Dual modulators of mGluR5 and 5-HT2A receptors and uses thereof

Abstract

Dual modulators of mGluR5 and 5-HT2A receptors and their uses are disclosed. More specifically, compounds that simultaneously act as modulators of mGluR5 and antagonists of 5-HT2A receptors and their use as pain treatment agents are disclosed.

Description

[Technical Field]

[0001] Dual modulators of mGluR5 and 5-HT2A receptors and their uses are disclosed. More specifically, compounds that simultaneously act as modulators of mGluR5 and antagonists of 5-HT2A receptors and their use as pain treatment agents are disclosed. [Background technology]

[0002] According to the definition of the International Association for the Study of Pain (ISAP), pain is an unpleasant sensory and emotional experience associated with or related to actual or potential tissue damage. Pain can be broadly divided into physiological pain and pathological pain. Physiological pain is an adaptive response of the body to protect itself from trauma and disappears when the source of pain is removed. Pathological pain is an inappropriate state that persists even after the noxious stimulus has disappeared and the damaged tissue has healed. Neuropathic pain is a typical chronic pain caused by nerve damage or abnormal nerve function. It can exhibit abnormal characteristics such as allodynia, which refers to pain caused by non-noxious stimuli, hyperalgesia, which refers to pain that is more severe in the presence of noxious stimuli, spontaneous pain, paresthesia, unpleasant dysesthesia, and hyperpathia.

[0003] In the pain delivery process, when harmful stimuli such as heat or strong mechanical stimulation are applied to peripheral tissues such as skin or muscle, peripheral nerve endings become electrically excited, and an action voltage is transmitted through the spinal cord to the central nervous system in the cerebrum. This process of transmitting pain signals via nerves involves the interaction of various neurotransmitters and receptors. Among these neurotransmitters, glutamate is a representative excitatory neurotransmitter in the central nervous system, inducing signal transmission in neurons via glutamate receptors.

[0004] Glutamate receptors are broadly divided into ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs). Metabotropic glutamate receptors are a type of G-protein-coupled receptor (GPCR) and are classified into three groups, I, II, and III, based on the characteristics of their signaling pathways. Group I, consisting of mGluR1 and mGluR5, regulates neuronal excitability depending on the synaptic location and activates C-type phospholipases (PLCs) via Gq proteins. Group II (mGluR2 and mGluR3) and Group III (mGluR4, mGluR6, mGluR7, and mGluR8) are known to act as presynaptic receptors and inhibit downstream signaling pathways of adenylate cyclase (AC) activated via Gi proteins.

[0005] Serotonin (5-HT, 5-hydroxytryptamine) is a typical neurotransmitter in the central nervous system and is produced in the raphe nucleus of the brainstem. Serotonin acts comprehensively on numerous central and peripheral nervous systems via serotonin receptors, significantly influencing the actions of other neurotransmitters such as dopamine and norepinephrine, thereby closely relating to various neural activities such as emotion, cognition, eating, and sleep. For example, pharmacological treatments for depression, obesity, smoking cessation, and irritable bowel syndrome have been developed by modulating the serotonin system. Serotonin receptors are classified into seven subtypes. With the exception of the 5-HT3 receptor, which is a ligand-gated ion channel, the remaining subtypes (5-HT1-2, 5-HT4-7) are all G-protein-coupled receptors (GPCRs). These GPCR-type serotonin receptors mediate excitatory or inhibitory neuromodulation by triggering intracellular second messenger pathways. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] WO2013 / 049255 [Patent Document 2] WO2013 / 081400 issue Summary of the Invention [Problem to be solved by the invention]

[0007] It is an object of the present invention to provide compounds that act simultaneously on the mGluR5 and 5-HT2A receptors.

[0008] Another object of the present invention is to provide the use of said compounds for treating pain. [Means for solving the problem]

[0009] In order to achieve the above object, a compound represented by the following formula (1) [ka] (wherein X1 and X2, together with the carbons to which they are attached, form a 4- to 7-membered aliphatic ring or a 4- to 6-membered heteroaliphatic ring; X3 is CH or N; R1 is hydroxy, halo, alkyl, heterocycloalkyl, or heterocycloalkyl-alkyl; R2 is hydroxy, halo, alkyl, alkoxy, heterocycloalkyl, hydroxyalkyl, haloalkyl, amino, alkylamino, dialkylamino, cycloalkyl-alkyl, cycloalkylamino, haloalkylamino, aminocarbonyl, alkylaminocarbonyl, alkoxycarbonylalkyl, carboxyalkyl, aminocarbonylalkyl, hydroxyaminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, or 5- or 6-membered heteroaryl; R3 is deuterium, halo, or alkyl; R4 and R5 are each independently halo or alkyl; m is an integer from 0 to 3; n is 0 or 1; l, p, and q each independently represent an integer of 0 to 2; The heteroaliphatic ring, heterocycloalkyl, or heteroaryl has one or more heteroatoms selected from the group consisting of N, O, and S; provided that X1 and X2, together with the carbons to which they are attached, form a 6-membered aliphatic ring or a 5-membered heteroaliphatic ring, and when X3 is CH, n and q are not simultaneously 0.) or a pharmaceutically acceptable salt thereof.

[0010] Also provided is a pharmaceutical composition for preventing or treating pain, which comprises a therapeutically effective amount of a compound of formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient, together with a pharmaceutically acceptable carrier or excipient.

[0011] Additionally provided is a method of treating pain comprising administering to a mammal a compound of formula (1) or a pharmaceutically acceptable salt thereof. [Effects of the Invention]

[0012] The compound of formula (1) or a pharmaceutically acceptable salt thereof acts as a dual modulator of mGluR5 and 5-HT2A receptors. The dual modulatory action on mGluR5 and 5-HT2A receptors can exhibit synergistic effects in the treatment of pain. Due to these properties, the compound of formula (1) or a pharmaceutically acceptable salt thereof can exhibit an analgesic effect even at low doses without specific side effects. [Brief explanation of the drawings]

[0013] [Figure 1] 1 is a graph showing that an mGluR5 modulator and a 5-HT2AR antagonist exert a synergistic analgesic effect. BEST MODE FOR CARRYING OUT THE INVENTION

[0014] The present invention will now be described in more detail.

[0015] mGluR5, a group I metabotropic glutamate receptor (mGluR), is expressed in the hippocampus, striatum, thalamus, and cerebral cortex and is closely associated with various neurological disorders. mGluRs are also distributed in the dorsal horn of the spinal cord and are known to play important roles in regulating somatosensory pathways and nociceptive neurotransmission. In fact, treatment with a negative allosteric modulator of mGluR5, i.e., an mGluR5 antagonist, has been reported to have significant analgesic effects in various animal models of inflammatory pain, neuropathic pain, visceral pain, postoperative pain, and orofacial pain.

[0016] Serotonin also plays an important role in the generation and modulation of pain. Depending on the site of action, cell type, and receptor type, it can induce pain or exert analgesic effects. In the trigeminal nervous system, serotonin acts on V-HT1B / D receptors, inhibiting neurotransmitter release and alleviating pain. However, when serotonin acts on 5-HT2A receptors in the periphery, it sensitizes afferent nerve fibers, inducing inflammatory and neuropathic hyperalgesia. 5-HT2A receptors are expressed not only in the periphery but also in the spinal cord introduction site, possibly functioning as an intermediate mediator for delivering serotonin-related pain signals to the brain. Increased 5-HT2A receptor expression has been reported in the dorsal root ganglion (DRG) and spinal dorsal horn, which are key pain pathways in animal models of neuropathic pain. Ketanserin, a representative 5-HT2A receptor antagonist, has also been shown to suppress pain induction.

[0017] Disclosed are compounds that act as dual modulators of mGluR5 and 5-HT2A receptors. When compounds exert synergistic effects by simultaneously acting on the two receptors, it is possible to use low-dose regimens that maximize the efficacy of pain treatment and prevention while minimizing side effects.

[0018] According to one aspect of the present invention, a compound represented by the following formula (1) [ka] (wherein X1 and X2, together with the carbons to which they are attached, form a 4- to 7-membered aliphatic ring or a 4- to 6-membered heteroaliphatic ring; X3 is CH or N; R1 is hydroxy, halo, alkyl, heterocycloalkyl, or heterocycloalkyl-alkyl; R2 is hydroxy, halo, alkyl, alkoxy, heterocycloalkyl, hydroxyalkyl, haloalkyl, amino, alkylamino, dialkylamino, cycloalkyl-alkyl, cycloalkylamino, haloalkylamino, aminocarbonyl, alkylaminocarbonyl, alkoxycarbonylalkyl, carboxyalkyl, aminocarbonylalkyl, hydroxyaminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, or 5- or 6-membered heteroaryl; R3 is deuterium, halo, or alkyl; R4 and R5 are each independently halo or alkyl; m is an integer from 0 to 3; n is 0 or 1; l, p, and q each independently represent an integer of 0 to 2; The heteroaliphatic ring, heterocycloalkyl, or heteroaryl has one or more heteroatoms selected from the group consisting of N, O, and S; provided that X1 and X2, together with the carbons to which they are attached, form a 6-membered aliphatic ring or a 5-membered heteroaliphatic ring, and when X3 is CH, n and q are not simultaneously 0.) or a pharmaceutically acceptable salt thereof.

[0019] For the purposes of this specification, the following concepts defined for substituents are used to define compounds of formula (1).

[0020] As used herein, the term "aliphatic ring" refers to a non-aromatic hydrocarbon ring, and the term "heteroaliphatic ring" refers to a non-aromatic hydrocarbon ring having one or more heteroatoms selected from the group consisting of N, O, and S, more specifically, N or O. Specific examples of aliphatic rings include, but are not limited to, rings having 4 to 7 carbon atoms, such as cyclobutane, cyclopropane, cyclohexane, and cycloheptane. Specific examples of heteroaliphatic rings include, but are not limited to, 4- to 6-membered heterocycles, such as oxetane, tetrahydrofuran, tetrahydropyran, dioxane, and piperidine.

[0021] As used herein, the term "halo," alone or in combination with an additional term (e.g., haloalkyl), refers to a radical of fluorine (F), chlorine (Cl), bromine (Br), or iodine (I). More specifically, it may be fluorine (F).

[0022] As used herein, the term "alkyl," alone or in combination with additional terms (e.g., haloalkyl), refers to a linear or branched, saturated or unsaturated aliphatic hydrocarbon radical having 1 to 10 carbon atoms, preferably 1 to 5 carbon atoms, and may contain single, double, or triple bonds. For example, alkyl includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, t-pentyl, 1-methylbutyl, 2-methylbutyl, 1-ethylpropyl, and 1,2-dimethylpropyl.

[0023] As used herein, the term "cycloalkyl" refers to a partially or fully saturated monocyclic or fused ring hydrocarbon, C3-C 12 It may be cycloalkyl, preferably C3-C7 cycloalkyl, more specifically C3-C6 cycloalkyl. For example, cycloalkyl includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexynyl, cycloheptyl, etc.

[0024] The term "alkoxy," as used herein, unless otherwise defined, refers to an alkyloxy having 1 to 10, preferably 1 to 5, carbon atoms.

[0025] The term "heterocycloalkyl" as used herein refers to a fully saturated hydrocarbon ring containing one or more heteroatoms selected from N, O, and S, preferably 1 to 3 heteroatoms selected from N and O, with 4- to 6-membered heterocycloalkyl being preferred. Examples of heterocycloalkyl include, but are not limited to, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, piperidinyl, morpholinyl, etc.

[0026] According to one embodiment of the present invention, in the formula (1), X1 and X2 together with the carbon atoms to which they are attached form a C4-C7 cycloalkyl or a 4- to 6-membered heterocycloalkyl; X3 is CH or N; R1 is hydroxy, halo, or C1-C5 alkyl; R2 is hydroxy, halo, C1-C5 alkyl, C1-C5 alkoxy, 4- to 6-membered heterocycloalkyl, hydroxy-C1-C5 alkyl, halo-C1-C5 alkyl, C1-C5 alkylamino, C3-C6 cycloalkyl-C1-C5 alkyl, C3-C6 cycloalkylamino, halo-C1-C5 alkylamino, C1-C5 alkylaminocarbonyl, C1-C5 alkoxycarbonyl-C1-C5 alkyl, carboxy-C1-C5 alkyl, aminocarbonyl-C1-C5 alkyl, hydroxyaminocarbonyl-C1-C5 alkyl, C1-C5 alkylaminocarbonyl-C1-C5 alkyl, di(C1-C5 alkyl)aminocarbonyl-C1-C5 alkyl or pyridyl; R3 is deuterium, fluoro, or C1-C5 alkyl; R4 and R5 are each independently halo or C1-C5 alkyl; m is an integer from 0 to 2; n is 0 or 1; l, p, and q each independently represent an integer of 0 to 2.

[0027] According to another embodiment of the present invention, specific examples of R1 include, but are not limited to, hydroxy, fluoro, methyl, oxetanylmethyl, oxetanyl, and the like.

[0028] According to another embodiment of the present invention, specific examples of R2 include, but are not limited to, hydroxy; methoxy; fluoro; methyl, ethyl, cyclopropylmethyl, fluoromethyl, hydroxymethyl, hydroxypropyl, carboxymethyl, carboxyethyl, methoxycarbonylmethyl, methoxycarbonylethyl, aminocarbonylmethyl, hydroxyaminocarbonylmethyl, methylaminocarbonylmethyl, dimethylaminocarbamoylmethyl; isopropylamino, 2,2-dimethylpropylamino, cyclopropylamino, 2,2,2-trifluoroamino, morpholinyl; methylaminocarbonyl; pyridyl, and the like.

[0029] According to another embodiment of the present invention, the 4- to 7-membered aliphatic ring is cyclobutane, cyclopentane, cyclohexane, or cycloheptane.

[0030] According to another embodiment of the present invention, the 4-6 membered heteroaliphatic ring is oxetane, tetrahydrofuran, tetrahydropyran, dioxane or piperidine.

[0031] According to another embodiment of the present invention, in the formula (1), X1 and X2 together with the carbon atom to which they are attached form oxetane, tetrahydrofuran, tetrahydropyran, cyclobutane, cyclopentane or cyclohexane.

[0032] According to another embodiment of the present invention, in the formula (1), p=0.

[0033] According to another embodiment of the present invention, in the formula (1), X3 is CH.

[0034] According to another embodiment of the present invention, in the formula (1), at least one of n and q is not 0.

[0035] According to another embodiment of the present invention, in the formula (1), R5 is fluoro and q is 1 or 2.

[0036] According to another embodiment of the present invention, in the formula (1), tr and X3 are CH, and R5 is substituted at the ortho- and / or para-position of the phenyl.

[0037] In another embodiment according to the present invention, representative examples of compounds of formula (1) above may include, but are not limited to, the following compounds: N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-(pyridin-2-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-(pyridin-4-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-3-fluoro-4-(pyridin-4-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-2-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-2-fluoro-4-(pyridin-4-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((3-fluoropyridin-4-yl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((3,4-difluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((3,4-difluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-methylpyridin-4-yl)ethynyl)benzamide; N-((4-(cyclopropylamino)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-morpholinocyclopentyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-(isopropylamino)tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclohexyl)methyl)benzamide; N-((1-(cyclopropylamino)-4-methylcyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(neopentylamino)cyclohexyl)methyl)benzamide; N-((4-(cyclopropylmethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclopentyl)methyl)benzamide; 4-(pyridin-4-ylethynyl)-N-((1-((2,2,2-trifluoroethyl)amino)cyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-hydroxycyclohexyl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(pyridin-3-yl)cyclopentyl)methyl)benzamide; 2-Fluoro-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)methyl)benzamide; N-((4,4-difluorocyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-fluorotetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-(phenylethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; N-((4-(fluoromethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1,4-dioxan-2-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; 4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)-N-methyltetrahydro-2H-pyran-4-carboxamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide; N-((1-(isopropylamino)cyclohexyl)methyl)-4-(phenylethynyl)benzamide; N-((3,3-difluorocyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-hydroxycyclobutyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(oxetan-2-ylmethyl)benzamide; Methyl 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoate; 3-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)propanoic acid; 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoic acid; 4-((2-fluorophenyl)ethynyl)-N-((1-(3-hydroxypropyl)cyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((2-hydroxycyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxycyclohexyl)methyl)benzamide; (4-((2-fluorophenyl)ethynyl)-N-((1-methoxycyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-methoxytetrahydro-2H-pyran-4-yl)methyl)benzamide; N-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl-d2)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; N-((5,5-dimethyltetrahydrofuran-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; N-((3-ethyloxetan-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((1-fluorocyclohexyl)methyl)benzamide; Methyl 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetate; Methyl 2-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)acetate; 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetic acid; (N-((1-(2-amino-2-oxoethyl)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; (N-((4-(2-amino-2-oxoethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(2-(hydroxyamino)-2-oxoethyl)cyclohexyl)methyl)benzamide; (4-((2-fluorophenyl)ethynyl)-N-((1-(2-(methylamino)-2-oxoethyl)cyclohexyl)methyl)benzamide; N-((1-(2-(dimethylamino)-2-oxoethyl)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxyoxetan-3-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; 3-Fluoro-4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(((1s,3s)-3-hydroxycyclobutyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(((1r,3r)-3-hydroxycyclobutyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(((1s,3s)-3-hydroxy-3-methylcyclobutyl)methyl)benzamide; N-((4,4-difluorocyclohexyl)methyl)-4-(pyridin-4-ylethynyl)benzamide; N-((3,3-difluorocyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide; N-((3,3-difluorocyclobutyl)methyl)-4-(phenylethynyl)benzamide; (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl-d)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-morpholinocyclobutyl)methyl)benzamide; N-((3,3-difluoro-1-methylcyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; N-((3-fluorooxetan-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((1-methylcyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((1-methylcyclopentyl)methyl)benzamide; (R)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; N-((3-ethyloxetan-3-yl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (R)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-(oxetan-2-ylmethyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; N-((3,3-difluorocyclobutyl)methyl)-4-((2,4-difluorophenyl)ethynyl)benzamide; N-((4,4-difluorocyclohexyl)methyl)-4-((2,4-difluorophenyl)ethynyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((3-ethyloxetan-3-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((3-fluorooxetan-3-yl)methyl)benzamide; (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; and 4-((2,4-difluorophenyl)ethynyl)-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)benzamide.

[0038] The compound of formula (1) acts as a dual modulator of mGluR5 and 5-HT2A receptors.

[0039] All of the compounds of formula (1) had IC values ​​of 2 μM or less for mGluR5 and 5-HT2A receptors. 50 In another embodiment according to the present invention, the compound of formula (1) has an IC value of 1.5 μM or less simultaneously for mGluR5 and 5-HT2A receptors. 50 In another embodiment according to the present invention, the compound of formula (1) has an IC value of 1.0 μM or less simultaneously for mGluR5 and 5-HT2A receptors. 50 It has.

[0040] In another embodiment according to the present invention, more specific examples of the compound of formula (1) include the following compounds: N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-(phenylethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxyoxetan-3-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(((1s,3s)-3-hydroxy-3-methylcyclobutyl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (R)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; and (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide. The compound exhibited an IC value of 1.0 μM or less simultaneously for mGluR5 and 5-HT2A receptors. 50 Furthermore, the compound exhibits excellent analgesic effects in a spinal nerve ligation model.

[0041] The efficacy of the compound according to one embodiment of the present invention may be maintained even in the form of a pharmaceutically acceptable salt. The pharmaceutically acceptable salt includes acid or base addition salts and their stereochemical isomers. The salt may include, but is not limited to, any salt that maintains the activity of the parent compound in the subject to which it is administered and does not induce any undesired effects. The term "addition salt" may be interpreted as including a solvate that the compound of formula (1) or a pharmaceutically acceptable salt thereof can form. Examples of these solvates include hydrates or alcoholates.

[0042] Furthermore, the compounds according to one embodiment of the present invention may have asymmetric carbon centers and therefore may exist as R or S isomers, racemic mixtures, diastereomeric mixtures, and individual diastereoisomers, all of which are within the scope of the present invention.

[0043] Pharmaceutical Composition According to another aspect of the present invention, there is provided a pharmaceutical composition for the prevention or treatment of pain, comprising a therapeutically effective amount of a compound of formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient, together with a pharmaceutically acceptable carrier or excipient.

[0044] The pharmaceutical compositions can be formulated into various oral or parenteral dosage forms, such as tablets, pills, hard / soft capsules, liquids, suspensions, emulsions, syrups, granules, elixirs, and other dosage forms for oral administration.

[0045] When the pharmaceutical composition is formulated into a parenteral dosage form, the pharmaceutical composition is administered by parenteral administration methods such as subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection. To formulate into the parenteral administration preparation, the pharmaceutical composition can be prepared as a solution or suspension by mixing the active ingredient, i.e., the compound of formula (1) or a pharmaceutically acceptable salt thereof, with a stabilizer or buffer in water, and such a solution or suspension can be prepared in a unit dosage form such as an ampule or a vial.

[0046] medical utility According to yet another aspect of the present invention, there is provided a method for reducing or treating pain in an animal, comprising administering to the animal a therapeutically effective amount of one or more compounds of formula (1) and pharmaceutically acceptable salts thereof.

[0047] The compound of formula (1) acts as a dual modulator of mGluR5 and 5-HT2A receptors. Specifically, the compound of formula (1) acts as an antagonist of the 5-HT2A receptor and functions as a negative modulator (regulatory function modulator) in the mGluR5 subreceptor signaling system. The compound of formula (1) with these characteristics can be administered to patients in small doses due to the synergistic effect between the targets, minimizing side effects and maximizing analgesic effects.

[0048] The compound of formula (1) can be used for the treatment and prevention of pain, particularly neuropathic pain. Neuropathic pain includes diabetic neuropathic pain, spinal stenosis, pain after spinal surgery, allodynia, causalgia, hyperalgesia, hyperpathia, neuralgia, post-herpetic neuralgia, post-thoracotomy pain, trigeminal neuralgia, multiple sclerosis-related pain, thalamic pain, phantom limb pain, anesthesia dolorosa, HIV-related neuropathic pain, paraplegic pain due to spinal cord injury, and complex regional pain syndrome. syndrome), post-stroke pain, neuropathy-related pain such as idiopathic or post-traumatic neuropathy and mononeuritis, cancer-related neuropathic pain, carpal tunnel-related neuropathic pain, spinal cord injury-related pain, fibromyalgia-related neuropathic pain, back and neck pain, reflex sympathetic dysregulation, phantom limb syndrome and spontaneous pain, trauma-induced neuropathic pain, pain due to demyelination, chemotherapy-induced neuropathy, back pain, bone pain, neuropathic pain due to chronic alcoholism, hypothyroidism, uremia or vitamin deficiency, and central post-stroke pain.

[0049] In one embodiment, the method for reducing or treating pain comprises administering to an animal a pharmaceutical composition comprising an effective amount of one or more compounds of Formula (1) and a pharmaceutically acceptable carrier. The method is particularly suitable for use in humans, but can also be used in other animals, particularly mammals.

[0050] The specific administration method and therapeutically effective amount of the compound of formula (1) or a pharmaceutically acceptable salt thereof can be determined by a person skilled in the art in consideration of the type of mammal to be treated, the type of disease, the type of compound of formula (1), and the like, and are not particularly limited.

[0051] For example, the compound of formula (1) or a pharmaceutically acceptable salt thereof may be contained in the pharmaceutical composition at an effective dose of 0.1 to 1,000 mg / kg (body weight), preferably 0.5 to 500 mg / kg (body weight) per day for mammals, including humans. This pharmaceutical composition may be administered orally or parenterally once or twice or more times a day.

[0052] The method for preparing the compound of formula (1) is described below. The following description is merely an exemplary method, and may be appropriately modified according to the selection of a person skilled in the art.

[0053] The compound of formula (1) can be obtained through an amide bond reaction between an amine compound of intermediate 4 and a carboxylic acid compound of intermediate 5, as shown in Reaction Scheme 1 below. <Reaction Scheme 1> [ka] The amine compounds of intermediate 4 can be prepared by a variety of methods depending on the substituents, including but not limited to the methods of Reaction Schemes 2-8. <Reaction Scheme 2> [ka] As starting materials, an imine compound is formed from amine compound 8 and ketone compound 7, followed by a nucleophilic addition reaction using potassium nitrile (KCN) to obtain intermediate 6a, which can then be reduced to obtain intermediate 4a, an amine compound. <Reaction Scheme 3> [ka] The ketone compound 7 is subjected to a nucleophilic addition reaction using potassium nitrile to obtain the cyanohydrin compound 6b, which is then subjected to a reduction reaction to obtain the amine compound intermediate 4b. <Reaction Scheme 4> [ka] The cyano compound 6c can be reduced to give the amine compound intermediate 4c. <Reaction Scheme 5> [ka] The cyano compound 6c can be subjected to a substitution reaction to give compound 6d, which can be reduced to give the amine compound intermediate 4d. Under hydrochloric acid conditions, intermediate 4e can be obtained in the form of an amine hydrochloride. <Reaction Scheme 6> [ka] The lactam compound 9 was subjected to ring-opening under strong acid conditions to give the carboxylic acid-containing intermediate 4f, an amine compound, and the ester-containing intermediate 4g was also obtained under acidic conditions. <Reaction Scheme 7> [ka] Carboxylic acid compound 10 can be coupled with acrylate compound 11 to give compound 6e, which can be deprotected using strong acid to give the amine compound intermediate 4h. <Reaction Scheme 8> [ka] Carboxylic acid compound 10 can be subjected to a coupling reaction using ditetrafluoroborate under visible light to give fluorine-substituted compound 6f, which can then be subjected to a deprotection reaction to give intermediate 4i, an amine compound. <Reaction Scheme 9> [ka] Compound 12 can be substituted under basic conditions to give ring-containing compound 6g, which can be reduced to the ester and nitrile to give intermediate amine 4j, which can be selectively protected to give alcohol 6h, which can then be substituted with hydroxy by fluoro to give intermediate amine 4k.

[0054] The carboxylic acid compound of intermediate 5 can be prepared by a variety of methods, including but not limited to the method of Reaction Scheme 10 below. <Reaction Scheme 10> [ka] Compound 13 can be obtained by Sonogashira coupling reaction of halogen-containing compound 14a or 15b with acetylene-containing compound 15a or 14b, and intermediate 5, a carboxylic acid compound, can be obtained by hydrolysis.

[0055] Example The present invention will be described in detail below with reference to examples, but it should be understood that the scope of protection of the present disclosure is not limited to these examples.

[0056] Example 1: Synthesis of N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-(pyridin-2-ylethynyl)benzamide [ka] Step 1: Synthesis of 4-(pyridin-2-ylethynyl)benzoic acid [ka] Methyl 4-ethynylbenzoate (1.500 g, 9.365 mmol), 2-iodopyridine (2.112 g, 10.302 mmol), tetrakis(triphenylphosphine)palladium (0.216 g, 0.187 mmol), copper iodide (0.036 g, 0.187 mmol), and piperidine (9.251 mL, 93.650 mmol) were dissolved in toluene (15 mL) at room temperature. The resulting solution was stirred at 90 °C for 18 hours and then cooled to room temperature to terminate the reaction. Saturated aqueous ammonium chloride solution was poured into the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give methyl 4-(pyridin-2-ylethynyl)benzoate (1.705 g, 76.7%) as a white solid. The resulting compound (1.705 g, 7.186 mmol) and lithium hydroxide monohydrate (0.603 g, 14.372 mmol) were dissolved in methanol (5 mL), water (5 mL), and tetrahydrofuran (5 mL) at room temperature, and the resulting mixture was stirred at the same temperature for 3 hours. The solvent was removed from the reaction mixture under reduced pressure, and then 1N aqueous hydrochloric acid was added to the concentrate and stirred. The precipitated solid was filtered, washed with water, and dried to give 4-(pyridin-2-ylethynyl)benzoic acid (0.695 g, 43.3%) as a yellow solid: LRMS (ES) m / z 224.00 [M+H]. + , calculated MW 223.23. Step 2: Synthesis of 1-(aminomethyl)-N-cyclopropylcycloheptan-1-amine [ka] Cyclopropanamine (5.700 g, 99.825 mmol) and cycloheptanone (11.197 g, 99.825 mmol) were dissolved in water (200 mL) at room temperature. Sodium bisulfite (NaHSO3, 40.00% aqueous solution, 12.984 mL, 49.912 mmol) was added to the resulting solution and stirred at the same temperature for 2 hours. Potassium cyanide (9.750 g, 149.737 mmol) was added to the reaction mixture and stirred at the same temperature for an additional 24 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give 1-(cyclopropylamino)cycloheptane-1-carbonitrile (12.670 g, 71.2%) as a colorless oil. The resulting product was dissolved in diethyl ether (200 mL) at 0 °C, and lithium aluminum hydride (2.40 M solution, 88.835 mL, 213.204 mmol) was added to the solution and stirred at room temperature for 16 hours. Water (7.684 mL, 426.408 mmol) and sodium hydroxide (1.00 M solution, 35.534 mL, 35.534 mmol) were then added to the reaction mixture at 0 °C and stirred for 30 minutes to quench the reaction. The reaction mixture was filtered through a Celite pad to remove solids, and the solvent was removed from the filtrate under reduced pressure. The resulting product was used without further purification (1-(aminomethyl)-N-cyclopropylcycloheptan-1-amine, 12.000 g, 92.6%, colorless oil): LRMS (ES) m / z 183.16 [M+H]. + , calculated MW 182.31. Step 3: Synthesis of N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-(pyridin-2-ylethynyl)benzamide [ka] 4-(Pyridin-2-ylethynyl)benzoic acid (0.031 g, 0.139 mmol), 1-(aminomethyl)-N-cyclopropylcycloheptan-1-amine (0.025 g, 0.139 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl, 0.040 g, 0.208 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (HOBt, 0.028 g, 0.208 mmol), and N,N-diisopropylethylamine (0.121 mL, 0.694 mmol) were dissolved in N,N-dimethylformamide (2 mL) at room temperature, and the resulting solution was stirred at the same temperature for 18 hours. Saturated aqueous sodium bicarbonate was poured into the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-(pyridin-2-ylethynyl)benzamide (0.008 g, 14.9%) as a yellow solid: LRMS (ES) m / z 388.41 [M+H] + , calculated MW 387.53; 1 H-NMR (400 MHz, CDCl3) d 9.24 (s, 1 H), 8.63 (d, J = 4.0 Hz, 1 H), 8.41 (t, J = 5.6 Hz, 1 H), 8.14 (d, J = 8.4 Hz, 2 H), 7.71 (t, J = 7.8 Hz, 1 H), 7.64 (d, J = 8.4 Hz, 2 H), 7.54 (d, J = 8.0 Hz, 1 H), 7.28 (m, 1 H), 3.93 (d, J = 5.6 Hz, 2 H), 2.54 (s, 1 H), 2.12 (m, 2 H), 1.98 (m, 2 H), 1.68 (m, 12 H). Example 2: Synthesis of N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-(pyridin-4-ylethynyl)benzamide [ka] Step 1: Synthesis of methyl 4-(pyridin-4-ylethynyl)benzoate [ka] Using 4-iodopyridine (2.816 g, 13.735 mmol) instead of 2-iodopyridine in a manner similar to Step 1 of Example 1, methyl 4-(pyridin-4-ylethynyl)benzoate (2.500 g, 84.4%) was obtained as a white solid, followed by 4-(pyridin-4-ylethynyl)benzoic acid (2.484 g, 97.6%) as a white solid.

[0057] Step 2: Synthesis of 1-(aminomethyl)-N-cyclopropylcyclopentan-1-amine [ka] Using cyclopentanone (10.000 mL, 112.934 mmol) instead of cycloheptanone in a manner similar to Step 2 of Example 1, 1-(cyclopropylamino)cyclopentane-1-carbonitrile (13.659 g, 80.5%) was obtained as a yellow liquid, followed by 1-(aminomethyl)-N-cyclopropylcyclopentan-1-amine (11.510 g, 82.1%, yellow liquid).

[0058] Step 3: Synthesis of N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-(pyridin-4-ylethynyl)benzamide [ka] Using 4-(pyridin-4-ylethynyl)benzoic acid (0.100 g, 0.448 mmol) and 1-(aminomethyl)-N-cyclopropylcyclopentan-1-amine (0.083 g, 0.538 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-(pyridin-4-ylethynyl)benzamide (0.097 g, 60.2%) as a yellow solid: LRMS (ES) m / z 360.19 [M+H]. +, calculated MW 359.47; 1 H-NMR (400 MHz, CDCl3) d 8.60 (d, J = 9.6 Hz, 2 H), 7.83 (d, J = 22.8 Hz, 2 H), 7.59 - 7.55 (m, 2 H), 7.37 (d, J = 6.0 Hz, 2 H), 3.57 (s, 2 H), 2.27 - 2.20 (m, 1 H), 1.88 - 1.71 (m, 8 H), 0.59 - 0.58 (m, 4 H). Example 3: Synthesis of N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide [ka] Step 1: Synthesis of 4-((5-fluoropyridin-2-yl)ethynyl)benzoic acid [ka] Methyl 4-ethynylbenzoate (1.000 g, 6.243 mmol), 2-bromo-5-fluoropyridine (1.099 g, 6.243 mmol), copper iodide (0.119 g, 0.624 mmol), tetrakis(triphenylphosphine)palladium (0.433 g, 0.375 mmol), and triethylamine (8.702 mL, 62.434 mmol) were dissolved in toluene (25 mL) at room temperature. The resulting solution was stirred at 100 °C for 16 hours and then cooled to room temperature to terminate the reaction. The reaction mixture was filtered through a Celite pad to remove solids, and water was added to the filtrate, followed by extraction with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give methyl 4-((5-fluoropyridin-2-yl)ethynyl)benzoate (0.980 g, 61.5%) as a brown solid. Next, a solution of the obtained product and lithium hydroxide monohydrate (0.322 g, 7.679 mmol) in tetrahydrofuran (5 mL), methanol (5 mL), and ethanol (5 mL) was stirred at 50 °C for 6 hours at room temperature, and then the temperature was lowered to room temperature to terminate the reaction. The solvent was removed from the reaction mixture under reduced pressure, and then 1N aqueous hydrochloric acid was added to the concentrate and stirred. The precipitated solid was filtered, washed with water, and dried to give 4-((5-fluoropyridin-2-yl)ethynyl)benzoic acid (0.860 g, 92.9%) as a brown solid: LRMS (ES) m / z 241.72 [M+H]. + , calculated MW 241.22. Step 2: Synthesis of N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide [ka] Using 4-((5-fluoropyridin-2-yl)ethynyl)benzoic acid (0.156 g, 0.648 mmol) and 1-(aminomethyl)-N-cyclopropylcyclopentan-1-amine (0.100 g, 0.648 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide (0.085 g, 34.7%) as a white solid: LRMS (ES) m / z 378.18 [M+H]. + , calculated MW 377.46; 1 H-NMR (400 MHz, CD3OD) d 8.48 (m, 1 H), 7.86 (d, J = 8.4 Hz, 2 H), 7.72 - 7.63 (m, 4 H), 3.56 (s, 2 H), 2.21 - 2.17 (m, 1 H), 1.79 - 1.62 (m, 8 H), 0.52 - 0.48 (m, 2 H), 0.37 - 0.35 (m, 2 H). Example 4: Synthesis of N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide [ka] Step 1: Synthesis of 1-(aminomethyl)-N-cyclopropylcyclobutan-1-amine [ka] 1-(Cyclopropylamino)cyclobutane-1-carbonitrile (0.823 g, 26.5%) was obtained as a yellow liquid in the same manner as in Step 2 of Example 1, except that cyclobutanone (1.706 mL, 22.828 mmol) was used instead of cycloheptanone. 1-(aminomethyl)-N-cyclopropylcyclobutan-1-amine was then obtained as a yellow solid (0.760 g, 92.3%): LRMS (ES) m / z 140.96 [M+H]. + , calculated MW 140.23 Step 2: Synthesis of N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide [ka] Using 4-((5-fluoropyridin-2-yl)ethynyl)benzoic acid (0.070 g, 0.290 mmol) and 1-(aminomethyl)-N-cyclopropylcyclobutan-1-amine (0.061 g, 0.435 mmol), a procedure similar to that of Step 3 of Example 1 was carried out to give N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide (0.044 g, 41.7%) as a yellow liquid: LRMS (ES) m / z 364.10 [M+H]. + , calculated MW 363.44; 1H-NMR (400 MHz, CD3OD) d 8.48 (d, J = 2.4 Hz, 1 H), 7.87 (d, J = 6.8 Hz, 2 H), 7.75 - 7.59 (m, 4 H), 3.61 (s, 2 H), 2.12 - 2.06 (m, 3 H), 2.01 - 1.98 (m, 2 H), 1.83 - 1.79 (m, 2 H), 0.52 - 0.48 (m, 2 H), 0.36 - 0.33 (m, 2 H). Example 5: Synthesis of N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide [ka] Step 1: Synthesis of N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide [ka] Using 4-(pyridin-4-ylethynyl)benzoic acid (0.070 g, 0.314 mmol) and 1-(aminomethyl)-N-cyclopropylcyclobutan-1-amine (0.066 g, 0.470 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide (0.078 g, 72.0%) as a yellow liquid: LRMS (ES) m / z 346.18 [M+H]. + , calculated MW 345.45; 1H-NMR (400 MHz, CD3OD) d 8.55 (d, J = 6.0 Hz, 2 H), 7.88 (d, J = 8.4 Hz, 2 H), 7.66 (d, J = 12.0 Hz, 2 H), 7.53 (d, J = 6.0 Hz, 2 H), 3.70 (s, 2 H), 2.14 - 2.09 (m, 3 H), 2.07 - 1.97 (m, 2 H), 1.84 - 1.81 (m, 2 H), 0.51 - 0.49 (m, 2 H), 0.37 - 0.35 (m, 2 H). Example 6: Synthesis of N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide [ka] Step 1: Synthesis of 4-((4-fluorophenyl)ethynyl)benzoic acid [ka] Using methyl 4-bromobenzoate (0.985 g, 4.578 mmol) and 1-ethynyl-4-fluorobenzene (0.500 g, 4.162 mmol) as starting materials, methyl 4-((4-fluorophenyl)ethynyl)benzoate (0.779 g, 73.6%) was obtained as a white solid in a similar manner to Step 1 of Example 3. Subsequently, 4-((4-fluorophenyl)ethynyl)benzoic acid (0.672 g, 91.3%) was obtained as a pale yellow solid: LRMS (ES) m / z 239.05 [M−H] + , calculated MW 240.23. Step 2: Synthesis of N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and 1-(aminomethyl)-N-cyclopropylcyclobutan-1-amine (0.061 g, 0.437 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide (0.078 g, 73.9%) as a yellow liquid: LRMS (ES) m / z 363.12 [M+H]. + , calculated MW 362.45; 1 H-NMR (400 MHz, CD3OD) d 7.84 (dt, J = 8.4, 1.9 Hz, 2 H), 7.60 - 7.53 (m, 4 H), 7.12 (t, J = 8.6 Hz, 2 H), 3.89 (s, 2 H), 2.13 - 2.06 (m, 3 H), 2.03 - 1.98 (m, 2 H), 1.85 - 1.79 (m, 2 H), 0.51 - 0.48 (m, 2 H), 0.36 - 0.34 (m, 2 H). Example 7: Synthesis of N-((1-(cyclopropylamino)cyclobutyl)methyl)-3-fluoro-4-(pyridin-4-ylethynyl)benzamide [ka] Step 1: Synthesis of 3-fluoro-4-(pyridin-4-ylethynyl)benzoic acid [ka] Using methyl 4-bromo-3-fluorobenzoate (1.000 g, 4.291 mmol) and 4-ethynylpyridine hydrochloride (0.493 g, 4.506 mmol) as starting materials, methyl 3-fluoro-4-(pyridin-4-ylethynyl)benzoate (0.868 g, 79.2%) was obtained as a brown solid in a similar manner to Step 1 of Example 3. Subsequently, 3-fluoro-4-(pyridin-4-ylethynyl)benzoic acid (0.813 g, 100.0%) was obtained as a pale yellow solid: LRMS (ES) m / z 242.09 [M+H].+ , calculated MW 241.22. Step 2: Synthesis of N-((1-(cyclopropylamino)cyclobutyl)methyl)-3-fluoro-4-(pyridin-4-ylethynyl)benzamide [ka] Using 3-fluoro-4-(pyridin-4-ylethynyl)benzoic acid (0.070 g, 0.290 mmol) and 1-(aminomethyl)-N-cyclopropylcyclobutan-1-amine (0.061 g, 0.435 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give N-((1-(cyclopropylamino)cyclobutyl)methyl)-3-fluoro-4-(pyridin-4-ylethynyl)benzamide (0.071 g, 67.3%) as a yellow liquid: LRMS (ES) m / z 364.10 [M+H]+, calculated MW 363.44; 1 H-NMR (400 MHz, CD3OD) d 8.57 (dd, J = 4.6, 1.8 Hz, 2 H), 7.73 - 7.68 (m, 3 H), 7.55 (dd, J = 4.2, 1.8 Hz, 2 H), 3.70 (s, 2 H), 2.15 - 2.07 (m, 3 H), 2.03 - 1.97 (m, 2 H), 1.85 - 1.77 (m, 2 H), 0.50 (dt, J = 8.8, 3.4 Hz, 2 H), 0.37 - 0.33 (m, 2 H). Example 8: Synthesis of N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-2-ylethynyl)benzamide [ka] Using 1-(aminomethyl)-N-cyclopropylcyclobutan-1-amine (0.066 g, 0.470 mmol) as the starting material instead of 1-(aminomethyl)-N-cyclopropylcycloheptan-1-amine, a procedure similar to that of Step 3 of Example 1 was carried out to give N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-2-ylethynyl)benzamide (0.071 g, 65.5%) as a yellow liquid: LRMS (ES) m / z 346.18 [M+H]. + , calculated MW 345.45; 1 H-NMR (400 MHz, CD3OD) d 8.54 (d, J = 4.4 Hz, 1 H), 7.89 - 7.85 (m, 3 H), 7.69 - 7.65 (m, 3 H), 7.44 - 7.40 (m, 1 H), 3.70 (s, 2 H), 2.13 - 2.07 (m, 3 H), 2.03 - 1.97 (m, 2 H), 1.88 - 1.77 (m, 2 H), 0.53 - 0.49 (m, 2 H), 0.37 - 0.33 (m, 2 H). Example 9: Synthesis of N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Step 1: Synthesis of 4-((2-fluorophenyl)ethynyl)benzoic acid [ka] Using 1-ethynyl-2-fluorobenzene (0.500 g, 4.162 mmol) and methyl 4-bromobenzoate (0.940 g, 4.370 mmol) as starting materials, methyl 4-((2-fluorophenyl)ethynyl)benzoate (0.775 g, 73.2%) was obtained as a white solid in the same manner as in Step 1 of Example 3. Subsequently, 4-((2-fluorophenyl)ethynyl)benzoic acid (0.703 g, 96.0%) was obtained as a pale yellow solid: LRMS (ES) m / z 239.12 [M−H] +, calculated MW 240.23. Step 2: Synthesis of N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and 1-(aminomethyl)-N-cyclopropylcyclobutan-1-amine (0.061 g, 0.437 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.087 g, 82.4%) as a pale yellow liquid: LRMS (ES) m / z 363.12 [M+H]. + , calculated MW 362.45; 1 H-NMR (400 MHz, CD3OD) d 7.83 (d, J = 11.2 Hz, 2 H), 7.61 (d, J = 10.0 Hz, 2 H), 7.55 (td, J = 7.6, 1.7 Hz, 1 H), 7.42 - 7.37 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.69 (s, 2 H), 2.14 - 2.06 (m, 3 H), 2.03 - 1.98 (m, 2 H), 1.85 - 1.79 (m, 2 H), 0.52 - 0.48 (m, 2 H), 0.36 - 0.32 (m, 2 H). Example 10: Synthesis of N-((1-(cyclopropylamino)cyclobutyl)methyl)-2-fluoro-4-(pyridin-4-ylethynyl)benzamide [ka] Step 1: Synthesis of 2-fluoro-4-(pyridin-4-ylethynyl)benzoic acid [ka] Using methyl 4-bromo-2-fluorobenzoate (1.000 g, 4.291 mmol) and 4-ethynylpyridine hydrochloride (0.629 g, 4.506 mmol) as starting materials, methyl 2-fluoro-4-(pyridin-4-ylethynyl)benzoate (0.786 g, 71.8%) was obtained as a pale yellow solid in a similar manner to Step 1 of Example 3. Subsequently, 2-fluoro-4-(pyridin-4-ylethynyl)benzoic acid (0.568 g, 77.1%) was obtained as a yellow solid: LRMS (ES) m / z 242.16 [M+H]. + , calculated MW 241.22. Step 2: Synthesis of N-((1-(cyclopropylamino)cyclobutyl)methyl)-2-fluoro-4-(pyridin-4-ylethynyl)benzamide [ka] Using 2-fluoro-4-(pyridin-4-ylethynyl)benzoic acid (0.070 g, 0.290 mmol) and 1-(aminomethyl)-N-cyclopropylcyclobutan-1-amine (0.061 g, 0.435 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give N-((1-(cyclopropylamino)cyclobutyl)methyl)-2-fluoro-4-(pyridin-4-ylethynyl)benzamide (0.082 g, 77.7%) as a pale yellow liquid: LRMS (ES) m / z 364.17 [M+H]. + , calculated MW 363.44; 1 H-NMR (400 MHz, CD3OD) d 8.56 (dd, J = 4.6, 1.8 Hz, 2 H), 7.81 (t, J = 7.8 Hz, 1 H), 7.54 (dd, J = 4.6, 1.4 Hz, 2 H), 7.49 - 7.43 (m, 2 H), 3.68 (s, 2 H), 2.12 - 2.04 (m, 3 H), 2.01 - 1.94 (m, 2 H), 1.85 - 1.77 (m, 2 H), 0.45 - 0.46 (m, 2 H), 0.33 - 0.30 (m, 2 H). Example 11: Synthesis of N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] A solution of 4-((2-fluorophenyl)ethynyl)benzoic acid (0.300 g, 1.249 mmol), 1-(aminomethyl)-N-cyclopropylcyclopentan-1-amine (0.231 g, 1.499 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU, 0.712 g, 1.873 mmol), and N,N-diisopropylethylamine (1.088 mL, 6.244 mmol) in N,N-dimethylformamide (10 mL) was stirred at room temperature for 18 hours. Saturated aqueous sodium bicarbonate was poured into the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.230 g, 48.9%) as a yellow solid: LRMS (ES) m / z 377.32 [M+H]+, calculated MW 376.48; 1H-NMR (400 MHz, CD3OD) d 7.85 (dt, J = 8.0, 1.8 Hz, 2 H), 7.62 (d, J = 6.4 Hz, 2 H), 7.57 - 7.53 (m, 1 H), 7.43 - 7.38 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.57 (s, 2 H), 2.24 (m, 1 H). 1.74 - 1.67 (m, 8 H), 0.59 - 0.51 (m, 2 H), 0.41 - 0.37 (m, 2 H). Example 12: Synthesis of N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.066 g, 0.274 mmol) and 1-(aminomethyl)-N-cyclopropylcycloheptan-1-amine (0.050 g, 0.274 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.040 g, 36.1%) as a white solid: LRMS (ES) m / z 405.20 [M+H]. + , calculated MW 404.53; 1 H-NMR (400 MHz, CD3OD) d 7.84 (d, J = 8.4 Hz, 2 H), 7.61 (d, J = 8.0 Hz, 3 H), 7.40 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.47 (s, 2 H), 2.17 (m, 1 H), 1.77 - 1.49 (m, 12 H), 0.49 (m, 2 H), 0.34 (m, 2 H). Example 13: Synthesis of N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.078 g, 0.324 mmol) as the starting material instead of 4-((2-fluorophenyl)ethynyl)benzoic acid, a procedure similar to that of Example 11 was carried out to give N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide (0.045 g, 36.9%) as a white solid: LRMS (ES) m / z 377.13 [M+H]. + , calculated MW 376.48; 1H-NMR (400 MHz, CD3OD) d 7.84 - 7.82 (m, 2 H), 7.60 - 7.52 (m, 4 H), 7.15 - 7.10 (m, 2 H), 3.56 (s, 2 H), 2.20 - 2.17 (m, 1 H), 1.75 - 1.62 (m, 8 H), 0.52 - 0.49 (m, 2 H), 0.37 - 0.33 (m, 2 H). Example 14: Synthesis of N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.066 g, 0.274 mmol) and 1-(aminomethyl)-N-cyclopropylcycloheptan-1-amine (0.050 g, 0.274 mmol) as starting materials, a procedure similar to that of Example 11 was carried out to give N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide (0.035 g, 31.5%) as a yellow solid: LRMS (ES) m / z 405.20 [M+H]+, calculated MW 404.53; 1 H-NMR (400 MHz, CD3OD) d 7.82 (dd, J = 6.8, 2.0 Hz, 2 H), 7.60 - 7.53 (m, 4 H), 7.15 - 7.10 (m, 2 H), 3.46 (s, 2 H), 2.16 (m, 1 H), 1.78 - 1.45 (m, 12 H), 0.50 - 0.46 (m, 2 H), 0.35 - 0.33 (m, 2 H). Example 15: Synthesis of N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide [ka] Using 4-((5-fluoropyridin-2-yl)ethynyl)benzoic acid (0.066 g, 0.274 mmol) and 1-(aminomethyl)-N-cyclopropylcycloheptan-1-amine (0.050 g, 0.274 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide (0.050 g, 45.0%) as a white solid: LRMS (ES) m / z 406.39 [M+H]. + , calculated MW 405.52; 1 H-NMR (400 MHz, CD3OD) d 8.48 (d, J = 2.8 Hz, 1 H), 7.86 (d, J = 8.0 Hz, 2 H), 7.71 - 7.66 (m, 4 H), 3.47 (s, 2 H), 2.17 (m, 1 H), 1.78 - 1.26 (m, 12 H), 0.50 - 0.47 (m, 2 H), 0.35 - 0.33 (m, 2 H). Example 16: Synthesis of N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((3-fluoropyridin-4-yl)ethynyl)benzamide [ka] Step 1: Synthesis of 4-((3-fluoropyridin-4-yl)ethynyl)benzoic acid [ka] Methyl 4-ethynylbenzoate (2.000 g, 12.487 mmol) and 3-fluoro-4-iodopyridine (2.784 g, 12.487 mmol) were used in a similar manner to Step 1 of Example 3 to give methyl 4-((3-fluoropyridin-4-yl)ethynyl)benzoate (2.300 g, 72.2%) as a yellow solid, followed by 4-((3-fluoropyridin-4-yl)ethynyl)benzoic acid (2.150 g, 98.9%) as a yellow solid: LRMS (ES) m / z 242.09 [M+H]. +, calculated MW 241.22. Step 2: Synthesis of N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((3-fluoropyridin-4-yl)ethynyl)benzamide [ka] N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((3-fluoropyridin-4-yl)ethynyl)benzamide (0.040 g, 36.0%) was obtained as a pale yellow solid in the same manner as in Example 11 using 4-((3-fluoropyridin-4-yl)ethynyl)benzoic acid (0.066 g, 0.274 mmol) and 1-(aminomethyl)-N-cyclopropylcycloheptan-1-amine (0.050 g, 0.274 mmol) as starting materials. LRMS (ES) m / z 406.18 [M+H] + , calculated MW 405.52; 1 H-NMR (400 MHz, CD3OD) d 8.55 (d, J = 1.6 Hz, 1 H), 8.41 (d, J = 5.2 Hz, 1 H), 7.88 (d, J = 8.4 Hz, 2 H), 7.69 (d, J = 8.4 Hz, 2 H), 7.63 (m, 1 H), 3.48 (s, 2 H), 2.19 (m, 1 H), 1.75 - 1.43 (m, 12 H), 0.52 - 0.48 (m, 2 H), 0.37 - 0.33 (m, 2 H). Example 17: Synthesis of N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((3,4-difluorophenyl)ethynyl)benzamide [ka] Step 1: Synthesis of 4-((3,4-difluorophenyl)ethynyl)benzoic acid [ka] Methyl 4-((3,4-difluorophenyl)ethynyl)benzoate (0.300 g, 17.6%) was obtained as a white solid in a manner similar to Step 1 of Example 3, except that 4-bromo-1,2-difluorobenzene (1.325 g, 6.868 mmol) was used instead of 2-bromo-5-fluoropyridine. 4-((3,4-difluorophenyl)ethynyl)benzoic acid (0.280 g, 98.4%) was then obtained as a white solid: LRMS (ES) m / z 257.05 [MH]. + , calculated MW 258.22. Step 2: Synthesis of N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((3,4-difluorophenyl)ethynyl)benzamide [ka] Using 4-((3,4-difluorophenyl)ethynyl)benzoic acid (0.084 g, 0.324 mmol) and 1-(aminomethyl)-N-cyclopropylcyclopentan-1-amine (0.050 g, 0.324 mmol) as starting materials, a procedure similar to that of Example 11 was carried out to give N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((3,4-difluorophenyl)ethynyl)benzamide (0.030 g, 23.5%) as a pale yellow solid: LRMS (ES) m / z 395.19 [M+H]. + , calculated MW 394.47; 1 H-NMR (400 MHz, CD3OD) d 7.85 - 7.82 (m, 2 H), 7.61 - 7.59 (m, 2 H), 7.47 (m, 1 H), 7.38 - 7.28 (m, 2 H), 3.56 (s, 2 H), 2.19 - 2.17 (m, 1 H), 1.88 - 1.62 (m, 8 H), 0.51 - 0.49 (m, 2 H), 0.37 - 0.34 (m, 2 H). Example 18: Synthesis of N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((3,4-difluorophenyl)ethynyl)benzamide [ka] Using 4-((3,4-difluorophenyl)ethynyl)benzoic acid (0.071 g, 0.274 mmol) and 1-(aminomethyl)-N-cyclopropylcycloheptan-1-amine (0.050 g, 0.274 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((3,4-difluorophenyl)ethynyl)benzamide (0.030 g, 25.9%) as a pale yellow solid: LRMS (ES) m / z 423.40 [M+H]. + , calculated MW 422.52; 1 H-NMR (400 MHz, CD3OD) d 7.84 - 7.82 (m, 2 H), 7.61 - 7.60 (m, 2 H), 7.46 (m, 1 H), 7.34 - 7.28 (m, 2 H), 3.46 (s, 2 H), 2.17 - 2.16 (m, 1 H), 1.78 - 1.25 (m, 12 H), 0.49 - 0.48 (m, 2 H), 0.35 - 0.33 (m, 2 H). Example 19: Synthesis of N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide [ka] Step 1: Synthesis of 1-(aminomethyl)-N-cyclopropylcyclohexan-1-amine [ka] 1-(aminomethyl)-N-cyclopropylcyclohexan-1-amine was prepared in a manner similar to Step 2 of Example 1, using cyclohexanone (2.112 mL, 20.377 mmol) instead of cycloheptanone. (2.921 g, 96.0%, white oil): LRMS (ES) m / z 169.11 [M+H]+, calculated MW 168.28. Step 2: Synthesis of N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and 1-(aminomethyl)-N-cyclopropylcyclohexan-1-amine (0.074 g, 0.437 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide (0.078 g, 68.5%) as a white solid: LRMS (ES) m / z 391.31 [M+H]+, calculated MW 390.5; 1 H-NMR (400 MHz, CD3OD) d 7.87 - 7.76 (m, 2 H), 7.63 - 7.49 (m, 4 H), 7.18 - 7.07 (m, 2 H), 3.55 (t, J = 14.8 Hz, 2 H), 2.22 - 2.12 (m, 1 H), 1.58 - 1.37 (m, 10 H), 0.54 - 0.42 (m, 2 H), 0.37 - 0.28 (m, 2 H). Example 20: Synthesis of N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and 1-(aminomethyl)-N-cyclopropylcyclohexan-1-amine (0.074 g, 0.437 mmol) as starting materials, a similar procedure to Step 3 of Example 1 was carried out to give N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.067 g, 58.9%) as a white solid: LRMS (ES) m / z 391.31 [M+H]. +, calculated MW 390.5; 1 H-NMR (400 MHz, CD3OD) d 7.85 - 7.79 (m, 2 H), 7.63 - 7.60 (m, 2 H), 7.57 - 7.53 (m, 1 H), 7.41 - 7.39 (m, 1 H), 7.25 - 7.13 (m, 2 H), 3.55 (t, J = 15.0 Hz, 2 H), 2.23 - 2.13 (m, 1 H), 1.61 - 1.44 (m, 10 H), 0.53 - 0.42 (m, 2 H), 0.40 - 0.30 (m, 2 H). Example 21: Synthesis of N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-methylpyridin-4-yl)ethynyl)benzamide [ka] Step 1: Synthesis of 4-((2-methylpyridin-4-yl)ethynyl)benzoic acid [ka] Using methyl 4-ethynylbenzoate (0.400 g, 2.497 mmol) and 4-bromo-2-methylpyridine (0.473 g, 2.747 mmol) as starting materials, methyl 4-((2-methylpyridin-4-yl)ethynyl)benzoate (0.531 g, 84.6%) was obtained as a pale yellow solid in the same manner as in Step 1 of Example 3. Subsequently, 4-((2-methylpyridin-4-yl)ethynyl)benzoic acid (0.337 g, 89.2%) was obtained as an ivory solid: LRMS (ES) m / z 238.06 [M+H]. + , calculated MW 237.26. Step 2: Synthesis of N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-methylpyridin-4-yl)ethynyl)benzamide [ka] In a manner similar to that of Example 11, except that 4-((2-methylpyridin-4-yl)ethynyl)benzoic acid (0.046 g, 0.194 mmol) was used instead of 4-((2-fluorophenyl)ethynyl)benzoic acid, N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-methylpyridin-4-yl)ethynyl)benzamide (0.020 g, 27.5%) was obtained as a yellow oil: LRMS (ES) m / z 374.21 [M+H]. + , calculated MW 373.5; 1 H-NMR (400 MHz, CD3OD) d 8.41 (d, J = 4.8 Hz, 1 H), 7.88 - 7.85 (m, 2 H), 7.66 (m, 2 H), 7.42 (s, 1 H), 7.34 - 7.33 (m, 1 H), 3.57 (s, 2 H), 2.53 (s, 3 H), 2.21 - 2.20 (m, 1 H), 1.78 - 1.66 (m, 8 H), 0.52 - 0.49 (m, 2 H), 0.38 - 0.36 (m, 2 H). Example 22: Synthesis of N-((4-(cyclopropylamino)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Step 1: Synthesis of 4-(aminomethyl)-N-cyclopropyltetrahydro-2H-pyran-4-amine [ka] Using tetrahydro-4H-pyran-4-one (8.767 g, 87.566 mmol) instead of cycloheptanone, 4-(cyclopropylamino)tetrahydro-2H-pyran-4-carbonitrile (12.000 g, 82.4%, colorless oil) was obtained in a manner similar to Step 2 of Example 1. The resulting product was subsequently used without further purification to give 4-(aminomethyl)-N-cyclopropyltetrahydro-2H-pyran-4-amine (5.100 g, 91.2%) as a colorless oil: LRMS (ES) m / z 171.09 [M+H]. + , calculated MW 170.26. Step 2: Synthesis of N-((4-(cyclopropylamino)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.282 g, 1.175 mmol) and 4-(aminomethyl)-N-cyclopropyltetrahydro-2H-pyran-4-amine (0.200 g, 1.175 mmol), a similar procedure to that described in Example 11 was carried out to give N-((4-(cyclopropylamino)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.230 g, 49.9%) as a white solid: LRMS (ES) m / z 393.09 [M+H]. + , calculated MW 392.47; 1 H-NMR (400 MHz, CD3OD) d 7.84 (d, J = 8.4 Hz, 2 H), 7.61 (d, J = 8.4 Hz, 2 H), 7.55 (m, 1 H), 7.39 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.77 - 3.75 (m, 2 H), 3.68 - 3.62 (m, 2 H), 3.61 (s, 2 H), 2.23 - 2.20 (m, 1 H), 1.70 - 1.63 (m, 4 H), 0.51 - 0.46 (m, 2 H), 0.35 - 0.32 (m, 2 H). Example 23: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-morpholinocyclopentyl)methyl)benzamide [ka] Step 1: Synthesis of (1-morpholinocyclopentyl)methanamine [ka] Using cyclopentanone (3.000 mL, 33.880 mmol) and morpholine (3.810 mL, 44.044 mmol) as starting materials, 1-morpholinocyclopentane-1-carbonitrile (5.510 g, 90.2%) was obtained as a white solid in a similar manner to Step 2 of Example 1. Subsequently, (1-morpholinocyclopentyl)methanamine was obtained (5.500 g, 97.6%, pale yellow liquid): LRMS (ES) m / z 185.09 [M+H]. + , calculated MW 184.28. Step 2: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-morpholinocyclopentyl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.091 g, 0.380 mmol) and (1-morpholinocyclopentyl)methanamine (0.070 g, 0.380 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((1-morpholinocyclopentyl)methyl)benzamide (0.020 g, 13.0%) was obtained as a colorless oil in the same manner as in Example 11: LRMS (ES) m / z 407.10 [M+H]. + , calculated MW 406.5; 1H-NMR (400 MHz, DMSO-d6) d 8.21 (t, J = 6.2 Hz, 1 H), 7.84 (d, J = 8.4 Hz, 2 H), 7.65 - 7.63 (m, 3 H), 7.48 (m, 1 H), 7.33 (m, 1 H), 7.25 (m, 1 H), 3.50 - 3.48 (m, 4 H), 3.37 (m, 2 H), 2.58 (m, 4 H), 1.60 (m, 8 H). Example 24: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((4-(isopropylamino)tetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Step 1: Synthesis of 4-(aminomethyl)-N-isopropyltetrahydro-2H-pyran-4-amine [ka] Using propan-2-amine (2.060 mL, 23.971 mmol) and tetrahydro-4H-pyran-4-one (1.845 mL, 19.976 mmol), 4-(isopropylamino)tetrahydro-2H-pyran-4-carbonitrile (2.108 g, 62.7%) was obtained in a manner similar to Step 2 of Example 1, followed by 4-(aminomethyl)-N-isopropyltetrahydro-2H-pyran-4-amine (2.100 g, 97.6%, ivory solid): LRMS (ES) m / z 173.07 [M+H], calculated MW 172.27. Step 2: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((4-(isopropylamino)tetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.100 g, 0.416 mmol) and 4-(aminomethyl)-N-isopropyltetrahydro-2H-pyran-4-amine (0.086 g, 0.500 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((4-(isopropylamino)tetrahydro-2H-pyran-4-yl)methyl)benzamide (0.018 g, 11.0%) was obtained as a yellow liquid in the same manner as in Example 11: LRMS (ES) m / z 395.08 [M+H]. + , calculated MW 394.49; 1 H-NMR (400 MHz, CD3OD) d 7.87 - 7.83 (m, 2 H), 7.63 - 7.60 (m, 2 H), 7.57 - 7.53 (m, 1 H), 7.43 - 7.38 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.83 - 3.79 (m, 2 H), 3.74 - 3.71 (m, 1 H), 3.69 - 3.63 (m, 2 H), 3.55 (s, 2 H), 1.65 (t, J = 5.4 Hz, 4 H), 1.11 (d, J = 6.4 Hz, 6 H). Example 25: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclohexyl)methyl)benzamide [ka] Step 1: Synthesis of 1-(aminomethyl)-N-isopropylcyclohexan-1-amine [ka] Using propan-2-amine (2.000 g, 33.835 mmol) and cyclohexanone (3.321 g, 33.835 mmol) as starting materials, 1-(aminomethyl)-N-isopropylcyclohexan-1-amine was prepared in a similar manner to Step 2 of Example 1 (3.000 g, 93.6%, colorless oil): LRMS (ES) m / z 171.09 [M+H]. +, calculated MW 170.3. Step 2: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclohexyl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.099 g, 0.411 mmol) and 1-(aminomethyl)-N-isopropylcyclohexan-1-amine (0.070 g, 0.411 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclohexyl)methyl)benzamide (0.085 g, 52.7%) as a colorless oil: LRMS (ES) m / z 393.23 [M+H]. + , calculated MW 392.52; 1 H-NMR (400 MHz, CD3OD) d 7.85 (d, J = 8.4 Hz, 2 H), 7.64 - 7.61 (m, 2 H), 7.65 (m, 1 H), 7.38 - 7.43 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.46 (s, 2 H), 1.65 - 1.35 (m, 11 H), 1.14 (s, 3 H), 1.13 (s, 3 H). Example 26: Synthesis of N-((1-(cyclopropylamino)-4-methylcyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Step 1: Synthesis of 1-(aminomethyl)-N-cyclopropyl-4-methylcyclohexan-1-amine [ka] Using 4-methylcyclohexan-1-one (1.000 mL, 6.865 mmol) instead of cycloheptanone, 1-(cyclopropylamino)-4-methylcyclohexane-1-carbonitrile (1.098 g, 89.7%) was obtained as a pale yellow liquid in a similar manner to Step 2 of Example 1. Subsequently, 1-(aminomethyl)-N-cyclopropyl-4-methylcyclohexan-1-amine was prepared (0.936 g, 83.4%, pale yellow liquid): LRMS (ES) m / z 183.12 [M+H]. + , calculated MW 182.31. Step 2: Synthesis of N-((1-(cyclopropylamino)-4-methylcyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.100 g, 0.416 mmol) and 1-(aminomethyl)-N-cyclopropyl-4-methylcyclohexan-1-amine (0.114 g, 0.624 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give N-((1-(cyclopropylamino)-4-methylcyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.065 g, 38.6%) as a yellow solid: LRMS (ES) m / z 405.26 [M+H]. + , calculated MW 404.53; 1H-NMR (400 MHz, CD3OD) d 7.84 (dt, J = 8.8, 2.3 Hz, 2 H), 7.61 (dt, J = 8.0, 1.8 Hz, 2 H), 7.55 (td, J = 7.4, 1.5 Hz, 1 H), 7.53 - 7.38 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.64 (s, 2 H), 2.26 - 2.18 (m, 1 H), 1.78 (d, J = 13.2 Hz, 2 H), 1.60 (dd, J = 13.6, 3.2 Hz, 2 H), 1.51 - 1.37 (m, 3 H), 1.25 - 1.18 (m, 2 H), 0.93 (d, J = 6.4 Hz, 3 H), 0.52 - 0.47 (m, 2 H), 0.35 - 0.31 (m, 2 H). Example 27: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (tetrahydro-2H-pyran-4-yl)methanamine (0.050 g, 0.437 mmol) as starting materials, a similar procedure to Step 3 of Example 1 was carried out to give 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide (0.075 g, 76.3%) as a white solid: LRMS (ES) m / z 338.21 [M+H]. + , calculated MW 337.39; 1H-NMR (400 MHz, CD3OD) d 7.82 (d, J = 8.8 Hz, 2 H), 7.60 (d, J = 8.8 Hz, 2 H), 7.55 (t, J = 7.6 Hz, 1 H), 7.45 - 7.37 (m, 1 H), 7.21 - 7.14 (m, 2 H), 3.93 (dd, J = 11.2, 4.0 Hz, 2 H), 3.39 (t, J = 11.8 Hz, 2 H), 3.28 - 3.26 (m, 2 H), 1.90 - 1.86 (m, 1 H), 1.69 (s, 2 H), 1.37 - 1.27 (m, 2 H). Example 28: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-(neopentylamino)cyclohexyl)methyl)benzamide [ka] Step 1: Synthesis of 1-(aminomethyl)-N-neopentylcyclohexan-1-amine [ka] Using 2,2-dimethylpropan-1-amine (2.861 mL, 24.452 mmol) and cyclohexanone (2.105 mL, 20.377 mmol) as starting materials, 1-(neopentylamino)cyclohexane-1-carbonitrile (3.600 g, 90.9%) was obtained as a clear liquid in a similar manner to Step 2 of Example 1. 1-(aminomethyl)-N-neopentylcyclohexan-1-amine was subsequently prepared (3.200 g, 87.1%, white solid): LRMS (ES) m / z 199.23 [M+H]+, calculated MW 198.35. Step 2: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-(neopentylamino)cyclohexyl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and 1-(aminomethyl)-N-neopentylcyclohexan-1-amine (0.087 g, 0.437 mmol), a procedure similar to that of Step 3 of Example 1 was carried out to give 4-((2-fluorophenyl)ethynyl)-N-((1-(neopentylamino)cyclohexyl)methyl)benzamide (0.119 g, 97.1%) as a pale yellow solid: LRMS (ES) m / z 421.30 [M+H]. + , calculated MW 420.57; 1 H-NMR (400 MHz, CD3OD) d 7.80 - 7.78 (m, 2 H), 7.62 - 7.60 (m, 2 H), 7.56 - 7.53 (m, 1 H), 7.42 - 7.38 (m, 1 H), 7.21 - 7.14 (m, 2 H), 3.33 (s, 2 H), 2.30 (s, 2 H), 1.60 - 1.37 (m, 10 H), 0.91 (s, 9 H). Example 29: Synthesis of N-((4-(cyclopropylmethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Step 1-1: Synthesis of 4-(cyclopropylmethyl)tetrahydro-2H-pyran-4-carbonitrile [ka] To a solution of tetrahydro-2H-pyran-4-carbonitrile (3.333 g, 29.989 mmol) in tetrahydrofuran (65 mL) at -78 °C, lithium bis(trimethylsilyl)amide (1.30 M solution in THF, 25.375 mL, 32.988 mmol) was added and stirred at the same temperature for 1 hour. (Bromomethyl)cyclopropane (3.490 mL, 35.987 mmol) was added to the reaction mixture, and the mixture was further stirred at room temperature for 12 hours. A saturated aqueous solution of ammonium chloride was poured into the reaction mixture, and the mixture was extracted with hexane. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give 4-(cyclopropylmethyl)tetrahydro-2H-pyran-4-carbonitrile (4.600 g, 92.8%) as a pale yellow liquid. 1 H-NMR (400 MHz, CDCl3) d 7.55 (d, J = 3.6 Hz, 2 H), 7.33 (bs, 1 H), 7.46 (s, 2 H), 5.52 (d, J = 5.2 Hz, 1 H), 2.08 (s, 3 H), 1.41 (s, 9 H), 1.35 - 1.34 (m, 1 H), 1.34 (d, J = 1.6 Hz, 1 H), 0.88 (m, 1 H), 0.76 (m, 1 H), 0.65 (m, 1 H). Step 1-2: Synthesis of (4-(cyclopropylmethyl)tetrahydro-2H-pyran-4-yl)methanamine hydrochloride [ka] To a solution of 4-(cyclopropylmethyl)tetrahydro-2H-pyran-4-carbonitrile (4.600 g, 27.838 mmol) in tetrahydrofuran (200 mL) at 0° C., lithium aluminum hydride (2.40 M solution in THF, 25.518 mL, 61.244 mmol) was added and stirred at room temperature for 3 hours. Water (3.010 mL, 167.030 mmol) was added to the reaction mixture at room temperature, and the reaction mixture was stirred at room temperature for 30 minutes to complete the reaction. 1H-NMR (400 MHz, CDCl3) d 4.24 - 4.23 (m, 1 H), 3.12, 3.12 (ABq, J = 0.7, 0.4 Hz, 2 H), 3.12 (q, J = 0.4 Hz, 2 H), 1.83 (t, J = 0.4 Hz, 1 H). To a solution of the obtained (4-(cyclopropylmethyl)tetrahydro-2H-pyran-4-yl)methanamine (4.000 g, 23.631 mmol) in methanol (200 mL) at 0 °C, hydrogen chloride (1.00 M solution in ethyl acetate, 47.262 mL, 47.262 mmol) was added, and the reaction mixture was stirred at the same temperature for 10 minutes. After removing the solvent from the reaction mixture under reduced pressure, ethyl acetate (200 mL) was added to the concentrate and stirred. The precipitated solid was filtered and washed with hexane to obtain (4-(cyclopropylmethyl)tetrahydro-2H-pyran-4-yl)methanamine hydrochloride (2.490 g, 51.2%) as a white solid.

[0059] Step 2: Synthesis of N-((4-(cyclopropylmethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.100 g, 0.416 mmol) and (4-(cyclopropylmethyl)tetrahydro-2H-pyran-4-yl)methanamine hydrochloride (0.127 g, 0.624 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give N-((4-(cyclopropylmethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.010 g, 6.1%) as a white solid: LRMS (ES) m / z 392.24 [M+H] + , calculated MW 391.49; 1H-NMR (400 MHz, CD3OD) d 7.82 (d, J = 0.4 Hz, 2 H), 7.61 (d, J = 8.4 Hz, 2 H), 7.55 (td, J = 7.5, 1.5 Hz, 1 H), 7.43 - 7.37 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.77 - 3.75 (m, 2 H), 3.68 - 3.64 (m, 2 H), 1.64 - 1.55 (m, 5 H), 1.41 - 1.39 (m, 3 H), 0.82 - 0.76 (m, 1 H), 0.50 - 0.48 (m, 2 H), 0.09 - 0.05 (m, 2 H). Example 30: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclopentyl)methyl)benzamide [ka] Step 1: Synthesis of 1-(aminomethyl)-N-isopropylcyclopentan-1-amine [ka] Using propan-2-amine (3.504 mL, 42.796 mmol) and cyclopentanone (3.155 mL, 35.663 mmol) as starting materials, 1-(isopropylamino)cyclopentane-1-carbonitrile (2.618 g, 48.2%) was obtained as a white solid in a manner similar to Step 2 of Example 1. 1-(aminomethyl)-N-isopropylcyclopentan-1-amine was subsequently prepared. (2.600 g, 96.8%, white solid): LRMS (ES) m / z 157.07 [M+H] + , calculated MW 156.27. Step 2: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclopentyl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and 1-(aminomethyl)-N-isopropylcyclopentan-1-amine (0.068 g, 0.437 mmol) as starting materials, a similar procedure to Step 3 of Example 1 was carried out to give 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclopentyl)methyl)benzamide (0.018 g, 16.3%) as a white solid: LRMS (ES) m / z 379.30 [M+H]. + , calculated MW 378.49; 1 H-NMR (400 MHz, CD3OD) d 7.85 (dd, J = 8.2, 1.8 Hz, 2 H), 7.62 (dd, J = 8.2, 1.4 Hz, 2 H), 7.55 - 7.53 (m, 1 H), 7.43 - 7.38 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.47 (s, 2 H), 3.08 (m, 1 H), 1.74 - 1.65 (m, 8 H), 1.12 - 1.10 (m, 6 H). Example 31: Synthesis of 4-(pyridin-4-ylethynyl)-N-((1-((2,2,2-trifluoroethyl)amino)cyclohexyl)methyl)benzamide [ka] Step 1: Synthesis of 1-(aminomethyl)-N-(2,2,2-trifluoroethyl)cyclohexan-1-amine [ka] Using cyclohexanone (3.000 g, 30.565 mmol) and 2,2,2-trifluoroethan-1-amine (3.633 g, 36.679 mmol) as starting materials, 1-(aminomethyl)-N-(2,2,2-trifluoroethyl)cyclohexan-1-amine was prepared in a similar manner to Step 2 of Example 1. (3.230 g, 94.3%, white solid): LRMS (ES) m / z 211.12 [M+H] +, calculated MW 210.24. Step 2: Synthesis of 4-(pyridin-4-ylethynyl)-N-((1-((2,2,2-trifluoroethyl)amino)cyclohexyl)methyl)benzamide [ka] Using 4-(pyridin-4-ylethynyl)benzoic acid (0.070 g, 0.314 mmol) and 1-(aminomethyl)-N-(2,2,2-trifluoroethyl)cyclohexan-1-amine (0.099 g, 0.470 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give 4-(pyridin-4-ylethynyl)-N-((1-((2,2,2-trifluoroethyl)amino)cyclohexyl)methyl)benzamide (0.060 g, 46.1%) as a white solid: LRMS (ES) m / z 416.29 [M+H]. + , calculated MW 415.46; 1 H-NMR (400 MHz, CD3OD) d 8.56 - 8.54 (m, 2 H), 7.83 (d, J = 8.4 Hz, 2 H), 7.66 (d, J = 8.4 Hz, 2 H), 7.54 - 7.53 (m, 2 H), 3.36 (s, 2 H), 3.27 - 3.20 (m, 2 H), 1.66 - 1.31 (m, 10 H). Example 32: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-hydroxycyclohexyl)methyl)benzamide [ka] Step 1: Synthesis of 1-(aminomethyl)cyclohexan-1-ol [ka] 1-Hydroxycyclohexane-1-carbonitrile (3.400 g, 88.9%, colorless oil) was obtained in a similar manner to Step 2 of Example 1, except that cyclohexanone (3.000 g, 30.565 mmol) was used instead of cyclopropanamine and cycloheptanone. 1-(aminomethyl)cyclohexan-1-ol was subsequently prepared (2.750 g, 98.7%, colorless oil): LRMS (ES) m / z 129.99 [M+H]+, calculated MW 129.2. Step 2: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-hydroxycyclohexyl)methyl)benzamide [ka] In a similar manner to Example 11, except that 1-(aminomethyl)cyclohexan-1-ol (0.200 g, 1.548 mmol) was used instead of 1-(aminomethyl)-N-cyclopropylcyclopentan-1-amine, 4-((2-fluorophenyl)ethynyl)-N-((1-hydroxycyclohexyl)methyl)benzamide (0.350 g, 64.3%) was obtained as a yellow solid: LRMS (ES) m / z 352.15 [M+H] + , calculated MW 351.42; 1 H-NMR (400 MHz, DMSO-d6) d 8.27 (t, J = 5.6 Hz, 1 H), 7.88 (m, 2 H), 7.65 - 7.61 (m, 3 H), 7.47 (m, 1 H), 7.43 (t, J = 23.4 Hz, 1 H), 7.28 (t, J = 14.8 Hz, 1 H), 4.33 (s, 1 H), 3.24 (d, J = 6.0 Hz, 2 H), 1.53 - 1.15 (m, 10 H). Example 33: Synthesis of 4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (tetrahydro-2H-pyran-4-yl)methanamine (0.050 g, 0.437 mmol) as starting materials, a similar procedure to Step 3 of Example 1 was carried out to give 4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide (0.073 g, 74.3%) as a white solid: LRMS (ES) m / z 338.15 [M+H]. + , calculated MW 337.39; 1 H-NMR (400 MHz, CD3OD) d 7.80 (d, J = 8.4 Hz, 2 H), 7.58 - 7.53 (m, 4 H), 7.12 (t, J = 9.0 Hz, 2 H), 3.93 (dd, J = 11.6, 2.8 Hz, 2 H), 3.39 (td, J = 11.7, 2.0 Hz, 2 H), 3.31 - 3.25 (m, 2 H), 1.94 - 1.83 (m, 1 H), 1.66 (dd, J = 13.4, 1.8 Hz, 2 H), 1.37 - 1.27 (m, 2 H). Example 34: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-(pyridin-3-yl)cyclopentyl)methyl)benzamide [ka] Step 1-1: Synthesis of 1-(pyridin-3-yl)cyclopentane-1-carbonitrile [ka] To a stirred solution of sodium hydride (NaH, 60.00%, 0.745 g, 18.622 mmol) in dimethyl sulfoxide (15 mL) and diethyl ether (5 mL) was added 2-(pyridin-3-yl)acetonitrile (1.000 g, 8.465 mmol) at 0 °C. The reaction mixture was stirred at the same temperature for 0.5 h, treated with 1,4-dibromobutane (1.828 g, 8.465 mmol) at room temperature, and further stirred for 1 h. The reaction mixture was poured into water and extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The concentrate was purified by column chromatography and concentrated to give 1-(pyridin-3-yl)cyclopentane-1-carbonitrile (0.387 g, 26.5%) as a pink liquid. LRMS (ES) m / z 173.00 [M+H] + , calculated MW 172.23. Step 1-2: Synthesis of (1-(pyridin-3-yl)cyclopentyl)methanamine [ka] 1-(Pyridin-3-yl)cyclopentane-1-carbonitrile (0.378 g, 2.195 mmol) and lithium aluminum hydride (2.40 M solution, 1.829 mL, 4.389 mmol) were dissolved in diethyl ether (50 mL). The resulting solution was stirred at 0 °C for 0.5 h and then at room temperature for 18 h. Sodium hydroxide (NaOH) (1.00 M aqueous solution, 1.097 mL, 1.097 mmol) and water (0.237 mL, 13.168 mmol) were then added to the reaction mixture at room temperature and stirred for 30 min to terminate the reaction. Water was poured into the reaction mixture, which was then extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting product was used without further purification ((1-(pyridin-3-yl)cyclopentyl)methanamine, 0.222 g, 57.4%, yellow liquid): LRMS (ES) m / z 177.02 [M+H]+, calculated MW 176.26. Step 2: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-(pyridin-3-yl)cyclopentyl)methyl)benzamide [ka] Using (1-(pyridin-3-yl)cyclopentyl)methanamine (0.050 g, 0.284 mmol) and 4-((2-fluorophenyl)ethynyl)benzoic acid (0.068 g, 0.284 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((1-(pyridin-3-yl)cyclopentyl)methyl)benzamide (0.055 g, 48.7%) was obtained as a yellow solid in the same manner as in Example 11: LRMS (ES) m / z 399.24 [M+H]. + , calculated MW 398.48; 1 H-NMR (400 MHz, DMSO-d6) d 8.48 (d, J = 2.4 Hz, 1 H), 8.32 (m, 2 H), 7.70 (d, J = 8.8 Hz, 2 H), 7.68 - 7.57 (m, 4 H), 7.48 (m, 1 H), 7.38 - 7.25 (m, 3 H), 3.42 (d, J = 6.4 Hz, 2 H), 2.08 (m, 2 H), 2.08 - 1.74 (m, 4 H), 1.61 (m, 2 H). Example 35: Synthesis of 2-fluoro-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Step 1: Synthesis of 2-fluoro-4-((2-fluorophenyl)ethynyl)benzoic acid [ka] Using methyl 4-bromo-2-fluorobenzoate (2.000 g, 8.582 mmol) and 1-ethynyl-2-fluorobenzene (1.031 g, 8.582 mmol) as starting materials, methyl 2-fluoro-4-((2-fluorophenyl)ethynyl)benzoate (2.000 g, 85.6%) was obtained as a white solid in a manner similar to Step 1 of Example 3. Subsequently, 2-fluoro-4-((2-fluorophenyl)ethynyl)benzoic acid (1.850 g, 97.5%) was obtained as a white solid: LRMS (ES) m / z 258.94 [M+H] + , calculated MW 258.22. Step 2: Synthesis of 2-fluoro-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Using 2-fluoro-4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.271 mmol) and (tetrahydro-2H-pyran-4-yl)methanamine (0.046 mL, 0.407 mmol) as starting materials, a similar procedure to Step 3 of Example 1 was carried out to give 2-fluoro-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide (0.077 g, 79.9%) as a white solid: LRMS (ES) m / z 356.11 [M+H]. + , calculated MW 355.38; 1H-NMR (400 MHz, CD3OD) d 7.68 (t, J = 7.6 Hz, 1 H), 7.56 (td, J = 7.6, 1.6 Hz, 1 H), 7.43 - 7.40 (m, 2 H), 7.36 (dd, J = 11.0, 1.4 Hz, 1 H), 7.22 - 7.13 (m, 2 H), 3.94 (dd, J = 11.6, 2.8 Hz, 2 H), 3.40 (td, J = 11.8, 1.9 Hz, 2 H), 3.32 - 3.26 (m, 2 H), 1.93 - 1.82 (m, 1 H), 1.68 (dd, J = 12.8, 2.0 Hz, 2H), 1.38 - 1.28 (m, 2 H). Example 36: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (4-methyltetrahydro-2H-pyran-4-yl)methanamine (0.056 g, 0.437 mmol) as starting materials, a similar procedure to Step 3 of Example 1 was carried out to give 4-((2-fluorophenyl)ethynyl)-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)benzamide (0.045 g, 43.9%) as a white solid: LRMS (ES) m / z 352.22 [M+H]. + , calculated MW 351.42; 1H-NMR (400 MHz, CD3OD) d 7.82 (dt, J = 8.8, 1.9 Hz, 2 H), 7.61 (d, J = 8.8 Hz, 2 H), 7.55 (td, J = 7.5, 1.5 Hz, 1 H), 7.43 - 7.37 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.72 - 3.74 (m, 2 H), 3.67 - 3.61 (m, 2 H), 3.32 (s, 2 H), 1.61 - 1.54 (m, 2 H), 1.37 - 1.33 (m, 2 H), 1.05 (s, 3 H). Example 37: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)benzamide [ka] Step 1: Synthesis of (1-(aminomethyl)cyclohexyl)methanol [ka] Ethyl 2-cyanoacetate (5.377 mL, 50.389 mmol) was dissolved in N,N-dimethylformamide (200 mL), and cesium carbonate (CsCO, 41.044 g, 125.972 mmol) and 1,5-dibromopentane (6.816 mL, 50.389 mmol) were added at 0 °C. The mixture was stirred at the same temperature for 30 minutes and then at room temperature for 12 hours. Water was poured into the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give ethyl 1-cyanocyclohexane-1-carboxylate (7.050 g, 77.2%, colorless liquid). The resulting product was dissolved in tetrahydrofuran (200 mL) at 0 °C, and lithium aluminum hydride (2.40 M solution in THF, 43.681 mL, 104.833 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours. Water (4.534 mL, 251.600 mmol) was then poured into the reaction mixture at room temperature and stirred for 30 minutes to quench the reaction. The reaction mixture was filtered through a Celite pad to remove solids, and the solvent was removed from the filtrate under reduced pressure. The resulting product was used without further purification ((1-(aminomethyl)cyclohexyl)methanol, 5.260 g, 87.6%, colorless liquid).

[0060] Step 2: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.450 g, 1.873 mmol) and (1-(aminomethyl)cyclohexyl)methanol (0.402 g, 2.810 mmol) as starting materials, a similar procedure to Step 3 of Example 1 was carried out to give 4-((2-fluorophenyl)ethynyl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)benzamide (0.461 g, 67.3%) as a white solid: LRMS (ES) m / z 366.32 [M+H]. + , calculated MW 365.45; 1H-NMR (400 MHz, DMSO-d6) d 8.40 (t, J = 6.0 Hz, 1 H), 7.85 (d, J = 8.4 Hz, 2 H), 7.64 - 7.61 (m, 3 H), 7.50 - 7.45 (m, 1 H), 7.35 - 7.23 (m, 2 H), 4.53 (t, J = 6.0 Hz, 1 H), 3.24 - 3.19 (m, 4 H), 1.41 - 1.25 (m, 10 H). Example 38: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Step 1: Synthesis of (4-(aminomethyl)tetrahydro-2H-pyran-4-yl)methanol [ka] Using 1-chloro-2-(2-chloroethoxy)ethane (21.761 mL, 185.644 mmol) instead of 1,5-dibromopentane, (4-(aminomethyl)tetrahydro-2H-pyran-4-yl)methanol was prepared in a similar manner to Step 1 of Example 37 (5.300 g, 95.5%, colorless liquid).

[0061] Step 2: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Using (4-(aminomethyl)tetrahydro-2H-pyran-4-yl)methanol (0.300 g, 2.066 mmol) and 4-((2-fluorophenyl)ethynyl)benzoic acid (0.496 g, 2.066 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)methyl)benzamide (0.450 g, 59.3%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 368.27 [M+H]+, calculated MW 367.42. 1 H-NMR (400 MHz, DMSO-d6) d 8.48 (t, J = 6.2 Hz, 1 H), 7.86 (d, J = 8.0 Hz, 2 H), 7.65 - 7.63 (m, 3 H), 7.48 (m, 1 H), 7.33 (m, 1 H), 7.27 - 7.25 (m, 1 H), 4.61 (t, J = 6.0 Hz, 1 H), 3.58 - 3.48 (m, 4 H), 3.32 - 3.25 (m, 4 H), 1.36 - 1.28 (m, 4 H). Example 39: Synthesis of N-((4,4-difluorocyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.200 g, 0.833 mmol) and (4,4-difluorocyclohexyl)methanamine hydrochloride (0.232 g, 1.249 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give N-((4,4-difluorocyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.175 g, 56.6%) as a white solid: LRMS (ES) m / z 372.23 [M+H]. + , calculated MW 371.4; 1H-NMR (400 MHz, DMSO-d6) d 8.63 (t, J = 6.0 Hz, 1 H), 7.87 (d, J = 8.8 Hz, 2 H), 7.65 - 7.61 (m, 3 H), 7.49 - 7.45 (m, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.25 (td, J = 7.6, 1.2 Hz, 1 H), 3.14 (t, J = 6.4 Hz, 2 H), 2.01 - 1.96 (m, 2 H), 1.81 - 1.66 (m, 5 H), 1.22 - 1.13 (m, 2 H). Example 40: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.200 g, 0.833 mmol) and (tetrahydro-2H-pyran-3-yl)methanamine (0.144 g, 1.249 mmol) as starting materials, a similar procedure to Step 3 of Example 1 was carried out to give 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide (0.157 g, 55.9%) as a white solid: LRMS (ES) m / z 338.21 [M+H]. + , calculated MW 337.39; 1H-NMR (400 MHz, DMSO-d6) d 8.56 (t, J = 5.8 Hz, 1 H), 7.86 (d, J = 8.8 Hz, 2 H), 7.65 - 7.61 (m, 3 H), 7.48 - 7.45 (m, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.24 (td, J = 14.9, 10.1 Hz, 1 H), 3.75 - 3.65 (m, 2 H), 3.28 - 3.23 (m, 1 H), 3.13 - 3.06 (m, 3 H), 1.82 - 1.72 (m, 2 H), 1.57 - 1.52 (m, 1 H), 1.47 - 1.37 (m, 1 H), 1.25 - 1.16 (m, 1 H). Example 41: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and 4-(aminomethyl)tetrahydro-2H-pyran-4-ol hydrochloride (0.073 g, 0.437 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give 4-((2-fluorophenyl)ethynyl)-N-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)benzamide (0.075 g, 72.8%) as a white solid: LRMS (ES) m / z 354.20 [M+H]. + , calculated MW 353.39; 1H-NMR (400 MHz, CD3OD) d 7.86 (d, J = 8.8 Hz, 2 H), 7.61 (d, J = 8.4 Hz, 2 H), 7.57 - 7.53 (m, 1 H), 7.43 - 7.38 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.78 - 3.73 (m, 4 H), 3.43 (s, 2 H), 1.75 - 1.67 (m, 2 H), 1.53 (d, J = 14.0 Hz, 2 H). Example 42: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide [ka] Step 1: Synthesis of (Z)-2-methyl-N-((tetrahydro-2H-pyran-4-yl)methylene)propane-2-sulfinamide [ka] 2-Methylpropane-2-sulfinamide (1.000 g, 8.251 mmol), tetrahydro-2H-pyran-4-carbaldehyde (2.072 g, 18.152 mmol), magnesium sulfate (MgSO4, 5.462 g, 45.380 mmol), and pyridinium p-toluenesulfonate (0.107 g, 0.495 mmol) were dissolved in 1,2-dichloroethane (14 mL) at room temperature. The resulting solution was stirred at the same temperature under visible light (blue LED, 40 W) for 24 hours. Water was poured into the reaction mixture, which was then extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give (Z)-2-methyl-N-((tetrahydro-2H-pyran-4-yl)methylene)propane-2-sulfinamide (0.800 g, 44.6%) as a white solid.

[0062] Step 2: Synthesis of 1-(tetrahydro-2H-pyran-4-yl)ethan-1-amine hydrochloride [ka] (Z)-2-Methyl-N-((tetrahydro-2H-pyran-4-yl)methylene)propane-2-sulfinamide (0.800 g, 3.681 mmol) and methylmagnesium bromide (1.40 M solution in THF / toluene, 5.259 mL, 7.362 mmol) were dissolved in dichloromethane (15 mL), and the resulting solution was stirred at room temperature for 1 hour and then further stirred at the same temperature for 18 hours. Water was poured into the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give 2-methyl-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)propane-2-sulfinamide (0.475 g, 55.3%) as a colorless liquid. The resulting product (0.400 g, 1.714 mmol) and hydrogen chloride (4.00 M solution in 1,4-dioxane, 1.286 mL, 5.142 mmol) were dissolved in methanol (2 mL) at room temperature, and the resulting solution was stirred at the same temperature for 30 minutes. After removing the solvent from the reaction mixture under reduced pressure, ethyl acetate (1 mL) and hexane (10 mL) were added to the concentrate and stirred. The precipitated solid was filtered, washed with hexane, and dried to give 1-(tetrahydro-2H-pyran-4-yl)ethan-1-amine hydrochloride (0.143 g, 50.4%) as a pink solid.

[0063] Step 3: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.051 g, 0.211 mmol) and 1-(tetrahydro-2H-pyran-4-yl)ethan-1-amine hydrochloride (0.035 g, 0.211 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide (0.045 g, 60.6%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 352.13 [M+H]. + , calculated MW 351.42; 1 H-NMR (400 MHz, DMSO-d6) d 8.27 (d, J = 8.4 Hz, 1 H), 7.87 (d, J = 8.4 Hz, 2 H), 7.63 - 7.61 (m, 3 H), 7.46 (m, 1 H), 7.32 (t, J = 15.4 Hz, 1 H), 7.26 (t, J = 4.0 Hz, 1 H), 3.88 - 3.77 (m, 3 H), 3.24 (q, J = 14.0 Hz, 2 H), 1.62 - 1.56 (m, 3 H), 1.22 - 1.15 (m, 2 H), 1.09 (d, J = 6.8Hz, 3H). Example 43: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.150 g, 0.624 mmol) and (tetrahydrofuran-3-yl)methanamine (0.098 mL, 0.937 mmol) as starting materials, a similar procedure to Step 3 of Example 1 was carried out to give 4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide (0.143 g, 70.8%) as a white solid: LRMS (ES) m / z 324.21 [M+H]. + , calculated MW 323.37; 1H-NMR (400 MHz, DMSO-d6) d 8.68 (t, J = 5.6 Hz, 1 H), 7.86 (dd, J = 6.8, 2.0 Hz, 2 H), 7.64 - 7.59 (m, 3 H), 7.50 - 7.44 (m, 1 H), 7.33 (t, J = 8.6 Hz, 1 H), 7.25 (td, J = 7.6, 0.9 Hz, 1 H), 3.71 - 3.54 (m, 3 H), 3.45 - 3.36 (m, 2 H), 3.30 - 3.13 (m, 2 H), 1.93 - 1.87 (m, 1 H), 1.62 - 1.50 (m, 1 H). Example 44: Synthesis of 4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Step 1: Synthesis of 4-((2,4-difluorophenyl)ethynyl)benzoic acid [ka] Methyl 4-((2,4-difluorophenyl)ethynyl)benzoate (0.780 g, 22.9%) was obtained as a white solid in a similar manner to Step 1 of Example 3 using methyl 4-ethynylbenzoate (2.000 g, 12.487 mmol) and 1-bromo-2,4-difluorobenzene (2.410 g, 12.487 mmol). 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.730 g, 98.7%) was subsequently obtained as a white solid: LRMS (ES) m / z 256.98 (M-1) [M+H]. + , calculated MW 258.22. Step 2: Synthesis of 4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Using 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.150 g, 0.581 mmol) and (tetrahydro-2H-pyran-4-yl)methanamine (0.074 g, 0.639 mmol), a similar procedure to that described in Example 11 was carried out to give 4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide (0.156 g, 75.6%) as a white solid: LRMS (ES) m / z 356.42 [M+H]. + , calculated MW 355.38; 1 H-NMR (400 MHz, DMSO-d6) d 8.58 (t, J = 5.6 Hz, 1 H), 7.86 (d, J = 8.4 Hz, 2 H), 7.70 (q, J = 7.9 Hz, 1 H), 7.61 (d, J = 8.0 Hz, 2 H), 7.42 (td, J = 9.6, 2.8 Hz, 1 H), 7.17 (td, J = 7.8, 2.5 Hz, 1 H), 3.80 (dd, J = 11.2, 2.4 Hz, 2 H), 3.22 (t, J = 11.8 Hz, 2 H), 3.12 (t, J = 6.2 Hz, 2 H), 1.78 - 1.73 (m, 1 H), 1.55 (d, J = 12.8 Hz, 2 H), 1.20 - 1.10 (m, 2 H). Example 45: Synthesis of (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide [ka] Using (R)-(tetrahydrofuran-2-yl)methanamine (0.030 g, 0.297 mmol) and 4-((2-fluorophenyl)ethynyl)benzoic acid (0.071 g, 0.297 mmol) as starting materials, (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide (0.065 g, 67.8%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 324.33 [M+H]. +, calculated MW 323.37; 1 H-NMR (400 MHz, DMSO-d6) d 8.64 (t, J = 6.0 Hz, 1 H), 7.88 (d, J = 8.8 Hz, 2 H), 7.63 (m, 3 H), 7.46 (m, 1 H), 7.33 (m, 1 H), 7.25 (td, J = 7.6, 0.8 Hz, 1 H), 3.97 - 3.91 (m, 1 H), 3.73 (m, 1 H), 3.60 (m, 1 H), 3.28 (m, 2 H), 1.92 - 1.72 (m, 3 H), 1.59 - 1.52 (m, 1 H). Example 46: Synthesis of (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.150 g, 0.624 mmol) and (S)-(tetrahydrofuran-2-yl)methanamine (0.095 g, 0.937 mmol) as starting materials, (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide (0.162 g, 80.2%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 324.54 [M+H]. + , calculated MW 323.37; 1H-NMR (400 MHz, DMSO-d6) d 8.65 (t, J = 5.8 Hz, 1 H), 7.87 (dd, J = 6.4, 1.6 Hz, 2 H), 7.65 - 7.61 (m, 3 H), 7.50 - 7.44 (m, 1 H), 7.33 (t, J = 9.6 Hz, 1 H), 7.25 (td, J = 7.6, 1.2 Hz, 1 H), 3.94 - 3.91 (m, 1 H), 3.76 - 3.71 (m, 1 H), 3.63 - 3.56 (m, 1 H), 3.28 - 3.24 (m, 2 H), 1.90 - 1.85 (m, 1 H), 1.83 - 1.68 (m, 2 H), 1.60 - 1.50 (m, 1 H). Example 47: Synthesis of (R)-4-((2-fluorophenyl)ethynyl)-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide [ka] Step 1: Synthesis of (S,E)-2-methyl-N-((tetrahydro-2H-pyran-4-yl)methylene)propane-2-sulfinamide [ka] Tetrahydro-2H-pyran-4-carbaldehyde (1.000 g, 8.761 mmol), pyridinium p-toluenesulfonate (0.047 g, 0.219 mmol), and magnesium sulfate (MgSO4, 2.636 g, 21.903 mmol) were dissolved in 1,2-dichloroethane (16 mL). The resulting solution was stirred at room temperature for 0.5 hours, after which (S)-2-methylpropane-2-sulfinamide (0.531 g, 4.381 mmol) was added and stirred at the same temperature for an additional 18 hours. Saturated aqueous sodium bicarbonate was poured into the reaction mixture, which was then extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give (S,E)-2-methyl-N-((tetrahydro-2H-pyran-4-yl)methylene)propane-2-sulfinamide (0.470 g, 24.7%) as a white solid: LRMS (ES) m / z 218.05 [M+H] + , calculated MW 217.33. Step 2: Synthesis of (R)-1-(tetrahydro-2H-pyran-4-yl)ethan-1-amine hydrochloride [ka] (S,E)-2-Methyl-N-((tetrahydro-2H-pyran-4-yl)methylene)propane-2-sulfinamide (0.470 g, 2.163 mmol) was used in a similar manner to Step 2 of Example 42 to give (R)-1-(tetrahydro-2H-pyran-4-yl)ethan-1-amine hydrochloride (0.310 g, 99.3%) as a yellow solid: LRMS (ES) m / z 129.97 [M+H] + , calculated MW 165.66. Step 3: Synthesis of (R)-4-((2-fluorophenyl)ethynyl)-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide [ka] Using (R)-1-(tetrahydro-2H-pyran-4-yl)ethan-1-amine hydrochloride (0.050 g, 0.302 mmol) and 4-((2-fluorophenyl)ethynyl)benzoic acid (0.073 g, 0.302 mmol) as starting materials, (R)-4-((2-fluorophenyl)ethynyl)-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide (0.075 g, 70.7%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 352.20 [M+H]. + , calculated MW 351.42; 1 H-NMR (400 MHz, DMSO-d6) d 8.27 (d, J = 8.8 Hz, 1 H), 7.87 (d, J = 8.4 Hz, 2 H), 7.65 - 7.61 (m, 3 H), 7.48 - 7.46 (m, 1 H), 7.33 (m, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 3.85 - 3.79 (m, 3 H), 3.20 (q, J = 11.9 Hz, 2 H), 1.68 - 1.52 (m, 3 H), 1.25 - 1.13 (m, 2 H), 1.09 (d, J = 6.4 Hz, 3H). Example 48: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((4-fluorotetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Diethylaminosulfur trifluoride (DAST, 0.068 mL, 0.514 mmol) was added to a solution of 4-((2-fluorophenyl)ethynyl)-N-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)benzamide (0.165 g, 0.467 mmol) obtained in Example 41 in dichloromethane (10 mL) at 0°C, and the mixture was stirred at room temperature for 0.5 hours. A saturated aqueous solution of sodium bicarbonate was poured into the reaction mixture, which was then extracted with dichloromethane. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified twice by column chromatography and concentrated to give 4-((2-fluorophenyl)ethynyl)-N-((4-fluorotetrahydro-2H-pyran-4-yl)methyl)benzamide (0.025 g, 15.1%) as a white solid: LRMS (ES) m / z 356.12 [M+H] + , calculated MW 355.38; 1 H-NMR (400 MHz, DMSO-d6) d 8.74 (t, J = 6.2 Hz, 1 H), 7.90 (d, J = 8.4 Hz, 2 H), 7.64 - 7.62 (m, 3 H), 7.45 (m, 1 H), 7.33 (m, 1 H), 7.26 (t, J = 4.4 Hz, 1 H), 3.71 - 3.67 (m, 2 H), 3.54 - 3.48 (m, 4 H), 1.80 - 1.60 (m, 4 H). Example 49: Synthesis of 4-(phenylethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Step 1: Synthesis of 4-(phenylethynyl)benzoic acid [ka] Methyl 4-ethynylbenzoate (0.500 g, 3.122 mmol) and iodobenzene (0.764 g, 3.746 mmol) were used as starting materials in a similar manner to Step 1 of Example 3 to give methyl 4-(phenylethynyl)benzoate (0.544 g, 73.8%) as a clear liquid, followed by 4-(phenylethynyl)benzoic acid (0.477 g, 93.2%) as a white solid: LRMS (ES) m / z 221.25 [M−H]. + , calculated MW 222.24. Step 2: Synthesis of 4-(phenylethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Using 4-(phenylethynyl)benzoic acid (0.070 g, 0.315 mmol) and (tetrahydro-2H-pyran-4-yl)methanamine (0.054 g, 0.472 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give 4-(phenylethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide (0.065 g, 64.6%) as a white solid: LRMS (ES) m / z 320.27 [M+H]. + , calculated MW 319.4; 1 H-NMR (400 MHz, CD3OD) d 7.81 (dd, J = 6.8, 2.0 Hz, 2 H), 7.59 - 7.56 (m, 2 H), 7.56 - 7.50 (m, 2 H), 7.38 - 7.35 (m, 3 H), 3.93 (dd, J = 11.6, 3.2 Hz, 2 H), 3.39 (td, J = 11.7, 2.1 Hz, 2 H), 3.25 (s, 2 H), 1.92 - 1.84 (m, 1 H), 1.67 (dd, J = 13.2, 1.6 Hz, 2 H), 1.37 - 1.27 (m, 2 H). Example 50: Synthesis of N-((4-(fluoromethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Step 1: Synthesis of tert-butyl ((4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)methyl)carbamate [ka] 2.520 g (17.355 mmol) of (4-(aminomethyl)tetrahydro-2H-pyran-4-yl)methanol obtained in Step 1 of Example 38 and di-tert-butyl dicarbonate (3.987 mL, 17.355 mmol) were dissolved in dichloromethane (150 mL) at room temperature, and the resulting solution was stirred at the same temperature for 24 hours. Water was poured into the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give tert-butyl ((4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)methyl)carbamate (2.606 g, 61.2%) as a white solid.

[0064] Step 2: Synthesis of (4-(fluoromethyl)tetrahydro-2H-pyran-4-yl)methanamine hydrochloride [ka] tert-Butyl ((4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)methyl)carbamate (0.300 g, 1.223 mmol), PyFluor (0.217 g, 1.345 mmol), and 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (DBU, 0.366 mL, 2.446 mmol) were dissolved in toluene (3 mL) at 60 °C. The resulting solution was stirred at the same temperature for 48 hours and then cooled to room temperature to terminate the reaction. Water was poured into the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give tert-butyl ((4-(fluoromethyl)tetrahydro-2H-pyran-4-yl)methyl)carbamate (0.140 g, 46.3%) as a white solid: 1 H-NMR (400 MHz, CDCl3) d 4.24 - 4.23 (m, 1 H), 3.12, 3.12 (ABq, J = 0.7, 0.4 Hz, 2 H), 3.12 (q, J = 0.4 Hz, 2 H), 1.83 (t, J = 0.4 Hz, 1 H). The resulting product (0.070 g, 0.283 mmol) was dissolved in hydrogen chloride (4.00 M solution in 1,4-dioxane, 0.212 mL, 0.849 mmol) and dichloromethane (2 mL) at room temperature, and the solution was stirred at the same temperature for 18 hours. After removing the solvent from the reaction mixture under reduced pressure, the resulting product was used without further purification ((4-(fluoromethyl)tetrahydro-2H-pyran-4-yl)methanamine hydrochloride, 0.051 g, 98.1%, white solid): LRMS (ES) m / z 148.18 [M+H]. + , calculated MW 147.19. Step 3: Synthesis of N-((4-(fluoromethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.050 g, 0.208 mmol) and (4-(fluoromethyl)tetrahydro-2H-pyran-4-yl)methanamine hydrochloride (0.057 g, 0.312 mmol) as starting materials, a procedure similar to that of Step 3 of Example 1 was carried out to give N-((4-(fluoromethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.032 g, 41.6%) as a white solid: LRMS (ES) m / z 370.12 [M+H]. + , calculated MW 369.41; 1 H-NMR (400 MHz, CD3OD) d 7.82 (dt, J = 8.4, 1.8 Hz, 2 H), 7.60 (dt, J = 6.8, 2.1 Hz, 2 H), 7.55 (td, J = 7.6, 1.6 Hz, 1 H), 7.43 - 7.37 (m, 1 H), 7.21 - 7.15 (m, 2 H), 4.45 - 4.31 (m, 2 H), 3.81 - 3.76 (m, 2 H), 3.72 - 3.67 (m, 2 H), 3.55 (s, 2 H), 1.61 - 1.48 (m, 4 H). Example 51: Synthesis of N-((1,4-dioxan-2-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.100 g, 0.416 mmol) and (1,4-dioxan-2-yl)methanamine (0.054 g, 0.458 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give N-((1,4-dioxan-2-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.120 g, 84.9%) as a white solid: LRMS (ES) m / z 340.33 [M+H]. + , calculated MW 339.37; 1H-NMR (400 MHz, DMSO-d6) d 8.66 - 8.64 (m, 1 H), 7.87 (d, J = 8.4 Hz, 2 H), 7.64 - 7.61 (m, 3 H), 7.50 - 7.45 (m, 1 H), 7.33 (t, J = 9.0 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 3.72 - 3.39 (m, 6 H), 3.29 - 3.17 (m, 3 H). Example 52: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (3-methyloxetan-3-yl)methanamine (0.044 g, 0.437 mmol) as starting materials, a similar procedure to Step 3 of Example 1 was carried out to give 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide (0.052 g, 55.2%) as a white solid: LRMS (ES) m / z 324.33 [M+H]. + , calculated MW 323.37; 1 H-NMR (400 MHz, DMSO-d6) d 8.71 (t, J = 6.0 Hz, 1 H), 7.88 (dd, J = 6.4, 2.0 Hz, 2 H), 7.66 - 7.61 (m, 3 H), 7.50 - 7.45 (m, 1 H), 7.33 (td, J = 9.1, 1.1 Hz, 1 H), 7.25 (td, J = 7.6, 1.1 Hz, 1 H), 4.44 (d, J = 5.2 Hz, 2 H), 4.17 (d, J = 5.2 Hz, 2 H), 3.44 (d, J = 6.0 Hz, 2 H), 1.22 (s, 3 H). Example 53: Synthesis of 4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)-N-methyltetrahydro-2H-pyran-4-carboxamide [ka] Step 1: Synthesis of ethyl 4-(aminomethyl)tetrahydro-2H-pyran-4-carboxylate [ka] Ethyl 4-cyanotetrahydro-2H-pyran-4-carboxylate (2.000 g, 10.916 mmol) and cobalt chloride (CoCl, 2.835 g, 21.833 mmol) were dissolved in ethanol (10 mL). The resulting solution was stirred at room temperature for 1 hour, and then sodium borohydride (4.130 g, 109.164 mmol) was added and stirred at the same temperature for an additional 18 hours. Water (0.197 mL, 10.916 mmol) was then poured into the reaction mixture at room temperature and stirred for 30 minutes to terminate the reaction. The reaction mixture was filtered through a Celite pad to remove solids, and the solvent was removed from the filtrate under reduced pressure. The resulting product was used without further purification (ethyl 4-(aminomethyl)tetrahydro-2H-pyran-4-carboxylate, 1.500 g, 73.4%, colorless oil): LRMS (ES) m / z 188.09 [M+H]. + , calculated MW 187.24. Step 2: Synthesis of ethyl 4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-carboxylate [ka] Using ethyl 4-(aminomethyl)tetrahydro-2H-pyran-4-carboxylate (0.450 g, 2.403 mmol) and 4-((2-fluorophenyl)ethynyl)benzoic acid (0.577 g, 2.403 mmol) as starting materials, a procedure similar to that of Example 11 was carried out to give ethyl 4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-carboxylate (0.680 g, 69.1%) as a white solid: LRMS (ES) m / z 410.38 [M+H] +, calculated MW 409.46. Step 3: Synthesis of 4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)-N-methyltetrahydro-2H-pyran-4-carboxamide [ka] Ethyl 4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-carboxylate (0.400 g, 0.977 mmol) and lithium hydroxide monohydrate (0.082 g, 1.954 mmol) were dissolved in methanol (5 mL) / tetrahydrofuran (5 mL) / water (5 mL) at room temperature, and the resulting solution was stirred at the same temperature for 16 hours. The solvent was removed from the reaction mixture under reduced pressure, and then 2N aqueous hydrochloric acid was added to the concentrate and stirred. The precipitated solid was filtered, washed with water, and dried to give 4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-carboxylic acid as a white solid: (0.360 g, 96.6%, LRMS (ES) m / z 382.31 [M+H] + , calculated MW 381.4). 0.040 g (0.105 mmol) of the resulting product was dissolved in N,N-dimethylformamide (2 mL) with methanamine hydrochloride (0.007 g, 0.105 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU, 0.052 g, 0.136 mmol), and N,N-diisopropylethylamine (0.091 mL, 0.524 mmol) at room temperature. The resulting solution was stirred at the same temperature for 16 hours. The solvent was removed from the reaction mixture under reduced pressure, and the resulting concentrate was poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give 4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)-N-methyltetrahydro-2H-pyran-4-carboxamide (0.035 g, 84.6%) as a white solid: LRMS (ES) m / z 395.40 [M+H] + , calculated MW 394.45; 1 H-NMR (400 MHz, DMSO-d6) d 8.37 (t, J = 6.2 Hz, 1 H), 7.82 (d, J = 8.4 Hz, 2 H), 7.77 - 7.61 (m, 4 H), 7.48 (m, 1 H), 7.35 (m, 1 H), 7.28 (t, J = 10.2 Hz, 1 H), 3.66 (d, J = 11.2 Hz, 2 H), 3.35 (m, 4 H), 2.58 (m, 3 H), 1.95 - 1.92 (m, 2 H), 1.49 - 1.45 (m, 2 H). Example 54: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.100 g, 0.416 mmol) and (tetrahydro-2H-pyran-2-yl)methanamine (0.058 g, 0.500 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide (0.120 g, 85.4%) was obtained as an ivory solid in the same manner as in Example 11: LRMS (ES) m / z 338.13 [M+H]. + , calculated MW 337.39; 1 H-NMR (400 MHz, DMSO-d6) d 8.62 (t, J = 5.8 Hz, 1 H), 7.89 - 7.87 (m, 2 H), 7.65 - 7.61 (m, 3 H), 7.48 - 7.64 (m, 1 H), 7.35 - 7.31 (m, 1 H), 7.27 - 7.23 (m, 1 H), 3.83 (dd, J = 10.4, 2.4 Hz, 1 H), 3.37 - 3.32 (m, 1 H), 3.25 - 3.24 (m, 1 H), 3.23 - 3.21 (m, 2 H), 1.73 (d, J = 3.2 Hz, 1 H), 1.57 (d, J = 13.2 Hz, 1 H), 1.45 - 1.34 (m, 3 H), 1.17 - 1.06 (m, 1 H). Example 55: Synthesis of N-((1-(isopropylamino)cyclohexyl)methyl)-4-(phenylethynyl)benzamide [ka] Using 4-(phenylethynyl)benzoic acid (0.100 g, 0.450 mmol) and 1-(aminomethyl)-N-isopropylcyclohexan-1-amine (0.084 g, 0.495 mmol) as starting materials, N-((1-(isopropylamino)cyclohexyl)methyl)-4-(phenylethynyl)benzamide (0.102 g, 60.5%) was obtained as an ivory solid in the same manner as in Example 11: LRMS (ES) m / z 375.17 [M+H]. +, calculated MW 374.53; 1 H-NMR (400 MHz, CD3OD) d 7.84 (d, J = 7.6 Hz, 2 H), 7.62 (d, J = 8.4 Hz, 2 H), 7.59 - 7.51 (m, 2 H), 7.42 (s, 3 H), 3.40 (s, 2 H), 3.11 - 3.03 (m, 1 H), 1.58 - 1.36 (m, 10 H), 1.08 - 1.05 (m, 6 H). Example 56: Synthesis of N-((3,3-difluorocyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (3,3-difluorocyclobutyl)methanamine hydrochloride (0.069 g, 0.437 mmol) as starting materials, N-((3,3-difluorocyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.075 g, 75.0%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 344.22 [M+H]. + , calculated MW 343.35; 1 H-NMR (400 MHz, DMSO-d6) d 8.72 (t, J = 5.6 Hz, 1 H), 7.86 (d, J = 7.6 Hz, 2 H), 7.64 - 7.61 (m, 3 H), 7.47 (q, J = 6.4 Hz, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 2.63 - 2.55 (m, 3 H), 2.38 - 2.29 (m, 4 H). Example 57: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-hydroxycyclobutyl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and 1-(aminomethyl)cyclobutan-1-ol (0.044 g, 0.437 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((1-hydroxycyclobutyl)methyl)benzamide (0.063 g, 66.9%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 324.21 [M+H]. + , calculated MW 323.37; 1 H-NMR (400 MHz, DMSO-d6) d 8.42 (t, J = 6.8 Hz, 1 H), 7.90 (d, J = 8.4 Hz, 2 H), 7.64 - 7.62 (m, 3 H), 7.47 (q, J = 6.4 Hz, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 5.15 (s, 1 H), 3.39 (d, J = 5.6 Hz, 2 H), 2.03 - 1.98 (m, 2 H), 1.91 - 1.84 (m, 2 H), 1.63 - 1.58 (m, 1 H), 1.49 - 1.38 (m, 1 H). Example 58: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-(oxetan-2-ylmethyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and oxetan-2-ylmethanamine (0.038 g, 0.437 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-(oxetan-2-ylmethyl)benzamide (0.065 g, 72.1%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 310.19 [M+H]. + , calculated MW 309.34; 1H-NMR (400 MHz, DMSO-d6) d 8.74 (t, J = 5.4 Hz, 1 H), 7.89 (d, J = 8.0 Hz, 2 H), 7.64 - 7.62 (m, 3 H), 7.47 (q, J = 6.4 Hz, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 4.78 (q, J = 6.3 Hz, 1 H), 4.49 - 4.36 (m, 2 H), 3.57 - 3.38 (m, 2 H), 2.65 - 2.55 (m, 2 H). Example 59: Synthesis of methyl 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoate [ka] Step 1: Synthesis of methyl 3-(1-(aminomethyl)cyclohexyl)propanoate hydrochloride [ka] 1-(((tert-Butoxycarbonyl)amino)methyl)cyclohexane-1-carboxylic acid (0.250 g, 0.972 mmol), benzyl acrylate (0.149 mL, 0.972 mmol), [Ir{dF(CF3)ppy}2(dtbpy)]PF6 (0.011 g, 0.010 mmol), and potassium hydrogen phosphate (K2HPO4, 0.203 g, 1.166 mmol) were dissolved in N,N-dimethylacetamide (4 mL) at room temperature. The resulting solution was stirred at the same temperature under visible light (blue LED, 40 W) for 24 hours. Water was poured into the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give benzyl 3-(1-(((tert-butoxycarbonyl)amino)methyl)cyclohexyl)propanoate as a colorless liquid (0.268 g, 73.5%, LRMS (ES) m / z No detection [M+H] +, calculated MW 375.51) A solution of the obtained product and hydrochloric acid (0.129 g, 3.529 mmol) in methanol (10 mL) at room temperature was stirred at the same temperature for 1 hour. After removing the solvent from the reaction mixture under reduced pressure, ethyl acetate (20 mL) and hexane (10 mL) were added to the concentrate and stirred. The precipitated solid was filtered, washed with hexane, and dried to obtain methyl 3-(1-(aminomethyl)cyclohexyl)propanoate hydrochloride (0.145 g, 87.2%) as a colorless liquid.

[0065] Step 2: Synthesis of methyl 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoate [ka] Methyl 3-(1-(aminomethyl)cyclohexyl)propanoate hydrochloride (0.150 g, 0.636 mmol) and 4-((2-fluorophenyl)ethynyl)benzoic acid (0.153 g, 0.636 mmol) were used as starting materials in a similar manner to that in Example 11 to give methyl 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoate (0.211 g, 78.7%) as a white solid: LRMS (ES) m / z 422.36 [M+H] + , calculated MW 421.51; 1 H-NMR (400 MHz, CD3OD) d 7.80 (d, J = 8.4 Hz, 2 H), 7.61 - 7.53 (m, 3 H), 7.41 (m, 1 H), 7.20 - 7.15 (m, 2 H), 3.64 (s, 3 H), 2.40 (t, J = 5.2 Hz, 2 H), 1.65 (t, J = 7.4 Hz, 2 H), 1.55 - 1.47 (m, 2 H), 1.44 - 1.26 (m, 10 H). Example 60: Synthesis of 3-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)propanoic acid [ka] Step 1: Synthesis of methyl 3-(4-(aminomethyl)tetrahydro-2H-pyran-4-yl)propanoate hydrochloride [ka] Using 4-(((tert-butoxycarbonyl)amino)methyl)tetrahydro-2H-pyran-4-carboxylic acid (0.130 g, 0.501 mmol) as the starting material, benzyl 3-(4-(((tert-butoxycarbonyl)amino)methyl)tetrahydro-2H-pyran-4-yl)propanoate (0.165 g, 87.2%) was obtained as a pale yellow liquid in a similar manner to Step 1 of Example 59. Subsequently, methyl 3-(4-(aminomethyl)tetrahydro-2H-pyran-4-yl)propanoate hydrochloride (0.094 g, 90.5%) was obtained as a colorless liquid.

[0066] Step 2: Synthesis of methyl 3-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)propanoate [ka] Methyl 3-(4-(aminomethyl)tetrahydro-2H-pyran-4-yl)propanoate hydrochloride (0.100 g, 0.421 mmol) and 4-((2-fluorophenyl)ethynyl)benzoic acid (0.101 g, 0.421 mmol) were used as starting materials in the same manner as in Example 11 to give methyl 3-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)propanoate (0.084 g, 47.2%) as a white solid: LRMS (ES) m / z 424.34 [M+H] + , calculated MW 423.48. Step 3: Synthesis of 3-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)propanoic acid [ka] Methyl 3-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)propanoate (0.080 g, 0.189 mmol) and sodium hydroxide (NaOH, 5.00 M solution, 0.189 mL, 0.945 mmol) were dissolved in methanol (1 mL) / tetrahydrofuran (1 mL) at room temperature, and the resulting solution was stirred at the same temperature for 3 hours. Next, hydrochloric acid (0.069 g, 1.889 mmol) was added to the reaction mixture at room temperature and stirred for 3 minutes to terminate the reaction. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give 3-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)propanoic acid. (0.074g, 95.7%, white solid):LRMS (ES) m / z 408.16 [MH] + , calculated MW 409.46; 1 H-NMR (400 MHz, CD3OD) d 7.84 - 7.81 (m, 2 H), 7.61 (dd, J = 8.6, 1.8 Hz, 2 H), 7.57 - 7.53 (m, 1 H), 7.43 - 7.38 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.77 - 3.75 (m, 2 H), 3.70 - 3.68 (m, 2 H), 3.47 - 3.68 (m, 2 H), 2.42 (t, J = 7.8 Hz, 2 H), 1.74 (t, J = 7.8 Hz, 2 H), 1.51 - 1.50 (m, 2 H), 1.47 - 1.45 (m, 2 H). Example 61: Synthesis of 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoic acid [ka] Using methyl 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoate (Example 59, 0.120 g, 0.285 mmol) as the starting material, 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoic acid was obtained in a similar manner to Step 3 of Example 60. (0.094 g, 81.0%, white solid): LRMS (ES) m / z 406.18 [MH] + , calculated MW 407.49; 1 H-NMR (400 MHz, CD3OD) d 7.81 (dt, J = 8.4, 1.9 Hz, 2 H), 7.61 - 7.59 (m, 2 H), 7.56 - 7.55 (m, 1 H), 7.41 - 7.39 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.30 - 3.29 (m, 2 H), 2.39 - 2.35 (m, 2 H), 1.66 (t, J = 8.0 Hz, 2 H), 1.56 - 1.31 (m, 10 H). Example 62: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-(3-hydroxypropyl)cyclohexyl)methyl)benzamide [ka] 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoic acid (0.050 g, 0.123 mmol) obtained in Example 61 and 4-methylmorpholine (0.015 mL, 0.135 mmol) were dissolved in tetrahydrofuran (2 mL) at 0° C., and isopropyl carbonochloridate (0.016 mL, 0.135 mmol) was added to the resulting solution, followed by stirring for 1 hour. Sodium borohydride (0.009 g, 0.245 mmol) was added to the reaction mixture, followed by stirring at the same temperature for 1 hour. Water was poured into the reaction mixture, which was then extracted with dichloromethane. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give 4-((2-fluorophenyl)ethynyl)-N-((1-(3-hydroxypropyl)cyclohexyl)methyl)benzamide (0.037 g, 76.6%) as a white solid: LRMS (ES) m / z 394.35 [M+H] + , calculated MW 393.5; 1 H-NMR (400 MHz, CD3OD) d 7.80 (dd, J = 6.8, 2.0 Hz, 2 H), 7.60 (dd, J = 6.8, 2.0 Hz, 2 H), 7.56 - 7.55 (m, 1 H), 7.41 - 7.39 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.54 (t, J = 6.2 Hz, 2 H), 1.56 - 1.47 (m, 8 H), 1.47 - 1.34 (m, 8 H). Example 63: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((2-hydroxycyclohexyl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and 2-(aminomethyl)cyclohexan-1-ol (0.056 g, 0.437 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((2-hydroxycyclohexyl)methyl)benzamide (0.060 g, 58.6%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 352.28 [M+H]. + , calculated MW 351.42; 1 H-NMR (400 MHz, DMSO-d6) d 8.50 - 8.46 (m, 1 H), 7.86 (d, J = 8.0 Hz, 2 H), 7.62 (d, J = 8.0 Hz, 3 H), 7.47 (q, J = 6.4 Hz, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 4.52 (m, 1 H), 3.47 - 3.44 (m, 1 H), 3.26 - 3.08 (m, 2 H), 1.80 - 1.53 (m, 4 H), 1.39 - 1.31 (m, 2 H), 1.14 - 0.86 (m, 3 H). Example 64: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxycyclohexyl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and 3-(aminomethyl)cyclohexan-1-ol (0.056 g, 0.437 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxycyclohexyl)methyl)benzamide (0.085 g, 83.0%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 352.22 [M+H]. + , calculated MW 351.42; 1H-NMR (400 MHz, DMSO-d6) d 8.55 - 8.54 (m, 1 H), 7.86 (d, J = 8.4 Hz, 2 H), 7.62 (d, J = 7.6 Hz, 3 H), 7.47 (q, J = 6.3 Hz, 1 H), 7.33 (t, J = 9.0 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 4.48 (s, 1 H), 3.12 - 3.06 (m, 2 H), 2.65 - 2.65 (m, 4 H), 1.86 - 1.75 (m, 1 H), 1.66 - 1.57 (m, 2 H), 1.19 - 1.10 (m, 1 H), 1.03 - 0.94 (m, 1 H), 0.81 - 0.72 (m, 1 H). Example 65: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-methoxycyclohexyl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (1-methoxycyclohexyl)methanamine hydrochloride (0.052 g, 0.291 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((1-methoxycyclohexyl)methyl)benzamide was obtained in the same manner as in Example 11. (0.085 g, 79.8%, pale yellow oil): LRMS (ES) m / z 366.29 [M+H] + , calculated MW 365.45; 1 H-NMR (400 MHz, CDCl3) d 7.77 (m, 2 H), 7.61 (m, 2 H), 7.58 - 7.50 (m, 1 H), 7.34 (m, 1 H), 7.15 - 7.11 (m, 2 H), 6.34 (s, 1 H), 3.50 (d, J = 4.8 Hz, 2 H), 3.26 (s, 3 H), 1.77 (m, 2 H), 1.63 - 1.26 (m, 8 H). Example 66: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((4-methoxytetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (4-methoxytetrahydro-2H-pyran-4-yl)methanamine (0.042 g, 0.291 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((4-methoxytetrahydro-2H-pyran-4-yl)methyl)benzamide (0.080 g, 74.7%) was obtained as a pale yellow oil in the same manner as in Example 11: LRMS (ES) m / z 368.20 [M+H]. + , calculated MW 367.42; 1 H-NMR (400 MHz, CDCl3) d 7.76 (d, J = 8.0 Hz, 2 H), 7.61 (d, J = 7.6 Hz, 2 H), 7.52 (m, 1 H), 7.35 - 7.33 (m, 1 H), 7.16 - 7.11 (m, 2 H), 6.32 (bs, 1 H), 3.73 (m, 4 H), 3.57 (d, J = 4.8 Hz, 2 H), 3.26 (s, 3 H), 1.82 - 1.67 (m, 4 H). Example 67: Synthesis of N-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Step 1: Synthesis of (2,2-dimethyltetrahydro-2H-pyran-4-yl)methanamine [ka] Using 2,2-dimethyltetrahydro-2H-pyran-4-carbonitrile (1.000 g, 7.184 mmol) as the starting material, (2,2-dimethyltetrahydro-2H-pyran-4-yl)methanamine was obtained in the same manner as in Step 1-2 of Example 34 (0.470 g, 45.7%, yellow oil): LRMS (ES) m / z 144.07 [M+H] + , calculated MW 143.23. Step 2: Synthesis of N-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (2,2-dimethyltetrahydro-2H-pyran-4-yl)methanamine (0.042 g, 0.291 mmol) as starting materials, a procedure similar to that of Example 11 was carried out to give N-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.035 g, 32.9%) in the form of a pale yellow oil: LRMS (ES) m / z 366.29 [M+H] + , calculated MW 365.45; 1 H-NMR (400 MHz, CDCl3) d 7.76 (m, 2 H), 7.62 (m, 2 H), 7.54 - 7.50 (m, 1 H), 7.35 - 7.30 (m, 1 H), 7.18 - 7.11 (m, 2 H), 6.23 (bs, 1 H), 3.79 - 3.75 (m, 1 H), 3.68 - 3.61 (m, 1 H), 3.38 - 3.29 (m, 2 H), 2.07 - 2.03 (m, 1 H), 1.66 - 1.55 (m, 2 H), 1.29 - 1.16 (m, 8 H). Example 68: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl-d2)benzamide [ka] Step 1: Synthesis of tetrahydro-2H-pyran-4-yl)methan-d2-amine [ka] Tetrahydro-2H-pyran-4-carbonitrile (1.000 g, 8.998 mmol) was dissolved in diethyl ether (12 mL) at 0 °C. Lithium aluminum deuteride (2.40 M solution, 7.498 mL, 17.995 mmol) was added to the resulting solution and stirred at room temperature for 18 hours. Sodium hydroxide (NaOH, 1.00 M solution, 4.499 mL, 4.499 mmol) and water (0.973 mL, 53.986 mmol) were then added to the reaction mixture at 0 °C and stirred for 30 minutes to quench the reaction. The reaction mixture was filtered through a Celite pad to remove solids. The solvent was removed from the filtrate under reduced pressure, and the resulting product was used without further purification ((tetrahydro-2H-pyran-4-yl)methan-d2-amine, 0.370 g, 35.1%, yellow oil): LRMS (ES) m / z 118.10 [M+H]. + , calculated MW 117.19. Step 2: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl-d2)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.720 g, 2.997 mmol) and (tetrahydro-2H-pyran-4-yl)methan-d-amine (0.351 g, 2.997 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl-d)benzamide (0.210 g, 20.6%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 340.33 [M+H]. + , calculated MW 339.41; 1H-NMR (400 MHz, DMSO-d6) d 8.57 (s, 1 H), 7.86 (d, J = 8.4 Hz, 2 H), 7.63 (m, 3 H), 7.48 - 7.46 (m, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 3.82 - 3.79 (m, 2 H), 3.22 (t, J = 11.8 Hz, 2 H), 1.80 - 1.74 (m, 1 H), 1.57 - 1.54 (m, 2 H), 1.20 - 1.10 (m, 2 H). Example 69: Synthesis of (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (R)-(tetrahydrofuran-3-yl)methanamine hydrochloride (0.043 g, 0.321 mmol) as starting materials, (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide (0.080 g, 84.9%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 324.23 [M+H]. + , calculated MW 323.37; 1 H-NMR (400 MHz, DMSO-d6) d 8.67 (t, J = 5.4 Hz, 1 H), 7.86 (d, J = 8.4 Hz, 2 H), 7.64 - 7.62 (m, 3 H), 7.50 - 7.45 (m, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 3.71 - 3.55 (m, 3 H), 3.45 - 3.42 (m, 1 H), 3.27 - 3.19 (m, 2 H), 3.13 - 3.12 (m, 1 H), 1.95 - 1.86 (m, 1 H), 1.60 - 1.52 (m, 1 H). Example 70: Synthesis of N-((5,5-dimethyltetrahydrofuran-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.050 g, 0.208 mmol) and (5,5-dimethyltetrahydrofuran-3-yl)methanamine (0.030 g, 0.229 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give N-((5,5-dimethyltetrahydrofuran-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.036 g, 49.2%) as a white solid: LRMS (ES) m / z 352.23 [M+H]. + , calculated MW 351.42; 1 H-NMR (400 MHz, DMSO-d6) d 8.63 (t, J = 5.2 Hz, 1 H), 7.86 (d, J = 8.0 Hz, 2 H), 7.64 - 7.62 (m, 3 H), 7.50 - 7.42 (m, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 3.77 (t, J = 8.0 Hz, 1 H), 3.46 (t, J = 7.8 Hz, 1 H), 3.25 - 3.20 (m, 2 H), 2.59 - 2.52 (m, 1 H), 1.83 (q, J = 6.8 Hz, 1 H), 1.38 (q, J = 6.8 Hz, 1 H), 1.18 (s, 3 H), 1.08 (s, 3 H). Example 71: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (tetrahydrofuran-2-yl)methanamine (0.032 g, 0.321 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide (0.076 g, 80.7%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 324.21 [M+H]. + , calculated MW 323.37; 1 H-NMR (400 MHz, DMSO-d6) d 8.64 (t, J = 5.6 Hz, 1 H), 7.87 (d, J = 7.6 Hz, 2 H), 7.62 (d, J = 7.6 Hz, 3 H), 7.47 (q, J = 6.4 Hz, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 3.97 - 3.91 (m, 1 H), 3.75 - 3.71 (m, 1 H), 3.61 - 3.56 (m, 1 H), 3.28 - 3.26 (m, 2 H), 1.89 - 1.72 (m, 3H), 1.58 - 1.50 (m, 1 H). Example 72: Synthesis of N-((3-ethyloxetan-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.100 g, 0.416 mmol) and (3-ethyloxetan-3-yl)methanamine (0.055 g, 0.479 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give N-((3-ethyloxetan-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.091 g, 64.8%) as a white solid: LRMS (ES) m / z 338.15 [M+H]. + , calculated MW 337.39; 1H-NMR (400 MHz, DMSO-d6) d 8.65 (t, J = 6.2 Hz, 1 H), 7.88 (d, J = 6.8 Hz, 2 H), 7.65 - 7.61 (m, 3 H), 7.49 - 7.46 (m, 1 H), 7.33 (td, J = 9.1, 1.1 Hz, 1 H), 7.25 (td, J = 7.5, 1.2 Hz, 1 H), 4.40 (d, J = 6.0 Hz, 2 H), 4.20 (d, J = 5.6 Hz, 2 H), 3.47 (d, J = 6.0 Hz, 2 H), 1.61 (q, J = 7.5 Hz, 2 H), 0.86 (t, J = 7.6 Hz, 3 H). Example 73: Synthesis of 4-((2,4-difluorophenyl)ethynyl)-N-((1-fluorocyclohexyl)methyl)benzamide [ka] Step 1: Synthesis of (1-fluorocyclohexyl)methanamine hydrochloride [ka] 1-(((tert-Butoxycarbonyl)amino)methyl)cyclohexane-1-carboxylic acid (0.200 g, 0.777 mmol), 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane ditetrafluoroborate (Selectfluor® 0.826 g, 2.332 mmol), [Ir{dF(CF3)ppy}2(dtbpy)]PF6 (0.009 g, 0.008 mmol), and sodium hydrogen phosphate (Na2HPO4, 0.221 g, 1.554 mmol) were dissolved in water (3.5 mL) / acetonitrile (3.5 mL) at room temperature. The resulting solution was stirred at the same temperature under visible light (blue LED, 60 W) for 18 hours. Saturated aqueous sodium bicarbonate solution was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give tert-butyl ((1-fluorocyclohexyl)methyl)carbamate (0.095 g, 52.8%) as a white solid: LRMS (ES) m / z No detection [M+H] + , calculated MW 231.31. The resulting product (0.070 g, 0.303 mmol) and hydrogen chloride (4.00 M solution in 1,4-dioxane, 0.227 mL, 0.908 mmol) were dissolved in dichloromethane (10 mL) at room temperature, and the resulting solution was stirred at the same temperature for 18 hours. After removing the solvent from the reaction mixture under reduced pressure, the precipitated solid was filtered, washed with diethyl ether, and dried to give (1-fluorocyclohexyl)methanamine hydrochloride (0.057 g, 112.3%) as a white solid: LRMS (ES) m / z no detection [M+H]. + , calculated MW 167.73; 1 H-NMR (400 MHz, DMSO-d6) d 8.03 (s, 2 H), 3.01 - 2.96 (m, 2 H), 1.87 - 1.76 (m, 2 H), 1.50 - 1.41 (m, 8 H). Step 2: Synthesis of 4-((2,4-difluorophenyl)ethynyl)-N-((1-fluorocyclohexyl)methyl)benzamide [ka] Using 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.035 g, 0.136 mmol) and (1-fluorocyclohexyl)methanamine hydrochloride (0.025 g, 0.149 mmol) as starting materials, 4-((2,4-difluorophenyl)ethynyl)-N-((1-fluorocyclohexyl)methyl)benzamide (0.032 g, 63.6%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 372.23 [M+H]. + , calculated MW 371.4; 1 H-NMR (400 MHz, DMSO-d6) d 7.03 - 7.02 (m, 2 H), 6.80 - 6.78 (m, 4 H), 6.29 - 6.18 (m, 2 H), 2.72 (d, J = 3.2 Hz, 2 H), 1.06 - 0.96 (m, 2 H), 0.78 (s, 6 H), 0.70 - 0.65 (m, 1 H), 0.52 - 0.51 (m, 1 H). Example 74: Synthesis of methyl 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetate [ka] Step 1: Synthesis of methyl 2-(1-(aminomethyl)cyclohexyl)acetate hydrochloride [ka] 2-(1-(aminomethyl)cyclohexyl)acetic acid (3.000 g, 17.519 mmol) was dissolved in methanol (50 mL) at 0 °C. Thionyl chloride (2.545 mL, 35.039 mmol) was added to the resulting solution, and the mixture was stirred at 50 °C for 14 hours. The temperature was then lowered to room temperature to terminate the reaction. The solvent was removed from the reaction mixture under reduced pressure, and the resulting product was used without further purification (methyl 2-(1-(aminomethyl)cyclohexyl)acetate hydrochloride, 3.850 g, 99.1%, yellow solid): LRMS (ES) m / z 185.75 [M+H]. + , calculated MW 221.73. Step 2: Synthesis of methyl 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetate [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.400 g, 1.665 mmol) and methyl 2-(1-(aminomethyl)cyclohexyl)acetate hydrochloride (0.369 g, 1.665 mmol) as starting materials, a procedure similar to that of Example 11 was carried out to give methyl 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetate (0.450 g, 66.3%) as a yellow solid: LRMS (ES) m / z 408.29 [M+H] + , calculated MW 407.49; 1 H-NMR (400 MHz, DMSO-d6) d 8.30 (t, J = 6.4 Hz, 1 H), 7.86 (d, J = 8.8 Hz, 2 H), 7.64 (m, 3 H), 7.48 (m, 1 H), 7.35 - 7.33 (m, 1 H), 7.27 - 7.23 (m, 1 H), 3.53 (s, 3 H), 3.36 (m, 2 H), 2.33 (s, 2 H), 1.52 - 1.25 (m, 10 H). Example 75: Synthesis of methyl 2-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)acetate [ka] Step 1: Synthesis of methyl 2-(4-(aminomethyl)tetrahydro-2H-pyran-4-yl)acetate hydrochloride [ka] A mixture of 8-oxa-2-azaspiro[4.5]decan-3-one (0.500 g, 3.222 mmol) and hydrochloric acid (12.00 M solution, 5.369 mL, 64.433 mmol) was heated to reflux at room temperature for 8 hours, and then the temperature was lowered to room temperature. After removing the solvent from the reaction mixture under reduced pressure, the precipitated solid was filtered, washed with dichloromethane, and dried to give 2-(4-(aminomethyl)tetrahydro-2H-pyran-4-yl)acetic acid hydrochloride (0.620 g, 91.8%) as a white solid: LRMS (ES) m / z 174.06 [M+H]. + , calculated MW 209.67. To a solution of 0.514 g (2.967 mmol) of the obtained product in methanol (50 mL) at 0°C, thionyl chloride (0.431 mL, 5.935 mmol) was added and the mixture was stirred at 50°C for 14 hours. The temperature was lowered to room temperature to terminate the reaction. The solvent was removed from the reaction mixture under reduced pressure, and the obtained product was used without further purification. Methyl 2-(4-(aminomethyl)tetrahydro-2H-pyran-4-yl)acetate hydrochloride, 0.660 g, 99.4%, yellow solid: LRMS (ES) m / z 188.13 [M+H] + , calculated MW 223.7. Step 2: Synthesis of methyl 2-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)acetate [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.600 g, 2.498 mmol) and methyl 2-(4-(aminomethyl)tetrahydro-2H-pyran-4-yl)acetate hydrochloride (0.559 g, 2.498 mmol) as starting materials, a similar procedure to that in Example 11 was carried out to give methyl 2-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)acetate (0.450 g, 44.0%) as a yellow solid: LRMS (ES) m / z 410.21 [M+H] + , calculated MW 409.46; 1 H-NMR (400 MHz, DMSO-d6) d 8.43 (t, J = 6.2 Hz, 1 H), 7.88 - 7.86 (m, 2 H), 7.64 - 7.62 (m, 3 H), 7.48 (m, 1 H), 7.33 (m, 1 H), 7.26 (t, J = 3.6 Hz, 1 H), 3.60 (m, 2 H), 3.53 (m, 5 H), 3.44 (d, J = 6.4 Hz, 2 H), 2.42 (s, 2 H), 1.48 - 1.46 (m, 4 H). Example 76: Synthesis of 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetic acid [ka] To a solution of methyl 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetate (0.300 g, 0.736 mmol) obtained in Example 74 dissolved in methanol (8 mL) / tetrahydrofuran (8 mL) / water (8 mL) at room temperature, lithium hydroxide monohydrate (0.062 g, 1.472 mmol) was added and stirred at the same temperature for 5 hours. The solvent was removed from the reaction mixture under reduced pressure, and the resulting concentrate was poured into 1N aqueous hydrochloric acid solution and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetic acid (0.230 g, 79.4%) as a white solid: LRMS (ES) m / z 394.29 [M+H] + , calculated MW 393.46; 1 H-NMR (400 MHz, CD3OD) d 7.84 - 7.82 (m, 2 H), 7.62 - 7.60 (m, 2 H), 7.55 (m, 1 H), 7.40 (m, 1 H), 7.21 - 7.17 (m, 2 H), 3.49 (s, 2 H), 2.39 (s, 2 H), 1.57 - 1.44 (m, 10 H). Example 77: Synthesis of N-((1-(2-amino-2-oxoethyl)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetic acid (0.080 g, 0.203 mmol) obtained in Example 76, ammonium chloride (NH4Cl, 0.109 g, 2.033 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU, 0.101 g, 0.264 mmol), and N,N-diisopropylethylamine (0.177 mL, 1.017 mmol) were dissolved in N,N-dimethylformamide (2 mL) at room temperature, and the resulting solution was stirred at 50°C for 16 hours. The temperature was then lowered to room temperature to terminate the reaction. The reaction mixture was filtered through a Celite pad to remove solids. The solvent was removed from the filtrate under reduced pressure, and the concentrate was poured into a saturated aqueous solution of sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. N-((1-(2-amino-2-oxoethyl)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide, 0.055 g, 68.9%, white solid: LRMS (ES) m / z 393.30 [M+H] + , calculated MW 392.47; 1 H-NMR (400 MHz, DMSO-d6) d 8.95 (t, J = 5.8 Hz, 1 H), 7.86 (d, J = 8.8 Hz, 2 H), 7.40 - 7.62 (m, 4 H), 7.48 (m, 1 H), 7.32 (m, 1 H), 7.25 (m, 1 H), 7.06 (bs, 1 H), 3.33 (s, 2 H), 2.16 (s, 2 H), 1.43 - 1.30 (m, 10 H). Example 78: Synthesis of N-((4-(2-amino-2-oxoethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Step 1: Synthesis of 2-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)acetic acid [ka] 2-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)acetic acid was prepared in the same manner as in Example 76, using methyl 2-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)acetate (0.070 g, 0.171 mmol) obtained in Example 75 as the starting material. The product obtained was used without further purification. (0.055 g, 81.4%, white solid): LRMS (ES) m / z 396.27 [M+H] + , calculated MW 395.43. Step 2: Synthesis of N-((4-(2-amino-2-oxoethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] N-((4-(2-amino-2-oxoethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide was prepared in a similar manner to Example 77 using 2-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)acetic acid (0.070 g, 0.177 mmol) as the starting material. (0.045 g, 64.4%, yellow oil): LRMS (ES) m / z 395.08 [M+H] + , calculated MW 394.45; 1H-NMR (400 MHz, DMSO-d6) d 8.84 (t, J = 6.0 Hz, 1 H), 7.86 (m, 2 H), 7.64 - 7.62 (m, 4 H), 7.51 - 7.43 (m, 1 H), 7.32 (m, 1 H), 7.26 (m, 1 H), 7.06 (bs, 1 H), 3.62 - 3.52 (m, 4 H), 3.41 (m, 2 H), 2.23 (s, 2 H), 1.45 - 1.40 (m, 4 H). Example 79: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-(2-(hydroxyamino)-2-oxoethyl)cyclohexyl)methyl)benzamide [ka] To a solution of methyl 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetate (Compound 2965, 0.050 g, 0.123 mmol) obtained in Example 74 in methanol (2 mL) / tetrahydrofuran (1 mL) at 0°C, potassium hydroxide (KOH, 0.014 g, 0.245 mmol) and hydroxylamine (50.00% solution in water, 0.081 mL, 1.227 mmol) were added and stirred at room temperature for 1 hour. The solvent was removed from the reaction mixture under reduced pressure, and then saturated aqueous sodium bicarbonate solution was added to the concentrate and stirred. The precipitated solid was filtered, washed with water, and dried to give 4-((2-fluorophenyl)ethynyl)-N-((1-(2-(hydroxyamino)-2-oxoethyl)cyclohexyl)methyl)benzamide (0.040 g, 79.8%) as a white solid: LRMS (ES) m / z 409.15 [M+H] + , calculated MW 408.47; 1H-NMR (400 MHz, CD3OD) d 7.90 - 7.88 (m, 2 H), 7.63 - 7.61 (m, 2 H), 7.55 (m, 1 H), 7.40 (m, 1 H), 7.21 - 7.15 (m, 2 H), 3.47 (s, 2 H), 2.19 (s, 2 H), 1.56 - 1.37 (m, 10 H). Example 80: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-(2-(methylamino)-2-oxoethyl)cyclohexyl)methyl)benzamide [ka] Using 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetic acid (0.050 g, 0.127 mmol) obtained in Example 76 and methanamine hydrochloride (0.017 g, 0.254 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((1-(2-(methylamino)-2-oxoethyl)cyclohexyl)methyl)benzamide was prepared in the same manner as in Example 77 (0.045 g, 87.1%, white solid): LRMS (ES) m / z 406.97 [M+H] + , calculated MW 406.5; 1 H-NMR (400 MHz, DMSO-d6) d 8.80 (t, J = 5.6 Hz, 1 H), 8.06 (d, J = 4.8 Hz, 1 H), 7.81 (d, J = 48.4 Hz, 2 H), 7.65 (m, 3 H), 7.48 (m, 1 H), 7.32 (t, J = 9.2 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 3.31 (s, 2 H), 2.57 (d, J = 4.8 Hz, 3 H), 2.15 (s, 2 H), 1.42 - 1.25 (m, 10 H). Example 81: Synthesis of N-((1-(2-(dimethylamino)-2-oxoethyl)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] N-((1-(2-(dimethylamino)-2-oxoethyl)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide was obtained in the same manner as in Example 77 using 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetic acid (0.050 g, 0.127 mmol) obtained in Example 76 and dimethylamine hydrochloride (0.021 g, 0.254 mmol) as starting materials, and the obtained product was purified by column chromatography to give the product in the form of a white solid (0.050 g, 93.6%): LRMS (ES) m / z 421.04 [M+H] + , calculated MW 420.53; 1 H-NMR (400 MHz, DMSO-d6) d 8.69 (t, J = 6.0 Hz, 1 H), 7.85 (d, J = 8.8 Hz, 2 H), 7.65 - 7.62 (m, 3 H), 7.48 (m, 1 H), 7.33 (m, 1 H), 7.26 (t, J = 3.8 Hz, 1 H), 3.39 (d, J = 6.0 Hz, 2 H), 2.99 (s, 3 H), 2.81 (s, 3 H), 2.35 (s, 2 H), 1.45 - 1.28 (m, 10 H). Example 82: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxyoxetan-3-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.100 g, 0.416 mmol) and 3-(aminomethyl)oxetan-3-ol (0.052 g, 0.500 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxyoxetan-3-yl)methyl)benzamide (0.082 g, 60.5%) was obtained as an ivory solid in the same manner as in Example 11: LRMS (ES) m / z 326.22 [M+H]. +, calculated MW 325.34; 1 H-NMR (400 MHz, DMSO-d6) d 8.71 (t, J = 6.2 Hz, 1 H), 7.90 (dd, J = 6.8, 1.6 Hz, 2 H), 7.65 - 7.61 (m, 3 H), 7.49 - 7.47 (m, 1 H), 7.33 (t, J = 8.4 Hz, 1 H), 7.25 (td, J = 7.5, 0.9 Hz, 1 H), 5.86 (s, 1 H), 4.46 (d, J = 6.8 Hz, 2 H), 4.36 (d, J = 6.4 Hz, 2 H), 3.53 (d, J = 6.0 Hz, 2 H). Example 83: Synthesis of 4-((4-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (3-methyloxetan-3-yl)methanamine (0.035 g, 0.350 mmol) as starting materials, 4-((4-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide (0.089 g, 94.5%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 324.11 [M+H]. + , calculated MW 323.37; 1 H-NMR (400 MHz, DMSO-d6) d 8.69 (t, J = 6.2 Hz, 1 H), 7.87 (d, J = 8.0 Hz, 2 H), 7.64 - 7.58 (m, 4 H), 7.29 - 7.23 (m, 2 H), 4.44 (d, J = 5.6 Hz, 2 H), 4.17 (d, J = 6.0 Hz, 2 H), 3.43 (d, J = 6.0 Hz, 2 H), 1.22 (s, 3 H). Example 84: Synthesis of 3-fluoro-4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide [ka] Step 1: Synthesis of 3-fluoro-4-((2-fluorophenyl)ethynyl)benzoic acid [ka] Methyl 3-fluoro-4-((2-fluorophenyl)ethynyl)benzoate (1.800 g, 77.0%, LRMS (ES) m / z 272.94 [M+H]) was obtained in a similar manner to Step 1 of Example 3, using methyl 4-bromo-3-fluorobenzoate (2.000 g, 8.582 mmol) and 1-ethynyl-2-fluorobenzene (1.031 g, 8.582 mmol) as starting materials. + , calculated MW 272.25) as a white solid, followed by 3-fluoro-4-((2-fluorophenyl)ethynyl)benzoic acid (1.700 g, 99.6%) as a white solid: LRMS (ES) m / z 257.03 [M−H] + , calculated MW 258.22. Step 2: Synthesis of 3-fluoro-4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide [ka] Using 3-fluoro-4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.271 mmol) and (3-methyloxetan-3-yl)methanamine (0.036 g, 0.352 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give 3-fluoro-4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide (0.065 g, 70.2%) as a white solid: LRMS (ES) m / z 342.11 [M+H]. + , calculated MW 341.36;1 H-NMR (400 MHz, DMSO-d6) d 8.76 (t, J = 6.0 Hz, 1 H), 7.78 - 7.71 (m, 3 H), 7.64 (td, J = 7.5, 1.7 Hz, 1 H), 7.54 - 7.48 (m, 1 H), 7.35 (t, J = 8.6 Hz, 1 H), 7.27 (td, J = 7.5, 0.9 Hz, 1 H), 4.43 (d, J = 6.0 Hz, 2 H), 4.17 (d, J = 6.0 Hz, 2 H), 3.45 (d, J = 6.4 Hz, 2 H), 1.22 (s, 3 H). Example 85: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-(((1s,3s)-3-hydroxycyclobutyl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.050 g, 0.208 mmol) and (1s,3s)-3-(aminomethyl)cyclobutan-1-ol (0.025 g, 0.250 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-(((1s,3s)-3-hydroxycyclobutyl)methyl)benzamide (0.059 g, 87.7%) was obtained as an ivory solid in the same manner as in Example 11: LRMS (ES) m / z 324.24 [M+H]. + , calculated MW 323.37; 1H-NMR (400 MHz, DMSO-d6) d 8.54 (t, J = 5.8 Hz, 1 H), 7.87 - 7.85 (m, 2 H), 7.65 - 7.61 (m, 3 H), 7.48 - 7.44 (m, 1 H), 7.33 (t, J = 8.8 Hz, 1 H), 7.25 (td, J = 7.6, 1.1 Hz, 1 H), 4.91 (d, J = 6.4 Hz, 1 H), 3.88 - 3.79 (m, 1 H), 3.23 (t, J = 6.0 Hz, 2 H), 2.21 - 2.17 (m, 2 H), 1.92 - 1.82 (m, 1 H), 1.53 - 1.46 (m, 2 H). Example 86: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-(((1r,3r)-3-hydroxycyclobutyl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.050 g, 0.208 mmol) and (1r,3r)-3-(aminomethyl)cyclobutan-1-ol (0.025 g, 0.250 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-(((1r,3r)-3-hydroxycyclobutyl)methyl)benzamide (0.053 g, 78.7%) was obtained as an ivory solid in the same manner as in Example 11: LRMS (ES) m / z 324.14 [M+H]. + , calculated MW 323.37; 1H-NMR (400 MHz, DMSO-d6) d 8.58 (t, J = 5.4 Hz, 1 H), 7.86 (dd, J = 6.6, 1.8 Hz, 2 H), 7.65 - 7.61 (m, 3 H), 7.48 - 7.45 (m, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.25 (td, J = 7.6, 0.9 Hz, 1 H), 4.92 (d, J = 6.0 Hz, 1 H), 4.22 - 4.13 (m, 1 H), 3.30 - 3.25 (m, 2 H), 2.29 - 2.22 (m, 1) H), 2.02 - 1.95 (m, 2 H), 1.89 - 1.82 (m, 2 H). Example 87: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-(((1s,3s)-3-hydroxy-3-methylcyclobutyl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (1s,3s)-3-(aminomethyl)-1-methylcyclobutan-1-ol (0.044 g, 0.379 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-(((1s,3s)-3-hydroxy-3-methylcyclobutyl)methyl)benzamide (0.097 g, 98.7%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 338.08 [M+H]. + , calculated MW 337.39; 1H-NMR (400 MHz, DMSO-d6) d 8.53 (t, J = 5.8 Hz, 1 H), 7.86 (dd, J = 6.4, 2.0 Hz, 2 H), 7.65 - 7.61 (m, 3 H), 7.53 - 7.44 (m, 1 H), 7.33 (t, J = 9.6 Hz, 1 H), 7.25 (td, J = 7.6, 0.9 Hz, 1 H), 4.84 (s, 1 H), 3.24 (t, J = 6.0 Hz, 2 H), 1.97 - 1.92 (m, 3 H), 1.73 - 1.67 (m, 2 H), 1.16 (s, 3 H). Example 88: Synthesis of N-((4,4-difluorocyclohexyl)methyl)-4-(pyridin-4-ylethynyl)benzamide [ka] Using 4-(pyridin-4-ylethynyl)benzoic acid (0.200 g, 0.896 mmol) and (4,4-difluorocyclohexyl)methanamine (0.160 g, 1.075 mmol) as starting materials, a procedure similar to that of Example 11 was carried out to give N-((4,4-difluorocyclohexyl)methyl)-4-(pyridin-4-ylethynyl)benzamide (0.210 g, 66.1%) as a white solid: LRMS (ES) m / z 354.79 [M+H]. + , calculated MW 354.4; 1 H-NMR (400 MHz, DMSO-d6) d 8.64 (t, J = 5.8 Hz, 1 H), 8.62 - 8.60 (m, 2 H), 7.88 (d, J = 8.8 Hz, 2 H), 7.67 (d, J = 6.8 Hz, 2 H), 7.52 (dd, J = 4.4, 2.0 Hz, 2 H), 3.14 (t, J = 6.4 Hz, 2 H), 1.98 - 1.96 (m, 2 H), 1.77 - 1.65 (m, 5 H), 1.22 - 1.13 (m, 2 H). Example 89: Synthesis of N-((3,3-difluorocyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide [ka] Using 4-(pyridin-4-ylethynyl)benzoic acid (0.100 g, 0.448 mmol) and (3,3-difluorocyclobutyl)methanamine (0.065 g, 0.538 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give N-((3,3-difluorocyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide (0.089 g, 60.9%) as a white solid: LRMS (ES) m / z 327.18 [M+H]. + , calculated MW 326.35; 1 H-NMR (400 MHz, DMSO-d6) d 8.75 (t, J = 5.6 Hz, 1 H), 8.65 (dd, J = 4.4, 1.6 Hz, 2 H), 7.91 (d, J = 8.4 Hz, 2 H), 7.72 (d, J = 8.8 Hz, 2 H), 7.56 (dd, J = 4.2, 1.8 Hz, 2 H), 3.40 (t, J = 5.0 Hz, 2 H), 2.67 - 2.62 (m, 2 H), 2.42 - 2.33 (m, 3 H). Example 90: Synthesis of N-((3,3-difluorocyclobutyl)methyl)-4-(phenylethynyl)benzamide [ka] Using 4-(phenylethynyl)benzoic acid (0.070 g, 0.315 mmol) and (3,3-difluorocyclobutyl)methanamine hydrochloride (0.050 g, 0.315 mmol) as starting materials, N-((3,3-difluorocyclobutyl)methyl)-4-(phenylethynyl)benzamide (0.080 g, 78.1%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 326.13 [M+H]. + , calculated MW 325.36; 1H-NMR (400 MHz, DMSO-d6) d 8.70 (t, J = 5.6 Hz, 1 H), 7.85 (dd, J = 6.4, 2.0 Hz, 2 H), 7.62 (d, J = 8.0 Hz, 2 H), 7.54 (m, 2 H), 7.42 - 7.40 (m, 3 H), 3.35 (t, J = 5.4 Hz, 2 H), 2.63 - 2.52 (m, 2 H), 2.40 - 2.32 (m, 3 H). Example 91: Synthesis of (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.050 g, 0.208 mmol) and (S)-(tetrahydro-2H-pyran-3-yl)methanamine hydrochloride (0.035 g, 0.229 mmol) as starting materials, (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide (0.066 g, 93.3%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 338.13 [M+H]. + , calculated MW 337.39; 1 H-NMR (400 MHz, DMSO-d6) d 8.58 (t, J = 6.0 Hz, 1 H), 7.86 (d, J = 8.0 Hz, 2 H), 7.65 - 7.56 (m, 3 H), 7.50 - 7.44 (m, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.25 (td, J = 7.6, 1.1 Hz, 1 H), 3.75 - 3.61 (m, 2 H), 3.31 - 3.28 (m, 2 H), 3.13 - 3.05 (m, 3 H), 1.77 - 1.69 (m, 2 H), 1.56 - 1.40 (m, 2 H). Example 92: Synthesis of (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.050 g, 0.208 mmol) and (R)-(tetrahydro-2H-pyran-3-yl)methanamine hydrochloride (0.035 g, 0.229 mmol) as starting materials, (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide (0.055 g, 78.3%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 338.20 [M+H]. + , calculated MW 337.39; 1 H-NMR (400 MHz, DMSO-d6) d 8.58 (t, J = 5.8 Hz, 1 H), 7.86 (dd, J = 6.6, 1.8 Hz, 2 H), 7.65 - 7.61 (m, 3 H), 7.44 - 7.35 (m, 1 H), 7.33 (td, J = 9.2, 0.8 Hz, 1 H), 7.25 (td, J = 7.6, 1.1 Hz, 1 H), 3.75 - 3.72 (m, 1 H), 3.69 (s, 1 H), 3.30 - 3.25 (m, 1 H), 3.15 - 3.05 (m, 3 H), 1.79 - 1.72 (m, 2 H), 1.57 - 1.52 (m, 1 H), 1.49 - 1.35 (m, 1 H), 1.26 - 1.21 (m, 1 H). Example 93: Synthesis of (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (S)-(tetrahydrofuran-3-yl)methanamine (0.032 g, 0.321 mmol), a similar procedure to that described in Example 11 was carried out to give (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide (0.089 g, 94.5%) as a clear liquid: LRMS (ES) m / z 324.05 [M+H]. + , calculated MW 323.37; 1 H-NMR (400 MHz, DMSO-d6) d 8.68 (t, J = 5.8 Hz, 1 H), 7.86 (dd, J = 6.8, 2.0 Hz, 2 H), 7.65 - 7.61 (m, 3 H), 7.50 - 7.43 (m, 1 H), 7.33 (td, J = 9.1, 1.1 Hz, 1 H), 7.25 (td, J = 7.7, 1.1 Hz, 1 H), 3.75 - 3.69 (m, 1 H), 3.68 - 3.62 (m, 1 H), 3.60 - 3.55 (m, 1 H), 3.45 - 3.40 (m, 1 H), 3.33 - 3.19 (m, 3 H), 1.95 - 1.87 (m, 1 H), 1.61 - 1.51 (m, 1 H). Example 94: Synthesis of 4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (tetrahydrofuran-3-yl)methanamine (0.035 g, 0.350 mmol) as starting materials, 4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide (0.079 g, 83.8%) was obtained as an ivory solid in the same manner as in Example 11: LRMS (ES) m / z 324.14 [M+H]. + , calculated MW 323.37;1 H-NMR (400 MHz, DMSO-d6) d 8.64 (t, J = 5.8 Hz, 1 H), 7.85 (dd, J = 6.8, 2.0 Hz, 2 H), 7.64 - 7.58 (m, 4 H), 7.29 - 7.23 (m, 2 H), 3.73 - 3.68 (m, 1 H), 3.65 - 3.63 (m, 1 H), 3.61 - 3.55 (m, 1 H), 3.45 - 3.42 (m, 1 H), 3.22 - 3.15 (m, 3 H), 1.95 - 1.86 (m, 1 H), 1.60 - 1.52 (m, 1 H). Example 95: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl-d)benzamide [ka] Step 1: Synthesis of (3-methyloxetan-3-yl)methan-d-amine [ka] 3-Methyloxetane-3-carbaldehyde (2.000 g, 19.976 mmol), phenylmethanamine (2.141 g, 19.976 mmol), and acetic acid (0.114 mL, 1.998 mmol) were dissolved in tetrahydrofuran (18 mL), and the resulting solution was stirred at room temperature for 1 hour. Sodium borodeuteride (1.254 g, 29.964 mmol) was added, and the mixture was further stirred at the same temperature for 24 hours. Saturated aqueous sodium bicarbonate was poured into the reaction mixture, which was then extracted with dichloromethane. The organic layer was washed with saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give N-benzyl-1-(3-methyloxetan-3-yl)methan-d-amine (3.800 g, 98.9%, pale yellow oil). LRMS (ES) m / z 193.15 [M+H] + , calculated MW 192.28. The resulting product was dissolved in 10% Pd / C (600 mg) and ammonium formate (4.985 g, 79.051 mmol) in methanol (20 mL) at room temperature. The resulting solution was stirred at 65 °C for 14 hours, and then the temperature was lowered to room temperature to terminate the reaction. The reaction mixture was filtered through a Celite pad to remove solids, and the filtrate was evaporated under reduced pressure to give (3-methyloxetan-3-yl)methan-d-amine (1.280 g, 63.4%), a yellow oil: LRMS (ES) m / z 102.97 [M+H]. + , calculated MW 102.16. Step 2: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl-d)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (3.010 g, 12.529 mmol) and (3-methyloxetan-3-yl)methan-d-amine (1.280 g, 12.529 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl-d)benzamide (1.750 g, 43.1%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 325.14 [M+H]. + , calculated MW 324.37; 1 H-NMR (400 MHz, DMSO-d6) d 8.69 (d, J = 6.0 Hz, 1 H), 7.88 (dd, J = 7.0, 1.8 Hz, 2 H), 7.65 - 7.63 (m, 3 H), 7.51 - 7.45 (m, 1 H), 7.33 (m, 1 H), 7.25 (m, 1 H), 4.44 (d, J = 6.0 Hz, 2 H), 4.17 (d, J = 5.6 Hz, 2 H), 3.41 (d, J = 6.0 Hz, 1 H), 1.22 (s, 3 H). Example 96: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-morpholinocyclobutyl)methyl)benzamide [ka] Step 1: Synthesis of (1-morpholinocyclobutyl)methanamine [ka] 1-Morpholinocyclobutane-1-carbonitrile (4.210 g, 88.8%, LRMS (ES) m / z No detection [M+H]) was prepared in the same manner as in Step 2 of Example 1 using cyclobutanone (2.000 g, 28.535 mmol) and morpholine (3.209 mL, 37.095 mmol) as starting materials. + (1-Morpholinocyclobutyl)methanamine (2.000g, 46.5%, clear liquid): LRMS (ES) m / z 171.02 [M+H] + , calculated MW 170.26. Step 2: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-morpholinocyclobutyl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.100 g, 0.416 mmol) and (1-morpholinocyclobutyl)methanamine (0.085 g, 0.500 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((1-morpholinocyclobutyl)methyl)benzamide (0.119 g, 72.8%) was obtained as a yellow liquid in the same manner as in Example 11: LRMS (ES) m / z 392.77 [M+H]. + , calculated MW 392.47; 1H-NMR (400 MHz, DMSO-d6) d 8.41 (t, J = 6.2 Hz, 1 H), 7.86 (dd, J = 7.0, 1.8 Hz, 2 H), 7.65 - 7.61 (m, 3 H), 7.50 - 7.45 (m, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 4.08 (q, J = 5.1 Hz, 1 H), 3.50 - 3.48 (m, 5 H), 3.13 (d, J = 5.6 Hz, 3 H), 2.49 - 2.47 (m, 2 H), 1.93 - 1.83 (m, 3H), 1.69 - 1.61 (m, 2 H). Example 97: Synthesis of N-((3,3-difluoro-1-methylcyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (3,3-difluoro-1-methylcyclobutyl)methanamine (0.047 g, 0.350 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give N-((3,3-difluoro-1-methylcyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.075 g, 72.0%) as a white solid: LRMS (ES) m / z 358.16 [M+H]. + , calculated MW 357.38; 1H-NMR (400 MHz, DMSO-d6) d 8.72 (t, J = 6.2 Hz, 1 H), 7.88 (d, J = 6.4 Hz, 2 H), 7.66 - 7.63 (m, 3 H), 7.49 - 7.46 (m, 1 H), 7.33 (t, J = 8.8 Hz, 1 H), 7.25 (td, J = 7.6, 1.3 Hz, 1 H), 3.34 - 3.33 (m, 2 H), 2.67 - 2.57 (m, 2 H), 2.29 - 2.16 (m, 2 H), 1.17 (s, 3 H). Example 98: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide [ka] Using 4-((2-fluorophenyl)ethynyl)benzoic acid (0.070 g, 0.291 mmol) and (2-methyltetrahydrofuran-2-yl)methanamine (0.045 mL, 0.350 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide (0.074 g, 75.3%) was obtained as a yellow solid in the same manner as in Example 11: LRMS (ES) m / z 338.15 [M+H]. + , calculated MW 337.39; 1 H-NMR (400 MHz, DMSO-d6) d 8.50 (t, J = 6.2 Hz, 1 H), 7.88 (dd, J = 6.4, 2.0 Hz, 2 H), 7.66 - 7.61 (m, 3 H), 7.48 - 7.46 (m, 1 H), 7.35 - 7.30 (m, 1 H), 7.25 (td, J = 7.6, 1.1 Hz, 1 H), 3.73 - 3.69 (m, 2 H), 3.29 - 3.27 (m, 2 H), 1.87 - 1.79 (m, 3 H), 1.57 - 1.46 (m, 1 H), 1.11 (s, 3 H). Example 99: Synthesis of (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.120 g, 0.500 mmol) and (R)-(tetrahydro-2H-pyran-3-yl)methanamine hydrochloride (0.083 g, 0.549 mmol) as starting materials, (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide (0.130 g, 77.1%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 338.21 [M+H]. + , calculated MW 337.39; 1 H-NMR (400 MHz, DMSO-d6) d 8.55 (t, J = 6.8 Hz, 1 H), 7.84 (d, J = 8.0 Hz, 2 H), 7.64 - 7.59 (m, 4 H), 7.29 - 7.23 (m, 2 H), 3.75 - 3.62 (m, 2 H), 3.28 (s, 1 H), 3.16 - 3.05 (m, 3 H), 1.82 - 1.71 (m, 2 H), 1.57 - 1.52 (m, 1 H), 1.46 - 1.37 (m, 1 H), 1.25 - 1.15 (m, 1 H). Example 100: Synthesis of (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.150 g, 0.624 mmol) and (S)-(tetrahydro-2H-pyran-3-yl)methanamine hydrochloride (0.104 g, 0.687 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide (0.194 g, 92.1%) as a white solid: LRMS (ES) m / z 338.21 [M+H]. + , calculated MW 337.39; 1 H-NMR (400 MHz, DMSO-d6) d 8.55 (t, J = 5.6 Hz, 1 H), 7.84 (d, J = 8.0 Hz, 2 H), 7.64 - 7.56 (m, 4 H), 7.31 - 7.21 (m, 2 H), 3.75 - 3.62 (m, 2 H), 3.32 - 3.27 (m, 1 H), 3.13 - 3.05 (m, 3 H), 1.83 - 1.68 (m, 2 H), 1.54 - 1.52 (m, 1 H), 1.43 - 1.39 (m, 1 H), 1.24 - 1.18 (m, 1 H). Example 101: Synthesis of (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.100 g, 0.416 mmol) and (R)-(tetrahydrofuran-3-yl)methanamine hydrochloride (0.069 g, 0.500 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide (0.096 g, 71.3%) as a yellow solid: LRMS (ES) m / z 324.14 [M+H]. + , calculated MW 323.37; 1H-NMR (400 MHz, DMSO-d6) d 8.65 (t, J = 4.8 Hz, 1 H), 7.85 (d, J = 6.8 Hz, 2 H), 7.64 - 7.58 (m, 4 H), 7.29 - 7.23 (m, 2 H), 3.73 - 3.68 (m, 1 H), 3.66 - 3.32 (m, 1 H), 3.60 - 3.55 (m, 1 H), 3.45 - 3.42 (m, 1 H), 3.30 - 3.12 (m, 3 H), 1.96 - 1.84 (m, 1 H), 1.60 - 1.49 (m, 1 H). Example 102: Synthesis of (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.150 g, 0.624 mmol) and (S)-(tetrahydrofuran-3-yl)methanamine (0.076 g, 0.749 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide (0.152 g, 75.3%) as a yellow solid: LRMS (ES) m / z 324.08 [M+H]. + , calculated MW 323.37; 1 H-NMR (400 MHz, DMSO-d6) d 8.66 (t, J = 5.6 Hz, 1 H), 7.85 (d, J = 8.4 Hz, 2 H), 7.63 - 7.60 (m, 4 H), 7.29 - 7.24 (m, 2 H), 3.73 - 3.68 (m, 1 H), 3.66 - 3.62 (m, 1 H), 3.60 - 3.55 (m, 1 H), 3.45 - 3.42 (m, 1 H), 3.29 - 3.12 (m, 3 H), 1.94 - 1.86 (m, 1 H), 1.60 - 1.52 (m, 1 H). Example 103: Synthesis of N-((3-fluorooxetan-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide [ka] To a solution of 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxyoxetan-3-yl)methyl)benzamide (0.100 g, 0.307 mmol) obtained in Example 82 as the starting material dissolved in dichloromethane (5 mL), diethylaminosulfur trifluoride (DAST, 0.049 mL, 0.369 mmol) was added at −78° C. and stirred at the same temperature for 1 hour. The solvent was removed from the reaction mixture under reduced pressure, and a saturated aqueous solution of sodium bicarbonate was poured into the resulting concentrate, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography and concentrated to give N-((3-fluorooxetan-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide (0.017 g, 16.9%) as a white solid: LRMS (ES) m / z 328.24 [M+H] + , calculated MW 327.33; 1 H-NMR (400 MHz, DMSO-d6) d 8.88 (t, J = 5.8 Hz, 1 H), 7.90 (dd, J = 7.0, 1.8 Hz, 2 H), 7.66 - 7.60 (m, 3 H), 7.50 - 7.45 (m, 1 H), 7.35 - 7.30 (m, 1 H), 7.28 - 7.23 (m, 1 H), 4.68 - 4.53 (m, 4 H), 3.78 (dd, J = 19.8, 6.2 Hz, 2 H). Example 104: Synthesis of 4-((4-fluorophenyl)ethynyl)-N-((1-methylcyclohexyl)methyl)benzamide [ka] Using (1-methylcyclohexyl)methanamine (0.100 g, 0.786 mmol) and 4-((4-fluorophenyl)ethynyl)benzoic acid (0.208 g, 0.865 mmol) as starting materials, 4-((4-fluorophenyl)ethynyl)-N-((1-methylcyclohexyl)methyl)benzamide (0.056 g, 20.4%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 350.24 [M+H]. + , calculated MW 349.45; 1 H-NMR (400 MHz, DMSO-d6) d 8.36 (t, J = 6.2 Hz, 1 H), 7.85 (d, J = 8.8 Hz, 2 H), 7.59 - 7.63 (m, 4 H), 7.26 (t, J = 9.0 Hz, 2 H), 3.12 (d, J = 6.0 Hz, 2 H), 1.16 - 1.45 (m, 10 H), 0.84 (s, 3 H). Example 105: Synthesis of 4-((2-fluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide [ka] Using (1-methylcyclobutyl)methanamine hydrochloride (0.050 g, 0.369 mmol) and 4-((2-fluorophenyl)ethynyl)benzoic acid (0.097 g, 0.405 mmol) as starting materials, 4-((2-fluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide (0.068 g, 57.4%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 322.16 [M+H]. + , calculated MW 321.4; 1H-NMR (400 MHz, CDCl3) d 7.74 (d, J = 8.0 Hz, 2 H), 7.59 (d, J = 8.4 Hz, 2 H), 7.51 (t, J = 6.8 Hz, 1 H), 7.32 (dd, J = 13.2, 6.4 Hz, 1 H), 7.11 (dd, J = 18.2, 8.6 Hz, 2 H), 6.22 (s, 1 H), 3.44 (d, J = 6.0 Hz, 2 H), 1.84 - 1.94 (m, 4 H), 1.72 - 1.76 (m, 2 H), 1.17 (s, 3 H). Example 106: Synthesis of 4-((4-fluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide [ka] Using (1-methylcyclobutyl)methanamine hydrochloride (0.050 g, 0.369 mmol) and 4-((4-fluorophenyl)ethynyl)benzoic acid (0.097 g, 0.405 mmol) as starting materials, 4-((4-fluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide (0.070 g, 59.1%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 322.16 [M+H]. + , calculated MW 321.4; 1 H-NMR (400 MHz, CDCl3) d 7.74 (d, J = 8.8 Hz, 2 H), 7.57 (d, J = 8.8 Hz, 2 H), 7.52 (dd, J = 9.0, 5.0 Hz, 2 H), 7.05 (t, J = 8.6 Hz, 2 H), 3.46 (d, J = 6.0 Hz, 2 H), 1.89 - 1.93 (m, 4 H), 1.71 - 1.78 (m, 2 H), 1.19 (s, 3 H). Example 107: Synthesis of 4-((2,4-difluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide [ka] Using (1-methylcyclobutyl)methanamine hydrochloride (0.050 g, 0.369 mmol) and 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.095 g, 0.369 mmol) as starting materials, 4-((2,4-difluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide (0.077 g, 61.5%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 340.20 [M+H]. + , calculated MW 339.39; 1 H-NMR (400 MHz, CDCl3) 7.74 (d, J = 8.4 Hz, 2 H), 7.58 (d, J = 8.8 Hz, 2 H), 7.47 - 7.52 (m, 1 H), 6.84 - 6.90 (m, 2 H), 6.13 (bs, 1 H), 3.45 (d, J = 6.0 Hz, 2 H), 1.90 - 1.92 (m, 4 H), 1.73 (m, 2 H), 1.16 (s, 3 H). Example 108: Synthesis of 4-((2,4-difluorophenyl)ethynyl)-N-((1-methylcyclopentyl)methyl)benzamide [ka] Using (1-methylcyclopentyl)methanamine hydrochloride (0.050 g, 0.334 mmol) and 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.086 g, 0.334 mmol) as starting materials, 4-((2,4-difluorophenyl)ethynyl)-N-((1-methylcyclopentyl)methyl)benzamide (0.069 g, 58.4%) was obtained as an ivory solid in the same manner as in Example 11: LRMS (ES) m / z 354.20 [M+H]. + , calculated MW 353.41; 1H-NMR (400 MHz, CDCl3) d 7.74 (d, J = 8.4 Hz, 2 H), 7.59 (d, J = 8.0 Hz, 2 H), 7.47 - 7.53 (m, 1 H), 6.85 - 6.91 (m, 2 H), 6.14 (bs, 1 H), 3.37 (d, J = 6.0 Hz, 2 H), 1.37 - 1.70 (m, 8 H), 1.05 (s, 3 H). Example 109: Synthesis of (R)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide [ka] Using 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.200 g, 0.775 mmol) and (R)-(tetrahydrofuran-3-yl)methanamine (0.086 g, 0.852 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give (R)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide (0.230 g, 87.0%) as a white solid: LRMS (ES) m / z 342.18 [M+H]. + , calculated MW 341.36; 1 H-NMR (400 MHz, DMSO-d6) d 8.66 (t, J = 5.8 Hz, 1 H), 7.86 (d, J = 8.8 Hz, 2 H), 7.74 - 7.68 (m, 1 H), 7.63 (d, J = 14.8 Hz, 2 H), 7.47 - 7.38 (m, 1 H), 7.19 - 7.15 (m, 1 H), 3.73 - 3.69 (m, 1 H), 3.67 - 3.63 (m, 1 H), 3.61 - 3.55 (m, 1 H), 3.45 - 3.42 (m, 1 H), 3.26 - 3.17 (m, 2 H), 3.13 (d, J = 5.6 Hz, 1 H), 1.96 - 1.84 (m, 1 H), 1.60 - 1.52 (m, 1 H). Example 110: Synthesis of (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.050 g, 0.208 mmol) and (R)-(tetrahydrofuran-2-yl)methanamine (0.025 g, 0.250 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide (0.032 g, 47.5%) as a yellow solid: LRMS (ES) m / z 324.14 [M+H]. + , calculated MW 323.37; 1 H-NMR (400 MHz, DMSO-d6) d 8.65 - 8.63 (m, 1 H), 7.86 (dd, J = 6.8, 1.6 Hz, 2 H), 7.37 - 7.56 (m, 4 H), 7.30 - 7.24 (m, 2 H), 3.97 - 3.90 (m, 1 H), 3.75 - 3.73 (m, 1 H), 3.61 - 3.56 (m, 1 H), 3.29 - 3.26 (m, 2 H), 1.91 - 1.85 (m, 1 H), 1.81 - 1.70 (m, 2 H), 1.58 - 1.50 (m, 1 H). Example 111: Synthesis of (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.050 g, 0.208 mmol) and (S)-(tetrahydrofuran-2-yl)methanamine (0.025 g, 0.250 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide (0.052 g, 77.3%) as a yellow solid: LRMS (ES) m / z 324.21 [M+H]. + , calculated MW 323.37; 1 H-NMR (400 MHz, DMSO-d6) d 8.63 (t, J = 5.8 Hz, 1 H), 7.91 (d, J = 32.0 Hz, 2 H), 7.63 - 7.60 (m, 4 H), 7.29 - 7.23 (m, 2 H), 3.97 - 3.91 (m, 1 H), 3.75 - 3.72 (m, 1 H), 3.61 - 3.56 (m, 1 H), 3.29 - 3.26 (m, 2 H), 1.91 - 1.85 (m, 1 H), 1.80 - 1.70 (m, 2 H), 1.58 - 1.50 (m, 1 H). Example 112: Synthesis of N-((3-ethyloxetan-3-yl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.050 g, 0.208 mmol) and (3-ethyloxetan-3-yl)methanamine (0.029 g, 0.250 mmol) as starting materials, a procedure similar to that of Example 11 was carried out to give N-((3-ethyloxetan-3-yl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide (0.020 g, 28.5%) as a yellow liquid: LRMS (ES) m / z 338.21 [M+H]. + , calculated MW 337.39; 1H-NMR (400 MHz, DMSO-d6) d 8.64 (t, J = 6.0 Hz, 1 H), 7.86 (d, J = 8.4 Hz, 2 H), 7.67 - 7.56 (m, 4 H), 7.30 - 7.24 (m, 2 H), 4.39 (d, J = 6.0 Hz, 2 H), 4.20 (d, J = 6.0 Hz, 2 H), 3.47 (d, J = 6.0 Hz, 2 H), 1.61 (q, J = 7.2 Hz, 2 H), 0.86 (t, J = 7.4 Hz, 3 H). Example 113: Synthesis of (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide [ka] Using 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.060 g, 0.232 mmol) and (S)-(tetrahydrofuran-3-yl)methanamine (0.026 g, 0.256 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide (0.073 g, 92.0%) as a white solid: LRMS (ES) m / z 342.18 [M+H]. + , calculated MW 341.36; 1 H-NMR (400 MHz, DMSO-d6) d 8.66 (t, J = 5.6 Hz, 1 H), 7.86 (dd, J = 6.6, 2.2 Hz, 2 H), 7.71 (q, J = 7.9 Hz, 1 H), 7.62 (d, J = 8.8 Hz, 2 H), 7.43 (dt, J = 16.4, 4.8 Hz, 1 H), 7.18 (d, J = 26.0 Hz, 1 H), 3.73 - 3.63 (m, 2 H), 3.61 - 3.42 (m, 2 H), 3.26 - 3.16 (m, 3 H), 1.95 - 1.86 (m, 1 H), 1.61 - 1.52 (m, 1 H). Example 114: Synthesis of (R)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide [ka] Using 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.060 g, 0.232 mmol) and (R)-(tetrahydrofuran-2-yl)methanamine (0.026 g, 0.256 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give (R)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide (0.075 g, 94.6%) as a white solid: LRMS (ES) m / z 342.11 [M+H]. + , calculated MW 341.36; 1 H-NMR (400 MHz, DMSO-d6) d 8.63 (t, J = 6.0 Hz, 1 H), 7.87 (d, J = 8.8 Hz, 2 H), 7.74 - 7.68 (m, 1 H), 7.62 (d, J = 8.8 Hz, 2 H), 7.45 - 7.40 (m, 1 H), 7.21 - 7.14 (m, 1 H), 3.96 - 3.91 (m, 1 H), 3.75 - 3.56 (m, 2 H), 3.28 - 3.26 (m, 2 H), 1.92 - 1.50 (m, 4 H). Example 115: Synthesis of 4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide [ka] Using 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.060 g, 0.232 mmol) and (tetrahydro-2H-pyran-2-yl)methanamine (0.029 g, 0.256 mmol) as starting materials, 4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide (0.051 g, 61.8%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 356.25 [M+H]. + , calculated MW 355.38; 1 H-NMR (400 MHz, DMSO-d6) d 8.57 (t, J = 18.8 Hz, 1 H), 7.87 (dd, J = 6.4, 1.6 Hz, 2 H), 7.74 - 7.68 (m, 1 H), 7.61 (dd, J = 6.4, 1.6 Hz, 2 H), 7.42 (td, J = 9.6, 2.8 Hz, 1 H), 7.21 - 7.14 (m, 1 H), 3.83 (d, J = 11.2 Hz, 1 H), 3.42 - 3.33 (m, 1 H), 3.25 - 3.20 (m, 3 H), 1.74 - 1.74 (m, 1 H), 1.58 (d, J = 12.8 Hz, 1 H), 1.42 - 1.34 (m, 3 H), 1.17 - 1.08 (m, 1 H). Example 116: Synthesis of 4-((4-fluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide [ka] Using 4-((4-fluorophenyl)ethynyl)benzoic acid (0.060 g, 0.250 mmol) and (2-methyltetrahydrofuran-2-yl)methanamine (0.032 g, 0.275 mmol) as starting materials, a similar procedure to that described in Example 11 was carried out to give 4-((4-fluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide (0.025 g, 29.7%) as a yellow solid: LRMS (ES) m / z 338.21 [M+H].+ , calculated MW 337.39; 1 H-NMR (400 MHz, DMSO-d6) d 8.46 (t, J = 6.4 Hz, 1 H), 7.86 (d, J = 8.8 Hz, 2 H), 7.64 - 7.56 (m, 4 H), 7.29 - 7.23 (m, 2 H), 3.73 - 3.69 (m, 2 H), 3.37 - 3.22 (m, 2 H), 1.89 - 1.79 (m, 3 H), 1.56 - 1.46 (m, 1 H), 1.11 (s, 3 H). Example 117: Synthesis of (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide [ka] Using 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.060 g, 0.232 mmol) and (S)-(tetrahydrofuran-2-yl)methanamine (0.026 g, 0.256 mmol) as starting materials, (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide (0.073 g, 92.0%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 342.18 [M+H]. + , calculated MW 341.36; 1 H-NMR (400 MHz, DMSO-d6) d 8.63 (t, J = 5.8 Hz, 1 H), 7.87 (d, J = 8.8 Hz, 2 H), 7.74 - 7.68 (m, 1 H), 7.62 (d, J = 8.8 Hz, 2 H), 7.45 - 7.40 (m, 1 H), 7.21 - 7.14 (m, 1 H), 3.96 - 3.91 (m, 1 H), 3.75 - 3.56 (m, 2 H), 3.27 - 3.21 (m, 2 H), 1.92 - 1.50 (m, 4 H). Example 118: Synthesis of 4-((2,4-difluorophenyl)ethynyl)-N-(oxetan-2-ylmethyl)benzamide [ka] Using 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.060 g, 0.232 mmol) and oxetan-2-ylmethanamine (0.022 g, 0.256 mmol) as starting materials, 4-((2,4-difluorophenyl)ethynyl)-N-(oxetan-2-ylmethyl)benzamide (0.064 g, 84.1%) was obtained as an ivory solid in the same manner as in Example 11: LRMS (ES) m / z 328.17 [M+H]. + , calculated MW 327.33; 1 H-NMR (400 MHz, DMSO-d6) d 8.73 (t, J = 5.8 Hz, 1 H), 7.89 (d, J = 8.4 Hz, 2 H), 7.74 - 7.61 (m, 1 H), 7.62 (d, J = 8.8 Hz, 2 H), 7.45 - 7.40 (m, 1 H), 7.21 - 7.15 (m, 1 H), 4.82 - 4.76 (m, 1 H), 4.48 - 4.38 (m, 2 H), 3.55 - 3.42 (m, 2 H), 2.61 - 2.57 (m, 1 H), 2.41 - 2.34 (m, 1 H). Example 119: Synthesis of 4-((2,4-difluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide [ka] Using 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.060 g, 0.232 mmol) and (2-methyltetrahydrofuran-2-yl)methanamine (0.029 g, 0.256 mmol) as starting materials, 4-((2,4-difluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide (0.064 g, 77.5%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 356.25 [M+H]. + , calculated MW 355.38; 1 H-NMR (400 MHz, DMSO-d6) d 8.48 (t, J = 6.4 Hz, 1 H), 7.88 (dd, J = 6.4, 2.0 Hz, 2 H), 7.72 - 7.68 (m, 1 H), 7.61 (d, J = 8.4 Hz, 2 H), 7.42 (td. 1.11 (s, 3 H). Example 120: Synthesis of N-((3,3-difluorocyclobutyl)methyl)-4-((2,4-difluorophenyl)ethynyl)benzamide [ka] Using (3,3-difluorocyclobutyl)methanamine hydrochloride (0.050 g, 0.317 mmol) and 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.098 g, 0.381 mmol) as starting materials, N-((3,3-difluorocyclobutyl)methyl)-4-((2,4-difluorophenyl)ethynyl)benzamide (0.049 g, 42.7%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 362.19 [M+H]. + , calculated MW 361.34; 1H-NMR (400 MHz, CD3OD) d 7.75 - 7.81 (m, 2 H), 7.54 - 7.59 (m, 3 H), 7.02 (m, 2 H), 3.48 (d, J = 6.0 Hz, 2 H), 3.28 - 3.29 (m, 1 H), 2.62 (m, 2 H), 2.32 (m, 2 H). Example 121: Synthesis of N-((4,4-difluorocyclohexyl)methyl)-4-((2,4-difluorophenyl)ethynyl)benzamide [ka] Using (4,4-difluorocyclohexyl)methanamine hydrochloride (0.050 g, 0.269 mmol) and 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.083 g, 0.323 mmol) as starting materials, N-((4,4-difluorocyclohexyl)methyl)-4-((2,4-difluorophenyl)ethynyl)benzamide (0.048 g, 63.7%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 390.26 [M+H]. + , calculated MW 389.39; 1 H-NMR (400 MHz, CD3OD) d 8.58 (t, J = 5.2 Hz, 1 H), 7.81 (d, J = 8.4 Hz, 2 H), 7.55 - 7.65 (m, 3 H), 6.97 - 7.08 (m, 2 H), 3.28 - 3.29 (m, 3 H), 2.01 - 2.05 (m, 2 H), 1.69 - 1.85 (m, 4 H), 1.25 - 1.33 (m, 2 H). Example 122: Synthesis of 4-((2,4-difluorophenyl)ethynyl)-N-((3-ethyloxetan-3-yl)methyl)benzamide [ka] Using (3-ethyloxetan-3-yl)methanamine (0.050 g, 0.434 mmol) and 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.135 g, 0.521 mmol) as starting materials, 4-((2,4-difluorophenyl)ethynyl)-N-((3-ethyloxetan-3-yl)methyl)benzamide (0.070 g, 45.4%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 356.18 [M+H]. + , calculated MW 355.38; 1 H-NMR (400 MHz, CD3OD) d 7.82 (d, J = 8.4 Hz, 2 H), 7.58 (d, J = 8.4 Hz, 2 H), 7.54 - 7.60 (m, 1 H), 6.96 - 7.07 (m, 2 H), 4.56 (d, J = 6.4 Hz, 2 H), 4.39 (d, J = 6.0 Hz, 2 H), 3.59 (s, 2 H), 1.74 (q, J = 7.5 Hz, 2 H), 0.97 (t, J = 7.4 Hz, 3 H). Example 123: Synthesis of 4-((2,4-difluorophenyl)ethynyl)-N-((3-fluorooxetan-3-yl)methyl)benzamide [ka] Using (3-fluorooxetan-3-yl)methanamine (0.050 g, 0.476 mmol) and 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.147 g, 0.571 mmol) as starting materials, 4-((2,4-difluorophenyl)ethynyl)-N-((3-fluorooxetan-3-yl)methyl)benzamide (0.090 g, 54.8%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 346.21 [M+H]. + , calculated MW 345.32; 1H-NMR (400 MHz, CD3OD) d 7.83 (d, J = 8.0 Hz, 2 H), 7.58 (d, J = 8.4 Hz, 2 H), 7.54 - 7.60 (m, 1 H), 7.04 (td, J = 9.4, 2.4 Hz, 1 H), 6.99 (td, J = 8.6, 2.0 Hz, 1 H), 4.74 (s, 2 H), 4.69 (s, 2 H), 3.90 (d, J = 20.0 Hz, 2 H). Example 124: Synthesis of (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide [ka] Using (S)-(tetrahydro-2H-pyran-3-yl)methanamine hydrochloride (0.050 g, 0.330 mmol) and 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.102 g, 0.396 mmol) as starting materials, (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide (0.050 g, 42.7%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 356.18 [M+H]. + , calculated MW 355.38; 1 H-NMR (400 MHz, CD3OD) d 8.54 (bs, 1 H), 7.81 (d, J = 6.4 Hz, 2 H), 7.58 (d, J = 7.2 Hz, 3 H), 6.98 - 7.05 (m, 2 H), 3.79 - 3.88 (m, 2 H), 3.42 (m, 1 H), 3.25 (m, 2 H), 1.89 (m, 2 H), 1.56 - 1.64 (m, 2 H), 1.30 - 1.32 (m, 2 H). Example 125: Synthesis of 4-((2,4-difluorophenyl)ethynyl)-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)benzamide [ka] Using (4-methyltetrahydro-2H-pyran-4-yl)methanamine (0.050 g, 0.387 mmol) and 4-((2,4-difluorophenyl)ethynyl)benzoic acid (0.120 g, 0.464 mmol) as starting materials, 4-((2,4-difluorophenyl)ethynyl)-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)benzamide (0.042 g, 29.4%) was obtained as a white solid in the same manner as in Example 11: LRMS (ES) m / z 370.25 [M+H]. + , calculated MW 369.41; 1 H-NMR (400 MHz, CD3OD) d 7.82 (d, J = 8.0 Hz, 2 H), 7.59 (d, J = 8.8 Hz, 2 H), 7.55 - 7.61 (m, 1 H), 6.97 - 7.09 (m, 2 H), 3.58 - 3.76 (m, 4 H), 3.26 - 3.35 (m, 2 H), 1.52 - 1.57 (m, 2 H), 1.34 (m, 2 H), 1.02 (s, 3 H). Experimental Example 1: Confirmation of synergistic analgesic effect due to dual action The synergistic analgesic effect of the dual action of mGluR5 and 5-HT2AR was confirmed using the spinal nerve ligation model, a neuropathic pain model, with MPEP (2-methyl-6-(phenylethynyl)pyridine), a representative mGluR5 antagonist, and MDL11,939, a 5-HT2AR antagonist.

[0067] To confirm the analgesic effects of MPEP and MDL11,939, the analgesic parameter pain reversal rate (% reversal) was calculated according to the method of Experimental Example 4 below when administered alone or simultaneously, and the results are shown in Figure 1. As shown in Figure 1, MPEP or MDL11,939 alone did not show a significant analgesic effect at a sub-effective dose (a dose less than the effective dose that induces a significant analgesic effect). However, when they were administered simultaneously, a significant analgesic effect was evident. As a result, it was revealed that MPEP and MDL11,939 synergistically alleviate pain.

[0068] Experimental example 2: Fluorescence-based Ca 2+ Recruitment assay To measure activity against the mGlu5 receptor, we used a HEK293 cell line that persistently overexpresses the mGlu5 receptor to measure intracellular Ca. 2+ An experiment was conducted to confirm the change in CaCa levels. Cells in cell culture medium were dispensed into a 384-well plate coated with poly-D-lysine and cultured in a 37°C incubator with 5% CO2. The next day, the medium was removed and CaCa 2+ A dye loading buffer containing a reagent capable of measuring EC was added, followed by serial dilution to prepare a working solution (a diluted standard solution of the test compound). The cells were then incubated at 7°C for 60 minutes. The diluted standard solution of the test compound was added to the cells incubated in the dye loading buffer, and the cells were incubated at room temperature for 30 minutes in the dark before measurement. EC was measured using a FLIPR Tetra (MDS). 80 Ca induced by L-glutamate at concentrations 2+ Changes in the level of fluorescent Ca in the presence of test compounds were measured for 2 min. 2+ The signal value was calculated as the EC 80 The fluorescence value at each concentration was set as 100% and the fluorescence signal induced by the vehicle was set as 0%, and the % inhibition of the test compound was estimated. The efficacy of the test compound was calculated as IC 50The values ​​were calculated and shown in Table 1 (+: 1,000-2,000 nM, ++: 500-1,000 nM, +++: 100-500 nM, ++++: less than 100 nM).

[0069] Experimental Example 3: HTRF-based IP1 accumulation assay The 5-HT2AR antagonistic activity of the test compounds was confirmed by measuring IP1 production using a HEK293 cell line permanently overexpressing human 5-HT2AR. Test compounds were dissolved in 100% DMSO to a final concentration of 10 mM. A starting concentration of 10 μM was prepared from the stock solution, which was then serially diluted to prepare a working solution in a buffer containing lithium chloride (LiCl). Cells and compounds prepared in test buffer were placed in a 96-well plate and incubated in a greenhouse for 10 minutes. EC 80 Serotonin was added at a concentration of 0.01% and the cells were incubated at 37°C for 30 minutes in the dark. To measure intracellular IP1 accumulation, IP1-d2 acceptor and IP1-Cryptate donor (an HTRF-based fluorescent signal) were added and incubated at room temperature for 1 hour in the dark. The fluorescence emission signals of the acceptor and donor were detected, and the HTRF ratio values ​​were subtracted by the mean values ​​of the serotonin control. The percentage of activation was calculated by normalizing to the serotonin control (0%) and IP1 control (100%). The IC of the test compound was calculated. 50 The values ​​are shown in Table 1 (+: 1,000-2,000 nM, ++: 500-1,000 nM, +++: 100-500 nM, ++++: less than 100 nM). [Table 1-1] [Table 1-2] [Table 1-3] Experimental Example 4: Experiment on analgesic effect using an animal model (Chung model) The Chung model (spinal nerve ligation model) is a representative animal model of neuropathic pain and is widely used by global pharmaceutical companies around the world as the gold standard of pain animal models.

[0070] Male Sprague-Dawley rats (100-120 g) purchased from Koatech (Korea) were used in this experiment. The rats were housed in a room maintained at a constant temperature and humidity with a 12-hour light / dark cycle. The rats were allowed to eat and drink freely during the experiment.

[0071] For the Chung procedure, rats were anesthetized with isoflurane inhalation, and the left lumbar nerves L5 and L6 were tightly ligated with 6-0 silk sutures between the end of the dorsal ganglion and the entrance to the sciatic ganglion, as previously described (Kim and Chung (1992), Pain 50(3):355-63). After suturing the incision, rats were allowed to recover in a controlled environment for 2 weeks. Then, allodynia was induced physically in the left hind paw of the rats. To measure physical (tactile) allodynia, rats were placed in a cage with a wire mesh bottom. The intensity of the stimulus that elicited a pain response (sudden lifting, licking, or sucking of the paw) was recorded as the stimulus intensity was gradually increased. Paw withdrawal thresholds (PWTs) were determined by increasing or decreasing the intensity of the continuous stimulus, and the results were analyzed using the Dixon up-down method, as described in Chaplan et al. (1994) J. Neurosci. Methods 53(1):55-63. Only rats that did not exhibit behavioral disorders (e.g., limping or dropping their paws) were selected for inclusion in the study, and the PWT of the rats used was ≤3.16 g.

[0072] After measuring the basic reactivity before drug injection, each compound and the vehicle were orally administered (12.5-100 mg / kg), and measurements were repeated at regular intervals (60 minutes, 120 minutes) after drug injection.

[0073] The experimenters performed PWT in a blinded condition, unaware of which rats were administered which drug. The control group received gabapentin (65 mg / kg, intraperitoneal administration), which was randomly mixed during the measurement. Statistical analysis was performed on the measured pain response thresholds by calculating the % reversal rate from pain using the following formula (1). A high recovery rate indicates a significant reduction in allodynia after drug administration.

[0074] Pain recovery rate (% reversal) = [(PWT after drug administration) - (PWT before drug administration)] x 100 / [(15 g, estimated PWT in normal animals) - (PWT before drug administration)] The PWT used here is the logarithm of the gram, a unit of force, multiplied by 10,000, and is a method commonly used in academia. The results are shown in Table 2 below.

[0075] Each experiment consisted of a compound group, a compound vehicle group, and a gabapentin (GBP) group as a positive control group. 0.5% HPMC (hydroxypropyl methylcellulose) was used as the compound vehicle. [Table 2] As can be seen from Table 2 above, it was confirmed that the compound according to an embodiment of the present invention has excellent analgesic effect. Furthermore, the present invention includes the following aspects. [Aspect 1] The following formula (1) [ka] (In the formula, X 1 and X 2 together with the carbon to which they are attached form a 4- to 7-membered aliphatic ring or a 4- to 6-membered heteroaliphatic ring; X 3 is CH or N; R 1 is hydroxy, halo, alkyl, heterocycloalkyl, or heterocycloalkyl-alkyl; R 2 is hydroxy, halo, alkyl, alkoxy, heterocycloalkyl, hydroxyalkyl, haloalkyl, amino, alkylamino, dialkylamino, cycloalkyl-alkyl, cycloalkylamino, haloalkylamino, aminocarbonyl, alkylaminocarbonyl, alkoxycarbonylalkyl, carboxyalkyl, aminocarbonylalkyl, hydroxyaminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, or 5- or 6-membered heteroaryl; R 3 is deuterium, halo, or alkyl; R 4 and R 5 are each independently halo or alkyl; m is an integer from 0 to 3; n is 0 or 1; l, p, and q each independently represent an integer of 0 to 2; The heteroaliphatic ring, heterocycloalkyl, or heteroaryl has one or more heteroatoms selected from the group consisting of N, O, and S; However, X 1 and X 2 together with the carbons to which they are attached form a 6-membered aliphatic ring or a 5-membered heteroaliphatic ring, and X 3 is CH, then n and q are not simultaneously 0. or a pharmaceutically acceptable salt thereof. [Aspect 2] X 1 and X 2 together with the carbon to which they are attached, C 4 -C 7 forms a cycloalkyl or a 4- to 6-membered heterocycloalkyl; X 3 is CH or N; R 1 is hydroxy, halo or C 1 -C 5 is alkyl; R 2 are hydroxy, halo, C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy, 4- to 6-membered heterocycloalkyl, hydroxy-C 1 -C 5 Alkyl, Halo-C 1 -C 5 Alkyl, C 1 -C 5 Alkylamino, C 3 -C 6 Cycloalkyl-C 1 -C 5 Alkyl, C 3 -C 6 Cycloalkylamino, halo-C 1 -C 5 Alkylamino, C 1 -C 5 Alkylaminocarbonyl, C 1 -C 5 Alkoxycarbonyl-C 1 -C 5 Alkyl, carboxy-C 1 -C 5 Alkyl, aminocarbonyl-C1 -C 5 Alkyl, hydroxyaminocarbonyl-C 1 -C 5 Alkyl, C 1 -C 5 Alkylaminocarbonyl-C 1 -C 5 Alkyl, di(C 1 -C 5 Alkyl)aminocarbonyl-C 1 -C 5 alkyl or pyridyl; R 3 is deuterium, fluoro or C 1 -C 5 is alkyl; R 4 and R 5 are each independently halo or C 1 -C 5 is alkyl; m is an integer from 0 to 2; n is 0 or 1; l, p, and q each independently represent an integer of 0 to 2; The compound according to aspect 1, or a pharmaceutically acceptable salt thereof, wherein the heterocycloalkyl has 1 to 3 heteroatoms selected from the group consisting of N and O. [Aspect 3] The compound or a pharmaceutically acceptable salt thereof according to aspect 1, wherein the 4- to 7-membered aliphatic ring is cyclobutane, cyclopentane, cyclohexane, or cycloheptane. [Aspect 4] The compound or a pharmaceutically acceptable salt thereof according to aspect 1, wherein the 4- to 6-membered heteroaliphatic ring is oxetane, tetrahydrofuran, tetrahydropyran, dioxane, or piperidine. [Aspect 5] X 1 and X 2 or a pharmaceutically acceptable salt thereof, wherein: together with the carbon to which they are attached, form an oxetane, tetrahydrofuran, tetrahydropyran, cyclobutane, cyclopentane, or cyclohexane. [Aspect 6] The compound according to aspect 1, or a pharmaceutically acceptable salt thereof, wherein p=0. [Aspect 7] X 3 or a pharmaceutically acceptable salt thereof according to aspect 1, wherein [Aspect 8] A compound according to aspect 7, or a pharmaceutically acceptable salt thereof, wherein at least one of n and q is not 0. [Aspect 9] R 5 8. The compound according to aspect 7, or a pharmaceutically acceptable salt thereof, wherein: is fluoro; and q is 1 or 2. [Aspect 10] R 5 is substituted at the ortho- and / or para-position of the phenyl, or a pharmaceutically acceptable salt thereof. [Aspect 11] The compound according to aspect 1, wherein the compound of formula (1) is selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof: N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-(pyridin-2-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-(pyridin-4-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-3-fluoro-4-(pyridin-4-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-2-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-2-fluoro-4-(pyridin-4-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((3-fluoropyridin-4-yl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((3,4-difluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((3,4-difluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-methylpyridin-4-yl)ethynyl)benzamide; N-((4-(cyclopropylamino)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-morpholinocyclopentyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-(isopropylamino)tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclohexyl)methyl)benzamide; N-((1-(cyclopropylamino)-4-methylcyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(neopentylamino)cyclohexyl)methyl)benzamide; N-((4-(cyclopropylmethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclopentyl)methyl)benzamide; 4-(pyridin-4-ylethynyl)-N-((1-((2,2,2-trifluoroethyl)amino)cyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-hydroxycyclohexyl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(pyridin-3-yl)cyclopentyl)methyl)benzamide; 2-Fluoro-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)methyl)benzamide; N-((4,4-difluorocyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-fluorotetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-(phenylethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; N-((4-(fluoromethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1,4-dioxan-2-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; 4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)-N-methyltetrahydro-2H-pyran-4-carboxamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide; N-((1-(isopropylamino)cyclohexyl)methyl)-4-(phenylethynyl)benzamide; N-((3,3-difluorocyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-hydroxycyclobutyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(oxetan-2-ylmethyl)benzamide; Methyl 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoate; 3-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)propanoic acid; 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoic acid; 4-((2-fluorophenyl)ethynyl)-N-((1-(3-hydroxypropyl)cyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((2-hydroxycyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxycyclohexyl)methyl)benzamide; (4-((2-fluorophenyl)ethynyl)-N-((1-methoxycyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-methoxytetrahydro-2H-pyran-4-yl)methyl)benzamide; N-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl-d2)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; N-((5,5-dimethyltetrahydrofuran-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; N-((3-ethyloxetan-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((1-fluorocyclohexyl)methyl)benzamide; Methyl 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetate; Methyl 2-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)acetate; 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetic acid; (N-((1-(2-amino-2-oxoethyl)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; (N-((4-(2-amino-2-oxoethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(2-(hydroxyamino)-2-oxoethyl)cyclohexyl)methyl)benzamide; (4-((2-fluorophenyl)ethynyl)-N-((1-(2-(methylamino)-2-oxoethyl)cyclohexyl)methyl)benzamide; N-((1-(2-(dimethylamino)-2-oxoethyl)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxyoxetan-3-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; 3-Fluoro-4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(((1s,3s)-3-hydroxycyclobutyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(((1r,3r)-3-hydroxycyclobutyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(((1s,3s)-3-hydroxy-3-methylcyclobutyl)methyl)benzamide; N-((4,4-difluorocyclohexyl)methyl)-4-(pyridin-4-ylethynyl)benzamide; N-((3,3-difluorocyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide; N-((3,3-difluorocyclobutyl)methyl)-4-(phenylethynyl)benzamide; (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl-d)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-morpholinocyclobutyl)methyl)benzamide; N-((3,3-difluoro-1-methylcyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; N-((3-fluorooxetan-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((1-methylcyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((1-methylcyclopentyl)methyl)benzamide; (R)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; N-((3-ethyloxetan-3-yl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (R)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-(oxetan-2-ylmethyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; N-((3,3-difluorocyclobutyl)methyl)-4-((2,4-difluorophenyl)ethynyl)benzamide; N-((4,4-difluorocyclohexyl)methyl)-4-((2,4-difluorophenyl)ethynyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((3-ethyloxetan-3-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((3-fluorooxetan-3-yl)methyl)benzamide; (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; and 4-((2,4-difluorophenyl)ethynyl)-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)benzamide. [Aspect 12] 12. The compound according to embodiment 11, selected from the following compounds, or a pharmaceutically acceptable salt thereof: N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-(phenylethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxyoxetan-3-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(((1s,3s)-3-hydroxy-3-methylcyclobutyl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (R)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; and (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide. [Aspect 13] A pharmaceutical composition for preventing or treating pain, comprising, as an active ingredient, a therapeutically effective amount of a compound of formula (1) according to any one of Aspects 1 to 12 or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or excipient. [Aspect 14] 14. The pharmaceutical composition according to aspect 13, wherein the pain is neuropathic pain.

Claims

1. The following formula (1) 【Chemistry 1】 (In the formula, X 1 and X 2 together with the carbons to which they are attached form a 4- to 7-membered aliphatic ring or a 4- to 6-membered heteroaliphatic ring; X 3 is CH or N; R 1 is hydroxy, halo, alkyl, heterocycloalkyl, or heterocycloalkyl-alkyl; R 2 is hydroxy, halo, alkyl, alkoxy, heterocycloalkyl, hydroxyalkyl, haloalkyl, amino, alkylamino, dialkylamino, cycloalkyl-alkyl, cycloalkylamino, haloalkylamino, aminocarbonyl, alkylaminocarbonyl, alkoxycarbonylalkyl, carboxyalkyl, aminocarbonylalkyl, hydroxyaminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, or a 5- or 6-membered heteroaryl; R 3 is deuterium, halo, or alkyl; R4 is halo or alkyl; R 5 is fluoro; m is an integer from 0 to 3; n is 0 or 1; l and p are each independently an integer from 0 to 2; q is 1 or 2; The heteroaliphatic ring, heterocycloalkyl, or heteroaryl has one or more heteroatoms selected from the group consisting of N, O, and S. or a pharmaceutically acceptable salt thereof.

2. X 1 and X 2 together with the carbon to which they are attached, C 4 -C 7 forms a cycloalkyl or a 4-6 membered heterocycloalkyl; X 3 is CH or N; R 1 is hydroxy, halo or C 1 -C 5 is alkyl; R 2 is hydroxy, halo, C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy, 4- to 6-membered heterocycloalkyl, hydroxy-C 1 -C 5 Alkyl, halo-C 1 -C 5 Alkyl, C 1 -C 5 Alkylamino, C 3 -C 6 Cycloalkyl-C 1 -C 5 Alkyl, C 3 -C 6 Cycloalkylamino, halo-C 1 -C 5 Alkylamino, C 1 -C 5 Alkylaminocarbonyl, C 1 -C 5 Alkoxycarbonyl-C 1 -C 5 Alkyl, carboxy-C 1 -C 5 Alkyl, aminocarbonyl-C 1 -C 5 Alkyl, hydroxyaminocarbonyl-C 1 -C 5 Alkyl, C 1 -C 5 Alkylaminocarbonyl-C 1 -C 5 Alkyl, di(C 1 -C 5 alkyl)aminocarbonyl-C 1 -C 5 alkyl or pyridyl; R 3 is deuterium, fluoro or C 1 -C 5 is alkyl; R4 is halo or C 1 -C 5 is alkyl; R 5 is fluoro; m is an integer from 0 to 2; n is 0 or 1; l and p are each independently an integer from 0 to 2; q is 1 or 2; 2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein the heterocycloalkyl has 1 to 3 heteroatoms selected from the group consisting of N and O.

3. 2. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein the 4- to 7-membered aliphatic ring is cyclobutane, cyclopentane, cyclohexane, or cycloheptane.

4. 2. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein the 4- to 6-membered heteroaliphatic ring is oxetane, tetrahydrofuran, tetrahydropyran, dioxane, or piperidine.

5. X 1 and X 2 10. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: together with the carbon to which they are attached, form an oxetane, tetrahydrofuran, tetrahydropyran, cyclobutane, cyclopentane, or cyclohexane.

6. 2. The compound according to claim 1, wherein p=0, or a pharmaceutically acceptable salt thereof.

7. X 3 2. The compound according to claim 1, wherein is CH, or a pharmaceutically acceptable salt thereof.

8. The compound or pharmaceutically acceptable salt thereof according to claim 7, wherein n is not 0.

9. R 5 2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein: is substituted at the ortho and / or para positions of the phenyl.

10. A compound selected from the group consisting of the following or a pharmaceutically acceptable salt thereof: N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-(pyridin-2-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-(pyridin-4-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-3-fluoro-4-(pyridin-4-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-(pyridin-2-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclobutyl)methyl)-2-fluoro-4-(pyridin-4-ylethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((5-fluoropyridin-2-yl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((3-fluoropyridin-4-yl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((3,4-difluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cycloheptyl)methyl)-4-((3,4-difluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-methylpyridin-4-yl)ethynyl)benzamide; N-((4-(cyclopropylamino)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-morpholinocyclopentyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-(isopropylamino)tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclohexyl)methyl)benzamide; N-((1-(cyclopropylamino)-4-methylcyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(neopentylamino)cyclohexyl)methyl)benzamide; N-((4-(cyclopropylmethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclopentyl)methyl)benzamide; 4-(pyridin-4-ylethynyl)-N-((1-((2,2,2-trifluoroethyl)amino)cyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-hydroxycyclohexyl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(pyridin-3-yl)cyclopentyl)methyl)benzamide; 2-fluoro-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)methyl)benzamide; N-((4,4-difluorocyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-fluorotetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-(phenylethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; N-((4-(fluoromethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1,4-dioxan-2-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; 4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)-N-methyltetrahydro-2H-pyran-4-carboxamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide; N-((1-(isopropylamino)cyclohexyl)methyl)-4-(phenylethynyl)benzamide; N-((3,3-difluorocyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-hydroxycyclobutyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(oxetan-2-ylmethyl)benzamide; Methyl 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoate; 3-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)propanoic acid; 3-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)propanoic acid; 4-((2-fluorophenyl)ethynyl)-N-((1-(3-hydroxypropyl)cyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((2-hydroxycyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxycyclohexyl)methyl)benzamide; (4-((2-fluorophenyl)ethynyl)-N-((1-methoxycyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((4-methoxytetrahydro-2H-pyran-4-yl)methyl)benzamide; N-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl-d2)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; N-((5,5-dimethyltetrahydrofuran-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; N-((3-ethyloxetan-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((1-fluorocyclohexyl)methyl)benzamide; Methyl 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetate; Methyl 2-(4-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)tetrahydro-2H-pyran-4-yl)acetate; 2-(1-((4-((2-fluorophenyl)ethynyl)benzamido)methyl)cyclohexyl)acetic acid; (N-((1-(2-amino-2-oxoethyl)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; (N-((4-(2-amino-2-oxoethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(2-(hydroxyamino)-2-oxoethyl)cyclohexyl)methyl)benzamide; (4-((2-fluorophenyl)ethynyl)-N-((1-(2-(methylamino)-2-oxoethyl)cyclohexyl)methyl)benzamide; N-((1-(2-(dimethylamino)-2-oxoethyl)cyclohexyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxyoxetan-3-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; 3-fluoro-4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(((1s,3s)-3-hydroxycyclobutyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(((1r,3r)-3-hydroxycyclobutyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(((1s,3s)-3-hydroxy-3-methylcyclobutyl)methyl)benzamide; N-((4,4-difluorocyclohexyl)methyl)-4-(pyridin-4-ylethynyl)benzamide; N-((3,3-difluorocyclobutyl)methyl)-4-(pyridin-4-ylethynyl)benzamide; N-((3,3-difluorocyclobutyl)methyl)-4-(phenylethynyl)benzamide; (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; (S)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl-d)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-morpholinocyclobutyl)methyl)benzamide; N-((3,3-difluoro-1-methylcyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; N-((3-fluorooxetan-3-yl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((1-methylcyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((1-methylcyclobutyl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((1-methylcyclopentyl)methyl)benzamide; (R)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (R)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; N-((3-ethyloxetan-3-yl)methyl)-4-((4-fluorophenyl)ethynyl)benzamide; (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (R)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-2-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-(oxetan-2-ylmethyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; N-((3,3-difluorocyclobutyl)methyl)-4-((2,4-difluorophenyl)ethynyl)benzamide; N-((4,4-difluorocyclohexyl)methyl)-4-((2,4-difluorophenyl)ethynyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((3-ethyloxetan-3-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((3-fluorooxetan-3-yl)methyl)benzamide; (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; and 4-((2,4-difluorophenyl)ethynyl)-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)benzamide.

11. 11. The compound of claim 10, selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof: N-((1-(cyclopropylamino)cyclobutyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; N-((1-(cyclopropylamino)cyclopentyl)methyl)-4-((2-fluorophenyl)ethynyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((1-(isopropylamino)cyclohexyl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-(phenylethynyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; (R)-4-((2-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-((3-hydroxyoxetan-3-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((3-methyloxetan-3-yl)methyl)benzamide; 4-((2-fluorophenyl)ethynyl)-N-(((1s,3s)-3-hydroxy-3-methylcyclobutyl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (S)-4-((4-fluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; (R)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydrofuran-3-yl)methyl)benzamide; 4-((4-fluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; 4-((2,4-difluorophenyl)ethynyl)-N-((2-methyltetrahydrofuran-2-yl)methyl)benzamide; and (S)-4-((2,4-difluorophenyl)ethynyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)benzamide.

12. A pharmaceutical composition for the prevention or treatment of pain, comprising a therapeutically effective amount of the compound of formula (1) according to any one of claims 1 to 11 or a pharmaceutically acceptable salt thereof as an active ingredient, together with a pharmaceutically acceptable carrier or excipient.

13. 13. The pharmaceutical composition according to claim 12, wherein the pain is neuropathic pain.

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