ALIPHATIC ACID AMIDE DERIVATIVE

Abstract

The present invention relates to a compound represented by formula (1) (see Formula), the compound having antagonistic activity against serotonin 5-HT2A receptors and serotonin 5-HT7 receptors; or a pharmaceutically acceptable salt of the compound; (in the formula, Z is a nitrogen atom and the like; Y is carbonyl and the like; myn are 1 and the like; R1a to R1d, R2a to R2d, and R4a to R4d are hydrogen atoms and the like; R3 is alkyl and the like; and Q is a specific bicyclic group).

Description

ALIPHATIC ACID AMIDE DERIVATIVE TECHNICAL FIELD OF THE INVENTION The present invention relates to an aliphatic acid amide derivative having antagonist activity for the serotonin 5-HT2A receptor and serotonin 5-HT2A receptor, or a pharmaceutically acceptable salt thereof, and a medicament for the treatment of neuropsychiatric diseases comprising the same as an active ingredient. BACKGROUND OF THE INVENTION Serotonin (5-hydroxytryptamine; hereafter also referred to as 5-HT) is known as one of the main neurotransmitters of the central nervous system, and serotonin is also known to be involved in various brain functions such as emotional reaction and cognitive function. The 5-HT2A receptor, one of the 5-HT receptor subtypes, is a Gq / 11 protein-coupled receptor and is expressed, for example, in the cerebral cortex, hippocampus, and raphe nucleus. Drugs with 5-HT2A receptor antagonist activity include antidepressants, mianserin, and mirtazapine. Atypical antipsychotics with 5-HT2A receptor antagonist activity are used to treat conditions such as schizophrenia, bipolar disorder, major depression, and autism spectrum disorder (Non-Patent Literature 1, Non-Patent Literature 2). The 5-HTβ receptor is a Gs protein-coupled receptor and is widely expressed, for example, in the hypothalamus, thalamus, hippocampus, and raphe nucleus (Non-patent literature 9). Drugs that have antagonistic activity at the 5-HTβ receptor include lurasidone, which is used to treat schizophrenia and bipolar disorder, and vortioxetine, which is used to treat major depression. However, there are no commercially available drugs that have selective antagonistic activity at the 5-HTβ receptor. Lurasidone is used to treat schizophrenia and bipolar disorder, and vortioxetine is used to treat major depression (Non-patent literature 3, Non-patent literature 4, and Non-patent literature 5). It is also known that in some animal models, antagonism of the 5-HT7 receptor leads to an antidepressant and anxiolytic effect, and an effect of improving cognitive function (Non-patent literature 6, Non-patent literature 7).It is also known that mice deficient in the 5-HTβ receptor exhibit an antidepressant effect (Non-patent literature 8). As described above, antagonists for receptor 52 are shown to be HTza and the 5-HT7 receptor are useful separately for many neuropsychiatric diseases, but no drug has antagonistic activity of the 5-HTza receptor and the 5-HT7 receptor in a selective and potent manner. List of Appointments NON-PATENT LITERATURE [Non-Patent Literature 1] P. Seeman, Can. J. Psychiatry. 4:27-38, 2002 [Non-Patent Literature 2] CJ Schmidt, Life Science. 56(25): 2209-2222, 1995 [Non-proprietary literature 3] L. Citrome, 1 Clinical Practice. 65(2): 189-210, 2011 [Non-proprietary literature 4]: YS. Woo, Neuropsychiatric Disease and Treatment. 9: 1521-1529, 2013 [Non-proprietary literature 5] C. Sánchez, Pharmacology & Therapeutics. 145: 43-57, 2015 [Non-proprietary literature 6] Bonaventure P, J Pharmacol Exp Ther. 321:690-8, 2007 [Non-proprietary literature 7] Horisawa T, Behavioral Brain Research. 220: 83-90, 2011 [Non-proprietary literature 8] M. Guscott, Neuropharmacology. 48: 492-502, 2005 [Non-proprietary literature 9] T W. Lovenberg, Neuron. 11: 449-458, 1993 BRIEF DESCRIPTION OF THE INVENTION Problems that will be solved by the invention An object of the present invention is the provision of novel compounds that have antagonistic activity for both the serotonin 5-HT1A receptor and the 5-HT7 receptor, and are useful as a drug for treating neuropsychiatric diseases. Means to solve the problems The present inventors have extensively studied to achieve the foregoing object, and have subsequently found that a compound of formula (1) as shown below, or a pharmaceutically acceptable salt thereof (hereinafter also referred to as the present compound), has antagonistic activity for both the serotonin 5-HT2A receptor and the 5-HT7 receptor. Based on these new discoveries, the present invention has been achieved. The present invention is illustrated as follows. [Point 1] A compound of formula (1): (1) or a pharmaceutically acceptable salt thereof, wherein Z is a nitrogen atom or -CRA-; And it is carbonyl or sulfonyl; m is 1, 2, 3, or 4; n is 0, 1, 2, or 3; provided that when Y is sulfonyl, n is not 0; RA is hydrogen, hydroxy, Ci-6 alkyl, or Ci-6 alkoxy, Rla, Rlb, Rlc, and Rldson are each independently hydrogen, hydroxy, halogen or alkyl of Ci-6 optionally substituted with the same or different 1 to 3 halogen; R2a, R2b, R2c, and R2d are each independently, and each of R2cs or each of R2ds is independently when R2co R2d exist in the plural, hydrogen, halogen or C1-e alkyl (in which the alkyl may be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy, C3-8 cycloalkyl and C1-6 alkoxy), provided that when R2ay R2b, or R2cy R2d that are attached to the same carbon atom are each independently said C1-6 alkyl, they may combine together with the carbon atom to which they are attached to form a saturated 3- to 6-membered carbocycle; R3 is C1-6 alkyl, wherein the alkyl can be optionally substituted with 1 to 5 identical or different substituents selected from the group consisting of halogen, hydroxy, cyano, C3-8 cycloalkyl and C3-8 alkoxy; R4a, R4b, R4cy, and R4d are each independently, and each of R4cs or each of R4ds is independently when R4co and R4d exist in the plural, hydrogen, halogen, C6 alkyl (in which the alkyl may be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy, cyano, C3-8 cycloalkyl, C1-6 alkoxy, C1-6 alkyl ester, and amino optionally substituted with the same or different 1 or 2 C1-6 alkyl (in which the alkyl may be optionally substituted with oxo)), C2-6 alkynyl, or amino (in which the amino may be optionally substituted with the same or different 1 or 2 C1-θ alkyl);provided that when any two of R4a, R4b, R4cy, R4d are each independently said Ci-β alkyl, they may combine together with the carbon atom or carbon atoms to which they are attached to form a saturated 3- to 6-membered carbocycle or a saturated 4- to 6-membered heterocycle wherein when said Ci-e alkyl groups have a substituent, the substituent may be included as a member of the ring of the carbocycle or heterocycle; provided that when Y is sulfonyl and n is 1, any of R4co R4des hydrogen; and when Y is sulfonyl and n is 2 or 3, any of R4co R4d bonded to the carbon atom adjacent to Y is hydrogen; and The ring Q is a group of the following formula (2a), (2b), (2c), (2d), (2e), or (2f): R6 (2d) (2e) (2f) where R5a, R5b, R5c, and R5d are each independently hydrogen, halogen, cyano, Ci-e alkyl, Ci-6 alkoxy (where alkyl and alkoxy can be independent and optionally substituted with the same or different 1 to 3 halogen atoms), or amino optionally substituted with 1 or 2 alkyl of the same or different Ci-e; and R6 is hydrogen, Ci-6 alkyl or C3-8 cycloalkyl, wherein the alkyl and cycloalkyl can each be optionally substituted independently with 1 to 3 identical or different halogens. [Point 2] The compound of point 1, or a pharmaceutically acceptable salt thereof, further characterized in that Rla, Rlb, Rlc, and Rldson are hydrogen. [Point 3] The compound of point 1 or 2, or a pharmaceutically acceptable salt thereof, further characterized in that R2a, R2b, R2c, and R2d are hydrogen. [Item 4] The compound of any of Items 1 to 3 or a pharmaceutically acceptable salt thereof, wherein m is 1. [Item 5] The compound of any of Items 1 to 4 or a pharmaceutically acceptable salt thereof, wherein R3 is alkyl of Ci-6. [Item 6] The compound of any of Items 1 to 5, or a pharmaceutically acceptable salt thereof, wherein Z is -CRA-. [Item 7] The compound of any of Items 1 to 6, or a pharmaceutically acceptable salt thereof, wherein RA is hydrogen. [Item 8] The compound of any of Items 1 to 7, or a pharmaceutically acceptable salt thereof, wherein R5a, R5b, R5c, and R5d are each independently hydrogen, halogen, or Ci-6 alkyl. [Item 9] The compound of any of Items 1 to 8, or a pharmaceutically acceptable salt thereof, wherein R5a, R5c, and R5d are hydrogen. [Item 10] The compound of any of Items 1 to 9 or a pharmaceutically acceptable salt thereof, wherein R5 is hydrogen, halogen or Ci-6 alkyl. [Item 11] The compound of any of Items 1 to 10, or a pharmaceutically acceptable salt thereof, wherein R6 is hydrogen. [Point 12] The compound of any of points 1 to 11, or a pharmaceutically acceptable salt thereof, wherein R4a, R4b, R4c and R4d are each independently, and each of R4cs or each of R4ds is independently when R4c and R exists in the plural, hydrogen, halogen or Ci-6 alkyl, wherein the alkyl may be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy and Ci-6 alkoxy. ML / a / ZUZZ / UU 1341 [Item 13] The compound of any of Items 1 to 12 or a pharmaceutically acceptable salt thereof, wherein n is 0 or 1. [Item 14] The compound of any of Items 1 to 13 or a pharmaceutically acceptable salt thereof, wherein Y is carbonyl. [Item 15] The compound of any of Items 1 to 13 or a pharmaceutically acceptable salt thereof, wherein Y is sulfonyl. [Item 16] The compound of Item 1, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of: [Item 17] A drug comprising a compound according to any of Items 1 to 16, or a pharmaceutically acceptable salt thereof, as an active ingredient. [Item 18] A medicament for treating a mental illness or a disease of the central nervous system, comprising a compound of any of items 1 to 16, or a pharmaceutically acceptable salt thereof, as an active ingredient. [Item 19] The medicinal product of item 18, wherein the mental illness or disease of the central nervous system is schizophrenia, a bipolar disorder, a sleep disorder, an autism spectrum disorder, major depression, treatment-resistant depression or a psychopathic symptom or dementia associated with Alzheimer's disease or Parkinson's disease. [Item 20] A method for treating a mental illness or a disease of the central nervous system, comprising administering a therapeutically effective amount of a compound from any of Items 1 to 16, or a pharmaceutically acceptable salt thereof, to a patient in need. [Item 21] Use of a compound from any of items 1 to 16, or a pharmaceutically acceptable salt thereof, in the manufacture of a drug to treat a mental illness or a disease of the central nervous system. [Item 22] The compound of any of items 1 to 16, or a pharmaceutically acceptable salt thereof, for use in the treatment of a mental illness or a disease of the central nervous system. [Point 23] A medicament for treating a mental illness or a disease of the central nervous system, comprising a compound from any of points 1 to 16, or a pharmaceutically acceptable salt thereof, in combination with at least one drug selected from the group consisting of a drug for treating a developmental disorder such as autism spectrum disorder and attention deficit hyperactivity disorder, an antipsychotic drug and a schizophrenic drug, a drug for treating bipolar disorder, an antidepressant drug, an anti-anxiety drug, a drug for treating obsessive-compulsive disorder, a drug for treating a stress disorder such as post-traumatic stress disorder, a drug for treating a mood disorder, a drug for treating an eating disorder, a drug for treating a sleep disorder such as insomnia, narcolepsy,a sleep apnea syndrome and circadian rhythm disorder, a drug to treat sexual dysfunction, a drug to treat drug dependence, a drug to treat dementia such as Alzheimer's disease, a drug to treat a behavioral and psychological symptom associated with dementia, a drug to improve cerebral metabolism and circulation, a drug to treat a movement disorder such as, Parkinson's disease, an analgesic drug, an antiepileptic drug, an anticonvulsant, a migraine drug, an anesthetic, and a central stimulant. [Item 24] A medicament for treating a mental illness or a disease of the central nervous system, comprising a compound from any of Items 1 to 16, or a pharmaceutically acceptable salt thereof, as an active ingredient, wherein the medicament is used in concomitant treatment with at least one drug selected from the group consisting of a drug for treating a developmental disorder such as autism spectrum disorder and attention deficit hyperactivity disorder, an antipsychotic drug and a schizophrenic drug, a drug for treating bipolar disorder, an antidepressant drug, an anti-anxiety drug, a drug for treating obsessive-compulsive disorder, a drug for treating a stress disorder such as post-traumatic stress disorder, a drug for treating a mood disorder, a drug for treating an eating disorder,A drug for the treatment of a sleep disorder such as insomnia, narcolepsy, sleep apnea syndrome, and a circadian rhythm disorder; a drug for treating sexual dysfunction; a drug for treating drug dependence; a drug for treating dementia such as Alzheimer's disease; a drug for treating a behavioral and psychological symptom associated with dementia; a drug to improve cerebral metabolism and circulation; a drug for treating a movement disorder such as Parkinson's disease; an analgesic drug; an antiepileptic drug; an anticonvulsant; a migraine drug; an anesthetic; and a central stimulant. [Item 25] A crystal of a compound of any of Examples 17, 77, 78, 79 and 80, characterized by powder XRD patterns comprising powder XRD peaks of 4 or more (preferably 10 or more) 2 θ ± 0.2 values ​​selected from those measured in each of the Examples. Effect of the Invention This compound has antagonistic activity for the S-HT1A receptor and the 5-HT7 receptor. This compound is useful as a medication for treating a neuropsychiatric disorder and a central nervous system disorder. BRIEF DESCRIPTION OF THE DRAWINGS ινΐΛ / a / zuzz / uu Figure 1 shows the results of the fear conditioning test using the compound from Example 17 (Test 6). Figure 2 shows the results of measuring the amount of glutamic acid released in rat brain using the compound from Example 17 (Test 7). Figure 3 shows an XRD measurement chart of powder from Example 78. DETAILED DESCRIPTION OF THE INVENTION The present invention is described in detail below. In the description, the number of carbon atoms in the definition of substituents may indicate, for example, Ci-e. Specifically, the term alkyl in Ci-e means an alkyl group having from 1 to 6 carbon atoms. The halogen used here includes, for example, a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Preferably, it includes one fluorine atom and one chlorine atom. The C1-6 alkyl used herein means a saturated hydrocarbon group of linear or branched chain having from 1 to 6 carbon atoms. Preferably, the C1-6 alkyl includes C1-4 alkyl, and more preferably C1-3 alkyl. The C1-3 alkyl includes, for example, methyl, ethyl, propyl, and 1-methylethyl. The C1-4 alkyl includes, for example, butyl, 1,1-dimethylethyl, 1-methylpropyl, and 2-methylpropyl, in addition to the examples listed above for the C1-3 alkyl. The Ci-e alkyl includes, for example, pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylbutyl, 2-methylbutyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, and hexyl, in addition to the examples listed before the Ci-4 alkyl. The phrase "the alkyl is substituted with oxo" used here means that a keto group (C=O) is formed with any of the carbon atoms that make up the alkyl. The C3-8 cycloalkyl used herein means a saturated cyclic hydrocarbon group having 3 to 8 carbon atoms, including those with a partially unsaturated bond and a bridging structure. C3-8 cycloalkyl preferably includes C3-6 cycloalkyl. C3-6 cycloalkyl includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. C3-8 cycloalkyl includes, for example, cycloheptyl and cyclooctyl, in addition to the examples listed for C3-6 cycloalkyl. The alkoxy Ci e is used interchangeably with Ci-e alkoxy in this document, and the alkyl part of Ci-e is the same as the alkyl of Ci< above. The Ci-e alkoxy preferably includes C1-4 alkoxy, more preferably C1-3 alkoxy. The C1-3 alkoxy includes, for example, methoxy, ethoxy, propoxy, and 1-methylethoxy. The Cu alkoxy includes, for example, butoxy, 1,1-dimethylethoxy, 1-methylpropoxy, and 2-methylpropoxy, in addition to the examples listed before the C1-3 alkoxy. The C1-4 alkoxy includes, for example, pentyloxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 1-methylbutoxy, 2-methylbutoxy, 4-methylpentyloxy, 3-methylpentyloxy, 2-methylpentyloxy, 1-methylpentyloxy, and hexyloxy, in addition to the examples listed above for the C1-4 alkoxy. The Ci-β alkyl ester used here means an ester (-COOR') of which the R' part is the Ci-e alkyl group above. The Ci-e alkyl ester preferably includes C1-4 alkyl esters, more preferably C1-3 alkyl esters. The C1-3 alkyl ester includes, for example, methyl ester, ethyl ester, propyl ester, and 1-methylethyl ester. The C1-4 alkyl ester includes, for example, butyl ester, 1,1-dimethylethyl ester, 1-methylpropyl ester, and 2-methylpropyl ester, in addition to the examples listed before the C1-3 alkyl ester. The C1-e alkyl ester includes, for example, pentyl ester, 1,1-dimethylpropyl ester, 1,2-dimethylpropyl ester, 1-methylbutyl ester, 2-methylbutyl ester, 4-methylpentyl ester, 3-methylpentyl ester, 2-methylpentyl ester, 1-methylpentyl ester, and hexyl ester, in addition to the examples listed before the C1-4 alkyl ester. The C2-6 alkynyl used herein means a linear or branched unsaturated hydrocarbon group having from 2 to 6 carbon atoms. The C2-6 alkynyl preferably includes the C2-4 alkynyl, and more preferably the C2-3 alkynyl. The C2-3 alkynyl includes, for example, ethynyl and propynyl. The C2-4 alkynyl includes, for example, butynyl, in addition to the examples listed before the C2-3 alkynyl. The C2-6 alkynyl includes, for example, pentynyl and hexynyl, in addition to the examples listed before the C2-4 alkynyl. The 3- to 6-membered carbocycle used here refers to a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms, including those with a partially unsaturated bond and a bridging structure. The 3- to 6-membered saturated carbocycle preferably includes 5- to 6-membered saturated carbocycles. Examples of 5- or 6-membered monocyclic saturated carbocycles include cyclopentane and cyclohexane. Examples of 3- to 6-membered saturated carbocycles include cyclopropane and cyclobutane, in addition to the examples of 5- or 6-membered monocyclic saturated carbocycles listed above. A saturated 4- to 6-membered heterocycle group means a saturated ring composed of 4 to 6 atoms comprising one or two atoms selected independently from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom, in addition to the carbon atoms. The saturated 4- to 6-membered heterocycle group includes those having a partially unsaturated bond or a bridging structure. The saturated 4- to 6-membered heterocycle group preferably includes the saturated 5- or 6-membered monocyclic heterocycle group. The saturated 5- or 6-membered monocyclic heterocycle includes, for example, tetrahydrofuryl, pyrrolidinyl, imidazolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl, hexamethyleneiminyl, oxazolidinyl, thiazolidinyl, oxoimidazolidinyl, dioxoimidazolidinyl, and oxooxazolidinyl. IVIA / a / ZUZZ / UU ÍWf iviA / a / zuzz / uu dioxooxazolidinyl, dioxotiazolidinyl, tetrahydrofuranyl, tetrahydropyranyl. The saturated 4- to 6-membered heterocycle includes, for example, oxetanyl and azetidinyl, in addition to the examples listed above of the saturated 5- or 6-membered monocyclic heterocycle group. In a compound of Formula (1), the preferred examples of Z, Y, m, n, RA, Rla, Rlb, Rlc, Rld, R2a, R2b, R2c, R2d, R3, R4a, R4b, R4c, R4d, Q, R5a, R5b, R5c, R5d, and R6 are shown below, but the scope of the present invention is not limited to the scope of the following compounds. One form of Z includes -CRA-. Another form of Z includes a nitrogen atom. One form of Y includes carbonyl. Another form of Y includes sulfonyl. A preferred modality of m includes 1 and 2. A more preferred modality of m includes 1. A preferred form of n includes 0, 1, and 2. A more preferred form of n includes 0 and 1. A particularly preferred form of n includes 1. A preferred embodiment of RA includes hydrogen, hydroxyl, and alkyl of Ci-e. A more preferred embodiment includes hydrogen and alkyl of Ci 3. An additional preferred embodiment includes hydrogen, ethyl, and methyl. The most preferred embodiment includes hydrogen. The preferred embodiments of Rla, Rlb, Rlc, and Rld each independently include hydrogen, hydroxyl, halogen, and C1-6 alkyl. Further preferred embodiments include hydrogen, halogen, and C1-3 alkyl. Other preferred embodiments include hydrogen, fluorine atom, chlorine atom, ethyl, and methyl. Especially preferred embodiments include hydrogen, fluorine atom, and methyl. Most preferred embodiments include hydrogen. The preferred embodiments of R2a, R2b, R2c, and R2d each independently include hydrogen, halogen, and C1-6 alkyl. Further preferred embodiments include hydrogen, halogen, and C1-3 alkyl. Other preferred embodiments include hydrogen, fluorine atom, chlorine atom, ethyl, and methyl. Especially preferred embodiments include hydrogen, fluorine atom, and methyl. Most preferred embodiments include hydrogen. In preferred embodiments, R3 includes C1-6 alkyl. The most preferred embodiment includes C1-3 alkyl. An additional preferred embodiment includes ethyl and methyl. A particularly preferred embodiment includes ethyl. The preferred embodiments of R4a, R4b, R4c, and R4d each independently include hydrogen, halogen, C1-6 alkyl, C2-6 alkynyl, and amino optionally substituted with the same or different 1- or 2-C1-6 alkyl. The most preferred embodiments include hydrogen, halogen, C1-6 alkyl, and amino optionally substituted with the same or different 1- or 2-C1-6 alkyl. Additional preferred embodiments include hydrogen, halogen, and C1-6 alkyl. Especially preferred embodiments include hydrogen and C1-6 alkyl. Especially preferred embodiments include hydrogen, methyl, and methoxymethyl. The most preferred embodiments include hydrogen. A preferred modality of Q includes (2a), (2c), (2d), (2e), and (2f). A more preferred modality includes (2a), (2d), and (2e). A particularly preferred modality includes (2a). The preferred embodiments of R5a, R5b, R5c, and R5d each independently include hydrogen, halogen, cyano, Ci-e alkyl, Ci-6 alkoxy, and amino optionally substituted with the same or different 1- or 2-Ci-β alkyl. The most preferred embodiments include hydrogen, halogen, cyano, Ci-β alkyl, and Ci-β alkoxy. Other preferred embodiments include hydrogen, a fluorine atom, and a chlorine atom. The most preferred embodiments include hydrogen and fluorine atoms. A preferred embodiment of R6 includes hydrogen, C1-6 alkyl, and C3-8 cycloalkyl. A further preferred embodiment includes hydrogen and C1-6 alkyl. An additional preferred embodiment includes hydrogen and C1-3 alkyl. A particularly preferred embodiment includes hydrogen. One modality of a Formula compound (1) includes the following modality (A). (A) A pharmaceutically acceptable compound or salt thereof, wherein Z is a nitrogen atom or -CRA-; And it is carbonyl or sulfonyl; m is 1 or 2; n is 0, 1, 2, or 3; provided that when Y is sulfonyl, n is not 0; Raes hydrogen or alkyl of Ci-e; Rla, Rlb, Rlc, and Rldson are each independently hydrogen or alkyl of Cí e; R2a, R2b, R2cy, and R2d are each independently, and each of R2cs or each of R2ds is independently when R2co and R2d exist in the plural, hydrogen or alkyl Cí e; R3es alkyl of Cí e; R4a, R4b, R4c, and R4d are each independently, and each of R4cs or each of R4ds is independently when R4co R4d exist plurally, hydrogen, halogen, C1-6 alkyl (in which the alkyl may be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy, C1-6 alkoxy, C1-6 alkyl ester and amino optionally substituted with the same or different 1 or 2 C1-6 alkyl (in which the alkyl may be optionally substituted with oxo)), C2-6 alkynyl or amino (in which the amino may be optionally substituted with the same or different 1 or 2 C1-ε alkyl); provided that when any two of R4a, R4b, R4cy, or R4d are each independently said C1-6 alkyl, they can combine together with the carbon atom or carbon atoms to which they are attached to form a saturated 3- to 6-membered cabocyclocycle or a saturated 4- to 6-membered heterocycle in ML / a / ZUZZ / UU 1341 that when said Ci-e alkyl groups have a substituent, the substituent may be included as a member of the carbocycle or heterocycle ring; provided that when Y is sulfonyl and n is 1, any of R4co R4des hydrogen; and when Y is sulfonyl and n is 2 or 3, any of R4co R4d bonded to the carbon atom adjacent to Y is hydrogen; and The ring Q is a group of the following formula (2a), (2b), (2c), (2d), (2e), or (2f): (2d) (2e) (2f) where R5a, R5b, R5c, and R5d are each independently hydrogen, halogen, or alkyl of Ci e; and R6 is hydrogen or alkyl of Ci-6. Another form of a compound of Formula (1) includes the following form (B): (B) A compound or a pharmaceutically acceptable salt thereof, wherein Z is a nitrogen atom or -CRA-; And it is carbonyl; m is 1 or 2; n is 0, 1, 2, or 3; RAes hydrogen or alkyl of Cí e; Rla, Rlb, Rlc, and Rldson are each independently hydrogen or alkyl of Cí e; R2a, R2b, R2cy, and R2d are each independently, and each of R2cs or each of R2ds is independently when R2co and R2d exist in the plural, hydrogen or alkyl Ci s; R3es alkyl of Cí e; R4a, R4b, R4cy, and R4d are each independently, and each of R4cs or each of R4ds is independently when R4co and R4d exist in the plural, hydrogen, halogen, C6 alkyl (in which the alkyl may be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy, cyano, C3-6 cycloalkyl, C3-6 alkoxy, C3-6 alkyl ester, and amino optionally substituted with the same or different 1 or 2 alkyl C3-6 (in which the alkyl may be optionally substituted with oxo)), C2-6 alkynyl, or amino (in which the amino may be optionally substituted with the same or different 1 or 2 alkyl C3-6);provided that when any two of R4a, R4b, R4cy, R4d are each independently said C1-6 alkyl, they may combine together with the carbon atom or carbon atoms to which they are attached to form a saturated 3- to 6-membered carbocycle or a saturated 4- to 6-membered heterocycle wherein when said C1-e alkyl groups have a substituent, the substituent may be included as a member of the ring of the carbocycle or heterocycle; The ring Q is a group of the following formula (2a), (2b), (2c), (2d), (2e), or (2f): (2a) (2b) (2c) R6 (2d) (2e) (2f) where R5a, R5b, R5c, and R5d are each independently hydrogen, halogen, or alkyl of Ci-e; and R6 is hydrogen or C1-6 alkyl. Another form of a compound of Formula (1) includes the following form (C): (C) A compound or a pharmaceutically acceptable salt thereof, wherein Z is a nitrogen atom or -CRA-; And it's sulfonyl; m is 1 or 2; n is 1, 2 or 3; RAes hydrogen or alkyl of Ci-&; Rla, Rlb, Rlc, and Rldson are each independently hydrogen or alkyl of Ci-e; R2a, R2b, R2cy, and R2d are each independently, and each of R2cs or each of R2ds is independently when R2co and R2d exist in the plural, hydrogen or alkyl Ci-e; R3es alkyl of Ci-e; R4a, R4b, R4cy, and R4d are each independently, and each of R4cs or each of R4ds is independently when R4co and R4d exist in the plural, hydrogen, halogen, Ci6 alkyl (in which the alkyl may be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy, cyano, C3-6 cycloalkyl, Ci-6 alkoxy, Ci-e alkyl ester, and amino optionally substituted with the same or different 1 or 2 Ci-6 alkyl (in which the alkyl may be optionally substituted with oxo)), C2-6 alkynyl, or amino (in which the amino may be optionally substituted with the same or different 1 or 2 Ci-e alkyl);provided that when any two of R4a, R4b, R4cy, R4d are each independently said C1-6 alkyl, they may combine together with the carbon atom or carbon atoms to which they are attached to form a saturated 3- to 6-membered carbocycle or a saturated 4- to 6-membered heterocycle wherein when said C1-e alkyl groups have a substituent, the substituent may be included as a member of the ring of the carbocycle or heterocycle; with the condition that when n is 1, any of R4co R4des hydrogen; and when n is 2 or 3, any of R4co R4d bonded to the carbon atom adjacent to Y is hydrogen; and The ring Q is a group of the following formula (2a), (2b), (2c), (2d), (2e), or (2f): (2d) (2e) (2f) where R5a, R5b, R5c, and R5d are each independently hydrogen, halogen, or alkyl of Ci-6j and R6 is hydrogen or alkyl of Ci-e. Another form of a compound of Formula (1) includes the following form (D): (D) A compound or a pharmaceutically acceptable salt thereof, wherein Z is -CRA-; And it is carbonyl; m is 1; n is 0 or 1; RAes hydrogen; Rla, Rlb, Rlc, and Rldson hydrogen; R2a, R2b, R2c, and R2d are hydrogen; R3 is alkyl of Ci-s; R4a, R4b, R4cy, and R4d are each independently, and each of R4cs or each of R4ds is independently when R4co and R4d exist in the plural, hydrogen, halogen, Ci6 alkyl (in which the alkyl may be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy, cyano, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 alkyl ester, and amino optionally substituted with the same or different 1 or 2 C1-6 alkyl (in which the alkyl may be optionally substituted with oxo)), C2-6 alkynyl, or amino (in which the amino may be optionally substituted with the same or different 1 or 2 Ci-s alkyl);provided that when any two of R4a, R4b, R4cy, R4d are each independently said C1-6 alkyl, they can combine together with the carbon atom or carbon atoms to which they are attached to form a saturated 3- to 6-membered carbocycle or a saturated 4- to 6-membered heterocycle wherein when said C1-6 alkyl groups have a substituent, the substituent can be included as a member of the ring of the carbocycle or heterocycle; and; The ring Q is a group of formula (2a). Another form of a compound of Formula (1) includes the following form (E): (E) A compound or a pharmaceutically acceptable salt thereof, wherein Z is -CRA-; And it is carbonyl; m is 1; n is 0 or 1; RAes hydrogen; Rla, Rlb, Rlc, and R2a are each independently hydrogen; R2a, R2b, R2c, and R2d are each independently hydrogen; R3es alkyl of Ci-e; R4a, R4b, R4cy, and R4d are each independently, and each of R4cs or each of R4ds is independently when R4co and R4d exist in the plural, hydrogen, halogen, C6 alkyl (in which the alkyl may be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy, cyano, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 alkyl ester, and amino optionally substituted with the same or different 1 or 2 C2-β alkyl (in which the alkyl may be optionally substituted with oxo)), C2-6 alkynyl, or amino (in which the amino may be optionally substituted with the same or different 1 or 2 C2-γ alkyl);provided that when any two of R4a, R4b, R4cy, R4d are each independently said C1-6 alkyl, they can combine together with the carbon atom or carbon atoms to which they are attached to form a saturated 3- to 6-membered carbocycle or a saturated 4- to 6-membered heterocycle wherein when said C1-6 alkyl groups have a substituent, the substituent can be included as a member of the ring of the carbocycle or heterocycle; and; The ring Q is a group of formula (2d). Another form of a compound of Formula (1) includes the following form (F): (F) A compound or a pharmaceutically acceptable salt thereof, wherein Z is -CRA-; And it is carbonyl; m is 1; n is 0 or 1; RAes hydrogen; Rla, Rlb, Rlc, and Rldson hydrogen; R2a, R2b, R2c, and R2d are hydrogen; R3es alkyl of Ci-e; R4a, R4b, R4cy, and R4d are each independently, and each of R4cs or each of R4ds is independently when R4co and R4d exist in the plural, hydrogen, halogen, C1-6 alkyl (in which the alkyl may be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy, cyano, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 alkyl ester, and amino optionally substituted with the same or different 1- or 2-C1-6 alkyl (in which the alkyl may be optionally substituted with oxo)), C2-6 alkynyl, or amino (in which the amino may be optionally substituted with the same or different 1- or 2-C1-6 alkyl);provided that when any two of R4a, R4b, R4cy, R4d are each independently said C1-6 alkyl, they can combine together with the carbon atom or carbon atoms to which they are attached to form a saturated 3- to 6-membered carbocycle or a saturated 4- to 6-membered heterocycle wherein when said C1-6 alkyl groups have a substituent, the substituent can be included as a member of the ring of the carbocycle or heterocycle; and ινΐΛ / a / zuzz / uu; The ring Q is a group of formula (2e). Another form of a compound of Formula (1) includes the following form (G): (G) A compound or a pharmaceutically acceptable salt thereof, wherein Z is -CRA-; And it's sulfonyl; m is 1; n is 1; RAes hydrogen; Rla, Rlb, Rlc, and Rldson hydrogen; R2a, R2b, R2c, and R2d are hydrogen; R3 is alkyl of Ci-s; R4a, R4b, R4cy, and R4d are each independently, and each of R4cs or each of R4ds is independently when R4co and R4d exist in the plural, hydrogen, halogen, C6 alkyl (in which the alkyl may be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy, cyano, C3 cycloalkyl, C6 alkoxy, C1-6 alkyl ester, and amino optionally substituted with the same or different 1 or 2 C1-6 alkyl (in which the alkyl may be optionally substituted with oxo)), C2-6 alkynyl, or amino (in which the amino may be optionally substituted with the same or different 1 or 2 C1-6 alkyl);provided that when any two of R4a, R4b, R4cy, R4d are each independently said C1-6 alkyl, they may combine together with the carbon atom or carbon atoms to which they are attached to form a saturated 3- to 6-membered carbocycle or a saturated 4- to 6-membered heterocycle wherein when said C1-6 alkyl groups have a substituent, the substituent may be included as a member of the ring of the carbocycle or heterocycle; provided that R4co R4dsea hydrogen; and The ring Q is a group of formula (2a). Another form of a compound of Formula (1) includes the following form (H): (H) A compound or a pharmaceutically acceptable salt thereof, wherein Z is -CRA-; And it's sulfonyl; m is 1; n is 1; RAes hydrogen; Rla, Rlb, Rlc, and Rldson hydrogen; R2a, R2b, R2c, and R2d are hydrogen; R3es alkyl of Ci-e; R4a, R4b, R4c, and R4d are each independently, and each of R4cs or each of R4ds is independently when R4co R4d exist plurally, hydrogen, halogen, Ci-6 alkyl (in which the alkyl may be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy, Ci-β alkoxy, Ci-6 alkyl ester and amino optionally substituted with the same or different 1 or 2 Ci-6 alkyl (in which the alkyl may be optionally substituted with oxo)), C2-6 alkynyl or amino (in which the amino may be optionally substituted with the same or different 1 or 2 Ci-e alkyl);provided that when any two of R4a, R4b, R4cy, R4d are each independently said C1-6 alkyl, they may combine together with the carbon atom or carbon atoms to which they are attached to form a saturated 3- to 6-membered carbocycle or a saturated 4- to 6-membered heterocycle wherein when said C1-6 alkyl groups have a substituent, the substituent may be included as a member of the ring of the carbocycle or heterocycle; provided that R4co R4dsea hydrogen; and The ring Q is a group of formula (2e). A compound of formula (1) may have at least one asymmetric carbon atom. The present compound, therefore, includes racemates of a compound of formula (1), as well as optically active isomers of a compound of formula (1). When a compound of formula (1) has two or more asymmetric carbon atoms, it may exhibit stereoisomerism. The present compound, therefore, includes stereoisomers of a compound of formula (1) and mixtures thereof. Furthermore, deuterated compounds in which one, two or more 4H in a compound of formula (1) are replaced with 2H (D) are included in a compound of formula (1). A compound of Formula (1) or a pharmaceutically acceptable salt thereof may exist in the form of a hydrate and / or solvate, and the hydrate and solvate, such as a solvate in ethanol, are included in the present compound. In addition, the present compound also includes those in crystalline forms of all their forms. When a compound of Formula (1) has an acid group, a pharmaceutically acceptable salt thereof includes, for example, an alkali metal salt such as a sodium salt and a potassium salt; an alkaline earth metal salt such as a calcium salt and a magnesium salt; an inorganic metal salt such as a zinc salt; and an organic base salt such as triethylamine, triethanolamine, trihydroxymethylaminomethane, and an amino acid. When a compound of formula (1) has a basic group, a pharmaceutically acceptable salt thereof includes, for example, an inorganic acid salt such as hydrochloride, hydrobromide, sulfate, phosphate, and nitrate; and an organic acid salt such as acetate, propionate, succinate, lactate, malate, tartrate, citrate, maleate, fumarate, methanesulfonate, p20 toluenesulfonate, benzenesulfonate, ascorbate, and orotate. From here on, the procedures for preparing the present compound are explained together with examples, but the present invention should not be limited to them. Preparation procedure The present compound can be prepared by any of the preparation processes mentioned below and combined with known processes. Each compound appearing in the following schemes can also exist in its salt form, and such salts may include, for example, a corresponding salt exemplified as a salt of a compound of formula (1). The reactions mentioned below are only examples; therefore, the present compound may optionally be prepared by other means based on the knowledge of an expert in organic synthesis. If there is a functional group that needs to be protected in the preparation procedures mentioned below, the functional group may be protected as appropriate and then unprotected after completion of the reaction or reaction sequences to obtain a desired compound, although the use of any protecting groups is not specifically indicated. The protecting group used herein includes, for example, general protecting groups described in T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 3rd ed., John Wuey and Sons, Inc., New York (1999). More specifically, a protecting group for an amino group includes, for example, benzyloxycarbonyl, tert-butoxycarbonyl, acetyl, and benzyl. A protecting group for a hydroxyl group includes, for example, trialkylsilyl, acetyl, and benzyl. The protection and deprotection can be carried out by conventional means in organic synthesis chemistry (e.g., the methods described in T. V. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wuey and Sons, Inc., New York (1999)), or similar means. Preparation procedure 1 In the compound of formula (la), among the compounds of formula (1) it can be prepared, for example, by the following procedure: ινΐΛ / a / zuzz / uu / 341 where Z, m, n, Rla, Rlb, Rlc, Rld, R2a, R2b, R2c, R2d, R3, R4a, R4b, R4c, R4d, and Ring Q are as defined in the previous point [1]. Compound (a) is prepared by reacting compound (4) and the carboxylic acid of Formula (5) in a suitable inert solvent in the presence of a suitable condensing agent. The reaction may be carried out in the presence of a suitable base. The reaction temperature generally ranges from approximately -20°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the condensing agent used, the starting materials, and the solvent used, and generally ranges from 10 minutes to 48 hours. Examples of the condensing agents used here include dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIPC), l-ethyl-3-(3-dimethylaminepropyl)carbodiimide (WSC), benzotriazol-l-l-tris(dimethylamine)phosphonium hexafluorophosphate (BOP), diphenylphosphonyldiamide (DPPA), N,N-carbonyldiimidazole (CDI), benzotriazol-l-l-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU), and O-(7-azabenzotriazol-l-l)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU). As needed, additives such as N-hydroxysuccinimide (HOSu), 1-hydroxybenzotriazole (HOBt), 3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine (HOOBt) can be added. Examples of the base used here include organic bases such as triethylamine, diisopropylethylamine, and pyridine; inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, potassium hydroxide, sodium hydroxide, and sodium hydride; and metal alkoxides such as sodium methoxide and potassium tert-butoxide. Examples of the inert solvent used here include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as benzene and toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF) and 1,4-dioxane; polar aprotic solvents such as acetonitrile, acetone, methyl ethyl ketone, dimethylformamide, N-methyl-2-pyrrolidinone and dimethyl sulfoxide; basic solvents such as pyridine; and mixtures of solvents thereof. Preparation procedure 2 Among the compounds of formula (4), the compound of formula (4a) can be prepared, for example, by the following procedure. (6) (8) (4a) In the scheme, Z, Rla, Rlb, Rlc, Rld, R2a, R2b, R2c, R2d, R3, and Ring Q are as defined in the previous Article [1]; and I is 0, 1, 2 or 3. Compound (8) is prepared by reacting compound (6) and an aldehyde of formula (7) under reductive amination with a suitable reducing agent in a suitable inert solvent. The reaction may be carried out in the presence of a suitable base or acid, as appropriate. The reaction temperature generally ranges from approximately -20°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the reducing agent used, the starting materials, and the solvent used, and generally ranges from 10 minutes to 48 hours. Examples of reducing agents used here include complex hydride compounds such as sodium triacetoxyborohydride, lithium aluminum hydride, sodium borohydride, and sodium cyanoborohydride; and borane complexes such as borane-dimethyl sulfide complex and borane-tetrahydrofuran complex. Examples of the base used here include organic bases such as triethylamine, diisopropylethylamine, and pyridine; inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, potassium hydroxide, sodium hydroxide, and sodium hydride; and metal alkoxides such as sodium methoxide and potassium tert-butoxide. Examples of acids used here include acetic acid, trifluoroacetic acid, and methanesulfonic acid, and inorganic acids such as hydrochloric acid and sulfuric acid. Examples of inert solvents used here include water; acetonitrile; halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as benzene and toluene; ether solvents such as 1,2-dimethoxyethane, tetrahydrofuran, and 1,423-dioxane; alcohol solvents such as methanol, ethanol, and 2-propanol; polar aprotic solvents such as dimethylformamide and N-methyl-2-pyrrolidinine; and mixtures of solvents thereof. Compound (4a) is prepared by processing compound (8) with a suitable acid in a suitable inert solvent. The reaction temperature generally ranges from -20°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the acid used, the starting materials, and the solvent, and generally ranges from 10 minutes to 48 hours. Examples of acids used here include organic acids such as trifluoroacetic acid and inorganic acids such as hydrochloric acid and sulfuric acid. Examples of inert solvents used here include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as benzene and toluene; ether solvents such as diethyl ether, tetrahydrofuran, 1,4-dioxane and 1,2-dimethoxyethane; lower alcohols such as methanol, ethanol and 2-propanol; polar aprotic solvents such as acetonitrile, dimethylformamide, N-methyl-2-pyrrolidone and dimethyl sulfoxide; and mixtures of solvents thereof. Preparation procedure 3 The compound of formula (8) can be prepared, for example, by the following procedure. (11) In the scheme, Z, m, Rla, Rlb, Rlc, Rld, R2a, R2b, R2c, R2d, R3, and ring Q are as defined in point [1] above; LG is a leaving group such as iodine, bromine, chlorine, and substituted sulfonyl (e.g., methanesulfonyl and p-toluenesulfonyl). Compound (8) is prepared by reacting compound (6) and an alkylating agent of formula (9) in a suitable inert solvent. The reaction can be carried out in the presence of a suitable base, as required, and also in the presence of a suitable phase-transfer catalyst. The reaction temperature generally ranges from approximately -20°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the base used, the starting materials, and the solvent, and generally ranges from 10 minutes to 48 hours. Examples of the base used here include organic bases such as triethylamine, diisopropylethylamine, and pyridine; inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, potassium hydroxide, sodium hydroxide, and sodium hydride; and metal alkoxides such as sodium methoxide and potassium tert-butoxide. Examples of the phase transfer catalyst used here include tetrabutylammonium hydrogen sulfate. Examples of inert solvents used here include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as benzene and toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF) and 1,4-dioxane; lower alcohols such as methanol, ethanol and 2-propanol; polar aprotic solvents such as acetonitrile, acetone, methyl ethyl ketone, dimethylformamide, N-methyl-2-pyrrolidinone and dimethyl sulfoxide; and mixtures of solvents thereof. Compound (11) is prepared by reacting compound (6) and an alkylating agent of formula (10) in a suitable inert solvent. The reaction may be carried out in the presence of a suitable base as required and also in the presence of a suitable phase-transfer catalyst, as appropriate. The reaction temperature generally ranges from approximately -20°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the base used, the starting materials, and the solvent used, and generally ranges from 10 minutes to 48 hours. Examples of the bases used here include organic bases such as triethylamine, diisopropylethylamine, and pyridine; inorganic bases such as potassium carbonate, sodium carbonate, ML / a / ZUZZ / UU 1341 cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, potassium hydroxide, sodium hydroxide and sodium hydride; and metal alkoxides such as sodium methoxide and potassium tert-butoxide. Examples of the phase transfer catalyst used here include tetrabutylammonium hydrogen sulfate. Examples of inert solvents used here include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as benzene and toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF) and 1,4-dioxane; lower alcohols such as methanol, ethanol and 2-propanol; polar aprotic solvents such as acetonitrile, acetone, methyl ethyl ketone, dimethylformamide, N-methyl-2-pyrrolidinone and dimethyl sulfoxide; and mixtures of solvents thereof. Compound (8) is prepared by reacting compound (11) and an alkylating agent of formula (12) in a suitable inert solvent. The reaction may be carried out in the presence of a suitable base as required and also in the presence of a suitable phase-transfer catalyst, as appropriate. The reaction temperature generally ranges from approximately -20°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the base used, the starting materials, and the solvent used, and generally ranges from 10 minutes to 48 hours. Examples of the base used here include organic bases such as triethylamine, diisopropylethylamine, and pyridine; inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, potassium hydroxide, sodium hydroxide, and sodium hydride; and metal alkoxides such as sodium methoxide and potassium tert-butoxide. Examples of the phase transfer catalyst used here include tetrabutylammonium hydrogen sulfate. Examples of inert solvents used here include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as benzene and toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF) and 1,4-dioxane; lower alcohols such as methanol, ethanol and 2-propanol; polar aprotic solvents such as acetonitrile, acetone, methyl ethyl ketone, dimethylformamide, N-methyl-2-pyrrolidinone and dimethyl sulfoxide; and mixtures of solvents thereof. ML / a / ZUZZ / UU 1341 Preparation procedure 4 ινΐΛ / a / zuzz / uu Among the compounds of formula (1), the compound of formula (If) can be prepared, for example, by the following procedure. In the scheme, Z, m, Rla, Rlb, Rlc, Rld, R2a, R2b, R2c, R2d, R3, R4a, R4b, R4c, and Ring Q are as defined in the previous point [1], Compound (14) can be prepared by reacting compound (4) with a sulfonyl chloride of Formula (13) in the presence of a suitable inert solvent. The reaction can be carried out in the presence of a suitable base. The reaction temperature generally ranges from approximately -20°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the starting materials used, and the solvent, and generally ranges from 10 minutes to 48 hours. Examples of the base used here include organic bases such as triethylamine, diisopropylethylamine, and pyridine; inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, potassium hydroxide, sodium hydroxide, and sodium hydride; and metal alkoxides such as sodium methoxide and potassium tert-butoxide. Examples of the inert solvent used here include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as benzene and toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF) and 1,4-dioxane; polar aprotic solvents such as acetonitrile, acetone, methyl ethyl ketone, dimethylformamide, N-methyl-2-pyrrolidinone and dimethyl sulfoxide; basic solvents such as pyridine; and mixtures of solvents thereof. Compound (If) can be prepared by reacting compound (14) with a hydroxide such as tetrabutylammonium hydroxide and sodium hydroxide in a suitable inert solvent. The reaction temperature generally ranges from approximately -20°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the starting materials used, and the solvent employed, and generally ranges from 10 minutes to 48 hours. Examples of inert solvents used here include aromatic hydrocarbon solvents such as benzene and toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF) and 1,4-dioxane; polar aprotic solvents such as acetonitrile, acetone, methyl ethyl ketone, dimethylformamide and N-methyl-2-pyrrolidinone; and dimethyl sulfoxide and mixtures thereof. Preparation procedure 5 Among the compounds of formula (6), the compound of formula (6a) can be prepared, for example, by the following procedure. In the scheme, R5a, R5b, R5c, and R5d are as defined in point [1] above; and A is iodine, bromine, and chlorine. Compound (15) is prepared by reacting 1-(tert-butoxycarbonyl)pyridine-4-carboxylic acid and N,O-dimethylhydroxyamine or its hydrochloride in the presence of a suitable condensing agent in a suitable inert solvent. The reaction may be carried out in the presence of a suitable base. The reaction temperature generally ranges from approximately -20°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the condensing agent used, the starting materials, and the solvent used, and generally ranges from 10 minutes to 48 hours. Compound (15) is also prepared by reacting N,O-dimethylhydroxyamine or its salt with an acid halide or acid anhydride derived from 1-(tert-butoxycarbonyl)pyridine-4-carboxylic acid in the presence of a suitable base in a suitable inert solvent. The reaction temperature generally ranges from approximately -20°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the condensing agent used, the starting materials, and the solvent used, and generally ranges from 10 minutes to 48 hours. Examples of the condensing agents used here include dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIPC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (WSC), benzotriazol-1-1-tris(dimethylamino)phosphophonium hexafluorophosphate (BOP), diphenylphosphonyldiamide (DPPA), N,N-carbonyldiimidazole (CDI), and benzotriazol-1-1-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU). The reaction can be carried out by adding an additive such as N-hydroxysuccinimide (HOSu), 1-hydroxybenzotriazole (HOBt), and 3-hydroxy-4-oxo-3,4-dihydro1,2,3-benzotriazine (HOOBt), as required. Examples of the base used here include organic bases such as triethylamine, diisopropylethylamine, and pyridine; inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, potassium hydroxide, sodium hydroxide, and sodium hydride; and metal alkoxides such as sodium methoxide and potassium tert-butoxide. Examples of the inert solvent used here include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as benzene and toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF) and 1,4-dioxane; polar aprotic solvents such as acetonitrile, acetone, methyl ethyl ketone, dimethylformamide, N-methyl-2-pyrrolidinone and dimethyl sulfoxide; basic solvents such as pyridine; and mixtures of solvents thereof. Compound (17) can be prepared by reacting Compound (15) with a lithiated compound produced by treating Compound (16) with an organolithium compound such as n-butyllithium in a suitable inert solvent. The reaction temperature generally ranges from approximately -78°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the reagent used, the starting materials, and the solvent, and generally ranges from 10 minutes to 48 hours. ML / a / ZUZZ / UU 1341 Examples of inert solvents used here include aromatic hydrocarbons such as benzene and toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF) and 1,4-dioxane; and mixtures of solvents thereof. Compound

[18] can be prepared by reacting Compound

[17] with hydroxylamine or its salt in the presence of a suitable base as required. The reaction temperature generally ranges from approximately -20°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the base used, the starting materials, and the solvent, and generally ranges from 10 minutes to 48 hours. Examples of the base used here include organic bases such as triethylamine, diisopropylethylamine, and pyridine; inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, potassium hydroxide, sodium hydroxide, and sodium hydride; and metal alkoxides such as sodium methoxide, potassium tert-butoxide, and sodium acetate. Examples of inert solvents used here include aromatic hydrocarbons such as benzene and toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF) and 1,4-dioxane; lower alcohols such as methanol, ethanol and 2-propanol; polar aprotic solvents such as dimethylformamide and N-methyl-2-pyrrolidinone; water; and mixtures of solvents thereof. Compound (19) is prepared by treating compound (18) with a suitable base in a suitable inert solvent. The reaction temperature generally ranges from approximately -20°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the base used, the starting materials, and the solvent used, and generally ranges from 10 minutes to 48 hours. Examples of the base used here include organic bases such as triethylamine, diisopropylethylamine, and pyridine; inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, potassium hydroxide, sodium hydroxide, and sodium hydride; and metal alkoxides such as sodium methoxide and potassium tert-butoxide. Examples of inert solvents used herein include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as benzene and toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF) and 1,4-dioxane; lower alcohols such as methanol, ethanol and 2-propanol; polar aprotic solvents such as acetonitrile, acetone, methyl ethyl ketone, dimethylformamide, N-methyl-2-pyrrolidone and dimethyl sulfoxide; and mixtures of solvents thereof. Compound (6a) is prepared by processing compound (19) with a suitable acid in a suitable inert solvent. The reaction temperature generally ranges from -20°C to the boiling point of the solvent used. The reaction time depends on the reaction conditions, such as the reaction temperature, the acid used, the starting materials, and the solvent, and generally ranges from 10 minutes to 48 hours. Examples of inert solvents used here include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as benzene and toluene; ether solvents such as diethyl ether, tetrahydrofuran, 1,4-dioxane and 1,2-dimethoxyethane; lower alcohols such as methanol, ethanol and 2-propanol; polar aprotic solvents such as acetonitrile, dimethylformamide, N-methyl-2-pyrrolidone and dimethyl sulfoxide; and mixtures of solvents thereof. Examples of the acid used here include inorganic acids such as hydrochloric acid and sulfuric acid, and organic acids such as trifluoroacetic acid. The present compound, having a desired functional group in a desired position, can be prepared by appropriately combining the above preparation procedures. The isolation and purification of each intermediate or product in the above preparation processes can be carried out by conventional methods in organic synthesis, for example, by appropriately combining filtration, extraction, washing, drying, concentration, crystallization, and various chromatographic techniques. Some intermediates can be used in the next step without any purification. Some starting compounds or intermediates in the above preparation procedures may exist in the form of a salt, such as hydrochloride, depending on the reaction conditions, etc., but they can be used as is or in their free form. When a starting compound or intermediate is obtained in the form of a salt and it is necessary to use or obtain it in its free form, it can be transformed into its free form by dissolving or suspending it in a suitable solvent and neutralizing the solution or suspension with a base such as aqueous sodium bicarbonate. Some of the compounds of formula (1) or a pharmaceutically acceptable salt thereof may exist as isomers such as tautomers (e.g., keto-enol form), regioisomers, geometric isomers, and optical isomers. The present invention encompasses all possible isomers, including those listed above, and a mixture thereof having various mixing ratios. Optical isomers can be resolved using a known method, such as one with an optically active column and fractional crystallization in a suitable step of the preparation procedures mentioned above. Additionally, an optically active starting material can be used. To obtain the compound of formula (1) as a salt thereof, when the product is a salt of the compound of formula (1), the product must be purified directly; or when the product is in the free form of the compound of formula (1), the product must be dissolved or suspended in an appropriate solvent and then an acid or a base must be added to form a salt thereof. This compound has antagonistic activity at the 5-HT2A receptor and antagonistic activity at the 5-HTβ receptor and has a different mechanism of action than other existing medications for treating mental disorders. This compound may provide a new medication option for various mental disorders. Specifically, this compound is beneficial for the treatment of mental disorders. This compound is also beneficial for the treatment of central nervous system disorders. Mental illnesses or diseases of the central nervous system that are expected to be treated effectively include, for example, F00-F09: organic mental disorders, including symptomatic ones, F10-F19: mental and behavioral disorders due to the use of psychoactive substances, F20-F29: schizophrenia, schizotypal disorders, and delusional disorders, F30-F39: mood [affective] disorders, F40-F48: neurotic disorders, stress-related disorders, and somatoform disorders, F51: non-organic sleep disorders, F52: sexual dysfunction, not caused by a disorder or disease, F84: pervasive developmental disorders, F90-F98: behavioral and emotional disorders usually occurring in childhood and adolescence, G20-G26: extrapyramidal and movement disorders, G30-G32: other degenerative diseases of the nervous system, and G47: sleep disorders in the International Classification of Diseases, Tenth Revision (ICD-10). F00-F09: Organic mental disorders, including symptomatic ones, include, for example, dementia in Alzheimer's disease, vascular dementia, dementia with Lewy bodies, dementia in Parkinson's disease, mental disorders due to other diseases such as brain damage, and other mental disorders due to brain dysfunction and physical disease. F10-F19: Mental and behavioral disorders due to the use of psychoactive substances include delirium tremens, psychotic disorder, and amnesic syndrome, due to the use of various substances. F20-F29: Schizophrenia, schizotypal disorders and delusional disorders include paranoid schizophrenia, simple schizophrenia and delusional disorders. F30-F39: Mood [affective] disorders include manic episode, bipolar affective disorder, and depressive episode. F40-F48: Neurotic disorders, stress-related disorders, and somatoform disorders include phobic anxiety disorders, obsessive-compulsive disorder, and somatoform disorders. F51: Non-organic sleep disorders include non-organic insomnia, sleepwalking, and nightmares. F52: Sexual dysfunction, not caused by an organic disorder or disease, includes lack or loss of sexual desire and unspecified sexual dysfunction. F84: Pervasive developmental disorders include, for example, autism and hyperactive disorder associated with mental retardation and stereotyped movements. F90-F98: Hyperkinetic and behavioral disorders that typically appear in childhood and adolescence include hyperkinetic disorders, conduct disorders, and mixed disorders of conduct and emotions. G20-G26: Extrapyramidal and movement disorders include Parkinson's disease and secondary parkinsonism. G30-G32: Other degenerative diseases of the nervous system include Alzheimer's disease, frontotemporal dementia, frontotemporal lobar degeneration, Lewy body dementia, senile degeneration of the brain. G47: Sleep disorders include sleep initiation and maintenance disorders [insomnias], sleep-wake timing disorders, and narcolepsy and cataplexy. This compound is useful for the treatment or prevention of relapse of various symptoms associated with these diseases such as psychopathic symptoms, sleep disorders, depressive symptoms, anxiety symptoms, and cognitive dysfunction. Serotonin (5-hydroxytryptamine: 5-HT), one of the major neurotransmitters in the central nervous system, is known to be involved in various brain functions, including emotional response and cognitive function. The 5-HT1A receptor, one of the 5-HT receptor subtypes, is highly expressed in areas such as the cerebral cortex, hippocampus, and raphe nuclei. 5-HT2A, expressed in the prefrontal cortex, is also known to upregulate a dopamine pathway in the ventral tegmental area (non-patent bibliography 2). In other words, inhibition of the 5-HT2A receptor in the prefrontal cortex is thought to have an inhibitory effect on psychotic symptoms. The 5-HTβ receptor is widely expressed, for example, in the hypothalamus, thalamus, hippocampus, and raphe nucleus, and is involved in the regulation of circadian rhythms in mammals (Non-proprietary reference 9). Circadian rhythm dysfunction is known to be associated with several CNS disorders, particularly depression, seasonal affective disorder, sleep disorders, shift work syndrome, and jet lag. Drugs that have antagonistic activity at the 5-HTβ receptor include lurasidone, used to treat schizophrenia and bipolar disorder, and vortioxetine, used to treat major depression. However, no drug has selective antagonistic activity at the 5-HTβ receptor. It is also known that in some animal models, antagonism of the 5HT7 receptor leads to an antidepressant and anxiolytic effect, and an effect of improving cognitive function (Non-patent literature 6, Non-patent literature 7). Based on previous pharmacological knowledge, it is expected that 5-HT2A receptor inhibition, along with 5-HT7 receptor inhibition, will be useful in various neuropsychiatric disorders such as depression, sleep disorders, and psychotic symptoms. There are no reports of any drug that has potent and selective antagonistic activity at both the 5-HT2A and 5-HT7 receptors. The present compound has a potent binding affinity to the 5-HT2A receptor and the 5-HT7 receptor (Test 1), and exhibits antagonistic activity at both the 5-HT2A and 5-HT7 receptors. In a preferred embodiment of the present invention, the present compound can exert a pharmacological effect based on its antagonistic capacity for the 5-HT2A and 5-HT7 receptors at blood concentrations that do not cause side effects such as extrapyramidal symptoms and hyperprolactinemia due to D2 antagonist activity, because the binding affinity of the present compound to the 5-HT2A and 5-HT7 receptors is 100 times greater than that of the D2 receptor. In another preferred embodiment of the present invention, the present compound is expected to have a small effect on the cardiovascular system because there is a large difference between the inhibitory concentration of the hERG channel, which is an express indicator of long QT arrhythmia, and the express concentration of the expected pharmacological effect (Test 5). The disappearance half-life (T1 / 2) of a drug is a factor in determining the frequency of administration required to maintain its effect. Multiple daily administrations of a drug with a short T1 / 2 are believed to lead to missed doses or medication discontinuation, which can hinder adherence to medication regimens. Furthermore, increased administration frequency raises concerns that the incidence of side effects may increase or tolerability may decrease, particularly with higher doses. Therefore, if a drug with a long T1 / 2 is discovered, it is expected to be a long-acting drug with fewer of the aforementioned concerns, which may alleviate the responsibility of patients taking it. In a preferred embodiment of the present compound, the estimated human disappearance half-life (T1 / 2) of the present compound is 8 hours or more (Test 4). Therefore, it is expected that the drug's efficacy can be maintained for a prolonged period in the human body, medication adherence in treated patients can be improved, and high tolerability can be exhibited during administration. This compound can be administered orally or parenterally. For oral administration, the compound can be administered in the conventionally used dosage form. For parenteral administration, the compound can be administered, for example, in a topical, injectable, transdermal, or nasal form. Oral and rectal forms include, for example, capsules, tablets, pills, powders, lozenges, suppositories, and liquids. Injectable forms include, for example, aseptic solutions and suspensions. Topical forms include, for example, creams, ointments, lotions, and transdermal formulations (e.g., standard patches and matrices). The dosage forms mentioned above can be prepared with a pharmaceutically acceptable excipient and additive in a conventional manner. Pharmaceutically acceptable excipients and additives include vehicle, binder, flavoring, pH regulator, thickener, colorant, stabilizing agent, emulsifier, dispersant, suspending agent, and preservative. The pharmaceutically acceptable vehicle includes, for example, magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, low-melting-point wax, and cocoa butter. The capsule form can be prepared by filling a capsule with the present compound and a pharmaceutically acceptable vehicle. The present compound can be placed in a capsule with or without a pharmaceutically acceptable excipient. The seal can also be prepared similarly. The injectable liquid form includes solution, suspension, and emulsion, including, for example, water solution and water-propylene glycol solution. The liquid form may comprise water and may also be prepared in a polyethylene glycol and / or propylene glycol solution. The liquid form suitable for oral administration may be prepared by adding the present compound to water and also by adding colorant, flavoring, stabilizing agent, sweetener, solubilizer, thickener, etc., as appropriate. Alternatively, the liquid form suitable for oral administration may be prepared by adding the present compound with a dispersant to water and making the liquid viscous. The thickener used herein includes, for example, pharmaceutically acceptable natural or synthetic gum, resin, methylcellulose, sodium carboxymethylcellulose, and a known suspending agent. The dosage of each compound may depend on the patient's condition, age, body weight, sex, symptoms, and route of administration. Generally, this compound is administered to an adult (body weight: 50 kg) at a dose of 0.1 to 1000 mg / day, preferably 1 to 300 mg / day, once daily or in 2 to 3 divided doses. Alternatively, it may be administered once every few days or weeks. To enhance the effect and / or reduce its side effects, this compound can be used in combination with another drug. For example, this compound can be used ML / a / ZUZZ / UU 1341 can be used in combination with an anti-anxiety drug such as a selective serotonin reuptake inhibitor. Drugs with which this compound can be used in combination are referred to as concomitant drugs. Examples of concomitant drugs used in the present include a drug to treat a developmental disorder such as autism spectrum disorder and attention deficit hyperactivity disorder, an antipsychotic drug and a schizophrenic drug, a drug to treat bipolar disorder, an antidepressant drug, an anti-anxiety drug, a drug to treat obsessive-compulsive disorder, a drug to treat a stress disorder such as post-traumatic stress disorder, a drug to treat a mood disorder, a drug to treat an eating disorder, a drug to treat a sleep disorder such as insomnia, narcolepsy, sleep apnea syndrome and circadian rhythm disorder, a drug to treat sexual dysfunction, a drug to treat drug dependence, a drug to treat dementia such as Alzheimer's disease,A drug to treat a behavioral and psychological symptom associated with dementia, a drug to improve cerebral metabolism and circulation, a drug to treat a movement disorder such as Parkinson's disease, an analgesic drug, an antiepileptic drug, an anticonvulsant, a migraine drug, an anesthetic, and a central stimulant. The dosage interval between the present compound and its concomitant drug is not limited; that is, the concomitant drug may be administered to a patient at the same time as the present compound or at an appropriate interval. Alternatively, the present compound and its concomitant drug may be formulated as a combination drug comprising them. The dosage of the concomitant drug may be appropriately determined based on its clinically used dosage. The combination ratio of the present compound and its concomitant drug may be appropriately determined based on the patient, route of administration, disease, pathology, and combinations thereof. For example, when the patient is a human, the concomitant drug may be used at a ratio of 0.01 to 100 parts by weight to the present compound.In order to reduce side effects, a concomitant drug can be used, such as an antiemetic drug, a sleep-inducing drug, and an anticonvulsant in combination. EXAMPLES The present invention is explained in more detail below by reference to reference examples, examples, and proofs; however, the scope of the present invention is not limited to these. The names of the compounds used in the reference examples and examples are not always based on the IUPAC nomenclature system. Abbreviations may be used for brevity, and these abbreviations have the same meanings as described above. The compounds were identified by proton nuclear magnetic resonance (¹H NMR) absorption spectroscopy or LC-EM. Amino chromatography in the Reference Examples and Examples was performed using a Yamazen Corporation amino column. LC-EM was carried out under the conditions shown in the table below. The time of IVIA / a / ZUZZ / UU Z 34 Z retention (RT) denotes the time when a peak of a mass spectrum appears in the LC-EM measurement. Shimadzu LCMS-2020 Analytical Apparatus, Phenomenex Kinetex Column 1.7 pm C18 (50 mm x 2.10 mm), Eluent A: MeOH, B: 0.05% TFA / H2O, Gradient Condition: 0.0 min; A / B = 30:70, 0.0 to 1.90 min; A / B = 99:1, 1.91 to 3.00 min; A / B = 30:70, Flow Rate: 0.5 mL / min, Wavelength (UV): 220 nm, Column Temperature: 40°C The powder X-ray diffraction (powder XRD) measurement was carried out under various conditions shown in the following table. Analytical apparatus Empyrian (Spectris Co., Ltd.) x-ray CuKa / 45 kV / 40 mA Divergence slit 1 / 4° Sun slit 0.04 rad Anti-scatter slit 5.5 mm Step size 0.013° Scan range 4 to 40°(20) Cumulative time 100 seconds / step Measurement temperature 23°C (296 K) Differential scanning calorimetry (DSC) measurements were performed under various conditions shown in the following table. iviA / a / zuzz / uu Analytical apparatus DSC2500 or DSCQ1000 (TA Instruments Inc.) Measuring temperature range 10 to 250°C Heating rate 10°C / minutes Containing TzeroPan or Airtight Aluminum Pan (Pinhole) Atmospheric gas flow rate Dry nitrogen: about 50 ml / minutes The following abbreviations may be used in the specification. In the NMR data of the Reference Examples and the Examples, the following abbreviations are used. Me: Methyl DMF: N,N-Dimethylformamide THF: Tetrahydrofuran tere-: Tertiary CDCh: Deuterated Chloroform DMSO-de: deuterated dimethyl sulfoxide Proton nuclear magnetic resonance spectra were measured using an FT-NMR spectrometer (300 MHz or 400 MHz, JEOL). Chemical changes are shown as δ values ​​(ppm). The symbols used in NMR denote the following meanings: s is singlet, d is doublet, dd is double doublet, dt is double triplet, t is triplet, q is quartet, m is multiplet, br is wide, brs is wide singlet, and J is the coupling constant. EXAMPLE 1 (2R)-N-Et¡lN-{2-[4-(6-fluoro-l,2-benzolsoxazol-3-¡l)p¡perídin-l-¡l]ethyl}-2hydroxypropanamide To a suspension of the compound from reference example 1 (20.0 mg) in N,N-dimethylformamide (0.5 mL) were added D-lactic acid (6.18 mg), triethylamine (20.8 mg), and 2-(1Hbenzo[d][1,2,3]tnazol-1-1)-1,1,3,3-tetramethylisouroniohexafluorophosphate (33.8 mg). The mixture was stirred at room temperature for 16 hours and then water (4.0 mL) was added. The mixture was extracted with chloroform (10 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrated residue was purified by high-performance liquid chromatography (column; C-18 semi-preparative column, separation condition; acetonitrile / trifluoroacetic acid: water / trifluoroacetic acid), and desalted with MP-carbonate resin to obtain the title compound (9.73 mg). L-EM: RT = 1.433 min ObsMS = 364 [M+l] EXAMPLE 2 N-Et¡lN-{2-[4-(5-fluoro-lH-¡ndazol-l-¡l)p¡períd¡nl-¡l]et¡l}-3-hydroxy¡propanamide N^\ A suspension of the compound from reference example 2 (50.0 mg) in dichloromethane (1.0 mL) was mixed with triethylamine (0.077 mL), 30% 3-hydroxypropionic acid (0.046 mL), and 2-(1H-benzo[d][1,2,3]trazol-1-11)-1,1,3,3-tetramethylisouronico hexafluorophosphate (67.9 mg). The mixture was stirred at room temperature for 2 hours and purified by silica gel column chromatography (chloroform / methanol) to obtain the title compound (43.2 mg). ^-NMR (400 MHz, CDCI3) δ: 7.89-7.86 (1H, m), 7.37-7.30 (1H, m), 7.29-7.24 (1H, m), 7.11-7.04 (1H, m), 4.44-4.27 (1H, m), 3.87-3.77 (2H, m), 3.72-3.57 (1H, m), 3.51-3.42 (1H, m), 3.42-3.27 (3H, m), 3.17-2.96 (2H, m), 2.59-2.47 (4H, m), 2.36-2.17 (4H, m), 2.05-1.89 (2H, m), 1,181.05 (3H, m). EXAMPLE 3 (2R)-N-ethylN-{2-[4-(5-fluoro-lH-índazol-l-íl)píperídin-l-íl]ethyl}-2-hydroxy¡propanamide HO A suspension of the compound from reference example 2 (50.0 mg) in dichloromethane (1.0 mL) was mixed with triethylamine (0.077 mL), D-lactic acid (14.9 mg), and 2-(1Hbenzo[d][1,2,3]trazol-1-II)-1,1,3,3-tetramethylisouronium hexafluorophosphate (67.9 mg). The mixture was stirred at room temperature for 4 hours and purified by silica gel column chromatography (chloroform / methanol) to obtain the title compound (13.9 mg). 1H-NMR (400 MHz, CDCh) δ: 7.93 (1H, s), 7.42-7.28 (2H, m), 7.18-7.08 (1H, m), 4.50- 4.20 (2H, m), 3.80-3.62 (1H, m), 3.59-2.88 (4H, m), 2.68-2.53 (1H, m), 2.44-2.20 (3H, m), 2.11-1.94 (1H, m), 1.67-1.44 (5H, m), 1.37-1.10 (6H, m). EXAMPLES 4 to 15 According to the method in example 3, the compounds in examples 4 to 15 were prepared from the corresponding reference example compounds. iviA / a / zuzz / uu Example Chemical structure Data of instrumental analysis 4 n-° [1 2^ 0 'L. LC-EM: RT = 1.417 min ObsMS = 364 [M+l] 5 LL XX o \ / z Λ '—z Z- / o^ / / —K / ° O '--- O LC-EM: RT = 1.517 min ObsMS = 436 [M+l] 6 N'°}l 2--λ 0 ι^^Γ\ F LC-EM: RT = 1,500 min ObsMS = 378 [M+l] 7 Ν-θ II 2--, 0 ί^ιΥ ϋ·— II 1 \ / —FJ ΗΟ LC-EM: RT = 1,517 min ObsMS = 392 [M+l] 8 Ν—R 1' 2^ 0 l^itV II 1 \__ / F ΗΟ. JL _____ .1+ J '^Ζ LC-EM: RT = 1.567 min ObsMS = 392 [M+l] 9 Ν11 2^ 0 ί^^ΊΓχ II । Z^f --- J ^=== / < >< Ν ΗΟ''^-^ LC-EM: RT = 1.258 min ObsMS = 418 [M+l] 10 Ν-° JL / ^Λ ΟΗ 0 Ι^^ΓΧ' \\ | II 1 \^__Z~F ^Ν. J '-^ΪΖ Ν^ LC-EM: RT = 1,467 min ObsMS = 378 [M+l] 11 N'° [1 / X 0 \ ϋ— OH 11 1 \ Z^F JL _____ < N LC-EM: R.T. = 1.483 min ObsMS = 420 [M+l] 12 N'° II 0 Í^^TV V-. II 1 \__Z^F HO. JL ___. J N LC-EM: R.T. = 1.150 min ObsMS = 350 [M+l] 13 N-° 0 ho, f N — \ íH-RMN (400 MHz, CDCh) δ: 7.58-7.53 (1H, m), 7.16-7.11 (1H, m), 4.48-4.32 (1H, m), 3.75-3.59 (1H, m), 3.56-2.80 (5H, m), 2.652.43 (1H, m), 2.31 (3H, s), 2.29-1.85 (5H, m), 1.57-1.44 (4H, m), 1.32-1.27 (3H, m), 1.22-1.06 (3H, m). 14 N-° [1 X 0 I^^Tx / íH-RMN (400 MHz, CDCh) δ: 7.52-7.40 (1H, m), 7.37 (1H, d, J = 8.5 Hz), 7.27 (1H, d, J = 8.5 Hz), 4.47-4.26 (1H, m), 3.75-3.57 (1H, m), 3.56-2.88 (6H, m), 2.62-2.45 (2H, m), 2.40 (3H, s), 2.34-1.93 (5H, m), 1.57-1.40 (2H, m), 1.33-1.25 (3H, m), 1.21-1.07 (3H, m). 15 N-°. 11 X ° ^L. II । / --ci ho,. χ •p ^-RMN (400 MHz, CDCh) δ: 7.71-7.60 (1H, m), 7.57-7.54 (1H, m), 7.29-7.25 (1H, m), 4.58-4.28 (1H, m), 3.79-3.62 (1H, m), 3.582.87 (6H, m), 2.72-2.49 (2H, m), 2.40-1.93 (5H, m), 1.61-1.43 (2H, m), 1.37-1.29 (3H, m), 1.26-1.08 (3H, m). Example 16 ML / a / ZUZZ / UU 1341 ML / a / ZUZZ / UU 1341 To a suspension of the compound from reference example 1 (400 mg) in tetrahydrofuran (1.1 mL) were added triethylamine (0.763 mL), L-lactic acid (0.098 mL), and O-(7-azabenzotriazol-L-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (0.501 mg). The mixture was stirred at room temperature for 4 hours. Methanol (6.0 mL), 2 mol / L aqueous sodium hydroxide (3.0 mL), and water (1.0 mL) were added to the mixture. The mixture was stirred at room temperature for 1 hour. Then, water (30 mL) was added, and the mixture was extracted with chloroform (30 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrated residue was purified by silica gel column chromatography (chloroform / methanol) to obtain the title compound (279 mg). ^-RMN (400 MHz, CDCh) δ: 7.72-7.56 (1H, m), 7.17 (1H, dd, J = 8.5, 1.8 Hz), 6.99 (1H, td, J = 8.8, 1.8 Hz), 4.48-4.32 (1H, m), 3.75-3.59 (1H, m), 3.52-2.86 (7H, m), 2.58-2.44 (2H, m), 2.32-2.11 (2H, m), 2.09-1.87 (4H, m), 1.32-1.25 (3H, m), 1.17 (2H, t, J = 7.0 Hz), 1.09 (1H, t, J = 7.0 Hz). EJEMPLO 17 N-Et¡lN-{2-[4-(6-fluoro-l,2-benzoisoxazol-3-¡l)p¡per¡din-l-¡l]et¡l}-3hidroxipropanamida To a suspension of the compound from Reference Example 1 (3.97 g) in acetonitrile (50 mL) were added triethylamine (6.08 mL), 3-hydroxypropionic acid (4.91 g), and O-(7-azabenzotrazol-1-11)-N,N,N,,N,-tetramethylluronium hexafluorophosphate (6.22 g). The mixture was stirred at room temperature for 2 hours. Methanol (50 mL) and cesium carbonate (14.2 g) were added to the mixture. The mixture was stirred at 70°C for 2 hours, then filtered and concentrated. Chloroform (50 mL) was added to the residue, and the insolubles were filtered out. The eluent was concentrated. The concentrated residue was purified by silica gel column chromatography (hexane / ethyl acetate and chloroform / methanol) and further purified by silica gel column chromatography (chloroform / methanol) to obtain the title compound (2.97 g). ^-NMR (400 MHz, CD3OD) δ: 7.93-7.84 (1H, m), 7.42-7.33 (1H, m), 7.20-7.12 (1H, m), 3.88-3.79 (2H, m), 3.62-3.37 (4H, m), 3.23-3.04 (4H, m), 2.69-2.54 (4H, m), 2.42-2.26 (2H, m), 2.15-1.95 (4H, m), 1.29-1.07 (3H, m). XRD Powder D(°, 2θ±0.2) 8.32, 9.72, 13.30, 13.62, 13.83, 14.24, 16.77, 17.81, 19.89, 19.95, 21.58, 22.02, 24.03, 26.77, 26.84 (Among them, the 10 characteristic peaks were 8.32, 9.72, 13.83, 14.24, 16.77, 19.89, 19.95, 21.58, 22.02, 24.03, and the 4 most characteristic peaks were 8.32, 9.72, 13.83, 16.77.) DSC Enthalpy (normalized): 71.71 J / g Start x: 67.55°C IVIA / S / ZUZZ / UU EXAMPLE 18 N-Ethyl-N-{2-[4-(6-fluoro-l,2-benzo¡soxazol-3-yl)piper¡dinl-yl]ethyl}-2-hydroxy-3methoxypropanamide To a suspension of Reference Compound 1 (70.0 mg) in tetrahydrofuran (1.9 mL) were added triethylamine (0.134 mL), 2-hydroxy-3-methoxypropionic acid (27.7 mg), and O-(7-azabenzotrazol-1-1)-N,N,N',N'-tetramethylluronium hexafluorophosphate (88.0 mg). The reaction mixture was stirred at room temperature for 3 hours and concentrated. The residue was purified by silica gel column chromatography (chloroform / methanol) to obtain the title compound (51.7 mg). H-NMR (400 MHz, CDCI3) δ: 7.78-7.62 (1H, m), 7.24-7.19 (1H, m), 7.03 (1H, td, J = 8.9, 2.2 Hz), 4.58-4.47 (1H, m), 3.82-2.89 (13H, m), 2.64-2.48 (2H, m), 2.39-1.96 (6H, m), 1.26-1.08 (3H, m). EXAMPLE 19 N-Et¡lN-{2-[4-(6-fluoro-lH-¡ndazol-3-¡l)p¡per¡d¡nl-¡l]et¡l}-2-hydroxy¡propanamide n^nh ¡i II I \.__ / -F HO. JL _____ J N To a solution of the compound from Reference Example 6 (400 mg) in N,N-dimethylformamide (4.0 mL), 0.577 mL of diisopropylethylamine, DL-lactic acid (0.082 mL), and O-(7-azabenzotrazol-1-1)-N,N,N',N'-tetramethyluroniohexafluorophosphate (628 mg) were added. The mixture was stirred at room temperature for 1 hour. Aqueous sodium hydroxide solution (3.0 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. Water (10 mL) was added to the reaction mixture. The mixture was extracted with chloroform (5.0 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrated residue was purified by silica gel column chromatography (chloroform / methanol) to obtain the title compound (217 mg). 1H-RMN (400 MHz, CDCh) δ: 10.01-9.79 (1H, m), 7.74-7.63 (1H, m), 7.06 (1H, dd, J = 9.1, 1.8 Hz), 6.88 (1H, t, J = 7.9 Hz), 4.52-4.37 (1H, m), 3.88-3.74 (2H, m), 3.74-3.59 (2H, m), 3.58-3.14 (3H, m), 3.11-2.93 (3H, m), 2.65-2.49 (2H, m), 2.36-1.95 (5H, m), 1.38-1.30 (3H, m), 1.261.10 (3H, m). EJEMPLO 20 (2S)-N-Et¡l-N-{2-[4-(6-fluoro-lH-¡ndol-3-il)p¡per¡d¡n-l-¡l]et¡l}-2-h¡drox¡propanam¡da _-NH0|| I \. / —F HO, *·κ N — To a suspension of the compound from reference example 7 (30.0 mg) in tetrahydrofuran (1.83 mL), triethylamine (0.0575 mL), L-lactic acid (8.95 mL), and O-(7-azabenzotriazol-1-1)-N,N,N',N'-tetramethylluronium hexafluorophosphate (37.8 mg) were added. The mixture was stirred at room temperature for 2 hours. Methanol (0.8 mL) and 2 mol / L aqueous sodium hydroxide (0.4 mL) were added to the reaction mixture. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated, and chloroform (10 mL) was added. The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated again. The concentrated residue was purified by silica gel column chromatography (chloroform / methanol) to obtain the title compound (24.3 mg). íH-RMN (400 MHz, CDCb) δ: 8.01 (1H, s), 7.45 (1H, dd, J = 8.5, 5.5 Hz), 6.97 (1H, dd, J = 9.8, 2.4 Hz), 6.87 (1H, s), 6.82-6.77 (1H, m), 4.47-4.32 (1H, m), 3.77-2.87 (6H, m), 2.79-2.68 (1H, m), 2.60-2.44 (2H, m), 2.30-2.13 (2H, m), 2.06-1.67 (4H, m), 1.33-1.25 (3H, m), 1.22-1.06 (3H, m). EJEMPLO 21 (2S)-N-et¡lN-{2-[4-(5-fluoro-lH-¡ndazol-l-il)piper¡d¡nl-¡l]etil}-2-h¡droxipropanamida To a suspension of the compound from reference example 2 (400 mg) in tetrahydrofuran (4.0 mL) were added triethylamine (0.768 mL), L-lactic acid (161 mL), and O-(7-azabenzotrazol-1-1)-N,N,N',N'-tetramethylluronium hexafluorophosphate (786 mg). The mixture was stirred at room temperature for 3 hours. A 15% aqueous sodium hydroxide solution (4.0 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. Concentrated hydrochloric acid was then added until the pH of the reaction mixture reached 7, and the mixture was concentrated. The concentrated residue was purified by silica gel column chromatography (chloroform / methanol) to obtain the title compound (269 mg). ^-NMR (400 MHz, CDCh) δ: 7.88 (1H, s), 7.38-7.24 (2H, m), 7.12-7.04 (1H, m), 4.484.29 (2H, m), 3.77-3.56 (2H, m), 3.50-2.93 (5H, m), 2.72-2.48 (2H, m), 2.38-2.18 (3H, m), 2.12-1.88 (2H, m), 1.32-1.25 (3H, m), 1.23-1.06 (3H, m). iviA / a / zuzz / uu EXAMPLE 22 N-Ethyl-2-hydroxy-N-{2-[4-(lH-indol-3-¡l)piperidin-l-yl]ethyl}propanamide To a suspension of the compound from reference example 8 (300 mg) in tetrahydrofuran (8.7 mL) were added triethylamine (0.606 mL), L-lactic acid (94.0 mL), and O-(7-azabenzotriazol-l-l-11-N11N11N11N1)-tetramethyluronium hexafluorophosphate (398 mg). The mixture was stirred at room temperature for 3 hours, and then methanol (6.0 mL) and 2 mol / L aqueous sodium hydroxide (3.0 mL) were added. The mixture was stirred at room temperature for 1 hour. The reaction mixture was then concentrated, and chloroform (30 mL) was added to the residue. The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrated residue was purified by silica gel column chromatography (chloroform / methanol) to obtain the title compound (258 mg). XH-RMN (400 MHz, CDCb) δ: 7.93-7.85 (1H, m), 7.57 (1H, d, J = 7.9 Hz), 7.29 (1H, d, J = 8.5 Hz), 7.12 (1H, t, J = 7.3 Hz), 7.03 (1H, t, J = 7.0 Hz), 6.91 (1H, s), 4.47-4.33 (1H, m), 3.803.08 (4H, m), 3.05-2.87 (2H, m), 2.83-2.73 (1H, m), 2.59-2.43 (2H, m), 2.30-2.13 (2H, m), 2.06-1.93 (2H, m), 1.83-1.66 (2H, m), 1.29 (3H, t, J = 6.4 Hz), 1.21-1.06 (3H, m). EJEMPLO 23 (2S)-N-Et¡l-2-h¡droxi-N-{2-[4-(lH-¡ndol-3-il)piperidin-l-¡l]et¡l}propanamida To a suspension of the compound from reference example 8 (300 mg) in tetrahydrofuran (8.7 mL) were added triethylamine (0.606 mL), L-lactic acid (94.0 mL), and O-(7-azabenzotrazol-1-1)-N,N,N',N'-tetramethyluroniohexafluorophosphate (398 mg). The mixture was stirred at room temperature for 3 hours, and then methanol (6.0 mL) and 2 mol / L aqueous sodium hydroxide (3.0 mL) were added. The mixture was stirred at room temperature for 1 hour. The reaction mixture was then concentrated, and chloroform (30 mL) was added to the residue. The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated again. The concentrated residue was purified by silica gel column chromatography (chloroform / methanol) to obtain the title compound (258 mg). 1H-NMR (400 MHz, CDCb) δ: 8.06-7.92 (1H, m), 7.61 (1H, d, J = 7.9 Hz), 7.35 (1H, d, J = 7.9 Hz), 7.17 (1H, t, J = 7.3 Hz), 7.08 (1H, t, J = 7.6 Hz), 6.99-6.94 (1H, m), 4.51-4.36 (1H, m), 3.82-1.74 (16H, m), 1.34 (3H, t, J = 6.1 Hz), 1.26-1.11 (3H, m). MA / a / xíUZZ / UU 1341 EXAMPLES 24 TO 50 According to the method of example 23, the compounds of examples 24 to 50 were prepared from the corresponding reference example compounds. Ejemplo Estructura química Datos de análisis instrumental 24 °2 O 3 'N^ ,N N'° 1' Ύύ V ^-RMN (400 MHz, CDCh) δ: 7.74 (1H, dd, J = 8.8, 5.2 Hz), 7.21 (1H, dd, J = 8.5, 1.8 Hz), 7.05-7.00 (1H, m), 3.83-3.74 (2H, m), 3.45-3.31 (2H, m), 3.19-3.01 (3H, m), 2.68-2.59 (2H, m), 2.51-2.37 (2H, m), 2.25-2.09 (2H, m), 2.05-1.95 (2H, m), 1.19-1.06 (6H, m), 0.96-0.90 (2H, m). 25 ho. O [1 2^ γγΛ J LC-EM : R.T. = 1.142 min ObsMS = 346 [M+l] 26 Ί 'N^ ,N N-0 [1 2—, ^-RMN (400 MHz, CDCh) δ: 7.65 (1H, d, J = 7.9 Hz), 7.49-7.42 (2H, m), 7.24-7.19 (1H, m), 4.43 (1H, td, J = 13.3, 6.5 Hz), 3.75-3.19 (8H, m), 2.78-2.57 (5H, m), 1.36-1.30 (3H, m), 1.25-1.11 (3H, m). 27 Ί 'N^ ,N N'° 11 2-^ 1 F LC-EM : R.T. = 1.167 min ObsMS = 365 [M+l] 28 HO 1 0 1 N-° 1' 2Ύύ V LC-EM : R.T. = 1.450 min ObsMS = 374 [M+l] 29 N'° [1 ° ΓΥΥ / --f LC-EM : RT = 1.258 min ObsMS = 378 [M+l] 30 I Ο ^=° <0 Ζ —ν / ^ζ / \ .ο ί γ LC-EM : RT = 1.467 min ObsMS = 390 [M+l] 31 N'0. ι> y-, 0 'L. LC-EM : RT = 1.450 min ObsMS = 378 [M+l] 32 N'° η 0 ί^Υν V 1 \ Z~~F ΗΟ. JL ___. .N^ J '-<=Z >< N ^CN LC-EM : RT = 1.314 min ObsMS = 375 [M+l] 33 N'° ¿,ν0^ LC-EM : RT = 1.400 min ObsMS = 418 [M+l] 34 N~° [1 2-, 0 ί^^ιχ II 1 \. / T ΗΟ. JL J ν=:=ζ >< N cf3 LC-EM : RT = 1.333 min ObsMS = 418 [M+l] 35 N'θ II 2^ 0 ί^^ιχ Λ— II 1 \__ / F Jk ^N. J '-'iZ H O N ^-RMN (400 MHz, CDCl) δ: 7.70-7.63 (1H, m), 7.23-7.19 (1H, m), 7.07-7.00 (1H, m), 4.06-3.82 (3H, m), 3.42-3.30 (2H, m), 3.15-2.99 (3H, m), 2.62-2.48 (4H, m), 2.30-2.21 (2H, m), 2.09-2.01 (5H, m), 1.24-1.12 (6H, m). 36 N11 2^ ° ί^^ιχ II 1 V—Z'F Jk ^N. J ^=== / HO N FF ^-RMN (400 MHz, CDCb) δ: 7.69-7.63 (1H, m), 7.24-7.20 (1H, m), 7.07-7.00 (1H, m), 4.03-3.92 (2H, m), 3.68-3.57 (2H, m), 3.55-3.22 (3H, m), 3.12-3.00 (3H, m), 2.66-2.55 (2H, m), 2.31-2.20 (2H, m), 2.10-1.98 (4H, m), 1.26-1.15 (3H, m). ΜΛ / a / ZUZZ / UU 1341 37 N'° II 0 L— II 1 \__ / —F .--- ____ J '-~=i / H O >< N ^-RMN (400 MHz, CDCl) δ: 7.78-7.70 (1H, m), 7.23-7.19 (1H, m), 7.07-7.00 (1H, m), 4.11-4.00 (1H, m), 3.76-3.51 (4H, m), 3.37-2.92 (6H, m), 2.67-1.93 (8H, m), 1.24-1.07 (6H, m). 38 N'° OH < \\ = 1 1 \__z^f / “X^ N N '___ν=^ζ o XH-RMN (400 MHz, CDCl) δ: 7.72-7.63 (1H, m), 7.23-7.20 (1H, m), 7.07-7.00 (1H, m), 4.58-4.36 (1H, m), 3.81-2.94 (7H, m), 2.43-2.33 (2H, m), 2.20-1.98 (6H, m), 1.84-1.63 (3H, m), 1.35-1.30 (3H, m), 1.24-1.10 (3H, m). 39 N'θ / 1 V-λ 0 η^ι\ δ— «γΑ^Μ ^-RMN (400 MHz, CDCh) d: 7.70-7.56 (1H, m), 7.19-7.14 (1H, m), 7.03-6.95 (1H, m), 4.49-4.33 (1H, m), 3.75-3.43 (2H, m), 3.31-2.81 (6H, m), 2.59-2.44 (2H, m), 2.32-1.88 (6H, m), 1.64-1.47 (2H, m), 1.33-1.22 (3H, m), 0.90-0.80 (3H, m). 40 N'th [1 0 i^^i \ 'L. J ^-RMN (400 MHz, CDCh) δ: 7.75-7.62 (1H, m), 7.23-7.20 (1H, m), 7.07-7.00 (1H, m), 3.75-2.92 (8H, m), 2.62-2.51 (2H, m), 2.37-1.94 (6H, m), 1.37-1.27 (3H, m), 1.27-1.11 (3H, m). 41 N'° 1' 0 C| \ Z~~F the, Á.___^== / F ^-RMN (400 MHz, CDCh) δ: 7.74-7.63 (1H, m), 7.23-7.18 (1H, m), 7.08-6.99 (1H, m), 4.53-4.38 (1H, m), 3.97-3.82 (2H, m), 3.54-3.21 (2H, m), 3.19-2.95 (3H, m), 2.63-2.49 (2H, m), 2.34-2.18 (2H, m), 2.15-1.97 (4H, m), 1.38-1.28 (3H, m), 1.28-1.11 (6H, m). 42 Ν-° 1' 0 Ι^^Γ \ υ— II 1 \. Z~~F ΗΟ* JL . Ν. J ^-== / ν JH-RMN (400 MHz, CDCh) δ: 7.72-7.63 (1H, m), 7.23-7.18 (1H, m), 7.07-7.00 (1H, m), 4.52-4.39 (1H, m), 3.97-3.84 (1H, m), 3.53-3.21 (2H, m), 3.16-2.96 (3H, m), 2.61-2.50 (2H, m), 2.34-2.20 (2H, m), 2.12-1.96 (4H, m), 1.78-1.62 (1H, m), 1.36-1.28 (3H, m), 1.28-1.17 (6H, m). 43 Ν'° [1 2^ 0 Γ^τν \L || 1 \__Ζ~~ F < Ν ΗΟ'*’^^ ^-RMN (400 MHz, CDCh) δ: 7.68-7.61 (1H, m), 7.23-7.19 (1H, m), 7.07-6.99 (1H, m), 3.73-3.58 (1H, m), 3.49-3.31 (4H, m), 3.11-2.94 (3H, m), 2.57-2.49 (2H, m), 2.44-2.16 (3H, m), 2.11-1.97 (6H, m), 1.84-1.52 (6H, m), 1.35-1.05 (4H, m). 44 N'° II 0 1 \__Z^FJ '^Z < N H(Γ--- ^-RMN (400 MHz, CDCl) δ: 7.69-7.61 (1H, m), 7.23-7.18 (1H, m), 7.07-7.00 (1H, m), 4.05-3.97 (1H, m), 3.50-3.31 (4H, m), 3.13-2.97 (3H, m), 2.59-2.42 (3H, m), 2.31-2.17 (2H, m), 2.10-1.81 (7H, m), 1.71-1.42 (6H, m), 1.23-1.05 (3H, m). 45 N'θ [1 2^ 0 / 'x F ^-RMN (400 MHz, CDCb) d: 7.52-7.46 (1H, m), 7.44-7.31 (1H, m), 7.30-7.25 (1H, m), 4.57-4.37 (1H, m), 3.80-2.91 (8H, m), 2.74-2.49 (2H, m), 2.39-1.98 (6H, m), 1.37-1.29 (3H, m), 1.26-1.10 (3H, m). 46 N'O P 2--, o II 1 \.__Z~~F N HO^^ 1H-RMN (400 MHz, CDCb) δ: 7.77-7.61 (1H, m), 7.24-7.20 (1H, m), 7.09-7.01 (1H, m), 4.24-4.13 (1H, m), 3.72-1.94 (20H, m), 1.75-1.51 (1H, m), 1.20-1.07 (3H, m). 47 ^NH JL J HO N ^-RMN (400 MHz, CDCb) δ: 8.05-7.94 (1H, m), 7.61 (1H, d, J = 7.9 Hz), 7.35 (1H, d, J = 7.9 Hz), 7.17 (1H, t, J = 7.0 Hz), 7.09 (1H, t, 1 = 7.3 Hz), 6.97 (1H, dd, J = 6.1, 2.4 Hz), 3.92-3.56 (4H, m), 3.46-1.43 (15H, m), 1.24-1.11 (3H, m). 48 ^NH II 1 \^Z^F >\ ^X HO N 1H-RMN (400 MHz, CDCl) δ: 8.12-7.97 (1H, m), 7.50 (1H, dd, J = 8.5, 5.5 Hz), 7.02 (1H, dd, J = 9.5, 2.1 Hz), 6.96-6.91 (1H, m), 6.85 (1H, td, J = 9.2, 2.0 Hz), 3.95-3.52 (4H, m), 3.50-1.45 (16H, m), 1.22-1.10 (3H, m). 49 ^-ΝΗ Γ 0 (^^\ \ / ΗΟ. JL S η< ν ^-RMN (400 MHz, CDCb) δ: 8.00 (1H, br s), 7.61 (1H, d, J = 7.9 Hz), 7.35 (1H, d, J = 7.9 Hz), 7.17 (1H, t, J = 7.6 Hz), 7.08 (1H, t, J = 7.3 Hz), 6.99-6.94 (1H, m), 4.74-4.34 (2H, m), 3.87-1.71 (15H, m), 1.34 (3H, t, J = 6.4 Hz), 1.25-1.11 (3H, m). 50 ° Γ Τ^ V '1 || 1 \.__ / F ΗΟ. JL .zs. _Ν. J ^=7 Ν ^-RMN (400 MHz, CDCb) δ: 7.29-7.22 (2H, m), 6.94 (1H, td, J = 9.2, 2.4 Hz), 6.47 (1H, d, J = 3.7 Hz), 4.53-4.12 (2H, m), 3.80-3.64 (2H, m), 3.56-2.88 (5H, m), 2.69-2.54 (2H, m), 2.42-2.25 (2H, m), 2.15-1.98 (4H, m), 1.38-1.33 (3H, m), 1.29-1.13 (3H, m). ινΐΛ / a / zuzz / uu EJEMPLO 51 N-Et¡l-N-{2-[4-(6-fluoro-l,2-benzo¡soxazol-3-¡l)p¡per¡d¡n-l-¡l]et¡l}-2-h¡drox¡etan-lsulfonamida A solution of the compound from reference example 23 (636 mg) in tetrahydrofuran (20 mL) was mixed with 10% aqueous tetrabutylammonium hydroxide (17.3 mg). The mixture was stirred at 60°C for 2 hours and concentrated. The residue was purified by silica gel column chromatography (chloroform / methanol), and further purified by silica amino gel column chromatography (chloroform / methanol) to obtain the title compound (330 mg). NMR 4.03-3.95 (2H, m), 3.60-3.53 (2H, m), 3.33-3.24 (4H, m), 3.21-3.09 (3H, m), 2.59-2.52 (2H, m), 2.31-2.13 (4H, m), 2.11-2.00 (2H, m), 1.25 (3H, t, J = 7.0 Hz). EXAMPLES 52 TO 64 According to the method of example 51, the compounds of examples 52 to 64 were prepared from the corresponding reference example compounds. Ejemplo Estructura química Datos de análisis instrumental 52 HO^ 0 0 Γ \\ / / 1 . N N'° 1' Λ-' Z~-F ^-RMN (400 MHz, CDCh) δ: 7.90-7.81 (1H, m), 7.17 (1H, dd, J = 8.2, 2.1 Hz), 7.07 (1H, td, J = 9.0, 2.2 Hz), 3.65-2.21 (17H, m), 1.67-1.56 (1H, m), 1.43-1.31 (1H, m), 1.26 (3H, d, J = 6.7 Hz), 1.09 (3H, t, J = 7.0 Hz). 53 ho .Λ. ^.N £ O O N-0 Ύύ V XH-RMN (400 MHz, CDCh) δ: 7.69-7.60 (1H, m), 7.19-7.15 (1H, m), 7.04-6.96 (1H, m), 4.03-3.95 (2H, m), 3.32-3.22 (4H, m), 3.16-3.09 (2H, m), 3.09-2.96 (3H, m), 2.92-2.81 (1H, m), 2.47-2.36 (2H, m), 2.27-1.93 (6H, m), 1.87-1.74 (2H, m), 1.17 (3H, t, J = 7.3 Hz). Ν'° [1 ^-RMN (400 MHz, CD3OD) δ: 7.91-7.88 (1Η, m), 7.61-7.58 (2Η, m), 7.40-7.32 (1Η, m), 3.91 (1H, dd, J = 11.6, 4.9 Hz), 54 ηο. JL ^Ν. Ζ / \\ Ο 0 ζ\^Ν τ \ ') ι ν^^. / 3.68-3.62 (1H, m), 3.39-3.08 (9H, m), 2.52-2.45 (2H, m), 2.31-2.22 (2H, m), 2.16-2.03 (4H, m), 1.92-1.82 (2H, m), 1.35 (3H, d, J = 6.7 Hz), 1.24 (3H, t, J = 7.3 Hz). 55 ηο. 1 Jk. . & 0 0 Ν-° II ΧΝ^γ \\ 1 V=í / F ^-RMN (400 MHz, CD3OD) δ: 7.89 (1H, dd, J = 8.9, 5.2 Hz), 7.25 (1H, dd, J = 8.9, 2.1 Hz), 7.08 (1H, td, J = 9.2, 2.4 Hz), 3.91 (1H, dd, J = 11.0, 4.9 Hz), 3.67-3.61 (1H, m), 3.58-3.51 (4H, m), 3.40-3.23 (6H, m), 2.72-2.63 (4H, m), 2.52-2.44 (2H, m), 1.92-1.80 (2H, m), 1.35 (3H, d, J = 6.7 Hz), 1.27-1.19 (3H, m). 56 ηο. 1 -Ν^ . Λ 0 0 Ν'θ Π 2^ Ύύ V 1 V-y~F ^-RMN (400 MHz, CD3OD) δ: 7.91 (1H, dd, J = 8.9, 5.2 Hz), 7.38 (1H, dd, J = 8.9, 2.1 Hz), 7.17 (1H, td, J = 9.0, 2.0 Hz), 3.91 (1H, dd, J = 11.6, 4.9 Hz), 3.64 (1H, dd, J = 11.6, 6.7 Hz), 3.39-3.05 (8H, m), 2.51-2.44 (2H, m), 2.30-2.21 (2H, m), 2.15-1.99 (5H, m), 1.91-1.81 (2H, m), 1.35 (3H, d, J = 6.7 Hz), 1.23 (3H, t, J = 7.0 Hz). 57 ΗΟ^ 0 0 ^ΝΗ γύΛ ^-RMN (400 MHz, CDCI3) δ: 7.96 (1H, s), 7.59 (1H, d, J = 7.9 Hz), 7.30 (1H, d, J = 7.9 Hz), 7.15-7.09 (1H, m), 7.07-7.01 (1H, m), 6.96-6.91 (1H, m), 3.96-3.87 (2H, m), 3.72-3.51 (3H, m), 3.35-3.12 (6H, m), 2.93-1.85 (9H, m), 1.25-1.13 (3H, m). 58 ΗΟ^ 0 0 'X ΧΝ Ν'θ Π 2^ ΓΎ V J ^== / F JH-RMN (400 MHz, CDCh) δ: 7.65 (1H, d, J = 7.3 Hz), 7.18 (1H, d, J = 9.1 Hz), 5.98 (1H, br s), 4.04-3.96 (2H, m), 3.60-3.54 (2H, m), 3.34-3.26 (4H, m), 3.21-3.06 (3H, m), 2.61-2.51 (2H, m), 2.36-2.32 (3H, m), 2.30-2.14 (4H, m), 2.10-1.98 (2H, m), 1.25 (3H, t, J = 7.0 Hz). 59 ΗΟ^ 0. ,0 'X / - Ν^χ Ν'° II 2~^ Γ\ ντ*». / ^-RMN (400 MHz, CDCh) δ: 7.61 (1H, s), 7.42 (1H, d, J = 8.5 Hz), 7.32 (1H, dd, J = 8.5, 1.8 Hz), 6.13-5.86 (1H, m), 4.043.98 (2H, m), 3.61-3.55 (2H, m), 3.373.24 (4H, m), 3.23-3.09 (3H, m), 2.622.53 (2H, m), 2.45 (3H, s), 2.37-2.17 (4H, m), 2.13-1.99 (2H, m), 1.25 (3H, t, J = 7.0 Hz). IVIA / a / ZUZZ / UU60 HCT 0 0 N N'° li 2—, τ \ V J ~CI 1H-RMN (400 MHz, CDCb) δ: 7.72 (1H, d, J = 8.5 Hz), 7.53-7.49 (1H, m), 7.24-7.20 (1H, m), 5.80 (1H, br s), 4.00-3.90 (2H, m), 3.57-3.48 (2H, m), 3.31-3.18 (4H, m), 3.18-3.05 (3H, m), 2.63-2.44 (2H, m), 2.36-2.08 (4H, m), 2.08-1.96 (2H, m), 1.20 (3H, t, J = 7.0 Hz). 61 HCT 0 O N ,N. N-° ii T\ ^-RMN (400 MHz, CDCb) δ: 7.78 (1H, d, J = 7.9 Hz), 7.52-7.44 (2H, m), 7.26-7.20 (1H, m), 5.88 (1H, br s), 3.98-3.92 (2H, m), 3.58-3.49 (2H, m), 3.31-3.19 (4H, m), 3.19-3.05 (3H, m), 2.57-2.49 (2H, m), 2.33-2.12 (4H, m), 2.10-1.98 (2H, m), 1.20 (3H, t, J = 7.0 Hz). 62 HCT O 0 N Ns NH Υ\ Λ- J / F JH-RMN (400 MHz, CDCb) δ: 8.06 (1H, s), 7.53 (1H, dd, J = 8.9, 5.2 Hz), 7.03 (1H, dd, J = 9.5, 2.1 Hz), 6.97-6.92 (1H, m), 6.89-6.81 (1H, m), 4.00-3.92 (2H, m), 3.65-3.55 (2H, m), 3.34-3.15 (6H, m), 2.91-1.58 (10H, m), 1.29-1.20 (3H, m). 63 HCT O O 'X / n N NíS\ 1 \__ υνύΛ ~F XH-RMN (400 MHz, CDCb) δ: 7.92 (1H, s), 7.43 (1H, dd, J = 9.2, 3.7 Hz), 7.33 (1H, dd, J = 8.5, 2.4 Hz), 7.13 (1H, td, J = 9.2, 2.4 Hz), 4.58-4.38 (1H, m), 4.08-4.00 (2H, m), 3.64-3.50 (2H, m), 3.40-3.13 (6H, m), 2.76-2.53 (2H, m), 2.51-2.22 (4H, m), 2.18-1.98 (1H, m), 1.79-1.47 (2H, m), 1.25 (3H, t, J = 7.3 Hz). 64 HCT O 0 y ^N, N=\ 1 \__ υνύΛ T JH-RMN (400 MHz, CDCb) δ: 7.92 (1H, s), 7.47-7.39 (1H, m), 7.33 (1H, dd, J = 8.5, 2.4 Hz), 7.17-7.10 (1H, m), 4.55-4.36 (1H, m), 3.98-3.68 (3H, m), 3.52-2.98 (5H, m), 2.79-2.14 (4H, m), 2.14-1.96 (1H, m), 1.69-1.46 (5H, m), 1.34 (3H, d, J = 7.3 Hz), 1.25 (3H, t, J = 7.0 Hz). EJEMPLO 65 3-Am¡no-N-et¡l-N-{2-[4-(6-fluoro-l,2-benzo¡soxazol-3-il)piper¡d¡n-l-¡l]et¡l}-25 hidroxipropanamida To a solution of 3-((tert-butoxycarbonyl)amino)-2-hydroxypropionic acid (40.6 mg) in N,N-dimethylformamide (2.0 mL), O-(7-azabenzotriazol-1-1)-N,N-hexafluorophosphate of N,N',N'-tetramethyluronium (75.0 mg) was added. The mixture was stirred at room temperature for 1 hour, and triethylamine (0.053 mL) and the compound from Reference Example 1 (60.0 mg) were added. The mixture was stirred at room temperature for 3 hours, and then water (10 mL) was added. The mixture was extracted with chloroform / methanol (10 mL x 6), dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrated residue was purified by silica gel column chromatography (chloroform / methanol). Then, 4 mol / L hydrochloric acid-ethyl acetate (2.0 mL) was added to the resulting compound (50 mg). The mixture was stirred at room temperature for 1 hour and concentrated.The residue was purified by amino silica gel column chromatography 10 (chloroform / methanol) to obtain the title compound (37.0 mg). ^-NMR (400 MHz, CDCb) δ: 7.77-7.58 (1H, m), 7.20 (1H, d, J = 7.9 Hz), 7.08-6.91 (1H, m), 4.76-4.24 (1H, m), 3.86-2.69 (9H, m), 2.69-2.41 (4H, m), 2.41-1.74 (7H, m), 1.35-0.89 (3H, m). EXAMPLES 66 TO 70 According to the method of example 65, the compounds of examples 66 to 70 were prepared from the corresponding reference example compounds. IVIA / S / ZUZZ / UU EXAMPLE Chemical structure Instrumental analysis data 66 Ν'0. ho o \ υ__ \ 1 \.__Z^FN HN-^ LC-EM: RT = 1.167 min ObsMS = 405 [M+l] 67 N-° OH O Vi NH LC-EM: RT = 1.200 min ObsMS = 419 [M+l] 68 N' ° HOF 1\Z. \—NH LC-EM: RT = 1.200 min ObsMS = 405 [M+l] 69 N'° Π OI^^T'x 'l. OHII 1 X^Z^F HN N LC-EM: RT = 1.300 min ObsMS = 419 [M+l] 70 N'° ll ° l^^Tx 'L·. HO II 1 X^Z^F LC-EM: RT = 1.100 min ObsMS = 405 [M+l] EXAMPLE 71 3-Acetam¡da-N-ethyl-N-{2-[4-(6-fluoro-l,2-benzo¡soxazol-3-¡l)p¡per¡d¡nl-¡l]et¡l}-25 hydroxypropanamide To a solution of the compound of Example 65 (20.0 mg) in tetrahydrofuran (2.0 mi) IVIA / a / ¿U¿¿ / UU 1341 Anhydrous acetic acid (0.00598 mL) was added. The mixture was stirred at room temperature for 1 hour. Then, 2 mol / L aqueous sodium hydroxide (0.1 mL) was added to the same, and the mixture was stirred at room temperature for 10 minutes. The reaction mixture was concentrated and purified by silica gel column chromatography (chloroform / methanol) to obtain the compound of the 5th grade (10.1 mg). 1H-NMR (400 MHz, CDCI3) δ: 7.77-7.55 (1H, m), 7.19-7.14 (1H, m), 7.05-6.97 (1H, m), 6.19-6.01 (1H, m), 4.49-4.34 (1H, m), 4.03-3.47 (4H, m), 3.47-2.84 (6H, m), 2.72-2.48 (2H, m), 2.43-2.19 (2H, m), 2.16-1.97 (4H, m), 1.96-1.90 (3H, m), 1.24-1.06 (3H, m). ML / a / ZUZZ / UU 1341 EXAMPLES 72 TO 74 According to the method of example 71, the compounds of examples 72 to 74 were prepared from the corresponding reference example compounds. Example Chemical Structure Instrumental Analysis Data 72 N-° ¡iv 0 0 r^r \\ II OH|| 1 \ / —F JL _____ JL ___. LC-EM: RT = 1.258 min ObsMS = 461 [M+l] 73 N'° HO O IT^ \ / N °K LC-EM: RT = 1.350 min ObsMS = 447 [M+l] 74 N-° OH O \\ N o^1^ LC-EM: RT = 1.270 min ObsMS = 461 [M+l] EXAMPLE 75 N-Et¡lN-{2-[4-(6-fluoro-l,2-benzo¡soxazol-3-¡l)p¡perídin-l-¡l]et¡l}-4-hydroxy¡-lmethylpyrrolidine-3-carboxamide A solution of the compound from Example 66 (10.0 mg) in methanol (0.5 mL) was mixed with 37% aqueous formaldehyde (0.002 mL), sodium cyanoborohydride (1.09 mg), and acetic acid (0.003 mL). The mixture was stirred at room temperature for 16 hours. Then, water (10 mL) was added, and the mixture was extracted with chloroform (10 mL x 2) and concentrated. The concentrated residue was purified by high-performance liquid chromatography (column; C-18 semipreparative column, separation condition; acetonitrile / trifluoroacetic acid: water / trifluoroacetic acid) and desalted with MP-carbonate resin to obtain the title compound (6.88 mg). LC-MS: RT = 1.083 min ObsMS = 419 [M+l] EXAMPLE 76 N-Ethyl-N-{2-[4-(6-fluoro-l,2-benzo¡soxazol-3-yl)piper¡dinl-¡l]ethyl}-4-hydroxy-lmethylpiperidine-3-carboxamide According to a method similar to Example 75, the title compound was prepared from the compound in Example 67. LC-MS: RT = 1.092 min ObsMS = 433 [M+l] EXAMPLE 77 N-Et¡lN-{2-[4-(6-fluoro-l,2-benzo¡soxazol-3-¡l)piper¡dinl-¡l]ethyl}-3hydroxypropanamide orotate To a solution of the compound from Example 17 (30 mg) in methanol (0.4 mL), orotic acid (14.4 mg) was added. The mixture was stirred at 60°C for 1 hour, and ethyl acetate (2.0 mL) and water were added. The mixture was stirred at room temperature for 1 hour, and the precipitated solid was collected by filtration to obtain the title compound (27.3 mg). íH-RMN (400 MHz, DMSO-D6) δ: 11.02 (1H, s), 9.94 (1H, brs), 8.03 (1H, dd, J = 8.8, 5.2 Hz), 7.74-7.68 (1H, m), 7.35-7.27 (1H, m), 5.79 (1H, d, J = 1.8 Hz), 4.53 (1H, brs), 3.65 (2H, t, J = 6.7 Hz), 3.62-3.49 (3H, m), 3.48-3.19 (6H, m), 3.18-2.62 (4H, m), 2.28-2.13 (2H, m), 2.13-1.91 (2H, m), 1.12 (2H, t, J = 7.0 Hz), 1.02 (1H, t, J = 7.0 Hz). Powder XRD (°, 2θ±0.2) 4.87, 7.24, 15.27, 15.75, 16.02, 16.39, 16.73, 17.62, 19.51, 20.04, 21.24, 22.05, 22.34, 24.23, 24.80 (Entre ellos, los 10 pics Characteristics were 4.87, 7.24, 15.27, 15.75, 16.02, 17.62, 19.51, 20.04, 21.24, 22.05, and the 4 most characteristic characteristics were 4.87, 19.51, 20.04, 21.24.) DSC Enthalpy (normalized): 62.81 J / g Start x: 157.09°C EXAMPLE 78 Hydrobromuro de N-Et¡lN-{2-[4-(6-fluoro-l,2-benzo¡soxazol-3-il)p¡per¡d¡nl-yl]et¡l}-3hidroxipropanamida in Form A To a solution of the compound from Example 17 (6.03 g) in acetonitrile (77 mL), 10–20% HBr-EtOH (14.1 g) was added dropwise. The mixture was stirred at room temperature for 1 hour, and the precipitation of a solid was confirmed. The mixture was then stirred at 80°C. After confirming that the precipitated solid was completely dissolved, the mixture was stirred for another 1 hour. The mixture was then gradually cooled and stirred at room temperature for 12 hours. The precipitated solid was collected by filtration, washed with acetonitrile (10 mL), and dried to obtain a white solid (7.0 g). The resulting white solid (7.0 g) was mixed with tetrahydrofuran (15 mL), and the mixture was stirred at 80°C for 3.5 hours. The mixture was then gradually cooled and stirred at room temperature for 12 hours. The solid was collected by filtration, washed with tetrahydrofuran (10 ml), and dried to obtain the title compound (6.20 g). XX-NMR (400 MHz, DMSO-D6) δ: 9.48 (0.2H, brs), 9.19 (0.8H, brs), 8.11-7.99 (1H, m), 7.78-7.70 (1H, m), 7.40-7.30 (1H, m), (4H, 3), (4H, brs). 3.78-3.56 (6H, m), 3.55-3.09 (8H, m), 2.402.18 (3H, m), 2.15-1.97 (2H, m), 1.19-0.97 (3H, m). Powder XRD(°, 2θ±0.2) 4.48, 8.98, 12.40, 13.63, 15.23, 16.35, 17.07, 17.88, 18.06, 21.19, 23.13, 23.83, 24.48, 25.22, 25.98, among the peaks (E characteristics were 4.48, 12.40, 15.23, 17.07, 17.88, 21.19, 23.13, 24.48, 25.22, 25.98, and the 4 most characteristic points were 12.48, 12.7, 15.7, 13.7. iviA / a / zuzz / uu 21.19.) DSC Enthalpy (normalized): 82.83 J / g Initial x: 163.64°C EXAMPLE 79 N-Et¡lN-{2-[4-(6-fluoro-l,2-benzo¡soxazol-3-¡l)p¡per¡d¡nl-¡l]et¡l}-3hydroxypropanamide hydrobromide in Form B To a solution of the compound from Example 17 (100 mg) in acetonitrile (2.0 mL) 10 to 20% HBr-EtOH (0.2 mL) was added dropwise. The mixture was stirred at room temperature for 1 hour, and the precipitated solid was collected by filtration to obtain the compound of the title (67.0 mg). XRD Powder(°, 20±0.2) 7.25, 7.65, 9.90, 11.17, 12.48, 15.34, 15.71, 22.36, 23.36, 23.74, 24.62, 25.05, 25.18, 25.26, 29.36 (Among them, the 10 characteristic peaks were 7.25, 7.65, 9.90, 15.34, 15.71, 23.36, 24.62, 25.05, 25.18, 25.26, and the 4 most characteristic peaks were 7.25, 7.65, 9.90, 15.34.) DSC Enthalpy (normalized): 86.51 J / g Start x: 164.04°C EXAMPLE 80 N-Et¡lN-{2-[4-(6-fluoro-l,2-benzo¡soxazol-3-¡l)p¡perídinl-¡l]ethyl}-3hydroxypropanamide tosylate A solution of the compound from Example 17 (66.7 g) in deuteromethanol (200 mL) was mixed with a solution of p-toluenesulfonic acid monohydrate (41.9 g) in acetone (150 mL). The mixture was stirred at room temperature for 2 hours. The precipitated solid was collected by filtration, washed with acetone (60 mL), and dried to obtain a white solid (78.8 g). The resulting white solid (78.8 g) and a mixture of acetone (608 mL) and water (33.4 mL) were stirred at 70°C. After confirming that the white solid was completely dissolved, the mixture was gradually cooled and stirred at room temperature for 12 hours. After stirring at 0°C for 1 hour, the resulting solid was collected by filtration, washed with a 5% water-acetone solvent mixture (70 ml) cooled to 0°C and dried to obtain the title compound (69.4 g). ^-NMR (400 MHz, DMSO-D6) δ: 9.39-9.00 (1H, m), 8.08-7.99 (1H, m), 7.77-7.71 (1H, ML / a / ZUZZ / UU 1341 m), 7.46 (2H, d, J = 7.9 Hz), 7.39-7.30 (1H, m), 7.10 (2H, d, J = 7.9 Hz), 4.53 (1H, brs), 3.76-3.56 (6H, m), 3.54-3.11 (8H, 6H, 6-8), m), 2.12-1.96 (2H, m), 1.16-0.98 (3H, m). Powder XRD(°, 20±0.2) 6.87, 7.03, 9.64, 13.74, 15.19, 15.37,15.68, 16.22, 19.82, 21.60, 21.67, 22.10, 23.15, 23.88, 27.67 (Among them, the 10 characteristic peaks were 7.03, 9.64, 15.19, 15.37, 15.68, 16.22, 21.60, 21.67, 23.15, 23.88, and the most characteristic peaks they were 7.03, 9.64, 15.19, 15.68.) DSC Enthalpy (normalized): 99.47 J / g Initial x: 162.26°C IVIA / a / ZUZZ / UU ÍWf REFERENCE EXAMPLE 1 N-Et¡l-2-[4-(6-fluoro-l,2-benzo¡soxazol-3-l)p¡per¡d¡nl-¡l]ethane-l- To a solution of 6-fluoro-3-(4-pyridine)-1,2-benzoisoxazole (5.78 g) in chloroform (131 mL), tert-butylethyl(2-oxoethyl)carbamate (4.91 g) and sodium triacetoxyborohydride (11.1 g) were added. The mixture was stirred at room temperature for 5 hours. Saturated aqueous sodium bicarbonate (100 mL) was added, and the mixture was extracted with chloroform (100 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (chloroform / methanol). To a solution of the resulting compound in chloroform (131 mL), 4 mol / L hydrochloric acid and ethyl acetate (60 mL) were added. The mixture was stirred at room temperature for 2 hours. The precipitated solid was collected by filtration, washed with ethyl acetate (20 mL x 2), and dried to obtain the title compound (6.24 g). íH-NMR (400 MHz, DMSO-De) δ: 9.31 (2H, brs), 8.18 (1H, dd, J = 8.5, 5.5 Hz), 7.74 (1H, dd, J = 8.9, 2.1 Hz), 7.35 (1H, ddd, J = 9.0, 9.0, 2.2 Hz), 3.81-3.72 (2H, m), 3.55-3.46 (5H, m), 3.28-3.15 (2H, m), 3.08-2.97 (2H, m), 2.43-2.23 (4H, m), 1.25 (3H, t, J = 7.3 Hz). REFERENCE EXAMPLES 2 TO 13 According to a similar method to reference example 1, the compounds in reference examples 2 to 13 were prepared from the reference example compounds or reagents. Reference Example Chemical Structure Instrumental Analysis Data 2 NSA 1 \__ 1 1 \^ / ^F 2HCI ^-NMR (400 MHz, CD3OD) δ: 8.07-7.98 (1H, m), 7.76-7.60 (1H, m-7), 7.4). (1H, ddd, J = 9.1, 9.1, 1.8 Hz), 5.06–4.94 (1H, m), 3.94–3.84 (2H, m), 3.643.55 (4H, m), 3.49–3.37), (2H, m), 7.3, q =2 2.77–2.64 (2H, m), 2.36–2.25 (2H, m), 1.39 (3H, t, J = 7.3 Hz). 3 N-° [l --( 2HCI HN^ \ JH-RMN (400 MHz, CDCh) δ: 7.55-7.47 (1H, m), 7.24 (1H, s), 7.18 (1H, d, J = 9.2 Hz), 3.47-2.6-H2 (8.4), m 2.34 (3H, d, J = 1.8 Hz), 2.30-2.16 (1H, m), 2.151.94 (4H, m), 1.10 (3H, t, J = 7.0 Hz) 4 N~° 11 \ Λ __δ: OD 3 ^0 Hz 2HCI). 7.81 (1H, s), 7.53-7.43 (2H, m), 3.92-3.83 (2H, m), 3.723.42 (5H, m), 3.40-3.32 (2H, m), 3.20 (2H, q, J = 7.3 7 -H), 2.2. (3H, t, J = 7.3 Hz). 8.5, 1.8 Hz), 3.92–3.81 (2H, m), 3.71–3.44 (5H, m), 3.40-3.32 (2H, m), 3.20 (2H, q, J = 6.9 Hz), 2.64-2.36 (4H, m), 1.39 (3H, t, J = 7.3 Hz). 6 n~nh ll <Ύύ V 1 V-^Z^F J --' 2HCI HN ^-RMN (400 MHz, CD3OD) δ: 8.06 (1H, dd, J = 8.8, 5.2 Hz), 7.26 (1H, d, J = 9.1 Hz), 7.06 (1H, dd, J = 9.1, 9.1 Hz), 3.92-3.80 (2H, m), 3.67-3.50 (5H, m), 3.42-3.33 (2H, m), 3.20 (2H, q, J = 7.1 Hz), 2.57-2.43 (2H, m), 2.41-2.27 (2H, m), 1.40 (3H, t, 1 = 7.3 Hz). 7 NH <YYVF 2HCI ^-RMN (400 MHz, DMSO-Ds) δ: 10.98 (1H, s), 10.72 (1H, s), 9.20 (2H, s), 7.67 (1H, dd, J = 8.5, 5.5 Hz), 7.15-7.09 (2H, m), 6.886.80 (1H, m), 3.74-3.65 (2H, m), 3.49-3.39 (4H, m), 3.21-3.09 (2H, m), 3.08-2.93 (3H, m), 2.18-2.07 (4H, m), 1.23 (3H, t, 1 = 7.0 Hz). 8 ^NH Ay} HN^^^ 2HCI ^-RMN (400 MHz, DMSO-D6) δ: 10.89 (1H, S), 10.70 (1H, s), 9.20 (2H, s), 7.67 (1H, d, J = 7.9 Hz), 7.35 (1H, d, J = 8.5 Hz), 7.12 (1H, d, J = 2.4 Hz), 7.09-7.04 (1H, m), 6.996.94 (1H, m), 3.75-3.65 (2H, m), 3.52-3.40 (4H, m), 3.22-3.11 (2H, m), 3.07-2.94 (3H, m), 2.22-2.07 (4H, m), 1.23 (3H, t, J = 7.3. Hz). 9 N-° 11 vV Λ JV!>»Z 2HCI ^-RMN (400 MHz, CD3OD) δ: 8.03-7.92 (1H, m), 7.67-7.61 (2H, m), 7.43-7.37 (1H, m, m), 2.3-3-3 (5H, m), 3.38–3.31 (2H, m), 3.19 (2H, q, J = 7.3 Hz), 2.55–2.33 (4H, m), 1.38 (3H, t, J = 7.3 Hz). 10 HN^ ,N N'° 11 Y 2HCI 1H-RMN (400 MHz, CD3OD) δ: 7.90 (1H, d, J = 7.9 Hz), 7.63-7.58 (1H, m), 7.53, (1H, d, J = 8.3 d 4), 7.6 Hz), 4.16–3.72 (4H, m), 3.69–3.40 (8H, m), 3.19 (2H, q, J = 7.1 Hz), 1.38 (3H, t, J = 7.3 Hz). 11 HN^ ,NN~° ii Y-, YJV?-»». / F 2HCI XH-RMN (400 MHz, CD3OD) δ: 7.93 (1H, dd, J = 9.2, 4.9 Hz), 7.33 (1H, dd, J = 8.1 ddd (1.1 Hz), = 2.2. 9.0, 9.0, 2.0 Hz), 4.33–3.71 (4H, m), 3.70–3.41 (8H, m), 3.19 (2H, q, J = 7.3 Hz), 1.38 (3H, t, J = 7.3 Hz). 12 HN7^ ZN N-°. ii γγΐ IF 2HCI ^-RMN (400 MHz, DMSO-D6) δ: 11.01 (1H, s), 9.20 (2H, s), 8.04-7.98 (1H, m), 7.81 (1H, dd, J = 4.5 ddd, Hz), 9.1, 9.1, 2.4 Hz), 3.82–3.70 (2H, m), 3.553.40 (4H, m), 3.26–3.12 (3H, m), 3.09–2.96 (2H, m), 2.42-2.22 (4H, m), 1.23 (3H, t, J = 7.3 Hz). 13 HN^' ,N 1 T 2HCI LC-EM : RT = 0.443 min ObsMS = 290 [M+l]. REFERENCE EXAMPLE 14 6-Fluoro-5-methyl-3-(piper¡d¡n-4-yl)-l,2-benzo¡soxazole monohydrochloride iviA / a / zuzz / uu Reference Example a) Preparation of 4-[methoxy(meth¡l)carbamoyl]piperid¡na-l-carbox¡ter-butyl late (compound IN-1-1) A mixture of l-(tert-butoxycarbonyl)properidine-4-carboxylic acid (5.00 g), N,O-dimethylhydroxylamine hydrochloride (3.19 g), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-l,3-diamine hydrochloride (5.02 g), triethylamine (4.41 g), and N,N-dimethylformamide (100 mL) was stirred at room temperature for 1.5 hours. Saturated aqueous ammonium chloride was then added, and the mixture was extracted with ethyl acetate. The combined organic layer was washed twice with saturated aqueous ammonium chloride and saturated aqueous sodium bicarbonate and brine, and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated to obtain the title compound (4.52 g). 1H-NMR (400 MHz, CDCh) δ: 4.03-4.24 (2H, m), 3.72 (3H, s), 3.19 (3H, s), 2.70-2.86 (3H, m), 1.63-1.76 (4H, m), 1.46 (9H, s). b) Preparation of 4-(2,4-difluoro-5-methylbenzoyl)piperidin-1-carboxylate of tere-butyl (compound IN-1-2) To a solution of l-bromo-2,4-difluoro-5-methylbenzene (2.28 g) in tetrahydrofuran (36 mL), 1.63 mol / L n-butyllithium / hexane (7.43 mL) was added dropwise for 3 minutes at 78°C. After stirring at -78°C for 1 hour, Compound IN-1-1 (1.50 g) was added, and the mixture was stirred for 2.5 hours at -78°C. Saturated aqueous ammonium chloride was then added, and the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrated residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the title compound (2.01 g). XH-RMN (400 MHz, CDCI3) δ: 7.17-7.25 (1H, m), 6.80-6.87 (1H, m), 1.83-1.92 (2H, m), 1.59-1.69 (2H, m), 1.45 (9H, s). c) Preparation of 4-(6-fluoro-5-methyl,2-benzoxazol-3-yl)pyridin-tert-butyl carboxylate (compound IN-1-3) A mixture of compound IN-1-2 (731 mg), hydroxylamine hydrochloride (599 mg), and sodium acetate (707 mg) in ethanol (10 mL) was stirred at 60°C for 4 hours. Water was then added, and the mixture was extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrated residue was purified by silica gel column chromatography (hexane / ethyl acetate). The resulting product (335 mg) was mixed with cesium carbonate (615 mg) and acetonitrile (9.0 mL), and the mixture was stirred in a sealed tube at 130°C for 3.5 hours. The reaction mixture was then filtered, concentrated, and purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the title compound (90.8 mg). ^-NMR (400 MHz, CDCh) δ: 7.47 (1H, d, J = 7.1 Hz), 7.21 (1H, d, J = 9.0 Hz), 4.114.36 (2H, m), 3.16-3.26 (1H, m), 2.89-3.03 (2H, m), 2.38 (3H, d, J = 1.7 Hz), 2.01-2.10 (2H, m), 1.87-1.99 (2H, m). d) Preparation of 6-fluoro-5-methyl-3-(piperidin-4-yl)-l,2-benzoisoxazole monohydrochloride (Reference example 14) To a solution of compound IN-1-3 (131 mg) in dichloromethane (1.0 mL) 4 mol / L hydrochloric acid / ethyl acetate (1.0 mL) was added, and the mixture was stirred at room temperature for 1.5 hours. Then, the reaction mixture was concentrated to obtain the title compound (114 mg). ^-NMR (400 MHz, CDCh) δ: 7.30 (1H, d, J = 7.3 Hz), 7.11 (1H, s), 7.06 (1H, d, J = 9.1 Hz), 4.12-4.04 (2H, m), 3.09-3.01 (1H, m), 2.84-2.75 (2H, m), 2.22 (3H, d, J = 1.8 Hz), 1.93-1.86 (2H, m), 1.84-1.71 (2H, m). REFERENCE EXAMPLE 15 ινΐΛ / a / zuzz / uu 1 y+1 5-Methyl-3-(p¡perídin-4-¡l)-l,2-benzo¡soxazole monohydrochloride According to a method similar to reference example 14, the title compound was prepared from l-fluoro-2-iodo-4-methylbenzene. íH-NMR (400 MHz, CDCI3) δ: 7.48-7.43 (2H, m), 7.38-7.34 (1H, m), 4.29-4.20 (2H, m), 3.28-3.18 (1H, m), 3.02-2.92 (2H, m), 2.48 (3H, s), 2.11-2.03 (2H, m), 2.03-1.90 (2H, m). REFERENCE EXAMPLE 16 N-(C¡cloprop¡lmethyl)-2-[4-(6-fluoro-l,2-benzo¡soxazol-3-¡l)p¡perídin-l-¡l]ethan-l-amine To a solution of 2-(4-(6-fluorobenzo[d]isoxazol-3-1)pyridine-1-1)ethanol-1-amine (50.0 mg) in chloroform (2.0 mL), cyclopropanecarbaldehyde (16.0 mg) was added, and the mixture was stirred at room temperature for 30 minutes. Then, sodium thacetoxyborohydride (60.4 mg) was added, and the mixture was stirred at room temperature for 1 hour. Saturated aqueous sodium bicarbonate (30 mL) was then added. The mixture was extracted with chloroform (30 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the title compound (26.0 mg). LC-MS: RT = 1250 min ObsMS = 318 [M+l] REFERENCE EXAMPLE 17 N-{2-[4-(6-Fluoro-l,2-benzoisoxazole-3-¡l)p¡per¡d¡nl-¡l]et¡l}propan-2-am¡na In accordance with a method similar to reference example 16, the title compound was prepared from acetone. LC-EM: RT = 1.176 min ObsMS = 306 [M+l] REFERENCE EXAMPLE 18 ({2-[4-(6-Fluoro-l,2-benzo¡soxazole-3-¡l)piper¡d¡nl-¡l]et¡l}amino)aceton¡tr¡lo ΜΛ / a / ZUZZ / UU 1341 To a 55% sodium hydride suspension (7.92 mg) in N,N-dimethylformamide (2.0 mL), the compound from reference example 20 (60.0 mg) was added, and the mixture was stirred at room temperature for 30 minutes. 2-Iodoacetonitrile (41.3 mg) was then added. The reaction mixture was stirred at room temperature for 1 hour, and water (30 mL) was added. The mixture was extracted with chloroform (30 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated. To the concentrated residue, 4 mol / L hydrochloric acid / ethyl acetate (3.0 mL) was added, the mixture was stirred at room temperature for 1 hour, and further concentrated. The concentrated residue was purified by amino silica gel column chromatography (hexane / ethyl acetate) to obtain the title compound (25.0 mg). LC-MS: RT = 0.530 min ObsMS = 303 [M+l] REFERENCE EXAMPLE 19 N-Ethyl-3-[4-(6-fluoro-l,2-benzoisoxazol-3-l)pyridin-l-yl]propan-1amine dihydrochloride According to a method similar to reference example 18, the title compound was prepared from the compound in reference example 21. REFERENCE EXAMPLE 20 Tert-butyl {2-[4-(6-fluoro-l,2-benzoisoxazol-3-¡l)p¡peridin-l-¡l]ethyl¡l}carbamate To a solution (60 mL) of 6-fluoro-3-(pyridine-4-yl)benzo[d]isoxazole (2.89 g) in chloroform, (2.30 g) tert-butyl (2-oxoethyl)carbamate was added, and the mixture was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (3.34 g) was added, and the mixture was stirred at room temperature for 3 hours. Saturated aqueous sodium bicarbonate (100 mL) was added, and the mixture was extracted with chloroform (100 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrated residue was purified by silica gel column chromatography (chloroform / methanol) to obtain the title compound (3.98 g). íH-NMR (400 MHz, CDCI3) δ: 7.67 (1H, dd, J = 8.8, 5.2 Hz), 7.24-7.20 (1H, m), 7.04 (1H, ddd, J = 8.8, 8.8, 2.0 Hz), 5.02 (1H, s), 3.29-3.20 (2H, m), 3.10-2.98 (3H, m), 2.53-2.46 (2H, m), 2.22-2.13 (2H, m), 2.09-2.00 (4H, m), 1.45 (9H, s). REFERENCE EXAMPLE 21 Tert-butyl {3-[4-(6-fluoro-l,2-benzoisoxazol-3-¡l)piper¡dinl-¡l]prop¡l}carbamate To a solution of 6-fluoro-3-(piperidln-4-1)benzo[d]isoxazola (2.00 g) in acetonitrile (50 mL), tert-butyl(3-bromopropyl)carbamate (2.59 g) and potassium carbonate (3.76 g) were added. The mixture was stirred at 60°C for 3.5 hours, and water (200 mL) was added. The mixture was extracted with ethyl acetate (200 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrated residue was purified by silica gel column chromatography (chloroform / methanol) to obtain the title compound (3.46 g). ^-RMN (400 MHz, CDCI3) δ: 7.67 (1H, ddd, J = 8.8, 5.2 Hz), 7.22 (1H, dd, J = 8.5, 2.4 Hz), 7.02 (1H, ddd, J - 8.8, 8.8, 2.2 Hz), 5.50 (1H, s), 3.23-3.17 (2H, m), 3.12-3.00 (3H, m), 2.46 (2Η, t, J = 6.7 Hz), 2.16-1.99 (6H, m), 1.72-1.64 (2H, m), 1.43 (9H, s). REFERENCE EXAMPLE 22 N-{2-[4-(6-Fluoro-lz2-benzoisoxazol-3-¡l)p¡per¡d¡nl-il]et¡l}propan-l-am¡na IVIA / a / ZUZZ / UU / MI Ejemplo de Referencia a) Preparation of 3-[l-(2-chloroeth¡l)p¡pendin-4-¡l]-6-fluoro-l,2-benzo¡soxazole (Compuesto IN-2-1) To a solution (25 mL) of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole (3.00 g) in tetrahydrofuran, water (6.3 mL), potassium hydroxide (1.68 g), and l-bromo-2-chloroethane (5.65 mL) were added, and the mixture was stirred at room temperature for 24 hours. Water (15 mL) was then added. The mixture was extracted with chloroform (10 mL x 3), dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrated residue was purified by silica gel column chromatography (ethyl acetate / methanol) to obtain the title compound (1.94 g). 1H-NMR (400 MHz, CDCh) δ: 7.70 (1H, dd, J = 8.5, 5.3 Hz), 7.25 (1H, dd, J = 8.9, 2.5 Hz), 7.06 (1H, ddd, J = 8.8, 8.8, 2.1 Hz), 3.64 (2H, t, J = 6.9 Hz), 3.01-3.15 (3H, m), 2.81 (2H, t, J = 6.9 Hz), 2.24-2.39 (2H, m), 2.02-2.18 (4H, m). b) Preparation of N-{2-[4-(6-fluoro-1,2-benzoisoxazol-3-1)piperidin1-1]ethyl}propan1-amine (Reference example 22) To a solution of compound IN-2-1 (80.0 mg) in acetonitrile (1.4 mL) were added n-propylamine (0.0349 mL), potassium carbonate (117 mg), and potassium iodide (9.39 mg), and the mixture was stirred at 90°C for 4 hours. The reaction mixture was filtered and concentrated. The residue was purified by amino silica gel column chromatography (chloroform / methanol) to obtain the title compound (50.9 mg). 1H-NMR (400 MHz, CDCh) δ: 7.66 (1H, dd, J = 8.8, 5.2 Hz), 7.22 (1H, dd, J = 8.5, 2.4 Hz), 7.03 (1H, ddd, J = 8.8, 8.8, 2.2 Hz), 3.10-2.99 (3H, m), 2.72 (2H, t, J = 6.1 Hz), 2.58 (2H, t, J = 7.0 Hz), 2.53 (2H, t, J = 6.4 Hz), 2.21-1.99 (6H, m), 1.56-1.46 (2H, m), 0.91 (3H, t, J = 7.3 Hz). REFERENCE EXAMPLE 23 N-Et¡lN-{2-[4-(6-fluoro-l,2-benzo¡soxazol-3-¡l)p¡períd¡nl-¡l]et¡l}ethensulfonamide To a solution of the compound from reference example 1 (1.00 g) in dichloromethane (40 ml) triethylamine (2.39 ml) and 2-chloroethanesulfonyl chloride (0.433 ml) were added and the mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated, and the concentrated residue was purified by silica gel column chromatography (chloroform / methanol) to obtain the title compound (0.670 g). ^-NMR (400 MHz, CDCh) δ: 7.65 (1H, dd, J = 8.5, 4.9 Hz), 7.22 (1H, dd, J = 8.5, 2.4 Hz), 7.04 (1H, ddd, J = 8.9, 8.9, 2.2 Hz), 6.54 (1H, dd, J = 16.5, 9.8 Hz), 6.20 (1H, d, J = 16.5 Hz), 5.89 (1H, d, J = 9.8 Hz), 3.31 (2H, t, J = 7.0 Hz), 3.25 (2H, q, J = 7.1 Hz), 3.11-3.00 (3H, m), 2.61 (2H, t, J = 6.7 Hz), 2.32-2.17 (2H, m), 2.10-1.97 (4H, m), 1.20 (3H, t, J = 7.3 Hz). REFERENCE EXAMPLES 24 TO 36 IVIA / a / ZUZZ / UU Z iR Z According to the method of example 23, the compounds of examples 24 to 36 were prepared from the corresponding reference example compounds. Reference example Chemical structure Instrumental analysis data 24 N-° Jl λ-, θ ON LC-EM : RT = 1.566 min ObsMS = 396 [M+l] 25 N-°. < <Υύ V 1 1 \_ZT 'Ay 0 0 ^-NMR (400 MHz, CDCb) δ: 7.67 (1H, dd, J = 8.5, 5.5 Hz), 7.22 (1H, dd, J = 8.5, 1.8 Hz), 7.22 (1H, dd, J = 8.5, 1.8 Hz). 8.9, 2.0 Hz), 6.42 (1H, dd, J = 16.5, 9.8 Hz), 6.19 (1H, d, J = 16.5 Hz), 5.89 (1H, d, J = 9.8 Hz), 3.28-3.14 (4H, m), 3.1-3.6 (m), 2.502.38 (2H, m), 2.24-1.99 (6H, m), 1.88-1.78 (2H, m), 1.19 (3H, t, J = 7.3 Hz). 26 Ν'0, π 1 f ? / L ^N. .1+ J !==✓ 0 0 ^-NMR (400 MHz, CDCb) δ: 7.73 (1H, d, J = 7.9 Hz), 7.57-7.47 (2H, m), 7.30-7.24 (1H, m), 5.95 (1H, s-5.5), (1H, 5.5), m 3.32-3.22 (4H, m), 3.17-2.99 (3H, m), 2.512.36 (2H, m), 2.28-2.05 (6H, m), 2.02 (3H, s), 1.90-1.77 (2H, m), 1.19 J (3H, 7.0 Hz). 27 Νθ. 11 1 / \\ JL _-N _,N > 0 0 Ή-NMR (400 MHz, CDCb) δ: 7.60 (1H, dd, J = 8.8, 5.2 Hz), 7.11 (1H, dd, J = 8.5, 2.4 Hz), 6.9, dd, J = 8.8, 2.4 Hz. 8.8, 2.0 Hz), 5.96-5.93 (1H, m), 5.57-5.54 (1H, m), 3.593.48 (4H, m), 3.31-3.23 (4H, m), 2.68-2.57 (4H, m), 2.50-2.39 (2H, m), 2.02 (3H, s), 1.89-1.77 (2H, m), 1.19 (3H, t, J = 7.3 Hz). 28 N'° 1 r 1 1 \^Z^F .N. J / A\ 0 0 ^-RMN (400 MHz, CDCb) δ: 7.62 (1H, dd, J = 8.5, 4.9 Hz), 7.17 (1H, dd, J = 8.2, 1.5 Hz), 6.99 (1H, ddd, J = 8.8, 8.8, 2.0 Hz), 5.92-5.88 (1H, m), 5.53-5.48 (1H, m), 3.273.16 (4H, m), 3.09-2.93 (3H, m), 2.43-2.32 (2H, m), 2.16-1.92 (9H, m), 1.86-1.69 (2H, m), 1.14 (3H, t, J = 7.3 Hz). 29 __NH o o ιΊΓ \ 9 Oí Á J o ^-RMN (400 MHz, CDCb) δ: 7.99 (1H, s), 7.61 (1H, d, J = 7.9 Hz), 7.35 (1H, d, J = 8.5 Hz), 7.17 (1H, ddd, J = 7.6, 7.6, 1.2 Hz), 7.12-7.06 (1H, m), 6.97 (1H, d, J = 2.4 Hz), 6.54 (1H, dd, J = 16.5, 9.8 Hz), 6.21 (1H, d, J = 17.1 Hz), 5.89 (1H, d, J = 10.4 Hz), 3.46-3.34 (2H, m), 3.26 (2H, q, J = 7.1 Hz), 3.20-3.05 (2H, m), 2.93-2.81 (1H, m),. 2.76- 2.61 (2Η, m), 2.43-2.22 (2H, m), 2.142.02 (2H, m), 1.99-1.79 (2H, m), 1.22 (3H, t, J = 7.0 Hz)._________________________________ ^-RMN (400 MHz, CDCb) δ: 7.57-7.46 (1H, m), 7.19 (1H, d, J = 9.1 Hz), 6.52 (1H, dd, J = 15.2, 9.1 Hz), 6.21 (1H, d, J = 16.5 Hz), 5.91 (1H, d, J = 8.5 Hz), 3.47-3.00 (8H, m), 2.79-2.60 (1H, m), 2.42-1.94 (9H, m), 1.22 (3H, t, J = 7.0 Hz).___________ ^-RMN (400 MHz, CDCb) δ: 7.46 (1H, s), 7.42 (1H, d, J = 8.5 Hz), 7.34-7.29 (1H, m), 6.55 (1H, dd, J = 16.8, 10.1 Hz), 6.20 (1H, d, J = 16.5 Hz), 5.89 (1H, d, J = 9.8 Hz), 3.37-3.29 (2H, m), 3.25 (2H, q, J = 7.1 Hz), 3.12-3.00 (3H, m), 2.68-2.57 (2H, m), 2.44 (3H, s), 2.34-2.19 (2H, m), 2.14-2.01 (4H, m), 1.21 (3H, t, J = 7.3 Hz).________________ ^-RMN (400 MHz, CDCb) δ: 7.62 (1H, d, J = 8.5 Hz), 7.56 (1H, d, J = 1.8 Hz), 7.26 (1H, dd, J = 8.2, 1.5 Hz), 6.53 (1H, dd, J = 16.8, 10.1 Hz), 6.20 (1H, d, J = 17.1 Hz), 5.89 (1H, d, J = 9.8 Hz), 3.31 (2H, t, J = 7.0 Hz), 3.25 (2H, q, J = 7.1 Hz), 3.12-2.98 (3H, m), 2.66-2.56 (2H, m), 2.33-2.18 (2H, m), 2.12-1.98 (4H, m), 1.20 (3H, t, J = 7.0 _. ^-RMN (400 MHz, CDCb) δ: 7.73-7.69 (1H, m), 7.57-7.49 (2H, m), 7.30-7.25 (1H, m), 6.55 (1H, dd, J = 16.5, 9.8 Hz), 6.20 (1H, d, J = 16.5 Hz), 5.89 (1H, d, J = 9.8 Hz), 3.32 (2H, t, J = 7.0 Hz), 3.25 (2H, q, J = 7.1 Hz), 3.16-3.00 (3H, m), 2.61 (2H, t, J = 6.7 Hz), 2.34-2.19 (2H, m), 2.14-2.01 (4H, m), 1.21 (3H, t, J = 7.0 Hz)._______________ ^-RMN (400 MHz, CDCb) δ: 7.99 (1H, s), 7.50 (1H, dd, J = 8.8, 5.2 Hz), 7.02 (1H, dd, J = 9.8, 1.8 Hz), 6.93 (1H, d, J = 1.8 Hz), 6.85 (1H, ddd, J = 9.1, 9.1, 2.4 Hz), 6.53 (1H, dd, J = 16.8, 10.1 Hz), 6.20 (1H, d, J = 16.5 Hz), 5.90 (1H, d, J = 10.4 Hz), 3.453.32 (2H, m), 3.26 (2H, q, J = 7.1 Hz), 3.213.00 (2H, m), 2.91-2.55 (3H, m), 2.39-1.99 (4H, m), 1.98-1.75 (2H, m), 1.22 (3H, t, J = 7.0 Hz).__________ ^-RMN (400 MHz, CDCb) δ: 7.93 (1H, s), 7.37 (1H, dd, J = 9.2,4.3 Hz), 7.32 (1H, dd, J = 8.5, 2.4 Hz), 7.12 (1H, ddd, J = 8.9, 8.9, 2.4 Hz), 6.54 (1H, dd, J = 16.8, 10.1 Hz), 6.20 (1H, d, J = 16.5 Hz), 5.90 (1H, d, J = 10.4 Hz), 4.43-4.31 (1H, m), 3.36-3.22 (4H, m), 3.17-3.04 (2H, m), 2.67-2.57 (2H, m), 2.38-2.22 (4H, m), 2.08-1.95 (2H, m),. 1.21 (3H, t, J = 7.0 Hz). 36 1 \__ 0 0 1 T \ ')__ J '^ZN >> ^-RMN (400 MHz, CDCh) δ: 7.93 (1H, s), 7.40-7.35 (1H, m), 7.34-7.29 (1H, m), 7.167.0 (1H, m), (1H, 198), (1H, m). s), 5.56 (1H, br s), 4.44-4.29 (1H, m), 3.42-3.26 (4H, m), 3.17-2.99 (2H, m), 2.72-2.55 (2H, m), 2.382.18 (4H, m), 2.0-1.29 (5.2.3 m), (3H, t, J = 7.3 Hz). MA / a / ZUZZ / UU 1341 REFERENCE EXAMPLE 37 3-[4-(l,2-Benzo¡soxazole-3-¡l)p¡per¡d¡nl-¡l]-N-ethylpropan-l-amine In accordance with a similar method of reference examples 18 and 21 , the title compound was prepared from 3-(piperidin-4-yl)benzo[d]isoxazole. REFERENCE EXAMPLE 38 N-Ethyl-3-[4-(6-fluoro-l,2-benzoisoxazol-3-yl)p¡peridin-l-yl dichloride] propan-1amine According to a method similar to reference examples 18 and 21, the title compound was prepared from 6-fluoro-3-(piperazin-l-l)benzo[d]isoxazole monohydrochloride. Test 1: Evaluation of binding activity for the human 5-HTza receptor, the human 5-HTza receptor, and the human Dz receptor The binding affinity of the present compound for the human 5-HTza receptor, the human 5-HTβ receptor, and the human Dz receptor was measured using the following procedures. The CHO cell membrane fraction expressing the human 5-HTza receptor, the human 5-HTβ receptor, or the human Dz receptor was acquired from PerkinElmer, Inc. In a test to evaluate binding affinity, a test compound dissolved in dimethyl sulfoxide (DMSO) and each receptor membrane sample diluted in pH buffer were mixed with [3H]Ketanserin, [3H]SB-269970, or [3H]Spiperone (all acquired from PerkinElmer, Inc.) for the 5-HT1A receptor, the 5-HT2 receptor, or the D2 receptor, respectively. Each mixture was incubated at room temperature for 60 minutes. Nonspecific receptor binding was obtained from a competitive binding assay in the presence of 10 pmol / L of 8-OH-DPAT, 10 pmol / L of mianserin, or 10 pmol / L of Spiperone, respectively. The radioactivity induced by binding to the receptors was measured using a liquid scintillation counter (PerkinElmer, Inc.), and the 50% inhibition concentration was calculated. The Ki value was evaluated from the dissociation constant, which was calculated from saturated binding tests and a substrate concentration, and was used as an index for binding affinity. The results are shown in the following table. IVIA / S / ZUZZ / UU ÍWf Example 5-HT2A Ki (nmol / l) 5-HT7 Ki (nmol / l) D2 Ki (nmol / l) D2 Ki / 5-HT2A Ki D2 Ki / 5-HT7 Ki 1 2.0 2.5 226 113 89 2 2.1 9.3 >1000 >483 >108 3 4.7 5.2 >1000 >212 >192 4 0.4 0.7 267 738 390 5 0.6 2.4 116 191 48 6 0.8 5.7 278 364 49 7 0.2 1.0 79 519 80 8 1.4 6.2 294 216 47 9 0.4 1.6 <100 <231 <64 10 1.7 2.7 <100 <59 <38 11 1.5 5.2 <100 <68 <19 12 1.7 6.9 711 425 103 13 4.6 20.3 >1000 >217 >49 14 5.5 14.6 >1000 >183 >68 15 4.8 26.4 >1000 >208 >38 16 2.5 5.9 389 157 66 17 0.8 4.9 155 187 31 18 2.5 3.7 198 79 53 19 1.3 2.3 105 81 46 20 0.5 1.5 46 96 31 21 3.4 3.4 >1000 >296 >295 22 2.1 5.8 528 252 91 23 1.8 7.9 >1000 >552 >127 24 1.1 1.1 <100 <95 <91 25 6.4 7.7 1389 217 182 26 58.0 22.1 >10000 >172 >453 27 10.3 11.1 2164 210 195 28 2.2 10.0 <100 <45 <10 29 1.1 2.6 146 135 24.9 30 0.8 6.6 153 184 23 31 1.0 1.2 89 91 77 32 97.0 109.7 >10000 >103 >91 33 0.3 1.6 24.9 200 34 34 0.6 4.6 247 386 53 35 1.5 3.8 <100 <67 <27 36 0.9 1.0 80 93 84 37 0.9 1.1 <100 <110 <94 38 8.3 9.6 352 42 36 39 0.8 0.7 <100 <126 <137 40 1.1 1.2 214 202 185 41 4.6 1.8 <100 <22 <57 42 2.1 2.5 74 35 30 43 1.1 4.3 <100 <87 <23 44 0.5 3.2 <100 <194 <31 45 15.0 22.6 >300 >20 >13 46 0.9 4.2 75 80 18 47 2.8 8.9 457 166 51 48 0.6 2.7 80 134 30 49 9.8 22.6 >1000 >102 >44 50 4.0 13.5 >1000 >252 >74 51 2.7 1.9 309 113 164 52 298.2 332.6 >10000 >34 >30 53 1.1 1.4 <100 <92 <71 54 2.0 2.6 116 58 45 55 1.1 0.1 78 69 890 56 1.2 0.4 <100 <86 <254 57 1.6 8.7 210 128 24 58 53.2 19.4 >1000 >19 >52 59 44.7 13.6 >1000 >22 >74 60 19.9 24.3 >1000 >50 >41 61 10.9 12.7 514 47 41 62 0.5 2.8 104 192 37 63 3.1 6.9 532 172 77 64 1.5 2.4 348 228 147 65 4.0 7.6 195 48 26 66 0.8 5.4 212 273 18.1 67 6.1 0.9 <100 <16 <110 68 9.9 48.5 910 92 19 69 0.6 1.5 <100 <165 <65 70 2.0 3.7 52 26 14 71 2.2 6.2 223 99 36 72 1.6 10.6 <100 <61 <9 73 5.7 14.4 205 36 14 74 2.4 6.8 138 57 20 75 1.0 3.6 124 127 34 76 7.2 14.4 193 12.2 13 Test 2: Evaluation of antagonist activity for the human 5-HT1A receptor vs the human 5-HT1A receptor Equaorin, Gal6 protein, and each receptor were transiently expressed in CHO-K1 cells (Chinese hamster ovary). Cells were cultured overnight in a CO2 incubator at 37°C, seeded in a 384-well plate, and incubated at room temperature for 2 hours. Each compound, dissolved in DMSO, was added to the cells, and changes in luminescence were measured using the FDSS / pCELL functional drug selection system (Hamamatsu Photonics KK). For antagonistic activity, the inhibitory activity of each compound was calculated by establishing the luminescence level of the wells to which 10 pmol / L of the compound was added. ML / a / ZUZZ / UU 1341 endogenous ligand at 100%. The results are shown in the following table. Example: 5-HT2A antagonist activity. 5-HT antagonist activity? ICso(nmol / l) ICso (nmol / l) 1 8 37 2 12 94 3 62 95 4 44 31 5 9 66 6 48 66 7 8 11 8 26 8 9 15 8 10 18.1 9 11 9 67 12 78 82 13 76 81 14 79 82 15 27.2 86 16 59 90 17 49 66 18 58 72 19 76 61 20 19 48 21 73 68 22 738 18.1 23 277 68 24 7 41 25 90 26 26 843 71 27 64 73 28 95 80 29 39 99 30 45 39 31 24.9 64 32 890 73 33 8 59 34 6 78 35 33 81 36 13 82 37 21 66 38 756 59 39 8 9 40 9 2 41 7 7 42 8 9 43 9 82 44 10 77 45 640 49 46 9 83 47 94 43 48 10 18 49 633 16 50 49 81 51 57 62 52 946 177 53 72 44 54 31 1 55 7 3 56 7 6 57 56 100 58 3643 103 59 5888 62 60 819 72 61 94 15 62 53 28 63 65 46 64 44 101 65 103 81 66 37 70 67 94 72 68 949 91 69 745 85 70 67 9 71 25 78 72 42 8 73 68 81 74 68 77 75 306 80 76 551 65 Test 3-1: Metabolic stability test in human liver microsome The metabolic stability of this compound in the human liver microsome was evaluated as described below. The human liver microsome was obtained from Xenontech. ινΐΛ / a / zuzz / uu / 341 The human liver microsome, NADPH, and each test compound were mixed in a 25 mmol / l phosphate buffer solution (pH 7.4) to achieve the following concentrations as shown below, and the mixture was incubated at 37°C for 30 minutes. - Human hepatic microsome: 0.1 mg / ml - NAPDH: 3.2 mmol / l - Test compound: 0.1 pmol / l The residual ratio of the test compound in each sample after 30 minutes was measured by LC-EM, and metabolic stability in the human liver microsome was calculated from the following formula. Metabolic stability in human liver microsome (ml / min / mg of protein) = - LN (residual ratio) / 30 / 0.1 The results are shown in the following table. ινΐΛ / a / zuzz / uu Example Metabolic stability in human liver microsome (ml / min / mg of protein) Example Metabolic stability in human liver microsome (ml / min / mg of protein) 1 <0.05 40 <0.05 2 <0.05 41 <0.05 3 <0.05 42 <0.05 4 <0.05 43 <0.05 5 0.186 44 <0.05 6 0.053 45 <0.05 7 0.08 46 <0.05 8 0.108 47 <0.05 9 <0.05 48 <0.05 10 <0.05 49 <0.05 11 <0.05 50 <0.05 12 0.089 51 <0.05 13 0.054 53 <0.05 16 <0.05 54 <0.05 17 <0.05 55 0.059 18 <0.05 56 <0.05 19 <0.05 57 0.02 20 <0.05 58 <0.05 21 <0.05 59 0.079 22 <0.05 61 <0.05 23 <0.05 62 <0.05 24 <0.05 63 <0.05 25 <0.05 64 0.097 26 <0.05 65 <0.05 27 <0.05 66 <0.05 29 <0.05 67 <0.05 30 <0.05 68 <0.05 31 <0.05 69 <0.05 33 0.268 70 <0.05 34 <0.05 71 <0.05 35 <0.05 72 0.057 36 <0.05 74 <0.05 37 <0.05 75 <0.05 38 <0.05 76 <0.05 39 <0.05 Test 3-2: Metabolic stability test in human liver microsome For a more precise assessment of metabolic stability in the human liver microsome, the metabolic stability of the present compound was evaluated in human liver microsome 5 at an appropriate concentration of human liver microsome as described below. The human liver microsome was obtained from Xenontech. The human liver microsome, NADPH, and each test compound were mixed in a 25 mmol / L phosphate buffer (pH 7.4) to achieve the concentrations shown below, and the mixture was incubated at 37°C for 60 minutes. - Human hepatic microsome: 0.5 or 1.0 mg / mL - NAPDH: 3.2 mmol / l - Test compound: 0.1 pmol / l The residual ratio of the test compound in each sample after 30 minutes was measured by LC-EM, and metabolic stability in the human liver microsome was calculated from the following formula. Metabolic stability in human liver microsome (ml / min / mg of protein) = -LN (residual ratio) / reaction time / human liver microsome concentration The results are shown in the following table. Example Metabolic stability in human liver microsome (ml / min / mq of protein) 16 0.018 17 0.0025 51 0.016 Test 4: Predictive test of human half-life The half-life of the present compound in humans was predicted in the manner described below. The present compound was administered intravenously to a rat as an aqueous solution of 0.01 mol / L hydrochloric acid. Blood was collected at 5, 15, 30 minutes, 1, 2, 4, 6, and 24 hours post-administration. Plasma was obtained from the collected blood, the drug concentration in the plasma was measured by LC-MS, and the rat's volume of distribution was calculated from the concentration transition. The rate of unbound fraction of the present compound in human or rat serum was measured using the equilibrium dialysis method. The human half-life was calculated according to the following formula using the results of rat volume of distribution, free fraction rate in human or rat serum, and metabolic stability in human liver microsome obtained in Test 3-2. Human volume of distribution = Rat volume of distribution x Rate of unbound fraction in human serum / Rate of unbound fraction in rat serum Human hepatic clearance = (human hepatic blood flow x human serum free fraction rate x 56.7 x metabolic stability in human hepatic microsome) / (human hepatic blood flow + human serum free fraction rate x 56.7 x metabolic stability in human hepatic microsome) Half-life in humans = 0.693 x Human hepatic clearance distribution volume / human The results are shown in the following table. IVIA / a / ZUZZ / UU ÍWf Example Half-life in plasma (h) 16 3 17 12.2 51 6 Test 5: Evaluation of hERG channel inhibitory activity The inhibitory activity of the present compound for the hERG channel was measured by the whole-cell patch-clamp method with an automated patch-clamp system using CHO cells in which the hERG channel involved in the human rapidly activating delayed rectifying potassium current (Iκγ) was strongly expressed. (Preparation of cell suspension) hERG-CHO cells purchased from ChanTest Cop. were grown in a CO2 incubator at 37°C and dissociated from a flask with trypsin shortly before hERG current measurement, to prepare a cell suspension. (Solution preparation) The extracellular and intracellular fluids used in the measurement were prepared as follows. Extracellular fluid: 2 mmol / l CaCb, 1 mmol / l MgCb, 10 mmol / l HEPES, 4 mmol / l KCl, 145 mmol / l NaCl, 10 mmol / l glucose Intracellular fluid: HEPES 10 mmol / l, EGTA 10 mmol / l, KCI 20 mmol / l, KF 130 mmol / l Test compound solution: The test compound was dissolved in DMSO to achieve a concentration of either 2 mmol / L or 20 mmol / L to prepare a test compound solution. This test compound solution was further diluted 200-fold with extracellular fluid and serially diluted with extracellular fluid to prepare a test compound solution at each concentration required to calculate the IC50 value for hERG inhibition. (Current value measurement and data analysis) The cell suspension, extracellular fluid, intracellular fluid, and measurement plate were placed in the automated patch-clamping system, and the hERG current was measured using the whole-cell patch-clamp method. The voltage protocol was as follows: the holding potential was set to -80 mV, the depolarization pulse was delivered from -50 mV to +20 mV for 5 seconds, the repolarization pulse was delivered from -50 mV for 5 seconds, and then the potential was returned to the holding potential. Each pulse interval was 15 seconds. Data analysis was performed using Qpatch assay software (Sophion). The assay was conducted by incrementally applying four concentrations of each assay compound, and the average of the peak tail currents obtained from the last three stimulations at each concentration was determined as the evaluated data.Based on the current inhibition rate for a previously applied current at each concentration of each test compound, the IC50 value was calculated using the Hill equation with the software. The results are shown in the following table. Example hERG Inhibition of ICso (pmol / L) hERG Inhibition of ICso (nmol / L) / 5-HT2A K1 (nmol / L) hERG Inhibition of IC50 (nmol / L) / 5-HT7 K1 (nmol / L) 1 4.8 2401 1896 2 7.4 3575 796 3 >10 >2122 >1922 4 7.1 19617 10367 5 1.1 1810 455 6 1.5 1958 265 7 3.5 22975 3526 8 4.2 3088 677 9 5.4 12480 3453 10 3.6 2135 1351 11 10.5 7172 2034 12 2.2 1313 319 13 2.9 629 143 14 9.6 1754 656 16 4.8 1939 814 17 2.8 3381 567 18 4.1 1637 1097 19 >10 >7705 >4405 20 4.2 8787 2849 21 15.3 4529 4520 22 >10 >4475 >1726 23 >10 >5520 >1266 24 5.5 5203 4988 25 >10 >1563 >1307 26 >10 >172 >453 27 >10 >968 >899 29 0.9 830 341 30 1.2 1441 182 31 3.1 3169 2694 33 2.2 8013 1374 34 7.3 11440 1578 35 4.3 2888 1143 36 1.3 1504 1361 37 >10 >10968 >9375 38 >10 >1200 >1036 39 4.7 5934 6462 40 9.9 9377 8589 IVIA / a / ZUZZ / UU 41 6.7 1461 3821 42 6.4 3022 2583 43 7.0 6091 1613 44 6.4 12428 1977 45 >10 >665 >442 46 5.7 6053 1373 47 5.4 1954 607 48 2.9 4870 1090 49 >10 >1017 >442 50 6.2 1563 458 51 6.9 2536 3665 53 7.2 6616 5125 54 7.4 3685 2855 55 7.4 6575 84634 56 2.1 1805 5341 57 6.2 3785 717 58 >10 >188 >516 59 >10 >224 >738 61 >10 >916 >790 62 5.4 9970 1944 63 14.5 4677 2101 64 >10 >6551 >4214 65 >10 >2477 >1314 66 >10 >12871 >1865 67 >10 >1632 >11030 69 >10 >16548 >6545 70 >10 >4913 >2739 71 >10 >4452 >1624 72 9.9 6029 933 74 6.7 2795 991 75 3.8 3881 1051 76 >10 >1394 >697 Test 6: Fear Conditioning Test SD male rats were used. For the preparation of an administration solution, a test compound was dissolved in 0.01 mol / L hydrochloric acid and the aqueous solution was used. The fear conditioning test was performed as described below using the J FZ2 image for the contextual and cued fear conditioning test by O'HARA & CO., LTD. An animal was placed in a chamber equipped with the J FZ2 imaging system for the contextual and cued fear conditioning test, and electrical stimulations were applied 7 times at 0.5 mA for 10 seconds. The rat was then gently removed from the chamber, and the following day, the administration solution (a solvent or test compound solution) was administered subcutaneously. The animal was then placed back into the chamber 30 minutes later. The percentage of freeze reaction time from when the animal was placed back into the chamber until 300 seconds later was used as the test outcome. The analysis of the test results was carried out as follows. Parametric Dunnett's multiple comparison test was performed in both the test compound administration group and the solvent administration group (significance level: 5% on both sides). When the test compound administration group showed a significant suppression of freeze reaction time compared to the solvent administration group, it was considered to have an anxiolytic effect. The results of this test using the compound from Example 17 are shown in Figure 1. Test 7: Measuring the amount of glutamic acid released in the rat brain A cannula was placed in a position of the prefrontal cortex in a male Wistar rat and the rat was tested after a recovery period of at least 1 week. A 5 mM glutamic acid solution and a 100 mM ascorbic acid solution were used to calibrate a biosensor. The released glutamic acid was measured using the calibrated biosensor. Measurement began 12 hours or more after inserting the biosensor into a guide cannula. After administration of a test compound, measurement was performed for 2 hours or more. The mean amount of glutamic acid released 30 minutes before administration was used as a standard, and the area under the curve was calculated 2 hours after administration. Data from the compound administration group were compared with those from the solvent administration group. The average values ​​of each group were compared using the parametric Dunnett multiple comparison test, and when the test compound administration group showed a significantly high value compared to the solvent administration group, it was considered to show a promoting effect of glutamic acid release (significance level: 5% on both sides). The results of this test using the compound from Example 17 are shown in Figure 2. Test 8: Evaluation of binding activity for the receptor related to side effects The binding affinity of the present compound for the receptor related to side effects, such as the olA adrenergic receptor, can be measured by the following method. The binding assay was performed as follows using the CHO cell membrane fraction in which the human target receptor was expressed. A test compound dissolved in dimethyl sulfoxide (DMSO), each receptor membrane sample diluted with pH buffer, and a [3H]-labeled ligand with a strong binding affinity for each target receptor were mixed. Each mixture was incubated at room temperature, rapidly added to a glass fiber filter plate (Multiscreen FB, Millipore, Inc.), and vacuum filtered. The radioactivity remaining on the filter was measured using a liquid scintillation counter (PerkinElmer, Inc.). The binding inhibition rate was calculated using the following formula. A control compound with a strong binding affinity for the target receptor was used to calculate the amount of nonspecific binding to the receptor membrane sample, instead of a test compound. Rate of inhibition of binding to the target receptor (%) = 100-100 x {(Amount of binding of [3H]-labeled ligand in the presence of the test compound)} - (Amount of binding of [3H]-labeled ligand in the presence of 10 pmol / l of control compound)} / {(Amount of binding of [3H]-labeled ligand in the absence of the test compound)} - (Amount of binding of [3H]-labeled ligand in the presence of 10 pmol / l of control compound)} Test 9: Evaluation of intracerebral transferability (intracerebral transferability test in rats) In this test, the intracerebral transferability of the present compound was evaluated using the following method. The present compounds were administered subcutaneously as a solution in saline, or orally as a suspension in methylcellulose, to 7-week-old SD or WKY rats. Plasma and brain tissue were collected 0.5 hours, 1 hour, or 2 hours after administration to measure drug concentrations in plasma and brain using LC-EM. The rates of binding of the present compound to plasma and brain proteins were measured using the equilibrium dialysis method. Kp,uu,brain (brain / plasma unbound drug concentration ratio) can be calculated by applying the compound concentrations in plasma and brain and the plasma and brain protein binding rates obtained from the previous test in the following formula. Kp,uu,cerebrum = (Concentration of the compound in the brain x (100 - Binding rate to brain protein (%)) / 100) / (Concentration of the compound in plasma x (100 - Binding rate to plasma protein (%)) / 100) The results of test 9 are shown in the following table. ΜΛ / a / zuzz / uu i y41 ινΐΛ / a / zuzz / uu Example Kp,uu, brain Example Kp,uu, brain 2 0.35 21 0.54 16 1.32 23 1.47 17 0.58 41 0.63 18 0.56 51 1.26 19 0.33 63 0.35 Test 10: Assessment of hepatotoxic risk (dansyl glutathione (dGSH) trapping assay) The present compound was metabolized in the hepatic microsome, and from the resulting metabolite, the reactive metabolite that reacts with dansyl glutathione (dGSH) was detected and quantified using the following method. The measurement was carried out with a screening robot (Tecan) for the metabolic reaction and with a UPLC fluorescence detection system (Waters) for the dGSH-binding metabolite concentration. (Solution preparation) The present compound was dissolved in DMSO to prepare a 10 mmol / L test compound solution. 7.6 mL of potassium phosphate pH regulator (500 mmol / L, pH 7.4), 1.9 mL of human liver microsome (Xenotech, 20 mg protein / mL), and 1.27 mL of pure water were mixed to prepare a microsome solution. 0.67 mL of pure water was added to 3.78 mL of the microsome solution to prepare a microsome solution (dGSH(-)). 1.14 mL of dGSH solution (20 mmol / L) was added to 6.48 mL of the microsome solution to prepare a microsome solution (dGSH(+)). 80.9 mg of NADPH was dissolved in 30 mL of pure water to prepare a cofactor solution. 33 mg of tris(2-carboxyethyl)phosphine (TECP) were dissolved in 115 ml of methanol to prepare a reaction stop solution. (Reaction) Twelve µL of the test compound solution were mixed with 388 µL of pure water, and the mixture was dispensed in 50 µL increments into six wells of a 96-well plate. The six wells were divided into three groups of two wells each, designated as the reaction group, unreacted group, and dGSH-free group. Microsome solution (dGSH(+)) was added to the reaction group and the unreacted group, and microsome solution (dGSH(-)) was added to the dGSH-free group, in 50 µL increments each. Cofactor solution was added to the reaction group and the dGSH-free group, and pure water was added to 50 µL increments each. After incubation at 37°C for 60 minutes, reaction stop solution was added in 450 µL increments to stop the reaction. Pure water was added to the reaction group and the dGSH-free group, and the cofactor solution was added to the unreacted group in 50 μL each.The plate was cooled to -20°C for 1 hour and the solutions were centrifuged (4000 rpm, 10 minutes). The supernatants were collected on another plate and subjected to analysis. (Analysis) The metabolite-dGSH binding concentration was measured under the following conditions, using the fluorescence detection UPLC system. Column: Waters ACQUITY UPLC BEHC18 1.7 pm 2.1 x 10 mm Eluent: A, 0.2% aqueous formic acid; B, 0.2% formic acid / acetonitrile Gradient: B, 20% (0 min) -> 70% (9.33 min) -> 90% (10.63 min) -> 20% (11 min) -> 20% (14 min) The fluorescence intensity was corrected for the organic solvent composition at the time of elution because the fluorescence intensity changes depending on the organic solvent composition. The results of test 10 are shown in the following table. ML / a / ZUZZ / UU 1341 Ejemplo Metabolito-dGSH Union Concentración (μΜ) EJEMPLO Metabolito-dGSH Concentración de union (μΜ) 1 ND 39 ND 2 0.127 18.1 0.125 3 ND 41 ND 4 0.165 42 ND 5 ND 43 0.177 6 ND 44 0.096 7 ND 45 ND 8 0.223 46 0.156 9 ND 47 ND 10 ND 48 ND 11 ND 49 0.45 12 ND 50 ND 13 0.214 51 ND 14 0.089 53 0.063 16 ND 54 ND 17 ND 55 0.057 18 ND 56 0.514 19 0.175 57 ND 20 1.661 58 ND 21 0.133 59 ND 22 0.509 61 ND 23 0.173 62 0.857 24 7.645 63 0.268 25 ND 64 0.432 26 ND 65 0.112 27 ND 66 0.222 29 0.091 67 0.113 30 0.101 69 ND 31 ND 70 0.257 33 ND 71 0.132 34 0.268 72 0.147 35 0.153 74 ND 36 0.161 75 ND 37 0.108 76 ND 38 ND Industrial Application The present compound exhibits antagonistic activity for the serotonin 5-HT2A receptor and the serotonin 5-HTia receptor and, therefore, the present compound is useful as a drug for treating neuropsychiatric disorders.

Claims

1. A compound of formula (1): or a pharmaceutically acceptable salt thereof, wherein Z is a nitrogen atom or -CRA-; Y is carbonyl or sulfonyl; m is 1, 2, 3, or 4; n is 0, 1, 2, or 3; provided that when Y is sulfonyl, n is not 0; RA is hydrogen, hydroxy, Ci-6 alkyl, or Ci-6 alkoxy, Rla, Rlb, Rlc, and Rld are each independently hydrogen, hydroxy, halogen, or Ci-6 alkyl optionally substituted with the same or different 1 to 3 halogen;R2a, R2b, R2c, and R2d are each independently, and each of R2cs or each of R2ds is independently when R2c or R2d exist in plural, hydrogen, halogen or Ci-6 alkyl (in which the alkyl may be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy, C3-8 cycloalkyl and Ci-6 alkoxy), provided that when R2a and R2b, or R2c and R2d that are attached to the same carbon atom are each independently said C1-6 alkyl, they may combine together with the carbon atom to which they are attached to form a saturated carbocycle of 3 to 6 members; R3 is Ci-β alkyl, wherein the alkyl can be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy, cyano, C3-8 cycloalkyl and Ci-e alkoxy;R4a, R4b, R4c and R4d are each independently, and each of R4cs or each of R4ds is independently when R4c or R4d exist plurally, hydrogen, halogen, C1-6 alkyl (in which the alkyl may be optionally substituted with 1 to 5 equal or different substituents selected from the group consisting of halogen, hydroxy, cyano, C3-8 cycloalkyl, C1-6 alkoxy, C1-e alkyl ester and amino optionally substituted with the same or different 1 or 2 C1-6 alkyl (in which the alkyl may be optionally substituted with oxo)), C2-6 alkynyl or amino (in which the amino may be optionally substituted with the same or different 1 or 2 C1-e alkyl);provided that when any two of R4a, R4b, R4c and R4d are each independently said C1-6 alkyl, they may combine together with the carbon atom or carbon atoms to which they are attached to form a saturated 3- to 6-membered carbocycle or a saturated 4- to 6-membered heterocycle wherein when said C1-e alkyl groups have a substituent, the substituent may be included as a member of the ring of the carbocycle or heterocycle; provided that when Y is sulfonyl and yn is 1, either of R4c or R4d is hydrogen; and when Y is sulfonyl and yn is 2 or 3, either of R4c or R4d that is attached to the carbon atom adjacent to Y is hydrogen;and ring Q is a group of the following formula (2a), (2b), (2c), (2d), (2e), or (2f): ML / a / zuzz / uu 1 1 (2d) (2e) (2f) wherein R5a, R5b, R5c, and R5d are each independently hydrogen, halogen, cyano, Ci-6 alkyl, Ci-e alkoxy (wherein alkyl and alkoxy may be independently and optionally substituted with the same or different 1 to 3 halogen atoms), or amino optionally substituted with the same or different 1 or 2 Ci-6 alkyl; and R6 is hydrogen, Ci-6 alkyl, or C3-8 cycloalkyl, wherein the alkyl and cycloalkyl may each be independently optionally substituted with the same or different 1 to 3 halogens.

2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, further characterized in that Rla, Rlb, Rlc, and Rld are hydrogen.

3. The compound according to claim 1 or 2 or a pharmaceutically acceptable salt thereof, further characterized in that R2a, R2b, R2c, and R2d are hydrogen.

4. The compound according to any of claims 1 to 3, or a pharmaceutically acceptable salt thereof, further characterized in that m is 1.

5. The compound according to any of claims 1 to 4 or a pharmaceutically acceptable salt thereof, further characterized in that R3 is Ci-6 alkyl.

6. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, further characterized in that Z is -CRA-, 7. The compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, further characterized in that RA is hydrogen.

8. The compound according to any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, further characterized in that R5a, R5b, R5c, and R5d are each independently hydrogen, halogen, or Ci-6 alkyl.

9. The compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, further characterized in that R5a, R5c, and R5d are hydrogen.

10. The compound according to any of claims 1 to 9 or a pharmaceutically acceptable salt thereof, further characterized in that R5b is hydrogen, halogen or Ci-6 alkyl.

11. The compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, further characterized in that R6 is hydrogen.

12. The compound according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, further characterized in that R4a, R4b, R4c and R4d are each independently, and each of R4cs or each of R4ds is independently when r4c or R4d exists in the plural, hydrogen, halogen or Ci-6 alkyl, wherein the alkyl may be optionally substituted with 1 to 5 identical or different substituents selected from the group consisting of halogen, hydroxy and Ci-6 alkoxy.

13. The compound according to any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, further characterized in that n is 0 or 1.

14. The compound according to any of claims 1 to 13, or a pharmaceutically acceptable salt thereof, further characterized in that Y is carbonyl.

15. The compound according to any of claims 1 to 13, or a pharmaceutically acceptable salt thereof, further characterized in that Y is sulfonyl.

16. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, further characterized in that the compound is selected from the group consisting of: ML / a / ZUZZ / UU 1341 17. A drug comprising a compound of any of claims 1 to 16 or a pharmaceutically acceptable salt thereof as an active ingredient.

18. A medicament for treating a mental illness or a disease of the central nervous system, comprising a compound of any of claims 1 to 16, or a pharmaceutically acceptable salt thereof, as an active ingredient.

19. The medicament according to claim 18, further characterized in that the mental illness or disease of the central nervous system is schizophrenia, a bipolar disorder, a sleep disorder, an autism spectrum disorder, major depression, 10 treatment-resistant depression or a psychopathic symptom or dementia associated with Alzheimer's disease or Parkinson's disease.

20. A method for treating a mental illness or a disease of the central nervous system, comprising administering a therapeutically effective amount of a compound of any of claims 1 to 16, or a pharmaceutically acceptable salt thereof, to a patient in need.

21. The use of a compound of any of claims 1 to 16, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating a mental illness or a disease of the central nervous system.

22. A compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, for use in the treatment of a mental illness or a disease of the central nervous system.

23. A medicament for treating a mental illness or a disease of the central nervous system, comprising a compound of any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, in combination with at least one drug selected from the group consisting of a drug for treating a developmental disorder such as autism spectrum disorder and attention deficit hyperactivity disorder, an antipsychotic drug and a schizophrenic drug, a drug for treating bipolar disorder, an antidepressant drug, an anti-anxiety drug, a drug for treating obsessive-compulsive disorder, a drug for treating a stress disorder such as post-traumatic stress disorder, a drug for treating a mood disorder, a drug for treating an eating disorder, a drug for treating a sleep disorder such as insomnia, narcolepsy,a sleep apnea syndrome and circadian rhythm disorder, a drug to treat sexual dysfunction, a drug to treat drug dependence, a drug to treat dementia such as Alzheimer's disease, a drug to treat a behavioral and psychological symptom associated with dementia, a drug to improve cerebral metabolism and circulation, a drug to treat a movement disorder such as Parkinson's disease, an analgesic drug, an antiepileptic drug, an anticonvulsant, a migraine drug, an anesthetic, and a central stimulant.

24. A medicament for treating a mental illness or a disease of the central nervous system, comprising a compound of any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, as an active ingredient, wherein the medicament is used in concomitant treatment with at least one drug selected from the group consisting of a drug for treating a developmental disorder such as autism spectrum disorder and attention deficit hyperactivity disorder, an antipsychotic drug and a schizophrenic drug, a drug for treating bipolar disorder, an antidepressant drug, an anti-anxiety drug, a drug for treating obsessive-compulsive disorder, a drug for treating a stress disorder such as post-traumatic stress disorder, a drug for treating a mood disorder, a drug for treating an eating disorder,A drug for the treatment of a sleep disorder such as insomnia, narcolepsy, sleep apnea syndrome, and a circadian rhythm disorder; a drug for treating sexual dysfunction; a drug for treating drug dependence; a drug for treating dementia such as Alzheimer's disease; a drug for treating a behavioral and psychological symptom associated with dementia; a drug to improve cerebral metabolism and circulation; a drug for treating a movement disorder such as Parkinson's disease; an analgesic drug; an antiepileptic drug; an anticonvulsant; a migraine drug; an anesthetic; and a central stimulant.