HT 2C More than 5-HT 2A Selectivity for 5-HT 1A More than 5-HT 2A Selectivity for is desirable.

[0020] definition As used herein, the term "about" can allow for a degree of variation in a value or range, for example, within 10%, 5%, or 1% of a stated value or the limits of a stated range, and includes the exact stated value or range.

[0021] The term "alkenyl" as used herein refers to straight and branched chain and cyclic alkyl groups as defined herein, except that there is at least one double bond between two carbon atoms. Thus, alkenyl groups have from 2 to 40 carbon atoms, or from 2 to about 20 carbon atoms, or from 2 to 12 carbon atoms, or in some embodiments, from 2 to 8 carbon atoms. Examples include vinyl, -CH=C=CCH, among others. 2 , -CH=CH(CH 3 ), -CH=C(CH 3 ) 2 , -C(CH 3 )=CH 2 , -C(CH 3 )=CH(CH 3 ), -C(CH 2 CH 3 )=CH 2 , cyclohexenyl, cyclopentenyl, cyclohexadienyl, butadienyl, pentadienyl, and hexadienyl.

[0022] The term "alkyl" as used herein refers to straight and branched chain alkyl groups and cycloalkyl groups having 1 to 40 carbon atoms, 1 to about 20 carbon atoms, 1 to 12 carbon atoms, or in some embodiments, 1 to 8 carbon atoms. Examples of straight chain alkyl groups include those having 1 to 8 carbon atoms, such as methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, and n-octyl groups. Examples of branched chain alkyl groups include, but are not limited to, isopropyl, iso-butyl, sec-butyl, t-butyl, neopentyl, isopentyl, and 2,2-dimethylpropyl groups. As used herein, the term "alkyl" encompasses n-alkyl, isoalkyl, and anteisoalkyl groups, as well as other branched chain forms of alkyl. Representative substituted alkyl groups may be substituted one or more times with any of the groups enumerated herein, such as amino, hydroxy, cyano, carboxy, nitro, thio, alkoxy, and halogen groups.

[0023] The term "alkynyl" as used herein refers to straight and branched chain alkyl groups, except that there is at least one triple bond between two carbon atoms. Thus, alkynyl groups have from 2 to 40 carbon atoms, from 2 to about 20 carbon atoms, or from 2 to 12 carbon atoms, or, in some embodiments, from 2 to 8 carbon atoms. Examples include, among others, -C≡CH, -C≡C(CH 3 ), -C≡C(CH 2 CH 3 ), -CH 2 C≡CH, -CH 2 C≡C(CH 3 ), and -CH 2 C≡C(CH 2 CH 3 ), but are not limited to these.

[0024] The term "acyl" as used herein refers to a group containing a carbonyl moiety, where the group is attached through the carbonyl carbon atom. The carbonyl carbon atom is either bonded to a hydrogen forming a "formyl" group or to another carbon atom which may be part of an alkyl, aryl, aralkylcycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl group, and the like. The acyl group may contain 0 to about 12, 0 to about 20, or 0 to about 40 additional carbon atoms bonded to the carbonyl group. The acyl group may contain a double bond or a triple bond within the meaning of the present specification. An acryloyl group is an example of an acyl group. An acyl group may also contain a heteroatom within the meaning of the present specification. A nicotinoyl group (pyridyl-3-carbonyl) is an example of an acyl group within the meaning of the present specification. Other examples include acetyl, benzoyl, phenylacetyl, pyridylacetyl, cinnamoyl, and acryloyl groups. When the group containing the carbon atom bonded to the carbonyl carbon atom contains a halogen, the group is referred to as a "haloacyl" group. One example is the trifluoroacetyl group.

[0025] The term "alkoxy" as used herein refers to an oxygen atom connected to an alkyl group, including cycloalkyl groups, as defined herein. Examples of straight-chain alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, and the like. Examples of branched-chain alkoxy groups include, but are not limited to, isopropoxy, sec-butoxy, tert-butoxy, isopentyloxy, isohexyloxy, and the like. Examples of cyclic alkoxy groups include, but are not limited to, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, and the like. An alkoxy group can contain about 1 to about 12, about 1 to about 20, or about 1 to about 40 carbon atoms bonded to an oxygen atom, and can further contain double or triple bonds and can also contain heteroatoms. For example, an allyloxy group or a methoxyethoxy group is also an alkoxy group within the meaning of this specification, as is a methylenedioxy group in the context in which two adjacent atoms of the structure are replaced therewith.

[0026] The term "amine" as used herein refers, for example, to an amine having the formula N(group) where each group can independently be H or non-H, such as alkyl, aryl, etc. 3 The term "amine" refers to primary, secondary, and tertiary amines having the formula: R-NH 2 , for example, alkylamines, arylamines, alkylarylamines; R 2 NH, where each R is independently selected such as a dialkylamine, diarylamine, aralkylamine, heterocyclylamine, and the like; and R 3 N, where each R is independently selected such as trialkylamines, dialkylarylamines, alkyldiarylamines, triarylamines, etc. The term "amine" as used herein also includes ammonium ions.

[0027] As used herein, the term "aromatic" refers to a carbocyclic or heterocyclic ring having one or more polyunsaturated rings and having aromatic character (i.e., having (4n+2) delocalized π (pi) electrons, where n is an integer).

[0028] The term "aryl" as used herein refers to a cyclic aromatic hydrocarbon group that does not contain a heteroatom in the ring. Thus, aryl groups include, but are not limited to, phenyl, azulenyl, heptalenyl, biphenyl, indacenyl, fluorenyl, phenanthrenyl, triphenylenyl, pyrenyl, naphthacenyl, chrysenyl, biphenylenyl, anthracenyl, and naphthyl groups. In some embodiments, the aryl group contains about 6 to about 14 carbons in the ring portion of the group. The aryl group may be unsubstituted or substituted as defined herein. Representative substituted aryl groups may be mono-substituted or substituted more than once, such as, but not limited to, a phenyl group substituted at any one or more of the 2-, 3-, 4-, 5-, or 6-positions of the phenyl ring, or a naphthyl group substituted at any one or more of the 2-, 3-, 4-, 5-, or 6-positions of the phenyl ring.

[0029] As used herein, “aryl-(C 1 ~C 6 The term "alkyl" refers to a 1 to 6 carbon alkylene chain that is an aryl group, e.g., -CH 2 CH 2 -phenyl or -CH 2 -phenyl (or benzyl). A specific example is the aryl CH 2 - and arylCH(CH 3 )-. "Substituted aryl-(C 1 ~C 6 The term "aryl-(C)alkyl" refers to an aryl group in which the aryl group is substituted. 1 ~C 6 ) alkyl functional groups. Specific examples include substituted aryl (CH 2 )-. Similarly, "heteroaryl-(C 1 ~C 6The term "alkyl" refers to a 1 to 3 carbon alkylene chain that is a heteroaryl group, e.g., -CH 2 CH 2 -pyridyl). A specific example is heteroaryl (CH 2 )-. "Substituted heteroaryl-(C 1 ~C 6 The term "heteroaryl-(C)alkyl" refers to a heteroaryl group in which the heteroaryl group is substituted. 1 ~C 6 ) alkyl functional groups. Specific examples include substituted heteroaryl (CH 2 )-.

[0030] In one aspect, the terms "co-administered" and "co-administration" with respect to a subject refer to administering to a subject a compound and / or composition of the present invention together with a compound and / or composition that can treat or prevent a disease or disorder contemplated herein. In certain embodiments, the co-administered compound and / or composition is administered separately or in any type of combination as part of a single therapeutic approach. The co-administered compound and / or composition can be formulated in any type of combination, as a mixture of solid and liquid under various solid, gel, and liquid formulations, and as a solution.

[0031] The term "cycloalkyl" as used herein refers to cyclic alkyl groups such as, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl groups. In some embodiments, cycloalkyl groups can have from 3 to about 8-12 ring members, while in other embodiments, the number of ring carbon atoms ranges from 3 to 4, 5, 6, or 7. Cycloalkyl groups further include polycyclic cycloalkyl groups, such as, but not limited to, norbornyl, adamantyl, bornyl, camphenyl, isocamphenyl, and carenyl groups, as well as fused rings, such as, but not limited to, decalinyl. Cycloalkyl groups also include rings substituted with straight or branched chain alkyl groups, as defined herein. Representative substituted cycloalkyl groups may be mono- or more than one substituted, such as 2,2-, 2,3-, 2,4-, 2,5-, or 2,6-disubstituted cyclohexyl groups, or mono-, di-, or tri-substituted norbornyl or cycloheptyl groups, which may be substituted with, for example, amino, hydroxy, cyano, carboxy, nitro, thio, alkoxy, and halogen groups. The term "cycloalkenyl," alone or in combination, refers to a cyclic alkenyl group.

[0032] As used herein, a "disease" is a state of health in a subject in which the subject is unable to maintain homeostasis and if the disease is not ameliorated, the subject's health will continue to deteriorate.

[0033] As used herein, a "disorder" in a subject is a health condition in which the subject is able to maintain homeostasis, but in which the subject's health condition is less favorable than it would be in the absence of the disorder. If left untreated, the disorder does not necessarily cause a further deterioration in the subject's health condition.

[0034] As used herein, the term "half maximal inhibitory concentration" or "IC 50 " refers to the concentration of a compound or composition required to obtain a 50% reduction in a biological or biochemical process upon administration of the compound and / or composition.

[0035] As used herein, the term "half maximal effective concentration" or "EC 50 " refers to the concentration of a compound or composition required to obtain a 50% increase in a biological or biochemical process upon administration of the compound and / or composition.

[0036] The terms "halo," "halogen," or "halide" group, as used herein, alone or as part of another substituent, mean, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom.

[0037] The term "haloalkyl" group, as used herein, includes monohaloalkyl groups, polyhaloalkyl groups where all halo atoms may be the same or different, and perhaloalkyl groups in which all hydrogen atoms are replaced by halogen atoms such as fluoro. Examples of haloalkyl include trifluoromethyl, 1,1-dichloroethyl, 1,2-dichloroethyl, 1,3-dibromo-3,3-difluoropropyl, perfluorobutyl, and the like.

[0038] As used herein, the term "heteroalkyl," by itself or in combination with another term, unless otherwise specified, refers to a stable straight or branched chain alkyl group consisting of the stated number of carbon atoms and one or two heteroatoms selected from the group consisting of O, N, and S, where the nitrogen and sulfur atoms may be optionally oxidized and the nitrogen heteroatom may be optionally quaternized. The heteroatom may be located at any position of the heteroalkyl group, including between the remainder of the heteroalkyl group and the fragment to which it is attached, and the portion attached to the most distal carbon atom in the heteroalkyl group. Non-limiting examples include -OCH 2 CH 2 CH 3 , -CH 2 CH 2 CH 2 OH, -CH 2 CH 2 NHCH 3, -NHCH 2 CH 2 CH 3 , -CH 2 CH 2 CH 2 NH 2 , -SCH 2 CH 2 CH 3 , -CH 2 SCH 2 CH 3 , C.H. 2 CH 2 CH 2 SH, and -CH 2 CH 2 S(=O)CH 3 Up to two heteroatoms include, for example, -CH 2 NH-OCH 3 , or -CH 2 CH 2 SSCH 3 The two may be consecutive.

[0039] The term "heteroarylalkyl," as used herein, refers to an alkyl group, as defined herein, in which a hydrogen or carbon bond of the alkyl group is replaced with a bond to a heteroaryl group, as defined herein.

[0040] The term "heteroaryl" as used herein refers to aromatic ring compounds containing five or more ring members, one or more of which are heteroatoms, such as, but not limited to, N, O, and S. For example, heteroaryl rings can have from 5 to about 8 to 12 ring members. Heteroaryl groups are a variety of heterocyclyl groups that have an aromatic electronic structure. C 2 A heteroaryl group designated as -heteroaryl can be a 5-ring group having 2 carbon atoms and 3 heteroatoms, a 6-ring group having 2 carbon atoms and 4 heteroatoms, etc. 4-Heteroaryl can be a 5-ring with one heteroatom, a 6-ring with two heteroatoms, etc. The sum of the number of carbon atoms and the number of heteroatoms is equal to the total number of ring atoms. Heteroaryl groups include, but are not limited to, groups such as pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridinyl, thiophenyl, benzothiophenyl, benzofuranyl, indolyl, azaindolyl, indazolyl, benzimidazolyl, azabenzimidazolyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, imidazopyridinyl, isoxazolopyridinyl, thianaphthalenyl, purinyl, xanthinyl, adeninyl, guaninyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, quinoxalinyl, and quinazolinyl groups. Heteroaryl groups can be unsubstituted or substituted with groups as discussed herein. Representative substituted heteroaryl groups may be substituted one or more times with groups such as those listed herein.

[0041] Additional examples of aryl and heteroaryl groups include phenyl, biphenyl, indenyl, naphthyl (1-naphthyl, 2-naphthyl), N-hydroxytetrazolyl, N-hydroxytriazolyl, N-hydroxyimidazolyl, anthracenyl (1-anthracenyl, 2-anthracenyl, 3-anthracenyl), thiophenyl (2-thienyl, 3-thienyl), furyl (2-furyl, 3-furyl), indolyl, and the like. aryl, oxadiazolyl, isoxazolyl, quinazolinyl, fluorenyl, xanthenyl, isoindanyl, benzhydryl, acridinyl, thiazolyl, pyrrolyl (2-pyrrolyl), pyrazolyl (3-pyrazolyl), imidazolyl (1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl), triazolyl (1,2,3-triazol-1-yl, 1,2,3-triazol-2-yl), 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl), oxazolyl (2-oxazolyl, 4-oxazolyl, 5-oxazolyl), thiazolyl (2-thiazolyl, 4-thiazolyl, 5-thiazolyl), pyridyl (2-pyridyl, 3-pyridyl, 4-pyridyl), pyrimidinyl (2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl), pyrazinyl, pyridazinyl (3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl), quinolyl (2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl), isoquinolyl (1-isoquinolyl, 3- isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl), benzo[b]furanyl (2-benzo[b]furanyl, 3-benzo[b]furanyl, 4-benzo[b]furanyl, 5-benzo[b]furanyl, 6-benzo[b]furanyl, 7-benzo[b]furanyl), 2,3-dihydro-benzo[b]furanyl (2-(2,3-dihydro-benzo[b]furanyl), 3-(2,3-dihydro-benzo[b]furanyl), 4-(2,3-dihydro-benzo[b]furanyl), 5-(2,3-dihydro-benzo[b]furanyl), 6-(2,3-dihydro-benzo[b]furanyl), 7-(2,3-Dihydro-benzo[b]furanyl), benzo[b]thiophenyl (2-benzo[b]thiophenyl, 3-benzo[b]thiophenyl, 4-benzo[b]thiophenyl, 5-benzo[b]thiophenyl, 6-benzo[b]thiophenyl, 7-benzo[b]thiophenyl), 2,3-dihydro-benzo[b]thiophenyl, (2-(2,3-dihydro-benzo[b]thiophenyl), 3-(2,3-dihydro-benzo[b]thiophenyl), 4-(2,3-dihydro-benzo[b]thiophenyl), 5-(2,3-dihydro-benzo[b]thiophenyl) nyl), 6-(2,3-dihydro-benzo[b]thiophenyl), 7-(2,3-dihydro-benzo[b]thiophenyl), indolyl (1-indolyl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl), indazole (1-indazolyl, 3-indazolyl, 4-indazolyl, 5-indazolyl, 6-indazolyl, 7-indazolyl), benzimidazolyl (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-indazolyl), benzothiazolyl (1-benzothiazolyl, 2-benzothiazolyl), benzothiazolyl (1-benzothiazolyl, 2-benzothiazolyl, 4-benzothiazolyl, 5-benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl), carbazolyl (1-carbazolyl, 2-carbazolyl, 3-carbazolyl, 4-carbazolyl), 5H-dibenz[b,f]azepine (5H-dibenz[b,f]azepin-1-yl, 5H-dibenz[b,f]azepin-2-yl, 5 H-dibenz[b,f]azepin-3-yl, 5H-dibenz[b,f]azepin-4-yl, 5H-dibenz[b,f]azepin-5-yl), 10,11-dihydro-5H-dibenz[b,f]azepine (10,11-dihydro-5H-dibenz[b,f]azepin-1-yl, 10,11-dihydro-5H-dibenz[b,f]azepin-2-yl, 10,11-dihydro-5H-dibenz[b,f]azepin-3-yl, 10,11-dihydro-5H-dibenz[b,f]azepin-4-yl, 10,11-dihydro-5H-dibenz[b,f]azepin-5-yl).

[0042] The term "heterocyclyl" as used herein refers to aromatic and non-aromatic ring compounds containing three or more ring members, one or more of which are heteroatoms, such as, but not limited to, N, O, and S. Thus, a heterocyclyl can be a cycloheteroalkyl, or heteroaryl, or any combination thereof, provided it is polycyclic. In some embodiments, heterocyclyl groups contain from 3 to about 20 ring members, while other such groups have from 3 to about 15 ring members. 2 A heterocyclyl group designated as -heterocyclyl can be a 5-ring group having 2 carbon atoms and 3 heteroatoms, a 6-ring group having 2 carbon atoms and 4 heteroatoms, etc. 4-Heterocyclyl can be a 5-ring with one heteroatom, a 6-ring with two heteroatoms, etc. The sum of the number of carbon atoms and the number of heteroatoms is equal to the total number of ring atoms. Heterocyclyl rings can also contain one or more double bonds. Heteroaryl rings are embodiments of heterocyclyl groups. The phrase "heterocyclyl group" includes fused ring species, including those containing fused aromatic and non-aromatic groups. For example, dioxolanyl rings and benzdioxolanyl ring systems (methylenedioxyphenyl ring systems) are both heterocyclyl groups within the meaning of this specification. This phrase also includes polycyclic ring systems containing heteroatoms, such as, but not limited to, quinuclidyl. Heterocyclyl groups can be unsubstituted or substituted as discussed herein. Heterocyclyl groups include, but are not limited to, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridinyl, thiophenyl, benzothiophenyl, benzofuranyl, dihydrobenzofuranyl, indolyl, dihydroindolyl, azaindolyl, indazolyl, benzimidazolyl, azabenzimidazolyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, imidazopyridinyl, isoxazolopyridinyl, thianaphthalenyl, purinyl, xanthinyl, adenyl, guaninyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, quinoxalinyl, and quinazolinyl groups. Representative substituted heterocyclyl groups include, but are not limited to, piperidinyl or quinolinyl groups which may be mono-substituted or substituted more than once, for example, 2-, 3-, 4-, 5-, or 6-substituted or di-substituted with groups such as those enumerated herein.

[0043] The term "heterocyclylalkyl" as used herein refers to an alkyl group, as defined herein, in which a hydrogen or carbon bond of the alkyl group, as defined herein, is replaced with a bond to a heterocyclyl group, as defined herein. Representative heterocyclylalkyl groups include, but are not limited to, furan-2-ylmethyl, furan-3-ylmethyl, pyridin-3-ylmethyl, tetrahydrofuran-2-ylethyl, and indol-2-ylpropyl.

[0044] The term "hydrocarbon" or "hydrocarbyl" as used herein refers to a molecule or functional group that contains carbon and hydrogen atoms. The term can also refer to a molecule or functional group that typically contains both carbon and hydrogen atoms, but in which all the hydrogen atoms have been replaced with other functional groups.

[0045] As used herein, the term "hydrocarbyl" refers to a functional group derived from a straight chain, branched chain, or cyclic hydrocarbon, and may be an alkyl, alkenyl, alkynyl, aryl, cycloalkyl, acyl, or any combination thereof. A hydrocarbyl group is one of the following: (C a ~C b )hydrocarbyl, where a and b are integers and mean that the group has any of a to b carbon atoms. For example, (C 1 ~C 4 ) hydrocarbyl is an alkyl group having a methyl group (C 1 ), ethyl (C 2 ), Propyl (C 3 ), or butyl (C 4 ), and (C 0 ~C b ) Hydrocarbyl, in certain embodiments, means that there are no hydrocarbyl groups present.

[0046] As used herein, the term "independently selected from" refers to referenced groups that are the same, different, or combinations thereof, unless the context clearly dictates otherwise. Thus, under this definition, "X 1 , X2 , and X 3 is independently selected from the noble gases" is intended to include, for example, 1 , X 2 , and X 3 A scenario where all are the same, X 1 , X 2 , and X 3 All are different scenarios, X 1 and X 2 is the same but X 3 may include different scenarios, and other similar permutations.

[0047] As used herein, the term "median effective dose" or "ED 50 " refers to a dose or concentration of a compound and / or composition that produces a therapeutic effect in 50% of a population receiving that dose.

[0048] The term "organic group" as used herein refers to any carbon-containing functional group. Examples can include oxygen-containing groups such as alkoxy groups, aryloxy groups, aralkyloxy groups, oxo(carbonyl) groups, carboxyl groups including carboxylic acids, carboxylates, and carboxylic esters, sulfur-containing groups such as alkyl and aryl sulfide groups, and other heteroatom-containing groups. Non-limiting examples of organic groups include OR, OOR, OC(O)N(R) 2 , C.N., C.F. 3 , OCF 3 , R, C(O), methylenedioxy, ethylenedioxy, N(R) 2 , SR, SOR, SO 2 R, SO 2 N(R) 2 , S.O. 3 R, C(O)R, C(O)C(O)R, C(O)CH 2 C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R) 2 , O.C.(O)N(R) 2 , C(S)N(R) 2 , (CH 2 ) 0~2 N(R)C(O)R, (CH 2 ) 0~2N(R)N(R) 2 , N(R)N(R)C(O)R, N(R)N(R)C(O)OR, N(R)N(R)CON(R) 2 , N(R)SO 2 R, N(R)SO 2 N(R) 2 , N(R)C(O)OR, N(R)C(O)R, N(R)C(S)R, N(R)C(O)N(R) 2 , N(R)C(S)N(R) 2 , N(COR)COR, N(OR)R, C(=NH)N(R) 2 , C(O)N(OR)R, C(=NOR)R, and substituted or unsubstituted (C 1 ~C 100 ) hydrocarbyl, where R can be hydrogen (in examples containing other carbon atoms) or a carbon-based moiety, which can be substituted or unsubstituted.

[0049] As used herein, the term "pharmaceutical composition" or "composition" refers to a mixture of at least one compound useful in the present invention with a pharma- ceutical composition facilitates administration of the compound to an organism.

[0050] As used herein, the term "pharmaceutical acceptable" refers to a material, such as a carrier or diluent, that does not abolish the biological activity or properties of a compound useful within the invention and that is relatively non-toxic, i.e., that may be administered to a subject without causing undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained.

[0051] As used herein, the term "pharmaceutical acceptable carrier" refers to a pharma- ceutically acceptable material, composition, or carrier, such as a liquid or solid filler, stabilizer, dispersant, suspending agent, diluent, excipient, thickener, solvent, or encapsulating material, that is involved in carrying or transporting a compound useful within the present invention into or to a subject so that it can perform its intended function. Typically, such constructs are carried or transported from one organ or part of the body to another organ or part of the body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation, including the compound useful within the present invention, and not harmful to the subject. Some examples of materials which can serve as pharma- ceutically acceptable carriers include sugars such as lactose, glucose, and sucrose, starches such as corn starch and potato starch, cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate, powdered tragacanth, malt, gelatin, talc, excipients such as cocoa butter and suppository waxes, oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil, glycols such as propylene glycol, polyols such as glycerin, sorbitol, mannitol, and polyethylene glycol, esters such as ethyl oleate and ethyl laurate, agar, buffers such as magnesium hydroxide and aluminum hydroxide, surface-active agents, alginic acid, pyrogen-free water, isotonic saline, Ringer's solution, ethyl alcohol, phosphate buffer solutions, and other non-toxic compatible substances used in pharmaceutical formulations. As used herein, "pharmaceutically acceptable carriers" also include any and all coatings, antibacterial and antifungal agents, absorption delaying agents, and the like, that are compatible with the activity of the compounds useful within the present invention and are physiologically acceptable to the subject. Supplementary active ingredients can also be incorporated into the compositions. "Pharmaceutically acceptable carriers" may further include pharmaceutically acceptable salts of the compounds useful within the present invention.Other additional ingredients that may be included in pharmaceutical compositions used in the practice of the invention are known in the art and described, for example, in Remington's Pharmaceutical Sciences (Genaro, Ed., Mack Publishing Co., 1985, Easton, Pa.), incorporated herein by reference.

[0052] As used herein, the term "pharmaceutically acceptable salts" refers to salts of the compound being administered prepared from pharmaceutically acceptable non-toxic acids and / or bases, including inorganic acids, inorganic bases, organic acids, inorganic bases, solvates (including hydrates), and clathrates thereof.

[0053] As used herein, a "pharmacologically effective amount," "therapeutically effective amount," or "effective amount" of a compound is the amount of the compound that is sufficient to provide a beneficial effect to the subject to which the compound is administered.

[0054] As used herein, the terms "prevent," "preventing," or "prevention" refer to avoiding or delaying the onset of symptoms associated with a disease or condition in a subject who does not experience such symptoms at the time administration of an agent or compound is initiated. Disease, disorder, and condition are used interchangeably herein.

[0055] The term "prodrug" as used herein refers to a biologically inactive compound that is metabolized in vivo to a biologically active compound.Non-limiting examples of metabolic reactions include hydrolysis and reduction.It is understood that prodrugs of the compounds of the present invention can include any heteroatom replacement with any of several unique prodrug moieties, including, but not limited to, esters, amides, carbamates, carbonates, ureas, imines, enamines, phosphates, thioesters, sulfates, sulfonamides, acyloxyalkyl esters, disulfides, and N-sulfonyl imidates.

[0056] As used herein, the term "room temperature" refers to a temperature between about 15°C and 28°C.

[0057] The term "solvent" as used herein refers to a liquid capable of dissolving a solid, liquid, or gas. Non-limiting examples of solvents are silicones, organic compounds, water, alcohols, ionic liquids, and supercritical fluids.

[0058] As used herein, the terms "subject," "individual," and "patient" can be used interchangeably and may refer to human or non-human mammals or birds. Non-human mammals include, for example, farm animals and pets, such as ovine, bovine, porcine, canine, feline, and murine mammals. In certain embodiments, the subject is a human.

[0059] As used herein, the term "substantially" refers to a majority or majority, such as at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more, or 100%. The term "substantially free" as used herein can mean that the amount of material present is completely absent such that it does not affect the material properties of the composition including the material, or that the composition has an insignificant amount such that the composition has between about 0% and about 5%, or between about 0% and about 1%, or less than about 5% by weight, or less than, equal to, or greater than about 4.5%, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.01, or about 0.001% by weight of the material. The term "substantially free" can mean that the composition has an insignificant amount such as about 0% to about 5%, or about 0% to about 1%, or less than about 5%, or less than, equal to, or greater than about 4.5%, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.01, or about 0.001% by weight of the material, or about 0% by weight.

[0060] The term "substituted" as used herein in conjunction with a molecule or organic group as defined herein refers to a state in which one or more hydrogen atoms contained therein are replaced by one or more non-hydrogen atoms. The term "functional group" or "substituent" as used herein refers to a group that may be or may be substituted on a molecule or organic group. Examples of substituents or functional groups include, but are not limited to, halogens (e.g., F, Cl, Br, and I); oxygen atoms in groups such as hydroxyl groups, alkoxy groups, aryloxy groups, aralkyloxy groups, oxo(carbonyl) groups, carboxyl groups including carboxylic acids, carboxylates, and carboxylic acid esters; sulfur atoms in groups such as thiol groups, alkyl and aryl sulfide groups, sulfoxide groups, sulfone groups, sulfonyl groups, and sulfonamide groups; nitrogen atoms in groups such as amines, hydroxylamine, nitriles, nitro groups, N-oxides, hydrazides, azides, and enamines; and other heteroatoms in various other groups. Non-limiting examples of substituents that may be attached to substituted carbon (or other) atoms include F, Cl, Br, I, OR, OC(O)N(R). 2 , CN, NO, NO 2 , O.N.O. 2 , azide, CF 3 , OCF 3 , R, O(oxo), S(thiono), C(O), S(O), methylenedioxy, ethylenedioxy, N(R) 2 , SR, SOR, SO 2 R, SO 2 N(R) 2 , S.O. 3 R, C(O)R, C(O)C(O)R, C(O)CH 2 C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R) 2 , O.C.(O)N(R) 2 , C(S)N(R) 2 , (CH 2 ) 0~2 N(R)C(O)R, (CH 2 ) 0~2 N(R)N(R) 2 , N(R)N(R)C(O)R, N(R)N(R)C(O)OR, N(R)N(R)CON(R)2, N(R)SO2 R, N(R)SO 2 N(R) 2 , N(R)C(O)OR, N(R)C(O)R, N(R)C(S)R, N(R)C(O)N(R) 2 , N(R)C(S)N(R) 2 , N(COR)COR, N(OR)R, C(=NH)N(R) 2 , C(O)N(OR)R, and C(═NOR)R, where R can be hydrogen or a carbon-based moiety, e.g., R can be hydrogen, (C 1 ~C 100 ) hydrocarbyl, alkyl, acyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl, or heteroarylalkyl, or two R groups attached to the nitrogen atom or adjacent nitrogen atoms may combine with one or more nitrogen atoms to form a heterocyclyl.

[0061] As used herein, the terms "treat," "treating," and "treatment" refer to reducing the frequency or severity with which symptoms of a disease or condition are experienced by a subject by administering an agent or compound to the subject.

[0062] Unless otherwise specified, when two substituents combine to form a ring having a specified number of ring atoms (e.g., R 2 and R 3 are combined with the nitrogen to which they are attached to form a ring having 3 to 7 ring members, the ring can have carbon atoms and, optionally, one or more (e.g., 1 to 3) additional heteroatoms independently selected from nitrogen, oxygen, or sulfur. The ring can be saturated or partially saturated and can be substituted.

[0063] Whenever a term or any of their prefix roots appears in a name of a substituent, the name should be interpreted as including those limitations provided herein. For example, whenever the terms "alkyl" or "aryl" or any of their prefix roots appear in a name of a substituent (e.g., arylalkyl, alkylamino), the name should be interpreted as including those limitations given elsewhere herein for "alkyl" and "aryl," respectively.

[0064] explanation Short-acting 5-HT 2A There is an urgent unmet need for 5-HT agonists, the current gold standard in clinical development. 2A The agonist is psilocybin, which has a duration of 5 to 8 hours. 5-HT like psilocybin 2A The psychoenhancement experience (acute subjective effect) induced by agonists (through their active metabolite psilocin) can be an intense psychological experience for the patient. This duration risks limiting patient access to this medication and restricting the number of patients clinicians can treat. Furthermore, longer durations are unlikely to be required for clinical benefit in most therapeutic indications. For example, ketamine, an atypical, fast-acting antidepressant, also induces a potent psychoenhancement effect, but with a duration of action of 1 hour. Thus, a 5-8 hour experience is likely not required for clinical outcome. Similarly, psilocybin and other 5-HT 2A The psychostimulant effects of 5-HT agonists can be strong, so patients should be monitored by a physician or other caregiver during administration. 2A Agonists can offer greater convenience to patients and their caregivers.

[0065] Many of the previously studied fluorinated tryptamines inhibit 5-HT 2AThe clearest and most powerful example of this is the use of hallucinogenic 5-HT antagonists such as psilocybin, which have been tested in humans and have been shown to lack or reduce the classical psychoactive effects associated with agonists. 2A The first compound, 6-fluoro-N,N-diethyltryptamine (6-F-DET), was found to lack the psychoactive effects characteristic of 5-HT agonists. 2A They have been used as inactive controls in clinical studies because they induce some physiological effects but not the strong psychological effects seen with agonists. Others have described fluorinated dimethyltryptamine (DMT) analogs as non-hallucinogenic synaptogenesis modulators. The duration of DMT analogs is generally short, less than 30 minutes, which may be too short for long-term effectiveness in disease states such as major depressive disorder, post-traumatic stress disorder, and substance use disorders. DMT and many of its analogs also lack oral activity. The fluorinated compounds of the present invention inhibit 5-HT 2A It acts as a receptor agonist and has a longer acting 5-HT receptor, like psilocybin. 2A It induces psychostimulant effects comparable to those of agonists but with a shorter duration of action. Fluorine substitution at the key site of the indole ring enhances 5-HT 2A It is possible to maintain efficacy and provide a powerful psychoactive effect.

[0066] In addition to the importance of the added fluorine, the N-alkylamine substitutions discovered herein improve the binding profile, bioavailability, half-life and therefore efficacy, side effect profile, and classical 5-HT 2A Uniquely modulate the pharmacokinetics of the compound, allowing one to tailor the desired pharmacological activity, including the duration of the 5-HT mediated psychoactive effect. 2A The completely novel asymmetric N,N-dialkylamine substitution on the tryptamine SAR offers a unique strategy to optimize the balance between pharmacodynamic activity and desired pharmacokinetic properties, such as duration of action.

[0067] compound In one aspect, the disclosure provides a compound of formula (I), or a salt, prodrug, solvate, isotopologue, or stereoisomer thereof, TIFF2024523822000003.tif27128 formula, A, TIFF2024523822000004.tif12128, In the formula, * indicates the relationship between L and N(R 1 )(R 2 ) L, TIFF2024523822000005.tif16128, R a1 and R a2 are each independently H, halogen, or C 1 ~C 6 Alkoxy and C 1 ~C 6 alkyl; or R a1 and R a2 may combine to form a carbonyl (C=O); R b1 and R b2 are each independently H and C 1 ~C 6 is selected from the group consisting of alkyl, R 1 and R 2 each independently represents an optionally substituted C 1 ~C 8 Alkyl, optionally substituted C 3 ~C 8 Cycloalkyl, optionally substituted C 1 ~C 8 Heteroalkyl, optionally substituted C 2 ~C 8 Heterocycloalkyl, optionally substituted C 2 ~C 8 Alkenyl, and optionally substituted C 2 ~C 8 alkynyl, Here, R 1 and R 2but are not identical, and Here, R 1 and R 2 One of them is R a1 , R a2 , R b1 , and R b2 and optionally substituted C 2 ~C 8 may form a heterocyclyl, However, R 1 and R 2 One of them is R b1 Or R b2 Combined with R to form a five-membered ring 5 If F, then R 4 , R 6 , and R 7 At least one of is not H or R 1 and R 2 One of them is R b1 Or R b2 When combined with to form a stereocenter, the compound consists essentially of one stereoisomer, R 3 is H, halogen, optionally substituted C 1 ~C 8 Alkyl, optionally substituted benzyl, optionally substituted C 3 ~C 8 Cycloalkyl, optionally substituted C 2 ~C 8 Alkenyl, and optionally substituted C 2 ~C 8 alkynyl, R 4 , R 5 , R 6 , and R 7 are independently H, F, Cl, Br, I, OR A , N(R A )(R B ), S.R. A , optionally substituted C 1 ~C 6 Alkyl, optionally substituted C 2 ~C 6Alkenyl, optionally substituted C 2 ~C 6 Alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C 2 ~C 9 Heteroaryl; Here, R 4 , R 5 , R 6 , and R 7 at least one of is F; R A Each occurrence of is independently H, C 1 ~C 6 Haloalkyl, C 2 ~C 6 Alkynyl, C 1 ~C 6 Alkyl, -C(=O)C 1 ~C 6 Alkyl, -C(=O)C 6 ~C 10 Aryl, -C(=O)NH(C 1 ~C 6 alkyl), -C(=O)NH(C 6 ~C 10 Aryl), -C(=O)N(C 1 ~C 6 Alkyl) 2 , -C(=O)N(C 1 ~C 6 Alkyl)(C 6 ~C 10 aryl), -C(=O)O(C 1 ~C 6 alkyl), -C(=O)O(C 6 ~C 10 aryl), -P(=O)(O(C 1 ~C 6 Alkyl) 2 , -P(=O)(O(C 1 ~C 6 Alkyl))(OH), -P(=O)(OH) 2 , -S(=O) 2 O(C 6 ~C 10 Aryl), -S(=O) 2 O(C 1 ~C6 Alkyl), -S(=O) 2 O(C 6 ~C 10 Aryl), -S(=O) 2 NH(C 1 ~C 6 Alkyl), -S(=O) 2 NH(C 6 ~C 10 Aryl), -S(=O) 2 N(C 1 ~C 6 Alkyl)(C 1 ~C 6 alkyl), and -S(=O) 2 N(C 1 ~C 6 Alkyl)(C 6 ~C 10 aryl), R B Each occurrence of is independently H, C 1 ~C 6 Alkyl, C 1 ~C 3 Haloalkyl, C 2 ~C 6 Alkenyl, benzyl, naphthyl, C 2 ~C 9 selected from the group consisting of heteroaryl, and phenyl; Isotopologues are R 1 Also R 2 Also F 18 Does not include The compound, or a salt, prodrug, solvate, isotopologue or stereoisomer thereof, is provided.

[0068] In certain embodiments, the compound of formula (I) is not N-ethyl-N-(2-(4-fluoro-1H-indol-3-yl)ethyl)propan-1-amine. In certain embodiments, the compound of formula (I) is not N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-1-amine. In certain embodiments, the compound of formula (I) is not N-ethyl-N-(2-(6-fluoro-1H-indol-3-yl)ethyl)propan-1-amine. In certain embodiments, the compound of formula (I) is not N-ethyl-N-(2-(7-fluoro-1H-indol-3-yl)ethyl)propan-1-amine. In certain embodiments, the compound of formula (I) is not N-ethyl-2-(4-fluoro-1H-indol-3-yl)-N-methylethan-1-amine. In certain embodiments, the compound of formula (I) is not N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine. In certain embodiments, the compound of formula (I) is not N-ethyl-2-(6-fluoro-1H-indol-3-yl)-N-methylethan-1-amine. In certain embodiments, the compound of formula (I) is not N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylethan-1-amine. In certain embodiments, the compound of formula (I) is not (R)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole. In certain embodiments, the compound of formula (I) is not (R)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole. In certain embodiments, the compound of formula (I) is not (R)-4-fluoro-3-(pyrrolidin-2-ylmethyl-d2)-1H-indole. In certain embodiments, the compound of formula (I) is not (S)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole.

[0069] In certain embodiments, (a)R 1 is ethyl, and R 2 is n-propyl (b)R1 is n-propyl, and R 2 is ethyl (c)R 1 is methyl, and R 2 is ethyl, or (d)R 1 is ethyl, and R 2 is methyl If one of the following is true, then R 4 , R 5 , R 6 , and R 7 Not more than two of them are H.

[0070] In certain embodiments, R 1 is n-butyl, R 2 is not 4-fluorobutyl. In certain embodiments, R 2 is n-butyl, R 1 is not 4-fluorobutyl. In certain embodiments, R 1 is n-butyl, R 2 is C 4 In certain embodiments, R 2 is n-butyl, R 1 is C 4 Not a fluoroalkyl.

[0071] In certain embodiments, R 4 , R 5 , R 6 , and R 7 At least two of them are F.

[0072] In certain embodiments, the compound of formula (I) is a compound of formula (I') or a salt, prodrug, solvate, isotopologue or stereoisomer thereof: TIFF2024523822000006.tif27128In formula, A, TIFF2024523822000007.tif12128, In the formula, * indicates the relationship between L and N(R 1 )(R 2) L, TIFF2024523822000008.tif15128, R a1 and R a2 are each independently H, halogen, or C 1 ~C 6 Alkoxy and C 1 ~C 6 alkyl; or R a1 and R a2 may combine to form a carbonyl (C=O); R b1 and R b2 are each independently H and C 1 ~C 6 is selected from the group consisting of alkyl, R 3 is H, halogen, optionally substituted C 1 ~C 8 Alkyl, optionally substituted benzyl, optionally substituted C 3 ~C 8 Cycloalkyl, optionally substituted C 2 ~C 8 Alkenyl, and optionally substituted C 2 ~C 8 alkynyl, R 4 , R 5 , R 6 , and R 7 are independently H, F, Cl, Br, I, OR A , N(R A )(R B ), S.R. A , optionally substituted C 1 ~C 6 Alkyl, optionally substituted C 2 ~C 6 Alkenyl, optionally substituted C 2 ~C 6 Alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C 2 ~C9 Heteroaryl; Here, R 4 , R 5 , R 6 , and R 7 at least one of is F; R A Each occurrence of is independently H, C 1 ~C 6 Haloalkyl, C 2 ~C 6 Alkynyl, C 1 ~C 6 Alkyl, -C(=O)C 1 ~C 6 Alkyl, -C(=O)C 6 ~C 10 Aryl, -C(=O)NH(C 1 ~C 6 alkyl), -C(=O)NH(C 6 ~C 10 Aryl), -C(=O)N(C 1 ~C 6 Alkyl) 2 , -C(=O)N(C 1 ~C 6 Alkyl)(C 6 ~C 10 aryl), -C(=O)O(C 1 ~C 6 alkyl), -C(=O)O(C 6 ~C 10 aryl), -P(=O)(O(C 1 ~C 6 Alkyl) 2 , -P(=O)(O(C 1 ~C 6 Alkyl))(OH), -P(=O)(OH) 2 , -S(=O) 2 O(C 6 ~C 10 Aryl), -S(=O) 2 O(C 1 ~C 6 Alkyl), -S(=O) 2 O(C 6 ~C 10 Aryl), -S(=O) 2 NH(C 1 ~C6 Alkyl), -S(=O) 2 NH(C 6 ~C 10 Aryl), -S(=O) 2 N(C 1 ~C 6 Alkyl)(C 1 ~C 6 alkyl), and -S(=O) 2 N(C 1 ~C 6 Alkyl)(C 6 ~C 10 aryl), R B Each occurrence of is independently H, C 1 ~C 6 Alkyl, C 1 ~C 3 Haloalkyl, C 2 ~C 6 Alkenyl, benzyl, naphthyl, C 2 ~C 9 selected from the group consisting of heteroaryl, and phenyl; One of the following applies: (a)R 1 is isopropyl, R 2 is ethyl, (b)R 1 is isopropyl, R 2 is methyl, (c)R 1 is sec-butyl, and R 2 is methyl, (d)R 1 is isopropyl, R 2 is n-propyl; (e)R 1 is isopropyl, R 2 is an allyl (f)R 1 is methyl, and R 2 is n-propyl; (g)R 1 is ethyl, and R 2 is sec-butyl; (h)R 1is n-propyl, and R 2 is sec-butyl; (i)R 1 is isopropyl, R 2 is sec-butyl; (j)R 1 is an aryl group, and R 2 is sec-butyl; (k)R 1 is an aryl group, and R 2 is ethyl, (l)R 1 is an aryl group, and R 2 is n-propyl; (m)R 1 is isopropyl, R 2 is cyanomethyl, (n)R 1 is isopropyl, R 2 is propargyl, (o)R 1 is methyl, and R 2 is 2-cyclopropyleth-2-yl; (p)R 1 is methyl, and R 2 is 3-thietanyl, (q)R 1 is ethyl, and R 2 is cyclobutyl; (r)R 1 is n-propyl, and R 2 is cyclobutyl; (s)R 1 is isopropyl, R 2 is cyclobutyl; (t)R 1 is an aryl group, and R 2 is cyclobutyl; (u)R 1 is methyl, and R 2 is iso-butyl; (v)R 1 is cyclobutyl, and R 2 is methyl, (w)R1 is methyl, and R 2 is an allyl (x)R 1 is isopropyl, R 2 is iso-butyl; (y)R 1 is methyl, and R 2 is cyclobutyl; (z)R 1 is ethyl, and R 2 is cyclobutyl; (aa)R 1 is propyl, and R 2 is cyclobutyl; (ab)R 1 is isopropyl, R 2 is cyclobutyl; (ac)R 1 is 1,2-dimethylpropyl, and R 2 is cyclobutyl; (ad)R 1 is cyclopropyl, and R 2 is cyclobutyl; (ae)R 1 is 1-methylpropyl, and R 2 is cyclobutyl; (af)R 1 is isopropyl, R 2 is methylcyclobutyl; (ag)R 1 is methyl, and R 2 is 1,2-dimethylpropyl; (ah)R 1 is methyl, and R 2 is 1-methylallyl; (ai)R 1 is propargyl, and R 2 is propyl, (aj)R 1 is propargyl, and R 2 is 1-methylpropyl; (ak)R 1 is cyanomethyl, R 2is propyl, (al)R 1 is cyanomethyl, R 2 is 1-methylpropyl; (am)R 1 is methyl, and R 2 is cyclopropylmethyl; (an)R 1 is methyl, and R 2 is cyanomethyl, (ao)R 1 is methyl, and R 2 is propargyl, (ap)R 1 is ethyl, and R 2 is propyl, (aq)R 1 is ethyl, and R 2 is iso-butyl; (ar)R 1 is ethyl, and R 2 is 3-thietanyl, (as)R 1 is ethyl, and R 2 is cyclopropyleth-2-yl; (at)R 1 is ethyl, and R 2 is cyclopropylmethyl; (au)R 1 is ethyl, and R 2 is 1,2-dimethylpropyl; (av)R 1 is ethyl, and R 2 is cyanomethyl, (aw)R 1 is propyl, and R 2 is iso-butyl; (ax)R 1 is propyl, and R 2 is 3-thietanyl, (ay)R 1 is propyl, and R 2 is cyclopropyleth-2-yl; (az)R1 is propyl, and R 2 is cyclopropylmethyl; (ba)R 1 is propyl, and R 2 is 1,2-dimethylpropyl; (bb)R 1 is isopropyl, R 2 is 3-thietanyl, (bc)R 1 is isopropyl, R 2 is cyclopropyleth-2-yl; (bd)R 1 is but-2-yl, and R 2 is cyclopropyl, (be)R 1 is but-2-yl, and R 2 is iso-butyl; (bf)R 1 is but-2-yl, and R 2 is 3-thietanyl, (bg)R 1 is but-2-yl, and R 2 is cyclopropyleth-2-yl; (bh)R 1 is but-2-yl, and R 2 is cyclopropylmethyl; (bi)R 1 is but-2-yl, and R 2 is 1,2-dimethylpropyl; (bj)R 1 is but-2-yl, and R 2 is 1-methylallyl; (bk)R 1 is cyclopropyl, and R 2 is an allyl (bl)R 1 is cyclopropyl, and R 2 is iso-butyl; (bm)R 1 is cyclopropyl, and R 2 is 3-thietanyl, (bn)R 1 is cyclopropyl, and R 2 is cyclopropylmethyl; (bo)R 1 is cyclopropyl, and R 2 is cyclopropyleth-2-yl; (bp)R 1 is cyclopropyl, and R 2 is 1,2-dimethylpropyl; (bq)R 1 is cyclopropyl, and R 2 is 1-methylallyl; (br)R 1 is cyclopropyl, and R 2 is cyanomethyl, (bs)R 1 is cyclopropyl, and R 2 is propargyl, (bt)R 1 is cyclobutyl, and R 2 is an allyl (bu)R 1 is cyclobutyl, and R 2 is iso-butyl; (bv)R 1 is cyclobutyl, and R 2 is 3-thietanyl, (bw)R 1 is cyclobutyl, and R 2 is cyclopropylmethyl; (bx)R 1 is cyclobutyl, and R 2 is cyclopropyleth-2-yl; (by)R 1 is cyclobutyl, and R 2 is 1,2-dimethylpropyl; (bz)R 1 is cyclobutyl, and R 2 is 1-methylallyl; (ca)R 1 is cyclobutyl, and R 2is cyanomethyl, (cb)R 1 is cyclobutyl, and R 2 is propargyl, (cc)R 1 iso-butyl, R 2 is an allyl (cd)R 1 iso-butyl, R 2 is 3-thietanyl, (ce)R 1 is iso-butyl, R 2 is cyclopropylmethyl; (cf)R 1 iso-butyl, R 2 is cyclopropyleth-2-yl; (cg)R 1 iso-butyl, R 2 is 1,2-dimethylpropyl; (ch)R 1 iso-butyl, R 2 is 1-methylallyl; (ci)R 1 is iso-butyl, R 2 is cyanomethyl, (cj)R 1 is iso-butyl, R 2 is propargyl, (ck)R 1 is an aryl group, and R 2 is iso-butyl; (cl)R 1 is an aryl group, and R 2 is 3-thietanyl, (cm)R 1 is an aryl group, and R 2 is cyclopropylmethyl; (cn)R 1 is an aryl group, and R 2 is cyclopropyleth-2-yl; (co)R 1 is an aryl group, and R 2 is 1,2-dimethylpropyl; (cp)R 1 is an aryl group, and R 2 is 1-methylallyl; (cq)R 1 is an aryl group, and R 2 is cyanomethyl, (cr)R 1 is an aryl group, and R 2 is propargyl, (cs)R 1 is 3-thietanyl, R 2 is cyclopropylmethyl; (ct)R 1 is 3-thietanyl, R 2 is cyclopropyleth-2-yl; (cu)R 1 is 3-thietanyl, R 2 is 1,2-dimethylpropyl; (cv)R 1 is 3-thietanyl, R 2 is 1-methylallyl; (cw)R 1 is 3-thietanyl, R 2 is cyanomethyl, (cx)R 1 is 3-thietanyl, R 2 is propargyl, (cy)R 1 is cyclopropyleth-2-yl, R 2 is cyclopropylmethyl; (cz)R 1 is cyclopropyleth-2-yl, R 2 is 1,2-dimethylpropyl; (da)R 1 is cyclopropyleth-2-yl, R 2 is 1-methylallyl; (db)R 1 is cyclopropyleth-2-yl, R 2 is cyanomethyl, (dc)R 1is cyclopropyleth-2-yl, R 2 is propargyl, (dd)R 1 is cyclopropylmethyl, R 2 is cyanomethyl, (de)R 1 is cyclopropylmethyl, R 2 is propargyl, (df)R 1 is 1,2-dimethylpropyl, and R 2 is 1-methylallyl; (dg)R 1 is 1,2-dimethylpropyl, and R 2 is propargyl, (dh)R 1 is 1,2-dimethylpropyl, and R 2 is cyanomethyl, (di)R 1 is 1-methylallyl, and R 2 is cyanomethyl, (dj)R 1 is 1-methylallyl, and R 2 is propargyl, or (dk)R 1 is propargyl, and R 2 is cyanomethyl.

[0073] In certain embodiments, the compound of formula (I) is a compound of formula (I"), or a salt, prodrug, solvate, isotopologue, or stereoisomer thereof: TIFF2024523822000009.tif27128In formula, A, TIFF2024523822000010.tif53145TIFF2024523822000011.tif226164TIFF2024523822000012.tif221165TIFF2024523822000013.tif208162TIFF2024523822000014.tif219165TIFF2024523822000015.tif227165; R 3 is H, halogen, optionally substituted C 1 ~C 8 Alkyl, optionally substituted benzyl, optionally substituted C 3 ~C 8 Cycloalkyl, optionally substituted C 2 ~C 8 Alkenyl, and optionally substituted C 2 ~C 8 alkynyl, R 4 , R 5 , R 6 , and R 7 are independently H, F, Cl, Br, I, OR A , N(R A )(R B ), S.R. A , optionally substituted C 1 ~C 6 Alkyl, optionally substituted C 2 ~C 6 Alkenyl, optionally substituted C 2 ~C 6 Alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C 2 ~C 9 Heteroaryl; Here, R 4 , R 5 , R 6 , and R 7 at least one of is F; R A Each occurrence of is independently H, C 1 ~C 6 Haloalkyl, C2 ~C 6 Alkynyl, C 1 ~C 6 Alkyl, -C(=O)C 1 ~C 6 Alkyl, -C(=O)C 6 ~C 10 Aryl, -C(=O)NH(C 1 ~C 6 alkyl), -C(=O)NH(C 6 ~C 10 Aryl), -C(=O)N(C 1 ~C 6 Alkyl) 2 , -C(=O)N(C 1 ~C 6 Alkyl)(C 6 ~C 10 aryl), -C(=O)O(C 1 ~C 6 alkyl), -C(=O)O(C 6 ~C 10 aryl), -P(=O)(O(C 1 ~C 6 Alkyl) 2 , -P(=O)(O(C 1 ~C 6 Alkyl))(OH), -P(=O)(OH) 2 , -S(=O) 2 O(C 6 ~C 10 Aryl), -S(=O) 2 O(C 1 ~C 6 Alkyl), -S(=O) 2 O(C 6 ~C 10 Aryl), -S(=O) 2 NH(C 1 ~C 6 Alkyl), -S(=O) 2 NH(C 6 ~C 10 Aryl), -S(=O) 2 N(C 1 ~C 6 Alkyl)(C 1 ~C 6 alkyl), and -S(=O) 2 N(C 1 ~C6 Alkyl)(C 6 ~C 10 aryl), R B Each occurrence of is independently H, C 1 ~C 6 Alkyl, C 1 ~C 3 Haloalkyl, C 2 ~C 6 Alkenyl, benzyl, naphthyl, C 2 ~C 9 It is selected from the group consisting of heteroaryl, and phenyl.

[0074] In certain embodiments, the compound of formula (I) is a compound of formula (I'"), or a salt, prodrug, solvate, isotopologue or stereoisomer thereof: TIFF2024523822000016.tif27128 formula, A, TIFF2024523822000017.tif24144, R a1 and R a2 each independently, if present, is H, halogen, C 1 ~C 6 Alkoxy and C 1 ~C 6 alkyl; R b1 and R b2 each, if present, independently represents H and C 1 ~C 6 is selected from the group consisting of alkyl, R c1 , R c2 , R d1 , R d2 , R e1 , and R e2 are each independently, if present, H, C 1 ~C 3 Alkyl, and C 1 ~C 3 haloalkyl; R 1may be substituted C 1 ~C 8 Alkyl, optionally substituted C 3 ~C 8 Cycloalkyl, optionally substituted C 1 ~C 8 Heteroalkyl, optionally substituted C 2 ~C 8 Alkenyl, and optionally substituted C 2 ~C 8 alkynyl, R 3 is H, halogen, optionally substituted C 1 ~C 8 Alkyl, optionally substituted benzyl, optionally substituted C 3 ~C 8 Cycloalkyl, optionally substituted C 2 ~C 8 Alkenyl, and optionally substituted C 2 ~C 8 alkynyl, R 4 , R 5 , R 6 , and R 7 are independently H, F, Cl, Br, I, OR A , N(R A )(R B ), S.R. A , optionally substituted C 1 ~C 6 Alkyl, optionally substituted C 2 ~C 6 Alkenyl, optionally substituted C 2 ~C 6 Alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C 2 ~C 9 Heteroaryl; Here, R 4 , R 5 , R 6 , and R 7 at least one of is F; R AEach occurrence of is independently H, C 1 ~C 6 Haloalkyl, C 2 ~C 6 Alkynyl, C 1 ~C 6 Alkyl, -C(=O)C 1 ~C 6 Alkyl, -C(=O)C 6 ~C 10 Aryl, -C(=O)NH(C 1 ~C 6 alkyl), -C(=O)NH(C 6 ~C 10 Aryl), -C(=O)N(C 1 ~C 6 alkyl)2, -C(=O)N(C 1 ~C 6 Alkyl)(C 6 ~C 10 aryl), -C(=O)O(C 1 ~C 6 alkyl), -C(=O)O(C 6 ~C 10 aryl), -P(=O)(O(C 1 ~C 6 Alkyl) 2 , -P(=O)(O(C 1 ~C 6 Alkyl))(OH), -P(=O)(OH) 2 , -S(=O) 2 O(C 6 ~C 10 Aryl), -S(=O) 2 O(C 1 ~C 6 Alkyl), -S(=O) 2 O(C 6 ~C 10 Aryl), -S(=O) 2 NH(C 1 ~C 6 Alkyl), -S(=O) 2 NH(C 6 ~C 10 Aryl), -S(=O) 2 N(C 1 ~C 6 Alkyl)(C 1 ~C 6alkyl), and -S(=O) 2 N(C 1 ~C 6 Alkyl)(C 6 ~C 10 aryl), R B Each occurrence of is independently H, C 1 ~C 6 Alkyl, C 1 ~C 3 Haloalkyl, C 2 ~C 6 Alkenyl, benzyl, naphthyl, C 2 ~C 9 It is selected from the group consisting of heteroaryl, and phenyl.

[0075] In certain embodiments, R 1 is optionally substituted C 1 ~C 3 is alkyl, R 2 is an optionally substituted branched chain C 3 ~C 8 In certain embodiments, R 1 is selected from the group consisting of methyl, allyl, and n-propyl; R 2 is an optionally substituted branched chain C 3 ~C 8 In certain embodiments, R 1 is C 1 ~C 3 is alkyl, R 2 is selected from the group consisting of iso-propyl, sec-butyl, iso-butyl, 1,2-dimethylpropyl, methylallyl, and 2-methylallyl. 1 is selected from the group consisting of methyl, allyl, and n-propyl; R 2 is selected from the group consisting of iso-propyl, sec-butyl, iso-butyl, 1,2-dimethylpropyl, methylallyl, and 2-methylallyl.

[0076] In certain embodiments, R 1 is optionally substituted C 1 ~C3 is alkyl, R 2 is optionally substituted C 3 ~C 8 In certain embodiments, R 1 is selected from the group consisting of methyl, allyl, and n-propyl; R 2 is optionally substituted C 3 ~C 8 In certain embodiments, R 1 is optionally substituted C 1 ~C 3 is alkyl, R 2 is selected from the group consisting of cyclopropyl and cyclobutyl. 1 is selected from the group consisting of methyl, allyl, and n-propyl; R 2 is selected from the group consisting of cyclopropyl and cyclobutyl.

[0077] In certain embodiments, R 1 is optionally substituted alkoxy. In certain embodiments, R 1 is optionally substituted C 1 ~C 8 In certain embodiments, R 1 is methyl. In certain embodiments, R 1 is ethyl. In certain embodiments, R 1 is n-propyl. In certain embodiments, R 1 is iso-propyl. In certain embodiments, R 1 is sec-butyl. In certain embodiments, R 1 is iso-butyl. In certain embodiments, R 1 is n-butyl. In certain embodiments, R 1 is cyclopropyl. In certain embodiments, R 1 is cyclopropylmethyl. In certain embodiments, R 1 is methylcyclopropyl. In certain embodiments, R 1 is cyclopropylethyl. In certain embodiments, R1 is 2-cyclopropyleth-2-yl. In certain embodiments, R 1 is cyclobutyl. In certain embodiments, R 1 is 2-thietanyl. In certain embodiments, R 1 is 3-thietanyl. In certain embodiments, R 1 is allyl. In certain embodiments, R 1 is methylallyl. In certain embodiments, R 1 is 2-methylallyl. In certain embodiments, R 1 is 3-methylallyl. In certain embodiments, R 1 is allylmethyl. In certain embodiments, R 1 is propargyl. In certain embodiments, R 1 is cyanomethyl. In certain embodiments, R 1 is 2-hydroxyethyl. In certain embodiments, R 1 and 2-methoxyethyl. In certain embodiments, R 1 is 1,2-dimethylpropyl.

[0078] In certain embodiments, R 2 is optionally substituted alkoxy. In certain embodiments, R 2 is optionally substituted C 1 ~C 8 In certain embodiments, R 2 is methyl. In certain embodiments, R 2 is ethyl. In certain embodiments, R 2 is n-propyl. In certain embodiments, R 2 is iso-propyl. In certain embodiments, R 2 is sec-butyl. In certain embodiments, R 2 is iso-butyl. In certain embodiments, R 2 is n-butyl. In certain embodiments, R 2 is cyclopropyl. In certain embodiments, R 2is cyclopropylmethyl. In certain embodiments, R 2 is methylcyclopropyl. In certain embodiments, R 2 is cyclopropylethyl. In certain embodiments, R 1 is 2-cyclopropyleth-2-yl. In certain embodiments, R 2 is cyclobutyl. In certain embodiments, R 1 is 2-thietanyl. In certain embodiments, R 1 is 3-thietanyl. In certain embodiments, R 2 is allyl. In certain embodiments, R 2 is methylallyl. In certain embodiments, R 2 is 2-methylallyl. In certain embodiments, R 2 is 3-methylallyl. In certain embodiments, R 2 is allylmethyl. In certain embodiments, R 2 is propargyl. In certain embodiments, R 2 is cyanomethyl. In certain embodiments, R 2 is 2-hydroxyethyl. In certain embodiments, R 2 and 2-methoxyethyl. In certain embodiments, R 2 is 1,2-dimethylpropyl.

[0079] In certain embodiments, R 3 is H. In certain embodiments, R 3 is methyl. In certain embodiments, R 3 is phenyl. In certain embodiments, R 3 is benzyl.

[0080] In certain embodiments, R 4 is H, Cl, Br, I, OR A , N(R A )(R B ), S.R. A , optionally substituted C 1 ~C 6 Alkyl, optionally substituted C2 ~C 6 Alkenyl, optionally substituted C 2 ~C 6 Alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C 2 ~C 9 heteroaryl; R 5 , R 6 , and R 7 are each independently H, F, Cl, Br, I, OR A , N(R A )(R B ), S.R. A , optionally substituted C 1 ~C 6 Alkyl, optionally substituted C 2 ~C 6 Alkenyl, optionally substituted C 2 ~C 6 Alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C 2 ~C 9 Heteroaryl; Here, R 5 , R 6 , and R 7 At least one of them is F.

[0081] In certain embodiments, R 4 is H and R 5 , R 6 , and R 7 are each independently H, F, Cl, Br, I, OR A , N(R A )(R B ), S.R. A , optionally substituted C 1 ~C 6 Alkyl, optionally substituted C 2 ~C 6 Alkenyl, optionally substituted C 2 ~C 6 Alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C 2~C 9 Heteroaryl; Here, R 5 , R 6 , and R 7 At least one of them is F.

[0082] In certain embodiments, R 4 is C 1 ~C 6 In certain embodiments, R 4 is H. In certain embodiments, R 4 is F. In certain embodiments, R 4 is OH. In certain embodiments, R 4 is OMe. In certain embodiments, R 4 is Cl.

[0083] In certain embodiments, R 5 is C 1 ~C 6 In certain embodiments, R 5 is H. In certain embodiments, R 5 is F. In certain embodiments, R 5 OR A , N(R A )(R B ), and S.R. A In certain embodiments, R 5 is OH. In certain embodiments, R 5 is OMe. In certain embodiments, R 5 is Cl. In certain embodiments, R 5 is Me.

[0084] In certain embodiments, R 6 is C 1 ~C 6 In certain embodiments, R 6 is H. In certain embodiments, R 6 is F. In certain embodiments, R 6 is OH. In certain embodiments, R 6is OMe. In certain embodiments, R 6 is Cl. In certain embodiments, R 6 is Me.

[0085] In certain embodiments, R 7 is C 1 ~C 6 In certain embodiments, R 7 is H. In certain embodiments, R 7 is F. In certain embodiments, R 7 is OH. In certain embodiments, R 7 is OMe. In certain embodiments, R 7 is Cl. In certain embodiments, R 7 is Br. In certain embodiments, R 7 is Me.

[0086] In certain embodiments, R 4 is F and R 5 , R 6 , and R 7 Each of R is H. In certain embodiments, 5 is F and R 4 , R 6 , and R 7 Each of R is H. In certain embodiments, 7 is F and R 4 , R 5 , and R 6 Each of R is H. In certain embodiments, 4 and R 5 Each of is F and R 6 and R 7 Each of R is H. In certain embodiments, 4 and R 6 Each of is F and R 5 and R 7 Each of R is H. In certain embodiments, 4 and R 7 Each of is F and R 5 and R 6 Each of R is H. In certain embodiments, 5 and R6 Each of is F and R 4 and R 7 Each of R is H. In certain embodiments, 5 and R 7 Each of is F and R 4 and R 6 Each of R is H. In certain embodiments, 6 and R 7 Each of is F and R 4 and R 5 Each of R is H. In certain embodiments, 5 is OMe, R 7 is F and R 4 and R 6 Each of R is H. In certain embodiments, 5 , R 6 , and R 7 are F and R 4 is H.

[0087] In certain embodiments, R 4 and R 6 Each of is H.

[0088] In certain embodiments, L is TIFF2024523822000018.tif6128. In certain embodiments, L is TIFF2024523822000019.tif9128. In certain embodiments, L is The file is TIFF2024523822000020.tif10128.

[0089] In certain embodiments, A is TIFF2024523822000021.tif45143, During the ceremony, R c1 , R c2 , R d1 , R d2 , R e1 , and R e2 are each independently, if present, H, C 1 ~C 3Alkyl, and C 1 ~C 3 haloalkyl.

[0090] In certain embodiments, R a1 , R a2 , R b1 , R b2 , R c1 , R c2 , R d1 , R d2 , R e1 , R e2 , R f1 , and R f2 Each, if present, is H.

[0091] In certain embodiments, R 1 is isopropyl, R 2 is ethyl. In certain embodiments, R 1 is isopropyl, R 2 is methyl. In certain embodiments, R 1 is sec-butyl, R 2 is methyl. In certain embodiments, R 1 is isopropyl, R 2 is n-propyl. In certain embodiments, R 1 is isopropyl, R 2 is allyl. In certain embodiments, R 1 is methyl, R 2 is ethyl. In certain embodiments, R 1 is methyl, R 2 is n-propyl. In certain embodiments, R 1 is ethyl, and R 2 is n-propyl. In certain embodiments, R 1 is ethyl, and R 2 is sec-butyl. In certain embodiments, R 1 is n-propyl, R 2 is sec-butyl. In certain embodiments, R 1 is isopropyl, R 2is sec-butyl. In certain embodiments, R 1 is an aryl group, and R 2 is sec-butyl. In certain embodiments, R 1 is an aryl group, and R 2 is ethyl. In certain embodiments, R 1 is an aryl group, and R 2 is n-propyl. In certain embodiments, R 1 is isopropyl, R 2 is cyanomethyl. In certain embodiments, R 1 is isopropyl, R 2 is propargyl. In certain embodiments, R 1 is methyl, R 2 is 2-cyclopropyleth-2-yl. In certain embodiments, R 1 is methyl, R 2 is 3-thietanyl. In certain embodiments, R 1 is ethyl, and R 2 is cyclobutyl. In certain embodiments, R 1 is n-propyl, R 2 is cyclobutyl. In certain embodiments, R 1 is isopropyl, R 2 is cyclobutyl. In certain embodiments, R 1 is an aryl group, and R 2 is cyclobutyl. In certain embodiments, R 1 is methyl, R 2 is iso-butyl. In certain embodiments, R 1 is cyclobutyl, and R 2 is methyl. In certain embodiments, R 1 is methyl, R 2 is allyl. In certain embodiments, R 1 is isopropyl, R 2 is iso-butyl. In certain embodiments, R 1 is methyl, R 2 is cyclobutyl. In certain embodiments, R1 is ethyl, and R 2 is cyclobutyl. In certain embodiments, R 1 is propyl, R 2 is cyclobutyl. In certain embodiments, R 1 is isopropyl, R 2 is cyclobutyl. In certain embodiments, R 1 is 1,2-dimethylpropyl, R 2 is cyclobutyl. In certain embodiments, R 1 is cyclopropyl, R 2 is cyclobutyl. In certain embodiments, R 1 is 1-methylpropyl, R 2 is cyclobutyl. In certain embodiments, R 1 is isopropyl, R 2 is methylcyclobutyl. In certain embodiments, R 1 is methyl, R 2 is 1,2-dimethylpropyl. In certain embodiments, R 1 is methyl, R 2 is 1-methylallyl. In certain embodiments, R 1 is propargyl, R 2 is propyl. In certain embodiments, R 1 is propargyl, R 2 is 1-methylpropyl. In certain embodiments, R 1 is cyanomethyl, R 2 is propyl. In certain embodiments, R 1 is cyanomethyl, R 2 is 1-methylpropyl. In certain embodiments, R 1 is methyl, R 2 is cyclopropylmethyl. In certain embodiments, R 1 is methyl, R 2 is cyanomethyl. In certain embodiments, R 1 is methyl, R 2 is propargyl. In certain embodiments, R1 is ethyl, and R 2 is propyl. In certain embodiments, R 1 is ethyl, and R 2 is iso-butyl. In certain embodiments, R 1 is ethyl, and R 2 is 3-thietanyl. In certain embodiments, R 1 is ethyl, and R 2 is cyclopropyleth-2-yl. In certain embodiments, R 1 is ethyl, and R 2 is cyclopropylmethyl. In certain embodiments, R 1 is ethyl, and R 2 is 1,2-dimethylpropyl. In certain embodiments, R 1 is ethyl, and R 2 is cyanomethyl. In certain embodiments, R 1 is propyl, and R 2 is iso-butyl. In certain embodiments, R 1 is propyl, and R 2 is 3-thietanyl. In certain embodiments, R 1 is propyl, and R 2 is cyclopropyleth-2-yl. In certain embodiments, R 1 is propyl, and R 2 is cyclopropylmethyl. In certain embodiments, R 1 is propyl, and R 2 is 1,2-dimethylpropyl. In certain embodiments, R 1 is isopropyl, R 2 is 3-thietanyl. In certain embodiments, R 1 is isopropyl, R 2 is cyclopropyleth-2-yl. In certain embodiments, R 1 is but-2-yl, R 2 is cyclopropyl. In certain embodiments, R 1 is but-2-yl, R 2is iso-butyl. In certain embodiments, R 1 is but-2-yl, R 2 is 3-thietanyl. In certain embodiments, R 1 is but-2-yl, R 2 is cyclopropyleth-2-yl. In certain embodiments, R 1 is but-2-yl, R 2 is cyclopropylmethyl. In certain embodiments, R 1 is but-2-yl, R 2 is 1,2-dimethylpropyl. In certain embodiments, R 1 is but-2-yl, R 2 is 1-methylallyl. In certain embodiments, R 1 is cyclopropyl, R 2 is allyl. In certain embodiments, R 1 is cyclopropyl, R 2 is iso-butyl. In certain embodiments, R 1 is cyclopropyl, R 2 is 3-thietanyl. In certain embodiments, R 1 is cyclopropyl, R 2 is cyclopropylmethyl. In certain embodiments, R 1 is cyclopropyl, R 2 is cyclopropyleth-2-yl. In certain embodiments, R 1 is cyclopropyl, R 2 is 1,2-dimethylpropyl. In certain embodiments, R 1 is cyclopropyl, R 2 is 1-methylallyl. In certain embodiments, R 1 is cyclopropyl, R 2 is cyanomethyl. In certain embodiments, R 1 is cyclopropyl, R 2 is propargyl. In certain embodiments, R 1 is cyclobutyl, and R 2is allyl. In certain embodiments, R 1 is cyclobutyl, and R 2 is iso-butyl. In certain embodiments, R 1 is cyclobutyl, and R 2 is 3-thietanyl. In certain embodiments, R 1 is cyclobutyl, and R 2 is cyclopropylmethyl. In certain embodiments, R 1 is cyclobutyl, and R 2 is cyclopropyleth-2-yl. In certain embodiments, R 1 is cyclobutyl, and R 2 is 1,2-dimethylpropyl. In certain embodiments, R 1 is cyclobutyl, and R 2 is 1-methylallyl. In certain embodiments, R 1 is cyclobutyl, and R 2 is cyanomethyl. In certain embodiments, R 1 is cyclobutyl, and R 2 is propargyl. In certain embodiments, R 1 is iso-butyl, R 2 is allyl. In certain embodiments, R 1 is iso-butyl, R 2 is 3-thietanyl. In certain embodiments, R 1 is iso-butyl, R 2 is cyclopropylmethyl. In certain embodiments, R 1 is iso-butyl, R 2 is cyclopropyleth-2-yl. In certain embodiments, R 1 is iso-butyl, R 2 is 1,2-dimethylpropyl. In certain embodiments, R 1 is iso-butyl, R 2 is 1-methylallyl. In certain embodiments, R 1 is iso-butyl, R 2 is cyanomethyl. In certain embodiments, R 1is iso-butyl, R 2 is propargyl. In certain embodiments, R 1 is an aryl group, and R 2 is iso-butyl. In certain embodiments, R 1 is an aryl group, and R 2 is 3-thietanyl. In certain embodiments, R 1 is an aryl group, and R 2 is cyclopropylmethyl. In certain embodiments, R 1 is an aryl group, and R 2 is cyclopropyleth-2-yl. In certain embodiments, R 1 is an aryl group, and R 2 is 1,2-dimethylpropyl. In certain embodiments, R 1 is an aryl group, and R 2 is 1-methylallyl. In certain embodiments, R 1 is an aryl group, and R 2 is cyanomethyl. In certain embodiments, R 1 is an aryl group, and R 2 is propargyl. In certain embodiments, R 1 is 3-thietanyl, R 2 is cyclopropylmethyl. In certain embodiments, R 1 is 3-thietanyl, R 2 is cyclopropyleth-2-yl. In certain embodiments, R 1 is 3-thietanyl, R 2 is 1,2-dimethylpropyl. In certain embodiments, R 1 is 3-thietanyl, R 2 is 1-methylallyl. In certain embodiments, R 1 is 3-thietanyl Yes, R 2 is cyanomethyl. In certain embodiments, R 1 is 3-thietanyl, R 2 is propargyl. In certain embodiments, R 1 is cyclopropyleth-2-yl, R 2is cyclopropylmethyl. In certain embodiments, R 1 is cyclopropyleth-2-yl, R 2 is 1,2-dimethylpropyl. In certain embodiments, R 1 is cyclopropyleth-2-yl, R 2 is 1-methylallyl. In certain embodiments, R 1 is cyclopropyleth-2-yl, R 2 is cyanomethyl. In certain embodiments, R 1 is cyclopropyleth-2-yl, R 2 is propargyl. In certain embodiments, R 1 is cyclopropylmethyl, R 2 is cyanomethyl. In certain embodiments, R 1 is cyclopropylmethyl, R 2 is propargyl. In certain embodiments, R 1 is 1,2-dimethylpropyl, R 2 is 1-methylallyl. In certain embodiments, R 1 is 1,2-dimethylpropyl, R 2 is propargyl. In certain embodiments, R 1 is 1,2-dimethylpropyl, R 2 is cyanomethyl. In certain embodiments, R 1 is 1-methylallyl, R 2 is cyanomethyl. In certain embodiments, R 1 is 1-methylallyl, R 2 is propargyl. In certain embodiments, R 1 is propargyl, R 2 is cyanomethyl.

[0092] In certain embodiments, A is TIFF2024523822000022.tif13128. In certain embodiments, A is TIFF2024523822000023.tif12128. In certain embodiments, A is TIFF2024523822000024.tif12128. In certain embodiments, A is TIFF2024523822000025.tif13128. In certain embodiments, A is TIFF2024523822000026.tif12128. In certain embodiments, A is TIFF2024523822000027.tif10128. In certain embodiments, A is TIFF2024523822000028.tif9128. In certain embodiments, A is TIFF2024523822000029.tif9128. In certain embodiments, A is TIFF2024523822000030.tif12128. In certain embodiments, A is TIFF2024523822000031.tif16128. In certain embodiments, A is TIFF2024523822000032.tif16128. In certain embodiments, A is TIFF2024523822000033.tif16128. In certain embodiments, A is TIFF2024523822000034.tif17128. In certain embodiments, A is TIFF2024523822000035.tif13128. In certain embodiments, A is TIFF2024523822000036.tif13128. In certain embodiments, A is TIFF2024523822000037.tif13128. In certain embodiments, A is TIFF2024523822000038.tif13128. In certain embodiments, A is TIFF2024523822000039.tif16128. In certain embodiments, A is TIFF2024523822000040.tif16128. In certain embodiments, A is TIFF2024523822000041.tif16128. In certain embodiments, A is TIFF2024523822000042.tif13128. In certain embodiments, A is TIFF2024523822000043.tif13128. In certain embodiments, A is TIFF2024523822000044.tif9128. In certain embodiments, A is TIFF2024523822000045.tif17128. In certain embodiments, A is TIFF2024523822000046.tif9128. In certain embodiments, A is TIFF2024523822000047.tif17128. In certain embodiments, A is TIFF2024523822000048.tif12128. In certain embodiments, A is TIFF2024523822000049.tif10128. In certain embodiments, A is TIFF2024523822000050.tif13128. In certain embodiments, A is TIFF2024523822000051.tif11128. In certain embodiments, A is TIFF2024523822000052.tif12128. In certain embodiments, A is TIFF2024523822000053.tif12128. In certain embodiments, A is TIFF2024523822000054.tif12128. In certain embodiments, A is TIFF2024523822000055.tif14128. In certain embodiments, A is TIFF2024523822000056.tif12128. In certain embodiments, A is TIFF2024523822000057.tif15128. In certain embodiments, A is TIFF2024523822000058.tif13128. In certain embodiments, A is TIFF2024523822000059.tif15128. In certain embodiments, A is TIFF2024523822000060.tif15128. In certain embodiments, A is TIFF2024523822000061.tif15128. In certain embodiments, A is TIFF2024523822000062.tif21128. In certain embodiments, A is TIFF2024523822000063.tif18128. In certain embodiments, A is TIFF2024523822000064.tif21128. In certain embodiments, A is TIFF2024523822000065.tif12128. In certain embodiments, A is TIFF2024523822000066.tif13128. In certain embodiments, A is TIFF2024523822000067.tif16128. In certain embodiments, A is TIFF2024523822000068.tif16128. In certain embodiments, A is TIFF2024523822000069.tif13128. In certain embodiments, A is TIFF2024523822000070.tif13128. In certain embodiments, A is TIFF2024523822000071.tif15128. In certain embodiments, A is TIFF2024523822000072.tif19128. In certain embodiments, A is TIFF2024523822000073.tif16128. In certain embodiments, A is TIFF2024523822000074.tif20128. In certain embodiments, A is TIFF2024523822000075.tif15128. In certain embodiments, A is TIFF2024523822000076.tif15128. In certain embodiments, A is TIFF2024523822000077.tif11128. In certain embodiments, A is TIFF2024523822000078.tif11128. In certain embodiments, A is TIFF2024523822000079.tif15128. In certain embodiments, A is TIFF2024523822000080.tif11128. In certain embodiments, A is TIFF2024523822000081.tif14128. In certain embodiments, A is TIFF2024523822000082.tif15128. In certain embodiments, A is TIFF2024523822000083.tif11128. In certain embodiments, A is TIFF2024523822000084.tif14128. In certain embodiments, A is TIFF2024523822000085.tif14128. In certain embodiments, A is TIFF2024523822000086.tif15128. In certain embodiments, A is TIFF2024523822000087.tif15128. In certain embodiments, A is TIFF2024523822000088.tif16128. In certain embodiments, A is TIFF2024523822000089.tif21128. In certain embodiments, A is TIFF2024523822000090.tif13128. In certain embodiments, A is TIFF2024523822000091.tif16128. In certain embodiments, A is TIFF2024523822000092.tif10128. In certain embodiments, A is TIFF2024523822000093.tif10128. In certain embodiments, A is TIFF2024523822000094.tif10128. In certain embodiments, A is TIFF2024523822000095.tif12128. In certain embodiments, A is TIFF2024523822000096.tif12128. In certain embodiments, A is TIFF2024523822000097.tif16128. In certain embodiments, A is TIFF2024523822000098.tif16128. In certain embodiments, A is TIFF2024523822000099.tif12128. In certain embodiments, A is TIFF2024523822000100.tif16128. In certain embodiments, A is TIFF2024523822000101.tif12128. In certain embodiments, A is TIFF2024523822000102.tif17128. In certain embodiments, A is TIFF2024523822000103.tif21128. In certain embodiments, A is TIFF2024523822000104.tif21128. In certain embodiments, A is TIFF2024523822000105.tif17128. In certain embodiments, A is TIFF2024523822000106.tif21128. In certain embodiments, A is TIFF2024523822000107.tif16128. In certain embodiments, A is TIFF2024523822000108.tif16128. In certain embodiments, A is TIFF2024523822000109.tif15128. In certain embodiments, A is TIFF2024523822000110.tif19128. In certain embodiments, A is TIFF2024523822000111.tif16128. In certain embodiments, A is TIFF2024523822000112.tif16128. In certain embodiments, A is TIFF2024523822000113.tif12128. In certain embodiments, A is TIFF2024523822000114.tif19128. In certain embodiments, A is TIFF2024523822000115.tif18128. In certain embodiments, A is TIFF2024523822000116.tif14128. In certain embodiments, A is TIFF2024523822000117.tif14128. In certain embodiments, A is TIFF2024523822000118.tif18128. In certain embodiments, A is TIFF2024523822000119.tif14128. In certain embodiments, A is TIFF2024523822000120.tif18128. In certain embodiments, A is TIFF2024523822000121.tif18128. In certain embodiments, A is TIFF2024523822000122.tif18128. In certain embodiments, A is TIFF2024523822000123.tif14128. In certain embodiments, A is TIFF2024523822000124.tif14128. In certain embodiments, A is TIFF2024523822000125.tif17128. In certain embodiments, A is TIFF2024523822000126.tif21128. In certain embodiments, A is TIFF2024523822000127.tif21128. In certain embodiments, A is TIFF2024523822000128.tif17128. In certain embodiments, A is TIFF2024523822000129.tif23128. In certain embodiments, A is TIFF2024523822000130.tif23128. In certain embodiments, A is TIFF2024523822000131.tif17128. In certain embodiments, A is TIFF2024523822000132.tif17128. In certain embodiments, A is TIFF2024523822000133.tif17128. In certain embodiments, A is TIFF2024523822000134.tif17128. In certain embodiments, A is TIFF2024523822000135.tif21128. In certain embodiments, A is TIFF2024523822000136.tif25128. In certain embodiments, A is TIFF2024523822000137.tif25128. In certain embodiments, A is TIFF2024523822000138.tif24128. In certain embodiments, A is TIFF2024523822000139.tif24128. In certain embodiments, A is TIFF2024523822000140.tif17128. In certain embodiments, A is TIFF2024523822000141.tif17128. In certain embodiments, A is TIFF2024523822000142.tif16128. In certain embodiments, A is TIFF2024523822000143.tif21128. In certain embodiments, A is TIFF2024523822000144.tif21128. In certain embodiments, A is TIFF2024523822000145.tif19128. In certain embodiments, A is TIFF2024523822000146.tif18128. In certain embodiments, A is TIFF2024523822000147.tif12128. In certain embodiments, A is TIFF2024523822000148.tif12128. In certain embodiments, A is TIFF2024523822000149.tif17128. In certain embodiments, A is TIFF2024523822000150.tif22128. In certain embodiments, A is TIFF2024523822000151.tif24128. In certain embodiments, A is TIFF2024523822000152.tif24128. In certain embodiments, A is TIFF2024523822000153.tif18128. In certain embodiments, A is TIFF2024523822000154.tif17128. In certain embodiments, A is TIFF2024523822000155.tif16128. In certain embodiments, A is TIFF2024523822000156.tif23128. In certain embodiments, A is TIFF2024523822000157.tif23128. In certain embodiments, A is TIFF2024523822000158.tif17128. In certain embodiments, A is TIFF2024523822000159.tif16128. In certain embodiments, A is TIFF2024523822000160.tif23128. In certain embodiments, A is TIFF2024523822000161.tif23128. In certain embodiments, A is TIFF2024523822000162.tif16128. In certain embodiments, A is TIFF2024523822000163.tif16128. In certain embodiments, A is TIFF2024523822000164.tif24128. In certain embodiments, A is TIFF2024523822000165.tif17128. In certain embodiments, A is TIFF2024523822000166.tif17128. In certain embodiments, A is TIFF2024523822000167.tif12128. In certain embodiments, A is TIFF2024523822000168.tif12128. In certain embodiments, A is TIFF2024523822000169.tif13128. In certain embodiments, A is TIFF2024523822000170.tif9128. In certain embodiments, A is TIFF2024523822000171.tif13128. In certain embodiments, A is TIFF2024523822000172.tif13128. In certain embodiments, A is TIFF2024523822000173.tif13128. In certain embodiments, A is TIFF2024523822000174.tif10128. In certain embodiments, A is TIFF2024523822000175.tif13128. In certain embodiments, A is TIFF2024523822000176.tif13128. In certain embodiments, A is TIFF2024523822000177.tif9128. In certain embodiments, A is TIFF2024523822000178.tif13128. In certain embodiments, A is TIFF2024523822000179.tif13128. In certain embodiments, A is TIFF2024523822000180.tif14128. In certain embodiments, A is TIFF2024523822000181.tif11128. In certain embodiments, A is TIFF2024523822000182.tif11128. In certain embodiments, A is TIFF2024523822000183.tif16128. In certain embodiments, A is TIFF2024523822000184.tif18128. In certain embodiments, A is TIFF2024523822000185.tif15128. In certain embodiments, A is TIFF2024523822000186.tif15128. In certain embodiments, A is TIFF2024523822000187.tif11128. In certain embodiments, A is TIFF2024523822000188.tif11128. In certain embodiments, A is TIFF2024523822000189.tif16128. In certain embodiments, A is TIFF2024523822000190.tif16128. In certain embodiments, A is TIFF2024523822000191.tif11128. In certain embodiments, A is TIFF2024523822000192.tif18128. In certain embodiments, A is TIFF2024523822000193.tif18128. In certain embodiments, A is TIFF2024523822000194.tif19128. In certain embodiments, A is TIFF2024523822000195.tif19128. In certain embodiments, A is TIFF2024523822000196.tif16128. In certain embodiments, A is TIFF2024523822000197.tif15128. In certain embodiments, A is TIFF2024523822000198.tif16128. In certain embodiments, A is TIFF2024523822000199.tif21128. In certain embodiments, A is TIFF2024523822000200.tif17128. In certain embodiments, A is TIFF2024523822000201.tif17128. In certain embodiments, A is TIFF2024523822000202.tif17128. In certain embodiments, A is TIFF2024523822000203.tif19128. In certain embodiments, A is TIFF2024523822000204.tif19128. In certain embodiments, A is TIFF2024523822000205.tif19128. In certain embodiments, A is TIFF2024523822000206.tif17128. In certain embodiments, A is TIFF2024523822000207.tif17128. In certain embodiments, A is TIFF2024523822000208.tif17128. In certain embodiments, A is TIFF2024523822000209.tif17128. In certain embodiments, A is TIFF2024523822000210.tif17128. In certain embodiments, A is TIFF2024523822000211.tif17128. In certain embodiments, A is TIFF2024523822000212.tif21128. In certain embodiments, A is TIFF2024523822000213.tif21128. In certain embodiments, A is TIFF2024523822000214.tif21128. In certain embodiments, A is TIFF2024523822000215.tif15128. In certain embodiments, A is TIFF2024523822000216.tif14128. In certain embodiments, A is TIFF2024523822000217.tif14128. In certain embodiments, A is TIFF2024523822000218.tif19128. In certain embodiments, A is TIFF2024523822000219.tif19128. In certain embodiments, A is TIFF2024523822000220.tif18128. In certain embodiments, A is TIFF2024523822000221.tif22128. In certain embodiments, A is TIFF2024523822000222.tif23128. In certain embodiments, A is TIFF2024523822000223.tif22128. In certain embodiments, A is TIFF2024523822000224.tif22128. In certain embodiments, A is TIFF2024523822000225.tif23128. In certain embodiments, A is TIFF2024523822000226.tif22128. In certain embodiments, A is TIFF2024523822000227.tif21128. In certain embodiments, A is TIFF2024523822000228.tif21128. In certain embodiments, A is TIFF2024523822000229.tif21128. In certain embodiments, A is TIFF2024523822000230.tif19128. In certain embodiments, A is TIFF2024523822000231.tif19128. In certain embodiments, A is TIFF2024523822000232.tif19128. In certain embodiments, A is TIFF2024523822000233.tif19128. In certain embodiments, A is TIFF2024523822000234.tif19128. In certain embodiments, A is TIFF2024523822000235.tif19128. In certain embodiments, A is TIFF2024523822000236.tif20128. In certain embodiments, A is TIFF2024523822000237.tif20128. In certain embodiments, A is TIFF2024523822000238.tif20128. In certain embodiments, A is TIFF2024523822000239.tif16128. In certain embodiments, A is TIFF2024523822000240.tif16128. In certain embodiments, A is TIFF2024523822000241.tif16128. In certain embodiments, A is TIFF2024523822000242.tif21128. In certain embodiments, A is TIFF2024523822000243.tif21128. In certain embodiments, A is TIFF2024523822000244.tif21128. In certain embodiments, A is TIFF2024523822000245.tif17128. In certain embodiments, A is TIFF2024523822000246.tif17128. In certain embodiments, A is TIFF2024523822000247.tif17128. In certain embodiments, A is TIFF2024523822000248.tif21128. In certain embodiments, A is TIFF2024523822000249.tif21128. In certain embodiments, A is TIFF2024523822000250.tif21128. In certain embodiments, A is TIFF2024523822000251.tif21128. In certain embodiments, A is TIFF2024523822000252.tif21128. In certain embodiments, A is TIFF2024523822000253.tif21128. In certain embodiments, A is TIFF2024523822000254.tif19128. In certain embodiments, A is TIFF2024523822000255.tif19128. In certain embodiments, A is TIFF2024523822000256.tif19128. In certain embodiments, A is TIFF2024523822000257.tif21128. In certain embodiments, A is TIFF2024523822000258.tif21128. In certain embodiments, A is TIFF2024523822000259.tif21128. In certain embodiments, A is TIFF2024523822000260.tif22128. In certain embodiments, A is TIFF2024523822000261.tif22128. In certain embodiments, A is TIFF2024523822000262.tif22128. In certain embodiments, A is TIFF2024523822000263.tif22128. In certain embodiments, A is TIFF2024523822000264.tif22128. In certain embodiments, A is TIFF2024523822000265.tif22128. In certain embodiments, A is TIFF2024523822000266.tif20128. In certain embodiments, A is TIFF2024523822000267.tif20128. In certain embodiments, A is TIFF2024523822000268.tif20128. In certain embodiments, A is TIFF2024523822000269.tif20128. In certain embodiments, A is TIFF2024523822000270.tif20128. In certain embodiments, A is TIFF2024523822000271.tif20128. In certain embodiments, A is TIFF2024523822000272.tif20128. In certain embodiments, A is TIFF2024523822000273.tif20128. In certain embodiments, A is TIFF2024523822000274.tif18128. In certain embodiments, A is TIFF2024523822000275.tif20128. In certain embodiments, A is TIFF2024523822000276.tif20128. In certain embodiments, A is TIFF2024523822000277.tif18128. In certain embodiments, A is TIFF2024523822000278.tif20128. In certain embodiments, A is TIFF2024523822000279.tif20128. In certain embodiments, A is TIFF2024523822000280.tif18128. In certain embodiments, A is TIFF2024523822000281.tif21128. In certain embodiments, A is TIFF2024523822000282.tif21128. In certain embodiments, A is TIFF2024523822000283.tif19128. In certain embodiments, A is TIFF2024523822000284.tif11128. In certain embodiments, A is TIFF2024523822000285.tif13128. In certain embodiments, A is TIFF2024523822000286.tif11128. In certain embodiments, A is TIFF2024523822000287.tif11128. In certain embodiments, A is TIFF2024523822000288.tif11128. In certain embodiments, A is TIFF2024523822000289.tif10128. In certain embodiments, A is TIFF2024523822000290.tif13128. In certain embodiments, A is TIFF2024523822000291.tif15128. In certain embodiments, A is TIFF2024523822000292.tif11128. In certain embodiments, A is TIFF2024523822000293.tif14128. In certain embodiments, A is TIFF2024523822000294.tif13128. In certain embodiments, A is TIFF2024523822000295.tif14128. In certain embodiments, A is TIFF2024523822000296.tif14128. In certain embodiments, A is TIFF2024523822000297.tif13128. In certain embodiments, A is TIFF2024523822000298.tif14128. In certain embodiments, A is TIFF2024523822000299.tif12128. In certain embodiments, A is TIFF2024523822000300.tif12128. In certain embodiments, A is TIFF2024523822000301.tif16128. In certain embodiments, A is TIFF2024523822000302.tif16128. In certain embodiments, A is TIFF2024523822000303.tif14128. In certain embodiments, A is TIFF2024523822000304.tif15128. In certain embodiments, A is TIFF2024523822000305.tif12128. In certain embodiments, A is TIFF2024523822000306.tif19128. In certain embodiments, A is TIFF2024523822000307.tif16128. In certain embodiments, A is TIFF2024523822000308.tif16128. In certain embodiments, A is TIFF2024523822000309.tif12128. In certain embodiments, A is TIFF2024523822000310.tif19128. In certain embodiments, A is TIFF2024523822000311.tif19128. In certain embodiments, A is TIFF2024523822000312.tif20128. In certain embodiments, A is The file is TIFF2024523822000313.tif20128.

[0093] In certain embodiments, the compound is N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylbutan-2-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylpropan-1-amine, N-(2-(5,6-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylprop-2-en-1-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-allyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine, N-allyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine, 2-((2-(5-fluoro-1H-indol-3-yl)ethyl)(isopropyl)amino)acetonitrile, 5,6-difluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylthietan-3-amine, N-(2-(4,5-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylbutan-2-amine, 7-fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, 2-(ethyl(propyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one, 2-(ethyl(methyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one, (S)-5-fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, (R)-5-fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, 5-fluoro-3-(1-methylazetidin-3-yl)-1H-indole, N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine, N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylbutan-2-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylcyclobutanamine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylprop-2-yn-1-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylprop-2-en-1-amine, N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)prop-2-en-1-amine, N-(2-(6-chloro-5-fluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine, 1-cyclopropyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylethan-1-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylcyclobutanamine, N-ethyl-N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)propan-1-amine, N-(2-(4-fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-(2-(4-fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-ethyl-N-(2-(4-fluoro-1H-indol-3-yl)ethyl)propan-2-amine, N-(2-(4-fluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(4-fluoro-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(4-fluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(4-fluoro-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, N-(2-(7-fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-(2-(7-fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-ethyl-N-(2-(7-fluoro-1H-indol-3-yl)ethyl)propan-2-amine, N-(2-(7-fluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(7-fluoro-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(7-fluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(7-fluoro-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, 2-(5,6-difluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine, N-(2-(5,6-difluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-(2-(5,6-difluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-(2-(5,6-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-2-amine, N-(2-(5,6-difluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(5,6-difluoro-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(5,6-difluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(5,6-difluoro-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, 2-(5,7-difluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine, N-(2-(5,7-difluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-(2-(5,7-difluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-(2-(5,7-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine, N-(2-(5,7-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-2-amine, N-(2-(5,7-difluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(5,7-difluoro-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(5,7-difluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(5,7-difluoro-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, 2-(6,7-difluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine, N-(2-(6,7-difluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-(2-(6,7-difluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-(2-(6,7-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine, N-(2-(6,7-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-2-amine, N-(2-(6,7-difluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(6,7-difluoro-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(6,7-difluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(6,7-difluoro-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, N-ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-N-methylethan-1-amine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-ethyl-N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)propan-2-amine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, 3-(2-(ethyl(methyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 7-fluoro-3-(2-(methyl(propyl)amino)ethyl)-1H-indol-5-ol, 7-fluoro-3-(2-(isopropyl(methyl)amino)ethyl)-1H-indol-5-ol, 3-(2-(ethyl(propyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 3-(2-(ethyl(isopropyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 7-fluoro-3-(2-(isobutyl(methyl)amino)ethyl)-1H-indol-5-ol, 3-(2-(cyclobutyl(methyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 3-(2-(allyl(methyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 7-fluoro-3-(2-(isobutyl(isopropyl)amino)ethyl)-1H-indol-5-ol, 4-fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, 6-fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, 4,5-difluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, 4,6-difluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, 5,7-difluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, 6,7-difluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, 4-fluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 5-fluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 6-Fluoro-3-(1-methylpiperidin-3-yl)-1H-indole 7-fluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 4,5-difluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 4,6-difluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 5,6-difluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 5,7-difluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 6,7-difluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 4-fluoro-3-(methylprolyl)-1H-indole, 6-fluoro-3-(methylprolyl)-1H-indole, 7-fluoro-3-(methylprolyl)-1H-indole, 4,5-difluoro-3-(methylprolyl)-1H-indole, 4,6-difluoro-3-(methylprolyl)-1H-indole, 5,6-difluoro-3-(methylprolyl)-1H-indole, 5,7-difluoro-3-(methylprolyl)-1H-indole, 6,7-difluoro-3-(methylprolyl)-1H-indole, 4-fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, 6-fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, 7-fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, 4,5-difluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, 4,6-difluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, 5,6-difluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, 5,7-difluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, 6,7-difluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, N-(sec-butyl)-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine, N-(cyclopropylmethyl)-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylcyclopropanamine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylcyclopropanamine, N-(2-(7-fluoro-1H-indol-3-yl)ethyl)-N-propylcyclobutanamine, N-(2-(7-fluoro-1H-indol-3-yl)ethyl)-N-propylbutan-2-amine, N-ethyl-N-methyl-2-(5,6,7-trifluoro-1H-indol-3-yl)ethan-1-amine, N-ethyl-N-(2-(5,6,7-trifluoro-1H-indol-3-yl)ethyl)propan-1-amine, N-ethyl-N-(2-(7-fluoro-5-methyl-1H-indol-3-yl)ethyl)propan-1-amine, N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclopropanamine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylcyclopropanamine, N-ethyl-2-(5-fluoro-7-methyl-1H-indol-3-yl)-N-methylethan-1-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N,3-dimethylbutan-2-amine, N-(sec-butyl)-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclopropanamine, N-cyclopropyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine, 2-(7-bromo-5-fluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine, N-ethyl-2-(5-fluoro-6-methyl-1H-indol-3-yl)-N-methylethan-1-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-(prop-2-yn-1-yl)butan-2-amine, 2-(sec-butyl(2-(5-fluoro-1H-indol-3-yl)ethyl)amino)acetonitrile, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylbut-3-en-2-amine, 2-(5-chloro-6-fluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine, N-(2-(7-fluoro-1H-indol-3-yl)ethyl)-N-propylprop-2-yn-1-amine, 2-((2-(7-fluoro-1H-indol-3-yl)ethyl)(propyl)amino)acetonitrile, 2-(7-chloro-5-fluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine, (R)-3-((1-ethylpyrrolidin-2-yl)methyl)-5-fluoro-1H-indole, (R)-5-fluoro-3-(pyrrolidin-2-ylmethyl)-1H-indole, (R)-5-fluoro-3-((1-propylpyrrolidin-2-yl)methyl)-1H-indole, (R)-5,6-difluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, (R)-7-fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, N-isopropyl-N-(2-(5,6,7-trifluoro-1H-indol-3-yl)ethyl)propan-1-amine, N-methyl-N-(2-(5,6,7-trifluoro-1H-indol-3-yl)ethyl)butan-2-amine, N-methyl-N-(2-(5,6,7-trifluoro-1H-indol-3-yl)ethyl)cyclobutanamine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-isopropylpropan-1-amine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylbutan-2-amine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylbut-3-en-2-amine, N-(2-(5,6-difluoro-1H-indol-3-yl)ethyl)-N-methylbut-3-en-2-amine, N-(2-(6,7-difluoro-1H-indol-3-yl)ethyl)-N-methylbut-3-en-2-amine, N-(2-(5,7-difluoro-1H-indol-3-yl)ethyl)-N-methylbut-3-en-2-amine, N-methyl-N-(2-(5,6,7-trifluoro-1H-indol-3-yl)ethyl)but-3-en-2-amine, 3-(((2R)-1-(sec-butyl)pyrrolidin-2-yl)methyl)-5-fluoro-1H-indole, (R)-5-fluoro-3-((1-isopropylpyrrolidin-2-yl)methyl)-1H-indole, (R)-3-((1-cyclobutylpyrrolidin-2-yl)methyl)-5-fluoro-1H-indole, (R)-3-((1-cyclopropylpyrrolidin-2-yl)methyl)-5-fluoro-1H-indole, (R)-3-((1-allylpyrrolidin-2-yl)methyl)-5-fluoro-1H-indole, 3-(((2R)-1-(but-3-en-2-yl)pyrrolidin-2-yl)methyl)-5-fluoro-1H-indole, (R)-5-fluoro-3-((1-(prop-2-yn-1-yl)pyrrolidin-2-yl)methyl)-1H-indole, 3-(((2R)-1-(sec-butyl)pyrrolidin-2-yl)methyl)-5,6,7-trifluoro-1H-indole, (R)-5,6,7-trifluoro-3-((1-isopropylpyrrolidin-2-yl)methyl)-1H-indole, (R)-3-((1-cyclobutylpyrrolidin-2-yl)methyl)-5,6,7-trifluoro-1H-indole, (R)-3-((1-cyclopropylpyrrolidin-2-yl)methyl)-5,6,7-trifluoro-1H-indole, (R)-3-((1-allylpyrrolidin-2-yl)methyl)-5,6,7-trifluoro-1H-indole, 3-(((2R)-1-(but-3-en-2-yl)pyrrolidin-2-yl)methyl)-5,6,7-trifluoro-1H-indole, (R)-5,6,7-trifluoro-3-((1-(prop-2-yn-1-yl)pyrrolidin-2-yl)methyl)-1H-indole, 3-(((2R)-1-(sec-butyl)pyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, (R)-7-fluoro-3-((1-isopropylpyrrolidin-2-yl)methyl)-5-methoxy-1H-indole, (R)-3-((1-cyclobutylpyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, (R)-3-((1-cyclopropylpyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, (R)-3-((1-allylpyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, 3-(((2R)-1-(but-3-en-2-yl)pyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, and (R)-7-Fluoro-5-methoxy-3-((1-(prop-2-yn-1-yl)pyrrolidin-2-yl)methyl)-1H-indole is selected from the group consisting of:

[0094] In another aspect, the disclosure provides a compound of formula (II) or a salt, prodrug, solvate, isotopologue or stereoisomer thereof, TIFF2024523822000314.tif34128 formula, R 3 is H, optionally substituted C 1 ~C8 Alkyl, optionally substituted benzyl, optionally substituted C 3 ~C 8 Cycloalkyl, optionally substituted C 2 ~C 8 Alkenyl, and optionally substituted C 2 ~C 8 alkynyl, R 4 , R 5 , R 6 , and R 7 are independently H, F, Cl, Br, I, OR A , N(R A )(R B ), S.R. A , optionally substituted C 1 ~C 6 Alkyl, optionally substituted C 2 ~C 6 Alkenyl, optionally substituted C 2 ~C 6 Alkynyl, optionally substituted C 1 ~C 8 Heteroalkyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C 2 ~C 9 Heteroaryl; Here, R 4 , R 5 , R 6 , and R 7 at least one of is F; R 8 and R 9 each independently represents an optionally substituted C 1 ~C 8 Alkyl, optionally substituted C 3 ~C 8 Cycloalkyl, optionally substituted C 2 ~C 8 Alkenyl, and optionally substituted C 2 ~C 8 alkynyl, R 10 is H, optionally substituted C1 ~C 6 Alkyl, optionally substituted C 2 ~C 6 Alkenyl, optionally substituted C 2 ~C 6 Alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C 2 ~C 9 Heteroaryl; R f1 and R f2 are each independently H and C 1 ~C 6 is selected from the group consisting of alkyl, R A Each occurrence of is independently H, C 1 ~C 6 Haloalkyl, C 2 ~C 6 Alkynyl, C 1 ~C 6 Alkyl, -C(=O)C 1 ~C 6 Alkyl, -C(=O)C 6 ~C 10 Aryl, -C(=O)NH(C 1 ~C 6 alkyl), -C(=O)NH(C 6 ~C 10 Aryl), -C(=O)N(C 1 ~C 6 Alkyl) 2 , -C(=O)N(C 1 ~C 6 Alkyl)(C 6 ~C 10 aryl), -C(=O)O(C 1 ~C 6 alkyl), -C(=O)O(C 6 ~C 10 aryl), -P(=O)(O(C 1 ~C 6 Alkyl) 2 , -P(=O)(O(C 1 ~C 6 Alkyl))(OH), -P(=O)(OH) 2 , -S(=O) 2 O(C6 ~C 10 Aryl), -S(=O) 2 O(C 1 ~C 6 Alkyl), -S(=O) 2 O(C 6 ~C 10 Aryl), -S(=O) 2 NH(C 1 ~C 6 Alkyl), -S(=O) 2 NH(C 6 ~C 10 Aryl), -S(=O) 2 N(C 1 ~C 6 Alkyl)(C 1 ~C 6 alkyl), and -S(=O) 2 N(C 1 ~C 6 Alkyl)(C 6 ~C 10 aryl), R B Each occurrence of is independently H, C 1 ~C 6 Alkyl, C 1 ~C 3 Haloalkyl, C 2 ~C 6 Alkenyl, benzyl, naphthyl, C 2 ~C 9 selected from the group consisting of heteroaryl, and phenyl; The compound, or a salt, prodrug, solvate, isotopologue or stereoisomer thereof, is provided.

[0095] In certain embodiments, R 3 is H. In certain embodiments, R 3 is methyl. In certain embodiments, R 3 is phenyl. In certain embodiments, R 3 is benzyl.

[0096] In certain embodiments, R 4 is optionally substituted C 1 ~C 8In certain embodiments, R 4 is H. In certain embodiments, R 4 is F. In certain embodiments, R 4 is OH. In certain embodiments, R 4 is OMe.

[0097] In certain embodiments, R 5 is optionally substituted C 1 ~C 8 In certain embodiments, R 5 is H. In certain embodiments, R 5 is F. In certain embodiments, R 5 is OH. In certain embodiments, R 5 is OMe.

[0098] In certain embodiments, R 6 is optionally substituted C 1 ~C 8 In certain embodiments, R 6 is H. In certain embodiments, R 6 is F. In certain embodiments, R 6 is OH. In certain embodiments, R 6 is OMe.

[0099] In certain embodiments, R 7 is optionally substituted C 1 ~C 8 In certain embodiments, R 7 is H. In certain embodiments, R 7 is F. In certain embodiments, R 7 is OH. In certain embodiments, R 7 is OMe.

[0100] In certain embodiments, R 8 is methyl. In certain embodiments, R 8 is ethyl. In certain embodiments, R 8is n-propyl. In certain embodiments, R 8 is iso-propyl. In certain embodiments, R 8 is sec-butyl. In certain embodiments, R 8 is iso-butyl. In certain embodiments, R 8 is n-butyl. In certain embodiments, R 8 is cyclopropyl. In certain embodiments, R 8 is cyclopropylmethyl. In certain embodiments, R 8 is methylcyclopropyl. In certain embodiments, R 8 is cyclopropylethyl. In certain embodiments, R 8 is cyclobutyl. In certain embodiments, R 8 is allyl. In certain embodiments, R 8 is methylallyl. In certain embodiments, R 8 is 2-methylallyl. In certain embodiments, R 8 is 3-methylallyl. In certain embodiments, R 8 is allylmethyl. In certain embodiments, R 8 is propargyl. In certain embodiments, R 8 is cyanomethyl. In certain embodiments, R 8 is 2-hydroxyethyl. In certain embodiments, R 8 and 2-methoxyethyl.

[0101] In certain embodiments, R 9 is methyl. In certain embodiments, R 9 is ethyl. In certain embodiments, R 9 is n-propyl. In certain embodiments, R 9 is iso-propyl. In certain embodiments, R 9 is sec-butyl. In certain embodiments, R 9 is iso-butyl. In certain embodiments, R 9 is n-butyl. In certain embodiments, R 9is cyclopropyl. In certain embodiments, R 9 is cyclopropylmethyl. In certain embodiments, R 9 is methylcyclopropyl. In certain embodiments, R 9 is cyclopropylethyl. In certain embodiments, R 9 is cyclobutyl. In certain embodiments, R 9 is allyl. In certain embodiments, R 9 is methylallyl. In certain embodiments, R 9 is 2-methylallyl. In certain embodiments, R 9 is 3-methylallyl. In certain embodiments, R 9 is allylmethyl. In certain embodiments, R 9 is propargyl. In certain embodiments, R 9 is cyanomethyl. In certain embodiments, R 9 is 2-hydroxyethyl. In certain embodiments, R 9 and 2-methoxyethyl.

[0102] In certain embodiments, R 8 and R 9 are different. In certain embodiments, R 8 and R 9 are identical. In certain embodiments, R 8 and R 9 is methyl. In certain embodiments, R 8 is methyl, R 9 is ethyl. In certain embodiments, R 8 is ethyl, and R 9 is n-propyl.

[0103] In certain embodiments, R 10 is H. In certain embodiments, R 10 is methyl. In certain embodiments, R 10 is phenyl. In certain embodiments, R 10 is benzyl.

[0104] In certain embodiments, R f1 is H. In certain embodiments, R f2 is H.

[0105] In certain embodiments, R 4 is F and R 5 , R 6 , and R 7 Each of R is H. In certain embodiments, 5 is F and R 4 , R 6 , and R 7 Each of R is H. In certain embodiments, 6 is F and R 4 , R 5 , and R 7 Each of R is H. In certain embodiments, 7 is F and R 4 , R 5 , and R 6 Each of R is H. In certain embodiments, 4 and R 5 Each of is F and R 6 and R 7 Each of R is H. In certain embodiments, 4 and R 6 Each of is F and R 5 and R 7 Each of R is H. In certain embodiments, 4 and R 7 Each of is F and R 5 and R 6 Each of R is H. In certain embodiments, 5 and R 6 Each of is F and R 4 and R 7 Each of R is H. In certain embodiments, 5 and R 7 Each of is F and R 4 and R 6 Each of R is H. In certain embodiments, 6 and R 7 Each of is F and R 4 and R 5 Each of is H.

[0106] In certain embodiments, the compound is 2-(ethyl(propyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one, 2-(ethyl(methyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one, 2-(dimethylamino)-1-(4-fluoro-1H-indol-3-yl)ethan-1-one, 2-(dimethylamino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one, 2-(dimethylamino)-1-(6-fluoro-1H-indol-3-yl)ethan-1-one, 2-(dimethylamino)-1-(7-fluoro-1H-indol-3-yl)ethan-1-one, 1-(4,5-difluoro-1H-indol-3-yl)-2-(dimethylamino)ethan-1-one, 1-(4,6-difluoro-1H-indol-3-yl)-2-(dimethylamino)ethan-1-one, 1-(5,6-difluoro-1H-indol-3-yl)-2-(dimethylamino)ethan-1-one, 1-(5,7-difluoro-1H-indol-3-yl)-2-(dimethylamino)ethan-1-one, and 1-(6,7-difluoro-1H-indol-3-yl)-2-(dimethylamino)ethan-1-one is selected from the group consisting of:

[0107] In another aspect, the disclosure provides a compound of formula (III), or a salt, prodrug, solvate, isotopologue, or stereoisomer thereof, TIFF2024523822000315.tif34128 formula, R 8 and R 9 each independently represents an optionally substituted C 1 ~C 8 Alkyl, optionally substituted C3 ~C 8 Cycloalkyl, optionally substituted C 2 ~C 8 Alkenyl, and optionally substituted C 2 ~C 8 alkynyl, R 10 is H, optionally substituted C 1 ~C 6 Alkyl, optionally substituted C 2 ~C 6 Alkenyl, optionally substituted C 2 ~C 6 Alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C 2 ~C 9 Heteroaryl; R 11 and R 12 are independently H, F, Cl, Br, I, OR A , N(R A )(R B ), optionally substituted C 1 ~C 6 Alkyl, optionally substituted C 2 ~C 6 Alkenyl, optionally substituted C 2 ~C 6 Alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C 2 ~C 9 Heteroaryl; R 13 may be substituted C 1 ~C 6 Alkyl, optionally substituted C 1 ~C 6 Alkenyl, optionally substituted C 1 ~C 6 Alkynyl, optionally substituted C 1 ~C 3 Haloalkyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C 2 ~C9 Heteroaryl; R f1 and R f2 are each independently H and C 1 ~C 6 is selected from the group consisting of alkyl, R g1 and R g2 are each independently H and C 1 ~C 6 is selected from the group consisting of alkyl, R A Each occurrence of is independently H, C 1 ~C 6 Alkyl, C 2 ~C 6 Alkenyl, C 1 ~C 6 Haloalkyl, -C(=O)C 1 ~C 6 Alkyl, -C(=O)C 6 ~C 10 Aryl, -C(=O)NH(C 1 ~C 6 alkyl), -C(=O)NH(C 6 ~C 10 Aryl), -C(=O)N(C 1 ~C 6 Alkyl) 2 , -C(=O)N(C 1 ~C 6 Alkyl)(C 6 ~C 10 aryl), -C(=O)O(C 1 ~C 6 alkyl), -C(=O)O(C 6 ~C 10 aryl), -P(=O)(O(C 1 ~C 6 Alkyl) 2 , -P(=O)(O(C 1 ~C 6 Alkyl))(OH), -P(=O)(OH) 2 , -S(=O) 2 O(C 6 ~C 10 Aryl), -S(=O) 2 O(C 1 ~C6 Alkyl), -S(=O) 2 O(C 6 ~C 10 Aryl), -S(=O) 2 NH(C 1 ~C 6 Alkyl), -S(=O) 2 NH(C 6 ~C 10 Aryl), -S(=O) 2 N(C 1 ~C 6 Alkyl)(C 1 ~C 6 alkyl), and -S(=O) 2 N(C 1 ~C 6 Alkyl)(C 6 ~C 10 aryl), R B Each occurrence of is independently H, C 1 ~C 6 Alkyl, C 1 ~C 3 Haloalkyl, C 2 ~C 6 Alkenyl, benzyl, naphthyl, C 2 ~C 9 selected from the group consisting of heteroaryl, and phenyl; The compound, or a salt, prodrug, solvate, isotopologue or stereoisomer thereof, is provided.

[0108] In certain embodiments, R 3 is H. In certain embodiments, R 3 is methyl. In certain embodiments, R 3 is phenyl. In certain embodiments, R 3 is benzyl.

[0109] In certain embodiments, R 8 is methyl. In certain embodiments, R 8 is ethyl. In certain embodiments, R 8 is n-propyl. In certain embodiments, R 8is iso-propyl. In certain embodiments, R 8 is sec-butyl. In certain embodiments, R 8 is iso-butyl. In certain embodiments, R 8 is n-butyl. In certain embodiments, R 8 is cyclopropyl. In certain embodiments, R 8 is cyclopropylmethyl. In certain embodiments, R 8 is methylcyclopropyl. In certain embodiments, R 8 is cyclopropylethyl. In certain embodiments, R 8 is cyclobutyl. In certain embodiments, R 8 is allyl. In certain embodiments, R 8 is methylallyl. In certain embodiments, R 8 is 2-methylallyl. In certain embodiments, R 8 is 3-methylallyl. In certain embodiments, R 8 is allylmethyl. In certain embodiments, R 8 is propargyl. In certain embodiments, R 8 is cyanomethyl. In certain embodiments, R 8 is 2-hydroxyethyl. In certain embodiments, R 8 and 2-methoxyethyl.

[0110] In certain embodiments, R 9 is methyl. In certain embodiments, R 9 is ethyl. In certain embodiments, R 9 is n-propyl. In certain embodiments, R 9 is iso-propyl. In certain embodiments, R 9 is sec-butyl. In certain embodiments, R 9 is iso-butyl. In certain embodiments, R 9 is n-butyl. In certain embodiments, R 9 is cyclopropyl. In certain embodiments, R 9is cyclopropylmethyl. In certain embodiments, R 9 is methylcyclopropyl. In certain embodiments, R 9 is cyclopropylethyl. In certain embodiments, R 9 is cyclobutyl. In certain embodiments, R 9 is allyl. In certain embodiments, R 9 is methylallyl. In certain embodiments, R 9 is 2-methylallyl. In certain embodiments, R 9 is 3-methylallyl. In certain embodiments, R 9 is allylmethyl. In certain embodiments, R 9 is propargyl. In certain embodiments, R 9 is cyanomethyl. In certain embodiments, R 9 is 2-hydroxyethyl. In certain embodiments, R 9 and 2-methoxyethyl.

[0111] In certain embodiments, R 10 is H. In certain embodiments, R 10 is methyl. In certain embodiments, R 10 is phenyl. In certain embodiments, R 10 is benzyl.

[0112] In certain embodiments, R 11 is optionally substituted C 1 ~C 6 In certain embodiments, R 11 is H. In certain embodiments, R 11 is F. In certain embodiments, R 11 is OH. In certain embodiments, R 11 is OMe.

[0113] In certain embodiments, R 12 is optionally substituted C 1 ~C 6In certain embodiments, R 12 is H. In certain embodiments, R 12 is F. In certain embodiments, R 12 is OH. In certain embodiments, R 12 is OMe.

[0114] In certain embodiments, R 13 is H. In certain embodiments, R 13 is methyl. In certain embodiments, R 13 is phenyl optionally substituted with at least one halogen. In certain embodiments, R 13 is benzyl. In certain embodiments, R 13 CF 3 In certain embodiments, R 13 is CHF 2 It is.

[0115] In certain embodiments, R f1 is H. In certain embodiments, R f2 is H. In certain embodiments, R g1 is H. In certain embodiments, R g2 is H.

[0116] In certain embodiments, the compound is N-ethyl-N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)propan-1-amine, 2-(7-fluoro-5-methoxy-1H-indol-3-yl)-N,N-dimethylethan-1-amine, N,N-diethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethan-1-amine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine, 3-(2-(dimethylamino)ethyl)-7-fluoro-1H-indol-5-ol, 3-(2-(diethylamino)ethyl)-7-fluoro-1H-indol-5-ol, 3-(2-(dipropylamino)ethyl)-7-fluoro-1H-indol-5-ol, N-ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-N-methylethan-1-amine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-ethyl-N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)propan-2-amine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, 3-(2-(ethyl(methyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 7-fluoro-3-(2-(methyl(propyl)amino)ethyl)-1H-indol-5-ol, 7-fluoro-3-(2-(isopropyl(methyl)amino)ethyl)-1H-indol-5-ol, 3-(2-(ethyl(propyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 3-(2-(ethyl(isopropyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 7-fluoro-3-(2-(isobutyl(methyl)amino)ethyl)-1H-indol-5-ol, 3-(2-(cyclobutyl(methyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 3-(2-(allyl(methyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 7-fluoro-3-(2-(isobutyl(isopropyl)amino)ethyl)-1H-indol-5-ol, 3-(((2R)-1-(sec-butyl)pyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, (R)-7-fluoro-3-((1-isopropylpyrrolidin-2-yl)methyl)-5-methoxy-1H-indole, (R)-3-((1-cyclobutylpyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, (R)-3-((1-cyclopropylpyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, (R)-3-((1-allylpyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, 3-(((2R)-1-(but-3-en-2-yl)pyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, and (R)-7-Fluoro-5-methoxy-3-((1-(prop-2-yn-1-yl)pyrrolidin-2-yl)methyl)-1H-indole is selected from the group consisting of:

[0117] In certain embodiments, each occurrence of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclyl is independently selected from the group consisting of C 1 ~C 6 Alkyl, C 3 ~C 8 Cycloalkyl, halo, cyano, OR A , optionally substituted benzyl, optionally substituted phenyl, optionally substituted C 2~C 9 Heteroaryl, C(=O)OR A ,OC(=O)OR A ,OC(=O)R A , S.R. A , S(=O)R A , S(=O) 2 R A , S(=O) 2 N(R A )(R B ), N(R A )S(=O) 2 R A , N(R A )C(=O)R A , C(=O)N(R A )(R B ), and N(R A )(R B ) may be substituted with at least one substituent selected from the group consisting of:

[0118] In certain embodiments, each occurrence of optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, and optionally substituted heterocyclyl is independently selected from the group consisting of C 1 ~C 6 Alkyl, C 3 ~C 8 Cycloalkyl, halo, cyano, OR A , optionally substituted benzyl, optionally substituted phenyl, optionally substituted C 2 ~C 9 Heteroaryl, C(=O)OR A ,OC(=O)OR A ,OC(=O)R A , S.R. A , S(=O)R A , S(=O) 2 R A , S(=O) 2 N(R A )(R B ), N(R A )S(=O) 2 R A , N(R A )C(=O)RA , C(=O)N(R A )(R B ), and N(R A )(R B ) may be substituted with at least one substituent selected from the group consisting of:

[0119] In certain embodiments, each occurrence of benzyl, phenyl, and heteroaryl is independently selected from the group consisting of C 1 ~C 6 Alkyl, C 3 ~C 8 Cycloalkyl, halo, cyano, OR A , C(=O)OR A ,OC(=O)OR A ,OC(=O)R A , S.R. A , S(=O)R A , S(=O) 2 R A , S(=O) 2 N(R A )(R B ), N(R A )S(=O) 2 R A , N(R A )C(=O)R A , C(=O)N(R A )(R B ), and N(R A )(R B ) may be substituted with at least one substituent selected from the group consisting of:

[0120] In certain embodiments, each occurrence of optionally substituted benzyl, optionally substituted phenyl, and optionally substituted heteroaryl is independently selected from the group consisting of C 1 ~C 6 Alkyl, C 3 ~C 8 Cycloalkyl, halo, cyano, OR A , C(=O)OR A ,OC(=O)OR A ,OC(=O)R A , S.R. A , S(=O)R A , S(=O) 2 RA , S(=O) 2 N(R A )(R B ), N(R A )S(=O) 2 R A , N(R A )C(=O)R A , C(=O)N(R A )(R B ), and N(R A )(R B ) may be substituted with at least one substituent selected from the group consisting of:

[0121] In another aspect, the present disclosure provides a method for producing a method for manufacturing a pharmaceutical composition comprising: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)prop-2-en-1-amine, 2-(5-fluoro-1H-indol-3-yl)-N,N-dimethylpropan-1-amine, N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine, N,N-diethyl-2-(4-fluoro-1H-indol-3-yl)ethan-1-amine, N-(2-(4-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine, N-(2-(7-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine, N-(2-(5,6-difluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine, 2-(5,7-difluoro-1H-indol-3-yl)-N,N-diethylethan-1-amine, N-(2-(5,7-difluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine, 2-(6,7-difluoro-1H-indol-3-yl)-N,N-diethylethan-1-amine, N-(2-(6,7-difluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine, and 2-(5-Fluoro-1H-indol-3-yl)propan-1-amine The present invention provides a compound selected from the group consisting of:

[0122] The compounds of the present invention may have one or more stereocenters, and each stereocenter may exist independently in either the (R) or (S) configuration. In certain embodiments, the compounds described herein exist in optically active or racemic forms. The compounds described herein include racemic, optically active, regioisomeric and stereoisomeric forms, or combinations thereof, that have the therapeutically useful properties described herein. Preparation of optically active forms is accomplished in any suitable manner, including, by way of non-limiting example, resolution of racemic forms by recrystallization techniques, synthesis from optically active starting materials, chiral synthesis, or chromatographic separation using chiral stationary phases. Compounds represented herein by racemic formulas further represent either of the two enantiomers or any mixture thereof, or, if two or more chiral centers are present, all diastereomers or any mixture thereof.

[0123] In certain embodiments, compounds of the invention exist as tautomers. All tautomers are included within the scope of the compounds described herein.

[0124] The compounds described herein also include isotopically labeled compounds, in which one or more atoms are replaced by an atom having the same atomic number but an atomic mass or mass number different from that normally found in nature. Examples of isotopes suitable for inclusion in the compounds described herein include: 2 H, 3 H, 11 C. 13 C. 14 C. 36 Cl, 18 F, 123 I, 125 I, 13 N, 15 N, 15 O. 17 O. 18 O. 32P, and 35 In certain embodiments, substitution with heavier isotopes such as deuterium provides greater chemical stability. Isotopically labeled compounds are prepared by any suitable method or process that uses a suitable isotopically labeled reagent in place of an otherwise non-labeled reagent.

[0125] In certain embodiments, the compounds described herein are labeled by other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels.

[0126] In all embodiments provided herein, the examples of suitable optional substituents are not intended to limit the scope of the claimed invention. The compounds of the invention may contain any of the substituents or combinations of substituents provided herein.

[0127] salt The compounds described herein may form salts with acids or bases, and such salts are included in the present invention. The term "salt" encompasses addition salts of free acids or bases that are useful within the methods of the present invention. The term "pharmaceutical acceptable salt" refers to a salt that has a toxicity profile within a range that provides usefulness in pharmaceutical applications. In certain embodiments, the salt is a pharmaceutical acceptable salt. Nevertheless, non-pharmaceutical acceptable salts may have properties, such as high crystallinity, that have utility in the practice of the present invention, for example, utility in the process of synthesis, purification, or formulation of compounds useful within the methods of the present invention.

[0128] Suitable pharma- ceutically acceptable acid addition salts can be prepared from inorganic or organic acids. Examples of inorganic acids include sulfuric acid, hydrogen sulfate, hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, carbonic acid, sulfuric acid, and phosphoric acid (including hydrogen phosphate and dihydrogen phosphate). Suitable organic acids may be selected from the aliphatic, alicyclic, aromatic, diastereoaliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, examples of which include formic acid, acetic acid, propionic acid, succinic acid, glycolic acid, gluconic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, glucuronic acid, maleic acid, fumaric acid, pyruvic acid, aspartic acid, glutamic acid, benzoic acid, anthranilic acid, 4-hydroxybenzoic acid, phenylacetic acid, mandelic acid, acetic ... Acids include embonic acid (or pamoic acid), methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, pantothenic acid, sulfanilic acid, 2-hydroxyethanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, cyclohexylaminosulfonic acid, stearic acid, alginic acid, β-hydroxybutyric acid, salicylic acid, galactaric acid, galacturonic acid, glycerophosphonic acid, and saccharin (e.g., saccharinate, sugarate). The salts may be comprised of one molar equivalent, one molar equivalent, or more than one molar equivalent of acid or base with respect to any compound of the invention.

[0129] Suitable pharma- ceutically acceptable base addition salts of the compounds of the present invention include, for example, ammonium salts, and metal salts including alkali metal, alkaline earth metal and transition metal salts such as calcium, magnesium, potassium, sodium and zinc salts. Pharmaceutically acceptable base addition salts also include organic salts made from basic amines such as, for example, N,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (or N-methylglucamine) and procaine. All of these salts can be prepared from the corresponding compound, for example, by reacting the appropriate acid or base with the compound.

[0130] synthesis The present invention further provides a method for preparing the compounds of the present invention. The compounds of the present teachings can be prepared from commercially available starting materials, compounds known in the literature, or easily prepared intermediates, by using standard synthetic methods and procedures known to those skilled in the art, according to the procedures outlined herein. Standard synthetic methods and procedures for the preparation of organic molecules and functional group transformations and manipulations can be readily obtained from the relevant scientific literature or standard textbooks in the field.

[0131] Where typical or preferred process conditions (i.e., reaction temperatures, times, molar ratios of reactants, solvents, pressures, etc.) are given, it will be understood that other process conditions can also be used unless otherwise specified. Optimum reaction conditions may vary with the particular reactants or solvents used, but such conditions can be determined by one of ordinary skill in the art by routine optimization procedures. Those skilled in the art of organic synthesis will recognize that the nature and order of the synthetic steps presented may be varied for the purpose of optimizing the formation of the compounds described herein.

[0132] The processes described herein can be monitored according to any suitable method known in the art. For example, product formation can be monitored by nuclear magnetic resonance spectroscopy (e.g., 1 H or 13 C), infrared spectroscopy, spectrophotometry (e.g., UV-visible), mass spectroscopy, or by chromatographic methods such as high performance liquid chromatography (HPLC), gas chromatography (GC), gel permeation chromatography (GPC), or thin layer chromatography (TLC).

[0133] Preparation of compounds may involve protection and deprotection of various chemical groups. The need for protection and deprotection, and the selection of appropriate protecting groups, can be readily determined by those skilled in the art. The chemistry of protecting groups can be found, for example, in Greene, et al., Protective Groups in Organic Synthesis, 2d.Ed. (Wiley & Sons, 1991), the entire disclosure of which is incorporated herein by reference for all purposes.

[0134] The reactions or processes described herein can be carried out in a suitable solvent that can be easily selected by those skilled in the art of organic synthesis. A suitable solvent is typically substantially non-reactive with the reactants, intermediates, and / or products at the temperature at which the reaction is carried out, i.e., a temperature that can range from the freezing temperature of the solvent to the boiling temperature of the solvent. A given reaction can be carried out in one solvent or a mixture of more than one solvent. Depending on the particular reaction step, a suitable solvent for a particular reaction step can be selected.

[0135] Compounds of formula (I), formula (II), or formula (III) can be prepared from commercially available or previously documented starting materials, for example, according to the synthetic methods outlined herein or according to methods known in the art. Fluorinated tryptamines (IV) can be obtained commercially or synthesized according to procedures known to those skilled in the art.

[0136] In the following schemes (Schemes 1 to 8), R I and R II are each independently H or optionally substituted C 1 ~C 8 is hydrocarbyl, R III is optionally substituted C 1 ~C 8 hydrocarbyl, X is Cl or Br, and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , L, Ra1 , R b1 , R b2 , R c1 , R c2 , and R are defined within the scope of this disclosure.

[0137] In the presence of a carbonyl compound (V), NaBH 3 Reductive alkylation of IV using a suitable hydride source, including but not limited to, CN, provides VI (Scheme 1). In certain embodiments, the carbonyl compound (V) is an aldehyde or ketone. In a non-limiting example, the subsequent reductive alkylation of VI can be carried out using NaBH in the presence of an aldehyde (VII). 3 CN to provide a compound of formula (Ia). In certain embodiments, compound (VI) is isolated as an intermediate. In other embodiments, compound (VI) is further reductively alkylated in situ to provide Ia without isolating compound (VI). Additionally, a compound of formula (Ia) can be prepared, in a non-limiting example, by reductive alkylation with NaBH in the presence of excess aldehyde (VII). 3 It can be prepared in one step by reductive amination of IV using CN. TIFF2024523822000316.tif59165

[0138] Formylation of IV to provide IX is accomplished using a suitable formylation reagent (non-limiting examples include compound (VIII) (e.g., ethyl formate)) under conditions including, but not limited to, heating and / or microwave irradiation (Scheme 2). Reduction of IX with a suitable reducing agent, including, but not limited to, Red-Al (i.e., sodium bis(2-methoxyethoxy)aluminum hydride), provides VIa. In a non-limiting example, reductive alkylation of VIa can be achieved using NaBH in the presence of aldehyde (VII). 3 CN is used to provide a compound of formula (Ib). TIFF2024523822000317.tif71164

[0139] Alternatively, alkylation of VI can be carried out with a suitable base (a non-limiting example is Et3 N), and a suitable alkylating agent (non-limiting examples include alkyl, aryl, propargyl, and / or benzyl halides (X)) to provide compounds of formula (Ic) (Scheme 3). TIFF2024523822000318.tif43128

[0140] In certain embodiments, compounds of formula (I), which are compounds of formula (Id), can be prepared from fluorinated indoles (XI). Acylation of XI with a suitable electrophilic oxalic acid derivative (XII) (non-limiting examples include oxalyl chloride), followed by treatment with a suitable nucleophilic amine (XIII) provides XIV (Scheme 4). The reaction with a suitable reducing agent (non-limiting examples include LiAlH 4 Subsequent reduction of XIV with a 2-aminopropyl group (including) provides compounds of formula (Id). TIFF2024523822000319.tif37164

[0141] In certain embodiments, compounds of formula (I), which are compounds of formula (Ie), are prepared from XI using a Michael addition / reduction sequence (Scheme 5). ZnCl 2 Treatment of XI with an α,β-unsaturated amide XV in the presence of a suitable Lewis acid, including but not limited to LiAlH, provides XIV. 4 Reduction of XIV with a suitable reducing agent, including but not limited to, provides compound (Ie). TIFF2024523822000320.tif43165

[0142] In certain embodiments, the compound of formula (I), which is a compound of formula (If), is a Friedel-Crafts acylation / S NIt is prepared from XI using a two-reaction sequence (Scheme 6). Treatment of XI with an α-halo-acyl halide (XV) in the presence of a base, including but not limited to pyridine, provides XVI. In certain embodiments, the acyl halide is an acyl chloride or acyl bromide. In certain embodiments, the α-haloacyl halide is an α-chloroacyl halide or an α-bromoacyl halide. Nucleophilic displacement of the α-halide (XVI) with an amine (XIII) in the presence of a suitable catalyst, including but not limited to potassium iodide, provides compound (If). TIFF2024523822000321.tif38165

[0143] In certain embodiments, compounds of formula (I), which are compounds of formula (Ig), are prepared from XVII in a sequence that includes incorporation of an α,β-unsaturated nitro group, followed by Michael addition, nitro reduction, and reductive alkylation (Scheme 7). 4 Treatment of aldehyde XVII with nitromethane in the presence of a suitable base, including but not limited to OAc, allows for [1,2]-carbonyl addition (i.e., Henry addition) with subsequent dehydration to give α,β-unsaturated nitro compound XVIII. Treatment of XVIII with a Grignard reagent under suitable conditions for reactivity provides Michael adduct XIX. Reducing by H 2 Reduction of XIX in the presence of NaBH provides the amine XX. 3 Reductive alkylation of amines XX using a suitable hydride source, including but not limited to CN, provides compounds of formula (Ig). TIFF2024523822000322.tif67164

[0144] In certain embodiments, compounds of formula (I), which are compounds of formula (Ih), are prepared from XI utilizing a [1,2]-carbonyl addition / reduction sequence (Scheme 8). Treatment of XI with a suitable base (non-limiting examples include KOH) in a suitable solvent (non-limiting examples include methanol) in the presence of an N-protected heterocyclyl ketone (XXII) provides XXIII. In certain embodiments, XXIII can be prepared by alternative methods. In certain embodiments, R is tert-butyl or benzyl. The addition of a suitable reducing agent (non-limiting examples include LiAlH 4 Reduction of XXIII with, for example, TIFF2024523822000323.tif46164

[0145] method In one aspect, the disclosure provides a pharmaceutical composition comprising at least one compound of the disclosure and a pharma- ceutically acceptable carrier.

[0146] In one aspect, the present disclosure provides a method of treating, preventing, and / or ameliorating a psychiatric disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of at least one compound of the present disclosure, or a pharmaceutical composition of the present disclosure.

[0147] In certain embodiments, the psychiatric disease or disorder is selected from the group consisting of a depressive disorder, an anxiety disorder, and an eating disorder.

[0148] In certain embodiments, the psychiatric disease or disorder is attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), treatment resistant depression, major depressive disorder (MDD), bipolar I disorder, bipolar II disorder, cyclothymic disorder, antisocial personality disorder, pain, sleep-wake disorder, severe mood dysregulation disorder, persistent depressive disorder (dysthymia), premenstrual dysphoric disorder, substance / medication induced depressive disorder, postpartum depression, depressive disorder due to another medical condition, separation anxiety disorder, specific phobia, social anxiety disorder, panic disorder, panic attacks, agoraphobia, generalized anxiety disorder, substance / medication induced depressive disorder, In one embodiment, the present invention relates to a disorder characterized by a psychiatric disorder, autism spectrum disorder, anxiety disorder due to another medical condition, somatic symptom disorder, illness anxiety disorder, obsessive-compulsive disorder (OCD), obsessive-compulsive and related disorders (OCRD), OCRD due to another medical condition, substance-related disorder, alcohol-related disorder, cannabis-related disorder, hallucinogen-related disorder, inhalant-related disorder, cocaine-related disorder, opioid-related disorder, sedative-related disorder, hypnotic-related disorder, and / or anxiolytic-related disorder, psychostimulant-related disorder, tobacco-related disorder, non-substance-related disorder (gambling addiction and / or gaming addiction), anorexia nervosa, bulimia nervosa, and binge eating disorder.

[0149] In certain embodiments, the subject is further administered at least one additional agent useful for treating, preventing, and / or ameliorating a psychiatric disease or disorder. In certain embodiments, the at least one additional agent is a selective serotonin reuptake inhibitor, a triple reuptake inhibitor, a serotonin and norepinephrine reuptake inhibitor, a tricyclic antidepressant, a tetracyclic antidepressant, a dopamine reuptake inhibitor, a mood stabilizer, an anticonvulsant, an antipsychotic, an anxiolytic, a benzodiazepine, a monoamine releasing agent, a dopamine receptor agonist, a cannabinoid, a triptan, a migraine medication, an analgesic, an anti-inflammatory, an immunomodulator, a 5-HT 1A Receptor antagonist, 5-HT 2 Receptor antagonist, 5-HT 3The compound is selected from the group consisting of receptor antagonists, monoamine oxidase inhibitors, and noradrenergic antagonists. In certain embodiments, the subject is co-administered at least one compound and at least one additional drug. In certain embodiments, the at least one compound and at least one additional drug are combined.

[0150] In certain embodiments, the subject is a mammal, hi certain embodiments, the mammal is a human.

[0151] Pharmaceutical Compositions and Formulations The present invention provides pharmaceutical compositions comprising at least one compound of the present invention, or a salt, prodrug, solvate, isotopologue, or stereoisomer thereof, which are useful for carrying out the method of the present invention. Such pharmaceutical compositions may consist of at least one compound of the present invention, or a salt or solvate thereof, in a form suitable for administration to a subject, or the pharmaceutical composition may comprise at least one compound of the present invention, or a salt or solvate thereof, and one or more pharma- ceutically acceptable carriers, one or more additional components, or any combination thereof. At least one compound of the present invention may be present in the pharmaceutical composition in the form of a physiologically acceptable salt, e.g., in combination with a physiologically acceptable cation or anion, as is well known in the art.

[0152] The relative amounts of the active ingredient, pharma- ceutically acceptable carrier, and / or any additional ingredients in a pharmaceutical composition of the present invention will vary depending on the identity, size, and condition of the subject being treated, as well as the route by which the composition is administered.

[0153] Combination therapy In one embodiment, the compounds of the invention are useful in the methods of the invention in combination with one or more additional agents useful for treating a psychiatric disorder. These additional agents may include compounds or compositions identified herein, or compounds (e.g., commercially available compounds) known to treat, prevent, or alleviate the symptoms of one or more of the psychiatric disorders described herein.

[0154] Administration / Dosage Dosage regimens can affect what constitutes an effective amount. Therapeutic formulations may be administered to a patient either before or after the onset of a disease or disorder. Furthermore, several divided and staggered dosages may be administered daily or continuously, or the dose may be continuously infused or bolus injected. Furthermore, the dosage of the therapeutic formulation may be proportionally increased or decreased as indicated by the exigencies of the therapeutic or prophylactic situation.

[0155] The administration of the compositions of the present invention to patients, such as mammals, such as humans, can be carried out using known procedures at dosages and for periods of time effective to treat the diseases or disorders contemplated herein. The effective amount of therapeutic compound required to achieve a therapeutic effect can vary according to factors such as the activity of the particular compound used, the time of administration, the rate of excretion of the compound, the duration of treatment, other drugs, compounds or materials used in combination with the compound, the state of the disease or disorder of the patient being treated, age, sex, weight, condition, general health and previous medical history, and similar factors well known in the medical field. The dosage regimen can be adjusted to provide an optimal therapeutic response. For example, several divided doses can be administered daily, or the dose can be proportionally reduced as indicated by the exigencies of the therapeutic situation.

[0156] Actual dosage levels of the active ingredients in the pharmaceutical compositions of the present invention may be varied to obtain an amount of the active ingredient effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration without being toxic to the patient.

[0157] A medical practitioner, e.g., a physician or veterinarian, having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required. For example, the physician or veterinarian can start dosing the compound of the present disclosure used in the pharmaceutical composition at a level lower than that required to achieve the desired therapeutic effect, and gradually increase the dosage until the desired effect is achieved.

[0158] Those skilled in the art will recognize or be able to ascertain, using no more than routine experimentation, numerous equivalents to the specific procedures, embodiments, claims and examples described herein. Such equivalents are considered to be within the scope of the present invention and covered by the appended claims. Modifications by art-recognized substitutions of reaction conditions, including but not limited to reaction times, reaction sizes / volumes, and experimental reagents such as solvents, catalysts, pressure, atmospheric conditions, e.g., nitrogen atmosphere, and reducing / oxidizing agents, and using no more than routine experimentation, are understood to be within the scope of this application.

[0159] Whenever values ​​and ranges are provided herein, it should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Thus, all values ​​and ranges encompassed by these values ​​and ranges are meant to be encompassed within the scope of the invention. Moreover, all values ​​falling within these ranges, as well as the upper or lower limits of values ​​of a range, are also contemplated by this application. The description of a range should be considered to have specifically disclosed all possible subranges and individual numerical values ​​within that range, and, where appropriate, partial integers of numerical values ​​within the range. For example, the description of a range such as 1 to 6 should be considered to have specifically disclosed subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, and the like, as well as the individual numbers within that range, e.g., 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range.

[0160] The following examples further illustrate aspects of the present invention, but do not in any way limit the teachings or disclosure of the present invention set forth herein. EXAMPLES

[0161] The invention will now be described with reference to the following examples, which are provided for illustrative purposes only, and the invention is not limited to these examples, but rather encompasses any variations that become evident as a result of the teachings provided herein.

[0162] Materials and Methods material All starting materials, reagents, and solvents used in the synthesis were obtained from the following chemical vendors: AK Scientific (Union City, CA), Matrix Scientific (Columbia, SC), 1PlusChem (San Diego, CA), Enamine (Ukraine), ChemScene LLC (Monmouth Junction, NJ), Oakwood Chemical (Columbia, SC), and Sigma Aldrich (St Louis, MO).

[0163] Mass and pH measurements pH readings were obtained with an Orion 3 star (Thermo Scientific, USA) pH meter fitted with a Thermo pH electrode (9142BN) filled with 3M KCl ROSS Orion filling solution (Thermos Scientific, USA). An Ohaus ADVENTURER AX124 analytical balance (Ohaus, New Jersey, USA) was used. Samples were weighed onto 3x3 inch low nitrogen weighing Fisherbrand paper (Fisherbrand, Pittsburgh, USA). For analytical samples, the analytical balance and pH meter were calibrated prior to use. The calibration of the analytical balance was verified with a 5 mg standard weight (Troemner, Thorofare, NJ) with a cutoff of 5±0.1 mg. The pH meter was calibrated by utilizing pH 4.01 and pH 7 buffers from Orion application solution (Thermo Scientific, USA) for two-point calibration.

[0164] High-performance liquid chromatography (HPLC) An Agilent 1260 Infinity system equipped with a 1260 Quaternary Pump VL, a 1260 ALS Autosampler, a 1260 Thermostatted Column Compartment, and a 1200 DAD Multiple Wavelength Detector (Agilent Technologies, Santa Clara, CA, USA) was used. The detection wavelengths were set at 220, 254 nm. Separation of tryptamines was achieved using a Zorbax Eclipse Plus-C18 analytical column (5 μm, 4.6 × 150 mm) from Agilent (Agilent Technologies, Santa Clara, CA, USA). Mobile phase A was 10 mM ammonium formate aqueous buffer titrated to pH 4.5 with 10 mM formic acid in water. Mobile phase B was acetonitrile. The sample injection volume was 40 μL, the flow rate was 1.0 mL / min, and the column temperature was set at 25 °C. For all samples, a wash (30:70 A:B) was injected between runs. Run times were 10 min using an isocratic mobile phase ratio of 70% A and 30% B (isocratic). Chromatograms and peak areas were analyzed using Agilent ChemStation Software (Agilent Technologies, Santa Clara, CA, USA).

[0165] High resolution mass spectrometry (HRMS) HRMS experiments were performed on a Thermo Orbitrap Exactive Mass Spectrometer equipped with an Orbitrap mass analyzer calibrated using electrospray ionization with PierceTM LTQ ESI Positive Ion Calibration Solution (ThermoFisher Scientific, USA). Samples were ionized via an atmospheric solids analysis probe (ASAP). Thermo Xcalibur Qual Browser software was used to analyze the results and confirm their originality if the error was less than 5 ppm. Measurement parameters: auxiliary gas flow rate -8, spray voltage -3.50 kV, capillary temperature -275 °C, capillary voltage -25.00 V, tube lens voltage -65.00 V, skimmer voltage -14.00 V, heater temperature -100 °C.

[0166] Gas Chromatography-Mass Spectrometry (GC-MS) A Thermo Scientific Trace 1300 Gas Chromatograph coupled to a Thermo Scientific ISQ QD Single Quadrupole Mass Spectrometer was used for GC / MS experiments. A Thermo Scientific TraceGold TG-5MS GC Column (30 m x 0.25 mm x 0.25 μm) was used for separation of any components. All samples were made at a concentration of 1 mg / mL in ethyl acetate. Ionization was achieved by electron impact (EI) at 70 eV. Data were analyzed using Thermo Xcalibur TM Software (version 3.1.66.10). The transfer line and ion source were set to 210 °C and 200 °C, respectively. The oven starting temperature was set to 100 °C and held for 1 min. The temperature was increased to 220 °C at a rate of 8 °C / min, at which point it was held for the remainder of the run time. Total run times ranged from 20 to 40 min depending on the target compounds.

[0167] Nuclear magnetic resonance spectroscopy (NMR) 1D and 2D 1H, 13 C. 19 F NMR spectral data were obtained on a Bruker Avance III (Bruker Corporation, Billerica, MA, USA) with a PA BBO 400S1 BBF-HD-05 Z Plus probe. Unless otherwise stated, samples were prepared as salt forms at a concentration of approximately 20 mg / mL in DMSO (Sigma-Aldrich, St. Louis, MO). Chemical shifts are 13 For C (δ = 39.52 ppm), relative to the DMSO standard (δ = 2.50 ppm), and 19 F (δ=0 ppm) is reported in parts per million (ppm) relative to trichlorofluoromethane. 1 H, 13 C. 19 F APT, 1 H- 13 C HSQC, 1 H- 13 C HMBC and 1 H- 1 H COSY experiment was performed.

[0168] Melting point Melting point data were obtained on a Digimelt A160 SRS digital melting point apparatus (Stanford Research Systems, Sunnyvale, Calif., USA) at a ramp rate of 2° C. / min.

[0169] Atmospheric Solids Analysis Probe Mass Spectrometry (ASAP-MS) Advion Expression with Quadrupole Mass Spectrometer sASAP MS experiments were performed on a CMS Spectrometer. Samples were ionized via an Atmospheric Solids Analysis source using an Atmospheric Pressure Chemical Ionization (APCI) attachment. Data were analyzed via Advion Data Express software. Measurement parameters were set as follows: capillary temperature = 150 °C, capillary voltage = 120 V, source gas temperature = 200 °C, and APCI corona discharge = 5 μA.

[0170] Column chromatography Flash column chromatography was performed using a Biotage Isolera One Flash Chromatograph with Spektra UV detection. UV absorption was measured at wavelengths of 254 and 280 nm. KP-Sil 50 g and 100 g cartridges were utilized for the separation. Cartridges were manually packed using 230-400 mesh, 60 Å silica gel (Sigma Aldrich, St Louis, MO). Unless otherwise indicated, 1% Et 3 A gradient of 5–20% EtOH in EtOAc with N was used as the mobile phase. The flow rate was 100 mL / min.

[0171] Short Path Distillation Short-path distillation was performed using a Kugelrohr short-path distillation apparatus (Sigma Aldrich, St Louis, Mo.) under high vacuum (approximately 0.1 mm Hg) using a Welch (Skokie, Ill.) Gem 8890 Vacuum pump.

[0172] Microwave Reaction A CEM Discover-SP w / activent was used as the microwave reactor. Reaction vessels were obtained from CEM in both 35 mL and 10 mL sizes. 2 Gas was used for cooling.

[0173] Docking studies Rigid docking was used using UCSD Autodock 4.2.6. The receptor used was 6WGT (Kim et al. 2020). Receptor and ligand structures were prepared using Discovery Studio Visualizer. Docking was performed using AutodockTools 1.5.6. Receptor preparation included removal of ligands, addition of polar hydrogen atoms, binding of nonpolar hydrogen atoms, and addition of Gasteiger charges. The grid was centered on the orthosteric LSD binding site. A genetic algorithm was used for the search parameters, and the output was a Lamarckian genetic algorithm. Docking results were ranked by energy, exported, and then displayed individually in PyMol.

[0174] Example 1: N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) 5-Fluorotryptamine hydrochloride (0.8 g, 3.73 mmol) was dissolved in MeOH (20 mL, dried over 3 Å molecular sieves) under argon and glacial acetic acid (21.33 μL) was added. 3 (0.26 g, 4.10 mmol) was added and the mixture was allowed to stir for 3 minutes to dissolve the particulates. Acetone (0.82 mL, 11.2 mmol) was then added and the reaction was stirred at room temperature for 4 hours. Upon completion (as confirmed by GC-MS, TLC, and ASAP-MS), acetaldehyde (0.63 mL, 11.2 mmol) was added and the reaction was stirred at room temperature for 1 hour. The reaction was then poured into 300 mL of 0.2 M HCl and extracted with EtOAc (3×50 mL). These organic phases were pooled and extracted with 0.2 M aqueous HCl (3×75 mL) and the aqueous phase was combined with the original aqueous phase. The combined aqueous phase was basified by the addition of KOH flakes and extracted with EtOAc (3×100 mL). The organic phases were combined and the pooled organic phase was washed with brine (20 mL) and anhydrous Na 2 SO 4After drying over high vacuum, the solvent was removed to give the crude product (0.98 g) as a tan oil. The crude product was purified by elution with 50% EtOH / EtOAc (1% Et 3 Purification by silica gel chromatography using N v / v) mobile phase gave the title compound as a tan solid (0.83 g, 3.34 mmol, 89.54% yield). The solid was dissolved in boiling cyclohexane and EtOAc (1 mL) and cooled to room temperature. The solution was further cooled to 4° C. until thermodynamic equilibrium was achieved, followed by standing at −20° C. for 72 h. The solution was decanted and the resulting crystals were washed with hexane. The crystallization was repeated once to give the title compound as a white crystalline solid (mp 77.1-78.1° C.). HR-ASAP-MS: m / z 249.1752 (theoretical [M+H] + ,C 15 H 22 FN 2 + ), m / z 249.1762 (observed, Δ=-4 ppm). (free base) 1 H-NMR (400MHz, d 6 -DMSO)δ 10.84(s,1H),7.29(dd,J=8.8,4.6Hz,1H),7.21(d,J=2.3Hz,1H),7.18(dd,J=10.1,2.5Hz,1H),6.86(td,J=9.2,2.5Hz,1H),2.9 4(septet,J=6.6Hz,1H),2.74-2.66(m,2H),2.61-2.54(m,2H),2.52-2.48(m,2H),0.98(t,J=7.1Hz,3H),0.92(d,J=6.6Hz,6H). 13 C-NMR (101MHz, d 6-DMSO)δ 156.55(d,J=230.8Hz,1C),132.79(s,1C),127.51(d,J=9.5Hz,1C),124.65(s,1C),113.36(d,J=4.4Hz,1C),112.16(d,J=9.7Hz,1C),10 8.77(d,J=26.2Hz,1C),102.80(d,J=22.8Hz,1C),50.17(s,1C),49.74(s,1C),43.46(s,1C),25.14(s,1C),18.32(s,2C),14.45(s,1C). 19 F-NMR (377MHz,d 6 -DMSO) δ-125.38(s,1F).

[0175] Example 2: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine (2) TIFF2024523822000325.tif30128N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine (2) was dissolved in 5-fluorotryptamine hydrochloride (0.8 g, 3.73 mmol), acetone (0.65 g, 11.2 mmol), and formaldehyde (0.93 mL, 11.2 mmol, H 2 N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 36% (v / v) in 2H2O. The crude product was purified by Kugelrohr distillation at 170-195 °C to give the title compound as a yellow crystalline solid (0.81 g, 3.46 mmol, 92.8% yield). The solid was then acidified to give the HCl salt of the title compound as a white crystalline powder. HR-ASAP-MS: m / z 235.1600 (theoretical [M+H] + ,C 14 H 20 FN 2 + ), m / z 235.1605 (measured value, Δ=-2.1 ppm). 1 H-NMR (400MHz, d 6-DMSO)δ 11.14(s,1H),10.69(s,1H),7.46(dd,J=10.1,2.5Hz,1H),7.36(dd,J=8.8,4.5Hz,2H),7.34(d,J =2.3Hz,1H),6.93(td,J=9.2,2.5Hz,1H),3.60(double septet,J=6.6,2.3Hz,1H),3.30-3.17(m, 2H),3.17-3.09(m,2H),2.71(d,J=5.1Hz,3H),1.30(d,J=6.6Hz,3H),1.23(d,J=6.6Hz,3H). 13 C-NMR (101MHz, d 6 -DMSO)δ 156.74(d,J=231.1Hz,1C),132.86(s,1C),126.99(d,J=10.0Hz,1C),125.46(s,1C),112.45(d,J=9.7Hz,1C),109.63(d,J=4.9Hz,1C),1 09.30(d,J=26.1Hz,1C),103.15(d,J=23.0Hz,1C),55.69(s,1C),52.27(s,1C),34.07(s,1C),20.05(s,1C),16.82(s,1C),14.90(s,1C). 19 F-NMR (377MHz,d 6 -DMSO) δ -124.76(s,1F).

[0176] Example 3: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylbutan-2-amine (3) TIFF2024523822000326.tif31128N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylbutan-2-amine (3) was dissolved in 5-fluorotryptamine hydrochloride (0.8 g, 3.73 mmol), methyl ethyl ketone (0.81 g, 11.2 mmol), and formaldehyde (0.93 mL, 11.2 mmol, H 2Synthesis in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 36% (v / v) in 2H2O to give the title compound as a yellow crystalline solid (0.82 g, 3.30 mmol, 88.5% yield) followed by the HCl salt as a white crystalline solid (mp 136.5-142 °C). HR-ASAP-MS: m / z 249.1756 (theoretical [M+H] + ,C 15 H 22 FN 2 + ), m / z 249.1762 (measured value, Δ=-2.4 ppm). 1 H NMR(400MHz,DMSO)δ 10.89(s,1H),7.31(dd,J=8.8,4.6Hz,1H),7.22(d,J=2.2Hz,1H),7.21(dd,J=9.8,2.5Hz,1H),6.88(td,J=9.2,2.5,Hz,1H),2.82-2.66(m, 2H),2.66-2.58(m,1H),2.58-2.51(m,2H),2.20(s,3H),1.50-1.37(m,1H),1.27-1.16(m,1H),0.87(d,J=6.5Hz,1H),0.82(t,J=7.4Hz,1H). 13 C NMR(101MHz,DMSO)δ 156.56(d,J=230.5Hz,1C),132.81(s,1C),127.52(d,J=9.5Hz,1C),124 .67(s,1C),113.26(d,J=4.9Hz,1C),112.16(d,J=9.9Hz,1C),108.77(d ,J=26.0Hz,1C),102.83(d,J=22.8Hz,1C),59.21(s,1C),53.87(s,1C), 36.34(s,1C),26.10(s,1C),23.90(s,1C),13.03(s,1C),11.38(s,1C). 19 F-NMR (377MHz,d 6 -DMSO)δ -124.78(d,J=10.1Hz,1F).

[0177] Example 4: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylpropan-1-amine (4) TIFF2024523822000327.tif32128 N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylpropan-1-amine (4) was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluorotryptamine hydrochloride (0.8 g, 3.73 mmol), acetone (0.65 g, 11.2 mmol), and propionaldehyde (0.65 g, 11.2 mmol) to give the title compound as a yellow oil (0.68 g, 2.59 mmol, 69.4% yield) and then the HCl salt as a white crystalline solid (mp 155.8-158 °C). HR-ASAP-MS: m / z 263.1912 (theoretically [M+H] + ,C 14 H 20 FN 2 + ), m / z 263.1918 (measured value, Δ=-2.3 ppm). 1 H-NMR (400MHz, d 6 -DMSO)δ 11.14(s,1H),10.39(s,1H),7.44(dd,J=10.0,2.3Hz,1H),7.39-7.33(m,2H),6.93(td,J=9.2,2.4Hz,1H),3.72-3.6 2(m,1H),3.26-3.14(m,4H),3.11-2.96(m,2H),1.79(sx,J=7.7Hz,2H),1.30(d,J=6.6Hz,6H),0.94(t,J=7.3Hz,3H). 13 C-NMR (101MHz, d 6-DMSO)δ 156.77(d,J=231.2Hz,1C),132.86(s,1C),126.99(d,J=9.8Hz,1C),125.54 (s,1C),112.50(d,J=9.8Hz,1C),109.79(d,J=4.4Hz,1C),109.32(d,J=26. 2Hz,1C),103.07(d,J=23.2Hz,1C),53.92(s,1C),50.63(s,1C),49.94(s,1 C),20.36(s,1C),17.99(s,1C),16.20(s,1C),15.88(s,1C),11.16(s,1C). 19 F-NMR (377MHz,d 6 -DMSO) δ-124.69(s,1F).

[0178] Example 5: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine (5) 5-Fluorotryptamine hydrochloride (0.8 g, 3.73 mmol) was dissolved in MeOH (20 mL, dried over 3 Å molecular sieves) under argon and glacial acetic acid (21.33 μL) was added to the reaction. NaBH 3 CN (0.26 g, 0.00410 mol) was added and the mixture was allowed to stir for 3 minutes to dissolve particulates. Propionaldehyde (1.6 mL, 22.3 mmol) was then added and the reaction was allowed to stir at room temperature for 2 hours. Upon completion (as confirmed by GC-MS, TLC, and ASAP-MS), the reaction was poured into 300 mL of 0.2 M aqueous hydrochloric acid (HCl) and washed with EtOAc (3×50 mL). The organic phases were pooled and extracted with 0.2 M HCl (3×75 mL). The aqueous extracts were then combined with the original aqueous phase. The combined aqueous phases were basified by the addition of KOH flakes and then extracted with EtOAc (3×100 mL). The pooled organic phases were then washed with brine (20 mL) and anhydrous Na 2 SO 4The mixture was dried over high vacuum and the solvent was removed to give the crude product (0.92 g) as a yellow oil. The crude product was purified by short-path high-vacuum distillation (i.e., Kugelrohr distillation) at 170-195° C. under high vacuum to give the title compound as a yellow solid (0.91 g, 3.46 mmol, 92.9% yield).

[0179] The free base was converted to the HCl salt by titrating the free base with a concentrated HCl solution in ethanol until the pH was < 2. The solvent was then evaporated several times under a stream of warm air to give a crystalline material free of excess acid or water. The resulting solid was dissolved in Et 2 The solid was dissolved in boiling EtOH (8 mL) and then washed with Et 2 2 mL of HO was slowly added to give a milky, opaque solution, which was then cooled to room temperature. The solution was further cooled to 4° C. until thermodynamic equilibrium was achieved, and then stored at −20° C. overnight. The solution was decanted and the resulting crystals were dissolved in Et 2 The mixture was washed with 2×O (3×10 mL) and dried under gentle heating. The crystallization was repeated twice to give the HCl salt of the title compound as a white crystalline solid (mp 187.5-188.0° C.). HR-ASAP-MS: m / z 263.1911 (theoretical [M+H] + ,C 16 H 24 FN 2 + ), 263.1918 (actual value, = Δ-2.7 ppm). 1 H-NMR (400MHz, d 6 -DMSO)δ 11.14(s,1H),10.64(s,1H),7.44(dd,J=10.1,2.5Hz,1H),7.38-7.33(m,2H),6.93(td,J=9.2,2.5Hz,1H) ,3.27-3.21(m,2H),3.18-3.11(m,2H),3.11-2.98(m,4H),1.72(sx,J=7.7Hz,4H),0.92(t,J=7.4Hz,6H). 13 C-NMR (101MHz, d 6-DMSO)δ 157.23(d,J=231.1Hz,1C),133.34(s,1C),127.45(d,J=10.1Hz,1C),125.97(s,1C),112.97(d,J=9.9Hz,1C),110.07(d,J=4.6Hz ,1C),109.80(d,J=26.2Hz,1C),103.57(d,J=23.1Hz,1C),53.52(s,1C),52.71(s,1C),19.84(s,2C),16.92(s,2C),11.41(s,2C). 19 F-NMR (377MHz,d 6 -DMSO) δ -124.75(s,1F).

[0180] Example 6: N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-1-amine (6) TIFF2024523822000329.tif28128Synthesis of N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-1-amine TIFF2024523822000330.tif25128N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-1-amine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluorotryptamine hydrochloride (0.8 g, 3.73 mmol) and propionaldehyde (0.22 g, 3.73 mmol) using only 1 molar equivalent of propionaldehyde to give the title compound as a yellow oil (0.3 g, 1.36 mmol, 36.5% yield). HR-ASAP-MS: m / z 221.1444 (theoretical [M+H] + ,C 13 H 18 FN 2 + ), m / z 221.1449 (measured value, Δ=-2.3 ppm).

[0181] Synthesis of N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-1-amine (6) TIFF2024523822000331.tif28128 N-Ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-1-amine (6) was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine (5) starting from N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-1-amine (0.26 g, 1.18 mmol) and acetaldehyde (0.31 g, 7.08 mmol). The crude product was purified by 20% EtOH / EtOAc (1% (v / v) EtOH) as mobile phase as opposed to Kugelrohr distillation. 3 N) to give the title compound as a yellow oil (0.21 g, 0.846 mmol) followed by the corresponding HCl salt as a white crystalline solid (mp 154.5-155.4 °C). r ) = 17.02 min, HPLC: 99.4615% purity, HR-ASAP-MS: m / z 249.1757 (theoretical [M+H] + ,C 15 H 22 FN 2 + ), m / z 249.1762 (measured value, =Δ-2 ppm). 1 H-NMR (400MHz, d 6 -DMSO)δ 11.14(s,1H),10.65(s,1H),7.44(dd,J=10.1,2.5Hz,1H),7.38-7.33(m,2H),6.93(td,J=9.2,2.5Hz,1H),3.27-3.17(m 4H),3.16-3.10(m,2H),3.10-2.99(m,2H),1.71(sx,J=7.7Hz,2H),1.26(t,J=7.2Hz,3H),0.92(t,J=7.4Hz,3H). 13 C-NMR (101MHz, d 6-DMSO)δ 156.76(d,J=231.2Hz,1C),132.87(s,1C),126.97(d,J=9.8Hz,1C),125.49(s,1C),112.50(d,J=9.9Hz,1C),109.59(d,J=4.7Hz,1C),109.33( d,J=26.3Hz,1C),103.08(d,J=23.3Hz,1C),52.39(s,1C),51.59(s,1C) ,46.45(s,1C),19.37(s,1C),16.50(s,1C),10.95(s,1C),8.36(s,1C). 19 F-NMR (377MHz,d 6 -DMSO) δ -124.74.

[0182] Example 7: N-Ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylethan-1-amine (7) TIFF2024523822000332.tif30128 Synthesis of intermediate N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methyl-2-oxoacetamide A two-necked round-bottom flask (RBF), dropping funnel, rubber septum, and magnetic stir bar were dried overnight in an oven. The reaction apparatus was assembled and then purged with argon. Et 2 20 mL of ethyl acetate was added to the flask through a dropping funnel and the solvent was cooled to 0° C. in an ice-water bath. 3.81 mL of oxalyl chloride (44.4 mmol) was added to the round-bottom flask via syringe. 7-Fluoroindole (5 g, 37.0 mmol) in Et 2 A solution of N-methylethanamine (9.85 mL, 0.115 mol) in EtO (40 mL) was added dropwise over 30 min. Once the addition was complete, the reaction was allowed to stir at 0° C. for 1 h, during which time a yellow precipitate formed. The reaction was allowed to warm to room temperature and stirred for an additional 3 h. N-methylethanamine (9.85 mL, 0.115 mol) in Et 2 A vigorously stirred solution of 200 mL of ethyl acetate was added dropwise with mixing over a period of approximately 10 minutes under positive pressure of argon (exothermic). After addition, volatiles (e.g., Et 2O and amine) were removed in high vacuum to give a whitish brown solid. The solid was washed with water and collected by high vacuum filtration. The resulting brownish tan solid was dried overnight in a fume hood and then placed in a desiccator for >24 h to give the title compound (6.7 g, 27.0 mmol, 73% yield). The compound was used in the next step without further purification.

[0183] Synthesis of N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylethan-1-amine (7) TIFF2024523822000334.tif30128A 500 mL round bottom flask with three necks, a 300 mL dropping funnel, a stir bar, and a dried condenser were dried in an oven overnight. The reaction apparatus was assembled and then purged with argon. THF (100 mL, dried over 3 Å molecular sieves) was then added to the flask and cooled to 0° C. Lithium aluminum hydride (LAH) (3.07 g, 0.081 mol) was slowly added to the round bottom flask under argon atmosphere with stirring. Once the addition was complete, a solution of N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methyl-2-oxoacetamide (6.7 g, 27.0 mmol) in 100 mL of THF was added dropwise over 1 h at 0° C. The funnel was then rinsed with additional THF (20 mL) which was added to the reaction over a period of 10 min.

[0184] The reaction was then heated at reflux for 1.5 h, then cooled to 0° C. and diluted with THF / Et 2 The reaction mixture was quenched with a mixture of 0.2 M HCl (aq) (approximately 1:1) and ice. Once quenched, brine and aqueous KOH were added to ensure basicity, followed by EtOAc (100 mL). The inorganic solids were removed by gravity filtration onto Whatman paper (24 cm diameter). The removed solids were then washed extensively with EtOAc. The filtrate was extracted with 0.2 M HCl (aq) (3×166 mL). The aqueous phase was then made basic by the addition of KOH pellets and extracted with EtOAc (3×100 mL). The pooled organic phase was washed with brine (20 mL) and anhydrous Na2 SO 4 The crude product (free base) was recrystallized from boiling hexanes with a small amount of EtOAc and stored at -20°C. The recrystallization was repeated three times to give the title compound as pale yellow transparent crystals (1.8 g, 7.25 mmol, 34.03% yield). The purified material was converted to the HCl salt as a white crystalline solid (mp 133.8-135°C). High Resolution Atmospheric Pressure Solid Analysis Probe Mass Spectrometry (HR-ASAP-MS): m / z 221.1445 (theoretical [M+H] + C 13 H 18 FN 2 + , m / z 221.1449, Δ=-1.8 ppm). 1 H-NMR (400MHz, d 6 -DMSO)δ 11.50(s,1H),10.86(s,1H),7.48(d,J=7.7Hz,1H),7.33(d,J=2.4Hz,1H),7.02-6.96(m,1H),6.96 -6.89(m,1H),3.39-3.18(m,4H),3.18-3.02(m,2H),2.78(d,J=3.7Hz,3H),1.26(t,J=7.3Hz,3H). 13 C-NMR (101MHz, d 6 -DMSO)δ 149.24(d,J=242.8Hz,1C),130.78(d,J=6.0Hz,1C),124.46(s,1C),123.94(d,J=13.3Hz,1C),118.83(d,J=6.3Hz,1C),114.60(d,J= 3.0Hz,1C),110.45(d,J=2.1Hz,1C),106.04(d,J=16.1Hz,1C),54.26(s,1C),49.80(s,1C),38.17(s,1C),19.63(s,1C),8.75(s,1C). 19 F-NMR (377MHz,d 6 -DMSO) δ -133.11(s,1F).

[0185] Example 8: N,N-diethyl-2-(4-fluoro-1H-indol-3-yl)ethan-1-amine (8) TIFF2024523822000335.tif28128N,N-Diethyl-2-(4-fluoro-1H-indol-3-yl)ethan-1-amine (8) was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 4-fluoroindole (5 g, 37 mmol) to give the intermediate N,N-diethyl-2-(4-fluoro-1H-indol-3-yl)-2-oxoacetamide 1.6 g, 6.10 mmol, 16.5% yield, which was further reacted to give the title compound as an orange oil (0.81 g, 3.46 mmol, 56.7%) after column chromatography on an alumina stationary phase with EtOAc eluent. The free base was then converted to the corresponding fumarate salt and washed with acetone to give a white crystalline solid. High Resolution Atmospheric Pressure Solid Analysis Probe Mass Spectrometry (HR-ASAP-MS): m / z 235.1601 (theoretical [M+H] + C 14 H 20 FN 2 + , m / z 235.1605, Δ=-1.7 ppm). 1 H-NMR (400MHz, d 6 -DMSO)δ 11.25(s,1H),7.24(d,J=2.1Hz,1H),7.18(d,J=8.1Hz,1H),7.05-7.00(m,1H),6.72(dd,J =11.6,7.8Hz,1H),6.52(s,2H),3.03(s,4H),2.94(q,J=7.2Hz,4H),1.14(t,J=7.2Hz,6H). 13 C-NMR (101MHz, d 6-DMSO)δ 167.42(s,1C),156.26(d,J=242.8Hz,1C),139.27(d,J=12.0Hz,1C),134.81(s,1C),123.85(s,1C),121.53(d,J=7.9Hz,1C),115.19(d,J =19.8Hz,1C),108.89(s,1C),108.14(d,J=3.3Hz,1C),103.33(d,J=19.2Hz,1C),52.28(s,1C),46.01(s,1C),21.55(s,2C),9.66(s,2C). 19 F-NMR (377MHz,d 6 -DMSO) δ -124.58(s,1F).

[0186] Example 9: N-(2-(5,6-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine (9) TIFF2024523822000336.tif28128N-(2-(5,6-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine (9) was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 5,6-difluoroindole (2.5 g, 16.3 mmol) to give the intermediate 2-(5,6-difluoro-1H-indol-3-yl)-N-ethyl-2-oxo-N-propylacetamide (3.5 g, 13.9 mmol, 85.3% yield), some of which was purified under modified conditions (i.e., NH instead of KOH and HCl, respectively). 4 Further reaction under reduced pressure (using 500 sulphuric acid, 0.1% OH and AcOH) gave the crude product (2.14 g, 8.04 mmol, mp 83-86 °C, 76.6% yield), which was purified by column chromatography using an alumina stationary phase and EtOAc eluent. High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 267.1665 (theoretical [M+H] + C 15 H 21 F 2 N 2 +, m / z 267.1667, Δ=-0.7 ppm). (free base) 1 H-NMR (400MHz, d 6 -DMSO)δ 10.93(s,1H),7.44(dd,J=11.4,8.0Hz,1H),7.30(dd,J=11.3,7.0Hz,1H),7.21(d,J=2.1Hz,1H),2.78-2.69(m,2H),2.68-2 .61(m,2H),2.58-2.51(m,2H),2.41(t,J=7.3Hz,2H),1.40(sx,J=7.4Hz,2H),0.97(t,J=7.1Hz,3H),0.84(d,J=14.7Hz,3H). 19 F-NMR (377MHz,d 6 -DMSO)δ -145.11(d,J=21.9Hz,1F),-148.53(d,J=22.0Hz,1F).

[0187] Example 10: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine (10) TIFF2024523822000337.tif28128N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine (10) was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 5-fluoroindole (3 g, 22.2 mmol) to give the intermediate N- [2-(5-fluoro-1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine (4.5 g, 17.3 mmol, 77.9% yield) was obtained, a portion of which was further reacted to give the title compound as a yellow oil (2.18 g, 9.38 mmol, 55.55% yield) after purification by column chromatography using a silica gel stationary phase and then an alumina stationary phase and EtOAc eluent. High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 233.1443 (theoretical [M+H] + C 14 H 18 FN 2 +, m / z 233.1449, Δ=-2.6 ppm). (free base) 1 H-NMR (400MHz, d 6 -DMSO)δ 10.86(s,1H),7.31(dd,J=8.8,4.6Hz,1H),7.22(dd,J=9.9,2.4Hz,1H),7.21(d,J=2.3Hz,1H)6.88(dt,J=9.2,2.5Hz,1H),5.89-5.78(m ,1H),5.19(d,J=20Hz,1H),5.11(td,J=10.2,0.9Hz,1H),3.03(d,J=6.4Hz,1H),2.79(t,J=7.8Hz,1H),2.61-2.54(m,1H),2.23(s,1H). 19 F-NMR (377MHz,d 6 -DMSO) δ -125.32(s,1F).

[0188] Example 11: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylprop-2-en-1-amine (11) TIFF2024523822000338.tif31128Synthesis of N-[2-(5-fluoro-1H-indol-3-yl)ethyl]propan-2-amine TIFF2024523822000339.tif30128N-[2-(5-fluoro-1H-indol-3-yl)ethyl]propan-2-amine was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine (5) starting from 5-fluorotryptamine (1.3g, 6.06mmol) and acetone (2.11g, 36.4mmol) to obtain the title compound as a tan solid (1.47g, quantitative).The product was used in the next reaction without further purification.

[0189] Synthesis of N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylprop-2-en-1-amine (11) TIFF2024523822000340.tif31128N-[2-(5-fluoro-1H-indol-3-yl)ethyl]propan-2-amine (0.7 g, 3.18 mmol) was dissolved in dry ACN (15 mL) in a heat-dried 50 mL round-bottom flask with stirring under an argon atmosphere. Triethylamine (2.66 mL, 19.1 mmol) was added to the reaction vessel followed by allyl iodide (1.45 mL, 15.9 mmol) resulting in an exothermic reaction (approximately 38° C.). The flask was wrapped in aluminum foil and stirred at room temperature for 44 h. The reaction was poured into 200 mL of 0.2 M AcOH(aq) and extracted with EtOAc (3×50 mL). The organic phases were combined and extracted with 0.2 M AcOH(aq) (3×50 mL), then the aqueous phase was combined with the original aqueous phase. The combined aqueous phase was diluted with NH 4 OH (28-30% NH 3 ) and extracted with EtOAc (3×100 mL). The pooled organic phase was washed with brine and 2 SO 4 The crude product was extracted with 20% EtOH / EtOAc (1% (v / v) of EtOH) and concentrated in high vacuum to give the crude product as a viscous tan / brown oil (699 mg). 3 The product was purified by silica gel chromatography using 100% N to give the title compound as an off-white solid (120 mg, mp 45.5-47°C, 14.49% yield). The purified material was then converted to the HCl salt as described herein to give a white crystalline solid (mp 132-134°C). High Resolution Atmospheric Pressure Solid Analysis Probe Mass Spectrometry (HR-ASAP-MS): m / z 261.1756 (theoretical [M+H] + C 16 H 22 FN 2 + , m / z 261.1762, Δ=-2.3 ppm). 1 H-NMR (400MHz, d 6-DMSO)δ 11.14(s,1H),10.87(s,1H),7.40(dd,J=10,2.5Hz,1H),7.38-7.33(m,2H ),6.93(dt,J=9.2,2.5Hz,1H),6.24-6.11(m,1H),5.57(dd,J=17.1,1.0Hz ,1H),5.47(d,J=10.3Hz,1H),3.88-3.79(m,2H),3.71-3.61(m,1H),3.29- 3.21(m,1H),3.21-3.15(m,2H),3.15-3.06(m,1H),1.32(q,J=4.9Hz,6H). 13 C-NMR (101MHz, d 6 -DMSO)δ 156.75(d,J=231.2Hz,1C),132.86(s,1C),128.87(s,1C),126.94(d,J=9.9 Hz,1C),125.55(s,1C),123.69(s,1C),112.52(d,J=9.7Hz,1C),109.70(d,J =4.7Hz,1C),109.32(d,J=26.0Hz,1C),103.01(d,J=23.0Hz,1C),53.78(s, 1C),51.81(s,1C),49.07(s,1C),20.28(s,1C),16.19(s,1C),15.88(s,1C). 19 F-NMR (377MHz,d 6 -DMSO) δ -124.66(s,1F).

[0190] Example 12: N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine (12) TIFF2024523822000341.tif28128Synthesis of N-[2-(5-fluoro-1H-indol-3-yl)ethyl]formamide TIFF2024523822000342.tif31128 5-Fluorotryptamine hydrochloride (3 g, 14.0 mmol) in H2SO4 with stirring until a precipitate is obtained. 2 To the 200 mL solution was added KOH. The aqueous mixture was extracted with EtOAc (3×70 mL), and the organic phases were pooled, washed with brine, and washed with anhydrous Na 2 SO 4The mixture was dried over 100 ml and concentrated in high vacuum. Residual EtOAc was removed by azeotropic distillation with ethyl formate (3×20 mL). The resulting 5-fluorotryptamine free base was transferred to a 30 mL oven-dried microwave vessel containing 3 Å molecular sieves (3.3 g). Ethyl formate (20 mL, 248 mmol) was added to the microwave vessel and the mixture was reacted in a microwave reactor at 80° C. for 2.5 h at 150 W. Upon completion, the ethyl formate was removed under reduced pressure to give N-[2-(5-fluoro-1H-indol-3-yl)ethyl]formamide (1.7 g, 8.24 mmol, 58.9% yield). The product was used in the next reaction without further purification.

[0191] Synthesis of 2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine A 500 mL round-bottom flask with three necks, a 300 mL dropping funnel, a stir bar, and a condenser were dried overnight in a 70° C. oven and then further dried with external heating while flowing argon through the sealed system. Once drying was deemed complete, the round-bottom flask was placed in an ice bath (0° C.) and the apparatus was allowed to cool to room temperature. THF (100 mL) was added via the dropping funnel and after reaching 0° C., sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) (18.41 mL, 59.6 mmol) was added to the reaction vessel. N-[2-(5-fluoro-1H-indol-3-yl)ethyl]formamide (4.1 g, 19.8 mmol) in THF (20 mL) was then added dropwise to the reaction vessel over 30 min with stirring at 0° C. under argon. After the addition, the reaction was heated at reflux for 4 h. Upon completion, the reaction was cooled to 0° C. and diluted with THF / H 2The mixture was carefully quenched by dropwise addition of 2H2O (1:1, v / v) with ice. After quenching with a small amount of KOH(aq), 100 mL of EtOAc was added. The inorganic solids were then gravity filtered and washed with EtOAc. The filtrate was extracted with 0.2 M HCl(aq) (3 x 166 mL). The pooled aqueous phase was then basified with KOH pellets and extracted with EtOAc (3 x 100 mL). The pooled organic extracts were washed with brine (20 mL) and anhydrous Na 2 SO 4 After drying over high vacuum, 2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine was obtained as a yellow oil (3.14 g, 0.0163 mol, 82.32% yield). The product was used in the next reaction without further purification. ASAP-MS: m / z 193.2 (theoretical [M+H] + ,C 11 H 13 FN 2 + ), m / z 193.2 (measured value).

[0192] Synthesis of N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine (12) TIFF2024523822000344.tif28128 N-Ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine (12) was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine (5) starting from 2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine (0.7 g, 3.64 mmol) and acetaldehyde (0.96 g, 21.8 mmol) using silica gel as the stationary phase and 20% EtOH / EtOAc (1% (v / v) of EtOH) as the mobile phase. 3 After purification by column chromatography using 1,2-dichloro-2,4-diphenyl-2,4-tetramethylphenyl-2,5-diphenyl-2,6-tetramethylphenyl-2,7-diphenyl-2,6-di ...+ , C 13 H 18 FN 2 + ), m / z 221.1449 (measured value, Δ = -3.2 ppm). 1 H-NMR (400 MHz, d 6 -DMSO) δ 11.15 (s, 1H), 10.74 (s, 1H), 7.44 (dd, J = 10.1, 2.5 Hz, 1H), 7.36 (dd, J = 8.8, 4.6 Hz, 1H), 7.33 (d, J = 2.3 Hz, 1H), 6.93 (dt, J = 9.2, 2.5 Hz, 1H), 3.31 - 3.13 (m, 4H), 3.13 - 3.05 (m, 2H), 2.78 (d, J = 3.1 Hz, 3H), 1.26 (t, J = 7.3 Hz, 3H). 13 C-NMR (101 MHz, d 6 -DMSO) δ 156.74 (d, J = 231.1 Hz, 1C), 132.88 (s, 1C), 126.96 (d, J = 10.0 Hz, 1C), 125.42 (s, 1C), 112.48 (d, J = 9.9 Hz, 1C), 109.51 (s, 1C), 109.32 (d, J = 26.0 Hz, 1C), 103.13 (d, J = 23.1 Hz, 1C), 54.37 (s, 1C), 49.82 (s, 1C), 38.13 (s, 1C), 19.68 (s, 1C), 8.79 (s, 1C). 19 F-NMR (377 MHz, d 6 -DMSO) δ -124.79 (s, 1F).

[0193] Example 13: N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine (13) TIFF2024523822000345.tif28128N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine (13) was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine (5) starting from 2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine (0.7 g, 3.64 mmol) and propionaldehyde (1.27 g, 21.8 mmol) to give the title compound as a white crystalline solid (0.2 g, 0.854 mmol, mp 80-82 °C, 23.46% yield). HR-ASAP-MS: m / z 235.1600 (theoretically [M+H] + ,C 14 H 20 FN 2 + ), m / z 235.1605 (measured, Δ=-2.1 ppm). (free base) 1 H-NMR (400MHz, d 6 -DMSO)δ 10.86(s,1H),7.31(dd,J=8.8,4.6Hz,1H),7.25-7.20(m,2H),6.88(td,J=9.2,2.5Hz,1H) ,2.77(t,J=7.8Hz,2H),2.59-2.52(m,2H),2.32(t,J=7.3Hz,2H),2.22(s,3H),1.43(sx,J =7.4Hz,2H),0.85(t,J=7.4Hz,3H). 13 C NMR (101MHz, d 6 -DMSO)δ 156.56(d,J=230.9Hz,1C),132.80(s,1C),127.47(d,J=9.5Hz,1C),124.64(s,1C),113.11(d,J=5.0Hz,1C),112.16(d,J=9.7Hz,1C),10 8.82(d,J=26.0Hz,1C),102.88(d,J=22.9Hz,1C),59.04(s,1C),58.02(s,1C),41.76(s,1C),22.58(s,1C),20.04(s,1C),11.82(s,1C). 19 F-NMR (377MHz,d 6-DMSO) δ -125.33(s,1F).

[0194] Example 14: N-allyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine (14) TIFF2024523822000346.tif31128Synthesis of N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine TIFF2024523822000347.tif29128N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)cyclobutanamine was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine (5) starting from 5-fluorotryptamine (1.0 g, 4.66 mmol) and cyclobutanone (1.96 g, 28.0 mmol) using silica gel as the stationary phase and 20% EtOH / EtOAc (1% (v / v) of EtOH) as the mobile phase. 3 After purification by column chromatography using 2,4-dichloromethane (N), the title compound was obtained (456 mg, 1.99 mmol, 42.7% yield).

[0195] Synthesis of N-allyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine (14) TIFF2024523822000348.tif31128N-Allyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine (14) was prepared from N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine (0.21 g, 0.000904 mol) and allyl iodide (0.77 g, 0.00461 mol) as starting materials. Starting from N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylprop-2-en-1-amine (11) was synthesized in a similar manner as described above for N-allyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine (0.11 g, 0.000404 mol, 44.7% yield) as an off-white solid. The HCl salt was collected as a white crystalline solid. mp 196.3-199.0 °C. High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 273.1759 (theoretical [M+H] + C 17 H 22 FN 2 + ,m / z273.1762,Δ=-1.1ppm). [HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.38(s,1H),11.13(s,1H),7.39-7.32(m,3H),6.93(td,J=9.2,2.4Hz,1H),6.11-6.00(m,1H),5.63(dd,J=17.0,0.9Hz,1H),5.51(dd,J=10 .2,1.1Hz,1H),3.86-3.73(m,2H),3.73-3.64(m,1H),3.17-2.99(m,4H ),2.49-2.38(m,2H)*,2.27-2.14(m,2H),1.80-1.58(m,2H).*=Fusion with water. [HCl] 13 C NMR (101MHz, d 6-DMSO)δ 156.76(d,J=231.4Hz,1C),132.85(s,1C),127.04(s,1C),126.88(d,J=9.8Hz,1 C),125.51(s,1C),124.81(s,1C),112.56(d,J=9.8Hz,1C),109.56(d,J=4.7Hz,1 C),109.35(d,J=26.0Hz,1C),102.88(d,J=23.2Hz,1C),56.44(s,1C),50.80(s,1 C),48.95(s,1C),25.85(s,1C),25.78(s,1C),19.03(s,1C),13.38(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -124.82(s,1F).

[0196] Example 15: 5-Fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole (15) TIFF2024523822000349.tif28128Synthesis of 3-(5-fluoro-1H-indol-3-yl)-1-methylpyrrolidine-2,5-dione TIFF2024523822000350.tif32128 An oven-dried 35 mL microwave reaction vessel was charged with 5-fluoroindole (1.5 g, 11.1 mmol) and 1,2-dichloroethane (15 mL), followed by N-methylmaleimide (1.23 g, 11.1 mmol) and anhydrous ZnCl. 2 (300 mg, 2.2 mmol) was added. The reaction vessel was heated to 90° C. at 150 W in a microwave reactor for 24 h with stirring. Upon completion, the solvent was removed under high vacuum to give a crude oil. The crude oil was dissolved in EtOAc, washed with water (3×100 mL) and brine (10 mL), and purified with anhydrous Na 2 SO 4 The mixture was dried over 100 ml and concentrated in high vacuum to give the crude product, which was recrystallized from boiling EtOAc to give 3-(5-fluoro-1H-indol-3-yl)-1-methylpyrrolidine-2,5-dione as a yellow solid (2.4 g, 9.75 mmol, 87.8% yield).

[0197] Synthesis of 5-fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole (15) A 500 mL round-bottom flask with three necks, a 300 mL dropping funnel, a stir bar, and a condenser were dried overnight at 70 °C. The reaction apparatus was assembled and then purged with argon and then placed in an ice-water bath (0 °C). Dry THF (100 mL, dried over 3 Å molecular sieves) was added to the round-bottom flask and allowed to reach 0 °C. The reaction vessel was then charged with LiAlH 4 (0.84 g, 0.022 mol) was added slowly. Once the addition was complete, a solution of 3-(5-fluoro-1H-indol-3-yl)-1-methylpyrrolidine-2,5-dione (1.82 g, 0.00740 mol) in THF (100 mL) was added dropwise over 1 h at 0° C. The addition funnel was washed with additional THF (20 mL), which was added over 10 min. The reaction was heated at reflux for 2 h. Upon completion, the reaction was cooled to 0° C. and rehydrated with iced THF / H2O. 2 The reaction mixture was quenched by the addition of a mixture of 0:1 HCl (1:1 v / v). Brine and KOH(aq) were then added, followed by EtOAc (100 mL). The inorganic solids were removed by gravity filtration onto Whatman paper (24 cm diameter). The removed solids were then washed with EtOAc and the filtrate was extracted with 0.2 M HCl(aq) (3×166 mL). The aqueous phases were pooled, basified by the addition of KOH flakes, and then extracted with EtOAc (3×100 mL). The organic phases were pooled, washed with brine (20 mL) and diluted with anhydrous Na 2 SO 4 The crude material was purified by flash column chromatography using silica as the stationary phase and 20% EtOH / EtOAc to give the title compound as an off-white solid (1.13 g, 5.18 mmol, 70.0% yield, mp 122.8-125.1 °C). High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 219.1287 (theoretical [M+H]+ C 13 H 16 FN 2 + , m / z 219.1292, Δ=-2.3 ppm). (free base) 1 H-NMR (400MHz, d 6 -DMSO)δ 10.89(s,1H),7.35(dd,J=10.2,2.6Hz,1H)*,7.33(dd,J=8.8,4.4Hz,1H)*,7.22(d,J=2.4Hz,1H),6.90(dt,J=9.2,2.5Hz,1H),3.56-3. 45(m,1H),2.93(t,J=8.4Hz,1H),2.70-2.56(m,2H),2.49-2.44(m,1H),2.33(s,3H),2.29-2.21(m,1H),1.92-1.81(m,1H).*=Fusion, **=Fusion 13 C NMR(101MHz,DMSO)δ 156.42(d,J=230.5Hz,1C),133.30(s,1C),126.44(d,J=9.6Hz,1C),123.28(s,1C),118.43(d,J=4.6Hz,1C),112.27(d,J=9.9Hz, 1C),108.95(d,J=26.2Hz,1C),103.53(d,J=23.0Hz,1C),62.44(s,1C),55.90(s,1C),42.01(s,1C),34.52(s,1C),31.96(s,1C). 19 F-NMR (377MHz,d 6 -DMSO) δ -125.17(s,1F).

[0198] Example 16: N-allyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine (16) TIFF2024523822000352.tif31128Synthesis of N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine TIFF2024523822000353.tif31128 N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluorotryptamine hydrochloride (1 g, 0.00466 mol) and methyl ethyl ketone (2.02 g, 0.0280 mol) as starting materials to give N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine as an off-yellow crystalline solid (0.69 g, 0.00294 mol, 63.1% yield). The material was purified by column chromatography utilizing silica gel as the stationary phase and a gradient of 5% to 20% EtOH in EtOAc with 1% TEA as the mobile phase.

[0199] Synthesis of N-allyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine (16) TIFF2024523822000354.tif31128 N-allyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylprop-2-en-1-amine (11) starting from N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine (0.56 g, 0.00239 mol) and allyl iodide (2.02 g, 0.0120 mol) to give N-allyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine (0.18 g, 0.000656 mol, 27.5% yield) as a yellow oil. The HCl salt was collected as a white crystalline solid (mp 157.0-161.8 °C). High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 275.1915 (theoretical [M+H] + C 17 H 24 FN 2 +, m / z 275.1918, Δ = -1.1 ppm). [Free base] 1 H NMR (400 MHz, DMSO) δ 10.85 (s, 1H), 7.30 (dd, J = 8.8 Hz, 4.6 Hz, 1H), 7.19 (d, J = 2.3 Hz, 1H)*, 7.17 (dd, J = 10.1, 2.5 Hz, 1H)*, 6.88 (td, J = 9.2, 2.5 Hz, 1H), 5.82 (dddd, J = 17.2, 8.6, 5.4, 3.4 Hz, 1H), 5.20 (dq, J = 17.2, 1.7 Hz, 1H), 5.05 (d, J = 10.0 Hz, 1H), 3.21 (ddt, J = 14.5, 5.2, 1.6 Hz, 1H), 3.00 (dd, J = 14.6, 6.9 Hz, 1H), 2.83 - 2.73 (m, 1H)**, 2.73 - 2.61 (m, 3H)**, 2.57 - 2.51 (m, 1H)***, 1.49 - 1.37 (m, 1H), 1.27 - 1.15 (m, 1H), 0.88 (d, J = 6.5 Hz, 3H), 0.83 (t, J = 7.4 Hz, 3H). *=Fusion, **=Fusion, **=Fusion with DMSO reference peak. [Free base] 13 C NMR (101 MHz, DMSO) δ 156.55 (d, J = 230.8 Hz, 1C), 138.46 (s, 1C), 132.83 (s, 1C), 127.50 (d, J = 9.6 Hz, 1C), 124.68 (s, 1C), 115.61 (s, 1C), 113.20 (d, J = 4.9 Hz, 1C), 112.18 (d, J = 9.7 Hz, 1C), 108.78 (d, J = 26.0 Hz, 1C), 102.81 (d, J = 22.8 Hz, 1C), 56.14 (s, 1C), 52.78 (s, 1C), 50.15 (s, 1C), 26.48 (s, 1C), 24.83 (s, 1C), 13.85 (s, 1C), 11.50 (s, 1C). [Free base] 19 F NMR (377 MHz, DMSO) δ -125.38 (s, 1F).

[0200] Example 17: 2 - ((2 - (5 - Fluoro - 1H - indol - 3 - yl) ethyl)(isopropyl) amino) acetonitrile (17) TIFF2024523822000355.tif33128 2-((2-(5-Fluoro-1H-indol-3-yl)ethyl)(isopropyl)amino)acetonitrile was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylprop-2-en-1-amine (11) starting from N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (0.5 g, 0.00227 mol) and bromoacetonitrile (1.35 g, 0.0114 mol) to give 2-((2-(5-fluoro-1H-indol-3-yl)ethyl)(isopropyl)amino)acetonitrile (0.11 g, 0.000424 mol, 18.67% yield) as a yellow oil. The HCl salt was collected as a slightly yellow solid. mp 147.0-150.0 °C with decomposition. High resolution atmospheric pressure solids analytical probe mass spectrometry (HR-ASAP-MS): m / z 260.1552 (theoretical [M+H] + C 15 H 19 FN 3 + ,m / z 260.1558,Δ=-2.3 ppm).[HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.14(s,1H),7.43(dd,J=10.0,2.4Hz,1H),7.39-7.32(m,2H),6.93(td,J=9.2,2.5Hz,1H ),4.63(s,2H),3.72(bs,1H),3.29(s,2H),3.24-3.14(m,2H),1.33(d,J=6.5Hz,6H).[HCl] 13 C NMR (101MHz, d 6-DMSO)δ 156.79(d,J=231.2Hz,1C),132.88(s,1C),126.95(d,J=10.0Hz,1C),125.67(s,1C),114.22(s,1C),112.57(d,J=9.8Hz,1C),109.38(d ,J=26.2Hz,1C),109.33(s,1C),103.00(d,J=23.1Hz,1C),56.41(s,1C),50.60(s,1C),36.70(s,1C),20.38(s,1C),16.51(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -124.66(s,1F).

[0201] Example 18: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)prop-2-en-1-amine (18) TIFF2024523822000356.tif25128Synthesis of 2-(5-fluoro-1H-indol-3-yl)-2-oxo-N-(prop-2-en-1-yl)acetamide TIFF2024523822000357.tif25128 2-(5-Fluoro-1H-indol-3-yl)-2-oxo-N-(prop-2-en-1-yl)acetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 5-fluoro-indole (5 g, 0.0370 mol), oxalyl chloride (5.64 g, 0.0444 mol), and allylamine (7.59 g, 0.133 mol) as starting materials to give 2-(5-fluoro-1H-indol-3-yl)-2-oxo-N-(prop-2-en-1-yl)acetamide as an orange powder (9.5 g, 0.0386 mol, quantitative yield). The compound was used without further purification.

[0202] Synthesis of N-(2-(5-fluoro-1H-indol-3-yl)ethyl)prop-2-en-1-amine (18) TIFF2024523822000358.tif25128 N-(2-(5-fluoro-1H-indol-3-yl)ethyl)prop-2-en-1-amine was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 2-(5-fluoro-1H-indol-3-yl)-2-oxo-N-(prop-2-en-1-yl)acetamide (9.11 g, 0.0370 mol) as starting material to give N-(2-(5-fluoro-1H-indol-3-yl)ethyl)prop-2-en-1-amine as an orange oil (1.5 g, 0.00687 mol, 18.57% yield). High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 219.1287 (theoretical [M+H] + C 13 H 16 FN 2 + , m / z 219.1292, Δ=-2.3 ppm).[Free base] 1 H NMR (400MHz, d 6 -DMSO)δ 10.89(s,1H),7.32(dd,J=8.8,4.6Hz,1H),7.26(dd,J=10.1,2.5Hz,1H),7.22(d,J=2.2Hz,1H),6.89(td,J=9.2,2.5Hz,1H),5.85(ddt ,17.3,10.3,5.74Hz,1H),5.15(dq,J=17.2,1.7Hz,1H),5.03(dq,J=10.2,1.4Hz,1H),3.20(dt,J=5.7,1.3Hz,2H).2.83-2.72(m,4H). [Free base] 13 C NMR (101MHz, d 6-DMSO)δ 156.59(d,J=230.6Hz,1C),137.72(s,1C),132.87(s,1C),127.50(d,J=9.6Hz,1C),124.74(s,1C),115.09(s,1C),112.98(d,J=5.0Hz ,1C),112.20(d,J=9.9Hz,1C),108.88(d,J=26.2Hz,1C),102.97(d,J=23.0Hz,1C),51.57(s,1C),49.43(s,1C),25.30(s,1C).[Free base] 19 F NMR(377MHz,DMSO)δ -125.34(s,1F).

[0203] Example 19: 5,6-Difluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole (19) TIFF2024523822000359.tif28128Synthesis of 3-(5,6-difluoro-1H-indol-3-yl)-1-methylpyrrolidine-2,5-dione TIFF2024523822000360.tif321283-(5,6-difluoro-1H-indol-3-yl)-1-methylpyrrolidine-2,5-dione was synthesized in a similar manner as described above for 5-fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole (15), starting from 5,6-difluoroindole (1g, 0.00653mol) and N-methyl-maleimide (0.73g, 0.00653mol) as starting material, to obtain 3-(5,6-difluoro-1H-indol-3-yl)-1-methylpyrrolidine-2,5-dione as an orange solid (1.72g, 0.00651mol, 99.7% yield). Compound was used without further purification.

[0204] Synthesis of 5,6-difluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole (19) TIFF2024523822000361.tif281285,6-Difluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole was synthesized in a similar manner as described above for 5-fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole (15) starting from 3-(5,6-difluoro-1H-indol-3-yl)-1-methylpyrrolidine-2,5-dione (1.7 g, 0.00643 mol) as starting material to give the title compound (0.93 g, 0.00394 mol, 61.3% yield) (mp 119.5-120.3 °C). High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 237.1196 (theoretical [M+H] + C 13 H 15 F 2 N 2 + , m / z 237.1198, Δ=-0.8 ppm).[Free base] 1 H NMR (400MHz, d 6 -DMSO)δ 10.93(s,1H),7.57(dd,J=11.6,8.1Hz,1H),7.31(dd,J=11.3,7.0Hz,1H),7.20(d,J=2.3Hz,1H),3.48(dq,J=14.1,7.3Hz,1H),2 .88(t,J=8.3Hz,1H),2.65-2.54(m,2H),2.44(dd,J=8.8,7.1Hz,1H),2.30(s,3H),2.27-2.18(m,1H),1.87-1.76(m,1H).[Free base] 13 C NMR (101MHz, d 6 -DMSO)δ 146.45(dd,J=236.4,16.1Hz,1C),144.65(dd,J=233.6,14.9Hz,1C),131.55 (d,J=10.7Hz,1C),123.07(d,J=3.7Hz,1C),121.64(d,J=7.7Hz,1C),118.94 (dd,J=4.4,1.5Hz,1C),105.45(d,J=18.8Hz,1C),99.14(d,J=20.9Hz,1C),6 2.51(s,1C),55.91(s,1C),42.01(s,1C),34.38(s,1C),32.06(s,1C).[Free base]19 F NMR (377MHz,d 6 -DMSO)δ -145.54(d,J=22.8Hz,1F),-148.96(d,J=22.0Hz,1F).

[0205] Example 20: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylthietan-3-amine (20) TIFF2024523822000362.tif29128 N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylthietan-3-amine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluorotryptamine hydrochloride 5-fluorotryptamine hydrochloride (0.5 g, 0.00233 mol), thietan-3-one (0.62 g, 0.00699 mol), and 36% formaldehyde in water (0.58 mL, 0.00699 mol) as starting materials to give the title compound as a cloudy white oil (0.19 g, 0.000719 mol, 30.9% yield). HCl was collected as a white crystalline solid (mp 221.0-223.3 °C). High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 265.1166 (theoretical [M+H] + C 14 H 18 FSN 2 + ,m / z 265.1169,Δ=-1.1 ppm).[HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.68(s,1H),11.13(s,1H),7.44(dd,J=10,2.5,Hz,1H),7.36(dd,J=9.0,4.7Hz,1H)*,7.34(d,J=2.1Hz,1H ),6.93(dt,J=9.2,2.5,Hz,1H),4.61-4.47(m,1H),3.92-3.77(m,2H),3.25-2.99(m,6H),2.71(s,3H).*=Fusion. [HCl] 13 C NMR (101MHz, d 6-DMSO)δ 156.78(d,J=231.3Hz,1C),132.86(s,1C),126.92(d,J=9.9Hz,1C),125.55(s,1C),112.52(d,J=9.8Hz,1C),109.37(d,J=4.5Hz,1C)*,109. 37(d,J=26.1Hz,1C)*,103.09(d,J=23.1Hz,1C),58.80(s,1C),50.92(s,1C),34.39(s,1C),29.12(s,1C),28.76(s,1C),19.29(s,1C).*=Fusion. 19 F NMR(377MHz,DMSO)δ -124.69(s,1F).

[0206] Example 21: N-(2-(4,5-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine (21) TIFF2024523822000363.tif28128Synthesis of 2-(4,5-difluoro-1H-indol-3-yl)-N-ethyl-2-oxo-N-propylacetamide TIFF2024523822000364.tif28128 2-(4,5-difluoro-1H-indol-3-yl)-N-ethyl-2-oxo-N-propylacetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 4,5-difluoroindole (5 g, 0.0327 mol), oxalyl chloride (4.98 g, 0.0392 mol), and N-ethylpropylamine (4.1 g, 0.047 mol) as starting materials to give 2-(4,5-difluoro-1H-indol-3-yl)-N-ethyl-2-oxo-N-propylacetamide as an orange solid (6.9 g, 0.0234 mol, 71.6% yield). Column chromatography was performed utilizing silica gel with 1% triethylamine as the mobile phase and 20% EtOH in EtOAc as the stationary phase. The compound was used without further purification.

[0207] Synthesis of N-[2-(4,5-difluoro-1H-indol-3-yl)ethyl]-N-ethylpropan-1-amine (21) TIFF2024523822000365.tif28128N-(2-(4,5-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 2-(4,5-difluoro-1H-indol-3-yl)-N-ethyl-2-oxo-N-propylacetamide (6.9 g, 0.0234 mol) as starting material to give the fumarate salt of the title compound as a white crystalline solid (2.1 g, 0.00549 mol, 23.5% yield) (mp 182.1-183.3 °C). The free base was readily converted to the hemifumarate after evaporation. High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 267.1660 (theoretical [M+H] + C 15 H 21 F 2 N 2 + , m / z 267.1667, Δ=-2.6 ppm).[Hemifumarate] 1 H NMR (400MHz, d 6 -DMSO)δ 11.26(s,1H),7.28(d,J=2.1Hz,1H),7.13(dd,J=8.8,3.6Hz,1H),7.010-7.02(m,1H),6.50(s,1H),3.05-2.90(m,2H),2.9-2.8 1(m,2H),2.75(q,J=7.1Hz,2H),2.67-2.59(m,2H),1.57-1.42(m,2H),1.06(t,J=7.1Hz,3H),0.86(t,J=7.3Hz,3H).[Hemifumarate] 13C NMR(101MHz,DMSO)δ 167.53(s,1C),142.94(dd,J=11.3,230.7Hz,1C),142.69(dd,J=14.3,244.1Hz,1C),134.92(s ,1C)*,134.91(d,J=10.4Hz,1C)*,125.67(s,1C),116.24(d,J=15.4Hz,1C),110.57(dd,J=2.2 ,5.1Hz,1C)**,110.38(d,J=21.4Hz,1C)**,107.58(dd,J=3.8,7.8Hz,1C),54.12(s,1C),53.7 3(s,1C),46.77(s,1C),22.36(s,1C),18.83(s,1C),11.57(s,1C),10.71(s,1C).*=Fusion, **=Fusion. [Hemifumarate] 19 F NMR(377MHz,DMSO)δ -152.36(d,J=21.8Hz,1F),-154.01(d,J=21.8Hz,1F).

[0208] Example 22: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylbutan-2-amine (22) TIFF2024523822000366.tif36128 N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylbutan-2-amine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluorotryptamine hydrochloride 5-fluoro-tryptamine hydrochloride (0.5 g, 0.00233 mol), methyl ethyl ketone (0.51 g, 0.00699 mol), and propionaldehyde (0.41 g, 0.0699 mol) as starting materials to give the title compound as a yellow oil (0.34 g, 0.00110 mol, 47.2% yield). The hydrochloride salt was collected as a white solid (mp 153.2-155.4 °C). High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 277.2069 (theoretical [M+H] + C 13 H 26 FN 2 +, m / z 277.2075, Δ=-2.2 ppm).[Free base] 1 H NMR(400MHz,DMSO)δ 10.85(s,1H),7.31(dd,J=8.8,4.6Hz,1H),7.21(d,J=2.2Hz,1H),7.17(dd,J=10.0,2.5Hz,1H),6.88(td,J=9.1,2.5Hz,1H),2 .80-2.57(m,4H),2.55-2.5(m,1H)*,2.46-2.29(m,2H),1.48-1.31(m,3H),1.26-1.14(m,1H),0.89-0.91(m,9H).*=Fusion with DMSO. [Free base] 13 C NMR(101MHz,DMSO)δ 156.56(d,J=230.7Hz,1C),132.83(s,1C),127.49(d,J=9.6Hz,1C),124.70(s,1 C),113.28(d,J=4.6Hz,1C),112.18(d,J=9.9Hz,1C),108.76(d,J=26.0Hz,1C),1 02.71(d,J=22.8Hz,1C),56.33(s,1C),51.51(s,1C),50.61(s,1C),26.55(s,1C) ),25.26(s,1C),21.95(s,1C),13.78(s,1C),11.81(s,1C),11.60(s,1C).[Free base] 19 F NMR(377MHz,DMSO)δ -125.40(s,1F).

[0209] Example 23: 7-Fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole (23) TIFF2024523822000367.tif30128Synthesis of 3-(7-fluoro-1H-indol-3-yl)-1-methylpyrrolidine-2,5-dione TIFF2024523822000368.tif351283-(7-fluoro-1H-indol-3-yl)-1-methylpyrrolidine-2,5-dione was synthesized in a similar manner as described above for 5-fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole (15), starting from 7-fluoroindole (01g, 0.00740mol) and N-methylmaleimide (0.82g, 0.0074mol) as starting materials, to obtain 3-(7-fluoro-1H-indol-3-yl)-1-methylpyrrolidine-2,5-dione as a yellow / orange crystalline solid (1.4g, 0.00569mol, 76.9% yield).The compound was used without further purification.

[0210] 7-Fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole (23) TIFF2024523822000369.tif30128 7-Fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole was synthesized in a similar manner as described above for 5-fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole (15) utilizing 3-(7-fluoro-1H-indol-3-yl)-1-methylpyrrolidine-2,5-dione (1.4 g, 0.00569 mol) to afford the title compound as a pale orange crystalline solid which was recrystallized from ethyl acetate and hexane to afford white crystalline solid clusters which discolored slightly (beige to tan) on exposure to air (0.49 g, 0.00224 mol, 39.37% yield). mp129.0~132.1℃. High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 219.1291 (theory [M+H] + C 13 H 16 FN 2 + , m / z 219.1292, Δ=-0.5 ppm).[Free base] 1 H NMR (400MHz, d 6-DMSO)δ 11.26(s,1H),7.41(d,J=7.5Hz,1H),7.20(d,J=2.3Hz,1H),6.96-6.85(m,2H),3.59-3.50(m,1H),2.96(t,J=8.3Hz,1H),2.70( q,J=7.6Hz,1H),2.61-2.54(m,1H),2.50-2.44(m,1H)*,2.32(s,3H),2.30-2.22(m,1H),1.94-1.83(m,1H).*=Fusion with DMSO [free base] 13 C NMR (101MHz, d 6 -DMSO)δ 149.28(d,J=242.4Hz,1C),130.46(d,J=6.1Hz,1C),124.35(d,J=13.1Hz,1C),122.38(s,1C),119.18(d,J=1.8Hz,1C),118.41(d,J=6.1H [Free base] 19 F NMR (377MHz,d 6 -DMSO) δ -133.27(s,1F).

[0211] Example 24: 2-(Ethyl(propyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one (24) TIFF2024523822000370.tif28128Synthesis of 2-chloro-1-(5-fluoro-1H-indol-3-yl)ethan-1-one TIFF2024523822000371.tif261285-Fluoroindole (2.5 g, 0.0185 mol) was dissolved in 40 mL of toluene along with pyridine (1.46 g, 0.0185 mol). This was then placed in a 60° C. water bath and fitted with an addition funnel containing chloroacetyl chloride (2.09 g, 0.0185 mol) in 15 mL of toluene, which was added dropwise over 30 minutes. This was then allowed to react for an additional 30 minutes after the addition was complete. The reaction was removed from the heat and washed with 30 mL of H 2A solution of 20 and 6 mL of MeOH was added and stirred for 2 hours, after which the solid was filtered off from the reaction under high vacuum. After suction filtration was completed, 2-chloro-1-(5-fluoro-1H-indol-3-yl)ethan-1-one was obtained as a yellow crystalline solid (1.3 g, 0.00614 mol, 33.3% yield). The product was used without further purification.

[0212] Synthesis of 2-(ethyl(propyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one (24) TIFF2024523822000372.tif28128 In a dried 35 mL microwave vessel, the stir bar and cap were dried in an oven overnight and further heated externally with hot air from a heat gun to remove any moisture, then 25 mL of acetonitrile was added to the microwave vessel along with N-ethylpropylamine (0.75 g, 0.00860 mol). Potassium iodide (1.43 g, 0.00860 mol) was then added, and finally 2-chloro-1-(5-fluoro-1H-indol-3-yl)ethan-1-one (0.61 g, 0.00287 mol) was added to the reaction and allowed to react for about 3 hours. The reaction mixture was removed and dissolved in 250 mL of 0.174 M acetic acid solution. Two extractions were performed with EtOAc, using 50 mL each time. The extracts were pooled and extracted with 3×250 mL of 0.174 M acetic acid solution to extract any product that may have partitioned into the organic phase. The acetic acid washes were pooled with the first acetic acid solution to form a total of 500 mL of 0.174 M acetic acid solution. This was basified with KOH until pH>12 and the precipitate was extracted three times with 100 mL of EtOAc each time (3×100 mL). Once the EtOAc extractions were complete, they were combined and washed with 60 mL of brine solution. Finally, the organic phase was dried with sodium sulfate, decanted and removed under reduced pressure to give 635 mg as a yellow solid.

[0213] The free base was converted to the HCl salt by dissolving it in 20 mL of EtOH and then adding 206 μL of 36.5% HCl directly to the solution. The solvent was then evaporated several times under a stream of warm air to give a crystalline material free of excess acid or water. The resulting solid was diluted with EtOAc (2×5 mL) and Et 2 The solid was dissolved in 7 mL of boiling EtOH and then washed with 25 mL of EtOH until the solution became milky and opaque. 2 Crystallization was carried out by slow addition of O. The solution was allowed to recover to room temperature (RT) and allowed to stand for 1 h, then placed at 4 °C until thermodynamic equilibrium was achieved, and then stored at -20 °C overnight. The resulting crystals were collected by decanting the supernatant, and recrystallization was repeated a total of three times to give 340 mg (39.7% yield) of a yellow crystalline solid. mp 203.4-205.6 °C. High-resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 263.1549 (theoretical [M+H] + C 15 H 20 FON 2 + ,m / z 263.1554,Δ=-1.9 ppm).[HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 12.87(s,1H),9.83(s,1H),8.63(d,J=3.2Hz,1H),7.83(dd,J=9.7,2.5Hz,1H),7.58(dd,J=8.9,4.6Hz,1H),7.13(td,J=9.1,2.4Hz,1H), 4.80(s,2H),3.26(q,J=6.8Hz,2H),3.11(at,J=7.7Hz,2H),1.72(sex,J=7.7Hz,2H),1.27(t,J=7.2Hz,3H),0.90(t,J=7.3Hz,3H).[HCl] 13 C NMR (101MHz, d 6-DMSO)δ 185.74(s,1C),158.93(d,J=235.6Hz,1C),137.17(s,1C),133.23(s,1C) ,125.71(d,J=11.1Hz,1C),114.05(d,J=9.9Hz,1C),113.29(d,J=4.3Hz,1 C),111.62(d,J=25.9Hz,1C),105.87(d,J=24.7Hz,1C),56.75(s,1C),55 .03(s,1C),49.36(s,1C),16.83(s,1C),10.80(s,1C),8.89(s,1C).[HCl] 19 F NMR(377MHz,DMSO)δ -120.14(s,1F).

[0214] Example 25: 2-(Ethyl(methyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one (25) TIFF2024523822000373.tif291282-(Ethyl(methyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one was synthesized in a similar manner as described above for 2-(ethyl(propyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one, starting from 2-chloro-1-(5-fluoro-1H-indol-3-yl)ethan-1-one (0.6 g, 0.00284 mol) and N-methylethylamine (0.5 g, 0.00852 mol) as starting materials to give the title compound as a white / yellow crystalline solid (0.18 g, 0.000768 mol, 27.0% yield). mp 160.1-164.8 °C. The product was purified by column chromatography utilizing silica gel as the stationary phase and a mobile phase gradient of 2% EtOH to 20% EtOH in EtOAc containing 1% triethylamine. High resolution atmospheric pressure solids analytical probe mass spectrometry (HR-ASAP-MS): m / z 235.1233 (theoretical [M+H] + C 13 H 16 FON 2 + , m / z 235.1241, Δ=-3.4 ppm).[Free base] 1 H NMR (400MHz, d6 -DMSO)δ 11.99(s,1H),8.51(s,1H),7.85(dd,J=10.0,2.6Hz,1H),7.48(dd,J=8.8,4.6Hz,1H),7.06(td,J=9. [Free base] 13 C NMR(101MHz,DMSO)δ 193.44(s,1C),158.59(d,J=234.2Hz,1C),135.64(s,1C),132.81(s,1C),126.25(d,J=11.0Hz,1C),115.10(d,J=4.4Hz,1C),113.31( [Free base] 19 F NMR(377MHz,DMSO)δ -121.35(s,1F).

[0215] Example 26: 2-(5-fluoro-1H-indol-3-yl)-N,N-dimethylpropan-1-amine (26) TIFF2024523822000374.tif281285-Synthesis of fluoro-3-[2-nitroethenyl]-1H-indole TIFF2024523822000375.tif26128A dried 100 mL single neck round bottom flask was dried overnight in an oven and then heated externally with hot air from a heat gun while flowing argon internally and allowed to cool to room temperature while flowing argon. After the round bottom flask was cooled to room temperature, 5-fluoroindole-3-carboxyaldehyde (5 g, 0.0306 mol) was added to the flask. Nitromethane (40 mL) was then added to the round bottom flask along with ammonium acetate (1.34 g, 0.0174 mol) and reflux was initiated under a heating mantle. This reflux was maintained for 3 hours. After 3 hours, the reaction was stopped by removing the nitromethane under reduced pressure to give a red-orange crystalline material. This material was recrystallized in the same round bottom flask by dissolving the crystalline material in 60 mL of boiling isopropanol (IPA) and allowing it to cool to room temperature. After cooling to room temperature, the round bottom flask with septum was placed at -20°C and allowed to recrystallize overnight. After overnight recrystallization, the IPA was decanted and the crystalline material was dried under reduced pressure to give 5-fluoro-3-(2-nitroethenyl)-1H-indole as an orange crystalline solid (5.14 g, 0.0249 mol, 81.4% yield). The product was used without further purification.

[0216] Synthesis of 5-fluoro-3-(1-nitropropan-2-yl)-1H-indole TIFF2024523822000376.tif29128An oven dried 2-neck 250 mL round bottom flask was fitted with an addition funnel and 70 mL of THF was added to the round bottom flask. A 1.4 M solution of methylmagnesium bromide (43.47 mL, 0.0608 mol) in a 1:3 THF / toluene solution was then added to the round bottom flask via syringe while flushing with argon over 30 minutes. Once the addition was complete, 5-fluoro-3-[2-nitroethenyl]-1H-indole (5 g, 0.0243 mol) was added to the round bottom flask and dissolved in 30 mL of THF. Once dissolved in THF, the 5-fluoro-3-[2-nitroethenyl]-1H-indole was added dropwise over 30 minutes while maintaining the temperature below 35°C. Once the addition was complete, the reaction was allowed to stir for 1.5 hours. After 1.5 hours, a small aliquot of the reaction was removed and tested by TLC in 20% EtOAc in hexanes, but no starting material was detected. The reaction was then worked up by mixing the reaction in 700 mL of saturated ammonium chloride solution and extracted five times with 110 mL of EtOAc (5 x 110 mL). Once extracted, the EtOAc extracts were pooled and washed with 60 mL of brine (1 x 60 mL). The EtOAc was then dried over sodium sulfate, decanted, and the solvent removed under pressure. The dark brown oil was then purified by column chromatography using silica gel as the stationary phase and 20% EtOAc in hexanes (isomers) as the mobile phase to give pure 5-fluoro-3-(1-nitropropan-2-yl)-1H-indole as an orange-red oil (3.0 g, 0.0137 mol, 56.4% yield). The product was used without further purification.

[0217] Synthesis of 2-(5-fluoro-1H-indol-3-yl)propan-1-amine TIFF2024523822000377.tif25128A dry 100 mL single neck round bottom flask was dried overnight in an oven, then heated externally with hot air from a heat gun while flowing argon internally, and cooled back to room temperature while flowing argon. After cooling to room temperature, methanol (70 mL) was added to the round bottom flask along with 10% palladium on carbon (1.46 g, 0.0137 mol). 5-Fluoro-3-(1-nitropropan-2-yl)-1H-indole (3.04 g, 0.0137 mol) was then dissolved in methanol (30 mL) and added to the round bottom while flowing a constant argon stream. A hydrogen filled balloon was then attached to a modified syringe, the septum was pierced, and the reaction was allowed to proceed for 4 hours. After 4 hours, the reaction was terminated by filtering the Pd-C through a celite plug and collecting the filtrate. Methanol was removed under reduced pressure and the material was dissolved in 100 mL of EtOAc. It was then extracted five times (5 x 100 mL) with 100 mL each time of 0.285 M HCl. The extracts were pooled and basified with KOH to obtain a pH greater than 12. After basification, the product was then extracted from the aqueous phase three times (3 x 100 mL) with 100 mL each time of EtOAc. Once the final extractions were performed, they were pooled and washed once with 60 mL of brine (1 x 60 mL). The organic phase was dried over sodium sulfate, decanted and removed under reduced pressure to give 2.24 g of crude oil.

[0218] This was purified by column chromatography using silica gel as the stationary phase and a gradient of 20% to 50% EtOH in EtOAc containing 1% triethylamine to give the title compound as a yellow oil (1.27 g, 0.00661 mol, 48.3% yield). A portion of the free base was converted to the HCl salt by dissolving the free base in 20 mL of EtOH and then titrating until the pH was less than 2. The solvent was then evaporated several times under a stream of warm air to give a crystalline material free of excess acid or moisture. The resulting solid was diluted with 2×7 mL of EtOAc and 1×10 mL of EtOH to give a crystalline material. 2 The solid was dissolved in 7 mL of boiling EtOH and then washed with 25 mL of EtOH until the solution became milky and opaque.2 Crystallization was carried out by slow addition of O. The solution was allowed to recover to room temperature and stand for 1 h, then placed at 4 °C until thermodynamic equilibrium was achieved, and then stored at -20 °C overnight. The resulting crystals were collected by decanting the supernatant, and recrystallization was repeated a total of three times to give a white crystalline solid (mp 193.3-194.0 °C). High-resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 193.1135 (theoretical [M+H] + C 11 H 14 FN 2 + ,m / z 193.1136,Δ=-0.5 ppm).[HCl] 1 H NMR (400MHz, d 6 -DMSO) δ 11.17(s,1H), 8.08(s,3H), 7.42(dd,J=10.2,2.5Hz,1H), 7.36(dd,J=8.8,4.6Hz,1H), 7.31(d,J=2.5Hz,1H), 6.92(td,J=9.2,2.5Hz,1H), 3.36-3.27(m,1H)*, 3.14-2.99(m,1H), 2.99-2.86(m,1H), 1.36(d,J=7.0Hz,3H).*=fusion with water. [HCl] 13 C NMR (101MHz, d 6 -DMSO)δ 156.64(d,J=231.0Hz,1C),133.14(s,1C),126.22(d,J=9.7Hz,1C),124.34(s,1C),115.88(d,J=4.7Hz,1C),112.52( [HCl] 19 F NMR(377MHz,DMSO)δ -124.82(s,1F).

[0219] Synthesis of 2-(5-fluoro-1H-indol-3-yl)-N,N-dimethylpropan-1-amine (26) TIFF2024523822000378.tif281282-(5-Fluoro-1H-indol-3-yl)-N,N-dimethylpropan-1-amine was prepared using 2-(5-fluoro-1H-indol-3-yl)propan-1-amine (0.5 g, 0.00260 mol) as starting material and H 2 Synthesis in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine (5) starting from a 36% solution of formaldehyde in O (1.3 mL, 0.0156 mol) afforded the title compound as a white crystalline solid (0.36 g, 0.00164 mol, 63.2% yield). Column chromatography was performed using silica gel as the stationary phase and a gradient of 5% to 20% EtOH in EtOAc with 1% triethylamine. High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 221.1445 (theoretical [M+H] + C 13 H 18 FN 2 + ,m / z 221.1449,Δ=-1.8 ppm).[HCl] 1 H NMR (400MHz, d 6 -DMSO) δ 11.24(s,1H), 9.92(s,1H), 7.45(dd,J=10.2,2.5Hz,1H), 7.39(d,J=2.9Hz,1H)*, 7.37(dd,J=8.9,4.7Hz,1H)* 6.93(dt,J=2.5,9.2Hz,1H), 3.43-3.37(m,1H)* 3.57-3.45(m,1H), 3.32-3.25(m,1H), 2.75(dd,J=7.1,4.8Hz,6H), 1.38(d,J=6.8Hz,3H).*=fusion with water. [HCl] 13 C NMR (101MHz, d 6-DMSO)δ 156.67(d,J=231.0Hz,1C),133.09(s,1C),125.86(d,J=10.0Hz,1C),124.57(s,1C),115.65(d,J=4.7Hz,1C),112.58(d,J=9.8Hz,1C ),109.31(d,J=26.1Hz,1C),103.38(d,J=23.3Hz,1C),62.03(s,1C),43.46(s,1C),41.97(s,1C),26.49(s,1C),19.61(s,1C).[HCl] 19 F NMR(377MHz,DMSO)δ -124.67(s,1F).

[0220] Example 27: (S)-5-Fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole (27) TIFF2024523822000379.tif23128Synthesis of benzyl (2S)-2-(5-fluoro-1H-indole-3-carbonyl)pyrrolidine-1-carboxylate TIFF2024523822000380.tif35128All glassware was dried overnight in an oven, externally dried with hot air from a heat gun, and allowed to cool to room temperature before reaction. 5-Fluoroindole (5.41 g, 0.0400 mol) was dissolved in toluene (50 mL) and then 1.4 M methylmagnesium bromide (28.6 mL, 0.0400 mol) in 1:3 THF / toluene was added via syringe over 30 minutes and then reacted for a total of 3 hours. During the Grignard formation, N-benzyloxylcarbonyl-L-proline (5 g, 0.0200 mol) was dissolved in dichloromethane (50 mL) in a separate round-bottom flask with oxalyl chloride (3.8 g, 0.0300 mol) and allowed to react for 2 hours. After 2 hours, dichloromethane and excess oxalyl chloride were removed under reduced pressure. To ensure all oxalyl chloride was removed, all dichloromethane was removed and hexane and residual oxalyl chloride were removed under reduced pressure, followed by the addition of 4 Å of dry hexane. After removing the hexane, the acid chloride was dissolved in diethyl ether (75 mL) and added to the Grignard reagent. This was allowed to react overnight. A sample of the reaction was removed and tested by TLC to confirm the reaction was complete. The reaction was then poured into saturated bicarbonate solution (400 mL) and 100 mL of EtOAc was added and stirred for 1 hour. After 1 hour, the organic phase was separated and the aqueous phase was extracted twice more with 100 mL of EtOAc (2×100 mL). The organic phases were combined, washed with brine, dried over sodium sulfate, and the solvent was removed under reduced pressure. Once the solvent was removed, 30 mL of EtOAc and 100 mL of diethyl ether were added to the round bottom flask containing the product and after stirring for 1 h, the crystalline material was filtered under high vacuum to give the title compound (mp: 194.0-196.0° C.) as a white crystalline solid (3.54 g, 0.00966 mol, 48.3% yield). The product was used without further purification.

[0221] Synthesis of 5-fluoro-3-{[(2S)-1-methylpyrrolidin-2-yl]methyl}-1H-indole (27) TIFF2024523822000381.tif23128An oven-dried three-necked round-bottom flask was externally dried with a heat gun while argon was flowing through the system, and allowed to cool to room temperature before initiating the reaction. The three-necked flask was fitted with a condenser and a dropping funnel, which was used to add 80 mL of THF to the round-bottom flask. LiAlH 4 (1.04 g, 0.0273 mol) was added to the reaction. LiAlH 4 The LiAlH was rinsed with about 20 mL of THF. 4 After the addition, benzyl (2S)-2-(5-fluoro-1H-indole-3-carbonyl)pyrrolidine-1-carboxylate (2 g, 0.00546 mol) was added to the addition funnel, dissolved in 80 mL of THF, and added dropwise over 30 minutes. Once the addition was complete, the reaction was heated to moderate reflux using a heating mantle. Once reflux was obtained, the reaction was allowed to continue for 2 hours. After the 2 hour period, the reaction was placed in an ice bath and cooled to less than 10° C. The reaction was then diluted with 10 mL of H2O in a total volume of 60 mL at approximately 10° C. 2The reaction was quenched with 50% THF in 0. After quenching, a small amount of KOH was added to the quenched reaction, which was then filled with about 200 mL of EtOAc and stirred for several minutes. After stirring the solution, the solids in the reaction mixture were gravity filtered and washed with excess EtOAc. Washing was performed until no oil was eluted from the washes. The organic phase was then extracted three times with 0.3 M HCl (3 x 166 mL). These extracts were pooled, basified with KOH to a pH of >12, and extracted three times with 100 mL of EtOAc (3 x 100 mL). These organic extracts were pooled, washed with about 60 mL of brine (1 x 60 mL), dried over sodium sulfate, decanted, and removed under reduced pressure to give 1.25 g of a white / yellow solid. The material was purified by column chromatography utilizing silica gel as the stationary phase and 20% EtOH in EtOAc with 1% triethylamine as the mobile phase to give the title compound as a white solid with a slight yellow tinge (1.17 g, 0.00504 mol, 92.3% yield) (mp 135-136.4 °C). High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 233.1445 (theoretical [M+H] + C 14 H 18 F 1 N 2 + , m / z 233.1449, Δ=-1.7 ppm).[Free base] 1 H NMR (400MHz, d 6 -DMSO)δ 10.88(s,1H),7.31(dd,J=8.8,4.6Hz,1H),7.22(dd,J=10.3,2.4Hz,1H)*,7.2 1(d,J=2.3Hz,1H)*,6.88(td,J=9.2,2.5Hz,1H),3.02-2.90(m,2H),2.49-2.42 (m,1H)**,2.33(s,3H)***,2.36-2.25(m,1H)***,2.09(q,J=8.7Hz,1H),1.73 -1.63(m,1H),1.63-1.48(m,2H),1.48-1.38(m,1H).*=Fusion, **=DMSO Fusion, ***=Fusion. [Free base] 13 C NMR (101MHz, d 6-DMSO)δ 156.58(d,J=230.6Hz,1C),132.75(s,1C),127.76(d,J=9.7Hz,1C),125.06(s,1C),112.43(d,J=4.9Hz,1C),112.15(d,J=9.7Hz,1C),108.7 7(d,J=26.1Hz,1C),102.96(d,J=22.8Hz,1C),66.12(s,1C),56.93(s,1C),40.49(s,1C),30.81(s,1C),29.14(s,1C),21.57(s,1C).[Free base] 19 F NMR (377MHz,d 6 -DMSO) δ -125.34(s,1F).

[0222] Example 28: (R)-5-Fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole (28) TIFF2024523822000382.tif24128 Synthesis of benzyl (2R)-2-(5-fluoro-1H-indole-3-carbonyl)pyrrolidine-1-carboxylate TIFF2024523822000383.tif35128 Benzyl (2R)-2-(5-fluoro-1H-indole-3-carbonyl)pyrrolidine-1-carboxylate was prepared by the reaction of 5-fluoroindole (5.41 g, 0.0400 mol) as starting material, N-benzyloxylcarbonyl- D Starting from 1.4M methylmagnesium bromide in 1:3 THF / toluene (28.6mL, 0.0400mol), (S)-5-fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, synthesized in a similar manner as described above to obtain the title compound as a white solid (3.05g, 0.00832mol, 41.6% yield).The product was used without further purification.

[0223] Synthesis of (R)-5-fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole (28) TIFF2024523822000384.tif231285-Fluoro-3-(((2R)-1-methylpyrrolidin-2-yl)methyl)-1H-indole was synthesized in a similar manner as described above for (S)-5-fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, starting from benzyl (2R)-2-(5-fluoro-1H-indole-3-carbonyl)pyrrolidine-1-carboxylate (3 g, 0.00819 mol) as starting material to give the title compound as a white-yellow solid (1.42 g, 0.00611 mol, 74.6% yield). mp 127.6-131.7 °C. High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 233.1446 (theoretical [M+H] + C 14 H 18 F 1 N 2 + , m / z 233.1449, Δ=-1.3 ppm).[Free base] 1 H NMR (400MHz, d 6 -DMSO)δ 10.88(s,1H),7.31(dd,J=8.8,4.6Hz,1H),7.22(dd,J=10.4,2.4Hz,1H)*,7.21(d,J=2.4Hz)*,6.88(td,J=9.2,2.5Hz,1H),3.02-2.92(m,2H), 2.49-2.42(m,1H)*,2.33(s,3H),2.37-2.26(m,1H),2.09(q,J=8.7Hz,1 H),1.73-1.63(m,1H),1.63-1.48(m,2H),1.48-1.38(m,1H)=Fusion.[Free base] 13 C NMR (101MHz, d 6-DMSO)δ 156.59(d,J=230.6Hz,1C),132.75(s,1C),127.76(d,J=9.7Hz,1C),125.07(s,1C),112.41(d,J=4.6Hz,1C),112.16(d,J=9.7Hz,1C),108.7 7(d,J=26.0Hz,1C),102.96(d,J=22.8Hz,1C),66.13(s,1C),56.93(s,1C),40.48(s,1C),30.81(s,1C),29.13(s,1C),21.56(s,1C).[Free base] 19 F NMR (377MHz,d 6 -DMSO) δ -125.35(s,1F).

[0224] Example 29: 5-Fluoro-3-(1-methylazetidin-3-yl)-1H-indole (29) TIFF2024523822000385.tif29128Synthesis of tert-butyl 3-(5-fluoro-1H-indol-3-yl)-3-hydroxyazetidine-1-carboxylate TIFF2024523822000386.tif33128For this reaction, an oven-dried 100 mL round-bottom flask was utilized, which was heated externally with hot air from a heat gun and cooled to room temperature with downstream flow. 5-Fluoroindole (1 g, 0.00740 mol) was dissolved in MeOH (40 mL), then KOH (0.46 g, 0.00814 mol) was added and dissolved in solution. N-Boc-3-azetidinone (1.39 g, 0.00814 mol) was then added all at once and heated via a 50° C. water bath for 15 hours over two days. After two days, the reaction was worked up by removing MeOH under reduced pressure and then redissolving in EtOAc (150 mL). The organic phase was washed with 50 mL of H 2 O (3×50 mL), brine (1×60 mL), the organic phase was separated, dried over anhydrous sodium sulfate, decanted and removed under reduced pressure to give the title compound as an orange oil (1.78 g, 0.00581 mol, 78.5% yield). The product was used without further purification.

[0225] Synthesis of 5-fluoro-3-(1-methylazetidin-3-yl)-1H-indole (29) TIFF2024523822000387.tif29128An oven-dried three-necked round-bottom flask was externally dried with hot air from a heat gun while argon was flowing through the system, and allowed to cool to room temperature before starting the reaction. A condenser and dropping funnel were attached to the three neck, and 80 mL of THF was added to the round-bottom flask using this. LiAlH 4 (1.06 g, 0.0278 mol) was added to the reaction. LiAlH 4 The LiAlH 4 After the addition, tert-butyl 3-(5-fluoro-1H-indol-3-yl)-3-hydroxyazetidine-1-carboxylate (1.7 g, 0.00555 mol) was added to the dropping funnel and dissolved in 80 mL of THF. This was added dropwise over 30 minutes. Once the addition was complete, the reaction was heated to moderate reflux using a heating mantle. Once reflux was obtained, the reaction was allowed to continue for 2 hours. Then, after the 2 hour period, the reaction was placed in an ice bath and cooled to less than 10° C. The reaction was then rehydrated in 60 mL of H2O at approximately 10° C. 2The reaction mixture was quenched with 50% THF in 0. After quenching, a small amount of KOH was added to the quenched reaction, which was then filled with about 200 mL of EtOAc and stirred for several minutes. After stirring the solution, the solids in the reaction mixture were gravity filtered and washed with excess EtOAc. Washing was performed until no more oil was eluted from the washes. The organic phase was then extracted three times with 0.3 M HCl (3 x 166 mL). These extracts were pooled, basified with KOH to a pH of >12, and extracted three times with 100 mL of EtOAc (3 x 100 mL). These organic extracts were pooled, washed with about 60 mL of brine (1 x 60 mL), dried over sodium sulfate, decanted, and removed under reduced pressure to give 1.02 g of a yellow oil. This was purified by column chromatography utilizing silica gel as the stationary phase and a gradient of 5%-20% EtOH in EtOAc with 1% triethylamine as the mobile phase to give the title compound as an orange-white solid, which was crystallized from EtOAc and hexane to give a white solid (0.60 g, 0.00294 mol, 53.0%), mp 119.0-122.8 °C. High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 205.1133 (theoretical [M+H] + C 12 H 14 FN 2 + , m / z 205.1136, Δ=-1.5 ppm).[Free base] 1 H NMR (400MHz, d 6 -DMSO)δ 10.99(s,1H),7.37(dd,J=10.2,2.5Hz,1H),7.32(dd,J=9.0,4.9Hz,1H)*,7.30(d,J=2.8Hz,1H)* ,6.90(td,J=9.2,2.5Hz,1H),3.76-3.65(m,3H),3.17-3.09(m,2H),2.30(s,3H).*=Fusion peak [free base] 13 C NMR (101MHz, d 6-DMSO)δ 156.58(d,J=230.8Hz,1C),133.06(s,1C),126.42(d,J=9.7Hz,1C),124.23(s,1C),116.34(d,J=4.8Hz,1C),112.33(d ,J=9.8Hz,1C),109.12(d,J=26.2Hz,1C),103.27(d,J=23.1Hz,1C),62.91(s,2C),45.86(s,1C),26.55(s,1C).[Free base] 19 F NMR (377MHz,d 6 -DMSO) δ -125.05(s,1F).

[0226] Example 30: N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine (30) TIFF2024523822000388.tif29128N-Ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine was synthesized in a similar manner as described above for N-Ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluorotryptamine hydrochloride (0.5 g, 0.00233 mol), methyl ethyl ketone (0.5 g, 0.00699 mol), and acetaldehyde (0.62 g, 0.0140 mol) as starting materials to give the title compound as a clear oil (0.35 g, 0.00132 mol, 56.7% yield). The conditions used differ from those described for compound (1) in that 6 molar equivalents of acetaldehyde were utilized as opposed to 3 molar equivalents. High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 263.1914 (theoretical [M+H] + C 16 H 24 FN 2 + , m / z 263.1918, Δ=-1.5 ppm).[Free base] 1 H NMR (400MHz, d 6-DMSO) δ 10.85 (singlet, 1H), 7.31 (doublet of doublets, J = 8.8, 4.6 Hz, 1H), 7.21 (doublet, J = 2.1 Hz, 1H), 7.18 (doublet of doublets, J = 10.1, 2.4 Hz, 1H), 6.88 (triplet of doublets, J = 9.2, 2.5 Hz, 1H), 2.81 - 2.71 (multiplet, 1H), 2.71 - 2.61 (multiplet, 3H), 2.60 - 2.51 (multiplet, 2H)*, 2.44 - 2.36 (multiplet, 1H), 1.54 - 1.33 (multiplet, 1H), 1.27 - 1.13 (multiplet, 1H), 0.99 (triplet, J = 7.1 Hz, 3H), 0.87 (doublet, J = 6.5 Hz, 3H), 0.83 (triplet, J = 7.4 Hz, 3H). *= overlapping peak [free base] 13 C NMR (101 MHz, d 6 -DMSO) δ 156.58 (doublet, J = 230.6 Hz, 1C), 132.84 (singlet, 1C), 127.53 (doublet, J = 9.5 Hz, 1C), 124.71 (singlet, 1C), 113.36 (doublet, J = 5.0 Hz, 1C), 112.20 (doublet, J = 9.8 Hz, 1C), 108.79 (doublet, J = 26.2 Hz, 1C), 102.77 (doublet, J = 22.8 Hz, 1C), 56.09 (singlet, 1C), 50.22 (singlet, 1C), 43.32 (singlet, 1C), 26.54 (singlet, 1C), 25.27 (singlet, 1C), 14.66 (singlet, 1C), 13.92 (singlet, 1C), 11.57 (singlet, 1C). [free base] 19 F NMR (377 MHz, d 6 -DMSO) δ -125.41 (singlet, 1F).

[0227] Example 31: N-Ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine (31) TIFF2024523822000389.tif33128 N-Ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine (5) starting from N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine (0.33 g, 0.00142 mol) and acetaldehyde (0.38 g, 0.00853 mol) as starting materials to give the title compound as a yellow / white solid (0.27 g, 0.00102 mol, 71.8% yield). mp 89.4-90.3 °C. The only modification was that the material was purified by column chromatography using silica gel as the stationary phase and 5%-20% EtOH in EtOAc with 1% TEA as the mobile phase. High Resolution Atmospheric Pressure Solid Analysis Probe Mass Spectrometry (HR-ASAP-MS): m / z 261.1757 (theoretical [M+H] + C 15 H 21 F 2 N 2 + , m / z 261.1762, Δ=-1.9 ppm).[Free base] 1 H NMR (400MHz, d 6 -DMSO)δ 10.87(s,1H),7.31(dd,J=8.8,4.6Hz,H),7.21(d,J=2.2Hz,1H),7.18(dd,J=10.0,2.5Hz,1H),6.88(td,J=9.2,2.5Hz,1H),3.19-3.09(m,1H),2 .74-2.65(m,2H),2.65-2.56(m,2H),2.56-2.50(m,2H)*,2.03-1.94(m, 2H),1.85-1.71(m,2H),1.65-1.50(m,2H),0.96(t,J=7.1Hz,3H).*=Fusion. [Free base] 13 C NMR (101MHz, d 6-DMSO)δ 156.57(d,J=231.0Hz,1C),132.85(s,1C),127.43(d,J=9.6Hz,1C),124. 61(s,1C),113.22(d,J=4.9Hz,1C),112.24(d,J=9.7Hz,1C),108.84(d,J= 26.0Hz,1C),102.72(d,J=22.8Hz,1C),57.23(s,1C),49.46(s,1C),42.8 1(s,1C),28.10(s,2C),21.99(s,1C),14.09(s,1C),11.47(s,1C).[Free base] 19 F NMR (377MHz,d 6 -DMSO) δ -125.28(s,1F).

[0228] Example 32: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylbutan-2-amine (32) TIFF2024523822000390.tif32128N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-isopropylbutan-2-amine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluorotryptamine hydrochloride (0.5 g, 0.00233 mol), methyl ethyl ketone (0.5 g, 0.00699 mol), and acetone (23.52 g, 0.405 mol) as starting materials to give the title compound as a light brown oil (0.36 g, 0.00130 mol, 55.8% yield). The HCl salt was collected as a white fluffy solid (mp 193.7-195 °C). The only change from the method described for compound (1) was that 30 mL of acetone and 20 mL of MeOH were utilized as the solvent, as opposed to methanol. High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 277.2069 (theoretical [M+H] + C 17 H 25 FN 2 + , m / z 277.2075, Δ=-2.2 ppm).[Free base] 11H NMR (400 MHz, d 6 -DMSO) δ 10.86 (s, 1H), 7.31 (dd, J = 8.3, 4.3 Hz, 1H), 7.21 (s, 1H), 7.16 (d, J = 9.6 Hz, 1H), 6.88 (t, J = 8.4 Hz, 1H), 3.08 - 2.97 (m, 1H), 2.78 - 2.54 (m, 5H), 1.44 - 1.28 (m, 1H), 1.25 - 1.16 (m, 1H), 1.06 - 0.89 (m, 9H), 0.83 (t, J = 7.1 Hz, 3H). [Free base] 13 13C NMR (101 MHz, d 6 -DMSO) δ 156.56 (d, J = 230.9 Hz, 1C), 132.83 (s, 1C), 127.51 (d, J = 9.7 Hz, 1C), 124.70 (s, 1C), 113.38 (d, J = 5.4 Hz, 1C), 112.19 (d, J = 9.8 Hz, 1C), 108.74 (d, J = 26.1 Hz, 1C), 102.68 (d, J = 22.7 Hz, 1C), 53.71 (s, 1C), 47.67 (s, 1C), 45.64 (s, 1C), 28.11 (s, 1C), 26.82 (s, 1C), 22.11 (s, 1C), 19.89 (s, 1C), 17.31 (s, 1C), 11.68 (s, 1C). [Free base] 19 19F NMR (377 MHz, DMSO) δ -125.40 (s, 1F).

[0229] Example 33: N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-propylcyclobutanamine (33) TIFF2024523822000391.tif33128N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-propylcyclobutanamine was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine (5) starting from N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine (0.33 g, 0.00142 mol) and propionaldehyde (0.38 g, 0.00853 mol) as starting materials to give the title compound as a yellow / white solid (0.28 g, 0.00101 mol, 71.1% yield). mp 110.0-112.5°C. The product was purified by column chromatography using silica gel as the stationary phase and 5%-20% EtOH in EtOAc with 1% TEA as the mobile phase. [Free base] 1 H NMR(400MHz,DMSO)δ 10.86(s,1H),7.31(dd,J=8.8,4.6Hz,1H),7.21(d,J=2.3Hz,1H),7.17(dd,J= 10.0,2.5Hz,1H),6.88(td,J=9.1,2.5Hz,1H),3.21-3.10(m,1H),2.75-2.66(m ,2H),2.66-2.58(m,2H),2.43-2.35(m,2H),2.03-1.94(m,2H),1.84-1.71(m, 2H),1.63-1.51(m,2H),1.47(sex,J=7.4Hz,2H),0.85(t,J=7.3Hz,3H).[Free base] 13 C NMR(101MHz,DMSO)δ 156.57(d,J=230.9Hz,1C),132.85(s,1C),127.42(d,J=9.8Hz,1C),124.61( s,1C),113.22(d,J=4.9Hz,1C),112.24(d,J=9.7Hz,1C),108.84(d,J=25.9Hz ,1C),102.70(d,J=22.8Hz,1C),57.72(s,1C),51.56(s,1C),50.48(s,1C),2 8.09(s,2C),21.95(s,1C),19.88(s,1C),14.06(s,1C),12.00(s,1C).[Free base] 19F NMR(377MHz,DMSO)δ -125.29(s,1F).

[0230] Example 34: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylprop-2-yn-1-amine (34) TIFF2024523822000392.tif32128N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylprop-2-yn-1-amine was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylprop-2-en-1-amine (11) starting from N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (0.5 g, 0.00227 mol) as starting material to obtain the title compound as a brown oil (0.21 g, 0.00809 mol, 35.6% yield). The product was converted to the fumarate salt. High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 259.1601 (theoretical [M+H] + C 16 H 20 FN 2 + , m / z 259.1605, Δ=-1.5 ppm).

[0231] Example 35: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylprop-2-en-1-amine (35) TIFF2024523822000393.tif31128 N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylprop-2-en-1-amine was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine (5) starting from N-(2-(5-fluoro-1H-indol-3-yl)ethyl)prop-2-en-1-amine (0.5 g, 0.00229 mol) and propionaldehyde (495 μL, 0.00687 mol) as starting materials to give the title compound as a pale yellow odorless oil (0.48 g, 0.00198 mol, 80.5% yield). The material was converted to the HCl salt as described to give a white crystalline solid (mp 175.1-177.2 °C). Modifications from the method used to prepare compound (5) included the addition of 0.65 mol equivalents of NaBH 3 The use of CN, direct work-up with base, and silica gel as the stationary phase with EtOAc (0.5% Et 3 N) and EtOAc (0.5% Et 3 Purification by flash column chromatography using gradient elution to 5% EtOH in N. High resolution atmospheric pressure solids analytical probe mass spectrometry (HR-ASAP-MS): m / z 261.1755 (theoretical [M+H] + C 16 H 22 FN 2 + ,m / z 261.1762,Δ=-2.7 ppm).[HCl] 1 H NMR (400MHz, d 6-DMSO)δ 11.14(s,1H),11.04(s,1H),7.41(dd,J=10.1,2.5Hz,1H),7.36(dd,J=8.9,4.6Hz,1H)*,7.33(d,J=2.4Hz,1H)*,6.9 3(td,J=9.2,2.5Hz,1H),6.15-6.03(m,1H),5.60(dd,J=17.1,1.0Hz,1H),5.51(dd,J=10.3,1.0Hz,1H),3.89-3.79(m 2H),3.26-3.14(m,4H),3.12-2.99(m,2H),1.75(sex,J=7.7Hz,2H),0.91(t,J=7.4Hz,3H).[HCl] 13 C NMR (101MHz,d 6 -DMSO)δ 156.75(d,J=231.4Hz,1C),132.87(s,1C),127.54(s,1C),126.94(d,J=9. 8Hz,1C),125.49(s,1C),124.66(s,1C),112.52(d,J=9.8Hz,1C),109.53(s ,1C),109.34(d,J=26.0Hz,1C),103.05(d,J=23.1Hz,1C),53.91(s,1C),52 .95(s,1C),51.89(s,1C),19.31(s,1C),16.51(s,1C),10.94(s,1C).[HCl] 19 F NMR (377MHz, d 6 -DMSO)δ -124.77(s,1F).

[0232] Example 36: N-エチル-N-(2-(5-フルオロ-1H-インドール-3-イル)エチル)プロパ-2-エン-1-アミン (36) TIFF2024523822000394.tif31128 N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)prop-2-en-1-amine was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine (5) starting from N-(2-(5-fluoro-1H-indol-3-yl)ethyl)prop-2-en-1-amine (0.5 g, 0.00229 mol) and acetaldehyde (0.30 g, 0.00687 mol) as starting materials to give the title compound as a yellowish oil (0.42 g, 0.00161 mol, 74.4% yield). The hydrochloride salt was collected as a white crystalline material (mp 123.7-128.5 °C). Modifications from the method used to prepare compound (5) included the addition of 1.1 molar equivalents of acetic acid, 0.65 molar equivalents of NaBH 3 The products were purified by elution with EtOAc (0.5% Et 3 N) to EtOAc (0.5% Et 3 Purified by flash column chromatography using gradient elution to 10% EtOH in N). High resolution atmospheric pressure solids analytical probe mass spectrometry (HR-ASAP-MS): m / z 247.1600 (theoretical [M+H] + C 15 H 20 FN 2 + ,m / z 247.1605,Δ=-2.0 ppm).[HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.14(s,1H),11.08(s,1H),7.41(dd,J=10.0,2.4Hz,1H),7.36(dd,J=9.0,4.7Hz,1H),7.34(d,J=2.7Hz,1H),6.93(td,J=9.2,2.5Hz,1H), 6.14-5.99(m,1H),5.60(dd,J=6.1,1.3Hz,1H),5.51(d,J=10.5Hz,1H),3.89-3.77(m,2H),3.24-3.11(m,6H)*,1.28(t,J=7.2Hz,3H).*Fusion. [HCl]13 C NMR (101MHz, d 6 -DMSO)δ 156.75(d,J=231.2Hz,1C),132.87(s,1C),127.55(s,1C),126.94(d,J =10.1Hz,1C),125.49(s,1C),124.58(s,1C),112.52(d,J=9.9Hz,1C),1 09.52(s,1C),109.33(d,J=26.0Hz,1C),103.03(d,J=23.2Hz,1C),53.2 4(s,1C),51.27(s,1C),46.38(s,1C),19.34(s,1C),8.45(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -124.77(s,1F).

[0233] Example 37: N-(2-(6-chloro-5-fluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine (37) TIFF2024523822000395.tif31128Synthesis of 2-(6-chloro-5-fluoro-1H-indol-3-yl)-N-ethyl-2-oxo-N-propylacetamide TIFF2024523822000396.tif23128 2-(6-chloro-5-fluoro-1H-indol-3-yl)-N-ethyl-2-oxo-N-propylacetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 6-chloro-5-fluoro-1H-indole (4.83 g, 0.02843 mol), oxalyl chloride (2.99 mL, 35.58 mmol), and N-ethylpropylamine (4.95 mL, 0.0424 mol), and TEA (17.7 mL, 0.127 mol) as starting materials to give the crude material as a fine tan to sandy powder (8.16 g, 0.02626 mol, 89.0% yield). The product was used without further purification.

[0234] Synthesis of N-(2-(6-chloro-5-fluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine (37) TIFF2024523822000397.tif31128A three-necked 500 mL round bottom flask, 300 mL dropping funnel, stir bar, and condenser were assembled by drying overnight in an oven and then drying externally with a stream of hot air while maintaining a flow of argon through the system. Once deemed dry, the round bottom flask was placed in an ice-water bath (0°C) and allowed to cool. After cooling, 70 mL of dry (3 Å molecular sieves) tetrahydrofuran (THF) was added to the round bottom flask and allowed to reach approximately 0°C. Lithium aluminum hydride (LiAlH 4 ) (2.95 g, 0.0777 mol) was slowly added to a round bottom flask under argon atmosphere with stirring. Meanwhile, 100 mL of dry THF was added to an oven dried Erlenmeyer flask and placed in an ice water bath (approximately 0 °C) and allowed to cool. Once cooled, AlCl 3 (3.55 g, 0.02663 mol) was added in small portions with swirling. The solution was transferred to a dropping funnel and stirred and cooled LiAlH 4 The suspension was added dropwise. An additional 3×25 mL of THF was added to the dropping funnel to wash out any remaining material. Once the addition was complete, a solution of 2-(6-chloro-5-fluoro-1H-indol-3-yl)-N-ethyl-2-oxo-N-propylacetamide (8.05 g, 0.0259 mol) in 100 mL of THF was added dropwise over 1 h at 0° C. An additional 20 mL of THF was added to the dropping funnel and added over 10 min to wash out any remaining material. The reaction was then heated to reflux and maintained at reflux, stirring under argon (Teflon coated magnetic stir bar) while additional dry THF was added for 3 h and 15 min as the reaction evaporated. At this point, the reaction was determined to be complete (as determined by TLC and ASAP-MS). The reaction was then placed back on an ice-water bath and washed with approximately 1:1 THF / H2O with the addition of ice. 2The mixture was quenched by careful addition of 2×O. Once quenched, a few mL of brine and aqueous KOH were added to ensure basicity, followed by 100 mL of EtOAc. The inorganic solids were removed by gravity filtration onto Whatman paper (24 cm diameter). The removed solids were then washed extensively with EtOAc. After washing the solids, the mother liquor was removed and extracted with 4×125 mL of 0.2 M aqueous HCl. The aqueous phase was then basified with KOH pellets and extracted with 3×100 mL of EtOAc. The pooled organic phase was washed with brine (20 mL) and anhydrous Na 2 SO 4 The mixture was dried over hexane and the solvent removed under reduced pressure to give 4.56 g of an orange oil which crystallized to a white crystalline solid upon cooling. The free base was purified by column chromatography using silica gel as the stationary phase and gradient elution from EtOAc (1% TEA) to 10% EtOH in EtOAc (1% TEA) to give the title compound as a pale white solid (2.52 g, 0.00891 mol, 34.4% yield). mp 92.4-93.6°C. The hydrochloride salt was collected as a white powder (mp 231.0-232.6°C). High Resolution Atmospheric Pressure Solid Analysis Probe Mass Spectrometry (HR-ASAP-MS): m / z 283.1367 (theoretical [M+H] + C 15 H 21 FClN 2 + ,m / z 283.1372,Δ=-1.8 ppm).[HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.29(s,1H),10.68(s,1H),7.69(d,J=10.3Hz,1H),7.54(d,J=6.4Hz,1H),7.41(d,J=2.3Hz,1H),3.27-3. 11(m,6H)*,3.11-2.98(m,2H),1.71(sex,J=9.7Hz,2H),1.25(t,J=7.2Hz,3H),0.92(t,J=7.4Hz,3H).*Fusion. [HCl] 13 C NMR (101MHz, d 6-DMSO)δ 151.51(d,J=234.6Hz,1C),132.55(s,1C),126.32(s,1C),125.76(d,J=8.6Hz,1C),113.27(d,J=21.4Hz,1C),112.51(s,1C),109.99(d,J=4. 5Hz,1C),104.73(d,J=23.0Hz,1C),52.35(s,1C),51.51(s,1C),46.41(s,1C),19.24(s,1C),16.47(s,1C),10.94(s,1C),8.33(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -128.02(s,1F).

[0235] Example 38: 1-Cyclopropyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylethan-1-amine (38) TIFF2024523822000398.tif351281-Cyclopropyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylethan-1-amine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluorotryptamine hydrochloride (0.6 g, 0.00279 mol) and cyclopropyl methyl ketone (0.704 g, 0.00837 mol) and 37% aqueous formaldehyde solution (0.62 mL, 0.00837 mol) as starting materials to give the title compound as a white solid (0.44 g, 0.00169 mol, 60.4% yield). The hydrochloride salt of the title compound was collected as a white round pearl-shaped solid. The variations from the method used to synthesize compound (1) are as follows: the reaction mixture was heated to reflux to form the secondary amine intermediate, cooled to room temperature, and then fresh NaBH 3CN (0.114 g, 0.00181 mol) and formaldehyde were added and the reaction was worked up directly with base. The product was purified by flash column chromatography using silica gel as the stationary phase with gradient elution from EtOAc (0.5% TEA) to 35% EtOH in EtOAc (0.5% TEA). High resolution atmospheric pressure solids analytical probe mass spectrometry (HR-ASAP-MS): m / z 261.1757 (theoretical [M+H] + C 15 H 21 FN 2 + ,m / z 261.1762,Δ=-1.9 ppm).HCl mp100.7~101.5℃.[Free base] 1 H NMR (400MHz, d 6 -DMSO)δ 10.86(s,1H),7.31(dd,J=8.8,4.6Hz,1H),7.22(d,J=2.3Hz,1H)*,7.22(dd, J=9.8,2.5Hz,1H)*,6.88(td,J=9.1,2.4Hz,1H),2.79-2.68(m,4H),2.32(s, 3H),2.02-1.89(m,1H),1.00(d,J=6.6Hz,3H),0.81-0.70(m,1H),0.49-0.41 (m,1H),0.41-0.32(m,1H),0.27-0.17(m,1H),0.06-(-0.04)(m,1H).[Free base] 13 C NMR (101MHz, d 6 -DMSO)δ 156.56(d,J=230.6Hz,1C),132.81(s,1C),127.53(d,J=9.6Hz,1C),124.6 2(s,1C),113.30(d,J=4.9Hz,1C),112.15(d,J=9.5Hz,1C),108.79(d,J=26 .1Hz,1C),102.88(d,J=22.8Hz,1C),62.62(s,1C),54.49(s,1C),37.41(s ,1C),23.50(s,1C),15.43(s,1C),13.88(s,1C),4.93(s,1C),2.04(s,1C). 19 F NMR (377MHz,d 6 -DMSO) δ -125.37(s,1F).

[0236] Example 39: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine (39) TIFF2024523822000399.tif28128 N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluorotryptamine hydrochloride (0.6 g, 0.00279 mol) and isobutyraldehyde (0.604 g, 0.00837 mol) and a 37% aqueous solution of formaldehyde (623 μL, 0.00837 mmol) as starting materials to afford the title compound as a clear tan oil (0.23 g, 0.00926 mol, 33.0% yield). The crude product was purified by flash column chromatography using silica gel as the stationary phase and eluted with 50% hexane and 50% EtOAc (0.5% TEA). The hydrochloride salt of the title compound was collected as a white opaque shiny crystalline solid (mp 150.0-151.5 °C). High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 249.1757 (theoretical [M+H] + C 15 H 22 FN 2 + ,m / z 249.1762,Δ=-2.0 ppm).[HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.21(s,1H),10.46(s,1H),7.50(dd,J=10.1,2.5Hz,1H),7.36(dd,J=8.8,4.6Hz,1H),7.31(d,J=2.4Hz,1H),6.92(td,J=9.3,2.5Hz,1H),3.33- 3.12(m,4H),3.11-3.02(m,1H),2.98-2.85(m,1H),2.81(d,J=4.8Hz,3H ),2.16-2.01(m,1H),1.03(d,J=6.6Hz,3H),0.98(d,J=6.6Hz,3H).[HCl] 13C NMR (101MHz, d 6 -DMSO)δ 156.51(d,J=231.1Hz,1C),132.67(s,1C),126.76(d,J=10.1Hz,1C),125 .18(s,1C),112.26(d,J=9.8Hz,1C),109.27(d,J=4.9Hz,1C),109.07(d,J =26.1Hz,1C),103.00(d,J=23.2Hz,1C),61.53(s,1C),55.92(s,1C),39. 52(s,1C),23.47(s,1C),20.42(s,1C),20.19(s,1C),19.25(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -124.90(s,1F).

[0237] Example 40: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylcyclobutanamine (40) TIFF2024523822000400.tif33128N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-isopropylcyclobutanamine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluoro-tryptamine hydrochloride (0.6 g, 0.00279 mol) and acetone (0.205 mL, 0.00558 mol) as starting materials to give the title compound as a colorless oil that solidified into a white solid (110 mg, 0.0004 mol, 14.4% yield). The hydrochloride salt was collected as a white crystalline powder. mp 191.6-193.0 °C. The modification from method B was that the removal of the solvent was carried out under reduced pressure with continuous addition of MeOH after complete conversion was observed, the residue was redissolved in dry MeOH, followed by acetic acid (16 μL), NaBH 3 CN (0.114 g, 0.00181 mol) and cyclobutanone (0.83 mL, 0.01116 mol) were added and the reaction was set to reflux. After 24 h, fresh NaBH 3CN (0.114 g, 0.00181 mol) and cyclobutanone (0.42 mL, 0.00558 mmol) were added and reflux was continued until complete (GC-MS) after 44 h (total). The reaction was then cooled to room temperature and diluted with H 2 The crude product was diluted with 200 mL of ethyl acetate and worked up by basification and extraction as described elsewhere herein. Purification was achieved by flash column chromatography using silica gel as the stationary phase and elution with EtOAc (0.5% TEA). High resolution atmospheric pressure solids analytical probe mass spectrometry (HR-ASAP-MS): m / z 275.1912 (theoretical [M+H] + C 17 H 24 FN 2 + ,m / z 275.1918,Δ=-2.2 ppm).[HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.14(s,1H),10.83(s,1H),7.41-7.33(m,3H),6.93(td,J=9.2,2.5Hz,1H) ,3.97-3.83(m,1H),3.67-3.54(m,1H),3.21-3.09(m,3H),3.09-2.98(m,1H ),2.66(p,J=10.0Hz,1H),2.59-2.51(m,1H)*,2.30-2.14(m,1H),1.80-1.7 0(m,1H),1.70-1.60(m,1H),1.35(d,J=6.6Hz,3H),1.24(d,J=6.7Hz,3H).*d 6 -Fusion with DMSO.[HCl] 13 C NMR (101MHz, d 6-DMSO)δ 156.77(d,J=231.2Hz,1C),132.86(s,1C),126.87(d,J=9.7Hz,1C),125.56(s,1 C),112.53(d,J=9.7Hz,1C),109.96(d,J=4.9Hz,1C),109.32(d,J=26.2Hz,1C), 102.90(d,J=23.1Hz,1C),55.75(s,1C),52.66(s,1C),47.65(s,1C),27.09(s,1 C),27.04(s,1C),21.07(s,1C),16.89(s,1C),15.85(s,1C),14.19(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -124.65(s,1F).

[0238] Example 41: N-ethyl-N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)propan-1-amine (41) TIFF2024523822000401.tif31128Synthesis of N-ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-2-oxo-N-propylacetamide TIFF2024523822000402.tif22128 N-Ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-2-oxo-N-propylacetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1amine utilizing 5-methoxy-7-fluoroindole (1 g, 0.00605 mol), oxalyl chloride (0.99 g, 0.00787 mol), and ethylpropylamine (0.92 mL, 0.00787 mol) to give N-ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-2-oxo-N-propylacetamide as a yellow oil that crystallized upon cooling in a refrigerator (2.35 g, 0.00767 mol, quantitative).

[0239] Synthesis of N-ethyl-N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)propan-1-amine TIFF2024523822000403.tif31128 N-Ethyl-N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)propan-1-amine (41) was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) utilizing N-ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-2-oxo-N-propylacetamide (1.7 g, 0.00555 mol) to give N-ethyl-N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)propan-1-amine as a clear, pale yellow oil (0.76 g, 0.02273 mol, 49.19% yield). The HCl salt was collected as a white crystalline powder. High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 279.1871 (theoretical [M+H] + C 16 H 24 FN 2 O + , m / z 279.1867, Δ=1.4 ppm). 1 H NMR(400MHz,DMSO)δ 11.30(s,1H),10.60(s,1H),7.30(d,J=2.4Hz,1H),7.03(d,J=2.0Hz,1H),6.63(dd,J=12.7,2.0Hz,1H),3.79(s,3H),3.27-3. 22(m,4H),3.15-3.10(m,2H),3.09-3.02(m,2H),1.71(sex,J=7.7Hz,2H),1.26(t,J=7.2Hz,3H),0.92(t,J=7.3Hz,3H).[HCl] 13C NMR(101MHz,DMSO)δ 153.24(d,J=9.3Hz,1C),148.90(d,J=243.2Hz,1C),130.19(d,J=7.3Hz,1C), 125.10(s,1C),119.13(d,J=13.5Hz,1C),110.30(d,J=2.3Hz,1C),97.15(d,J= 19.4Hz,1C),96.48(d,J=3.1Hz,1C),55.91(s,1C),52.46(s,1C),51.40(s,1C) ),46.52(s,1C),19.44(s,1C),16.53(s,1C),10.98(s,1C),8.38(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -131.29(s,1F).

[0240] Example 42: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine (51) TIFF2024523822000404.tif33128 N-[2-(5-Fluoro-1H-indol-3-yl)ethyl]-N-methylcyclobutanamine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluorotryptamine hydrochloride (0.5 g, 0.00233 mol), cyclobutanone (0.98 g, 0.014 mol), and 37% formaldehyde in water (0.52 mL, 0.00699 mol) as starting materials to afford the title compound as a clear tan oil. The hydrochloride salt was collected as a white crystalline solid (0.26 g, 0.000920 mol, 39.5% yield) (mp 219.4-219.7 °C). High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 247.1616 (theoretical [M+H] + C 15 H 20 FN 2 + ,m / z 247.1605,Δ=4.5 ppm).[HCl] 1 H NMR (400MHz, d 6-DMSO)δ 11.18(s,1H),11.13(s,1H),7.42(dd,J=10.0,2.5Hz,1H),7.36(dd,J=8.8,4.6Hz,1H)*,7.33(d,J=2.4Hz,1H)*,6.93(td,J=9.2,2.5 Hz,1H),3.71(sex,J=8.3Hz,1H),3.23-2.99(m,4H),2.69(d,J=4.7Hz,3H),2.48-2.30(m,2H),2.25-2.11(m,2H),1.79-1.58(m,2H).* =fusion. [HCl] 13 C NMR (101MHz,d 6 -DMSO)δ 156.75(d,J=231.2Hz,1C),132.87(s,1C),126.91(d,J=10.1Hz,1C),125 .42(s,1C),112.50(d,J=9.7Hz,1C),109.55(d,J=4.8Hz,1C),109.33(d,J =26.2Hz,1C),103.01(d,J=23.1Hz,1C),58.43(s,1C),52.08(s,1C),35. 53(s,1C),25.41(s,1C),25.08(s,1C),19.45(s,1C),12.93(s,1C).[HCl] 19 F NMR (377MHz, d 6 -DMSO)δ -124.73(s,1F).

[0241] Example 43: N-(sec-ブチル)-N-(2-(5-フルオロ-1H-インドール-3-イル)エチル)シクロブタンアミン (158) TIFF2024523822000405.tif33128N-(butan-2-yl)-N-[2-(5-fluoro-1H-indol-3-yl)ethyl]cyclobutanamine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluorotryptamine hydrochloride (0.5 g, 0.00233 mol), methyl ethyl ketone (0.63 mL, 0.00699 mol), and cyclobutanone (0.65 g, 0.00932 mol) as starting materials to give the title compound as clear, colorless crystals (0.66 g, 0.00229 mol, 98% yield). The hydrochloride salt was collected as a white crystalline solid. The conditions used were different from those described for compound (1). The material was purified in 80% EtOAc in hexanes with 0.5% triethylamine, and the reaction was held at reflux for 7.5 hours after addition of cyclobutanone. High Resolution Atmospheric Pressure Solid Analysis Probe Mass Spectrometry (HR-ASAP-MS): m / z 289.2061 (theoretical [M+H] + C 18 H 26 FN 2 + , m / z 289.2075, Δ=-4.84 ppm).[Free base] 1 H NMR (400MHz, d 6 -DMSO)δ 10.90(s,1H),7.31(dd,J=8.8,4.6Hz,1H),7.22(d,J=1.7Hz,1H),7.16(dd,J=9.9,1.6Hz,1H),6.89(td,J=13.8,2.5Hz,1H),3.31-3.22(m,1H)* 2.82-2.59(m,4H)**,2.59-2.51(m,1H)* / **,2.04-1.75(m,4H),1.63-1.51(m,2H)***,1 .51-1.36(m,1H)***,1.31-1.15(m,1H),0.89(d,J=6.1Hz,3H),0.86(t,J=7.4Hz,3H).*=H 2 fused with O, **=fused with DMSO solvent peak, ***=fused. [Free base] 13 C NMR (101MHz, d 6-DMSO)δ 156.58(d,J=230.9Hz,1C),141.29(s,1C),132.86(s,1C),127.41(d,J=9. 2Hz,1C),124.74(s,1C),112.27(d,J=9.8Hz,1C),108.83(d,J=26.1Hz,1C) ,102.71(d,J=22.8Hz,1C),55.35(s,2C),47.24(s,1C),29.57(s,1C),29. 01(s,1C),26.95(s,1C),14.98(s,1C),14.67(s,2C),11.71(s,1C).[Free base] 19 F NMR (377MHz,d 6 -DMSO) δ -125.28(s,1F).

[0242] Example 44: N-(cyclopropylmethyl)-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (159) TIFF2024523822000406.tif33128 N-(cyclopropylmethyl)-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluorotryptamine hydrochloride (0.5 g, 0.00233 mol), acetone (0.41 g, 0.00699 mol), and cyclopropanecarboxaldehyde (0.49 g, 0.00699 mol) as starting materials to afford the title compound as a clear tan oil (0.58 g, 0.00211 mol, 91% yield). The hydrochloride salt was collected as a white crystalline solid (mp 191.0-192.5 °C). The conditions used were different from those described for compound (1). The material was purified starting from pure ethyl acetate with a gradient from 0.5% TEA to 5% EtOH in EtOAc with 0.5% TEA. High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 275.1908 (theoretical [M+H] + C 15 H 21 F 2 N2 + ,m / z 275.1918,Δ=-3.6 ppm)[HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.15(s,1H),10.32(s,1H),7.43(dd,J=10.1,2.5Hz,1H),7.36(dd,J=8.5,4.8Hz,1H)*,7. 36(d,J=3.0Hz,1H)*,6.93(td,J=9.2,2.5Hz,1H),3.91-3.76(m,1H),3.31-3.24(m,2H)*,3 .23-3.17 (m, 2H) **, 3.15-2.98 (m, 2H), 1.31 (d, J = 6.7 Hz, 3H) ***, 1.29 (d, J = 6.7 Hz, 3H) **, 1.26-1.18 (m, J = 4.0 Hz, 1H) **, 0.69-0.61 (m, 2H), 0.53-0.37 (m, 2H). * = fusion, ** = fusion, *** = fusion. [HCl] 13 C NMR (101MHz,d 6 -DMSO)δ 156.78(d,J=231.3Hz,1C),132.89(s,1C),127.00(d,J=10.1Hz,1C),125.5 1(s,1C),112.54(d,J=9.8Hz,1C),109.85(d,J=4.7Hz,1C),109.35(d,J=26. 0Hz,1C),103.05(d,J=23.1Hz,1C),53.57(s,1C),53.46(s,1C),49.13(s,1C ),20.39(s,1C),16.02(s,2C),6.26(s,1C),4.72(s,1C),4.37(s,1C).[HCl] 19 F NMR (377MHz, d 6 -DMSO)δ -124.70(s,1F).

[0243] Example 45: N-[2-(5,7-ジフルオロ-1H-インドール-3-イル)エチル]-N-エチルプロパン-1-アミン(72) TIFF2024523822000407.tif361282-(5,7-ジフルオロ- 1H-インドール-3-イル)-N-エチル-2-オキソ-N-プロピルアセトアミドの synthesis TIFF2024523822000408.tif361282-(5,7-difluoro-1H-indol-3-yl)-N-ethyl-2-oxo-N-propylacetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7), starting from 5,7-DiF-1H-indole (2.0g, 0.0131mol), oxalyl chloride (1.4mL, 0.017mol), and N-ethylpropylamine (1.4g, 0.017mol) and TEA (5.46mL, 0.0392mol) as starting materials, to obtain crude material as an orange solid (4.37g, 0.0263mol, quantitative yield).The product was used without further purification.

[0244] Synthesis of N-(2-(5,7-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine (72) TIFF2024523822000409.tif36128N-(2-(5,7-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 2-(5,7-difluoro-1H-indol-3-yl)-N-ethyl-2-oxo-N-propylacetamide (2.0 g, 0.00676 mol) as starting material to give the title compound as a clear yellow oil. The hydrochloride salt was collected as a white crystalline solid (0.77 g, 0.00254 mol, 37.6% yield). High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 267.1677 (theoretical [M+H] + C 15 H 21 F 2 N 2 + ,m / z 267.1667,Δ=3.7 ppm).[HCl] 1 H NMR (400MHz, d 6-DMSO)δ 11.63(s,1H),10.80(s,1H),7.43(d,J=2.2Hz,1H),7.36(dd,J=9.5,2.0Hz,1H),6.97(atd,J=15.8,1.6Hz,1H),3 .27-3.12(m,6H),3.11-3.00(m,2H),1.71(sex,J=7.8Hz,2H),1.26(t,J=7.2Hz,3H),0.92(t,J=7.3Hz,3H).[HCl] 13 C NMR (101MHz, d 6 -DMSO)δ 155.61(dd,J=233.7,10.0Hz,1C),148.23(dd,J=246.2,14.6Hz,1C),129.51(dd, J=11.2,7.3Hz,1C),126.45(s,1C),120.75(d,J=13.3Hz,1C),110.99(s,1C),99.5 4(dd,J=3.7,23.2Hz,1C),96.32(dd,J=30.5,20.8Hz,1C),52.35(s,1C),51.42(s ,1C),46.40(s,1C),19.24(s,1C),16.45(s,1C),10.94(s,1C),8.31(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO)δ -122.07(d,J=2.7Hz,1F),-129.43(d,J=1.4Hz,1F).

[0245] Example 46: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylcyclopropanamine (160) TIFF2024523822000410.tif29128Synthesis of N-[2-(5-fluoro-1H-indol-3-yl)ethyl]cyclopropanamine TIFF2024523822000411.tif29128 N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)cyclopropanamine was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylprop-2-en-1-amine (11) starting from 5-F-bromoethylindole (3.18 g, 13.14 mmol) and cyclopropylamine (3.64 mL, 52.54 mmol) to give the title compound as a clear tan oil (2.32 g, 0.0106 mol, 81% yield). The product was used in the next reaction without further purification. High Resolution Atmospheric Pressure Solid Analysis Probe Mass Spectrometry (HR-ASAP-MS): m / z 219.1296 (theoretical [M+H] + C 13 H 16 FN 2 + , m / z 219.1292, Δ=1.8 ppm).

[0246] Synthesis of N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylcyclopropanamine (160) TIFF2024523822000412.tif29128N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-methylcyclopropanamine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from N-[2-(5-fluoro-1H-indol-3-yl)ethyl]cyclopropanamine (0.4 g, 0.00183 mol) and 37% formaldehyde in water (0.38 mL, 0.00549 mol) to give the title compound as a white powder (0.38 g, 0.00163 mol, 89% yield). The hydrochloride salt was collected as a white crystalline solid (mp 218.8-219.3 °C). High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 233.1455 (theoretical [M+H] + C 14 H 18 FN 2 +,m / z 233.1449,Δ=2.6 ppm).[HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.12(s,1H),10.88(s,1H),7.43(dd,J=10.0,2.4Hz,1H),7.36(dd,J=8.8,4.6Hz,1H),7.33(d,J=2.3Hz,1H),6.93(td,J=9.2,2.5Hz,1H),3.47-3.36(m,2H)*,3.28-3.10(m,2H),2.98-2.81(m,1H)**,2.87(s,3H)**,1.37-1.19(m,1H),1.13-0.98(m,1H),0.96-0.75(m,2H).* = Fusion with water, ** = Fusion. [HCl] 13 C NMR (101MHz,d 6 -DMSO)δ 156.74(d,J=231.3Hz,1C),132.88(s,1C),126.92(d,J=9.7Hz,1C),125.33(s,1C),112.51(d,J=9.8Hz,1C),109.58(d,J=4.5Hz,1C),109 .33(d,J=26.2Hz,1C),103.03(d,J=23.1Hz,1C),56.38(s,1C),40.79(s,1C),38.56(s,1C),19.87(s,1C),5.01(s,1C),3.13(s,1C).[HCl] 19 F NMR (377MHz, d 6 -DMSO)δ -124.77(s,1F).

[0247] Example 47: N-[2-(5-フルオロ-1H-インドール-3-イル)エチル]-N-プロピルシクロプロパンアミン (161) TIFF2024523822000413.tif36128N-[2-(5-fluoro-1H-indol-3-yl)ethyl]-N-propylcyclopropanamine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from N-[2-(5-fluoro-1H-indol-3-yl)ethyl]cyclopropanamine (0.4g, 0.00183mol) and propionaldehyde (0.32g, 0.00549mol) to obtain the title compound as a colorless oil (0.30g, 0.00115mol, 63% yield).The hydrochloride salt was collected as a white crystalline solid. High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 261.1764 (theoretical [M+H] + C 16 H 22 FN 2 + ,m / z 261.1762,Δ=0.8 ppm).[HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.11(s,1H),10.60(s,1H),7.42(dd,J=10.0,2.4Hz,1H),7.36(dd,J=8.8 ,4.5Hz,1H)*,7.35(d,J=3.5Hz,1H)*,6.93(td,J=9.2,2.4Hz,1H),3.41-3 .34(m,2H)**,3.26-3.14(m,4H),2.94-2.85(m,1H),1.91-1.1.71(m,2H), 1.26-1.05(m,2H),0.93(t,J=7.4Hz,3H),0.89(d,J=7.2Hz,2H).*=Fusion, **=H 2 Fusion with O. [HCl] 13 C NMR (101MHz, d 6-DMSO)δ 156.76(d,J=231.2Hz,1C),132.87(s,1C),126.94(d,J=10.0Hz,1C),125.40 (s,1C),112.52(d,J=9.7Hz,1C),109.66(d,J=4.9Hz,1C),109.34(d,J=26.2 Hz,1C),102.97(d,J=23.3Hz,1C),55.81(s,1C),54.49(s,1C),36.50(s,1C) ,19.50(s,1C),16.75(s,1C),11.02(s,1C),4.20(s,1C),4.19(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -124.72(s,1F).

[0248] Example 48: N-(2-(7-fluoro-1H-indol-3-yl)ethyl)-N-propylcyclobutanamine (162) TIFF2024523822000414.tif39128Synthesis of 2-(7-fluoro-1H-indol-3-yl)-2-oxo-N-propylacetamide TIFF2024523822000415.tif401282-(7-fluoro-1H-indol-3-yl)-2-oxo-N-propylacetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 7-F-indole (3.0 g, 0.0222 mol), oxalyl chloride (2.44 mL, 0.0289 mol), N-propylamine (2.63 mL, 0.032 mol), and TEA (13.3 mL, 0.0955 mol) as starting materials to obtain a crude material as beige (5.87 g, 0.0236 mol, quantitative yield). The product was used without further purification.

[0249] Synthesis of N-(2-(7-fluoro-1H-indol-3-yl)ethyl)propan-1-amine TIFF2024523822000416.tif39128N-(2-(7-Fluoro-1H-indol-3-yl)ethyl)propan-1-amine was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 2-(7-fluoro-1H-indol-3-yl)-2-oxo-N-propylacetamide (5.85 g, 0.0236 mol) as starting material to give the title compound (1.7 g, 0.00772 mol, 32.7% yield). High resolution atmospheric pressure solids analytical probe mass spectrometry (HR-ASAP-MS): m / z 221.1457 (theoretical [M+H] + C 13 H 18 FN 2 + , m / z 221.1449, Δ=3.6 ppm).

[0250] Synthesis of N-(2-(7-fluoro-1H-indol-3-yl)ethyl)-N-propylcyclobutanamine (162) TIFF2024523822000417.tif39128N-[2-(7-Fluoro-1H-indol-3-yl)ethyl]-N-propylcyclobutanamine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from N-[2-(7-fluoro-1H-indol-3-yl)ethyl]propan-1-amine (0.4 g, 0.00182 mol) and cyclobutanone (0.38 g, 0.00545 mol) to give the title compound as a white to yellowish tinge solid (0.38 g, 0.000902 mol, 76% yield). The hydrochloride salt was collected as a white crystalline solid (mp 231.7-237.2 °C). High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 275.1931 (theoretical [M+H] + C 17 H 24 FN 2 + ,m / z 275.1918,Δ=4.7 ppm).[HCl] 1H NMR (400MHz, d 6 -DMSO)δ 11.48(s,1H),10.96(s,1H),7.43(d,J=7.8Hz,1H),7.36(s,1H),7.04-6.96(m,1H)*,6.96-6.88(m,1H)*,3.92-3.77(m,1H),3.22-3.07 (m,4H),3.07-2.90(m,2H),2.48-2.34(m,2H)**,2.26-2.13(m,2H),1.81-1.58(m,4H),0.92(t,J=7.2Hz,3H).*=Fusion, **=Fusion with DMSO solvent peak. [HCl] 13 C NMR (101MHz, d 6 -DMSO)δ 149.27(d,J=243.1Hz,1C),130.73(d,J=5.9Hz,1C),124.64(s,1C),123.95(d,J =13.2Hz,1C),118.96(d,J=6.0Hz,1C),114.38(d,J=3.1Hz,1C),110.53(s,1C), 106.06(d,J=16.2Hz,1C),56.64(s,1C),50.21(s,1C),48.86(s,1C),25.80(s,1 C),25.73(s,1C),18.92(s,1C),16.22(s,1C),13.30(s,1C),11.04(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -133.06(s,1F).

[0251] Example 49: 2-(5,6-difluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine (61) TIFF2024523822000418.tif28128Synthesis of 2-(5,6-difluoro-1H-indol-3-yl)-N-ethyl-N-methyl-2-oxoacetamide TIFF2024523822000419.tif281282-(5,6-difluoro-1H-indol-3-yl)-N-ethyl-N-methyl-2-oxoacetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7), starting from 5,6-DiF-1H-indole (2.0g, 0.0131mol), oxalyl chloride (1.34mL, 0.0157mol), and N-methylethylamine (1.11g, 0.0188mol), and TEA (8.75mL, 0.0628mol) as starting materials, to obtain crude material as pink powder (2.92g, 0.0110mol, 83.7% yield).The product was used without further purification.

[0252] Synthesis of 2-(5,6-difluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine (61) TIFF2024523822000420.tif281282-(5,6-difluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 2-(5,6-difluoro-1H-indol-3-yl)-N-ethyl-N-methyl-2-oxoacetamide (2.9 g, 0.0109 mol) as starting material to give the title compound as a white crystalline solid (0.82 g, 0.00344 mol, 31.6% yield). The hydrochloride salt was collected as a white crystalline solid (mp 166.3-168.7 °C). [HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.21(d,J=6.9Hz,1H),10.71(bs,1H),7.70(atd,J=14.6,1.3Hz,1H),7.37(dd,J=11.3,7.0Hz,1H),7. 32(d,J=1.8Hz,1H),3.31-3.13(m,4H)*,3.13-3.02(m,2H)*,2.78(s,3H),1.26(t,J=7.2Hz,3H).*=Fusion. [HCl] 13C NMR (101MHz, d 6 -DMSO)δ 146.61(dd,J=236.9,15.8Hz,1C),145.00(dd,J=234.1,14.9Hz,1C),131.18(d,J=10.8Hz,1C),125.30(s,1C),122.13(d,J=8.0Hz,1C),109 .76(s,1C),105.12(d,J=18.9Hz,1C),99.36(d,J=21.2Hz,1C),54.33(s,1C),49.82(s,1C),38.10(s,1C),19.63(s,1C),8.78(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO)δ -145.14(d,J=22.5Hz,1F),-148.60(d,J=21.7Hz,1F).

[0253] Example 50: N-[2-(7-fluoro-1H-indol-3-yl)ethyl]-N-propylbutan-2-amine (163) TIFF2024523822000421.tif39128N-[2-(7-Fluoro-1H-indol-3-yl)ethyl]-N-propylbutan-2-amine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from N-[2-(7-fluoro-1H-indol-3-yl)propan-1-amine (0.4 g, 0.00182 mol) and methyl ethyl ketone (0.79 g, 0.0109 mol) to give the title compound (0.43 g, 0.00156 mol, 86% yield). The hydrochloride salt was collected as an off-white solid (mp 136.5-137.1 °C). [Free base] 1 H NMR (400MHz, d 6-DMSO)δ 11.28(s,1H),7.28(d,J=7.8Hz,1H),7.19(s,1H),6.96-6.90(m,1H)*,6.90-6.83(m,1H)*,2.83-2.57(m,4H)**,2.57-2.51( m,1H)** / ***,2.46-2.29(m,2H),1.47-1.31(m,3H),1.26-1.14(m,1H),0.90-0.78(m,9H).*=Fusion, **=Fusion, ***=Fusion with DMSO solvent peak. [Free base] 13 C NMR (101MHz, d 6 -DMSO)δ 149.30(d,J=242.4Hz,1C),131.44(d,J=6.1Hz,1C),123.88(d,J=12.8Hz,1C),12 3.78(s,1C),118.40(d,J=6.3Hz,1C),114.37(d,J=3.0Hz,1C),114.12(d,J=1.6H z,1C),105.56(d,J=16.2Hz,1C),56.37(s,1C),51.55(s,1C),50.65(s,1C),26.5 8(s,1C),25.39(s,1C),21.97(s,1C),13.82(s,1C),11.83(s,1C),11.62(s,1C). [Free base] 19 F NMR (377MHz,d 6 -DMSO) δ -133.38(s,1F).

[0254] Example 51: 2-(5,7-difluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine (69) TIFF2024523822000422.tif31128Synthesis of 2-(5,7-difluoro-1H-indol-3-yl)-N-ethyl-N-methyl-2-oxoacetamide TIFF2024523822000423.tif311282-(5,7-difluoro-1H-indol-3-yl)-N-ethyl-N-methyl-2-oxoacetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7), starting from 5,7-DiF-1H-indole (1.0g, 0.00653mol), oxalyl chloride (1.08g, 0.00849mol), and N-methylethylamine (0.56g, 0.0094mol), and TEA (3.81mL, 0.0281mol) as starting materials, to obtain crude material as pink powder (1.61g, 0.00605mol, 93% yield).The product was used without further purification.

[0255] Synthesis of 2-(5,7-difluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine (69) TIFF2024523822000424.tif311282-(5,7-Difluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 2-(5,7-difluoro-1H-indol-3-yl)-N-ethyl-N-methyl-2-oxoacetamide (1.6 g, 0.006 mol) as starting material to give the title compound as a clear tan oil (1.32 g, 0.00546 mol, 92.3% yield). The hydrochloride salt was collected as a white crystalline solid (mp 152.7-153.5 °C). High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 239.1355 (theoretical [M+H] + C 13 H 17 F 2 N 2 + ,m / z 239.1354,Δ=2.8 ppm).[HCl] 1 H NMR (400MHz, d 6-DMSO)δ 11.63(s,1H),10.84(s,1H),7.41(d,J=2.2Hz,1H),7.37(dd,J=9.5,1.9Hz,1H),7.01-6.91(m,1H),3.32 -3.22(m,2H)*,3.22-3.15(m,2H)*,3.15-3.03(m,2H)*,(2.78(s,3H),1.26(t,J=7.2Hz,3H).*=Fusion. [HCl] 13 C NMR (101MHz, d 6 -DMSO)δ 155.61(dd,J=233.8,10.0Hz,1C),148.23(dd,J=246.2,14.7Hz,1C),129. 50(dd,J=11.3,7.3Hz,1C),126.41(s,1C),120.78(d,J=13.1Hz,1C),110.9 4(s,1C),99.58(dd,J=23.2,3.8Hz,1C),96.33(dd,J=30.5,20.9Hz,1C),5 4.19(s,1C),49.82(s,1C),38.12(s,1C),19.56(s,1C),8.76(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO)δ -122.11(d,J=2.7Hz,1F),-129.44(d,J=2.7Hz,1F).

[0256] Example 52: N-ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-N-methylethan-1-amine (88) TIFF2024523822000425.tif31128Synthesis of N-ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-N-methyl-2-oxoacetamide TIFF2024523822000426.tif31128 N-Ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-N-methyl-2-oxoacetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 5-MeO-7-F-indole (1.0 g, 0.00620 mol), oxalyl chloride (0.94 g, 0.00744 mol), and N-methylethylamine (0.53 g, 0.00893 mol), and TEA (3.02 g, 0.0298 mol) as starting materials to give the crude material as a tan powder (1.40 g, 0.00503 mol, 80.9% yield). The product was used without further purification.

[0257] Synthesis of N-ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-N-methylethan-1-amine (88) TIFF2024523822000427.tif31128N-Ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-N-methylethan-1-amine was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methyl-2-oxoacetamide (7) starting from N-ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-N-methyl-2-oxoacetamide (1.4 g, 0.00503 mol) as starting material to give the title compound as a clear purple-hued oil (1.18 g, 0.00471 mol, 93.7% yield). The hydrochloride salt was collected as a white crystalline solid (mp 142.7-143.2 °C). High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 251.1561 (theoretical [M+H] + C 14 H 20 FN 2 O + ,m / z 251.1554,Δ=2.8 ppm)[HCl] 1 H NMR (400MHz, d 6-DMSO)δ 11.29(s,1H),10.88(s,1H),7.27(d,J=2.0Hz,1H),7.05(m,1H),6.63(dd,J=12.7,1.5Hz,1H),3.79(s,3H) ),3.30-3.21(m,2H)*,3.21-3.13(m,2H)*,3.13-3.02(m,2H)*,2.78(s,3H),1.27(t,J=7.2Hz,3H).*=Fusion. [HCl] 13 C NMR (101MHz, d 6 -DMSO)δ 153.20(d,J=9.2Hz,1C),148.85(d,J=243.3Hz,1C),130.16(d,J=7.1Hz,1C),124.97(s,1C),119.11(d,J=13.4Hz,1C),110.21(s, [HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -131.36(s,1F).

[0258] Example 53: N-Ethyl-N-methyl-2-(5,6,7-trifluoro-1H-indol-3-yl)ethan-1-amine (164) TIFF2024523822000428.tif31128Synthesis of N-ethyl-N-methyl-2-oxo-2-(5,6,7-trifluoro-1H-indol-3-yl)acetamide TIFF2024523822000429.tif31128 N-Ethyl-N-methyl-2-oxo-2-(5,6,7-trifluoro-1H-indol-3-yl)acetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 5,6,7-TriF-indole (1.0 g, 0.00584 mol), oxalyl chloride (0.96 g, 0.00760 mol), and N-methylethylamine (0.50 g, 0.00842 mol), and TEA (2.54 g, 0.0251 mol) as starting materials to give the crude material as a tan solid (1.22 g, 0.00504 mol, 86.2% yield). The product was used without further purification.

[0259] Synthesis of N-ethyl-N-methyl-2-(5,6,7-trifluoro-1H-indol-3-yl)ethan-1-amine (164) TIFF2024523822000430.tif31128N-Ethyl-N-methyl-2-(5,6,7-trifluoro-1H-indol-3-yl)ethan-1-amine was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from N-ethyl-N-methyl-2-oxo-2-(5,6,7-trifluoro-1H-indol-3-yl)acetamide (1.4 g, 0.00503 mol) as starting material to give the title compound. The hydrochloride salt was collected as a white crystalline solid (0.35 g, 0.00162 mol, 32.2% yield) (mp 212.1-212.5 °C). High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 257.1269 (theoretical [M+H] + C 13 H 16 F 3 N 2 + ,m / z 257.1260,Δ=3.5 ppm).[HCl] 1 H NMR (400MHz, d 6-DMSO)δ 11.83(s,1H),10.76(s,1H),7.62(ddd,J=10.7,6.8,1.1Hz,1H),7.44(d,J=2.2Hz,1H),3.32- 3.22(m,2H),3.22-3.15(m,2H),3.15-3.03(m,2H),2.78(s,3H),1.26(t,J=7.3Hz,3H).[HCl] 13 C NMR (101MHz, d 6 -DMSO)δ 145.16(dd,J=235.7,12.1Hz,1C),137.31(ddd,J=247.9,13.2,4.7,Hz,1C),135.17( ddd,J=238.2,18.8,12.6Hz,1C),126.44(d,J=3.0Hz,1C),122.94(dd,J=9.1,6.3Hz, 1C),120.45(dd,J=9.5,1.5Hz,1C),110.95(d,J=4.9Hz,1C),100.46(dd,J=19.1,3.6 Hz,1C),54.14(s,1C),49.86(s,1C),38.13(s,1C),19.38(s,1C),8.78(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO)δ -146.19(dd,J=21.9,10.9Hz,1F),-155.18(dd,J=20.4,2.7Hz,1F),-170.45(td,J=21.8,6.8Hz,1F).

[0260] Example 54: N-Ethyl-N-[2-(5,6,7-trifluoro-1H-indol-3-yl)ethyl]propan-1-amine (165) TIFF2024523822000431.tif36128Synthesis of N-ethyl-2-oxo-N-propyl-2-(5,6,7-trifluoro-1H-indol-3-yl)acetamide TIFF2024523822000432.tif36128 N-Ethyl-2-oxo-N-propyl-2-(5,6,7-trifluoro-1H-indol-3-yl)acetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 5,6,7-TriF-indole (1.0 g, 0.00584 mol), oxalyl chloride (0.96 g, 0.00760 mol), and N-ethylpropylamine (0.89 mL, 0.00760 mol), and TEA (2.44 mL, 0.0175 mol) as starting materials to give the crude material as a brown solid (2.96 g, 0.00948 mol, quantitative yield). The product was used without further purification.

[0261] Synthesis of N-ethyl-N-[2-(5,6,7-trifluoro-1H-indol-3-yl)ethyl]propan-1-amine (165) TIFF2024523822000433.tif36128N-Ethyl-N-[2-(5,6,7-trifluoro-1H-indol-3-yl)ethyl]propan-1-amine was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from N-ethyl-2-oxo-N-propyl-2-(5,6,7-trifluoro-1H-indol-3-yl)acetamide (2.96 g, 0.00948 mol) as starting material to give the title compound as a tan oil (1.25 g, 0.00440, 46.4% yield). The hydrochloride salt was collected as a white crystalline solid (mp 188.0-188.8 °C). High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 285.1586 (theoretical [M+H] + C 15 H 21 F 3 N 2 + ,m / z 285.1573,Δ=4.6 ppm).[HCl] 1 H NMR (400MHz, d 6-DMSO)δ 11.84(s,1H),10.87(s,1H),7.62(ddd,J=10.8,6.7,1.2Hz,1H),7.46(d,J=2.1Hz,1H),3.28-3.3.12( m,6H),3.11-3.00(m,2H),1.71(sex,J=7.6Hz,2H),1.25(t,J=7.2Hz,3H),0.92(t,J=7.3Hz,3H).[HCl] 13 C NMR (101MHz, d 6 -DMSO)δ 145.14(dd,J=235.8,11.9Hz,1C),137.28(ddd,J=247.9,13.0,4.5Hz,1C),135.14(ddd,J= 238.4,18.8,12.2Hz,1C),126.44(d,J=2.7Hz,1C),122.94(dd,J=9.4,5.9Hz,1C),120.39(d d,J=9.9,2.0Hz,1C),111.07(d,J=2.5Hz,1C),100.42(dd,J=19.2,3.5Hz,1C),52.33(s,1C) ,51.39(s,1C),46.37(s,1C),19.06(s,1C),16.44(s,1C),10.93(s,1C),8.30(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO)δ -146.17(d,J=21.7Hz,1F),-155.19(d,J=20.4Hz,1F),-170.47(t,J=21.1Hz,1F).

[0262] Example 55: N-ethyl-N-(2-(7-fluoro-5-methyl-1H-indol-3-yl)ethyl)propan-1-amine (166) TIFF2024523822000434.tif36128Synthesis of N-ethyl-2-(7-fluoro-5-methyl-1H-indol-3-yl)-2-oxo-N-propylacetamide TIFF2024523822000435.tif36128N-ethyl-2-(7-fluoro-5-methyl-1H-indol-3-yl)-2-oxo-N-propylacetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7), starting from 5-Me-7-F-indole (1.0g, 0.00670mol), oxalyl chloride (0.74g, 0.00872mol), and N-ethylpropylamine (2.0mL, 0.0172mol) and TEA (4.00mL, 0.0287mol) as starting materials, to obtain crude material as a beige solid (2.32g, 0.00799mol, quantitative yield).The product was used without further purification.

[0263] Synthesis of N-ethyl-N-(2-(7-fluoro-5-methyl-1H-indol-3-yl)ethyl)propan-1-amine (166) TIFF2024523822000436.tif36128N-Ethyl-N-[2-(7-fluoro-5-methyl-1H-indol-3-yl)ethyl]propan-1-amine was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from N-ethyl-2-(7-fluoro-5-methyl-1H-indol-3-yl)-2-oxo-N-propylacetamide (1.83 g, 0.00629 mol) as starting material to obtain the title compound. The hydrochloride salt was collected as an off-white crystalline solid (0.85 g, 0.00284, 45.2% yield). High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 263.1919 (theory [M+H] + C 16 H 24 FN 2 + ,m / z 263.1918,Δ=0.4 ppm).[HCl] 1 H NMR (400MHz, d 6-DMSO)δ 11.34(s,1H),10.81(s,1H),7.29(d,J=2.2Hz,1H),7.24(s,1H),6.76(d,J=12.4Hz,1H),3.28-3.16(m,4H)*,3.16-3 .10(m,2H)*,3.10-3.01(m,2H)*,2.38(s,3H),1.72(sex,J=7.Hz,2H),1.26(t,J=7.2Hz,3H),0.92(t,J=7.4Hz,3H). *=Fusion. [HCl] 13 C NMR (101MHz, d 6 -DMSO)δ 148.82(d,J=242.8Hz,1C),130.78(d,J=6.1Hz,1C),128.19(d,J=5.7Hz,1C),1 24.52(s,1C),122.18(d,J=13.6Hz,1C),113.94(d,J=2.8Hz,1C),110.00(d,J= 2.1Hz,1C),107.53(d,J=15.8Hz,1C),52.44(s,1C),51.45(s,1C),46.48(s,1C) ),21.06(s,1C),19.30(s,1C),16.48(s,1C),10.95(s,1C),8.35(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -133.64(s,1F).

[0264] Example 56: N-(2-(6,7-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine (82) TIFF2024523822000437.tif36128Synthesis of 2-(6,7-difluoro-1H-indol-3-yl)-N-ethyl-2-oxo-N-propylacetamide TIFF2024523822000438.tif361282-(6,7-difluoro-1H-indol-3-yl)-N-ethyl-2-oxo-N-propylacetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7), starting from 6,7-DiF-indole (1.0g, 0.00653mol), oxalyl chloride (0.72mL, 0.00850mol), and N-ethylpropylamine (1.14g, 0.0131mol), and TEA (1.32g, 0.01306mol) as starting materials, to obtain crude material as a beige solid (1.22g, 0.00415mol, 63.55% yield).The product was used without further purification.

[0265] Synthesis of N-(2-(6,7-difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine (82) TIFF2024523822000439.tif36128N-[2-(6,7-difluoro-1H-indol-3-yl)ethyl]-N-ethylpropan-1-amine was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 2-(6,7-difluoro-1H-indol-3-yl)-N-ethyl-2-oxo-N-propylacetamide (1.22 g, 0.00415 mol) as starting material to obtain the title compound. The hydrochloride salt was collected as an off-white crystalline solid (0.17 g, 0.000638, 15.4% yield). High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 267.1668 (theoretical [M+H] + C 15 H 21 F 2 N 2 + ,m / z 267.1667,Δ=0.4 ppm).[HCl] 1 H NMR (400MHz, d 6-DMSO)δ 11.69(s,1H),10.85(s,1H),7.46(dd,J=8.7,4.1Hz,1H),7.38(d,J=2.2Hz,1H),7.10-7.00(m,1H),3.30-3.12(m,6H)*,3.12-2.99(m,2H)*,1.72(sex,J=7.7Hz,2H),1.26(t,J=7.2Hz,3H),0.92(t,J=7.4Hz,3H).*=fusion. [HCl] 13 C NMR (101MHz,d 6 -DMSO)δ 145.17(dd,J=234.3,9.2Hz,1C),136.84(dd,J=245.2,16.1Hz,1C),126.71(d,J =4.6Hz,1C),125.22(d,J=3.0Hz,1C),124.59(d,J=9.8Hz,1C),114.15(dd,J=8. 4,3.7Hz,1C),110.69(s,1C),108.29(d,J=20.1Hz,1C),52.39(s,1C),51.37(s, 1C),46.44(s,1C),19.11(s,1C),16.44(s,1C),10.94(s,1C),8.31(s,1C).[HCl] 19 F NMR (377MHz, d 6 -DMSO)δ -150.00(d,J=21.7Hz,1F),-159.49(d,J=21.8Hz,1F).

[0266] Example 57: N-エチル-N-(2-(5-フルオロ-1H-インドール-3-イル)エチル)シクロプロパンアミン (167) TIFF2024523822000440.tif33128N-Ethyl-N-[2-(5-fluoro-1H-indol-3-yl)ethyl]cyclopropanamine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from N-[2-(5-fluoro-1H-indol-3-yl)ethyl]cyclopropanamine (0.4 g, 0.00183 mol) and acetaldehyde (0.48 g, 0.0110 mol) to give the title compound as a colorless oil (0.41 g, 0.00166 mol, 91% yield). The hydrochloride salt was collected as a white crystalline powder (mp 219.7-220.1 °C). High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 247.1607 (theoretical [M+H] + C 16 H 22 FN 2 + ,m / z 247.1605,Δ=0.8 ppm).[HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.12(s,1H),10.80(s,1H),7.42(dd,J=10.0,2.4Hz,1H),7.36(dd,J=8. 6,4.6Hz,1H)*,7.35(d,J=3.1Hz,1H)*,6.93(td,J=9.2,2.4Hz,1H),3.36- 3.27(m,4H)**,3.26-3.11(m,2H)**,2.94-2.83(m,1H),1.32(t,J=7.3Hz ,3H),1.29-1.20(m,1H),1.20-1.10(m,1H),0.96-0.84(m,2H).*=Fusion,**=H 2 O peak and merging with other peaks. [HCl] 13 C NMR (101MHz, d 6-DMSO)δ 156.75(d,J=231.2Hz,1C),132.87(s,1C),126.94(d,J=9.8Hz,1C),125 .38(s,1C),112.51(d,J=9.8Hz,1C),109.69(d,J=4.8Hz,1C),109.33(d, J=26.0Hz,1C),102.96(d,J=23.2Hz,1C),53.74(s,1C),49.32(s,1C),3 5.92(s,1C),19.51(s,1C),8.77(s,1C),4.12(s,1C),3.99(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -124.71(s,1F).

[0267] Example 58: N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylcyclopropanamine (168) TIFF2024523822000441.tif33128N-[2-(5-fluoro-1H-indol-3-yl)ethyl]-N-(propan-2-yl)cyclopropanamine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from N-[2-(5-fluoro-1H-indol-3-yl)ethyl]cyclopropanamine (0.4 g, 0.00183 mol) and acetone (8.0 mL, 0.108 mol) to give the title compound as clear white crystals. The hydrochloride salt was collected as a white crystalline powder (0.42 g, 0.00142 mol, 77.6% yield) (mp 196.4-196.8 °C). The modification to (1) was the utilization of acetone as the solvent system as opposed to using MeOH. High resolution atmospheric pressure solid analytical probe mass spectrometry (HR-ASAP-MS): m / z 261.1774 (theoretical [M+H] + C 16 H 22 FN 2 + ,m / z 261.1762,Δ=4.6 ppm).[HCl] 1 H NMR (400MHz, d 6-DMSO)δ 11.12(s,1H),10.61(s,1H),7.42(dd,J=10.0,2.4Hz,1H),7.36(d,J=2.8Hz,1H)*,7.36(dd,J=8.7,4.7Hz,1H)*,6.93(td,J=9.2, 2.4Hz,1H),3.79-3.66(m,1H),3.32-3.17(m,4H)**,2.94-2.83(m,1H),1.43-1.29(m,7H),1.21-1.11(m,1H),0.97-0.84(m,2H).* =Fusion, **=H 2 Merged with O peak. [HCl] 13 C NMR (101MHz, d 6 -DMSO)δ 156.76(d,J=231.2Hz,1C),132.86(s,1C),126.98(d,J=9.8Hz,1C),125.43 (s,1C),112.50(d,J=9.7Hz,1C),109.83(d,J=4.7Hz,1C),109.32(d,J=26.2 Hz,1C),102.94(d,J=23.2Hz,1C),56.49(s,1C),50.86(s,1C),33.88(s,1C) ,20.02(s,1C),16.57(s,1C),16.50(s,1C),4.25(s,1C),4.10(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -124.69(s,1F).

[0268] Example 59: N-ethyl-2-(5-fluoro-7-methyl-1H-indol-3-yl)-N-methylethan-1-amine (169) TIFF2024523822000442.tif32128Synthesis of N-ethyl-2-(5-fluoro-7-methyl-1H-indol-3-yl)-N-methyl-2-oxoacetamide TIFF2024523822000443.tif32128 N-Ethyl-2-(5-fluoro-7-methyl-1H-indol-3-yl)-N-methyl-2-oxoacetamide was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 5-F-7-Me-indole (0.95 g, 0.00637 mol), oxalyl chloride (0.97 g, 0.00764 mol), and N-methylethylamine (0.54 g, 0.00917 mol), and TEA (3.1 g, 0.0306 mol) as starting materials to give the crude material as an orange solid (1.20 g, 0.00457 mol, 59.89% yield). The product was used without further purification.

[0269] Synthesis of N-ethyl-2-(5-fluoro-7-methyl-1H-indol-3-yl)-N-methylethan-1-amine (169) TIFF2024523822000444.tif32128N-ethyl-2-(5-fluoro-7-methyl-1H-indol-3-yl)-N-methylethan-1-amine was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from N-ethyl-2-(5-fluoro-7-methyl-1H-indol-3-yl)-N-methyl-2-oxoacetamide (1.15 g, 0.00438 mol) as starting material to give the title compound as a clear tan oil (0.77 g, 0.00329 mol, 75.1% yield).This material formed an amorphous solid when converted to its HCl salt, so it was converted back and kept as the free base. High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 235.1612 (theoretical [M+H] + C 14 H 20 FN 2 + , m / z 235.1605, Δ=3.0 ppm).[Free base] 1 H NMR (400MHz, d 6-DMSO)δ 10.84(s,1H),7.20(d,J=2.1Hz,1H),7.04(dd,J=9.9,2.2Hz,1H),6.72(dd,J=10.2,1.7Hz,1H),2.79-2.72 (m,2H),2.60-2.52(m,2H),2.43(s,3H)*,2.42(q,J=7.1Hz,1H)*,2.21(s,3H),0.99(t,J=7.1Hz,3H).*=Fusion. [Free base] 13 C NMR (101MHz, d 6 -DMSO)δ 156.60(d,J=230.6Hz,1C),132.29(s,1C),126.87(d,J=10.2Hz,1C),12 4.10(s,1C),122.09(d,J=9.5Hz,1C),113.55(d,J=5.0Hz,1C),109.30(d ,J=25.8Hz,1C),100.24(d,J=22.7Hz,1C),57.58(s,1C),50.73(s,1C),4 1.20(s,1C),22.73(s,1C),16.58(d,J=1.1Hz,1C),12.23(s,1C).[Free base] 19 F NMR (377MHz,d 6 -DMSO) δ -125.57(s,1F).

[0270] Example 60: (R)-3-((1-ethylpyrrolidin-2-yl)methyl)-5-fluoro-1H-indole (170) TIFF2024523822000445.tif33128Synthesis of benzyl (2R)-2-(5-fluoro-1H-indole-3-carbonyl)pyrrolidine-1-carboxylate TIFF2024523822000446.tif34128 Benzyl (2R)-2-(5-fluoro-1H-indole-3-carbonyl)pyrrolidine-1-carboxylate was prepared by the reaction of 5-fluoroindole (5.41 g, 0.0400 mol) as starting material, N-benzyloxylcarbonyl- DStarting from .beta.-proline (5 g, 0.0200 mol), oxalyl chloride (3.8 g, 0.0300 mol), and 1.4 M methylmagnesium bromide in 1:3 THF / toluene (28.6 mL, 0.0400 mol), in a similar manner as described above for (S)-5-fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, the title compound was obtained as a white solid (2.8 g, 0.00764 mol, 38.2% yield). The product was used without further purification.

[0271] Synthesis of (5-fluoro-1H-indol-3-yl)[(2R)-pyrrolidin-2-yl]methanone TIFF2024523822000447.tif25128 To an oven-dried 300 mL single-neck round-bottom flask was added benzyl (2R)-2-(5-fluoro-1H-indole-3-carbonyl)pyrrolidine-1-carboxylate (1 g, 0.00273 mol) and the solution was dissolved in 60 mL of MeOH by gentle heating. Once the material was dissolved, 10% Pd-C (0.29 g, 0.00273 mol) was added to the reaction, followed by a balloon of H 2 was flushed through the reaction vessel. When the balloon was empty, fresh H 2 A balloon was added to the reaction septum and allowed to react for 4 hours. After 4 hours, the reaction was determined to be complete by TLC and MS. The Pd-C was filtered and the mother liquor was filtered through Celite directly into a 500 mL RBF. The filtrate was removed under reduced pressure to give the title compound as an orange solid (0.60 g, 0.00258 mol, 94.5% yield). The product was used without further purification.

[0272] Synthesis of 1-[(2R)-2-(5-fluoro-1H-indole-3-carbonyl)pyrrolidin-1-yl]ethan-1-one TIFF2024523822000448.tif33128In a 100 mL single neck round bottom flask, 1-[(2R)-2-(5-fluoro-1H-indole-3-carbonyl)pyrrolidin-1-yl]ethan-1-one (0.4 g, 0.00172 mol) was added to 10 mL of dichloromethane, but did not dissolve. TEA (0.52 g, 0.00516 mol) was added to the reaction, then the round bottom flask was placed in an ice bath before adding acetyl chloride (0.16 g, 0.00206 mol). Once the acetyl chloride was added, the precipitate went into solution and allowed to react for 1 hour. After 1 hour, the reaction was shown to be complete by TLC and MS. The reaction was worked up by quenching with water and extracting with EtOAc three times (3 x 50 mL). Once the extraction is complete, the organic phase is washed with brine and 2 SO 4 The solvent was removed under reduced pressure to give the title compound as an orange solid (0.45 g, 0.00164 mol, 95.3% yield).

[0273] Synthesis of (R)-3-((1-ethylpyrrolidin-2-yl)methyl)-5-fluoro-1H-indole (170) TIFF2024523822000449.tif33128 (5-Fluoro-3-{[(2R)-pyrrolidin-2-yl]methyl}-1H-indole) was synthesized in a similar manner as described above for N-ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylene-1-amine (7) starting from 1-[(2R)-2-(5-fluoro-1H-indole-3-carbonyl)pyrrolidin-1-yl]ethan-1-one (0.45 g, 0.00164 mol) as starting material to give the title compound (0.28 g, 0.00114 mol, 69.51% yield). The free base was collected as a tan oil. [Free Base] 1 H NMR (400MHz, d 6-DMSO) δ 10.88 (singlet, 1H), 7.30 (doublet of doublets, J = 8.7, 4.6 Hz, 1H), 7.22 (doublet of doublets, J = 9.3, 2.3 Hz, 1H)*, 7.21 (doublet, J = 2.3 Hz, 1H)*, 6.89 (triplet of doublets, J = 13.7, 2.3 Hz, 1H), 3.13 - 3.03 (multiplet, 1H)**, 3.03 - 2.90 (multiplet, 2H)**, 2.61 - 2.51 (multiplet, 1H)***, 2.47 (doublet, J = 9.2 Hz, 1H), 2.26 - 2.12 (multiplet, 1H)****, 2.12 - 2.01 (multiplet, 1H)****, 1.73 - 1.58 (multiplet, 2H), 1.58 - 1.42 (multiplet, 2H), 1.07 (triplet, J = 7.2 Hz, 3H). *=fusion, **=fusion, ***=fusion with DMSO solvent, ****=fusion. [Free base] 13 C NMR (101 MHz, d 6 -DMSO) δ 156.59 (doublet, J = 230.6 Hz, 1C), 132.74 (singlet, 1C), 127.79 (doublet, J = 9.5 Hz, 1C), 125.13 (singlet, 1C), 112.42 (singlet, 1C), 112.15 (doublet, J = 9.9 Hz, 1C), 108.77 (doublet, J = 26.1 Hz, 1C), 102.96 (doublet, J = 22.8 Hz, 1C), 64.47 (singlet, 1C), 53.10 (singlet, 1C), 47.75 (singlet, 1C), 30.42 (singlet, 1C), 29.53 (singlet, 1C), 21.72 (singlet, 1C), 13.79 (singlet, 1C). [Free base] 19 F NMR (377 MHz, d 6 -DMSO) δ -125.40 (singlet, 1F).

[0274] Example 61: N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N,3-dimethylbutan-2-amine (171) TIFF2024523822000450.tif36128N-[2-(5-Fluoro-1H-indol-3-yl)ethyl]-N,3-dimethylbutan-2-amine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from 5-fluorotryptamine hydrochloride (0.5 g, 0.00233 mol), 3-methylbutan-2-one (1.2 g, 0.0140 mol) to give the title compound as a white solid (0.35 g, 0.0133 mol, 57% yield). The hydrochloride salt was collected as an off-white powder (mp 157.5-158.1 °C). High resolution atmospheric pressure solid analysis probe mass spectrometry (HR-ASAP-MS): m / z 263.1923 (theoretical [M+H] + C 16 H 24 FN 2 + , m / z 263.1918, Δ=1.9 ppm).[Free base] 1 H NMR (400MHz, d 6 -DMSO)δ 11.06(s,1H),7.31(dd,J=8.8,4.6Hz,1H),7.20(d,J=2.5Hz,1H)*,7.18(dd,J=10.1,2.4Hz,1H)*,6.87(td,J=9.2,2.4Hz,1H),2.83-2.58(m, 3H),2.50-2.44(m,1H),2.23-2.13(m,1H)*,2.19(s,3H)*,1.62-1.48(m,1H),0.88(d,J=6.6Hz,3H),0.83(dd,J=9.7,6.6Hz,6H).*=Fusion [free base] 13 C NMR (101MHz, d 6-DMSO)δ 156.57(d,J=230.9Hz,1C),132.89(s,1C),127.53(d,J=9.7Hz,1C),124.74( s,1C),113.16(d,J=4.8Hz,1C),112.23(d,J=9.7Hz,1C),108.72(d,J=26.1H z,1C),102.74(d,J=22.8Hz,1C),63.97(s,1C),54.17(s,1C),36.85(s,1C), 31.22(s,1C),23.85(s,1C),20.82(s,1C),20.00(s,1C),9.37(s,1C).[Free base] 19 F NMR (377MHz,d 6 -DMSO) δ -125.51(s,1F).

[0275] Example 62: N-(sec-butyl)-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclopropanamine (172) TIFF2024523822000451.tif33128N-(butan-2-yl)-N-[2-(5-fluoro-1H-indol-3-yl)ethyl]cyclopropanamine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from N-[2-(5-fluoro-1H-indol-3-yl)ethyl]cyclopropanamine (0.35 g, 0.00160 mol), methyl ethyl ketone (10 mL, 0.112 mol) to give the title compound as a colorless oil (0.35 g, 0.0128 mol, 79.6% yield). The hydrochloride salt was collected as a white solid. [Free base] 1 H NMR (400MHz, d 6-DMSO) δ 10.85 (singlet, 1H), 7.31 (doublet of doublets, J = 8.8, 4.6 Hz, 1H), 7.20 (doublet, J = 2.2 Hz, 1H), 7.17 (doublet of doublets, J = 10.0, 2.5 Hz, 1H), 6.88 (triplet of doublets, J = 9.2, 2.5 Hz, 1H), 2.92 - 2.68 (multiplet, 5H), 2.00 - 1.91 (multiplet, 1H), 1.56 - 1.43 (multiplet, 1H), 1.32 - 1.21 (multiplet, 1H), 0.98 (doublet, J = 6.6 Hz, 3H), 0.81 (triplet, J = 7.4 Hz, 3H), 0.56 - 0.47 (multiplet, 1H), 0.47 - 0.38 (multiplet, 2H), 0.28 - 0.20 (multiplet, 1H). [Free base] 13 C NMR (101 MHz, d 6 -DMSO) δ 156.56 (doublet, J = 230.7 Hz, 1C), 132.85 (singlet, 1C), 127.45 (doublet, J = 9.6 Hz, 1C), 124.59 (singlet, 1C), 113.44 (doublet, J = 4.6 Hz, 1C), 112.23 (doublet, J = 9.9 Hz, 1C), 108.81 (doublet, J = 26.0 Hz, 1C), 102.66 (doublet, J = 22.8 Hz, 1C), 58.41 (singlet, 1C), 51.08 (singlet, 1C), 33.39 (singlet, 1C), 26.63 (singlet, 1C), 24.77 (singlet, 1C), 14.77 (singlet, 1C), 11.53 (singlet, 1C), 7.86 (singlet, 1C), 5.71 (singlet, 1C). [Free base] 19 F NMR (377 MHz, d 6 -DMSO) δ -125.36 (singlet, 1F).

[0276] Example 63: N-Cyclopropyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine (173) TIFF2024523822000452.tif33128N-Cyclopropyl-N-[2-(5-fluoro-1H-indol-3-yl)ethyl]cyclobutanamine was synthesized in a similar manner as described above for N-ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine (1) starting from N-[2-(5-fluoro-1H-indol-3-yl)ethyl]cyclopropanamine (0.35 g, 0.00165 mol), cyclobutanone (0.49 mL, 0.00660 mol) to give the title compound as a semi-crystalline white solid (0.39 g, 0.00143 mol, 86.7% yield). The hydrochloride salt was collected as a beige crystalline solid (mp 211.7-212.3 °C). [HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.15(s,1H)*,11.12(s,1H)*,7.39(dd,J=10.0,2.3Hz,1H)**,7.36(dd,J=7.9,3.3Hz,1H)**,7.35(d,J=2.5Hz,1H)**,6.95( td,J=13.8,2.5Hz,1H),4.05-3.91(m,1H),3.25-3.17(m,4H),2.84-2.72(m,1H),2.61-2.51(m,1H)***,2.48-2.39(m,1H)*** 2.28-2.12(m,2H), 1.78-1.62(m,2H), 1.27-1.08(m,2H), 0.90-0.78(m,2H).* = merged, ** = merged, *** = merged with DMSO solvent peak. [HCl] 13 C NMR (101MHz, d 6-DMSO)δ 156.76(d,J=231.2Hz,1C),132.87(s,1C),126.89(d,J=9.7Hz,1C),125.39(s, 1C),112.56(d,J=9.8Hz,1C),109.77(d,J=4.7Hz,1C),109.35(d,J=26.2Hz,1C) ,102.84(d,J=23.2Hz,1C),58.74(s,1C),52.36(s,1C),34.22(s,1C),26.32(s, 1C),26.08(s,1C),19.19(s,1C),13.92(s,1C),3.55(s,1C),2.24(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -124.65(s,1F).

[0277] Example 64: 2-(7-bromo-5-fluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine (174) TIFF2024523822000453.tif361282-(7-Bromo-5-fluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine was prepared using the appropriate substituted indole and appropriate substituted amine as described above for (37) to give the substituted glyoxylamide as a yellow solid (1.02 g, 0.00311, 69.9% yield). The title compound was prepared from reduction of glyoxylamide to give the title compound as a slightly yellow solid (0.72, 0.00241 mol, 77.5% yield). The hydrochloride salt was collected as a crystalline solid with a yellow tint (mp 228.3-230.5 °C). [HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 11.35(s,1H),10.79(s,1H),7.56(dd,J=9.6,1.6Hz,1H),7.42(d,J=2.4Hz,1H),7.29(dd,J=9.0 ,2.1Hz,1H),3.31-3.21(m,2H)*,3.21-3.01(m,4H)*,2.78(s,3H),1.26(t,J=7.2Hz,3H).*=Fusion. [HCl] 13 C NMR (101MHz, d 6-DMSO)δ 156.11(d,J=235.4Hz,1C),131.61(s,1C),127.82(d,J=10.3Hz,1C),126.85(s,1C),112.23(d,J=29.3Hz,1C),111.24(d,J=5.1Hz,1 C),103.88(d,J=12.5Hz,1C),103.17(d,J=23.3Hz,1C),54.16(s,1C),49.83(s,1C),38.13(s,1C),19.66(s,1C),8.77(s,1C).[HCl] 19 F NMR (377MHz,d 6 -DMSO) δ -122.95(s,1F).

[0278] Example 65: N-Ethyl-2-(5-fluoro-6-methyl-1H-indol-3-yl)-N-methylethan-1-amine (175) TIFF2024523822000454.tif33128N-Ethyl-2-(5-fluoro-6-methyl-1H-indol-3-yl)-N-methylethan-1-amine was prepared using the appropriate substituted indole and appropriate substituted amine as described above for (7) to give the glyoxylamide as a yellow solid (1.42 g, 0.00541, 84.7% yield). The title compound was prepared from reduction of glyoxylamide to give the title compound as a slightly yellow solid (0.97, 0.00414 mol, 76.5% yield). The hydrochloride salt was collected as an off-yellow solid. [HCl] 1 H NMR (400MHz, d 6 -DMSO)δ 10.97(s,1H),10.60(s,1H),7.38(d,J=10.8Hz,1H),7.22(s,1H),7.22(d,J=8.4Hz,1H),3.31-3.1 1(m,4H)*,3.11-3.03(m,2H),2.78(s,3H),2.30(d,J=1.3Hz,3H),1.25(t,J=7.3Hz,3H).*=Fusion with water. [HCl] 13 C NMR (101MHz, d 6-DMSO)δ 155.7...

Claims

1. A compound of formula (I), or a salt, prodrug, solvate, isotopologue or stereoisomer thereof, wherein wherein A is and where * indicates the bond between L and N(R １ )(R ２ ), and L is and R ａ１ and R ａ２ are each independently selected from the group consisting of H, halogen, C １ to C ６ alkoxy, and C １ to C ６ alkyl, or or R ａ１ and R ａ２ may combine to form a carbonyl (C=O), R ｂ１ and R ｂ２ are each independently selected from the group consisting of H and C １ to C ６ alkyl, R １ and R ２ are each independently optionally substituted C １ to C ８ alkyl, optionally substituted C ３ to C ８ cycloalkyl, optionally substituted C １ to C ８ heteroalkyl, optionally substituted C ２ to C ８ heterocycloalkyl, optionally substituted C ２ to C ８ alkenyl, and optionally substituted C ２ to C ８ alkynyl, and are selected from the group consisting of Here, R １ and R ２ are not the same, and Here, R １ and R ２ One of them may combine with one of R ａ１ R ａ２ R ｂ１ and R ｂ２ to form an optionally substituted C ２ to C ８ heterocyclyl, However, R １ and R ２ One of them combines with R ｂ１ or R ｂ２ to form a five-membered ring. When R ５ is F, at least one of R ４ , R ６ , and R ７ is not H, or when one of R １ and R ２ combines with R ｂ１ or R ｂ２ to form a stereocenter, the compound consists essentially of one stereoisomer, R ３ is selected from the group consisting of H, halogen, optionally substituted C １ to C ８ alkyl, optionally substituted benzyl, optionally substituted C ３ to C ８ cycloalkyl, optionally substituted C ２ to C ８ alkenyl, and optionally substituted C ２ to C ８ alkynyl R ４ 、 R ５ 、 R ６ 、 and R ７ are each independently selected from the group consisting of H, F, Cl, Br, I, OR Ａ , N(R Ａ )(R Ｂ ), SR Ａ , optionally substituted C １ ~C ６ alkyl, optionally substituted C ２ ~C ６ alkenyl, optionally substituted C ２ ~C ６ alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C ２ ~C ９ heteroaryl Here, R ４ , R ５ , R ６ , and R ７ at least one of which is F, R Ａ Each occurrence of １ C ６ -haloalkyl, C ２ C ６ -alkynyl, C １ C ６ -alkyl, -C(=O)C １ C ６ -alkyl, -C(=O)C ６ C １０ -aryl, -C(=O)NH(C １ C ６ -alkyl), -C(=O)NH(C ６ C １０ -aryl), -C(=O)N(C １ C ６ -alkyl) ２ -C(=O)N(C １ C ６ -alkyl)(C ６ C １０ -aryl), -C(=O)O(C １ C ６ -alkyl), -C(=O)O(C ６ C １０ -aryl), -P(=O)(O(C １ C ６ -alkyl)) ２ -P(=O)(O(C １ C ６ -alkyl))(OH), -P(=O)(OH) ２ -S(=O) ２ O(C ６ C １０ -aryl), -S(=O) ２ O(C １ C ６ -alkyl), -S(=O) ２ O(C ６ C １０ -aryl), -S(=O) ２ NH(C １ C ６ -alkyl), -S(=O) ２ NH(C ６ C １０ -aryl), -S(=O) ２ N(C １ C ６ -alkyl)(C １ ~C ６ alkyl), and -S(=O) ２ N(C １ ~C ６ alkyl)(C ６ ~C １０ selected from the group consisting of aryl), R Ｂ each occurrence of which is independently selected from the group consisting of H, C １ to C ６ alkyl, C １ to C ３ haloalkyl, C ２ to C ６ alkenyl, benzyl, naphthyl, C ２ to C ９ heteroaryl, and phenyl, The isotopologue does not contain R １ nor R ２ nor F １８ and does not contain the compound of formula (I) is N-Ethyl-N-(2-(4-fluoro-1H-indol-3-yl)ethyl)propan-1-amine, N-Ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-1-amine, N-Ethyl-N-(2-(6-fluoro-1H-indol-3-yl)ethyl)propan-1-amine, N-Ethyl-N-(2-(7-fluoro-1H-indol-3-yl)ethyl)propan-1-amine, N-Ethyl-2-(4-fluoro-1H-indol-3-yl)-N-methylethan-1-amine, N-Ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine, N-Ethyl-2-(6-fluoro-1H-indol-3-yl)-N-methylethan-1-amine, N-Ethyl-2-(7-fluoro-1H-indol-3-yl)-N-methylethan-1-amine, (R)-4-Fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole, (R)-4-Fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole, (R)-4-Fluoro-3-(pyrrolidin-2-ylmethyl-d2)-1H-indole, and (S)-4-Fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole not selected from the group consisting of the said compound, or a salt, prodrug, solvate, isotopologue or stereoisomer thereof.

2. (i) R １ is optionally substituted C １ to C ３ alkyl, and R ２ is optionally substituted branched-chain C ３ to C ８ alkyl and optionally substituted C ３ to C ８ cycloalkyl, selected from the group consisting of; (ii) R1 is selected from the group consisting of methyl, allyl, and n-propyl; (iii) R2 is optionally substituted branched C3-C8 alkyl; (iv) Each of R1 and R2 is independently selected from the group consisting of methyl, ethyl, n-propyl, 1,2-dimethylpropyl, iso-propyl, sec-butyl, iso-butyl, n-butyl, cyclopropyl, cyclopropylmethyl, methylcyclopropyl, cyclopropylethyl, 2-cyclopropyleth-2-yl, cyclobutyl, 2-thietanyl, 3-thietanyl, allyl, methylallyl, 2-methylallyl, 3-methylallyl, propargyl, cyanomethyl, 2-hydroxyethyl, and 2-methoxyethyl, and preferably, R3 is H; (v) R2 is selected from the group consisting of iso-propyl, sec-butyl, iso-butyl, 1,2-dimethylpropyl, methylallyl, and 2-methylallyl; (vi) R3 is H; (vii) Each occurrence of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclyl is independently substituted with at least one substituent selected from the group consisting of C1-C6 alkyl, C3-C8 cycloalkyl, halo, cyano, ORA, optionally substituted benzyl, optionally substituted phenyl, optionally substituted C2-C9 heteroaryl, C(=O)ORA, OC(=O)ORA, OC(=O)RA, SRA, S(=O)RA, S(=O)2RA, S(=O)2N(RA)(RB), N(RA)S(=O)2RA, N(RA)C(=O)RA, C(=O)N(RA)(RB), and N(RA)(RB); and / or (viii) Each occurrence of benzyl, phenyl, and heteroaryl is independently substituted with at least one substituent selected from the group consisting of C1-C6 alkyl, C3-C8 cycloalkyl, halo, cyano, ORA, C(=O)ORA, OC(=O)ORA, OC(=O)RA, SRA, S(=O)RA, S(=O)2RA, S(=O)2N(RA)(RB), N(RA)S(=O)2RA, N(RA)C(=O)RA, C(=O)N(RA)(RB), and N(RA)(RB), the compound according to claim 1. **Claim 3**: R2 is optionally substituted C3-C8 cycloalkyl, preferably, (a) R2 is selected from the group consisting of cyclopropyl and cyclobutyl; and / or, (b) R3 is H, the compound according to claim 1.

4. (i) R ４ is F, and R ５ , R ６ , and R ７ are each H; (ii) R5 is F, and each of R4, R6, and R7 is H; (iii) R7 is F, and each of R4, R5, and R6 is H; (iv) Each of R4 and R5 is F, and each of R6 and R7 is H; (v) Each of R4 and R6 is F, and each of R5 and R7 is H; (vi) Each of R4 and R7 is F, and each of R5 and R6 is H; (vii) Each of R5 and R6 is F, and each of R4 and R7 is H; (viii) Each of R5 and R7 is F, and each of R4 and R6 is H; (ix) Each of R6 and R7 is F, and each of R4 and R5 is H; (x) R5 is OMe, R7 is F, and each of R4 and R6 is H; (xi) Each of R5, R6, and R7 is F, and R4 is H; (xii) R5 is selected from the group consisting of OR A, N(R A)(R B), and SR A; or, (xiii) R5 is selected from the group consisting of H, F, Cl, OMe, OH, and Me, preferably, (a) R5 is OMe, or, (b) R5 is F, the compound according to claim 1.

5. (i) R ６ is selected from the group consisting of H, F, Me, and Cl; (ii) R7 is selected from the group consisting of H, F, Cl, Br, and Me; and / or, (iii) Each of R4 and R6 is H, the compound according to claim 1. **Claim 6**: (i) L is selected from the group consisting of, preferably, L is ; (ii) A is selected from the group consisting of, wherein, when R c1, R c2, R d1, R d2, R e1, and R e2 are present, each is independently selected from the group consisting of H, C1-C3 alkyl, and C1-C3 haloalkyl, preferably, When each of Ra1, Ra2, Rb1, Rb2, Rc1, Rc2, Rd1, Rd2, Re1, Re2, Rf1, and Rf2 is present, it is H; or (iii) When each of Ra1, Ra2, Rb1, Rb2, Rc1, Rc2, Rd1, Rd2, Re1, Re2, Rf1, and Rf2 is present, it is H, the compound according to claim 1.

7. (i) A is selected from the group consisting of; and / or (ii) The compound is N-Ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-methylbutan-2-amine N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-isopropylpropan-1-amine N-(2-(5,6-Difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-isopropylprop-2-en-1-amine N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine N-Allyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine N-Allyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine 2-((2-(5-Fluoro-1H-indol-3-yl)ethyl)(isopropyl)amino)acetonitrile 5,6-Difluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-methylthietan-3-amine N-(2-(4,5-Difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-propylbutan-2-amine 7-Fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole 2-(ethyl(propyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one 2-(ethyl(methyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one (S)-5-Fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole (R)-5-Fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole 5-Fluoro-3-(1-methylazetidin-3-yl)-1H-indole N-Ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)butan-2-amine N-Ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylbutan-2-amine N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylcyclobutanamine N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylprop-2-yn-1-amine N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylprop-2-en-1-amine N-Ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)prop-2-en-1-amine N-(2-(6-chloro-5-fluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine 1-Cyclopropyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-methylethan-1-amine N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-isopropylcyclobutanamine N-Ethyl-N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)propan-1-amine N-(2-(4-fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine N-(2-(4-fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine N-Ethyl-N-(2-(4-fluoro-1H-indol-3-yl)ethyl)propan-2-amine, N-(2-(4-Fluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(4-Fluoro-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(4-Fluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(4-Fluoro-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, N-(2-(7-Fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-(2-(7-Fluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-Ethyl-N-(2-(7-Fluoro-1H-indol-3-yl)ethyl)propan-2-amine, N-(2-(7-Fluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(7-Fluoro-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(7-Fluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(7-Fluoro-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, 2-(5,6-Difluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine, N-(2-(5,6-Difluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-(2-(5,6-Difluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-(2-(5,6-Difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-2-amine, N-(2-(5,6-Difluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(5,6-Difluoro-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(5,6-Difluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(5,6-Difluoro-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, 2-(5,7-Difluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine, N-(2-(5,7-Difluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-(2-(5,7-Difluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-(2-(5,7-Difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine, N-(2-(5,7-Difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-2-amine, N-(2-(5,7-Difluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(5,7-Difluoro-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(5,7-Difluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(5,7-Difluoro-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, 2-(6,7-Difluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine, N-(2-(6,7-Difluoro-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-(2-(6,7-Difluoro-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-(2-(6,7-Difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-1-amine, N-(2-(6,7-Difluoro-1H-indol-3-yl)ethyl)-N-ethylpropan-2-amine, N-(2-(6,7-Difluoro-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(6,7-Difluoro-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(6,7-Difluoro-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(6,7-Difluoro-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, N-Ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-N-methylethan-1-amine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-Ethyl-N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)propan-2-amine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, 3-(2-(Ethyl(methyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 7-Fluoro-3-(2-(methyl(propyl)amino)ethyl)-1H-indol-5-ol, 7-Fluoro-3-(2-(isopropyl(methyl)amino)ethyl)-1H-indol-5-ol, 3-(2-(Ethyl(propyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 3-(2-(Ethyl(isopropyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 7-Fluoro-3-(2-(isobutyl(methyl)amino)ethyl)-1H-indol-5-ol, 3-(2-(cyclobutyl(methyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 3-(2-(allyl(methyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 7-Fluoro-3-(2-(isobutyl(isopropyl)amino)ethyl)-1H-indol-5-ol, 4-Fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, 6-Fluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, 4,5-Difluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, 4,6-Difluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, 5,7-Difluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, 6,7-Difluoro-3-(1-methylpyrrolidin-3-yl)-1H-indole, 4-Fluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 5-Fluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 6-Fluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 7-Fluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 4,5-Difluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 4,6-Difluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 5,6-Difluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 5,7-Difluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 6,7-Difluoro-3-(1-methylpiperidin-3-yl)-1H-indole, 4-Fluoro-3-(methylprolyl)-1H-indole, 6-Fluoro-3-(methylprolyl)-1H-indole, 7-Fluoro-3-(methylprolyl)-1H-indole, 4,5-Difluoro-3-(methylprolyl)-1H-indole, 4,6-Difluoro-3-(methylprolyl)-1H-indole, 5,6-Difluoro-3-(methylprolyl)-1H-indole, 5,7-Difluoro-3-(methylprolyl)-1H-indole, 6,7-Difluoro-3-(methylprolyl)-1H-indole, 4-Fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, 6-Fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, 7-Fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, 4,5-Difluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, 4,6-Difluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole 5,6-Difluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole 5,7-Difluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole 6,7-Difluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole N-(sec-Butyl)-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine N-(Cyclopropylmethyl)-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)propan-2-amine N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-methylcyclopropanamine N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-propylcyclopropanamine N-(2-(7-Fluoro-1H-indol-3-yl)ethyl)-N-propylcyclobutanamine N-(2-(7-Fluoro-1H-indol-3-yl)ethyl)-N-propylbutan-2-amine N-Ethyl-N-methyl-2-(5,6,7-trifluoro-1H-indol-3-yl)ethan-1-amine N-Ethyl-N-(2-(5,6,7-trifluoro-1H-indol-3-yl)ethyl)propan-1-amine N-Ethyl-N-(2-(7-fluoro-5-methyl-1H-indol-3-yl)ethyl)propan-1-amine N-Ethyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclopropanamine N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-isopropylcyclopropanamine N-Ethyl-2-(5-fluoro-7-methyl-1H-indol-3-yl)-N-methylethan-1-amine N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N,3-dimethylbutan-2-amine N-(sec-Butyl)-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclopropanamine N-Cyclopropyl-N-(2-(5-fluoro-1H-indol-3-yl)ethyl)cyclobutanamine 2-(7-Bromo-5-fluoro-1H-indol-3-yl)-N-ethyl-N-methylethan-1-amine N-Ethyl-2-(5-fluoro-6-methyl-1H-indol-3-yl)-N-methylethane-1-amine, N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-(prop-2-yn-1-yl)butan-2-amine, 2-(sec-Butyl(2-(5-fluoro-1H-indol-3-yl)ethyl)amino)acetonitrile, N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-methylbut-3-en-2-amine, 2-(5-Chloro-6-fluoro-1H-indol-3-yl)-N-ethyl-N-methylethane-1-amine, N-(2-(7-Fluoro-1H-indol-3-yl)ethyl)-N-propylprop-2-yn-1-amine, 2-((2-(7-Fluoro-1H-indol-3-yl)ethyl)(propyl)amino)acetonitrile, 2-(7-Chloro-5-fluoro-1H-indol-3-yl)-N-ethyl-N-methylethane-1-amine, (R)-3-((1-Ethylpyrrolidin-2-yl)methyl)-5-fluoro-1H-indole, (R)-5-Fluoro-3-(pyrrolidin-2-ylmethyl)-1H-indole, (R)-5-Fluoro-3-((1-propylpyrrolidin-2-yl)methyl)-1H-indole, (R)-5,6-Difluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, (R)-7-Fluoro-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole, 2-(Ethyl(propyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one, N-Isopropyl-N-(2-(5,6,7-trifluoro-1H-indol-3-yl)ethyl)propan-1-amine, N-Methyl-N-(2-(5,6,7-trifluoro-1H-indol-3-yl)ethyl)butan-2-amine, N-Methyl-N-(2-(5,6,7-trifluoro-1H-indol-3-yl)ethyl)cyclobutanamine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-isopropylpropan-1-amine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylbutan-2-amine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylbut-3-en-2-amine, N-(2-(5,6-Difluoro-1H-indol-3-yl)ethyl)-N-methylbut-3-en-2-amine, N-(2-(6,7-Difluoro-1H-indol-3-yl)ethyl)-N-methylbut-3-en-2-amine, N-(2-(5,7-Difluoro-1H-indol-3-yl)ethyl)-N-methylbut-3-en-2-amine, N-Methyl-N-(2-(5,6,7-trifluoro-1H-indol-3-yl)ethyl)but-3-en-2-amine, 3-(((2R)-1-(sec-Butyl)pyrrolidin-2-yl)methyl)-5-fluoro-1H-indole, (R)-5-Fluoro-3-((1-isopropylpyrrolidin-2-yl)methyl)-1H-indole, (R)-3-((1-cyclobutylpyrrolidin-2-yl)methyl)-5-fluoro-1H-indole, (R)-3-((1-cyclopropylpyrrolidin-2-yl)methyl)-5-fluoro-1H-indole, (R)-3-((1-allylpyrrolidin-2-yl)methyl)-5-fluoro-1H-indole, 3-(((2R)-1-(but-3-en-2-yl)pyrrolidin-2-yl)methyl)-5-fluoro-1H-indole, (R)-5-Fluoro-3-((1-(prop-2-yn-1-yl)pyrrolidin-2-yl)methyl)-1H-indole, 3-(((2R)-1-(sec-Butyl)pyrrolidin-2-yl)methyl)-5,6,7-trifluoro-1H-indole, (R)-5,6,7-Trifluoro-3-((1-isopropylpyrrolidin-2-yl)methyl)-1H-indole, (R)-3-((1-cyclobutylpyrrolidin-2-yl)methyl)-5,6,7-trifluoro-1H-indole, (R)-3-((1-cyclopropylpyrrolidin-2-yl)methyl)-5,6,7-trifluoro-1H-indole, (R)-3-((1-allylpyrrolidin-2-yl)methyl)-5,6,7-trifluoro-1H-indole, 3-(((2R)-1-(but-3-en-2-yl)pyrrolidin-2-yl)methyl)-5,6,7-trifluoro-1H-indole, (R)-5,6,7-Trifluoro-3-((1-(prop-2-yn-1-yl)pyrrolidin-2-yl)methyl)-1H-indole, 3-(((2R)-1-(sec-butyl)pyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, (R)-7-Fluoro-3-((1-isopropylpyrrolidin-2-yl)methyl)-5-methoxy-1H-indole, (R)-3-((1-cyclobutylpyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, (R)-3-((1-cyclopropylpyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, (R)-3-((1-allylpyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, 3-(((2R)-1-(but-3-en-2-yl)pyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, and (R)-7-Fluoro-5-methoxy-3-((1-(prop-2-yn-1-yl)pyrrolidin-2-yl)methyl)-1H-indole The compound according to claim 1, selected from the group consisting of.

8. A compound of formula (II), or a salt, prodrug, solvate, isotopologue or stereoisomer thereof, wherein In the formula,[ R ３ is H, optionally substituted C １ -C ８ alkyl, optionally substituted benzyl, optionally substituted C ３ -C ８ cycloalkyl, optionally substituted C ２ -C ８ alkenyl, and optionally substituted C ２ -C ８ alkynyl, and is selected from the group consisting of R ４ 、 R ５ 、 R ６ 、 and R ７ are each independently H, F, Cl, Br, I, OR Ａ , N(R Ａ )(R Ｂ ), SR Ａ , optionally substituted C １ ~C ６ alkyl, optionally substituted C ２ ~C ６ alkenyl, optionally substituted C ２ ~C ６ alkynyl, optionally substituted C １ ~C ８ heteroalkyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C ２ ~C ９ heteroaryl, and are selected from the group consisting of: Here, R ４ , R ５ , R ６ , and R ７ at least one of which is F, R ８ and R ９ are each independently optionally substituted C １ -C ８ alkyl, optionally substituted C ３ -C ８ cycloalkyl, optionally substituted C ２ -C ８ alkenyl, and optionally substituted C ２ -C ８ alkynyl, and are selected from the group consisting of R １０ is H, optionally substituted C １ ~C ６ alkyl, optionally substituted C ２ ~C ６ alkenyl, optionally substituted C ２ ~C ６ alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C ２ ~C ９ selected from the group consisting of heteroaryl, R ｆ１ and R ｆ２ are each independently selected from the group consisting of H and C １ -C ６ alkyl, R Ａ Each occurrence of １ C ６ -haloalkyl, C ２ C ６ -alkynyl, C １ C ６ -alkyl, -C(=O)C １ C ６ -alkyl, -C(=O)C ６ C １０ -aryl, -C(=O)NH(C １ C ６ -alkyl), -C(=O)NH(C ６ C １０ -aryl), -C(=O)N(C １ C ６ -alkyl) ２ -C(=O)N(C １ C ６ -alkyl)(C ６ C １０ -aryl), -C(=O)O(C １ C ６ -alkyl), -C(=O)O(C ６ C １０ -aryl), -P(=O)(O(C １ C ６ -alkyl)) ２ -P(=O)(O(C １ C ６ -alkyl))(OH), -P(=O)(OH) ２ -S(=O) ２ O(C ６ C １０ -aryl), -S(=O) ２ O(C １ C ６ -alkyl), -S(=O) ２ O(C ６ C １０ -aryl), -S(=O) ２ NH(C １ C ６ -alkyl), -S(=O) ２ NH(C ６ C １０ -aryl), -S(=O) ２ N(C １ C ６ -alkyl)(C １ ~C ６ alkyl), and -S(=O) ２ N(C １ ~C ６ alkyl)(C ６ ~C １０ selected from the group consisting of aryl), R Ｂ each occurrence of which is, independently, H, C １ ~C ６ alkyl, C １ ~C ３ haloalkyl, C ２ ~C ６ alkenyl, benzyl, naphthyl, C ２ ~C ９ heteroaryl, and phenyl, selected from the group consisting of Said compound, or a salt, prodrug, solvate, isotopologue or stereoisomer thereof.

9. (i) R ３ is H; (ii) R8 and R9 are each independently selected from the group consisting of methyl, ethyl, and n-propyl; (iii) R10 is H; (iv) Rf1 and Rf2 are H; (v) (a) R4 is F and each of R5, R6, and R7 is H, (b) R5 is F and each of R4, R6, and R7 is H, (c) R6 is F and each of R4, R5, and R7 is H, (d) R7 is F and each of R4, R5, and R6 is H, (e) Each of R4 and R5 is F and each of R6 and R7 is H, (f) Each of R4 and R6 is F and each of R5 and R7 is H, (g) Each of R4 and R7 is F and each of R5 and R6 is H (h) each of R5 and R6 is F, and each of R4 and R7 is H; (i) each of R5 and R7 is F, and each of R4 and R6 is H, or (j) each of R6 and R7 is F, and each of R4 and R5 is H; (vi) each occurrence of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclyl is independently substituted with at least one substituent selected from the group consisting of C1-C6 alkyl, C3-C8 cycloalkyl, halo, cyano, OR A, optionally substituted benzyl, optionally substituted phenyl, optionally substituted C2-C9 heteroaryl, C(=O)OR A, OC(=O)OR A, OC(=O)R A, SR A, S(=O)R A, S(=O)2R A, S(=O)2N(R A)(R B), N(R A)S(=O)2R A, N(R A)C(=O)R A, C(=O)N(R A)(R B), and N(R A)(R B); (vii) each occurrence of benzyl, phenyl, and heteroaryl is independently substituted with at least one substituent selected from the group consisting of C1-C6 alkyl, C3-C8 cycloalkyl, halo, cyano, OR A, C(=O)OR A, OC(=O)OR A, OC(=O)R A, SR A, S(=O)R A, S(=O)2R A, S(=O)2N(R A)(R B), N(R A)S(=O)2R A, N(R A)C(=O)R A, C(=O)N(R A)(R B), and N(R A)(R B); and / or (viii) the compound is 2-(ethyl(propyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one, 2-(ethyl(methyl)amino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one, 2-(dimethylamino)-1-(4-fluoro-1H-indol-3-yl)ethan-1-one, 2-(dimethylamino)-1-(5-fluoro-1H-indol-3-yl)ethan-1-one, 2-(Dimethylamino)-1-(6-fluoro-1H-indol-3-yl)ethan-1-one 2-(Dimethylamino)-1-(7-fluoro-1H-indol-3-yl)ethan-1-one 1-(4,5-Difluoro-1H-indol-3-yl)-2-(dimethylamino)ethan-1-one 1-(4,6-Difluoro-1H-indol-3-yl)-2-(dimethylamino)ethan-1-one 1-(5,6-Difluoro-1H-indol-3-yl)-2-(dimethylamino)ethan-1-one 1-(5,7-Difluoro-1H-indol-3-yl)-2-(dimethylamino)ethan-1-one, and 1-(6,7-Difluoro-1H-indol-3-yl)-2-(dimethylamino)ethan-1-one The compound according to claim 8, selected from the group consisting of

10. A compound of formula (III), or a salt, prodrug, solvate, isotopologue or stereoisomer thereof, wherein In the formula R ８ and R ９ are each independently optionally substituted C １ -C ８ alkyl, optionally substituted C ３ -C ８ cycloalkyl, optionally substituted C ２ -C ８ alkenyl, and optionally substituted C ２ -C ８ alkynyl, and are selected from the group consisting of R １０ is H, optionally substituted C １ ~C ６ alkyl, optionally substituted C ２ ~C ６ alkenyl, optionally substituted C ２ ~C ６ alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C ２ ~C ９ selected from the group consisting of heteroaryl, R １１ and R １２ are each independently selected from the group consisting of H, F, Cl, Br, I, OR Ａ , N(R Ａ )(R Ｂ ), optionally substituted C １ to C ６ alkyl, optionally substituted C ２ to C ６ alkenyl, optionally substituted C ２ to C ６ alkynyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C ２ to C ９ heteroaryl R １３ is H, optionally substituted C １ ~C ６ alkyl, optionally substituted C2-C ６ alkenyl, optionally substituted C2-C ６ alkynyl, optionally substituted C １ ~C ３ haloalkyl, optionally substituted benzyl, optionally substituted phenyl, and optionally substituted C ２ ~C ９ selected from the group consisting of heteroaryl, R ｆ１ and R ｆ２ are each independently selected from the group consisting of H and C １ -C ６ alkyl R ｇ１ and R ｇ２ are each independently selected from the group consisting of H and C １ ~C ６ alkyl, R Ａ each occurrence of １ C ６ to C ２ alkyl, C ６ to C １ alkenyl, C ６ to C １ haloalkyl, -C(=O)C ６ to C ６ alkyl, -C(=O)C １０ to C １ aryl, -C(=O)NH(C ６ to C ６ alkyl), -C(=O)NH(C １０ to C １ aryl), -C(=O)N(C ６ to C ２ alkyl), -C(=O)N(C １ to C ６ alkyl)(C ６ to C １０ aryl), -C(=O)O(C １ to C ６ alkyl), -C(=O)O(C ６ to C １０ aryl), -P(=O)(O(C １ to C ６ alkyl)), -P(=O)(O(C ２ to C １ alkyl))(OH), -P(=O)(OH) ６ ２ ２ ６ １０ aryl), -S(=O) ２ O(C １ to C ６ aryl), -S(=O) ２ O(C ６ to C １０ alkyl), -S(=O) ２ O(C １ to C ６ aryl), -S(=O) ２ NH(C ６ to C １０ alkyl), -S(=O) ２ NH(C １０ to C ２ aryl), -S(=O) １ N(C ６ alkyl)(C １ ~C ６ alkyl), and -S(=O) ２ N(C １ ~C ６ alkyl)(C ６ ~C １０ selected from the group consisting of aryl), R Ｂ each occurrence of which is, independently, H, C １ to C ６ alkyl, C １ to C ３ haloalkyl, C ２ to C ６ alkenyl, benzyl, naphthyl, C ２ to C ９ heteroaryl, and phenyl, selected from the group consisting of Said compound, or a salt, prodrug, solvate, isotopologue or stereoisomer thereof

11. (i) R ３ is H; (ii) Each of R8 and R9 is independently selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, sec-butyl, iso-butyl, n-butyl, cyclopropyl, cyclopropylmethyl, methylcyclopropyl, cyclopropylethyl, cyclobutyl, allyl, methylallyl, 2-methylallyl, 3-methylallyl, allylmethyl, propargyl, cyanomethyl, 2-hydroxyethyl, and 2-methoxyethyl; (iii) R10 is H; (iv) Each of R11 and R12 is H; (v) R13 is H or methyl; (vi) Each of Rf1, Rf2, Rg1, and Rg2 is H; (vii) The compound is N-Ethyl-N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)propan-1-amine 2-(7-Fluoro-5-methoxy-1H-indol-3-yl)-N,N-dimethylethan-1-amine N,N-Diethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethan-1-amine N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine 3-(2-(Dimethylamino)ethyl)-7-fluoro-1H-indol-5-ol, 3-(2-(Diethylamino)ethyl)-7-fluoro-1H-indol-5-ol, 3-(2-(Dipropylamino)ethyl)-7-fluoro-1H-indol-5-ol, N-Ethyl-2-(7-fluoro-5-methoxy-1H-indol-3-yl)-N-methylethan-1-amine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylpropan-1-amine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylpropan-2-amine, N-Ethyl-N-(2-(7-fluoro-5-methoxy-1H-indol-3-yl)ethyl)propan-2-amine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N,2-dimethylpropan-1-amine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylcyclobutanamine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-methylprop-2-en-1-amine, N-(2-(7-Fluoro-5-methoxy-1H-indol-3-yl)ethyl)-N-isopropyl-2-methylpropan-1-amine, 3-(2-(Ethyl(methyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 7-Fluoro-3-(2-(methyl(propyl)amino)ethyl)-1H-indol-5-ol, 7-Fluoro-3-(2-(isopropyl(methyl)amino)ethyl)-1H-indol-5-ol, 3-(2-(Ethyl(propyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 3-(2-(Ethyl(isopropyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 7-Fluoro-3-(2-(isobutyl(methyl)amino)ethyl)-1H-indol-5-ol, 3-(2-(cyclobutyl(methyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 3-(2-(allyl(methyl)amino)ethyl)-7-fluoro-1H-indol-5-ol, 7-Fluoro-3-(2-(isobutyl(isopropyl)amino)ethyl)-1H-indol-5-ol, 3-(((2R)-1-(sec-butyl)pyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, (R)-7-fluoro-3-((1-isopropylpyrrolidin-2-yl)methyl)-5-methoxy-1H-indole, (R)-3-((1-cyclobutylpyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, (R)-3-((1-cyclopropylpyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, (R)-3-((1-allylpyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, 3-(((2R)-1-(but-3-en-2-yl)pyrrolidin-2-yl)methyl)-7-fluoro-5-methoxy-1H-indole, and (R)-7-fluoro-5-methoxy-3-((1-(prop-2-yn-1-yl)pyrrolidin-2-yl)methyl)-1H-indole selected from the group consisting of; (viii) each occurrence of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclyl is independently substituted with at least one substituent selected from the group consisting of C1-C6 alkyl, C3-C8 cycloalkyl, halo, cyano, ORA, optionally substituted benzyl, optionally substituted phenyl, optionally substituted C2-C9 heteroaryl, C(=O)ORA, OC(=O)ORA, OC(=O)RA, SRA, S(=O)RA, S(=O)2RA, S(=O)2N(RA)(RB), N(RA)S(=O)2RA, N(RA)C(=O)RA, C(=O)N(RA)(RB), and N(RA)(RB); and / or, (ix) The compound according to claim 10, wherein each occurrence of benzyl, phenyl, and heteroaryl is independently optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkyl, C3-C8 cycloalkyl, halo, cyano, ORA, C(=O)ORA, OC(=O)ORA, OC(=O)RA, SRA, S(=O)RA, S(=O)2RA, S(=O)2N(RA)(RB), N(RA)S(=O)2RA, N(RA)C(=O)RA, C(=O)N(RA)(RB), and N(RA)(RB).

12. N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)prop-2-en-1-amine, 2-(5-Fluoro-1H-indol-3-yl)-N,N-dimethylpropan-1-amine, N-(2-(5-Fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine, N,N-Diethyl-2-(4-fluoro-1H-indol-3-yl)ethan-1-amine, N-(2-(4-Fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine, N-(2-(7-Fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine, N-(2-(5,6-Difluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine, 2-(5,7-Difluoro-1H-indol-3-yl)-N,N-diethylethan-1-amine, N-(2-(5,7-Difluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine, 2-(6,7-Difluoro-1H-indol-3-yl)-N,N-diethylethan-1-amine, N-(2-(6,7-Difluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine, and 2-(5-Fluoro-1H-indol-3-yl)propan-1-amine A compound selected from the group consisting of.

13. A pharmaceutical composition comprising at least one compound according to any one of claims 1 to 12 and a pharmaceutically acceptable carrier.

14. The pharmaceutical composition according to claim 13 for use in a method of treating, preventing, and / or ameliorating a mental illness or mental disorder in a subject in need thereof.

15. (i) The mental illness or mental disorder is selected from the group consisting of depressive disorders, anxiety disorders, and eating disorders; (ii) The mental illness or mental disorder is attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), treatment-resistant depression, major depressive disorder (MDD), bipolar type I disorder, bipolar type II disorder, cyclothymic disorder, antisocial personality disorder, pain, sleep / wake disorder, severe mood dysregulation, persistent depressive disorder (dysthymia), premenstrual dysphoric disorder, substance / medication-induced depressive disorder, postpartum depression, depressive disorder due to another medical condition, separation anxiety disorder, specific phobia, social anxiety disorder, panic disorder, panic attack, agoraphobia, generalized anxiety disorder, substance / medication-induced anxiety disorder, anxiety disorder due to another medical condition, somatic symptom disorder, illness anxiety disorder, obsessive-compulsive disorder (OCD), obsessive-compulsive disorder and related disorders (OCRD), OCRD due to another medical condition, substance-related disorders, alcohol-related disorders, cannabis-related disorders, hallucinogen-related disorders, inhalant-related disorders, cocaine-related disorders, opioid-related disorders, sedative-related disorders, hypnotic-related disorders, and / or anti-anxiety medication-related disorders, stimulant-related disorders, tobacco-related disorders, non-substance-related disorders (gambling disorder and / or game disorder), anorexia nervosa, bulimia nervosa, and binge eating disorder; (iii) The subject is further administered at least one additional agent useful for treating, preventing, and / or ameliorating the mental illness or mental disorder, preferably, (a) The at least one additional agent is selected from the group consisting of selective serotonin reuptake inhibitors, triple reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, tetracyclic antidepressants, dopamine reuptake inhibitors, mood stabilizers, antispasmodics, antipsychotics, anti-anxiety medications, benzodiazepines, monoamine releasing agents, dopamine receptor agonists, cannabinoids, triptans, migraine medications, analgesics, anti-inflammatory agents, immunomodulators, 5-HT1A receptor antagonists, 5-HT2 receptor antagonists, 5-HT3 receptor antagonists, monoamine oxidase inhibitors, and norepinephrine antagonists. (b) the subject is co-administered with the at least one compound and the at least one additional agent (c) the at least one compound and the at least one additional agent are formulated together; and / or, (d) the subject is a mammal; and / or, (iv) the subject is a mammal, preferably the mammal is a human, the pharmaceutical composition according to claim 14.

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