Spiroheterocycle derivative having serotonin receptor binding activity

Abstract

The present invention provides: a compound having a serotonin 5-HT2A receptor antagonist and / or inverse agonist activity or a pharmaceutically acceptable salt thereof; and a pharmaceutical composition containing same. A compound represented by formula (I) (in the formula, R1 represents a hydrogen atom or the like, each A1 independently represents CR2R2', each A2 independently represents CR3R3', each R2 independently represents a hydrogen atom or the like, each R2' independently represents a hydrogen atom or the like, each R3 independently represents a hydrogen atom or the like, each R3' independently represents a hydrogen atom or the like, m and n each independently represent 1 or the like, ring B represents a ring represented by formula (II) or the like (in the formula, R4 represents a group represented by formula (III) or the like (in the formula, each A3 independently represents CR13R13', each A4 independently represents CR14R14', each R13 independently represents a hydrogen atom or the like, each R13' independently represents a hydrogen atom or the like, each R14 independently represents a hydrogen atom or the like, each R14' independently represents a hydrogen atom or the like, q and r each independently represent 1 or the like, and R10 and R11 each independently represent a substituted or unsubstituted aromatic carbocyclic group or the like), and R8 represents a hydrogen atom or the like)), or a pharmaceutically acceptable salt thereof.

Description

Spiroheterocyclic derivatives with serotonin receptor binding activity

[0001] The present invention relates to a compound or a pharmaceutically acceptable salt thereof which has serotonin 5-HT2A receptor antagonistic and / or inverse agonist activity and is useful in the treatment and / or prevention of diseases caused by the serotonin 5-HT2A receptor, and to a pharmaceutical composition containing the compound or a pharmaceutically acceptable salt thereof.

[0002] Neurodegenerative disorders (NDs) are a group of related human diseases that share a common pathophysiological feature: the progressive degeneration of selective neuronal populations over time. These neurodegenerative disorders include, but are not limited to, Alzheimer's disease and related dementias, Parkinson's disease, Huntington's disease, Lewy body disease and related movement disorders. Each of these disorders has unique clinical aspects, including age of onset, time course of progression, neurological signs and symptoms, neuropsychiatric symptoms, and sensitivity to known therapeutic agents. Furthermore, the pathophysiological basis of each of these disorders is caused by genetic mechanisms unique to each disorder (Non-Patent Document 1).

[0003] Despite considerable progress in understanding the genetic causes underlying these disparate disorders, relatively little is known about the biochemical mechanisms underlying the selective neuronal degeneration common to all of them. Furthermore, while genetic factors that cause rare familial forms of the most common of these disorders, including Parkinson's disease and Alzheimer's disease, have been identified, the pathophysiological basis of the majority of sporadic cases remains unknown. Consequently, there are currently no specific therapeutic agents that can directly alter disease progression. Instead, clinicians rely on a variety of existing medications to achieve symptomatic relief of the motor, cognitive, and neuropsychiatric manifestations that characterize these disorders (Non-Patent Documents 2, 3).

[0004] Among the various neurological symptoms that characterize ND, the occurrence of motor abnormalities, including bradykinesia, dyskinesia, and chorea, as well as neuropsychiatric symptoms, including psychosis and emotional symptoms such as anxiety and depression, are common symptoms and seriously affect the functional status and quality of life of patients (Non-Patent Documents 4, 5). Most existing treatments, including antipsychotics and antidepressants, are often effective in these patients, but are significantly poorly tolerated (Non-Patent Document 6). Furthermore, available Parkinson's disease treatments, including L-dopa and dopamine agonists, are generally effective, but cause severe treatment-limiting side effects that cannot currently be addressed by pharmacological therapy.

[0005] For a long time, there were no approved drugs specifically for ND, but in 2016, the 5-HT2A receptor inverse agonist pimavanserin was approved in the United States for the first time for the treatment of hallucinations and delusions associated with Parkinson's disease (Non-Patent Document 7). Unlike existing antipsychotics, this drug has not been reported to cause side effects such as worsening of motor symptoms or impaired cognitive function. Pimavanserin's primary pharmacological action is serotonin 5-HT2A receptor inverse agonism / antagonism, but it also possesses serotonin 5-HT2C receptor inverse agonism (Non-Patent Document 8). The results of 5-HT2A occupancy measured in a PET study of pimavanserin in humans and the results of clinical trials of pimavanserin suggest that pimavanserin exerts its therapeutic effects via 5-HT2A and 2C receptors (Non-Patent Document 9). Furthermore, pimavanserin has significant adverse effects on the cardiovascular system, limiting its use.

[0006] These findings highlight the need to develop novel therapeutic agents specifically designed to be not only effective against these specific disabling conditions, but also well-tolerated in these specific patient populations. This can be achieved by improving the selectivity of drug-target interactions of new therapeutic agents, specifically by having potent activity and selectivity for the 5-HT2A and 2C targets, and reducing adverse cardiovascular effects.

[0007] Compounds having serotonin 5-HT2A receptor antagonistic and / or inverse agonistic activity are described in Patent Documents 3 to 14 and 16 to 25, but none of these documents describe or suggest compounds related to the present invention. ３ Although Patent Document 15 discloses quinuclidine derivatives having receptor inhibitory activity, it does not describe serotonin 5-HT2A receptor antagonistic and / or inverse agonistic activity and therapeutic effect against hallucinations and delusions, nor does it describe or suggest compounds related to the present invention.

[0008] International Publication No. WO 2018 / 131672 U.S. Patent No. 8,377,959 International Publication No. WO 2001 / 066521 International Publication No. WO 2004 / 064738 International Publication No. WO 2019 / 040104 International Publication No. WO 2019 / 040105 International Publication No. WO 2019 / 040106 International Publication No. WO 2019 / 040107 International Publication No. WO 2010 / 111353 International Publication No. WO 2004 / 000808 International Publication No. WO 2003 / 057698 Chinese Patent Application Publication No. WO 109111385 International Publication No. WO 2007 / 124136 International Publication No. WO 2004 / 000840 International Publication No. WO 2021 / 147818 International Publication No. WO 2021 / 147909 International Publication No. WO 2022 / 145408 Chinese Patent Application Publication No. 113214141 Chinese Patent Application Publication No. 113214231 Chinese Patent Application Publication No. 113214289 International Publication No. WO 2021 / 218863 Chinese Patent Application Publication No. 113549006 International Publication No. WO 2021 / 193790 International Publication No. WO 2022 / 017440

[0009] Nature Reviews Neurology volume 10, pages 620-633 (2014) Progress in Neurology and Psychiatry Vol. 22, Iss. 1, 30-35, 2018 Movement Disorders Vol. 24, No. 11, 2009, pp. 1641-1649 Parkisonism and related disorders 15S3, 2009, S105-S109 Neurology. 2004; 63 (2): 293-300. JAMA Neurol. 2016; 73 (5): 535-541. The Lancet; 383: 533-540 (2014) Journal of Pharmacology and Experimental Therapeutics May 2006, 317 (2) 910-918CNS Spectrams (2016), 21, 271-275

[0010] An object of the present invention is to provide novel compounds having serotonin 5-HT2A receptor antagonistic and / or inverse agonistic activity. More preferably, the present invention provides novel compounds having serotonin 5-HT2A receptor antagonistic and / or inverse agonistic activity and thereby having an effect on diseases involving serotonin, including hallucinations and delusions associated with Parkinson's disease and / or dementia, and pharmaceuticals containing the same.

[0011] The present invention relates to the following items (1) to (30): (1) Formula (I): (In the formula, R １ is a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; A １ are each independently, CR ２ R ２’ and ２ are each independently, CR ３ R ３’ and R ２are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ３ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ３’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２ and R ２’ and R ３ and R ３’ may be taken together with the same carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; m and n are each independently 1, 2, or 3; Ring B is a ring of the formula: (In the formula, R ４ is the formula: (In the formula, A ３ are each independently, CR １３ R １３’ and ４ are each independently, CR １４ R １４’ and R １３ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １３’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １４ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １４’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; q and r are each independently 0, 1, or 2; q' and r' are each independently 1 or 2; R １０ and R１１ are each independently a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R １２ is a hydrogen atom or a substituted or unsubstituted alkyl; ８ is a hydrogen atom or a substituted or unsubstituted alkyl; R ９ (2) R is a ring represented by the formula (I), or a pharmaceutically acceptable salt thereof. １ is a hydrogen atom or a substituted or unsubstituted alkyl. (3) The compound according to the above item (1) or (2), or a pharmaceutically acceptable salt thereof, wherein m and n are each independently 1 or 2. (4) The compound according to the above item (1) or (2), or a pharmaceutically acceptable salt thereof, wherein m and n are 2. (5) The compound according to the above item (1) or (2), or a pharmaceutically acceptable salt thereof, wherein ring B is a group represented by the formula: (6) A compound according to any one of the above items (1) to (4), wherein ring B is a ring represented by the formula: (7) The compound according to any one of the above items (1) to (4), wherein R is a ring represented by the formula: (wherein the symbols have the same meanings as in the above item (1)), or a pharmaceutically acceptable salt thereof. ４ But the formula: (8) A compound according to any one of the above items (1) to (6), wherein R is a group represented by the formula: (wherein the symbols have the same meanings as in the above item (1)), or a pharmaceutically acceptable salt thereof. １０ (9) The compound according to any one of the above items (1) to (7), wherein R is a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. １０ (10) The compound according to any one of the above items (1) to (8), wherein R is a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. １０(11) The compound according to any one of the above items (1) to (9), wherein R is a substituted or unsubstituted 5-membered aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. １１ is a substituted or unsubstituted aromatic carbocyclic group, or a pharmaceutically acceptable salt thereof. (12) The compound according to any one of the above items (1) to (11), wherein q, r, q', and r' are 1, or a pharmaceutically acceptable salt thereof. (13) A compound of formula (II): (In the formula, R １ is a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ２ is a hydrogen atom, halogen, or substituted or unsubstituted alkyl; R ２’ is a hydrogen atom, halogen, or substituted or unsubstituted alkyl; R ３ is a hydrogen atom, halogen, or substituted or unsubstituted alkyl; R ３’ (14) The compound according to any one of the above items (1) to (12), represented by formula (III): (In the formula, R ３１ is a hydrogen atom or a C1-C3 alkyl; R ３２ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３３ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３４ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ３５ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ３２ and R ３３ and R ３４ and R ３５may be taken together with the same carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; Ring B' is a ring of the formula: (In the formula, R ６ is the formula: (In the formula, A ６ are each independently, CR ２５ R ２５’ and R ２５ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２５’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; s is 0 or 1; s' is 0, 1, or 2; R ２４ is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ５ is a hydrogen atom or a substituted or unsubstituted alkyl; ６ ' is the formula: (In the formula, A ７ are each independently, CR ２７ R ２７’ and R ２７ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２７’ is a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; t is 0 or 1; R ２６ is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ７ is the formula: (In the formula, A ５ are each independently, CR ２８ R ２８’ and R ２８are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２８’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; u is 0, 1, or 2; R ２３ is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group), and R ２１ is a hydrogen atom or a substituted or unsubstituted alkyl; R ２２ are each independently a halogen atom or a substituted or unsubstituted alkyl group; and v is 0, 1, or 2), or a pharmaceutically acceptable salt thereof. (16) The compound according to the above item (14), wherein R is a ring represented by the formula (14), or a pharmaceutically acceptable salt thereof. ６ But the formula: (wherein the symbols have the same meanings as in the above item (14)), or a pharmaceutically acceptable salt thereof. (17) A compound according to any one of the above items (14) to (16), wherein R is a group represented by the formula: ２４ (19) The compound according to any one of the above items (14) to (18), wherein R is a substituted or unsubstituted aromatic carbocyclic group, or a pharmaceutically acceptable salt thereof. (20) The compound according to any one of the above items (14) to (18), wherein R is a substituted or unsubstituted aromatic carbocyclic group, or a pharmaceutically acceptable salt thereof. ２３ (21) The compound according to any one of the above items (14) to (19), wherein R is a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. ３２ and R ３３is a hydrogen atom. (22) A pharmaceutical composition containing a compound according to any one of items (1) to (21) above or a pharmaceutically acceptable salt thereof. (23) The pharmaceutical composition according to item (22) above, which is a serotonin 5-HT2A receptor antagonist and / or inverse agonist. (24) The pharmaceutical composition according to item (22) above, which is a serotonin 5-HT2A and 5-HT2C receptor antagonist and / or inverse agonist. (25) A method for treating and / or preventing a disease involving the 5-HT2A receptor, comprising administering a compound according to any one of items (1) to (21) above or a pharmaceutically acceptable salt thereof. (26) A method for treating and / or preventing a disease involving the 5-HT2A and 5-HT2C receptors, comprising administering a compound according to any one of items (1) to (21) above or a pharmaceutically acceptable salt thereof. (27) Use of the compound according to any one of the above items (1) to (21), or a pharmaceutically acceptable salt thereof, for the manufacture of an agent for the treatment and / or prevention of a disease associated with a 5-HT2A receptor antagonist and / or inverse agonist. (28) Use of the compound according to any one of the above items (1) to (21), or a pharmaceutically acceptable salt thereof, for the manufacture of an agent for the treatment and / or prevention of a disease associated with a 5-HT2A and 5-HT2C receptor antagonist and / or inverse agonist. (29) A compound according to any one of the above items (1) to (21), or a pharmaceutically acceptable salt thereof, for use in the treatment and / or prevention of a disease associated with a 5-HT2A receptor antagonist and / or inverse agonist. (30) A compound according to any one of the above items (1) to (21), or a pharmaceutically acceptable salt thereof, for use in the treatment and / or prevention of a disease associated with a 5-HT2A and 5-HT2C receptor antagonist and / or inverse agonist. (1') A compound of formula (I): (In the formula, R １ is a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; A １ are each independently, CR ２R ２’ and ２ are each independently, CR ３ R ３’ and R ２ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ３ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ３’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２ and R ２’ and R ３ and R ３’ may be taken together with the same carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; m and n are each independently 1, 2, or 3; Ring B is a ring of the formula: (In the formula, R ４ is the formula: (In the formula, A ３ are each independently, CR １３ R １３’ and ４ are each independently, CR １４ R １４’ and R １３ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １３’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １４ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １４’are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; q and r are each independently 0, 1, or 2; q' and r' are each independently 1 or 2; R １０ and R １１ are each independently a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R １２ is a hydrogen atom or a substituted or unsubstituted alkyl; ８ is a hydrogen atom or a substituted or unsubstituted alkyl; R ９ (2') R is a ring represented by the formula (I), or a pharmaceutically acceptable salt thereof. １ is a hydrogen atom or a substituted or unsubstituted alkyl. (3') The compound according to the above item (1') or (2') or a pharmaceutically acceptable salt thereof, wherein m and n are each independently 1 or 2. (4') The compound according to the above item (1') or (2') or a pharmaceutically acceptable salt thereof, wherein m and n are 2. (5') The compound according to the above item (1') or (2') or a pharmaceutically acceptable salt thereof, wherein ring B is a group represented by the formula: (6') A compound according to any one of the above items (1') to (4'), wherein ring B is a ring represented by the formula: (7') R is a ring represented by the formula (1') or (4'), or a pharmaceutically acceptable salt thereof. ４ But the formula: (8') R is a compound according to any one of the above items (1') to (6') or a pharmaceutically acceptable salt thereof, wherein R is a group represented by the formula: １０(9') The compound according to any one of the above items (1') to (7'), wherein R is a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. １０ (10') The compound according to any one of the above items (1') to (8'), wherein R is a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. １０ (11') The compound according to any one of the above items (1') to (9'), wherein R is a substituted or unsubstituted 5-membered aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. １１ is a substituted or unsubstituted aromatic carbocyclic group, or a pharmaceutically acceptable salt thereof. (12') The compound according to any one of the above items (1') to (11') or a pharmaceutically acceptable salt thereof, wherein q, r, q', and r' are 1. (13') A compound of formula (II): (In the formula, R １ is a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ２ is a hydrogen atom, halogen, or substituted or unsubstituted alkyl; R ２’ is a hydrogen atom, halogen, or substituted or unsubstituted alkyl; R ３ is a hydrogen atom, halogen, or substituted or unsubstituted alkyl; R ３’ (14') A compound according to any one of the above items (1') to (12'), represented by formula (II): (In the formula, R １ is a hydrogen atom or alkyl; R ２ is a hydrogen atom or a halogen; R ２’ is a hydrogen atom; R ３ is a hydrogen atom; R ３’ is a hydrogen atom; Ring B is a group of the formula: (In the formula, R ４ is the formula: (In the formula, A ３ is CR １３ R １３’ and ４ is CR １４ R １４’ and R １３ is a hydrogen atom; R １３’ is a hydrogen atom; R １４ is a hydrogen atom; R １４’ is a hydrogen atom; q and r are each 1; R １０ is a phenyl substituted with a halogen, a phenyl, a 5-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω (substituent group ω: alkyl, haloalkyl, and non-aromatic carbocyclic group), or a 6-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω′ (substituent group ω′: alkyl and halogen); R １１ is the formula: (In the formula, R １８ is a hydrogen atom or a halogen; R １９ is alkyl, haloalkyl, alkyl substituted with an aromatic carbocyclic group, alkyloxy, alkyloxy substituted with a non-aromatic carbocyclic group, alkyloxy or haloalkyloxy substituted with a non-aromatic carbocyclic group substituted with a halogen), a bicyclic 9-membered aromatic heterocyclic group, or a bicyclic 9-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ψ (substituent group ψ: halogen, alkyl, and alkyloxy); R ８ (15') The compound according to the above item (1'), or a pharmaceutically acceptable salt thereof, represented by the formula (III): (In the formula, R ３１ is a hydrogen atom or a C1-C3 alkyl; R ３２ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３３ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R３４ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ３５ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ３２ and R ３３ and R ３４ and R ３５ may be taken together with the same carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; Ring B' is a ring of the formula: (In the formula, R ６ is the formula: (In the formula, A ６ are each independently, CR ２５ R ２５’ and R ２５ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２５’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; s is 0 or 1; s' is 0, 1, or 2; R ２４ is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ５ is a hydrogen atom or a substituted or unsubstituted alkyl; ６ ' is the formula: (In the formula, A ７ is CR ２７ R ２７’ and R ２７ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２７’ is a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; t is 0 or 1; R ２６is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ７ is the formula: (In the formula, A ５ are each independently, CR ２８ R ２８’ and R ２８ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２８’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; u is 0, 1, or 2; R ２３ is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group), and R ２１ is a hydrogen atom or a substituted or unsubstituted alkyl; R ２２ are each independently a halogen or a substituted or unsubstituted alkyl; and v is 0, 1 or 2), or a pharmaceutically acceptable salt thereof. (17') R is a ring represented by the formula (15') or a pharmaceutically acceptable salt thereof. ６ But the formula: (wherein the symbols have the same meanings as in the above item (15')), or a pharmaceutically acceptable salt thereof. (18') A compound according to any one of the above items (15') to (17'), or a pharmaceutically acceptable salt thereof, wherein R ２４(20') The compound according to any one of the above items (15') to (19') or a pharmaceutically acceptable salt thereof, wherein R is a substituted or unsubstituted aromatic carbocyclic group. (21') The compound according to any one of the above items (15') to (19') or a pharmaceutically acceptable salt thereof, wherein R is a substituted or unsubstituted aromatic carbocyclic group. ２３ (22') The compound according to any one of the above items (15') to (20') or a pharmaceutically acceptable salt thereof, wherein R is a substituted or unsubstituted aromatic heterocyclic group. ３２ and R ３３is a hydrogen atom. (23') The compound according to any one of the above items (1') to (21') or a pharmaceutically acceptable salt thereof, wherein R is a serotonin 5-HT2A receptor antagonist and / or inverse agonist. (24') A pharmaceutical composition comprising the compound according to any one of the above items (1') to (23') or a pharmaceutically acceptable salt thereof. (25') The pharmaceutical composition according to the above item (24'), which is a serotonin 5-HT2A receptor antagonist and / or inverse agonist. (26') The pharmaceutical composition according to the above item (24'), which is a serotonin 5-HT2A and 5-HT2C receptor antagonist and / or inverse agonist. (27') A method for treating and / or preventing a disease involving the 5-HT2A receptor, comprising administering a compound according to any one of the above items (1') to (23') or a pharmaceutically acceptable salt thereof. (28') A method for treating and / or preventing a disease involving the 5-HT2A and 5-HT2C receptors, comprising administering a compound according to any one of the above items (1') to (23') or a pharmaceutically acceptable salt thereof. (29') A compound according to any one of the above items (1') to (23') or a pharmaceutically acceptable salt thereof for use in the treatment and / or prevention of a disease involving a 5-HT2A receptor antagonist and / or inverse agonist. (30') A compound according to any one of the above items (1') to (23') or a pharmaceutically acceptable salt thereof for use in the treatment and / or prevention of a disease involving a 5-HT2A and 5-HT2C receptor antagonist and / or inverse agonist. (31') Use of the compound according to any one of the above items (1') to (23') or a pharmaceutically acceptable salt thereof for the manufacture of an agent for the treatment and / or prevention of a disease associated with a 5-HT2A receptor antagonist and / or inverse agonist. (32') Use of the compound according to any one of the above items (1') to (23') or a pharmaceutically acceptable salt thereof for the manufacture of an agent for the treatment and / or prevention of a disease associated with a 5-HT2A and 5-HT2C receptor antagonist and / or inverse agonist.

[0012] The compounds according to the present invention have serotonin 5-HT2A receptor antagonistic and / or inverse agonistic activity and are useful as therapeutic and / or preventive agents for hallucinations and delusions associated with Parkinson's disease and / or dementia.

[0013] The meaning of each term used in this specification is explained below. Unless otherwise specified, each term has the same meaning whether used alone or in combination with other terms. The term "consisting of" means having only the constituent elements. The term "comprises" means not being limited to the constituent elements and does not exclude unrecited elements. The present invention will be explained below with reference to exemplary embodiments. Throughout this specification, singular expressions should be understood to include the plural concept unless otherwise specified. Therefore, singular articles (e.g., "a," "an," "the," etc. in English) should be understood to include the plural concept unless otherwise specified. Furthermore, terms used in this specification should be understood to have the meaning commonly used in the art unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In the event of conflict, the present specification (including definitions) will prevail.

[0014] The term "halogen" includes fluorine, chlorine, bromine, and iodine atoms. Particularly, fluorine and chlorine atoms are preferred.

[0015] The term "alkyl" includes straight-chain or branched hydrocarbon groups having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, and even more preferably 1 to 4 carbon atoms. Examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, n-heptyl, isoheptyl, n-octyl, isooctyl, n-nonyl, and n-decyl. Preferred embodiments of "alkyl" include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, and n-pentyl. More preferred embodiments include methyl, ethyl, n-propyl, isopropyl, and tert-butyl. R １１ , R ２４ or R ２６ In the case where R is an aromatic carbocyclic group substituted with alkyl, the "alkyl" moiety is preferably C2-C5 alkyl. Examples include ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, and n-pentyl. Furthermore, C3-C5 alkyl is more preferred. Examples include n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, and n-pentyl. １１ , R ２４ or R ２６ In the case where the aromatic carbocyclic group is substituted with alkyloxy, the "alkyl" portion of the alkyloxy is preferably C2-C5 alkyl. Examples include ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, and n-pentyl. C3-C5 alkyl is more preferred. Examples include n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, and n-pentyl.

[0016] "Haloalkyl" means the above alkyl substituted with one or more halogens. When substituted with two or more halogens, the halogens may be the same or different. Examples include fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2,2-difluoropropyl, 2,2,3,3-tetrafluoropropyl, 2,2,3,3,3-pentafluoropropyl, etc.

[0017] The term "alkenyl" encompasses straight-chain or branched hydrocarbon groups having 2 to 15 carbon atoms, preferably 2 to 10 carbon atoms, more preferably 2 to 6 carbon atoms, and even more preferably 2 to 4 carbon atoms, and having one or more double bonds at any position. Examples include vinyl, allyl, propenyl, isopropenyl, butenyl, isobutenyl, prenyl, butadienyl, pentenyl, isopentenyl, pentadienyl, hexenyl, isohexenyl, hexadienyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, and pentadecenyl. Preferred embodiments of "alkenyl" include vinyl, allyl, propenyl, isopropenyl, and butenyl. More preferred embodiments include vinyl and n-propenyl.

[0018] "Alkynyl" includes a straight-chain or branched hydrocarbon group having 2 to 10 carbon atoms, preferably 2 to 8 carbon atoms, more preferably 2 to 6 carbon atoms, and even more preferably 2 to 4 carbon atoms, and having one or more triple bonds at any position. It may further have a double bond at any position. Examples include ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, and the like. Preferred embodiments of "alkynyl" include ethynyl, propynyl, butynyl, and pentynyl. More preferred embodiments include ethynyl, propynyl, and the like.

[0019] The term "aromatic carbocyclic group" refers to a cyclic aromatic hydrocarbon group having one or more rings. Examples include phenyl, naphthyl, anthryl, and phenanthryl. A preferred embodiment of the "aromatic carbocyclic group" is phenyl.

[0020] The term "aromatic carbocyclic ring" refers to a ring derived from the above-mentioned "aromatic carbocyclic group".

[0021] The term "non-aromatic carbocyclic group" refers to a monocyclic or bicyclic or multicyclic saturated or non-aromatic unsaturated hydrocarbon group. A bicyclic or multicyclic "non-aromatic carbocyclic group" also includes a monocyclic or bicyclic or multicyclic non-aromatic carbocyclic group to which the ring of the above-mentioned "aromatic carbocyclic group" is fused. Furthermore, the term "non-aromatic carbocyclic group" also includes bridged groups or groups that form spiro rings as shown below. The monocyclic non-aromatic carbocyclic group preferably has 3 to 16 carbon atoms, more preferably 3 to 12 carbon atoms, and even more preferably 4 to 8 carbon atoms. Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclohexadienyl. The bicyclic or higher non-aromatic carbocyclic group preferably has 8 to 20 carbon atoms, more preferably 8 to 16 carbon atoms. Examples include indanyl, indenyl, acenaphthyl, tetrahydronaphthyl, and fluorenyl.

[0022] The term "non-aromatic carbocyclic ring" refers to a ring derived from the above-mentioned "non-aromatic carbocyclic group".

[0023] The term "aromatic heterocyclic group" refers to a monocyclic or bicyclic or multicyclic aromatic cyclic group having one or more identical or different heteroatoms selected from O, S, and N in the ring. Bicyclic or multicyclic aromatic heterocyclic groups also include those in which the rings in the "aromatic carbocyclic group" are fused to a monocyclic or bicyclic or multicyclic aromatic heterocyclic group, and the bond may be on any of the rings. Monocyclic aromatic heterocyclic groups are preferably 5- to 8-membered, and more preferably 5- or 6-membered. Examples of 5-membered aromatic heterocyclic groups include pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, thiadiazolyl, etc. Examples of 6-membered aromatic heterocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, etc. The bicyclic aromatic heterocyclic group is preferably 8- to 10-membered, and more preferably 9- or 10-membered. Examples include indolyl, isoindolyl, indazolyl, indolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, naphthyridinyl, quinoxalinyl, purinyl, pteridinyl, benzimidazolyl, benzisoxazolyl, benzoxazolyl, benzoxadiazolyl, benzisothiazolyl, benzothiazolyl, benzothiadiazolyl, benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, imidazopyridyl, triazolopyridyl, imidazothiazolyl, pyrazinopyridazinyl, oxazolopyridyl, and thiazolopyridyl. The tricyclic or more aromatic heterocyclic group is preferably 13- to 15-membered. Examples include carbazolyl, acridinyl, xanthenyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, dibenzofuryl, and the like.

[0024] The term "aromatic heterocycle" refers to a ring derived from the above-mentioned "aromatic heterocyclic group".

[0025] The term "aromatic nitrogen-containing heterocyclic group" refers to a monocyclic or bicyclic or more aromatic heterocyclic group containing one or more N atoms in the ring and optionally containing one or more identical or different heteroatoms selected from O and S in the ring. Bicyclic or more aromatic nitrogen-containing heterocyclic groups also include those in which a ring in the above-mentioned "aromatic carbocyclic group" is fused to a monocyclic or bicyclic or more aromatic nitrogen-containing heterocyclic group, and the bond may be on either ring.

[0026] The monocyclic aromatic nitrogen-containing heterocyclic group is preferably 5- to 8-membered, more preferably 5- or 6-membered. Examples of 5-membered aromatic nitrogen-containing heterocyclic groups include pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, and thiadiazolyl. Examples of 6-membered aromatic nitrogen-containing heterocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl. The bicyclic aromatic nitrogen-containing heterocyclic group is preferably 8- to 10-membered, more preferably 9- or 10-membered. Examples thereof include indolyl, isoindolyl, indazolyl, indolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, naphthyridinyl, quinoxalinyl, purinyl, pteridinyl, benzimidazolyl, benzisoxazolyl, benzoxazolyl, benzoxadiazolyl, benzisothiazolyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyl, imidazopyridyl, triazolopyridyl, imidazothiazolyl, pyrazinopyridazinyl, oxazolopyridyl, and thiazolopyridyl. The aromatic nitrogen-containing heterocyclic group having three or more rings is preferably 13 to 15-membered. Examples thereof include carbazolyl, acridinyl, and phenothiazinyl.

[0027] The term "non-aromatic heterocyclic group" refers to a monocyclic or bicyclic or more non-aromatic cyclic group having one or more identical or different heteroatoms selected from O, S, and N in the ring. Bicyclic or more non-aromatic heterocyclic groups include monocyclic or bicyclic or more non-aromatic heterocyclic groups fused with the respective rings of the above-mentioned "aromatic carbocyclic group," "non-aromatic carbocyclic group," and / or "aromatic heterocyclic group," as well as monocyclic or bicyclic or more non-aromatic carbocyclic groups fused with the rings of the above-mentioned "aromatic heterocyclic group," and the bond may be on any of the rings. Furthermore, the term "non-aromatic heterocyclic group" also includes bridged groups or groups forming spiro rings as described below. The monocyclic non-aromatic heterocyclic group is preferably 3 to 8 members, more preferably 5 or 6 members. Examples of 3-membered non-aromatic heterocyclic groups include thiiranyl, oxiranyl, and aziridinyl. Examples of 4-membered non-aromatic heterocyclic groups include oxetanyl and azetidinyl. Examples of 5-membered non-aromatic heterocyclic groups include oxathiolanyl, thiazolidinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, tetrahydrofuryl, dihydrothiazolyl, tetrahydroisothiazolyl, dioxolanyl, dioxolyl, and thiolanyl. Examples of 6-membered non-aromatic heterocyclic groups include dioxanyl, thianyl, piperidyl, piperazinyl, morpholinyl, morpholino, thiomorpholinyl, thiomorpholino, dihydropyridyl, tetrahydropyridyl, tetrahydropyranyl, dihydrooxazinyl, tetrahydropyridazinyl, hexahydropyrimidinyl, dioxazinyl, thiinyl, and thiazinyl. Examples of 7-membered non-aromatic heterocyclic groups include hexahydroazepinyl, tetrahydrodiazepinyl, and oxepanyl. Examples of 8-membered non-aromatic heterocyclic groups include azocane, thiocane, and oxocane. Non-aromatic heterocyclic groups having two or more rings preferably have 8 to 20 members, and more preferably have 8 to 10 members. Examples include indolinyl, isoindolinyl, chromanyl, and isochromanyl.

[0028] The term "non-aromatic nitrogen-containing heterocyclic group" refers to a monocyclic or bicyclic or more non-aromatic heterocyclic group having one or more nitrogen atoms in the ring. A bicyclic or more non-aromatic heterocyclic group includes a monocyclic or bicyclic or more non-aromatic nitrogen-containing heterocyclic group fused with any of the rings in the above-mentioned "aromatic carbocyclic group," "non-aromatic carbocyclic group," and / or "aromatic heterocyclic group," and the bond may be on any of the rings. For example, the following rings are shown: Furthermore, the term "non-aromatic nitrogen-containing heterocyclic group" also includes bridged groups or groups that form spiro rings, as shown below.

[0029] The term "non-aromatic heterocycle" refers to a ring derived from the above-mentioned "non-aromatic heterocyclic group".

[0030] R ２ and R ２’ , R ３ and R ３’ , R ３２ and R ３３ or R ３４ and R ３５ The non-aromatic carbocyclic ring formed by combining with the carbon atom to which it is attached includes, for example, the rings shown below.

[0031] "Trialkylsilyl" refers to a group in which three of the above-mentioned "alkyl" groups are bonded to a silicon atom. The three alkyl groups may be the same or different. Examples include trimethylsilyl, triethylsilyl, and tert-butyldimethylsilyl.

[0032] In this specification, "optionally substituted with substituent group α" means "optionally substituted with one or more groups selected from substituent group α." The same applies to substituent groups β, γ, and γ'.

[0033] Examples of substituents such as "substituted alkyl," "substituted alkenyl," "substituted alkynyl," "substituted alkyloxy," "substituted alkenyloxy," "substituted alkynyloxy," "substituted alkylcarbonyloxy," "substituted alkenylcarbonyloxy," "substituted alkynylcarbonyloxy," "substituted alkylcarbonyl," "substituted alkenylcarbonyl," "substituted alkynylcarbonyl," "substituted alkyloxycarbonyl," "substituted alkenyloxycarbonyl," "substituted alkynyloxycarbonyl," "substituted alkylsulfanyl," "substituted alkenylsulfanyl," "substituted alkynylsulfanyl," "substituted alkylsulfinyl," "substituted alkenylsulfinyl," "substituted alkynylsulfinyl," "substituted alkylsulfonyl," "substituted alkenylsulfonyl," and "substituted alkynylsulfonyl" include the following Substituent Group A. A carbon atom at any position may be bonded to one or more groups selected from the following Substituent Group A. Substituent group A: halogen, hydroxy, carboxy, formyl, formyloxy, sulfanyl, sulfino, sulfo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, cyano, nitro, nitroso, azido, hydrazino, ureido, amidino, guanidino, pentafluorothio, trialkylsilyl, alkyloxy optionally substituted with substituent group α, alkenyloxy optionally substituted with substituent group α, alkynyloxy optionally substituted with substituent group α, alkylcarbonyloxy optionally substituted with substituent group α, alkenylcarbonyloxy optionally substituted with substituent group α, alkynylcarbonyloxy optionally substituted with substituent group α, alkylcarbonyl optionally substituted with substituent group α, alkenylcarbonyl optionally substituted with substituent group α, alkynylcarbonyl optionally substituted with substituent group α, alkyloxycarbonyl optionally substituted with substituent group α, alkenyloxycarbonyl optionally substituted with substituent group α, alkynyloxycarbonyl optionally substituted with substituent group α, alkylsulfanyl optionally substituted with substituent group α, alkenylsulfanyl optionally substituted with substituent group α, alkynylsulfanyl optionally substituted with substituent group α,alkylsulfinyl optionally substituted with substituent group α, alkenylsulfinyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, alkylsulfonyl optionally substituted with substituent group α, alkenylsulfonyl optionally substituted with substituent group α, alkynylsulfonyl optionally substituted with substituent group α, amino optionally substituted with substituent group β, imino optionally substituted with substituent group β, carbamoyl optionally substituted with substituent group β, sulfamoyl optionally substituted with substituent group β, Aromatic carbocyclic group optionally substituted with substituent group γ, non-aromatic carbocyclic group optionally substituted with substituent group γ', aromatic heterocyclic group optionally substituted with substituent group γ, non-aromatic heterocyclic group optionally substituted with substituent group γ', aromatic carbocyclic oxy optionally substituted with substituent group γ, non-aromatic carbocyclic oxy optionally substituted with substituent group γ', aromatic heterocyclic oxy optionally substituted with substituent group γ, non-aromatic heterocyclic oxy optionally substituted with substituent group γ', aromatic carbocyclic carbonyloxy optionally substituted with substituent group γ, non-aromatic carbocyclic carbonyloxy optionally substituted with substituent group γ', aromatic heterocyclic carbonyloxy optionally substituted with substituent group γ, non-aromatic heterocyclic carbonyloxy optionally substituted with substituent group γ', aromatic carbocyclic carbonyl optionally substituted with substituent group γ, non-aromatic carbocyclic carbonyl optionally substituted by group γ', aromatic heterocyclic carbonyl optionally substituted by substituent group γ, non-aromatic heterocyclic carbonyl optionally substituted by substituent group γ', aromatic carbocyclic oxycarbonyl optionally substituted by substituent group γ, non-aromatic carbocyclic oxycarbonyl optionally substituted by substituent group γ', aromatic heterocyclic oxycarbonyl optionally substituted by substituent group γ, non-aromatic heterocyclic oxycarbonyl optionally substituted by substituent group γ', aromatic carbocyclic alkyloxy optionally substituted by substituent group γ, non-aromatic carbocyclic alkyloxy optionally substituted by substituent group γ', aromatic heterocyclic alkyloxy optionally substituted by substituent group γ, non-aromatic heterocyclic alkyloxy optionally substituted by substituent group γ', aromatic carbocyclic alkyloxycarbonyl optionally substituted by substituent group γ,Non-aromatic carbocyclic alkyloxycarbonyl optionally substituted with substituent group γ', aromatic heterocyclic alkyloxycarbonyl optionally substituted with substituent group γ, non-aromatic heterocyclic alkyloxycarbonyl optionally substituted with substituent group γ', aromatic carbocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfanyl optionally substituted with substituent group γ', aromatic heterocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfanyl optionally substituted with substituent group γ', aromatic carbocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfinyl optionally substituted with substituent group γ', aromatic heterocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfinyl optionally substituted with substituent group γ', aromatic carbocyclic sulfonyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfonyl optionally substituted with substituent group γ', aromatic heterocyclic sulfonyl optionally substituted with substituent group γ and non-aromatic heterocyclic sulfonyl optionally substituted with substituent group γ'.

[0034] Substituent group α: halogen, hydroxy, carboxy, alkyloxy, haloalkyloxy, alkenyloxy, alkynyloxy, sulfanyl, and cyano.

[0035] Substituent group β: halogen, hydroxy, carboxy, cyano, alkyl optionally substituted with substituent group α, alkenyl optionally substituted with substituent group α, alkynyl optionally substituted with substituent group α, alkylcarbonyl optionally substituted with substituent group α, alkenylcarbonyl optionally substituted with substituent group α, alkynylcarbonyl optionally substituted with substituent group α, alkylsulfanyl optionally substituted with substituent group α, alkenylsulfanyl optionally substituted with substituent group α, alkynylsulfanyl optionally substituted with substituent group α, alkylsulfinyl optionally substituted with substituent group α, alkenylsulfinyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, alkylsulfonyl optionally substituted with substituent group α, alkenylsulfonyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, alkylsulfonyl optionally substituted with substituent group α, alkenylsulfonyl optionally substituted with substituent group α, alkynylsulfonyl optionally substituted with substituent group α,Aromatic carbocyclic group optionally substituted with substituent group γ, non-aromatic carbocyclic group optionally substituted with substituent group γ', aromatic heterocyclic group optionally substituted with substituent group γ, non-aromatic heterocyclic group optionally substituted with substituent group γ', aromatic carbocyclic alkyl optionally substituted with substituent group γ, non-aromatic carbocyclic alkyl optionally substituted with substituent group γ', aromatic heterocyclic alkyl optionally substituted with substituent group γ, non-aromatic heterocyclic alkyl optionally substituted with substituent group γ', aromatic carbocyclic carbonyl optionally substituted with substituent group γ, non-aromatic carbocyclic carbonyl optionally substituted with substituent group γ', aromatic heterocyclic carbonyl optionally substituted with substituent group γ, non-aromatic heterocyclic carbonyl optionally substituted with substituent group γ', aromatic carbocyclic oxycarbonyl optionally substituted with substituent group γ, non-aromatic carbocyclic oxycarbonyl optionally substituted with substituent group γ', aromatic heterocyclic oxycarbonyl optionally substituted with substituent group γ', non-aromatic heterocyclic oxycarbonyl optionally substituted with substituent group γ', aromatic carbocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfanyl optionally substituted with substituent group γ', aromatic heterocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfanyl optionally substituted with substituent group γ', aromatic carbocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfinyl optionally substituted with substituent group γ', aromatic heterocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfinyl optionally substituted with substituent group γ', aromatic carbocyclic sulfonyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfonyl optionally substituted with substituent group γ', aromatic heterocyclic sulfonyl optionally substituted with substituent group γ and non-aromatic heterocyclic sulfonyl optionally substituted with substituent group γ'.

[0036] Substituent group γ: Substituent group α, alkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, alkylcarbonyl, haloalkylcarbonyl, alkenylcarbonyl, and alkynylcarbonyl.

[0037] Substituent group γ': Substituent group γ and oxo.

[0038] Substituents on the ring of an "aromatic carbocycle" and an "aromatic heterocycle", such as a "substituted aromatic carbocyclic group", "substituted aromatic heterocyclic group", "substituted aromatic nitrogen-containing heterocyclic group", "substituted aromatic carbocycleoxy", "substituted aromatic heterocycleoxy", "substituted aromatic carbocyclecarbonyloxy", "substituted aromatic heterocyclecarbonyloxy", "substituted aromatic carbocyclecarbonyl", "substituted aromatic heterocyclecarbonyl", "substituted aromatic carbocycleoxycarbonyl", "substituted aromatic heterocycleoxycarbonyl", "substituted aromatic carbocyclesulfanyl", "substituted aromatic heterocyclesulfanyl", "substituted aromatic carbocyclesulfinyl", "substituted aromatic heterocyclesulfinyl", "substituted aromatic carbocyclesulfonyl", and "substituted aromatic heterocyclesulfonyl", include the following substituent group B. An atom at any position on the ring may be bonded to one or more groups selected from the following substituent group B. Substituent group B: halogen, hydroxy, carboxy, formyl, formyloxy, sulfanyl, sulfino, sulfo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, cyano, nitro, nitroso, azido, hydrazino, ureido, amidino, guanidino, pentafluorothio, trialkylsilyl, alkyl optionally substituted with substituent group α, alkenyl optionally substituted with substituent group α, alkynyl optionally substituted with substituent group α, alkyloxy optionally substituted with substituent group α, alkenyloxy optionally substituted with substituent group α, alkynyloxy optionally substituted with substituent group α, alkylcarbonyloxy optionally substituted with substituent group α, alkenylcarbonyloxy optionally substituted with substituent group α, alkynylcarbonyloxy optionally substituted with substituent group α, alkylcarbonyl optionally substituted with substituent group α, alkenylcarbonyl optionally substituted with substituent group α, alkynylcarbonyl optionally substituted with substituent group α, alkyloxycarbonyl optionally substituted with substituent group α, alkenyloxycarbonyl optionally substituted with substituent group α, alkynyloxycarbonyl optionally substituted with substituent group α, alkylsulfanyl optionally substituted with substituent group α, alkenylsulfanyl optionally substituted with substituent group α, alkynylsulfanyl optionally substituted with substituent group α,alkylsulfinyl optionally substituted with substituent group α, alkenylsulfinyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, alkylsulfonyl optionally substituted with substituent group α, alkenylsulfonyl optionally substituted with substituent group α, alkynylsulfonyl optionally substituted with substituent group α, amino optionally substituted with substituent group β, imino optionally substituted with substituent group β, carbamoyl optionally substituted with substituent group β, sulfamoyl optionally substituted with substituent group β, Aromatic carbocyclic group optionally substituted with substituent group γ, non-aromatic carbocyclic group optionally substituted with substituent group γ', aromatic heterocyclic group optionally substituted with substituent group γ, non-aromatic heterocyclic group optionally substituted with substituent group γ', aromatic carbocyclic oxy optionally substituted with substituent group γ, non-aromatic carbocyclic oxy optionally substituted with substituent group γ', aromatic heterocyclic oxy optionally substituted with substituent group γ, non-aromatic heterocyclic oxy optionally substituted with substituent group γ', aromatic carbocyclic carbonyloxy optionally substituted with substituent group γ, non-aromatic carbocyclic carbonyloxy optionally substituted with substituent group γ', aromatic heterocyclic carbonyloxy optionally substituted with substituent group γ, and non-aromatic heterocyclic carbonyloxy optionally substituted with substituent group γ', aromatic carbocyclic carbonyloxy optionally substituted with substituent group γ ring carbonyl, non-aromatic carbocyclic carbonyl optionally substituted with substituent group γ', aromatic heterocyclic carbonyl optionally substituted with substituent group γ, non-aromatic heterocyclic carbonyl optionally substituted with substituent group γ', aromatic carbocyclic oxycarbonyl optionally substituted with substituent group γ', non-aromatic carbocyclic oxycarbonyl optionally substituted with substituent group γ, aromatic heterocyclic oxycarbonyl optionally substituted with substituent group γ, non-aromatic heterocyclic oxycarbonyl optionally substituted with substituent group γ', aromatic carbocyclic alkyl optionally substituted with substituent group γ, non-aromatic carbocyclic alkyl optionally substituted with substituent group γ', aromatic heterocyclic alkyl optionally substituted with substituent group γ, non-aromatic heterocyclic alkyl optionally substituted with substituent group γ', aromatic carbocyclic alkyloxy optionally substituted with substituent group γ,Non-aromatic carbocyclic alkyloxy optionally substituted with substituent group γ', aromatic heterocyclic alkyloxy optionally substituted with substituent group γ, non-aromatic heterocyclic alkyloxy optionally substituted with substituent group γ', aromatic carbocyclic alkyloxycarbonyl optionally substituted with substituent group γ', non-aromatic carbocyclic alkyloxycarbonyl optionally substituted with substituent group γ, aromatic heterocyclic alkyloxycarbonyl optionally substituted with substituent group γ, non-aromatic heterocyclic alkyloxycarbonyl optionally substituted with substituent group γ', aromatic carbocyclic alkyloxyalkyl optionally substituted with substituent group γ', non-aromatic carbocyclic alkyloxyalkyl optionally substituted with substituent group γ', aromatic heterocyclic alkyloxyalkyl optionally substituted with substituent group γ, non-aromatic heterocyclic alkyloxyalkyl optionally substituted with substituent group γ, non-aromatic heterocyclic alkyloxyalkyl optionally substituted with substituent group γ' alkyloxyalkyl, aromatic carbocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfanyl optionally substituted with substituent group γ', aromatic heterocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfanyl optionally substituted with substituent group γ', aromatic carbocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfinyl optionally substituted with substituent group γ', aromatic heterocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfinyl optionally substituted with substituent group γ', aromatic carbocyclic sulfonyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfonyl optionally substituted with substituent group γ', aromatic heterocyclic sulfonyl optionally substituted with substituent group γ and non-aromatic heterocyclic sulfonyl optionally substituted with substituent group γ'.

[0039] "Substituted non-aromatic carbocyclic group", "Substituted non-aromatic heterocyclic group", "Substituted non-aromatic nitrogen-containing heterocyclic group", "R ２ and R ２’ "a substituted non-aromatic carbocyclic ring formed together with the carbon to which R is attached," "R ２ and R ２’ "a substituted non-aromatic heterocyclic ring formed together with the carbon to which R is attached," "R ３ and R ３’ "a substituted non-aromatic carbocyclic ring formed together with the carbon to which R is attached," "R３ and R ３’ "a substituted non-aromatic heterocyclic ring formed together with the carbon to which R is attached," "R ３２ and R ３３ "a substituted non-aromatic carbocyclic ring formed by combining "R ３２ and R ３３ "a substituted non-aromatic heterocycle formed by combining "R ３４ and R ３５ "a substituted non-aromatic carbocyclic ring formed together with the carbon atom to which R is attached," "R ３４ and R ３５ ", "substituted non-aromatic carbocycle" and "non-aromatic heterocycle" of "substituted non-aromatic heterocycle" formed together with the carbon atom to which it is bonded," "substituted non-aromatic carbocycleoxy," "substituted non-aromatic heterocycleoxy," "substituted non-aromatic carbocyclecarbonyloxy," "substituted non-aromatic heterocyclecarbonyloxy," "substituted non-aromatic carbocyclecarbonyl," "substituted non-aromatic heterocyclecarbonyl," "substituted non-aromatic carbocycleoxycarbonyl," "substituted non-aromatic heterocycleoxycarbonyl," "substituted non-aromatic carbocyclesulfanyl," "substituted non-aromatic heterocyclesulfanyl," "substituted non-aromatic carbocyclesulfinyl," "substituted non-aromatic heterocyclesulfinyl," "substituted non-aromatic carbocyclesulfonyl," and "substituted non-aromatic heterocyclesulfonyl" include the following substituent group C. An atom at any position on the ring may be bonded to one or more groups selected from the following substituent group C. Substituent group C: Substituent group B and oxo.

[0040] When a "non-aromatic carbocycle," a "non-aromatic heterocycle," or a "non-aromatic nitrogen-containing heterocycle" is substituted with "oxo," it means a ring in which two hydrogen atoms on a carbon atom are replaced as follows:

[0041] Substituents for "substituted amino", "substituted imino", "substituted carbamoyl" and "substituted sulfamoyl" include the following Substituent Group D. Each group may be substituted with 1 or 2 groups selected from Substituent Group D. Substituent group D: halogen, hydroxy, carboxy, cyano, alkyl optionally substituted with substituent group α, alkenyl optionally substituted with substituent group α, alkynyl optionally substituted with substituent group α, alkylcarbonyl optionally substituted with substituent group α, alkenylcarbonyl optionally substituted with substituent group α, alkynylcarbonyl optionally substituted with substituent group α, alkylsulfanyl optionally substituted with substituent group α, alkenylsulfanyl optionally substituted with substituent group α, alkynylsulfanyl optionally substituted with substituent group α, alkylsulfinyl optionally substituted with substituent group α, alkenylsulfinyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, alkylsulfonyl optionally substituted with substituent group α, alkenylsulfonyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, alkylsulfonyl optionally substituted with substituent group α, alkenylsulfonyl optionally substituted with substituent group α, alkynylsulfonyl optionally substituted with substituent group α, amino optionally substituted with substituent group β, imino optionally substituted with substituent group β, carbamoyl optionally substituted with substituent group β, sulfamoyl optionally substituted with substituent group β,Aromatic carbocyclic group optionally substituted with substituent group γ, non-aromatic carbocyclic group optionally substituted with substituent group γ', aromatic heterocyclic group optionally substituted with substituent group γ, non-aromatic heterocyclic group optionally substituted with substituent group γ', aromatic carbocyclic alkyl optionally substituted with substituent group γ, non-aromatic carbocyclic alkyl optionally substituted with substituent group γ', aromatic heterocyclic alkyl optionally substituted with substituent group γ, non-aromatic heterocyclic alkyl optionally substituted with substituent group γ', aromatic carbocyclic carbonyl optionally substituted with substituent group γ, non-aromatic carbocyclic carbonyl optionally substituted with substituent group γ', aromatic heterocyclic carbonyl optionally substituted with substituent group γ, non-aromatic heterocyclic carbonyl optionally substituted with substituent group γ', aromatic carbocyclic oxycarbonyl optionally substituted with substituent group γ, non-aromatic carbocyclic oxycarbonyl optionally substituted with substituent group γ', aromatic heterocyclic oxycarbonyl optionally substituted with substituent group γ', non-aromatic heterocyclic oxycarbonyl optionally substituted with substituent group γ', aromatic carbocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfanyl optionally substituted with substituent group γ', aromatic heterocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfanyl optionally substituted with substituent group γ', aromatic carbocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfinyl optionally substituted with substituent group γ', aromatic heterocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfinyl optionally substituted with substituent group γ', aromatic carbocyclic sulfonyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfonyl optionally substituted with substituent group γ', aromatic heterocyclic sulfonyl optionally substituted with substituent group γ and non-aromatic heterocyclic sulfonyl optionally substituted with substituent group γ'.

[0042] In the compound of formula (I), R １ , A １ , A ２ Preferred embodiments of R, m, n, and ring B are shown below. The compounds represented by formula (I) include all combinations of the specific examples shown below. １R is a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as A-1). １ R is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as A-2). １ R is substituted or unsubstituted alkyl (hereinafter referred to as A-3). １ is a hydrogen atom or alkyl (hereinafter referred to as A-4). １ Examples of the alkyl group include alkyl (hereinafter referred to as A-5).

[0043] A １ is CR ２ R ２’ (where R ２ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２ and R ２’ may form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as B-1). １ is CR ２ R ２’ (where R ２ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ２’ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ２ and R ２’ may form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as B-2). １ is CR ２ R ２’ (where R ２are each independently a hydrogen atom or a halogen atom, and R ２’ are each independently a hydrogen atom or a halogen atom, and R ２ and R ２’ may form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as B-3). １ is CR ２ R ２’ (where R ２ are each independently a hydrogen atom or a halogen atom, and R ２’ are each independently a hydrogen atom or a halogen atom, and R ２ and R ２’ may form a substituted or unsubstituted non-aromatic carbocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as B-4). １ is CR ２ R ２’ (where R ２ is a hydrogen atom, and R ２’ is a hydrogen atom, and R ２ and R ２’ may form a substituted or unsubstituted non-aromatic carbocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as B-5). １ is CR ２ R ２’ (where R ２ are each independently a hydrogen atom or a halogen atom, and R ２’ are each independently a hydrogen atom or a halogen) (hereinafter referred to as B-6). １ is CR ２ R ２’ (where R ２ is a hydrogen atom, and R ２’ is a hydrogen atom) (hereinafter referred to as B-7).

[0044] A ２ is CR ３ R ３’ (where R ３are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ３’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ３ and R ３’ may form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as C-1). ２ is CR ３ R ３’ (where R ３ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ３’ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ３ and R ３’ may form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as C-2). ２ is CR ３ R ３’ (where R ３ are each independently a hydrogen atom or a halogen atom, and R ３’ are each independently a hydrogen atom or a halogen atom, and R ３ and R ３’ may form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as C-3). ２ is CR ３ R ３’ (where R ３ are each independently a hydrogen atom or a halogen atom, and R ３’ are each independently a hydrogen atom or a halogen atom, and R ３ and R ３’ may form a substituted or unsubstituted non-aromatic carbocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as C-4).２ is CR ３ R ３’ (where R ３ is a hydrogen atom, and R ３’ is a hydrogen atom, and R ３ and R ３’ may form a substituted or unsubstituted non-aromatic carbocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as C-5). ２ is CR ３ R ３’ (where R ３ are each independently a hydrogen atom or a halogen atom, and R ３’ are each independently a hydrogen atom or a halogen) (hereinafter referred to as C-6). ２ is CR ３ R ３’ (where R ３ is a hydrogen atom, and R ３’ is a hydrogen atom) (hereinafter referred to as C-7).

[0045] Examples of m include 1, 2, and 3 (hereinafter referred to as D-1). Examples of m include 1 or 2 (hereinafter referred to as D-2). Examples of m include 1 (hereinafter referred to as D-3). Examples of m include 2 (hereinafter referred to as D-4). Examples of m include 3 (hereinafter referred to as D-5).

[0046] n can be 1, 2, or 3 (hereinafter referred to as E-1). n can be 1 or 2 (hereinafter referred to as E-2). n can be 1 (hereinafter referred to as E-3). n can be 2 (hereinafter referred to as E-4). n can be 3 (hereinafter referred to as E-5).

[0047] Examples of ring B include rings represented by the following groups (hereinafter referred to as F-1). Examples of ring B include rings represented by the following groups (hereinafter referred to as F-2). Examples of ring B include rings represented by the following groups (hereinafter referred to as F-3). Examples of ring B include rings represented by the following groups (hereinafter referred to as F-4). Examples of ring B include rings represented by the following groups (hereinafter referred to as F-5). Examples of ring B include rings represented by the following groups (hereinafter referred to as F-6). Examples of ring B include rings represented by the following groups (hereinafter referred to as F-7).

[0048] R ４ Examples of the group include the following (hereinafter referred to as G-1): R ４ Examples of the group include the following (hereinafter referred to as G-2): R ４ Examples of the group include the following (hereinafter referred to as G-3): R ４ Examples of the group include the following (hereinafter referred to as G-4):

[0049] A ３ is CR １３ R １３’ (where R １３ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １３’ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy (hereinafter referred to as H-1). ３ is CR １３ R １３’ (where R １３ are each independently a hydrogen atom or a substituted or unsubstituted alkyl, and R １３’ are each independently a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as H-2). ３ is CR １３ R １３’ (where R １３ is a hydrogen atom, and R １３’ is a hydrogen atom) (hereinafter referred to as H-3).

[0050] A ４ is CR １４ R １４’ (where R １４are each independently a hydrogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １４’ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy (hereinafter referred to as I-1). ４ is CR １４ R １４’ (where R １４ are each independently a hydrogen atom or a substituted or unsubstituted alkyl, and R １４’ are each independently a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as I-2). ４ is CR １４ R １４’ (where R １４ is a hydrogen atom, and R １４’ is a hydrogen atom) (hereinafter referred to as I-3).

[0051] q may be 0, 1 or 2 (hereinafter referred to as J-1). q may be 1 or 2 (hereinafter referred to as J-2). q may be 1 (hereinafter referred to as J-3). q may be 2 (hereinafter referred to as J-4).

[0052] q' may be 1 or 2 (hereinafter referred to as K-1), q' may be 1 (hereinafter referred to as K-2), or q' may be 2 (hereinafter referred to as K-3).

[0053] r may be 0, 1, or 2 (hereinafter referred to as L-1). r may be 1 or 2 (hereinafter referred to as L-2). r may be 1 (hereinafter referred to as L-3). r may be 2 (hereinafter referred to as L-4).

[0054] Examples of r' include 1 or 2 (hereinafter referred to as M-1), 1 (hereinafter referred to as M-2), and 2 (hereinafter referred to as M-3).

[0055] R １０R may be a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as O-1). １０ R may be a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as O-2). １０ R is a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as O-3). １０ R is a substituted or unsubstituted 5-membered aromatic heterocyclic group (hereinafter referred to as O-4). １０ R includes substituted or unsubstituted oxazolyl (hereinafter referred to as O-5). １０ R includes substituted or unsubstituted pyrazolyl (hereinafter referred to as O-6). １０ R includes substituted or unsubstituted isoxazolyl (hereinafter referred to as O-7). １０ R includes substituted or unsubstituted furyl (hereinafter referred to as O-8). １０ R includes substituted or unsubstituted triazolyl (hereinafter referred to as O-9). １０ R includes phenyl substituted with halogen, phenyl, a 5-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω (substituent group ω: alkyl, haloalkyl, and non-aromatic carbocyclic group), and a 6-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω' (substituent group ω': alkyl and halogen) (hereinafter referred to as O-10). １０ R may be a phenyl group substituted with halogen or an unsubstituted phenyl group (hereinafter referred to as O-11). １０ R is a 5-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω (substituent group ω: alkyl, haloalkyl, and non-aromatic carbocyclic group) or a 6-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω' (substituent group ω': alkyl and halogen) (hereinafter referred to as O-12). １０R is a 5-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω (substituent group ω: alkyl, haloalkyl, and non-aromatic carbocyclic group) (hereinafter referred to as O-13). １０ Examples of the substituents include oxazolyl substituted with one or more substituents selected from the substituent group ω and triazolyl substituted with one or more substituents selected from the substituent group ω (substituent group ω: alkyl, haloalkyl, and non-aromatic carbocyclic group) (hereinafter referred to as O-14).

[0056] R １１ R may be a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as P-1). １１ R may be a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as P-2). １１ R is a substituted or unsubstituted aromatic carbocyclic group (hereinafter referred to as P-3). １１ R may be a substituted or unsubstituted phenyl (hereinafter referred to as P-4). １１ R includes phenyl substituted with a substituent group ψ' (substituent group ψ': alkyl, halogen, haloalkyl, alkyl substituted with an aromatic carbocyclic group, alkyloxy, alkyloxy substituted with a non-aromatic carbocyclic group, alkyloxy and haloalkyloxy substituted with a non-aromatic carbocyclic group substituted with a halogen), phenyl, a bicyclic 9-membered aromatic heterocyclic group, or a bicyclic 9-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ψ (substituent group ψ: halogen, alkyl and alkyloxy) (hereinafter referred to as P-5). １１ is the formula: (In the formula, R １８ is a hydrogen atom or a halogen; R １９is alkyl, haloalkyl, alkyl substituted with an aromatic carbocyclic group, alkyloxy, alkyloxy substituted with a non-aromatic carbocyclic group, alkyloxy or haloalkyloxy substituted with a non-aromatic carbocyclic group substituted with a halogen), a bicyclic 9-membered aromatic heterocyclic group, or a bicyclic 9-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ψ (substituent group ψ: halogen, alkyl, and alkyloxy) (hereinafter referred to as P-6). １１ is the formula: (In the formula, R １８ is a hydrogen atom or a halogen; R １９ is a C1-C6 alkyloxy or C1-C6 haloalkyloxy) (hereinafter referred to as P-7).

[0057] R １２ is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as Q-1). １２ is a hydrogen atom (hereinafter referred to as Q-2).

[0058] R ８ is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as R-1). ８ R is substituted or unsubstituted alkyl (hereinafter referred to as R-2). ８ is a hydrogen atom (hereinafter referred to as R-3).

[0059] R ９ R is independently a halogen atom or a substituted or unsubstituted alkyl group (hereinafter referred to as S-1). ９ Each of R is independently substituted or unsubstituted alkyl (hereinafter referred to as S-2). ９ are each independently a halogen (hereinafter referred to as S-3).

[0060] p may be any integer from 0 to 6 (hereinafter referred to as T-1), p may be 0, 1, or 2 (hereinafter referred to as T-2), p may be 1 (hereinafter referred to as T-3), or p may be 0 (hereinafter referred to as T-4).

[0061] In the compound of formula (II), R １ , R ２ , R ３ , R ２’ , R ３’ Preferred embodiments of R and ring B are shown below. The compound represented by formula (II) includes all combinations of the specific examples shown below. １ R is a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as AA-1). １ R is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as AA-2). １ R is substituted or unsubstituted alkyl (hereinafter referred to as AA-3). １ R is a hydrogen atom or alkyl (hereinafter referred to as AA-4). １ Examples of the alkyl group include alkyl (hereinafter referred to as AA-5).

[0062] R ２ R is a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl (hereinafter referred to as BA-1). ２ is a hydrogen atom (hereinafter referred to as BA-2). ２ R is a halogen (hereinafter referred to as BA-3). ２ is substituted or unsubstituted alkyl (hereinafter referred to as BA-4).

[0063] R ２’ R is a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl (hereinafter referred to as CA-1). ２’ is a hydrogen atom (hereinafter referred to as CA-2). ２’R is a halogen (hereinafter referred to as CA-3). ２’ is substituted or unsubstituted alkyl (hereinafter referred to as CA-4).

[0064] R ３ R is a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl (hereinafter referred to as DA-1). ３ is a hydrogen atom (hereinafter referred to as DA-2). ３ R is exemplified by halogen (hereinafter referred to as DA-3). ３ is substituted or unsubstituted alkyl (hereinafter referred to as DA-4).

[0065] R ３’ R is a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl (hereinafter referred to as EA-1). ３’ is a hydrogen atom (hereinafter referred to as EA-2). ３’ R is a halogen (hereinafter referred to as EA-3). ３’ is substituted or unsubstituted alkyl (hereinafter referred to as EA-4).

[0066] Examples of ring B include rings represented by the following groups (hereinafter referred to as FA-1). Examples of ring B include rings represented by the following groups (hereinafter referred to as FA-2). Examples of ring B include rings represented by the following groups (hereinafter referred to as FA-3). Examples of ring B include rings represented by the following groups (hereinafter referred to as FA-4). Examples of ring B include rings represented by the following groups (hereinafter referred to as FA-5). Examples of ring B include rings represented by the following groups (hereinafter referred to as FA-6). Examples of ring B include rings represented by the following groups (hereinafter referred to as FA-7).

[0067] R ４ Examples of the group include the following (hereinafter referred to as GA-1): R ４Examples of the group include the following (hereinafter referred to as GA-2): R ４ Examples of the group include the following group (hereinafter referred to as GA-3): R ４ Examples of the group include the following (hereinafter referred to as GA-4):

[0068] A ３ is CR １３ R １３’ (where R １３ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １３’ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy (hereinafter referred to as HA-1). ３ is CR １３ R １３’ (where R １３ are each independently a hydrogen atom or a substituted or unsubstituted alkyl, and R １３’ are each independently a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as HA-2). ３ is CR １３ R １３’ (where R １３ is a hydrogen atom, and R １３’ is a hydrogen atom) (hereinafter referred to as HA-3).

[0069] A ４ is CR １４ R １４’ (where R １４ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １４’ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy (hereinafter referred to as IA-1). ４ is CR １４ R １４’ (where R １４ are each independently a hydrogen atom or a substituted or unsubstituted alkyl, and R１４’ are each independently a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as IA-2). ４ is CR １４ R １４’ (where R １４ is a hydrogen atom, and R １４’ is a hydrogen atom) (hereinafter referred to as IA-3).

[0070] q may be 0, 1 or 2 (hereinafter referred to as JA-1). q may be 1 or 2 (hereinafter referred to as JA-2). q may be 1 (hereinafter referred to as JA-3). q may be 2 (hereinafter referred to as JA-4).

[0071] q' may be 1 or 2 (hereinafter referred to as KA-1). q' may be 1 (hereinafter referred to as KA-2). q' may be 2 (hereinafter referred to as KA-3).

[0072] r may be 0, 1 or 2 (hereinafter referred to as LA-1). r may be 1 or 2 (hereinafter referred to as LA-2). r may be 1 (hereinafter referred to as LA-3). r may be 2 (hereinafter referred to as LA-4).

[0073] Examples of r' include 1 or 2 (hereinafter referred to as MA-1), 1 (hereinafter referred to as MA-2), and 2 (hereinafter referred to as MA-3).

[0074] R １０ R may be a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as NA-1). １０ R may be a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as NA-2). １０ R is a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as NA-3). １０R is a substituted or unsubstituted 5-membered aromatic heterocyclic group (hereinafter referred to as NA-4). １０ R is substituted or unsubstituted oxazolyl (hereinafter referred to as NA-5). １０ R is substituted or unsubstituted pyrazolyl (hereinafter referred to as NA-6). １０ R is substituted or unsubstituted isoxazolyl (hereinafter referred to as NA-7). １０ R may be substituted or unsubstituted furyl (hereinafter referred to as NA-8). １０ R may be a substituted or unsubstituted triazolyl (hereinafter referred to as NA-9). １０ R includes phenyl substituted with halogen, phenyl, a 5-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω (substituent group ω: alkyl, haloalkyl, and non-aromatic carbocyclic group), and a 6-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω' (substituent group ω': alkyl and halogen) (hereinafter referred to as NA-10). １０ R may be phenyl substituted with halogen or unsubstituted phenyl (hereinafter referred to as NA-11). １０ R is a 5-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω (substituent group ω: alkyl, haloalkyl, and non-aromatic carbocyclic group) or a 6-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω' (substituent group ω': alkyl and halogen) (hereinafter referred to as NA-12). １０ R is a 5-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω (substituent group ω: alkyl, haloalkyl, and non-aromatic carbocyclic group) (hereinafter referred to as NA-13). １０ Examples of the substituents include oxazolyl substituted with one or more substituents selected from the substituent group ω, and triazolyl substituted with one or more substituents selected from the substituent group ω (substituent group ω: alkyl, haloalkyl, and non-aromatic carbocyclic group) (hereinafter referred to as NA-14).

[0075] R １１R may be a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as OA-1). １１ R may be a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as OA-2). １１ R is a substituted or unsubstituted aromatic carbocyclic group (hereinafter referred to as OA-3). １１ R may be a substituted or unsubstituted phenyl (hereinafter referred to as OA-4). １１ R includes phenyl substituted with a substituent group ψ' (substituent group ψ': alkyl, halogen, haloalkyl, alkyl substituted with an aromatic carbocyclic group, alkyloxy, alkyloxy substituted with a non-aromatic carbocyclic group, alkyloxy and haloalkyloxy substituted with a non-aromatic carbocyclic group substituted with a halogen), phenyl, a bicyclic 9-membered aromatic heterocyclic group, or a bicyclic 9-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ψ (substituent group ψ: halogen, alkyl and alkyloxy) (hereinafter referred to as OA-5). １１ is the formula: (In the formula, R １８ is a hydrogen atom or a halogen; R １９ is alkyl, haloalkyl, alkyl substituted with an aromatic carbocyclic group, alkyloxy, alkyloxy substituted with a non-aromatic carbocyclic group, alkyloxy or haloalkyloxy substituted with a non-aromatic carbocyclic group substituted with a halogen), a bicyclic 9-membered aromatic heterocyclic group, or a bicyclic 9-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ψ (substituent group ψ: halogen, alkyl, and alkyloxy) (hereinafter referred to as OA-6). １１ is the formula: (In the formula, R １８ is a hydrogen atom or a halogen; R １９is a group represented by the formula (hereinafter referred to as OA-7) in which:

[0076] R １２ R is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as PA-1). １２ is a hydrogen atom (hereinafter referred to as PA-2).

[0077] R ８ R is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as QA-1). ８ R is substituted or unsubstituted alkyl (hereinafter referred to as QA-2). ８ is a hydrogen atom (hereinafter referred to as QA-3).

[0078] R ９ Each of R is independently a halogen or a substituted or unsubstituted alkyl (hereinafter referred to as RA-1). ９ Each of R is independently substituted or unsubstituted alkyl (hereinafter referred to as RA-2). ９ are each independently a halogen (hereinafter referred to as RA-3).

[0079] p can be any integer from 0 to 6 (hereinafter referred to as SA-1). p can be 0, 1, or 2 (hereinafter referred to as SA-2). p can be 1 (hereinafter referred to as SA-3). p can be 0 (hereinafter referred to as SA-4).

[0080] In the compound represented by formula (III), R ３１ , R ３２ , R ３３ , R ３４ , R ３５ Preferred embodiments of R and ring B' are shown below. The compound represented by formula (III) includes all combinations of the specific examples shown below. ３１ is a hydrogen atom or a C1-C3 alkyl (hereinafter referred to as AB-1). ３１Examples of the alkyl group include C1-C3 alkyl (hereinafter referred to as AB-2).

[0081] R ３２ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３３ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３２ and R ３３ may form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as BB-1). ３２ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３３ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３２ and R ３３ may form a substituted or unsubstituted non-aromatic carbocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as BB-2). ３２ is a hydrogen atom, and R ３３ is a hydrogen atom, and R ３２ and R ３３ may form a substituted or unsubstituted non-aromatic carbocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as BB-3). ３２ is a hydrogen atom, and R ３３ is a hydrogen atom, and R ３２ and R ３３ may form a non-aromatic carbocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as BB-4). ３２ is a hydrogen atom, and R ３３ is a hydrogen atom (hereinafter referred to as BB-5).

[0082] R ３４ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ３５ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ３４ and R ３５may form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as CB-1). ３４ are each independently a hydrogen atom or a halogen atom, and R ３５ are each independently a hydrogen atom or a halogen atom, and R ３４ and R ３５ may form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as CB-2). ３４ are each independently a hydrogen atom or a halogen atom, and R ３５ are each independently a hydrogen atom or a halogen atom, and R ３４ and R ３５ may form a substituted or unsubstituted non-aromatic carbocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as CB-3). ３４ is a hydrogen atom, and R ３５ is a hydrogen atom, and R ３４ and R ３５ may form a substituted or unsubstituted non-aromatic carbocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as CB-4). ３４ is a hydrogen atom, and R ３５ is a hydrogen atom, and R ３４ and R ３５ may form a non-aromatic carbocyclic ring together with the same carbon atom to which it is attached (hereinafter referred to as CB-5). ３４ is a hydrogen atom, and R ３５ is a hydrogen atom (hereinafter referred to as CB-6).

[0083] Examples of ring B' include rings represented by the following groups (hereinafter referred to as DB-1). Examples of ring B' include rings represented by the following groups (hereinafter referred to as DB-2). Examples of ring B' include rings represented by the following group (hereinafter referred to as DB-3). Examples of ring B' include rings represented by the following group (hereinafter referred to as DB-4).

[0084] R ６ Examples of the EB-1 group include the following group (hereinafter referred to as EB-1). R ６ Examples of the EB-2 group include the following group (hereinafter referred to as EB-2). R ６ Examples of the EB-3 group include the following group (hereinafter referred to as EB-3).

[0085] A ６ is CR ２５ R ２５’ (where R ２５ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２５’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy (hereinafter referred to as FB-1). ６ is CR ２５ R ２５’ (where R ２５ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ２５’ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl (hereinafter referred to as FB-2). ６ is CR ２５ R ２５’ (where R ２５ are each independently a hydrogen atom or a substituted or unsubstituted alkyl, and R ２５’ are each independently a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as FB-3). ６ is CR ２５ R ２５’ (where R ２５ is a hydrogen atom, and R ２５’ is a hydrogen atom) (hereinafter referred to as FB-4).

[0086] s may be 0 or 1 (hereinafter referred to as GB-1), s may be 0 (hereinafter referred to as GB-2), or s may be 1 (hereinafter referred to as GB-3).

[0087] s' may be 0, 1 or 2 (hereinafter referred to as HB-1), s' may be 1 (hereinafter referred to as HB-2), or s' may be 2 (hereinafter referred to as HB-3).

[0088] R ２４ R may be a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as IB-1). ２４ R is a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as IB-2). ２４ R is a substituted or unsubstituted aromatic carbocyclic group (hereinafter referred to as IB-3). ２４ R may be a substituted or unsubstituted phenyl (hereinafter referred to as IB-4). ２４ R is phenyl substituted or unsubstituted with alkyl, halogen, haloalkyl, alkyloxy, non-aromatic carbocyclic oxy, or haloalkyloxy (hereinafter referred to as IB-5). ２４ Examples of the group include phenyl substituted or unsubstituted with alkyloxy, non-aromatic carbocyclic oxy, or haloalkyloxy (hereinafter referred to as IB-6).

[0089] R ５ R is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as JB-1). ５ is a hydrogen atom (hereinafter referred to as JB-2).

[0090] R ６’ is the formula: (In the formula, A ７ is CR ２７ R ２７’ (where R ２７ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R２７’ is a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy) (hereinafter referred to as KB-1). ６’ is the formula: (In the formula, A ７ is CR ２７ R ２７’ (where R ２７ is a hydrogen atom or a substituted or unsubstituted alkyl, and R ２７’ is a hydrogen atom or a substituted or unsubstituted alkyl) (hereinafter referred to as KB-2). ６’ is the formula: (In the formula, A ７ is CR ２７ R ２７’ (where R ２７ is a hydrogen atom, R ２７’ is a hydrogen atom) (hereinafter referred to as KB-3).

[0091] t may be 0 or 1 (hereinafter referred to as LB-1), or t may be 1 (hereinafter referred to as LB-2).

[0092] R ２６ R may be a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as MB-1). ２６ R may be a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as MB-2). ２６ is a substituted or unsubstituted aromatic carbocyclic group (hereinafter referred to as MB-3). ２６ R may be a substituted or unsubstituted phenyl (hereinafter referred to as MB-4). ２６ R is phenyl substituted or unsubstituted with alkyl, halogen, haloalkyl, alkyloxy, non-aromatic carbocyclic oxy, or haloalkyloxy (hereinafter referred to as MB-5). ２６Examples of the group include phenyl substituted or unsubstituted with alkyloxy, non-aromatic carbocyclic oxy, or haloalkyloxy (hereinafter referred to as MB-6).

[0093] R ７ is the formula: (In the formula, A ５ is CR ２８ R ２８’ (where R ２８ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２８’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy) (hereinafter referred to as NB-1). ７ is the formula: (In the formula, A ５ is CR ２８ R ２８’ (where R ２８ are each independently a hydrogen atom or a substituted or unsubstituted alkyl, and R ２８’ are each independently a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as NB-2). ７ is the formula: (In the formula, A ５ is CR ２８ R ２８’ (where R ２８ is a hydrogen atom, and R ２８’ is a hydrogen atom) (hereinafter referred to as NB-3).

[0094] u can be 0, 1 or 2 (hereinafter referred to as OB-1). u can be 1 or 2 (hereinafter referred to as OB-2). u can be 2 (hereinafter referred to as OB-3). u can be 1 (hereinafter referred to as OB-4).

[0095] R ２３R may be a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as PB-1). ２３ R may be a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as PB-2). ２３ R is a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as PB-3). ２３ R is substituted or unsubstituted pyrazolyl (hereinafter referred to as PB-4). ２３ R includes substituted or unsubstituted pyridyl (hereinafter referred to as PB-5). ２３ R is a substituted or unsubstituted aromatic carbocyclic group (hereinafter referred to as PB-6). ２３ R is exemplified by alkyl-substituted or unsubstituted pyrazolyl (hereinafter referred to as PB-7). ２３ R includes pyridyl substituted or unsubstituted with halogen (hereinafter referred to as PB-8). ２３ Examples of the phenyl group include phenyl unsubstituted or substituted with halogen, alkoxy, or hydroxy (hereinafter referred to as PB-9).

[0096] R ２１ is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as QB-1). ２１ is a hydrogen atom (hereinafter referred to as QB-2). ２１ is substituted or unsubstituted alkyl (hereinafter referred to as QB-3).

[0097] R ２２ Each of R is independently a halogen or a substituted or unsubstituted alkyl (hereinafter referred to as RB-1). ２２ are each independently substituted or unsubstituted alkyl (hereinafter referred to as RB-2). ２２are each independently a halogen (hereinafter referred to as RB-3). v is 0, 1 or 2 (hereinafter referred to as RB-1). v is 1 (hereinafter referred to as RB-2). v is 0 (hereinafter referred to as RB-3).

[0098] Particularly preferred are the following embodiments: (i) Formula (I): (In the formula, R １ is a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; A １ are each independently, CR ２ R ２’ and ２ are each independently, CR ３ R ３’ and R ２ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ３ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ３’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ２ and R ２’ and R ３ and R ３’ may be taken together with the same carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; m and n are each independently 1, 2, or 3; Ring B is a ring of the formula: (In the formula, R ４ is the formula: (In the formula, A ３ are each independently, CR １３ R １３’and ４ are each independently, CR １４ R １４’ and R １３ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １３’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １４ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １４’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; q and r are each independently 0, 1, or 2; q' and r' are each independently 1 or 2; R １０ and R １１ are each independently a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ８ is a hydrogen atom or a substituted or unsubstituted alkyl; R ９ are each independently a halogen atom or a substituted or unsubstituted alkyl group; and p is an integer of 0 to 6), or a pharmaceutically acceptable salt thereof. (In the formula, R １ is a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ２ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２’ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ３is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ３’ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２ and R ２’ and R ３ and R ３’ may be taken together with the same carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; Ring B is a ring of the formula: (In the formula, R ４ is the formula: (In the formula, A ３ are each independently, CR １３ R １３’ and ４ are each independently, CR １４ R １４’ and R １３ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １３’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １４ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R １４’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; q and r are each independently 0, 1, or 2; q' and r' are each independently 1 or 2; R １０ and R １１ are each independently a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ８ is a hydrogen atom or a substituted or unsubstituted alkyl; R ９(iii) A compound represented by formula (II): or a pharmaceutically acceptable salt thereof. (In the formula, R １ is a hydrogen atom or a substituted or unsubstituted alkyl; R ２ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２’ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ３ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ３’ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２ and R ２’ and R ３ and R ３’ may be taken together with the same carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; Ring B is a ring of the formula: (In the formula, R ４ is the formula: (In the formula, A ３ is CR １３ R １３’ and ４ is CR １４ R １４’ and R １３ is a hydrogen atom, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R １３’ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R １４ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R １４’is a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; q and r are each 1; q' and r' are each 1; R １０ and R １１ are each independently a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group; R ８ is a hydrogen atom or a substituted or unsubstituted alkyl; R ９ are each independently a halogen atom or a substituted or unsubstituted alkyl group; and p is an integer of 0 to 2), or a pharmaceutically acceptable salt thereof. (In the formula, R １ is a hydrogen atom or a substituted or unsubstituted alkyl; R ２ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２’ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ３ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ３’ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２ and R ２’ and R ３ and R ３’ may be taken together with the same carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; Ring B is a ring of the formula: (In the formula, R ４ is the formula: (In the formula, A ３ is CR １３ R １３’ and ４ is CR １４ R １４’ and R １３is a hydrogen atom, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R １３’ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R １４ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R １４’ is a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; q and r are each 1; R １０ and R １１ are each independently a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group; R ８ is a hydrogen atom or a substituted or unsubstituted alkyl; R ９ are each independently a halogen atom or a substituted or unsubstituted alkyl group; and p is an integer of 0 to 2), or a pharmaceutically acceptable salt thereof. (In the formula, R ３１ is a hydrogen atom or a C1-C3 alkyl; R ３２ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３３ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３４ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ３５ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ３２ and R ３３ and R ３４ and R ３５ may be taken together with the same carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; Ring B' is a ring of the formula: (In the formula, R ６ is the formula: (In the formula, A ６ is CR２５ R ２５’ and R ２５ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２５’ is a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; s' is 1; R ２４ is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ６ ' is the formula: (In the formula, A ７ is CR ２７ R ２７’ and R ２７ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２７’ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; t is 1; R ２６ is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ７ is the formula: (In the formula, A ５ is CR ２８ R ２８’ and R ２８ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２８’ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; u is 1; R ２３ is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group), and R ２１is a hydrogen atom or a substituted or unsubstituted alkyl; R ２２ are each independently a halogen or a substituted or unsubstituted alkyl; and v is 0, 1, or 2), or a pharmaceutically acceptable salt thereof. (In the formula, R ３１ is a hydrogen atom or a C1-C3 alkyl; R ３２ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３３ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３４ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ３５ are each independently a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl; R ３２ and R ３３ and R ３４ and R ３５ may be taken together with the same carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; Ring B' is a ring of the formula: (In the formula, R ６ is the formula: (In the formula, A ６ is CR ２５ R ２５’ and R ２５ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２５’ is a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; s' is 1; R ２４ is a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group; R ６ ' is the formula: (In the formula, A ７ is CR ２７ R ２７’ and R ２７is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２７’ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; t is 1; R ２６ is a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group; ７ is the formula: (In the formula, A ５ is CR ２８ R ２８’ and R ２８ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２８’ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; u is 1; R ２３ R is a group represented by the formula (a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group), ２１ is a hydrogen atom or a substituted or unsubstituted alkyl; R ２２ are each independently a halogen or a substituted or unsubstituted alkyl; and v is 0, 1, or 2), or a pharmaceutically acceptable salt thereof. (In the formula, R １ is a hydrogen atom or alkyl; R ２ is a hydrogen atom; R ２’ is a hydrogen atom; R ３ is a hydrogen atom; R ３’ is a hydrogen atom; Ring B is a group of the formula: (In the formula, R ４ is the formula: (In the formula, A ３ is CR １３ R １３’ and ４ is CR １４ R １４’ and R １３ is a hydrogen atom; R１３’ is a hydrogen atom; R １４ is a hydrogen atom; R １４’ is a hydrogen atom; q and r are each 1; R １０ is a 5-membered aromatic heterocyclic group substituted with a substituent group ω (substituent group ω: alkyl, haloalkyl, and non-aromatic carbocyclic group); R １１ is the formula: (In the formula, R １８ is a hydrogen atom or a halogen; R １９ is a group represented by the formula: R is an alkyloxy or haloalkyloxy; ８ is a hydrogen atom), or a pharmaceutically acceptable salt thereof.

[0099] The compounds represented by formula (I), formula (II) or formula (III) are not limited to specific isomers, and include all possible isomers (e.g., keto-enol isomers, imine-enamine isomers, diastereoisomers, optical isomers, rotamers, tautomers as described below, etc.), racemates or mixtures thereof.

[0100] One or more hydrogen, carbon and / or other atoms of the compounds of formula (I), formula (II) or formula (III) may be replaced with isotopes of hydrogen, carbon and / or other atoms, respectively. Examples of such isotopes include: ２ H. ３ H. １１ C. １３ C. １４ C. １５ N. １８ O. １７ O. ３１ P. ３２ P. ３５ S. １８ F. 123 I and ３６The isotope-substituted compounds are also useful as pharmaceuticals, and include all radiolabeled compounds of the formula (I), (II), or (III). The present invention also encompasses "radiolabeling methods" for producing the "radiolabeled compounds," which are useful as research and / or diagnostic tools in metabolism, pharmacokinetic studies, and binding assays.

[0101] Radiolabeled compounds of Formula (I), (II), or (III) can be prepared by methods well known in the art. For example, tritium-labeled compounds of Formula (I), (II), or (III) can be prepared by introducing tritium into a specific compound of Formula (I), (II), or (III) via catalytic dehalogenation using tritium. This method involves reacting an appropriately halogen-substituted precursor of Formula (I), (II), or (III) with tritium gas in the presence of a suitable catalyst, such as Pd / C, with or without a base. For other suitable methods for preparing tritium-labeled compounds, see "Isotopes in the Physical and Biomedical Sciences, Vol. 1, Labeled Compounds (Part A), Chapter 6 (1987)." １４ C-labeled compounds are １４ It can be prepared by using a raw material having C carbon.

[0102] Pharmaceutically acceptable salts of the compound represented by formula (I), formula (II) or formula (III) include, for example, salts of the compound represented by formula (I), formula (II) or formula (III) with an alkali metal (e.g., lithium, sodium, potassium, etc.), alkaline earth metal (e.g., calcium, barium, etc.), magnesium, transition metal (e.g., zinc, iron, etc.), ammonia, organic base (e.g., trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, meglumine, ethyl Examples of suitable salts include salts with carboxylic acids (e.g., diamine, pyridine, picoline, quinoline, etc.) and amino acids, or salts with inorganic acids (e.g., hydrochloric acid, sulfuric acid, nitric acid, carbonic acid, hydrobromic acid, phosphoric acid, hydroiodic acid, etc.) and organic acids (e.g., formic acid, acetic acid, propionic acid, trifluoroacetic acid, citric acid, lactic acid, tartaric acid, oxalic acid, maleic acid, fumaric acid, succinic acid, mandelic acid, glutaric acid, malic acid, benzoic acid, phthalic acid, ascorbic acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, trifluoroacetic acid, etc.). These salts can be formed by conventional methods.

[0103] The compound of the present invention represented by Formula (I), Formula (II), or Formula (III), or a pharmaceutically acceptable salt thereof, may form a solvate (e.g., a hydrate), a co-crystal, and / or a crystalline polymorph, and the present invention also encompasses such various solvates, co-crystals, and crystalline polymorphs. A "solvate" may be coordinated with a compound of Formula (I), Formula (II), or Formula (III) with any number of solvent molecules (e.g., water molecules). When a compound of Formula (I), Formula (II), or Formula (III), or a pharmaceutically acceptable salt thereof, is left in the atmosphere, it may absorb moisture, resulting in the adsorbed water adsorbing thereto or forming a hydrate. Furthermore, a crystalline polymorph may be formed by recrystallizing a compound of Formula (I), Formula (II), or Formula (III), or a pharmaceutically acceptable salt thereof. A "co-crystal" means that a compound of Formula (I), Formula (II), or Formula (III), or a salt thereof, and a counter molecule are present in the same crystal lattice, and may contain any number of counter molecules.

[0104] The compounds of the present invention represented by Formula (I), Formula (II), or Formula (III) or pharmaceutically acceptable salts thereof may form prodrugs, and the present invention also encompasses such various prodrugs. Prodrugs are derivatives of the compounds of the present invention having chemically or metabolically decomposable groups, and are compounds that become pharmaceutically active compounds of the present invention in vivo by solvolysis or under physiological conditions. Prodrugs include compounds that are converted to compounds of Formula (I), Formula (II), or Formula (III) by enzymatic oxidation, reduction, hydrolysis, etc. under physiological conditions in vivo, and compounds that are converted to compounds of Formula (I), Formula (II), or Formula (III) by hydrolysis with gastric acid, etc. Methods for selecting and preparing appropriate prodrug derivatives are described, for example, in "Design of Prodrugs, Elsevier, Amsterdam, 1985." Prodrugs may themselves be active.

[0105] When the compound represented by formula (I), formula (II) or formula (III) or a pharmaceutically acceptable salt thereof has a hydroxyl group, examples of the prodrug include acyloxy derivatives and sulfonyloxy derivatives produced by reacting the compound having a hydroxyl group with an appropriate acyl halide, an appropriate acid anhydride, an appropriate sulfonyl chloride, an appropriate sulfonyl anhydride and a mixed anhydride, or by reacting the compound using a condensing agent. For example, CH ３ COO-, C ２ H ５ COO-, tert-BuCOO-, C １５ H ３１ COO-, PhCOO-, (m-NaOOCPh)COO-, NaOOCCH ２ CH ２ COO-, CH ３ CH(NH ２ ) COO-, CH ２ N (CH ３ ) ２ COO-, CH ３ SO ３ -, CH ３ CH ２ SO３ -, CF ３ SO ３ -, CH ２ FSO ３ -, CF ３ CH ２ SO ３ -, p-CH ３ O-PhSO ３ -, PhSO ３ -, p-CH ３ PhSO ３ - are some examples.

[0106] The compounds according to the present invention have serotonin 5-HT2A receptor antagonistic and / or inverse agonistic activity and are therefore useful as therapeutic and / or preventive agents for diseases involving the serotonin 5-HT2A receptor. Examples of diseases involving the serotonin 5-HT2A receptor include serotonin-mediated diseases such as hallucinations and delusions associated with Parkinson's disease, hallucinations and delusions associated with dementia, hallucinations and delusions associated with schizophrenia, hallucinations and delusions associated with depression, hallucinations and delusions associated with neurodegenerative diseases, depression, schizophrenia, autism, addiction, dyskinesia, sleep disorders, irritability associated with Parkinson's disease, irritability associated with dementia, irritability associated with schizophrenia, and sexual dysfunction. Preferred examples include hallucinations and delusions associated with Parkinson's disease, hallucinations and delusions associated with dementia, hallucinations and delusions associated with schizophrenia, hallucinations and delusions associated with depression, irritability associated with Parkinson's disease, irritability associated with dementia, and irritability associated with schizophrenia. More preferred examples include hallucinations and delusions associated with Parkinson's disease and hallucinations and delusions associated with dementia. The term "serotonin 5-HT2A receptor antagonist and / or inverse agonist" refers to a pharmaceutical product having serotonin 5-HT2A receptor antagonistic and / or inverse agonist activity. The term "serotonin 5-HT2A receptor antagonist and / or inverse agonist composition" refers to a composition having serotonin 5-HT2A receptor antagonistic and / or inverse agonist activity, and is not limited to pharmaceutical use.

[0107] (Method for Producing the Compound of the Present Invention) The compound of the present invention represented by formula (I), formula (II) or formula (III) can be produced, for example, by the general synthesis method shown below. Extraction, purification, etc. may be carried out by treatments performed in ordinary organic chemistry experiments. The compound of the present invention can be synthesized by referring to methods known in the art.

[0108] General synthesis method 1 (Method A) where PG is a suitable protecting group for an amino group such as Boc, Z, etc., and R ４０ is alkyl, X is a leaving group such as halogen, and R ４１ and R ４２ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ４１ and R ４２may, together with the same carbon atom to which it is attached, form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring, and other symbols are as defined in item (1) above.) Step 1: Compound (a-3) can be obtained by reacting compounds (a-1) and (a-2) in the presence of an acid, either without a solvent or in a suitable solvent. Examples of acids include hydrochloric acid, sulfuric acid, TFA, formic acid, trifluoroborane, toluenesulfonic acid, and pyridinium toluenesulfonate. These acids can be used in an amount of 0.1 molar equivalents or more, preferably 0.1 to 10 molar equivalents, relative to compound (a-1). Reaction solvents include methanol, ethanol, tert-butanol, isopropanol, toluene, benzene, xylene, cyclohexane, hexane, tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane, chloroform, dichloromethane, DMF, DMSO, NMP, acetonitrile, and pyridine, and these can be used alone or in combination. The reaction temperature is 0 to 200°C, preferably 20 to 120°C. The reaction time is 0.1 to 24 hours, preferably 0.5 to 6 hours. Step 2: Compound (a-4) can be obtained by reacting compound (a-3) with hydroxylamine. 1 to 30 molar equivalents of hydroxylamine can be used. The reaction temperature is 0°C to the reflux temperature of the solvent, preferably 40 to 80°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of reaction solvents include methanol, ethanol, 2-propanol, tetrahydrofuran, toluene, chloroform, DMF, DMA, etc., which can be used alone or in combination. Step 3: Compound (a-5) can be obtained by reacting compound (a-4) with a condensing agent and 2-(trimethylsilyl)ethanol in the presence or absence of a base, followed by reacting with a fluoride. Examples of the base include NMM and triethylamine, which can be used in an amount of 1 to 10 molar equivalents relative to the compound (a-4). ３Examples of suitable solvents include P, CDI, MsCl, and TsCl, and these can be used in an amount of 1 to 10 molar equivalents relative to compound (a-4). 2-(trimethylsilyl)ethanol can be used in an amount of 1 to 10 molar equivalents relative to compound (a-4). Examples of suitable fluorides include TBAF, KF, and pyridinium fluoride, and these can be used in an amount of 1 to 10 molar equivalents relative to compound (a-4). The reaction temperature is 0°C to the reflux temperature of the solvent, preferably 40 to 80°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of suitable reaction solvents include tetrahydrofuran, toluene, chloroform, DMF, and DMA, and these can be used alone or in combination. Step 4: Compound (a-5) and compound (a-6) are reacted in the presence or absence of a condensing agent, followed by reduction with a reducing agent to obtain compound (a-7). Condensing agents include 4-toluenesulfonic acid, methanesulfonic acid, acetic acid, anhydrous magnesium sulfate, tetraisopropyl orthotitanate, titanium tetrachloride, molecular sieves, etc., and can be used in an amount of 1 to 10 molar equivalents relative to compound (a-5). Compound (a-6) can be used in an amount of 1 to 10 molar equivalents relative to compound (a-5). Bases include sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, calcium carbonate, cesium carbonate, pyridine, triethylamine, DMAP, etc., and can be used in an amount of 1 to 5 molar equivalents relative to compound (a-5). Reducing agents include sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, borane and its complexes, lithium borohydride, potassium borohydride, diisobutylaluminum hydride, etc., and can be used in an amount of 1 to 10 molar equivalents relative to compound (a-5). The reaction temperature is −78°C to the reflux temperature of the solvent, preferably 25 to 100°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of the reaction solvent include tetrahydrofuran, toluene, dichloromethane, chloroform, methanol, ethanol, etc., which can be used alone or in combination.Step 5: Compound (a-7) can be reacted with 2-(chloromethoxy)ethyltrimethylsilane in the presence of a base to obtain compound (a-8). 2-(chloromethoxy)ethyltrimethylsilane can be used in an amount of 1 to 10 molar equivalents relative to compound (a-7). Examples of bases include sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, calcium carbonate, cesium carbonate, pyridine, triethylamine, and DMAP, and can be used in an amount of 1 to 5 molar equivalents relative to compound (a-7). The reaction temperature is −10°C to 80°C, preferably 0°C to 25°C. The reaction time is 0.5 hours to 24 hours, preferably 0.5 to 6 hours. Examples of reaction solvents include DMF, DMA, DMSO, tetrahydrofuran, dioxane, and acetonitrile, which can be used alone or in combination. Step 6: Compound (a-10) can be obtained by reacting compound (a-9) with compound (a-8) in the presence of a base. The reaction temperature is 0°C to 40°C, preferably 0°C to 20°C. The reaction time is 0.5 to 12 hours, preferably 1 to 6 hours. Examples of bases that can be used include sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, and sodium hydride. Examples of reaction solvents include DMF, DMA, DMSO, tetrahydrofuran, dioxane, and acetonitrile, which can be used alone or in combination. Step 7: Compound (a-11) can be obtained by reacting compound (a-10) with a fluoride. Examples of fluorides include TBAF, KF, and pyridinium fluoride, and these can be used in an amount of 1 to 10 molar equivalents relative to compound (a-10). The reaction temperature is 0°C to the reflux temperature of the solvent, preferably 0 to 25°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of reaction solvents include tetrahydrofuran, toluene, chloroform, DMF, DMA, etc., and these can be used alone or in combination.Step 8: Compound (a-12) can be obtained by reacting compound (a-11) in the presence of an acid, either without a solvent or in a suitable solvent, or by reacting compound (a-11) with hydrogen gas in the presence of a metal catalyst. Examples of acids include hydrochloric acid, sulfuric acid, TFA, formic acid, and trifluoroborane. These acids can be used in an amount of 1.0 molar equivalent or more, preferably 1.0 to 30 molar equivalents, relative to compound (a-11). Examples of metal catalysts include palladium-carbon, platinum oxide, rhodium-aluminum oxide, and chlorotris(triphenylphosphine)rhodium(I). These metal catalysts can be used in an amount of 0.01 to 100 weight percent relative to compound (a-11). The hydrogen pressure can be 1 to 50 atmospheres. Cyclohexene, 1,4-cyclohexadiene, formic acid, and ammonium formate can also be used as hydrogen sources. Examples of reaction solvents include methanol, ethanol, tert-butanol, isopropanol, toluene, benzene, xylene, cyclohexane, hexane, tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane, etc.), chloroform, dichloromethane, DMF, DMSO, NMP, acetonitrile, pyridine, etc., and these can be used alone or in combination. The reaction temperature is 0 to 80°C, preferably 0 to 20°C. The reaction time is 0.1 to 24 hours, preferably 0.5 to 6 hours. Step 9: Compound (I-a) can be obtained by reacting compound (a-12) and compound (a-13) with an appropriate reducing agent, and optionally acetic acid, in an appropriate solvent. Examples of reducing agents include sodium triacetoxyborohydride and sodium cyanoborohydride, and can be used in an amount of 1.0 molar equivalent or more, preferably 1.0 to 2.0 molar equivalents, relative to compound (a-12). Acetic acid can be used in an amount of 1.0 molar equivalent or more, preferably 1.0 to 2.0 molar equivalents, relative to compound (a-12).Examples of reaction solvents include methanol, ethanol, tert-butanol, isopropanol, toluene, benzene, xylene, cyclohexane, hexane, tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane, chloroform, dichloromethane, DMF, DMSO, NMP, acetonitrile, and pyridine, and these can be used alone or in combination. The reaction temperature is 0 to 80°C, preferably 0 to 20°C. The reaction time is 0.1 to 24 hours, preferably 0.5 to 6 hours.

[0109] General synthesis method 2 (Method B) (The symbols in the formula are as defined in Method A or item (1) above.) Step 1: Compound (b-2) or (b-2') can be obtained by reacting compound (a-11) with compound (b-1) in the presence of a base. The reaction temperature is 0°C to 40°C, preferably 0°C to 20°C. The reaction time is 0.5 hours to 12 hours, preferably 1 hour to 6 hours. Usable bases include sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium hydride, and the like. Reaction solvents include methanol, ethanol, water, acetone, acetonitrile, tetrahydrofuran, and the like, which can be used alone or in combination. Reaction solvents include DMF, DMA, DMSO, tetrahydrofuran, dioxane, acetonitrile, and the like, which can be used alone or in combination. Step 2: Compound (b-3) or (b-3') can be obtained using compound (b-2) or (b-2') as the starting material in the same manner as in step 8 of Method A. Step 3: Compound (I-b) or (I-b') can be obtained using compound (b-3) or (b-3') as the starting material in the same manner as in step 9 of Method A.

[0110] General synthesis method 3 (C method) (The symbols in the formula are as defined in Method A or item (1) above.) Step 1: Compound (c-2) can be obtained by reacting compound (a-8) with compound (c-1) in the presence of a base. The reaction temperature is 0°C to 40°C, preferably 0°C to 20°C. The reaction time is 0.5 to 12 hours, preferably 1 to 6 hours. Usable bases include sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, and sodium hydride. Reaction solvents include DMF, DMA, DMSO, tetrahydrofuran, dioxane, and acetonitrile, which can be used alone or in combination. Step 2: Compound (c-3) can be obtained from compound (c-2) using a method similar to Step 7 in Method A above. Step 3: Compound (c-4) can be obtained from compound (c-3) using a method similar to Step 8 in Method A above. Step 4 Compound (Ic) can be obtained from compound (c-4) in the same manner as in Step 9 of Method A above.

[0111] General synthesis method 4 (D method) (The symbols in the formula are as defined in Method A or (1) above.) Step 1: Compound (d-2) can be obtained by reacting compound (d-1) with Lawesson's reagent and then with ethanolamine. The reaction temperature is 0 to 200°C, preferably 60 to 140°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of reaction solvents include tetrahydrofuran, DMF, DMA, DMSO, toluene, etc., which can be used alone or in combination. Step 2: Compound (d-3) can be obtained by adding methyl iodide to compound (d-2) in the presence of a base. Methyl iodide can be used in an amount of 1 to 10 molar equivalents relative to compound (d-2). Examples of bases include DIEA and triethylamine, which can be used in an amount of 1 to 5 molar equivalents relative to compound (d-2). The reaction temperature is −78°C to the reflux temperature of the solvent, preferably 0 to 25°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of reaction solvents include methanol, ethanol, tetrahydrofuran, DMF, DMA, toluene, dichloromethane, and chloroform, which can be used alone or in combination. Step 3: Compound (d-5) can be obtained by reacting compound (d-3) with compound (d-4). The reaction temperature is 0°C to the reflux temperature of the solvent, preferably 80 to 130°C. The reaction time is 0.5 to 48 hours, preferably 1 to 12 hours. Examples of reaction solvents include acetic acid, DMF, DMA, DMSO, tetrahydrofuran, toluene, t-BuOH, and t-amyl alcohol, which can be used alone or in combination. Step 4: Compound (d-6) can be obtained using a method similar to that in Step 8 of Method A above, starting from compound (d-5). Step 5: Compound (I-d) can be obtained using a method similar to that in Step 9 of Method A above, starting from compound (d-6).

[0112] General synthesis method 5 (E method) where PG is a suitable protecting group for an amino group such as Boc, Z, etc., and R ４３ and R ４４are each independently a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ４３ and R ４４may, together with the same carbon atom to which they are attached, form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring, and other symbols are as defined in item (14) above. Step 1: Compound (e-2) can be obtained by reacting compound (e-1) with hydroxylamine or hydroxylamine chloride in the presence or absence of a base. Examples of bases include sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, calcium carbonate, cesium carbonate, pyridine, triethylamine, DMAP, etc., and can be used in an amount of 1 to 5 molar equivalents relative to compound (e-1). The reaction temperature is −78°C to the reflux temperature of the solvent, preferably 0 to 25°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of reaction solvents include water, tetrahydrofuran, DMF, DMA, DMSO, toluene, dichloromethane, chloroform, methanol, ethanol, etc., and these can be used alone or in combination. Step 2: Compound (e-3) can be obtained by adding N-chlorosuccinimide to compound (e-2). N-chlorosuccinimide can be used in an amount of 1 to 10 molar equivalents relative to compound (e-2). The reaction temperature is −78°C to the reflux temperature of the solvent, preferably 0 to 25°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of reaction solvents include tetrahydrofuran, DMF, DMA, toluene, dichloromethane, and chloroform, which can be used alone or in combination. Step 3: Compound (e-4) can be condensed with compound (e-5) or a salt thereof in the presence or absence of a condensing agent to obtain compound (e-6). Examples of condensing agents include anhydrous magnesium sulfate, anhydrous sodium sulfate, titanium tetrachloride, and molecular sieves, which can be used in an amount of 1 to 10 molar equivalents relative to compound (e-4). The reaction temperature is −78°C to the reflux temperature of the solvent, preferably 25 to 120°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours.Examples of reaction solvents include tetrahydrofuran, DMF, DMA, DMSO, toluene, dichloromethane, chloroform, methanol, ethanol, etc., and these can be used alone or in combination. Step 4: Compound (e-7) can be obtained by reacting compound (e-6) with compound (e-3) in the presence of a base. Examples of bases include sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, calcium carbonate, cesium carbonate, pyridine, triethylamine, DMAP, etc., and these can be used in an amount of 1 to 5 molar equivalents relative to compound (e-6). The reaction temperature is −78°C to the reflux temperature of the solvent, preferably 0 to 25°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of reaction solvents include tetrahydrofuran, DMF, DMA, DMSO, toluene, dichloromethane, chloroform, water, etc., and these can be used alone or in combination. Step 5: Compound (e-8) can be obtained from compound (e-7) using a method similar to that of Step 8 of Method A above. Step 6 Compound (Ie) can be obtained from compound (e-8) in the same manner as in Step 9 of Method A above.

[0113] General synthesis method 6 (F method) (The symbols in the formula are as defined in Method E above.) Step 1: Compound (f-2) can be obtained by reacting compound (f-1) with aqueous ammonia. Ammonia can be used in an amount of 1 to 100 molar equivalents or more relative to compound (f-1). Examples of reaction solvents include methanol, ethanol, DMF, and DMA, which can be used alone or in combination. The reaction temperature is −78 to 100°C, preferably 0 to 25°C. The reaction time is 0.1 to 24 hours, preferably 0.5 to 6 hours. Step 2: Compound (f-3) can be obtained by reacting compound (f-2) in the presence of an acid, either solventless or in a suitable solvent. Examples of acids include hydrochloric acid, sulfuric acid, TFA, formic acid, and trifluoroborane, which can be used in an amount of 1.0 molar equivalent or more, preferably 1.0 to 30 molar equivalents, relative to compound (f-2). Examples of reaction solvents include tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane, chloroform, and dichloromethane, and these can be used alone or in combination. The reaction temperature is 0 to 80°C, preferably 0 to 20°C. The reaction time is 0.1 to 24 hours, preferably 0.5 to 6 hours. Step 3: Compound (f-5) can be obtained by reacting compound (f-3) with compound (f-4) in the presence of a condensing agent. Examples of condensing agents include acetic acid, anhydrous magnesium sulfate, and molecular sieves, and these can be used in an amount of 0.1 to 10 molar equivalents relative to compound (f-3). The reaction temperature is 0 to 150°C, preferably 80 to 120°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of reaction solvents include 2-propanol, tetrahydrofuran, toluene, DMF, and DMA, and these can be used alone or in combination. Step 4: Compound (f-5) and compound (f-6) are condensed in the presence or absence of a condensing agent, followed by reduction with a reducing agent to obtain compound (f-7). Examples of the condensing agent include 4-toluenesulfonic acid, methanesulfonic acid, acetic acid, anhydrous magnesium sulfate, tetraisopropyl orthotitanate, titanium tetrachloride, and molecular sieves, and these can be used in an amount of 1 to 10 molar equivalents relative to compound (f-5).Examples of reducing agents include sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, borane and its complexes, lithium borohydride, potassium borohydride, and diisobutylaluminum hydride. These reducing agents can be used in an amount of 1 to 10 molar equivalents relative to compound (f-5). The reaction temperature is −78°C to the reflux temperature of the solvent, preferably 0 to 25°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of reaction solvents include acetic acid, methanol, ethanol, tetrahydrofuran, dichloromethane, and chloroform, which can be used alone or in combination. Step 5: Compound (f-8) can be obtained from compound (f-7) using a method similar to that in Step 8 of Method A above. Step 6: Compound (If) can be obtained from compound (f-8) using a method similar to that in Step 9 of Method A above.

[0114] General synthesis method 7 (G method) (In the formula, X represents a leaving group such as a halogen atom, and the other symbols are as defined in Method E above.) Step 1: Compound (g-2) can be obtained by reacting compound (g-1) with monoethyl malonate and ammonium acetate. Monoethyl malonate and ammonium acetate can be used in an amount of 1 to 10 molar equivalents or more relative to compound (g-1). Examples of reaction solvents include methanol, ethanol, DMF, and DMA, which can be used alone or in combination. The reaction temperature is −78 to 100°C, preferably 60 to 80°C. The reaction time is 0.1 to 24 hours, preferably 0.5 to 6 hours. Step 2: Compound (g-3) can be obtained by reacting compound (g-2) with benzoyl isothiocyanate and then a base. Benzoyl isothiocyanate can be used in an amount of 1 to 10 molar equivalents relative to compound (g-2). Examples of bases include sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, calcium carbonate, and cesium carbonate, and can be used in an amount of 1 to 5 molar equivalents relative to compound (g-2). The reaction temperature is 0 to 150°C, preferably 0 to 80°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of reaction solvents include dichloromethane, ethanol, 2-propanol, tetrahydrofuran, and toluene, and these can be used alone or in combination. Step 3: Compound (g-4) can be obtained by adding methyl iodide to compound (g-3) in the presence of a base. Methyl iodide can be used in an amount of 1 to 10 molar equivalents relative to compound (g-3). Examples of bases include DIEA and triethylamine, and can be used in an amount of 1 to 5 molar equivalents relative to compound (g-3). The reaction temperature is −78°C to the reflux temperature of the solvent, preferably 0 to 25°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of the reaction solvent include methanol, ethanol, tetrahydrofuran, DMF, DMA, toluene, dichloromethane, chloroform, etc., which can be used alone or in combination. Step 4: Compound (g-6) can be obtained by reacting compound (g-4) with compound (g-5).The reaction temperature is 0°C to the reflux temperature of the solvent, preferably 80°C to 130°C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of reaction solvents include acetic acid, DMF, DMA, DMSO, tetrahydrofuran, toluene, t-BuOH, and t-amyl alcohol, which can be used alone or in combination. Step 5: Compound (g-8) can be obtained by reacting compound (g-7) with compound (g-6) in the presence of a base. The reaction temperature is 0°C to 40°C, preferably 0°C to 20°C. The reaction time is 0.5 to 12 hours, preferably 1 to 6 hours. Examples of bases that can be used include sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, and sodium hydride. Examples of reaction solvents include methanol, ethanol, water, acetone, acetonitrile, and tetrahydrofuran, which can be used alone or in combination. Examples of reaction solvents include DMF, DMA, DMSO, tetrahydrofuran, dioxane, acetonitrile, etc., which can be used alone or in combination. Step 5: Compound (g-9) can be obtained using compound (g-8) as a starting material in the same manner as in Step 8 of Method A above. Step 6: Compound (I-g) can be obtained using compound (g-9) as a starting material in the same manner as in Step 9 of Method A above.

[0115] General synthesis method 8 (H method) (In the formula, R ５０ are each independently phenyl, tert-butyl, isopropyl, or methyl; p' is 0 or 1; R ９are each independently substituted or unsubstituted alkyl, and other symbols are as defined in Method A above.) Step 1: Compound (h-3) can be obtained by reacting compound (h-1) with silylating agent (h-2) in the presence of a base. Examples of silylating agents include tert-butyldimethylchlorosilane, triisopropylsilyl chloride, tert-butyldiphenylchlorosilane, etc., and can be used in an amount of 1 to 10 molar equivalents or more relative to compound (h-1). Examples of bases include triethylamine, imidazole, pyridine, DMAP, etc., and can be used in an amount of 1 to 5 molar equivalents relative to compound (h-1). Examples of reaction solvents include dichloromethane, chloroform, DMF, DMA, toluene, tetrahydrofuran, etc., and can be used alone or in combination. The reaction temperature is -78 to 100°C, preferably 0 to 25°C. The reaction time is 0.1 to 24 hours, preferably 0.5 to 6 hours. Step 2: Compound (h-5) can be obtained by reacting compound (h-3) and compound (h-4) with an acylating agent in the presence or absence of a base. Examples of acylating agents include diphosgene, triphosgene, CDI, etc., and can be used in an amount of 1 to 10 molar equivalents or more relative to compound (h-3). Examples of bases include sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, calcium carbonate, cesium carbonate, pyridine, triethylamine, DMAP, etc., and can be used in an amount of 1 to 5 molar equivalents relative to compound (h-3). Examples of reaction solvents include water, ethyl acetate, dichloromethane, tetrahydrofuran, etc., and can be used alone or in combination. The reaction temperature is −78 to 100°C, preferably 0 to 25°C. The reaction time is 0.1 to 24 hours, preferably 0.5 to 6 hours. Step 3: Compound (h-6) can be obtained by reacting compound (h-5) with a fluoride. Examples of the fluoride include TBAF, KF, and pyridinium fluoride, and can be used in an amount of 1 to 10 molar equivalents relative to compound (h-5). The reaction temperature is 0° C. to the reflux temperature of the solvent, preferably 0 to 25° C. The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours.Examples of reaction solvents include tetrahydrofuran, toluene, chloroform, DMF, DMA, etc., and these can be used alone or in combination. Step 4: Compound (h-7) can be obtained by reacting compound (h-6) with a condensing agent. The reaction temperature is −78 to 150°C, preferably −78 to 80°C. Examples of condensing agents include DAST, dicyclohexylcarbodiimide, carbonyldiimidazole, dicyclohexylcarbodiimide-N-hydroxybenzotriazole, EDC, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, HATU, etc., and these can be used in an amount of 1 to 5 molar equivalents relative to compound (h-6). The reaction time is 0.5 to 48 hours, preferably 1 to 6 hours. Examples of reaction solvents include dichloromethane, ethanol, 2-propanol, tetrahydrofuran, toluene, etc., and these can be used alone or in combination. Step 5: Compound (h-8) can be obtained using compound (h-7) as a starting material in the same manner as in Step 8 of Method A. Step 6: Compound (I-h) can be obtained using compound (h-8) as a starting material in the same manner as in Step 9 of Method A.

[0116] General synthesis method 9 (Method I) where PG is a suitable protecting group for an amino group such as Boc, Z, etc., and R ４１ and R ４２ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ４１ and R ４２may, together with the same carbon atom to which it is attached, form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring, and other symbols are as defined in item (1) above.) Step 1: Compound (i-2) can be obtained by reacting compound (a-1) with compound (i-1) in the presence of an acid. The reaction temperature is 30°C to 150°C, preferably 100°C to 130°C. The reaction time is 0.5 hours to 12 hours, preferably 1 hour to 6 hours. Examples of acids include hydrochloric acid, sulfuric acid, TFA, formic acid, trifluoroborane, p-TsOH, and PPTS, and these acids can be used in an amount of 0.1 molar equivalents or more, preferably 0.1 to 1 molar equivalents, relative to compound (a-1). Examples of reaction solvents include methanol, ethanol, 2-propanol, t-butyl alcohol, water, acetone, acetonitrile, tetrahydrofuran, and dioxane, and these can be used alone or in combination. Step 2: Compound (i-4) can be obtained by reacting compound (i-2) with compound (i-3) in the presence of a base. The reaction temperature is 30°C to 150°C, preferably 100°C to 130°C. The reaction time is 1 hour to 24 hours, preferably 3 hours to 9 hours. Examples of bases include pyridine, triethylamine, DIPEA, DMAP, etc., and can be used in an amount of 1 to 5 molar equivalents relative to compound (i-2). Examples of reaction solvents include DMF, DMA, DMSO, tetrahydrofuran, dioxane, acetonitrile, etc., and these can be used alone or in combination. Step 3: Compound (i-5) can be obtained using a method similar to Step 8 in Method A above, starting from compound (i-4). Step 4: Compound (I-i) can be obtained using a method similar to Step 9 in Method A above, starting from compound (i-5).

[0117] The compounds of the present invention have serotonin 5-HT2A receptor antagonistic and / or inverse agonistic activity and are therefore useful as therapeutic and / or preventive agents for hallucinations and delusions associated with Parkinson's disease and / or dementia. Furthermore, the compounds of the present invention are useful as pharmaceuticals and preferably have one or more of the following excellent characteristics: a) weak inhibitory activity against CYP enzymes (e.g., CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, etc.); b) good pharmacokinetics, such as high bioavailability and moderate clearance; c) high metabolic stability; d) no irreversible inhibitory activity against CYP enzymes (e.g., CYP3A4) within the concentration ranges of the measurement conditions described herein; e) no mutagenicity; f) low cardiovascular risk; g) high solubility; and h) high serotonin 5-HT2A receptor binding ability. i) High serotonin 5-HT2C receptor binding ability, j) High brain penetration, k) Low P-gp substrate.

[0118] The pharmaceutical composition of the present invention can be administered orally or parenterally, including transdermal, subcutaneous, intravenous, intraarterial, intramuscular, intraperitoneal, transmucosal, inhalation, nasal, ophthalmic, otic, and vaginal administration.

[0119] For oral administration, the composition may be prepared and administered in any of the commonly used dosage forms, such as solid preparations for internal use (e.g., tablets, powders, granules, capsules, pills, films, etc.) and liquid preparations for internal use (e.g., suspensions, emulsions, elixirs, syrups, lemonades, spirits, perfumes, extracts, decoctions, tinctures, etc.), according to conventional methods. Tablets may be sugar-coated tablets, film-coated tablets, enteric-coated tablets, sustained-release tablets, troches, sublingual tablets, buccal tablets, chewable tablets, or orally disintegrating tablets; powders and granules may be dry syrups; and capsules may be soft capsules, microcapsules, or sustained-release capsules.

[0120] In the case of parenteral administration, the compound can be suitably administered in any of the commonly used dosage forms, such as injections, infusions, and topical preparations (e.g., eye drops, nasal drops, ear drops, aerosols, inhalants, lotions, infusions, liniments, mouthwashes, enemas, ointments, plasters, jellies, creams, patches, poultices, powders for topical use, suppositories, etc.). Injections may be emulsions such as O / W, W / O, O / W / O, and W / O / W types.

[0121] Pharmaceutical compositions can be prepared by mixing an effective amount of the compound of the present invention with various pharmaceutical additives, such as excipients, binders, disintegrants, and lubricants, appropriate for the dosage form, as needed. Furthermore, by appropriately modifying the effective amount of the compound of the present invention, the dosage form, and / or the various pharmaceutical additives, the pharmaceutical composition can also be prepared as a pharmaceutical composition for pediatrics, the elderly, critically ill patients, or surgical patients. For example, pediatric pharmaceutical compositions can be administered to newborns (less than 4 weeks old), infants (4 weeks old to less than 1 year old), toddlers (1 year old to less than 7 years old), children (7 years old to less than 15 years old), or patients aged 15 to 18 years. For example, pharmaceutical compositions for the elderly can be administered to patients aged 65 years or older.

[0122] The dosage of the pharmaceutical composition of the present invention is desirably determined taking into consideration the patient's age, body weight, type and severity of the disease, route of administration, etc., but when administered orally, it is usually 0.05 to 100 mg / kg / day, preferably 0.1 to 10 mg / kg / day. When administered parenterally, it varies greatly depending on the route of administration, but is usually 0.005 to 10 mg / kg / day, preferably 0.01 to 1 mg / kg / day. This dosage can be administered once or in divided doses several times a day.

[0123] The compound according to the present invention can be used in combination with an anti-Parkinson's drug, an anti-Alzheimer's drug, an antipsychotic drug, or an antidepressant drug (hereinafter referred to as a concomitant drug) for the purpose of enhancing the effect of the compound or reducing the dosage of the compound. In this case, the administration timing of the compound according to the present invention and the concomitant drug is not limited, and they may be administered to the subject simultaneously or at staggered times. Furthermore, the compound according to the present invention and the concomitant drug may be administered as two or more types of preparations containing the respective active ingredients, or as a single preparation containing these active ingredients.

[0124] The dose of the concomitant drug can be appropriately selected based on the dose used clinically. The compounding ratio of the compound of the present invention to the concomitant drug can be appropriately selected depending on the administration subject, administration route, target disease, symptoms, combination, etc. For example, when the administration subject is a human, 0.01 to 100 parts by weight of the concomitant drug may be used per 1 part by weight of the compound of the present invention.

[0125] Examples of anti-Parkinson's disease drugs include levodopa preparations, etc. Examples of anti-Alzheimer's drugs include donepezil, etc. Examples of antipsychotic drugs include quetiapine, etc. Examples of antidepressants include escitalopram, etc.

[0126] The present invention will be explained in more detail below with reference to Examples, Reference Examples and Test Examples, but the present invention is not limited to these.

[0127] The abbreviations used in this specification have the following meanings: CDCl3: deuterated chloroform DMSO-D6: deuterated dimethyl sulfoxide Boc: tert-butoxycarbonyl Z: benzyloxycarbonyl Cbz: benzyloxycarbonyl SEM: 2-(trimethylsilyl)ethoxymethyl DMF: N,N-dimethylformamide DMSO: dimethyl sulfoxide NMP: N-methylpyrrolidone DMA: N,N-dimethylacetamide NMM: N-methylmorpholine T ３P: 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide CDI: carbonyldiimidazole MsCl: methanesulfonyl chloride TsCl: paratoluenesulfonyl chloride TBAF: tetrabutylammonium fluoride KF: potassium fluoride DMAP: 4-dimethylaminopyridine TFA: trifluoroacetic acid DIEA: N,N-diisopropylethylamine CDI: carbonyldiimidazole EDC: 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide HATU: O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate DAST: N,N-diethylaminosulfur trifluoride THF: tetrahydrofuran DIAD: diisopropyl azodicarboxylate DIPEA: N,N-diisopropylethylamine TBS: tert-butyldimethylsilyl PPTS: pyridinium paratoluenesulfonate

[0128] (Method for identifying compounds) NMR analysis obtained in each example was carried out at 400 MHz, and DMSO-d ６ , CDCl ３Measurement was performed using a solvent other than 100% solvent [B]. NMR data may not include all measured peaks. RT in the specification refers to the retention time in LC / MS (liquid chromatography / mass spectrometry), and was measured under the following conditions. (Measurement Condition 1) Column: Shim-pack XR-ODS (2.2 μm i.d. 3.0 x 50 mm) (Shimadzu) Flow rate: 1.6 mL / min UV detection wavelength: 254 nm Mobile phase: [A] is an aqueous solution containing 0.1% formic acid, [B] is an acetonitrile solution containing 0.1% formic acid Gradient: A linear gradient of 10%-100% solvent [B] was performed over 3 minutes, followed by maintaining 100% solvent [B] for 0.5 minutes. (Measurement Condition 2) Column: ACQUITY UPLC (registered trademark) BEH C18 (1.7 μm i.d. 2.1×50 mm) (Waters) Flow rate: 0.8 mL / min UV detection wavelength: 254 nm Mobile phase: [A] is an aqueous solution containing 0.1% formic acid, [B] is an acetonitrile solution containing 0.1% formic acid Gradient: A linear gradient of 5%-100% solvent [B] was performed over 3.5 minutes, followed by maintaining 100% solvent [B] for 0.5 minutes. (Measurement Condition 3) Column: ACQUITY UPLC (registered trademark) BEH C18 (1.7 μm i.d. 2.1 x 50 mm) (Waters) Flow rate: 0.8 mL / min UV detection wavelength: 254 nm Mobile phase: [A] is an aqueous solution containing 10 mM ammonium carbonate, [B] is acetonitrile Gradient: A linear gradient of 5%-100% solvent [B] was performed over 3.5 minutes, followed by maintaining 100% solvent [B] for 0.5 minutes. In the specification, the term MS (m / z) refers to a value observed by mass spectrometry.

[0129] Synthesis of compound (I-009) Step 1: Synthesis of Compound 2 Ethyl aminohydroxyiminoacetate (25.0 g, 189 mmol) and Compound 1 (40.1 g, 172 mmol) were dissolved in 2-propanol (250 mL), pyridinium p-toluenesulfonate (8.65 g, 34.4 mmol) was added, and the mixture was stirred at 100°C for 5 hours. The mixture was allowed to cool to room temperature with stirring, and water (750 mL) was added to the resulting suspension, followed by stirring for 30 minutes. The precipitated solid was collected by filtration, washed three times with 2-propanol / water (1:3) (50 mL), and air-dried overnight to obtain 137 g of a white solid. The resulting solid was suspended in 2-propanol (200 mL), and 50% aqueous hydroxylamine solution (114 g, 1720 mmol) was added. The mixture was stirred at 75°C for 10 minutes. 2-Propanol (100 mL) was added, followed by stirring at room temperature for 30 minutes. The precipitated solid was collected by filtration and washed with 2-propanol (150 mL). The resulting solid was dried under reduced pressure with heating to obtain compound 2 (29.6 g, yield 52%) as a white solid. 1H-NMR (DMSO-D6) δ: 1.59-1.79 (m, 4H), 3.17-3.46 (m, 2H), 3.61-3.81 (m, 2H), 5.07 (s, 2H), 5.60 (s, 1H), 6.41 (s, 1H), 7.25-7.64 (m, 6H). Step 2: Synthesis of compound 3 Compound 2 (8.61 g, 25.8 mmol) was suspended in THF (86 mL), and N-methylmorpholine (7.08 mL, 64.4 mmol) was added. Then, under ice cooling, a 50% 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide / ethyl acetate solution (38.3 mL, 64.4 mmol) was added over approximately 7 minutes, and the mixture was stirred at room temperature for 1 hour. 2-(Trimethylsilyl)ethanol (18.4 mL, 129 mmol) was added, and the mixture was stirred at 60°C for 100 minutes. After adding 20% ​​aqueous potassium carbonate solution (170 mL), the mixture was extracted with ethyl acetate, the organic layer was washed with water, and the solvent was evaporated under reduced pressure. The resulting solid was suspended in methanol, collected by filtration, and dried under reduced pressure with heating to obtain compound 3 (6.54 g, yield 58%) as a white solid.H-NMR (DMSO-D) δ: 0.00 (s, 9H), 0.95 (t, J = 8.4 Hz, 2H), 1.64-1.79 (m, 4H), 2.87-3.15 (m, 3H), 3.75-3.89 (m, 2H), 4.13 (t, J = 8.4 Hz, 2H), 5.05 (s, 2H), 7.23-7.41 (m, 5H), 10.29 (s, 1H). Step 3 Synthesis of Compound 4 Compound 3 (5.51 g, 12.9 mmol) was suspended in THF (12.7 mL), and a 1 mol / L tetrabutylammonium fluoride / THF solution (15.2 mL, 15.2 mmol) was added, followed by heating to reflux for 2 hours. A 1 mol / L tetrabutylammonium fluoride / THF solution (3.80 mL, 3.80 mmol) was added again, and the mixture was heated to reflux for 1.5 hours. 2-Propanol (50 mL) was added, and the solvent was distilled off under reduced pressure until the total weight was 16.2 g. 2-Propanol (20 mL) was added again, and the solvent was distilled off under reduced pressure until the total weight was 18.7 g. 2-Propanol (10 mL) was added, and the precipitated solid was collected by filtration and dried under reduced pressure with heating to obtain compound 4 (3.34 g, yield 91%) as a white solid. Step 4: Synthesis of Compound 5 Compound 4 (3.00 g, 10.3 mmol) was suspended in THF (30 mL), and 4-isobutoxybenzaldehyde (2.39 g, 13.4 mmol) and tetraisobutoxytitanium (7.57 mL, 25.8 mmol) were added, followed by stirring under heating to reflux for 6 hours. After adjusting the temperature to 40°C, THF (30 mL) and sodium triacetoxyborohydride (8.76 g, 41.3 mmol) were added and stirred at that temperature for 2 hours. A 20% aqueous citric acid solution (60 mL) was added to the reaction mixture, followed by stirring for 10 minutes. Chloroform (50 mL) was added, and the mixture was made weakly basic (pH 9) with 20% aqueous potassium carbonate solution (240 mL), and the organic solvent was evaporated under reduced pressure. The residue was extracted with chloroform / methanol (3:1, 600 mL) and chloroform (150 mL). The organic layers were combined, and the solvent was evaporated under reduced pressure to obtain a yellow solid. This solid was suspended in methanol (100 mL), water (20 mL) was added, and the solid was collected by filtration. After washing with 90% aqueous methanol, the mixture was dried under reduced pressure under heating to obtain compound 5 (2.42 g, yield 52%) as a yellow solid.1H-NMR (DMSO-D6) δ: 0.96 (d, J = 6.5 Hz, 6H), 1.51-1.75 (m, 4H), 1.92-2.07 (m, 1H), 3.20-3.48 (m, 2H), 3.58-3.68 (m, 2H), 3.71 (d, J = 6.5 Hz, 2H), 4.01 (d, J = 6.0 Hz, 2H), 5.07 (s, 2H), 6.07 (t, J = 6.1 Hz, 1H), 6.34 (s, 1H), 6.86 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.5 Hz, 2H), 7.27-7.47 (m, 5H). Step 5 Synthesis of Compound 6 Compound 5 (2.42 g, 5.36 mmol) was dissolved in DMF (24 mL), and 2-(chloromethoxy)ethyltrimethylsilane (1.05 mL, 5.89 mmol) and cesium carbonate (2.62 g, 8.03 mmol) were added. The mixture was stirred at room temperature for 3 hours. N-Methylpiperazine (1.79 mL, 16.1 mmol) was added, and the mixture was stirred at room temperature for 15 minutes. Water (100 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (100 mL). The organic layer was washed with water, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give compound 6 (3.03 g, 97% yield) as a colorless oil.1H-NMR (CDCl3) δ: 0.00 (s, 9H), 0.92 (t, J = 8.4 Hz, 2H), 1.01 (d, J = 6.8 Hz, 6H), 1.69-1.91 (m, 4H), 2.02-2.12 (m, 1H), 3.38-3.51 (m, 2H), 3.63-3.75 (m, 4H), 3.75-3.86 (m, 2H), 4.12 (t, J = 5.3 Hz, 1H), 4.34 (d, J = 5.3 Hz, 2H), 4.55 (s, 2H), 5.13 (s, 2H), 6.85 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 7.28-7.38 (m, 5H). Step 6: Synthesis of Compound 7. Compound 6 (3.03 g, 5.20 mmol) was dissolved in DMF (15 mL) and THF (15 mL). Sodium hydride (0.624 g, 15.6 mmol) was added under ice cooling, and the mixture was stirred at room temperature for 10 minutes. 3-(Chloromethyl)-1-methyl-1H-pyrazole hydrochloride (1.04 g, 6.24 mmol) was added, and the mixture was stirred at room temperature for 17 hours. Sodium hydride (0.416 g, 10.4 mmol) was added again, and the mixture was stirred at 50°C for 2 hours and at 70°C for 4 hours. Water (100 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (200 mL). The organic layer was washed with water, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain Compound 7 (2.60 g, yield 74%) as a yellow oil.1H-NMR (CDCl3) δ: -0.01 (s, 9H), 0.93 (t, J = 8.4 Hz, 2H), 1.02 (d, J = 6.8 Hz, 6H), 1.72-1.91 (m, 4H), 1.99-2.15 (m, 1H), 3.53-3.76 (m, 8H), 3.86 (s, 3H), 4.31 (s, 2H), 4.32 (s, 2H), 4.67 (s, 2H), 5.14 (s, 2H), 6.19 (d, J = 2.3 Hz, 1H), 6.83 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.5 Hz, 2H), 7.27-7.39 (m, 6H). Step 7 Synthesis of Compound 8 Compound 7 (2.60 g, 3.83 mmol) was dissolved in methylene chloride (26 mL), and boron trifluoride diethyl ether complex (4.86 mL, 38.3 mmol) and dimethyl sulfide (8.51 mL, 115 mmol) were added. The mixture was stirred at 40 °C for 2 hours. 20% aqueous potassium carbonate solution (100 mL) was added, and the mixture was extracted with ethyl acetate (100 mL). The organic layer was washed with water, and the solvent was evaporated under reduced pressure. The resulting residue was purified by aminosilica gel column chromatography (chloroform-methanol) to give compound 8 (765 mg, 48% yield) as a white foam.1H-NMR (CDCl3) δ: 1.02 (d, J = 6.8 Hz, 6H), 1.71-1.80 (m, 2H), 1.88-1.98 (m, 2H), 2.00-2.15 (m, 1H), 2.85-2.94 (m, 2H), 2.98-3.10 (m, 2H), 3.71 (d, J = 6.5 Hz, 2H), 3.85 (s, 3H), 4.15 (s, 2H), 4.30 (s, 2H), 5.42 (br s, 1H), 6.01 (d, J = 2.3 Hz, 1H), 6.86 (d, J = 8.8 Hz, 2H), 7.24 (d, J = 8.5 Hz, 2H), 7.25-7.28 (m, 1H). Step 8: Synthesis of Compound (I-009) Compound 9 (765 mg, 1.85 mmol) was dissolved in ethanol (7.65 mL), and 37% aqueous formaldehyde solution (0.690 mL) and sodium triacetoxyborohydride (1.18 g, 5.56 mmol) were added, followed by stirring at room temperature for 3 hours. After adding 20% ​​aqueous potassium carbonate solution (20 mL), the mixture was extracted with ethyl acetate (40 mL). The organic layer was washed with water, and the solvent was evaporated under reduced pressure. The resulting residue was purified by diol silica gel column chromatography (chloroform-methanol) to obtain compound (I-009) (320 mg, yield 41%) as a colorless oil. 1H-NMR (CDCl3) δ: 1.02 (d, J = 6.8 Hz, 6H), 1.78-1.91 (m, 2H), 1.96-2.14 (m, 3H), 2.32 (s, 3H), 2.44-2.70 (m, 4H), 3.71 (d, J = 6.5 Hz, 2H), 3.85 (s, 3H), 4.14 (s, 2H), 4.30 (s, 2H), 5.41 (br s, 1H), 6.00 (d, J = 1.8 Hz, 1H), 6.86 (d, J = 8.5 Hz, 2H), 7.23-7.29 (m, 1H), 7.24 (d, J = 8.5 Hz, 2H).

[0130] Synthesis of compound (I-002) Step 1: Synthesis of Compound 9 N-(tert-butoxycarbonyl)-L-tyrosine methyl ester (15.0 g, 50.8 mmol) was dissolved in methanol (75 mL), and 30% aqueous ammonia (75 mL) was added dropwise over approximately 2 minutes under ice-cooling. After standing at room temperature for 10 days, methanol was distilled off under reduced pressure. The resulting suspension was extracted with ethyl acetate, the organic layer was washed with water, the solvent was distilled off under reduced pressure, and azeotropic dehydration with ethyl acetate was performed twice to obtain approximately 37 g of a white solid. This white solid was dissolved in tetrahydrofuran (225 mL), and triphenylphosphine (4.00 g, 15.2 mmol) and isobutanol (9.41 mL, 102 mmol) were added. DIAD (11.9 mL, 60.9 mmol) was then added dropwise over approximately 3 minutes under ice-cooling. The mixture was then heated to 50°C over 30 minutes and stirred at that temperature for 2 hours. Triphenylphosphine (4.00 g, 15.2 mmol), isobutanol (4.71 mL, 50.8 mmol), and DIAD (2.96 mL, 15.2 mmol) were added again, and the mixture was stirred at 50° C. for 30 minutes. The solvent was distilled off under reduced pressure until the reaction solution weighed 104 g. Water (7.5 mL) and ethanol (150 mL) were added, and the solvent was distilled off again under reduced pressure, yielding approximately 87 g of residue. Ethanol (75 mL) was added, and the solvent was distilled off under reduced pressure twice, yielding approximately 83 g of residue. Ethanol (225 mL) and water (225 mL) were added to this residue, and the resulting suspension was filtered. The collected mud was washed four times with 50% aqueous ethanol (30 mL) to yield approximately 60 g of white mud. This sludgy product was dissolved in 1,4-dioxane (120 mL) and ethanol (60 mL), and concentrated hydrochloric acid (31.7 mL) was added. The mixture was stirred at room temperature for 14 hours and at 50°C for 30 minutes. Under ice-cooling, 8 mol / L aqueous sodium hydroxide solution (45 mL) was added to neutralize the mixture, and the solvent was distilled off under reduced pressure until the total weight was approximately 100 g. Methanol (50 mL) was added to the resulting suspension, and the solid was separated by filtration. 20% aqueous potassium carbonate solution (5 mL) was added to the filtrate, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, and the solvent was distilled off under reduced pressure. The resulting residue was purified by aminosilica gel column chromatography (ethyl acetate-methanol) to give compound 9 (5.22 g, yield 43%) as a white solid. 1H-NMR (CDCl3) δ: 0.96 (d, J = 6.7 Hz, 6H), 1.92-2.04 (m, 1H), 2.52 (dd, J = 11.5, 9.8 Hz, 1H), 2.82 (dd, J = 13.4, 5.1 Hz, 1H), 3.26 (dd, J Step 2 Synthesis of compound 10 Compound 9 (500 mg, 2.12 mmol), acetic acid (0.242 mL, 0.423 mmol), and 1-methylpiperidin-4-one (479 mg, 4.23 mmol) were dissolved in 2-propanol (2.5 mL) and stirred at 100°C for 2 hours. A 20% aqueous potassium carbonate solution was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water, and the solvent was evaporated under reduced pressure. The resulting residue was purified by amino silica gel column chromatography (ethyl acetate-methanol) to give compound 10 (515 mg, yield 73%). 1H-NMR (CDCl3) δ: 1.02 (d, J = 6.7 Hz, 6H), 1.34-1.82 (m, 4H), 2.03-2.12 (m, 1H), 2.17-2.56 (m, 2H), 2.27 (s, 3H), 2.47 (t, J = 6.2 Hz, 1H), 2.72 (t, J = 6.1 Hz, 1H), 2.95-3.07 (m, 2H), 3.70 (d, J = 6.5 Hz, 2H), 3.80 (t, J = 5.3 Hz, 1H), 5.95 (s, 1H), 6.84 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H). Step 3 Synthesis of Compound (I-002) Compound 10 (200 mg, 0.603 mmol) and 4-fluorobenzaldehyde (0.127 mL, 1.21 mmol) were dissolved in acetic acid (1 mL) and stirred at room temperature for 15 minutes. Sodium triacetoxyborohydride (192 mg, 0.905 mmol) was then added, and the mixture was stirred at room temperature for 8 hours. Sodium triacetoxyborohydride (192 mg, 0.905 mmol) was added again, and the mixture was stirred at room temperature for 8 hours. 20% aqueous potassium carbonate solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, and the solvent was evaporated under reduced pressure. The resulting residue was purified by aminosilica gel column chromatography (hexane-ethyl acetate) to give 113 mg of a white solid. This solid was suspended in 20% ethyl acetate / hexane and collected by filtration to give compound (I-002) (75.3 mg, 28%) as a white solid. 1H-NMR (CDCl3) δ: 1.01 (d, J = 6.8 Hz, 6H), 1.08-1.16 (m, 1H), 1.52-1.69 (m, 3H), 1.76-1.86 (m, 1H), 1.90-1.99 (m, 1H), 2.00-2.13 (m, 2H), 2.22 (s, 3H), 2.68-2.78 (m, 2H), 2.85-2.93 (m, 2H), 3.65-3.71 (m, 3H), 3.96 (d, J = 14.4 Hz, 1H), 6.50 (s, 1H), 6.73 (d, J = 8.7 Hz, 2H), 6.94-7.03 (m, 4H), 7.24 (dd, J = 8.5, 5.6 Hz, 2H).

[0131] Synthesis of compound (I-005) Step 1: Synthesis of Compound 11 Monoethyl malonate (6.80 g, 51.4 mmol), benzyl 4-oxo-1-piperidinecarboxylate (10.0 g, 42.9 mmol), and ammonium acetate (4.96 g, 64.3 mmol) were dissolved in ethanol (50 mL) and stirred under reflux for 3 hours. Ethyl acetate was added, and the reaction mixture was washed with 20% aqueous potassium carbonate and water, and the solvent was evaporated under reduced pressure. Compound 11 (13.8 g, 100%) was obtained as a yellow oil. H-NMR (CDCl) δ: 1.26 (t, J = 7.2 Hz, 3H), 1.47-1.80 (m, 4H), 2.40 (s, 2H), 3.34-3.46 (m, 2H), 3.66-3.79 (m, 2H), 4.15 (q, J = 7.2 Hz, 2H), 5.12 (s, 2H), 7.29-7.42 (m, 5H). Step 2: Synthesis of Compound 12. Compound 11 (7.00 g, 17.5 mmol) was dissolved in methylene chloride (35 mL), and benzoyl isothiocyanate (2.82 mL, 21.0 mmol) was added dropwise under ice cooling. After stirring at room temperature for 20 minutes, the solvent was evaporated under reduced pressure. This residue was dissolved in ethanol (35 mL), potassium carbonate (4.83 g, 35.0 mmol) was added, and the mixture was stirred at 70°C for 20 minutes and at 90°C for 60 minutes. The pH was adjusted to 4 with a 20% aqueous solution of sodium dihydrogen phosphate, and then the mixture was extracted with ethyl acetate. The organic layer was washed with water, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give compound 12 (5.37 g, yield 61%) as a white solid. 1H-NMR (CDCl) δ: 1.58-1.90 (m, 4H), 2.65 (s, 2H), 3.50-3.71 (m, 4H), 5.14 (s, 2H), 7.31-7.42 (m, 5H), 7.46 (br s, 1H), 8.68 (br s, 1H). Step 3: Synthesis of Compound 13. Compound 12 (100 mg, 0.300 mmol) was dissolved in DMF (1 mL), and methyl iodide (0.0563 mL, 0.900 mmol) was added. The mixture was stirred at room temperature for 1 hour. A 5% aqueous solution of sodium bicarbonate was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride and dried over sodium sulfate. The solid was then filtered off, and the solvent was evaporated under reduced pressure. The resulting residue was dissolved in t-amyl alcohol (1 mL), and 4-isobutoxybenzylamine (108 mg, 0.600 mmol) and DIPEA (0.262 mL, 1.50 mmol) were added, followed by stirring at 100°C for 4 hours. Ethyl acetate was added to the reaction mixture, which was washed with 20% aqueous citric acid and water, and the solvent was evaporated under reduced pressure. The resulting residue was purified by diol silica gel column chromatography (chloroform-methanol) and amino silica gel column chromatography (chloroform-methanol) to give compound 13 (65.9 mg, yield 46%).1H-NMR (DMSO-D6) δ: 0.93-0.98 (m, 6H), 1.27-1.42 (m, 0.72H), 1.46-1.60 (m, 3.28H), 1.91-2.06 (m, 1H), 2.19 (s, 0.36H), 2.27 (s, 1.64H), 3.27-3.74 (m, 6H), 4.20 (d, J = 6.3 Hz, 0.36H), 4.31 (d, J = 5.8 Hz, 1.64H), 5.05 (s, 0.36H), 5.07 (s, 1.64H), 5.62-5.74 (br m, 0.18H), 6.59 (br s, 0.82H), 6.85 (d, J = 8.8 Hz, 0.36H), 6.89 (d, J = 8.5 Hz, 1.64H), 7.10-7.26 (m, 2.82H), 7.29-7.44 (m, 5H), 9.45 (s, 0.18H). Step 4: Synthesis of Compound 14. Compound 13 (65.0 mg, 0.136 mmol) was dissolved in DMF (0.65 mL) and THF (0.65 mL), and sodium hydride (6.0 mg, 0.149 mmol) was added and stirred at room temperature for 1 hour. 4-Fluorobenzyl bromide (0.0201 mL, 0.163 mmol) was added and stirred at room temperature for 1.5 hours. Aqueous ammonium chloride solution was added, followed by extraction with ethyl acetate. The organic layer was washed with water, and the solvent was evaporated under reduced pressure. The resulting residue was purified by aminosilica gel column chromatography (chloroform-methanol) to obtain Compound 14 (67.8 mg, yield 85%) as a colorless oil.1H-NMR (CDCl3) δ: 1.02 (d, J = 6.8 Hz, 6H), 1.35-1.69 (m, 4H), 1.96-2.16 (m, 1H), 2.46 (s, 2H), 3.14-3.37 (m, 2H), 3.69 (d, J = 6.5 Hz, 2H), 3.72-3.98 (m, 3H), 4.21 (s, 2H), 4.73-5.07 (m, 2H), 5.12 (s, 2H), 6.80 (d, J = 8.3 Hz, 2H), 6.93-7.09 (m, 4H), 7.10-7.21 (m, 2H), 7.29-7.40 (m, 5H). Step 5 Synthesis of Compound (I-005) Compound 14 (67.5 mg, 0.115 mmol) was dissolved in THF (0.625 mL) and methanol (0.625 mL), and 10 wt% palladium on carbon (15 mg) was added. The mixture was stirred under 1 atmosphere of hydrogen for 8 hours. The reaction mixture was filtered through Celite, and the solvent from the filtrate was evaporated under reduced pressure. The resulting residue was dissolved in THF (0.625 mL) and methanol (0.625 mL), and 37% aqueous formaldehyde solution (0.026 mL) and sodium triacetoxyborohydride (48.8 mg, 0.230 mmol) were added. The mixture was stirred at room temperature for 2 hours. 20% aqueous potassium carbonate solution was added, followed by extraction with ethyl acetate. The organic layer was washed with water, and the solvent was evaporated under reduced pressure. The resulting residue was purified by aminosilica gel column chromatography (chloroform-methanol) to yield a colorless oil. This oil was dissolved in ethyl acetate, and a 4 mol / L hydrochloric acid / ethyl acetate solution (0.022 mL) was added. The solvent was evaporated under reduced pressure to obtain compound (I-005) (40.1 mg, 69%) as a white powder.1H-NMR (DMSO-D6) δ: 0.96 (d, J = 6.5 Hz, 6H), 1.26-1.38 (m, 2H), 1.59-1.72 (m, 2H), 1.92-2.11 (m, 2H), 2.33-2.45 (m, 2H), 2.58-2.73 (m, 1H), 2.92-3.06 (m, 2H), 3.33 (s, 3H), 3.62-3.78 (m, 2H), 4.11-4.29 (m, 2H), 4.99 (s, 2H), 6.77 (d, J = 8.3 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 7.13-7.22 (m, 2H), 7.25-7.33 (m, 2H), 9.81 (br s, 1H). [Reference Example 1].

[0132] Synthesis of Compound 18 Step 1: Synthesis of Compound 16 Methoxymethyltriphenylphosphonium chloride (12.5 g, 36.5 mmol) was dissolved in tetrahydrofuran (50 mL), potassium tert-butoxide (4.10 g, 36.5 mmol) was added, and the mixture was stirred at room temperature for 1 hour. Compound 15 (5.0 g, 30.4 mmol) was added, and the mixture was stirred at room temperature for 18 hours. A saturated aqueous solution of ammonium chloride was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was dissolved in acetone (200 mL), to which 2 mol / L aqueous hydrochloric acid (22.8 mL, 45.7 mmol) was added, followed by stirring at 45°C for 4 hours. The reaction solvent was evaporated under reduced pressure, and saturated aqueous sodium bicarbonate was added, followed by extraction with diethyl ether. After drying over magnesium sulfate, the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give compound 16 (1.96 g, 36% yield) as a colorless oil. 1H-NMR (CDCl) δ: 1.04 (t, J = 7.4 Hz, 3H), 1.76–1.87 (m, 2H), 3.62 (s, 2H), 3.92 (t, J = 7.4 Hz, 3H), 6.90 (d, J = 8.5 Hz, 2H), 7.12 (d, J = 8.5 Hz, 2H), 9.72 (t, J = 2.3 Hz, 1H). Step 2: Synthesis of Compound 17. Compound 16 (1.94 g, 10.9 mmol) was dissolved in methanol (20 mL) and water (10 mL). Hydroxylamine chloride (2.27 g, 32.7 mmol) and sodium carbonate (3.46 g, 32.7 mmol) were added, and the mixture was stirred at room temperature for 24 hours. Saturated brine was added, and the mixture was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and hexane was added to the resulting residue to precipitate a solid, which was then collected by filtration to obtain Compound 17 (1.55 g, yield 74%) as a white solid. 1 H-NMR (CDCl) δ: 1.03 (t, J = 7.4 Hz, 3H), 1.75-1.85 (m, 2H), 3.69 (d, J = 6.0 Hz, 2H), 3.91 (t, J = 7.4 Hz, 3H), 6.83-6.93 (m, 3H), 7.13 (d, J = 8.5 Hz, 2H), 7.64 (s, 1H). Step 3: Synthesis of Compound 18. Compound 17 (300 mg, 1.55 mmol) was dissolved in DMF (3 mL), and N-chlorosuccinimide (207 mg, 1.55 mmol) was added. The mixture was stirred at room temperature for 1 hour. Saturated aqueous sodium bicarbonate was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain Compound 18 (366 mg, yield 104%) as a crude product. 1 H-NMR (CDCl3) δ: 1.03 (t, J = 7.4 Hz, 3H), 1.76-1.85 (m, 2H), 3.74 (s, 2H), 3.91 (t, J = 7.4 Hz, 3H), 6.88 (d, J = 8.5 Hz, 2H), 7.17 (d, J = 8.5Hz, 2H).

[0133] Synthesis of compound (I-027) Step 1: Synthesis of Compound 20 Compound 19 (200 mg, 0.89 mmol) was dissolved in toluene (2 mL), and (1-methyl-1H-pyrazol-3-yl)methanamine (99 mg, 0.89 mmol) and magnesium sulfate (321 mg, 3.66 mmol) were added, followed by stirring at 100°C for 3 hours. The solid was filtered off, and the solvent was evaporated under reduced pressure. The resulting residue was dissolved in tetrahydrofuran (2 mL), and compound 18 (202 mg, 0.89 mmol) and triethylamine (0.185 mL, 1.33 mmol) were added, followed by stirring at room temperature for 16 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give compound 20 (105 mg, 23% yield) as a yellow oil. 1H-NMR (CDCl3) δ: 0.14-0.30 (m, 2H), 0.33-0.49 (m, 1H), 0.58-0.65 (m, 1H), 1.04 (t, J = 7.4 Hz, 3H), 1.42 (m, 10H), 1.75-2.00 (m, 4H), 3.06-3.24 (m, 1H), 3.37-3.56 (m, 2H), 3.95-4.10 (m, 2H), 3.86 (s, 3H), 3.90 (t, J = 6.7 Hz, 2H), 4.00 (d, J = 17.2 Hz, 1H), 4.27 (d, J = 17.2 Hz, 1H), 6.00 (d, J = 1.8 Hz, 1H), 6.83 (d, J = 8.5 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 7.25 (br s, 1H). Step 2: Synthesis of Compound (I-027) Compound 20 (100 mg, 0.20 mmol) was dissolved in dichloromethane (1 mL), and 2,6-lutidine (0.14 mL, 1.18 mmol) and trimethylsilyl triflate (0.18 mL, 0.98 mmol) were added under ice-cooling, followed by stirring for 1 hour. Saturated aqueous sodium bicarbonate was added, and the mixture was extracted with ethyl acetate. The mixture was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure.The resulting residue was dissolved in methanol (1 mL), and 37% formaldehyde solution (0.15 mL, 1.96 mmol) and sodium triacetoxyborohydride (125 mg, 0.59 mmol) were added, followed by stirring at room temperature for 1 hour. Saturated aqueous sodium bicarbonate was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform-methanol) to obtain compound (I-027) (28 mg, yield 34%) as a yellow oil. 1H-NMR (CDCl3) δ: 0.05-0.12 (m, 1H), 0.37-0.40 (m, 2H), 0.54-0.59 (m, 1H), 1.03 (t, J = 7.4 Hz, 3H), 1.76-1.94 (m, 2H), 1.88-1.94 (m, 2H), 2.11 (td, J = 12.7 Hz, 4.7 Hz, 1H), 2.26 (s, 3H), 2.47 (t, J = 11.0 Hz, 1H), 2.78-2.84 (m, 2H), 3.41 (d, J = 15.6 Hz, 1H), 3.62 (d, J = 15.6 Hz, 1H), 3.86 (s, 3H), 3.90 (t, J = 6.7 Hz, 2H), 4.03 (d, J = 17.1 Hz, 1H), 4.26 (d, J = 17.1 Hz, 1H), 6.02 (d, J = 2.3 Hz, 1H), 6.82 (d, J = 8.5 Hz, 2H), 7.15 (d, J = 8.5 Hz, 2H), 7.25 (d, J = 2.3 Hz, 1H).

[0134] Synthesis of compound (I-040) Step 1: Synthesis of Compound 21 Compound 19 (2.00 g, 8.88 mmol) was dissolved in toluene (20 mL), and (1-methyl-1H-pyrazol-3-yl)methanamine (0.99 g, 8.88 mmol) and magnesium sulfate (1.60 g, 13.32 mmol) were added, followed by stirring at 100°C for 4 hours. The solid was filtered off, and the solvent was evaporated under reduced pressure. The resulting residue was dissolved in tetrahydrofuran (20 mL), and ethyl 2-chloro-2-(hydroxyimino)acetate (2.02 g, 13.32 mmol) and triethylamine (2.46 mL, 17.76 mmol) were added, followed by stirring at room temperature for 24 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give compound 21 (872 mg, 23% yield) as a colorless oil. 1H-NMR (CDCl3) δ: 0.27-0.35 (m, 1H), 0.39-0.62 (m, 2H), 0.77-0.86 (m, 1H), 1.35 (t, J = 7.2 Hz, 3H), 1.45 (m, 10H), 1.86-1.96 (m, 1H), 2.07-2.16 (m, 1H), 3.05-3.39 (m, 2H), 3.42-3.64 (m, 1H), 3.82 (s, 3H), 3.98-4.17 (m, 2H), 4.26-4.41 (m, 2H), 4.87 (d, J = 16.7 Hz, 1H), 6.04 (br s, 1H), 7.23 (br s, 1H). Step 2: Synthesis of Compound 22. Compound 21 (800 mg, 1.85 mmol) was dissolved in ethanol (8 mL), and hydroxylamine chloride (1.22 mL, 18.45 mmol) was added. The mixture was heated to reflux for 3 hours. The reaction solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (chloroform-methanol) to give compound 22 (655 mg, 84% yield) as a colorless oil.1H-NMR (CDCl3) δ: 0.27-0.36 (m, 1H), 0.37-0.60 (m, 2H), 0.78-0.86 (m, 1H), 1.45 (m, 10H), 1.80-1.96 (m, 1H), 2.07-2.18 (m, 1H), 3.05-3.28 (m, 1H), 3.40-3.66 (m, 2H), 3.83 (s, 3H), 4.00-4.20 (m, 2H),4.90 (d, J = 16.7 Hz, 1H), 6.06 (br s, 1H), 7.25 (br s, 1H). Step 3 Synthesis of compound 23 Compound 22 (400 mg, 1.85 mmol) was dissolved in tetrahydrofuran (2 mL), and a 50% tetrahydrofuran solution of propylphosphonic anhydride (cyclic trimer) (1.42 mL, 2.38 mmol) and N-methylmorpholine (0.26 mL, 2.38 mmol) were added, followed by stirring at room temperature for 1 hour. 2-(Trimethylsilyl)ethanol (0.68 mL, 4.76 mmol) was added, and the mixture was heated to reflux for 6 hours. Saturated aqueous sodium bicarbonate was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was dissolved in tetrahydrofuran (5.3 mL), and a 1 mol / L tetrahydrofuran solution of tetrabutylammonium fluoride (1.54 mL, 1.54 mmol) was added, followed by heating to reflux for 4 hours. The reaction solvent was evaporated under reduced pressure, and the resulting residue was purified by aminosilica gel column chromatography (chloroform-methanol) to give compound 23 (288 mg, 75% yield) as a white solid.1H-NMR (CDCl3) δ: 0.26-0.54 (m, 3H), 0.81-0.89 (m, 1H), 1.45 (m, 9H), 1.88-1.95 (m, 1H), 2.00-2.12 (m, 1H), 3.12-3.41 (m, 2H), 3.44-3.64 (m, 1H), 3.86 (s, 3H), 4.03 (d, J = 15.9 Hz, 1H), 4.07-4.24 (m, 1H), 4.27 (d, J = 15.9 Hz, 1H), 4.53 (br s, 2H), 6.12 (br s, 1H), 7.29 (br s, 1H). Step 4 Synthesis of Compound (I-040) Compound 23 (50 mg, 0.20 mmol) was dissolved in 2-propanol (0.5 mL), and compound 15 (26 mg, 0.16 mmol) and isopropyl orthotitanate (0.06 mL, 0.20 mmol) were added. The mixture was heated to reflux for 2 hours. After cooling, sodium borohydride (15 mg, 0.39 mmol) was added, and the mixture was stirred at room temperature for 1 hour. Saturated aqueous sodium bicarbonate was added, and the mixture was extracted with ethyl acetate. The mixture was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was dissolved in dichloromethane (1.2 mL), and 2,6-lutidine (0.016 mL, 0.137 mmol) and trimethylsilyl triflate (0.021 mL, 0.114 mmol) were added under ice-cooling, and the mixture was stirred for 1 hour. Saturated aqueous sodium bicarbonate was added, and the mixture was extracted with ethyl acetate. The mixture was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was dissolved in methanol (1.2 mL), and 37% formaldehyde solution (0.017 mL, 1.96 mmol) and sodium triacetoxyborohydride (15 mg, 0.069 mmol) were added, followed by stirring at room temperature for 1 hour. Saturated aqueous sodium bicarbonate was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform-methanol) to obtain compound (I-040) (5 mg, yield 8%).1H-NMR (CDCl3) δ: 0.14-0.23 (m, 1H), 0.40-0.54 (m, 2H), 0.76-0.83 (m, 1H), 1.03 (t, J = 7.4 Hz, 3H), 1.75-1.84 (m, 2H), 1.92-2.04 (m, 2H), 2.15-2.26 (m, 1H), 2.30 (s, 3H), 2.53-2.67 (m, 1H), 2.83-2.91 (m, 2H), 3.73 (s, 3H), 3.90 (t, J = 6.7 Hz, 2H), 4.02 (d, J = 16.1 Hz, 1H), 4.19-4.26 (m, 3H), 5.63 (br s, 1H), 6.07 (d, J = 2.3 Hz, 1H), 6.84 (d, J = 8.8 Hz, 2H), 7.21-7.25 (m, 3H).

[0135] Synthesis of compound (I-022) Step 1: Synthesis of Compound 25 Compound 24 (synthetic method described in WO2008014311A2) (1 g, 3.30 mmol) was dissolved in tetrahydrofuran (10 mL), Lawesson's reagent (1.33 g, 3.30 mmol) was added, and the mixture was stirred at 140°C for 30 minutes under microwave irradiation. An aqueous solution (5 mL) of ethanolamine (1.99 mL, 33.0 mmol) was added, and the mixture was stirred at 80°C for 1 hour. 2 mol / L hydrochloric acid (33.0 mL, 65.9 mmol) was added, and the mixture was stirred at 80°C for 4 hours. After cooling, 20% aqueous potassium carbonate solution (2 mL) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give compound 25 (731 mg, yield 70%). 1H-NMR (CDCl3) δ: 1.69-1.81 (2H, m), 1.98-2.09 (2H, m), 3.38-3.47 (2H, m), 3.94-4.05 (2H, m), 5.15 (2H, s), 7.31-7.42 (6H, m). Step 2: Synthesis of Compound 26. Compound 25 (720 mg, 2.25 mmol) was dissolved in ethanol (14 mL), and DIPEA (0.47 mL, 2.70 mmol) and methyl iodide (0.17 mL, 2.70 mmol) were added. The mixture was stirred at room temperature for 20 hours. DIPEA (0.47 mL, 2.70 mmol) and methyl iodide (0.17 mL, 2.70 mmol) were added, and the mixture was stirred at room temperature for 2 hours. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give Compound 26 (468 mg, yield 62%). 1 H-NMR (CDCl) δ: 1.43-1.55 (2H, m), 1.81-1.93 (2H, m), 2.55 (3H, s), 3.40-3.54 (2H, m), 3.98-4.15 (2H, m), 5.15 (2H, s), 7.29-7.41 (5H, m), 7.65 (1H, s). Step 3: Synthesis of Compound 28. Compound 26 (153 mg, 0.459 mmol) was added with acetic acid (1.5 mL) and compound 27 (synthetic method described in WO2019040105A2) (132 mg, 0.460 mmol), and the mixture was stirred at 130 °C for 9 hours. The solvent was evaporated under reduced pressure, and the resulting residue was added with saturated aqueous sodium bicarbonate and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate followed by chloroform-methanol) to give Compound 28 (127 mg, yield 49%). 1H-NMR (CDCl3) δ: 1.02 (6H, d, J = 6.6 Hz), 1.39-1.53 ​​(2H, m), 1.89-2.01 (2H, m), 2.03-2.14 (1H, m), 3.03-3.19 (2H, m), 3.70 (2H, d, J = 6.6 Hz), 3.95-4.07 (2H, m), 4.35 (2H, br s), 4.85 (2H, br s), 5.09 (2H, s), 5.22 (1H, s), 6.87 (2H, d, J = 8.3 Hz), 7.00-7.10 (4H, m), 7.28-7.39 (7H, m). Process 4 Synthesis of Compound (I-022) Under a hydrogen atmosphere, compound 28 (126 mg, 0.221 mmol) was dissolved in 2.5 mL of tetrahydrofuran, and 10 wt% palladium on carbon (47 mg) was added. The mixture was stirred under a hydrogen atmosphere at 1 atmosphere pressure for 5 hours. The reaction solution was filtered through Celite, and the solvent in the filtrate was evaporated under reduced pressure. The resulting residue was purified by aminosilica gel column chromatography (chloroform-methanol) to obtain compound (I-022) (77 mg, yield 79%). 1H-NMR (CDCl3) δ: 1.02 (6H, d, J = 6.5 Hz), 1.36-1.44 (2H, m), 1.90-2.00 (2H, m), 2.03-2.13 (1H, m), 2.38-2.49 (2H, m), 3.11-3.19 (2H, m), 3.71 (2H, d, J = 6.5 Hz), 4.38 (2H, br s), 4.87 (2H, br s), 5.29 (1H, s), 6.88 (2H, d, J = 8.5 Hz), 7.00-7.40 (6H, m).

[0136] Synthesis of compound (I-021) Step 1: Synthesis of Compound (I-021) Compound (I-022) (31.3 mg, 0.071 mmol) was dissolved in THF (0.470 mL) and methanol (0.470 mL), and 37% aqueous formaldehyde solution (0.017 mL) and sodium triacetoxyborohydride (30.3 mg, 0.143 mmol) were added, followed by stirring at room temperature for 1 hour. A saturated aqueous sodium bicarbonate solution was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform-methanol) to give a colorless oil. This oil was solidified with diisopropyl ether to give compound (I-021) (18.8 mg, 58%) as a white powder. 1H-NMR (CDCl3) δ: 1.03 (6H, d, J = 6.8 Hz), 1.44-1.54 (2H, m), 1.75-1.88 (2H, m), 2.02-2.16 (3H, m), 2.25 (3H, s), 2.82-2.93 (2H, m), 3.71 (2H, d, J = 6.5 Hz), 4.36 (2H, br s), 4.84 (2H, br s), 5.23 (1H, s), 6.88 (2H, d, J = 8.3 Hz), 6.98-7.39 (6H, m).

[0137] Synthesis of compound (I-020) Step 1: Synthesis of Compound 30 Compound 29 (250 mg, 1.09 mmol) was dissolved in dichloromethane (2.5 mL), and triethylamine (0.451 mL, 3.26 mmol) and tert-butyldimethylsilyl chloride (196 mg, 1.30 mmol) were added, followed by stirring at room temperature for 5 hours. tert-Butyldimethylsilyl chloride (94 mg, 0.625 mmol) was added, followed by stirring at room temperature for 18 hours. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give compound 30 (296 mg, yield 79%). 1H-NMR (CDCl3) δ: 0.05 (6H, s), 0.90 (9H, s), 1.29-1.38 (2H, m), 1.40-1.52 (2H, m), 3.18-3.28 (2H, m), 3.33 (2H, s), 3.64-3.78 (2H, m). Step 2: Synthesis of Compound 31. Compound 30 (278 mg, 0.807 mmol) was dissolved in ethyl acetate (2.8 mL), and an aqueous solution (1.7 mL) of potassium carbonate (558 mg, 4.04 mmol) was added. Under ice cooling, a solution (1.4 mL) of triphosgene (240 mg, 0.807 mmol) in ethyl acetate was added dropwise over approximately 5 minutes. After stirring at room temperature for 30 minutes, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was dissolved in THF (3.4 mL). A THF solution (2.8 mL) of compound 27 (240 mg, 0.834 mmol) was added, and the mixture was stirred at room temperature for 2.5 hours. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give compound 31 (389 mg, 77%). 1H-NMR (CDCl3) δ: 0.00 (6H, s), 0.84 (9H, s), 1.02 (6H, d, J = 6.7 Hz), 1.35-1.47 (2H, m), 1.44 (9H, s), 1.93-2.13 (3H, m), 2.63-2.78 (2H, m), 3.56-3.80 (6H, m), 4.11 (1H, s), 4.35 (2H, s), 4.46 (2H, s), 6.85 (2H, d, J = 8.2 Hz), 6.97-7.05 (2H, m), 7.11 (2H, d, J = 8.2 Hz), 7.17-7.24 (2H, m). Process 3 Synthesis of Compound 32 Compound 31 (198 mg, 0.301 mmol) was dissolved in THF (2.0 mL), and an aqueous solution (1.7 mL) of 1 mol / L TBAF-THF solution (0.904 mL, 0.904 mmol) was added, followed by stirring at room temperature for 16.5 hours. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give Compound 32 (144 mg, 88%). 1H-NMR (CDCl3) δ: 1.02 (6H, d, J = 6.5 Hz), 1.44 (10H, s), 1.49-1.62 (2H, m), 1.66-1.79 (2H, m), 2.01-2.13 (1H, m), 2.70 (2H, t, J = 11.5 Hz), 3.53-3.66 (4H, m), 3.70 (2H, d, J = 6.5 Hz), 4.32 (1H, s), 4.39 (2H, s), 4.52 (2H, s), 5.14 (1H, s), 6.87 (2H, d, J = 8.5 Hz), 7.01-7.08 (2H, m), 7.11 (2H, d, J = 8.5 Hz), 7.19-7.25 (2H, m). Step 4: Synthesis of Compound 33. Compound 32 (139 mg, 0.256 mmol) was dissolved in dichloromethane (4.2 mL) and cooled to −78°C with dry ice-acetone. N,N-Diethylaminosulfur trifluoride (0.034 mL, 0.256 mmol) was added, and the mixture was stirred at −78°C for 30 minutes. N,N-Diethylaminosulfur trifluoride (0.044 mL, 0.333 mmol) was added, and the mixture was stirred at −78°C for 30 minutes. A saturated aqueous solution of sodium bicarbonate was added, and the mixture was warmed to room temperature. Extraction was performed with ethyl acetate, and the organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give Compound 33 (119 mg, 89% yield). 1H-NMR (CDCl3) δ: 1.03 (6H, d, J = 6.6 Hz), 1.46 (9H, s), 1.58-1.65 (2H, m), 1.66-1.77 (2H, m), 2.02-2.14 (1H, m), 3.35-3.47 (2H, m), 3.58-3.67 (2H, m), 3.71 (2H, d, J = 6.6 Hz), 4.05 (2H, s), 4.30 (2H, s), 4.32 (2H, s), 6.84 (2H, d, J = 8.2 Hz), 6.95-7.04 (2H, m), 7.11 (2H, d, J = 8.2 Hz), 7.14-7.22 (2H, m). Step 5 Synthesis of Compound (I-020) Compound 33 (40.5 mg, 0.077 mmol) was dissolved in THF (0.81 mL), lithium aluminum hydride (8.8 mg, 0.231 mmol) was added, and the mixture was refluxed for 1.5 hours. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (chloroform-methanol-water) to obtain compound (I-020) (23.5 mg, 69%). 1H-NMR (CDCl3) δ: 1.02 (6H, d, J = 6.6 Hz), 1.64-1.73 (2H, m), 1.82-1.94 (2H, m), 2.01-2.26 (3H, m), 2.29 (3H, s), 2.67-2.79 (2H, m), 3.71 (2H, d, J = 6.6 Hz), 4.05 (2H, s), 4.29 (2H, s), 4.32 (2H, s), 6.84 (2H, d, J = 8.5 Hz), 6.99 (2H, t, J = 8.5 Hz), 7.10 (2H, d, J = 8.5 Hz), 7.17 (2H, t, J = 6.8 Hz).

[0138] Synthesis of compound (I-080) Step 1: Synthesis of Compound 34 4-Butoxybenzenemethanamine (4.84 g, 27.0 mmol) was dissolved in ethanol (15 mL), and 2-methyloxazole-4-carboxaldehyde (3.0 g, 27.0 mmol) was added, followed by stirring at 80°C for 1 hour. After ice cooling, sodium borohydride (1.02 g, 27.0 mmol) was added, followed by stirring at room temperature for 1 hour. Saturated aqueous sodium bicarbonate was added, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by amino column chromatography (hexane-ethyl acetate) to obtain Compound 34 (6.16 g, 83% yield). 1H-NMR (CDCl3) δ: 0.97 (3H, t, J = 7.5 Hz), 1.49 (2H, dt, J = 22.7, 7.5 Hz), 1.72-1.79 (2H, m), 2.44 (3H, s), 3.65 (2H, s), 3.74 (2H, Step 2 Synthesis of compound 35 4-Methylbenzenesulfonyl cyanide (25.1 g, 138 mmol) was dissolved in 2-propanol (125 mL), and 50% aqueous hydroxylamine solution (25.4 mL, 415 mmol) was added under ice-cooling, followed by stirring at room temperature for 3 hours. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting solid was washed with ethyl acetate-hexane to obtain compound 35 (25.2 g, yield 85%). 1H-NMR (DMSO-D6) δ: 2.42 (3H, s), 6.44 (2H, s), 7.49 (2H, d, J = 8.1 Hz), 7.80 (2H, d, J = 8.1 Hz), 10.71 (1H, br s). Step 3: Synthesis of Compound 36 Compound 35 (25.2 g, 117 mmol) was dissolved in 2-propanol (126 mL), and benzyl 4-oxopiperidine 1-carboxylate (30.1 g, 129 mmol) and PPTS (5.91 g, 23.5 mmol) were added, followed by stirring at 130°C for 3 hours. Benzyl 4-oxopiperidine 1-carboxylate (4.48 g, 19.2 mmol) and PPTS (1.20 g, 4.78 mmol) were added, and the mixture was stirred at 130°C for 3 hours. After cooling, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 36 (11.8 g, yield 16%). H-NMR (CDCl) δ: 1.66-1.78 (2H, m), 1.92-2.01 (2H, m), 2.48 (3H, s), 3.26-3.37 (2H, m), 3.82-3.93 (2H, m), 5.12 (2H, s), 7.30-7.38 (5H, m), 7.40 (2H, d, J = 8.3 Hz), 7.89 (2H, d, J = 8.3 Hz). Step 4 Synthesis of Compound 37 Compound 36 (4.51 g, 10.5 mmol) was dissolved in 1,4-dioxane (18 mL), and compound 34 (2.88 g, 10.5 mmol) and DIPEA (18 mL, 103 mmol) were added, followed by stirring at 130° C. for 9 hours. The solvent was evaporated under reduced pressure, and the resulting residue was purified by column chromatography (hexane-ethyl acetate) to obtain Compound 37 (2.99 g, yield 52%).1H-NMR (CDCl3) δ: 0.98 (3H, t, J = 7.3 Hz), 1.45-1.54 (3H, m), 1.71-1.84 (4H, m), 2.41 (3H, s), 3.49 (2H, dt, J = 16.9, 5.9 Hz), 3.77-3.90 (2H, m), 3.95 (2H, t, J = 6.5 Hz), 4.02 (2H, s), 4.28 (2H, s), 5.14 (2H, s), 5.88 (1H, s), 6.84 (2H, d, J = 8.5 Hz), 7.20 (2H, d, J = 8.5 Hz), 7.24 (1H, s), 7.30-7.39 (5H, m). Step 5: Synthesis of Compound 38. Compound 37 (2.40 g, 4.38 mmol) was dissolved in dichloromethane (36 mL), and dimethyl sulfide (6.48 mL, 88.0 mmol) and boron trifluoride diethyl ether complex (5.55 mL, 43.8 mmol) were added. The mixture was stirred at room temperature for 5 hours. 10% aqueous potassium carbonate solution was added, and the mixture was extracted with chloroform. The organic layer was washed with water and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by amino column chromatography (chloroform-methanol) to give compound 38 (1.45 g, 80% yield).1H-NMR (CDCl3) δ: 0.98 (3H, t, J = 7.4 Hz), 1.49 (3H, td, J = 14.9, 7.4 Hz), 1.72-1.85 (4H, m), 1.93-1.99 (1H, m), 2.42 (3H, s), 2.87-2.93 (2H, m), 3.03-3.09 (2H, m), 3.95 (2H, t, J = 6.5 Hz), 4.04 (2H, s), 4.29 (2H, s), 5.71 (1H, s), 6.85 (2H, d, J = 8.7 Hz), 7.21 (2H, d, J = 8.7 Hz), 7.26 (1H, s). Step 6 Synthesis of Compound (I-080) Compound 38 (1.43 g, 3.45 mmol) was dissolved in methanol (14 mL) and THF (14 mL), and 37% aqueous formaldehyde solution (0.77 mL, 10.4 mmol) and sodium borohydride triacetate (2.19 g, 10.4 mmol) were added, followed by stirring at room temperature for 2 hours. Saturated aqueous sodium bicarbonate was added, followed by extraction with chloroform, and the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (chloroform-methanol) to obtain compound (I-080) (1.16 g, yield 79%). 1H-NMR (CDCl3) δ: 0.98 (3H, t, J = 7.3 Hz), 1.44-1.55 (2H, m), 1.72-1.81 (2H, m), 1.83-1.94 (2H, m), 2.00-2.09 (2H, m), 2.31 (3H, s), 2.42 (3H, s), 2.48-2.60 (4H, m), 3.95 (2H, t, J = 6.5 Hz), 4.03 (2H, s), 4.29 (2H, s), 5.67 (1H, s), 6.84 (2H, d, J = 8.6 Hz), 7.20 (2H, d, J = 8.6 Hz), 7.25 (1H, s).

[0139] Synthesis of compound (I-114) Step 1: Synthesis of Compound 40 Compound 39 (0.8 g, 7.06 mmol) was dissolved in ethanol (12 mL), and 2-methyloxazole-4-carboxaldehyde (1.53 g, 7.76 mmol) was added, followed by stirring at 80°C for 1 hour. The mixture was ice-cooled, and sodium borohydride (0.294 g, 7.76 mmol) was added, followed by stirring at room temperature for 1 hour. Saturated aqueous sodium bicarbonate was added, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by amino column chromatography (hexane-ethyl acetate) to give compound 40 (2.18 g, yield 100%). 1H-NMR (CDCl3) δ: 0.98 (3H, t, J = 7.4 Hz), 1.43-1.53 ​​(2H, m), 1.72-1.79 (2H, m), 2.43 (3H, s), 3.65 (2H, s), 3.79 (2H, s), 3.93 (2H, t, J = 7.4 Hz), 6.59 (1H, dd, J = 12.0, 2.4 Hz), 6.64 (1H, dd, J = 8.5, 2.4 Hz),7.21 (1H, t, J = 8.7 Hz), 7.41 (1H, s). Step 2 Synthesis of compound 41 Compound 36 (0.705 g, 1.64 mmol) was dissolved in 1,4-dioxane (6 mL), and compound 40 (0.480 g, 1.64 mmol) and DIPEA (6 mL, 34.4 mmol) were added thereto, followed by stirring for 6 hours at 130° C. The solvent was evaporated under reduced pressure, and the resulting residue was purified by column chromatography (hexane-ethyl acetate) to give compound 41 (394 mg, yield 42%).1H-NMR (CDCl3) δ: 0.97 (3H, t, J = 7.4 Hz), 1.43-1.53 ​​(2H, m), 1.71-1.92 (4H, m), 1.98-2.05 (2H, m), 2.41 (3H, s), 3.44-3.54 (2H, m), 3.77-3.90 (2H, m), 3.93 (2H, t, J = 6.5 Hz), 4.05 (2H, s), 4.31 (2H, s), 5.14 (2H, s), 5.95 (1H, s), 6.58 (1H, dd, J = 12.0, 2.3 Hz), 6.66 (1H, dd, J = 8.9, 2.3 Hz), 7.29-7.40 (7H, m). Step 3: Synthesis of Compound 42. Compound 41 (394 mg, 0.697 mmol) was dissolved in dichloromethane (6 mL), and dimethyl sulfide (1.03 mL, 13.9 mmol) and boron trifluoride diethyl ether complex (0.883 mL, 6.97 mmol) were added. The mixture was stirred at room temperature for 17 hours. A 10% aqueous potassium carbonate solution was added, and the mixture was extracted with chloroform. The organic layer was washed with water and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by amino column chromatography (chloroform-methanol) to give compound 42 (224 mg, yield 73%). Step 4 Synthesis of Compound (I-114) Compound 42 (224 mg, 0.520 mmol) was dissolved in methanol (2.2 mL) and THF (2.2 mL), and 37% aqueous formaldehyde solution (0.116 mL, 1.56 mmol) and sodium borohydride triacetate (330 mg, 1.56 mmol) were added, followed by stirring at room temperature for 1 hour. Saturated aqueous sodium bicarbonate was added, followed by extraction with chloroform, and the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by amino column chromatography (chloroform-methanol) to obtain compound (I-114) (217 mg, yield 94%).1H-NMR (CDCl3) δ: 0.97 (3H, t, J = 7.4 Hz), 1.48 (2H, dd, J = 15.1, 7.4 Hz), 1.72-1.79 (2H, m), 1.84-1.93 (2H, m), 2.00-2.08 (2H, m), 2.32 (3H, s), 2.41 (3H, s), 2.49-2.60 (4H, m), 3.93 (2H, t, J = 6.5 Hz), 4.06 (2H, s), 4.32 (2H, s), 5.77 (1H, s), 6.58 (1H, dd, J = 12.0, 2.4 Hz), 6.66 (1H, dd, J = 8.6, 2.4 Hz), 7.36 (1H, s), 7.36 (1H, dd, J = 8.6, 8.6 Hz).

[0140] Synthesis of compound (I-113) Step 1: Synthesis of Compound 43 4-Butoxybenzenemethanamine (1.05 g, 5.85 mmol) was dissolved in ethanol (9.8 mL), and 2-methyl-2H-1,2,3-triazole-4-carbaldehyde (650 mg, 5.85 mmol) was added, followed by stirring at 80°C for 1 hour. After ice cooling, sodium borohydride (0.221 g, 5.85 mmol) was added, followed by stirring at room temperature for 1 hour. Saturated aqueous sodium bicarbonate was added, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by amino column chromatography (hexane-ethyl acetate) to obtain Compound 43 (1.38 g, yield 86%). 1H-NMR (CDCl3) δ: 0.97 (3H, t, J = 7.4 Hz), 1.43-1.54 (2H, m), 1.72-1.79 (2H, m), 3.76 (2H, s), 3.85 (2H, s), 3.95 (2H, t, J = 6.5 Step 2 Synthesis of compound 44 Compound 36 (0.910 g, 2.11 mmol) was dissolved in 1,4-dioxane (6 mL), and compound 43 (580 mg, 2.11 mmol) and DIPEA (6 mL, 34.4 mmol) were added thereto, followed by stirring for 8 hours at 130° C. The solvent was evaporated under reduced pressure, and the resulting residue was purified by column chromatography (hexane-ethyl acetate) to give compound 44 (716 mg, yield 62%).1H-NMR (CDCl3) δ: 0.98 (3H, t, J = 7.4 Hz), 1.44-1.55 (2H, m), 1.66-1.80 (4H, m), 1.95-2.06 (2H, m), 3.43 (2H, t, J = 10.5 Hz), 3.77-3.91 (2H, m), 3.95 (2H, t, J = 6.7 Hz), 4.15 (3H, s), 4.27 (4H, s), 4.66 (1H, s), 5.13 (2H, s), 6.86 (2H, d, J = 8.6 Hz), 7.19 (2H, d, J = 8.6 Hz), 7.29-7.40 (6H, m). Step 3 Synthesis of Compound 45 Compound 44 (716 mg, 1.31 mmol) was dissolved in dichloromethane (11 mL), and dimethyl sulfide (1.93 mL, 26.1 mmol) and boron trifluoride diethyl ether complex (1.66 mL, 13.1 mmol) were added. The mixture was stirred at room temperature overnight. 10% aqueous potassium carbonate solution was added, and the mixture was extracted with chloroform. The organic layer was washed with water and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by amino column chromatography (chloroform-methanol) to give compound 45 (502 mg, yield 93%). Step 4 Synthesis of Compound (I-113) Compound 45 (460 mg, 1.1 mmol) was dissolved in methanol (4.6 mL) and THF (4.6 mL), and 37% aqueous formaldehyde solution (0.249 mL, 3.34 mol) and sodium borohydride triacetate (708 mg, 3.34 mmol) were added, followed by stirring at room temperature for 2 hours. Saturated aqueous sodium bicarbonate was added, followed by extraction with chloroform, and the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by amino column chromatography (chloroform-methanol) to obtain compound (I-113) (415 mg, yield 87%).1H-NMR (CDCl3) δ: 0.98 (3H, t, J = 7.4 Hz), 1.50 (2H, td, J = 14.9, 7.4 Hz), 1.72-1.88 (4H, m), 1.99-2.07 (2H, m), 2.31 (3H, s), 2.44-2.59 (4H, m), 3.95 (2H, t, J = 6.5 Hz), 4.15 (3H, s), 4.27 (4H, s), 4.57 (1H, s), 6.86 (2H, d, J = 8.7 Hz), 7.20 (2H, d, J = 8.7 Hz), 7.36 (1H, s). .

[0141] Synthesis of compound (I-105) Step 1: Synthesis of Compound 46 4-Butoxybenzenemethanamine (540 mg, 3.01 mmol) was dissolved in ethanol (9 mL), and 2-fluoromethyl-4-oxazolecarboxaldehyde (389 mg, 3.01 mmol) was added, followed by stirring at 80°C for 1 hour. After ice cooling, sodium borohydride (0.114 g, 3.01 mmol) was added, followed by stirring at room temperature for 1 hour. Saturated aqueous sodium bicarbonate was added, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by amino column chromatography (hexane-ethyl acetate) to give Compound 46 (0.588 g, yield 67%). 1H-NMR (CDCl3) δ: 0.97 (3H, t, J = 7.5 Hz), 1.49 (2H, td, J = 15.0, 7.5 Hz), 1.73-1.80 (2H, m), 3.73 (2H, d, J = 0.9 Hz), 3.75 (2H, s), 3.95 (2H, t, J = 6.5Hz), 5.36 (2H, d, J = 47.4Hz), 6.86 (2H, d, J = 8.7Hz), 7.23 (2H, d, J = 8.7Hz), 7.58 (1H, s). Compound 36 (0.556 g, 1.30 mmol) was dissolved in 1,4-dioxane (2 mL), and compound 46 (379 mg, 1.30 mmol) and DIPEA (2 mL, 11.5 mmol) were added thereto, followed by stirring for 7 hours at 130° C. The solvent was evaporated under reduced pressure, and the resulting residue was purified by column chromatography (hexane-ethyl acetate) to give compound 47 (234 mg, yield 32%).1H-NMR (CDCl3) δ: 0.98 (3H, t, J = 7.6 Hz), 1.49 (2H, td, J = 15.2, 7.6 Hz), 1.73-1.80 (4H, m), 1.97-2.05 (2H, m), 3.46 (2H, t, J = 11.1 Hz), 3.77-3.91 (2H, m), 3.95 (2H, t, J = 6.5 Hz), 4.12 (2H, s), 4.31 (2H, s), 5.14 (2H, s), 5.27 (2H, s), 5.39 (1H, s), 6.85 (2H, d, J = 8.6 Hz), 7.19 (2H, d, J = 8.6 Hz), 7.29-7.39 (5H, m), 7.44 (1H, s). Step 3: Synthesis of Compound 48. Compound 47 (234 mg, 0.414 mmol) was dissolved in dichloromethane (3.5 mL), and dimethyl sulfide (0.613 mL, 8.28 mmol) and boron trifluoride diethyl ether complex (0.525 mL, 4.14 mmol) were added. The mixture was stirred at room temperature overnight. 10% aqueous potassium carbonate solution was added, and the mixture was extracted with chloroform. The organic layer was washed with water and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by amino column chromatography (chloroform-methanol) to give compound 48 (127 mg, yield 71%). Step 4 Synthesis of Compound (I-105) Compound 48 (127 mg, 0.294 mmol) was dissolved in methanol (1.3 mL) and THF (1.3 mL), and 37% aqueous formaldehyde solution (0.066 mL, 0.883 mol) and sodium borohydride triacetate (187 mg, 0.883 mmol) were added, followed by stirring at room temperature for 1 hour. Saturated aqueous sodium bicarbonate was added, followed by extraction with chloroform, and the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by amino column chromatography (chloroform-methanol) to obtain compound (I-105) (122 mg, yield 93%).1H-NMR (CDCl3) δ: 0.98 (3H, t, J = 7.4 Hz), 1.49 (2H, td, J = 15.0, 7.4 Hz), 1.73-1.80 (2H, m), 1.83-1.89 (2H, m), 2.00-2.09 (2H, m), 2.31 (3H, s), 2.45-2.62 (4H, m), 3.95 (2H, t, J = 6.5 Hz), 4.14 (2H, s), 4.31 (2H, s), 5.10 (1H, s), 5.34 (2H, d, J = 47.4 Hz), 6.85 (2H, d, J = 8.5 Hz), 7.20 (2H, d, J = 8.5 Hz), 7.46 (1H, s).

[0142] The following compounds were synthesized according to the above general synthesis method and the method described in the Examples. The structures and physical properties (LC / MS data) are shown in the table below. In the structural formulas, a "wedge" and a "dashed line" indicate the configuration. In particular, among compounds for which the configuration is described, compounds with "racemate" written in the "Stereo" section are racemic compounds with a specific relative configuration. Furthermore, among compounds in which the bond forming the asymmetric carbon is written with a solid line, compounds with "racemate" written in the "Stereo" section are racemic compounds. Compounds with "single isomer" written in the "Stereo" section are single compounds for which the configuration has not been determined.

[0143]

[0144]

[0145]

[0146]

[0147]

[0148]

[0149]

[0150]

[0151]

[0152]

[0153]

[0154]

[0155]

[0156]

[0157]

[0158]

[0159]

[0160]

[0161]

[0162]

[0163]

[0164]

[0165]

[0166]

[0167]

[0168]

[0169]

[0170]

[0171]

[0172]

[0173]

[0174]

[0175]

[0176]

[0177]

[0178]

[0179]

[0180]

[0181]

[0182]

[0183] Examples of biological tests for the compounds according to the present invention are described below. The compounds of the present invention can be tested essentially as in the test examples below. The compounds represented by formula (I), (II), or (III) according to the present invention may have serotonin 5-HT2A receptor antagonistic and / or inverse agonistic activity and antagonize the human serotonin 5-HT2A receptor. The compounds represented by formula (I), (II), or (III) according to the present invention may have serotonin 5-HT2A and 2C receptor antagonistic and / or inverse agonistic activity and antagonize the human serotonin 5-HT2A and 2C receptors. Specifically, in the evaluation methods described below, the Ki value is preferably 5000 nM or less, more preferably 1000 nM or less, and even more preferably 100 nM or less.

[0184] Test Example 1: 5-HT2A receptor binding inhibition test (experimental conditions) Cell membrane: 15 μg of Jump-In HEK cell membrane (expressing human recombinant 5-HT2A receptor) per well Assay buffer: NaCl 120 mmol / L, MgCl ２ ・6H ２ O 1 mmol / L, KCl 5 mmol / L, 0.1% BSA and CaCl ２ 2 mmol / L Tris-HCl 50 mmol / L (pH 7.4) Radioactive ligand: The final concentration is near the Kd value calculated by the following method [ ３[H]-Ketanserin Nonspecific ligand: Serotonin HCl (final concentration 500 μmol / L). The Kd value is calculated when the cell membrane lot is changed. 0.5 μL of 1 mmol / L nonspecific binding calculation compound or DMSO dissolved in DMSO is dispensed into a microplate, and the cell membrane is diluted with assay buffer. The radioactive ligand solution is serially diluted, and counts are confirmed using a liquid scintillator. 50 μL / well of the assay buffer containing the diluted cell membrane is dispensed into the microplate. Then, 50 μL / well of the radioactive ligand solution is dispensed into the microplate, and the plate is sealed. Allow to stand at room temperature (25°C) for 1.5 hours. During this time, 50 μL / well of 50 mmol / L Tris-HCl (pH 7.4) is dispensed into the GF / B UniFilter plate and left to stand at 4°C for at least 1 hour. Then, filtration is performed using a Cell Harvester (PerkinElmer). 10 μL / well of the radioactive ligand solution is dispensed into the empty wells of the GF / B UniFilter plate. After drying the GF / B UniFilter plate at room temperature, 50 μL / well of MicroScinti20 is dispensed into the GF / B UniFilter plate and the plate is sealed. The GF / B UniFilter plate is left to stand overnight at room temperature. The 5-HT2A receptor-bound [ ３The radioactivity of [H]-Ketanserin is measured using Microbeta2 (PerkinElmer) at a measurement time of 1 min / well. A saturation curve is plotted from the measured values, and the Kd value is calculated from the slope of the Scatchard Plot. (Binding Test of the Compound According to the Present Invention) 0.5 μL of compound solution dissolved in DMSO is dispensed into a microplate in advance, and the cell membrane and hot ligand are each diluted with assay buffer. Then, 50 μL / well of the assay buffer containing the diluted cell membrane is dispensed into the microplate. Then, 50 μL / well of the radioactive ligand solution is dispensed into the microplate, and the plate is sealed. Then, the plate is left to stand at room temperature (25°C) for 1.5 hours. During this time, 50 μL / well of 50 mmol / L Tris-HCl (pH 7.4) is dispensed into the GF / B UniFilter plate and left to stand at 4°C for at least 1 hour. Then, filtration is performed using a Cell Harvester (PerkinElmer). After drying the GF / B UniFilter plate at room temperature, 50 μL / well of MicroScinti20 is dispensed into the GF / B UniFilter plate and the plate is sealed. The GF / B UniFilter plate is left to stand overnight at room temperature. ３ The radioactivity of [H]-Ketanserin is measured using Microbeta2 (PerkinElmer) at a measurement time of 1 min / well. Non-specific binding is measured in the presence of 500 μmol / L unlabeled ligand Serotonin HCl, and total binding is measured in the absence of the compound of the present invention (vehicle). ３The binding activity of the compound of the present invention is calculated from the radioactivity of [H]-Ketanserin. Finally, the Ki value is calculated from the dose-response curve. (The binding activity of the compound of the present invention is calculated from the binding inhibition rate (%) below.) Inhibition rate (%) = [1 - (ca) / (ba)] x 100 a; mean cpm of non-specific binding b; mean cpm of total binding c; cpm in the presence of test compound The compounds of the present invention were tested essentially as described above. The results are shown below. (Results) The results of evaluation of the binding activity of the compound of the present invention to the human serotonin 5-HT2A receptor are shown below. Note that Ki values ​​are categorized as "A" for less than 10 nM, "B" for 10 nM or more but less than 100 nM, and "C" for 100 nM or more but less than 500 nM. Compound I-001: 4.82nM Compound I-002: 11.1nM Compound I-003: 19.8nM Compound I-005: 85.3nM Compound I-011: 1.22nM Compound I-027: 1.89nM Compound I-033: 10.1nM Compound I-049: 0.961nM Compound I-057: 5.20nM Compound I-067: 1.37nM Compound I-080: 0.823nM Compound I-087: 1.11nM Compound I-089: 1.49nM Compound I-099: 0.960nM Compound I-104: 1.56nM Compound I-105: 0.979nM Compound I-113: 1.20nM Compound I-114: 0.740nM Compound I-115: 0.703nM Compound I-125: 1.26nM Compound I-128: 1.36nM Compound I-130: 1.29nM

[0185] Test Example 2: 5-HT2C receptor binding inhibition test (experimental conditions) Cell membrane: 0.5 μg of Jump-In HEK cell membrane (expressing human recombinant 5-HT2C receptor) per well Assay buffer: NaCl 120 mmol / L, MgCl ２ ・6H ２ O 1 mmol / L, KCl 5 mmol / L, 0.1% BSA and CaCl ２2 mmol / L Tris-HCl 50 mmol / L (pH 7.4) Radioactive ligand: The final concentration is near the Kd value calculated by the following method [ ３ [H]-Mesulergine Nonspecific ligand: Serotonin HCl at a final concentration of 500 μmol / L. The Kd value is calculated when the cell membrane lot is changed. 0.5 μL of 1 mmol / L nonspecific binding calculation compound or DMSO dissolved in DMSO is dispensed into a microplate, and the cell membrane is diluted with assay buffer. The radioactive ligand solution is serially diluted, and counts are confirmed using a liquid scintillator. 50 μL / well of the assay buffer containing the diluted cell membrane is dispensed into the microplate. Then, 50 μL / well of the radioactive ligand solution is dispensed into the microplate, and the plate is sealed. Allow to stand at 37°C for 2 hours. During this time, 50 μL / well of 50 mmol / L Tris-HCl (pH 7.4) is dispensed into the GF / B UniFilter plate and left to stand at 4°C for at least 1 hour. Then, filtration is performed using a Cell Harvester (PerkinElmer). 10 μL / well of the radioactive ligand solution is dispensed into the empty wells of the GF / B UniFilter plate. After drying the GF / B UniFilter plate at room temperature, 50 μL / well of MicroScinti20 is dispensed into the GF / B UniFilter plate and the plate is sealed. The GF / B UniFilter plate is left to stand overnight at room temperature. The 5-HT2C receptor-bound [ ３The radioactivity of [H]-mesulergine is measured using Microbeta2 (PerkinElmer) at a measurement time of 1 min / well. A saturation curve is plotted from the measured values, and the Kd value is calculated from the slope of the Scatchard Plot. (Binding Test of the Compound According to the Present Invention) 0.5 μL of compound solution dissolved in DMSO is dispensed into a microplate in advance, and the cell membrane and hot ligand are each diluted with assay buffer. Then, 50 μL / well of the assay buffer containing the diluted cell membrane is dispensed into the microplate. Then, 50 μL / well of the radioactive ligand solution is dispensed into the microplate, and the plate is sealed. Then, the plate is left to stand at 37°C for 2 hours. During this time, 50 μL / well of 50 mmol / L Tris-HCl (pH 7.4) is dispensed into the GF / B UniFilter plate and left to stand at 4°C for at least 1 hour. Then, filtration is performed using a Cell Harvester (PerkinElmer). After drying the GF / B UniFilter plate at room temperature, 50 μL / well of MicroScinti20 is dispensed into the GF / B UniFilter plate and sealed. The GF / B UniFilter plate is left to stand overnight at room temperature. ３ The radioactivity of [H]-mesulergine is measured using Microbeta2 (PerkinElmer) at a measurement time of 1 min / well. Non-specific binding is measured in the presence of 500 μmol / L unlabeled ligand serotonin HCl, and total binding is measured in the absence of the compound of the present invention (vehicle). ３The binding activity of the compound according to the present invention is calculated from the radioactivity of [H]-mesulergine. Finally, the Ki value is calculated from the dose-response curve. (The binding activity of the compound according to the present invention is calculated from the binding inhibition rate (%) below.) Inhibition rate (%) = [1 - (ca) / (ba)] x 100 a; mean cpm of non-specific binding b; mean cpm of total binding c; cpm in the presence of test compound The compounds of the present invention were tested essentially as described above. The results are shown below. (Results) The evaluation results of the inhibitory activity of the compound according to the present invention on the binding to human serotonin 5-HT2C receptor are shown below. Note that Ki values ​​are categorized as "A" for less than 10 nM, "B" for 10 nM or more but less than 100 nM, and "C" for 100 nM or more but less than 500 nM. Compound I-001: 16.7nM Compound I-002: 27.1nM Compound I-003: 4.11nM Compound I-005: 219nM Compound I-011: 0.585nM Compound I-027: 2.21nM Compound I-033: 19.0nM Compound I-049: 0.524nM Compound I-057: 2.19nM Compound I-067: 0.950nM Compound I-080: 0.579nM Compound I-087: 0.787nM Compound I-089: 5.46nM Compound I-099: 3.08nM Compound I-104: 0.578nM Compound I-105: 1.13nM Compound I-113: 1.60nM Compound I-114: 0.543nM Compound I-115: 0.469nM Compound I-125: 0.694nM Compound I-128: 0.374nM Compound I-130: 0.535nM

[0186] Test Example 3: hERG Test To assess the risk of electrocardiogram QT interval prolongation of the compounds according to the present invention, the action of the compound is examined by evaluating potassium channel activity using CHO cells expressing the human ether-a-go-go related gene (hERG) channel. The evaluation is carried out using a FluxORII Green Potassium Ion Channel Assay Kit (Invitrogen: Molecular Probes). Cells are seeded in a 384 assay plate (8000 cells / well / 40 μL) and incubated overnight (37°C, 5% CO ２ After replacing the medium with wash buffer (1xHBSS, 20mM HEPES) using a microplate washer, a fluorescent indicator dye was added to the medium and incubated for 1 hour (37°C, 5% CO2) to allow the fluorescent indicator dye to be incorporated into the cells. ２ ) is placed on a cell-based kinetic assay system FLIPR (Molecular Devices), and a compound is added to the cells at the desired concentration and allowed to react for 10 minutes. When a mixture of potassium and thallium, which are stimulants, is added to the cells, the potassium channel opens, and the thallium that flows into the cells binds to the fluorescent indicator dye, increasing the intracellular fluorescent signal, and the potassium channel current is detected as a fluorescent signal. The inhibition rate at each concentration is calculated from the signal intensity at each concentration, with the signal intensity when E-4031 is added to the cells at a final concentration of 10.3 μmol / L defined as 100% inhibition, and the signal intensity when DMSO is added to the cells at a final concentration of 0.5% defined as 0% inhibition. The inhibition rate is calculated from the signal intensity at each concentration. The IC ５０ The compounds of the present invention were tested essentially as described above. The results are shown below. (Results) Compound I-067: IC ５０ =16.3 μM Compound I-080: IC ５０ >52.0 μM Compound I-104: IC ５０ =20.6 μM Compound I-105: IC ５０ =17.9 μM Compound I-113: IC ５０ >52.0 μM Compound I-114: IC ５０ >52.0 μM Compound I-115: IC５０ >52.0 μM Compound I-125: IC ５０ =20.0 μM Compound I-128: IC ５０ >52.0 μM

[0187] Test Example 4: BA Test - Examination of Oral Absorbability Experimental Materials and Methods (1) Animals: Mice or rats are used. (2) Breeding Conditions: Mice or rats are allowed free access to solid feed and sterilized tap water. (3) Dosage and Grouping: Oral and intravenous administration is performed at the specified dosage. Groups are set up as follows. The dosage is changed for each compound as needed. Oral Administration: 2-60 μmol / kg or 1-30 mg / kg (n=2-3) Intravenous Administration: 1-30 μmol / kg or 0.5-10 mg / kg (n=2-3) (4) Preparation of Dosage Solution: Oral administration is administered as a solution or suspension. Intravenous administration is administered after solubilization. (5) Administration Method: Oral administration is administered by forced administration into the stomach using an oral probe. Intravenous administration is administered via the tail vein using a syringe with an injection needle attached. (6) Evaluation item: Blood samples are collected over time, and the plasma concentration of the compound of the present invention is measured using LC / MS / MS. (7) Statistical analysis: The area under the plasma concentration-time curve (AUC) of the compound of the present invention is calculated using moment analysis for the plasma concentration profile of the compound of the present invention, and the bioavailability (BA) of the compound of the present invention is calculated from the dose ratio and AUC ratio between the oral and intravenous administration groups. The dilution concentration and dilution solvent are changed as necessary. The compound of the present invention can be tested essentially as described above.

[0188] Test Example 5: Clearance Evaluation Test Experimental Materials and Methods (1) Animals: SD rats were used. (2) Breeding Conditions: SD rats were allowed free access to solid feed and sterilized tap water. (3) Dose and Grouping: Intravenous administration was performed at a predetermined dose. Groups were set up as follows: Intravenous administration: 1 μmol / kg (n=2) (4) Preparation of Dosage Solution: Solubilized and administered using a dimethyl sulfoxide / propylene glycol = 1 / 1 solvent. (5) Administration Method: Administered via the tail vein using a syringe with an injection needle. (6) Evaluation Items: Blood was collected over time, and the plasma concentration of the compound of the present invention was measured using LC / MS / MS. (7) Statistical Analysis: The total body clearance (CLtot) was calculated using moment analysis based on the progression of the plasma concentration of the compound of the present invention. The dilution concentration and dilution solvent were changed as necessary. The compound of the present invention can be tested essentially as described above.

[0189] Test Example 6: Metabolic Stability Test Commercially available pooled human liver microsomes were reacted with the compound of the present invention for a certain period of time, and the residual percentage was calculated by comparing the reacted and unreacted samples to evaluate the extent of hepatic metabolism of the compound of the present invention. Human liver microsomes were reacted in 0.2 mL of buffer (50 mmol / L Tris-HCl pH 7.4, 150 mmol / L potassium chloride, 10 mmol / L magnesium chloride) containing 0.5 mg protein / mL in the presence of 1 mmol / L NADPH at 37°C for 0 or 30 minutes (oxidation reaction). After the reaction, 70 μL of the reaction mixture was added to 140 μL of a 1 / 1 (v / v) methanol / acetonitrile solution, mixed, and centrifuged at 3000 rpm for 15 minutes. The compound of the present invention in the supernatant was quantified by LC / MS / MS or solid-phase extraction (SPE) / MS. The residual percentage was expressed as the ratio of the amount of compound after the reaction to the amount of compound at 0 minutes, which is defined as 100%. The hydrolysis reaction is carried out in the absence of NADPH, and the glucuronidation reaction is carried out in the presence of 5 mmol / L UDP-glucuronic acid instead of NADPH, and the subsequent procedures are the same. The dilution concentration and dilution solvent may be changed as necessary. The compounds of the present invention can be tested essentially as described above.

[0190] Test Example 7: P-gp Substrate Test A compound of the present invention was added to one side of a Transwell (registered trademark, CORNING) containing a monolayer culture of human MDR1-expressing cells or parental cells, and allowed to react for a certain period of time. The membrane permeability coefficients for the MDR1-expressing cells and parental cells in the apical-to-basolateral direction (A→B) and the basolateral-to-apical direction (B→A) were calculated, and the efflux ratio (ER; ratio of the membrane permeability coefficients B→A and A→B) values ​​for the MDR1-expressing cells and parental cells were calculated. The efflux ratios (ER values) of the MDR1-expressing cells and parental cells were compared to determine whether a compound of the present invention is a P-gp substrate. The compounds of the present invention can be tested essentially as described above.

[0191] Test Example 8: CYP3A4 (MDZ) MBI Test This test evaluates the mechanism-based inhibition (MBI) ability of the compound of the present invention in terms of metabolic potentiation of CYP3A4 inhibition. Using pooled human liver microsomes, CYP3A4 inhibition was evaluated using the 1-hydroxylation reaction of midazolam (MDZ) as an indicator. The reaction conditions were as follows: substrate, 10 μmol / L MDZ; pre-reaction time, 0 or 30 minutes; reaction time, 2 minutes; reaction temperature, 37°C; pooled human liver microsomes, 0.5 mg / mL pre-reaction, 0.05 mg / mL (10-fold dilution) pre-reaction; and compound of the present invention concentrations in the pre-reaction, 0.83, 5, 10, and 20 μmol / L (4 points). Pooled human liver microsomes and a solution of the compound of the present invention were added to a 96-well plate as a pre-reaction solution in K-Pi buffer (pH 7.4) at the pre-reaction composition described above. A portion of this mixture was transferred to another 96-well plate so that it was diluted 1 / 10 with substrate and K-Pi buffer, and the coenzyme NADPH was added to initiate the reaction used as an indicator (no pre-reaction). After the specified reaction time, the reaction was stopped by adding a 1 / 1 (V / V) methanol / acetonitrile solution. NADPH was also added to the remaining pre-reaction solution to initiate the pre-reaction (pre-reaction). After the specified reaction time, a portion of this mixture was transferred to another plate so that it was diluted 1 / 10 with substrate and K-Pi buffer, and the reaction used as an indicator was started. After the specified reaction time, the reaction was stopped by adding a 1 / 1 (V / V) methanol / acetonitrile solution. Each plate in which the indicator reaction was performed was centrifuged at 3000 rpm for 15 minutes, and 1-hydroxymidazolam in the supernatant was quantified by LC / MS / MS. A control (100%) was prepared by adding only DMSO, the solvent in which the compound of the present invention was dissolved, to the reaction system. The residual activity (%) was calculated when each concentration of the compound of the present invention was added, and the IC was calculated by inverse estimation using a logistic model using the concentration and inhibition rate. The Shifted IC value was calculated as the IC at 0 min preincubation / IC at 30 min preincubation. A Shifted IC of 1.5 or greater was considered positive, and a Shifted IC of 1.0 or less was considered negative. The compounds of the present invention were tested essentially as described above. The results are shown below.(Results) Compound I-067: Negative Compound I-080: Negative Compound I-104: Negative Compound I-105: Negative Compound I-113: Negative Compound I-114: Negative Compound I-115: Negative Compound I-125: Negative Compound I-128: Negative.

[0192] Test Example 9: MK801-Induced Hyperlocomotion Inhibition Test 6-10 week-old Wistar male rats were used. Test compound administration solutions were prepared by dissolving the compound in 30 mmol / L HCl as the solvent, and MK801 administration solutions were prepared by dissolving the compound in physiological saline as the solvent. The MK801-induced hyperlocomotion inhibition test was carried out as follows using SCANET (Melquest), the data acquisition program SCL-40, and transparent plastic cages. In the breeding room, the compound administration solution (solvent or test compound solution) was administered subcutaneously and the rat was returned to its breeding cage. Thirty minutes later, the rat was brought into the laboratory and allowed to acclimate to the laboratory. 15 minutes later, the rat was gently removed, and an MK801 administration solution (solvent or MK801 solution) was administered intraperitoneally, followed by returning the rat to its breeding cage. 15 minutes after the intraperitoneal administration, the rat was removed and gently placed in the SCANET, and locomotion measurement was initiated. The measurements are completed 30 minutes after the start of the measurements, and the amount of locomotion for each individual over the 30 minutes is totaled. The test results are analyzed as follows: A Student-T Test (significance level: two-sided 5%) is performed on the test compound administration group and the vehicle administration group. If the test compound administration group shows a significant suppression of locomotion compared to the vehicle administration group, it is determined to have antipsychotic effects. The compounds of the present invention can be tested essentially as described above.

[0193] The following formulation examples are illustrative only and are not intended to limit the scope of the invention. The compounds of the present invention can be administered as pharmaceutical compositions by any conventional route, particularly enterally, e.g., orally, e.g., in the form of tablets or capsules, or parenterally, e.g., in the form of injection solutions or suspensions, topically, e.g., in the form of lotions, gels, ointments, or creams, or intranasally or in the form of suppositories. Pharmaceutical compositions containing the compounds of the present invention in free form or in the form of a pharmaceutically acceptable salt together with at least one pharmaceutically acceptable carrier or diluent can be prepared by conventional mixing, granulation, or coating methods. For example, oral compositions can be in the form of tablets, granules, or capsules containing excipients, disintegrants, binders, lubricants, etc., and active ingredients, etc. Injectable compositions can be in the form of solutions or suspensions, which may be sterilized and may contain preservatives, stabilizers, buffers, etc.

[0194] The compounds according to the present invention have serotonin 5-HT2A receptor antagonistic and / or inverse agonistic activity and are considered to be useful as therapeutic and / or preventive agents for diseases or conditions associated with the serotonin 5-HT2A receptor.

Claims

1. Formula (I): 【Chemical 1】 (In the formula, R １ is a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; A １ are each independently, CR ２ R ２’ and A ２ are each independently, CR ３ R ３’ and R ２ are each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２’ are each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ３ are each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ３’ are each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２ and R ２’ and R ３ and R ３’ may, together with the same carbon atom to which it is attached, form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; m and n are each independently 1, 2, or 3; Ring B is a group represented by the formula: 【Chemistry 2】 (In the formula, R ４ is the formula: 【Chemistry 3】 (In the formula, A ３ are each independently, CR １３ R １３’ and A ４ are each independently, CR １４ R １４’ and R １３ are each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R １３’ are each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R １４ are each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R １４’ are each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; q and r are each independently 0, 1, or 2; q' and r' are each independently 1 or 2; R １０ and R １１ are each independently a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R １２ is a hydrogen atom or a substituted or unsubstituted alkyl; R ８ is a hydrogen atom or substituted or unsubstituted alkyl; R ９ are each independently halogen or substituted or unsubstituted alkyl; and p is an integer of 0 to 6), or a pharmaceutically acceptable salt thereof.

2. R １ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein is a hydrogen atom or substituted or unsubstituted alkyl.

3. 2. The compound of claim 1, wherein m and n are 2, or a pharmaceutically acceptable salt thereof.

4. Ring B is a group of the formula: 【Chemistry 4】 2. The compound according to claim 1, wherein the ring is represented by the formula: wherein the symbols have the same meanings as in claim 1, or a pharmaceutically acceptable salt thereof.

5. Ring B is a group of the formula: 【Chemistry 5】 2. The compound according to claim 1, wherein the ring is represented by the formula: wherein the symbols have the same meanings as in claim 1, or a pharmaceutically acceptable salt thereof.

6. R ４ But the formula: 【Chemistry 6】 2. The compound according to claim 1, which is a group represented by the formula: wherein the symbols have the same meanings as in claim 1, or a pharmaceutically acceptable salt thereof.

7. R １０ 2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein is a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group.

8. R １０ 2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein is a substituted or unsubstituted 5-membered aromatic heterocyclic group.

9. R １１ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein is a substituted or unsubstituted aromatic carbocyclic group.

10. 2. The compound of claim 1, wherein q, r, q', and r' are 1, or a pharmaceutically acceptable salt thereof.

11. Formula (II): 【Chemistry 7】 (In the formula, R １ is a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ２ is a hydrogen atom, halogen, or substituted or unsubstituted alkyl; R ２’ is a hydrogen atom, halogen, or substituted or unsubstituted alkyl; R ３ is a hydrogen atom, halogen, or substituted or unsubstituted alkyl; R ３’ is a hydrogen atom, halogen, or substituted or unsubstituted alkyl; The compound according to claim 1, wherein the other symbols have the same meanings as in claim 1, or a pharmaceutically acceptable salt thereof.

12. Formula (II): 【Chemistry 8】 (In the formula, R １ is a hydrogen atom or alkyl; R ２ is a hydrogen atom or a halogen; R ２’ is a hydrogen atom; R ３ is a hydrogen atom; R ３’ is a hydrogen atom; Ring B is a group represented by the formula: 【Chemistry 9】 (In the formula, R ４ is the formula: 【Chemistry 10】 (In the formula, A ３ is CR １３ R １３’ and A ４ is CR １４ R １４’ and R １３ is a hydrogen atom; R １３’ is a hydrogen atom; R １４ is a hydrogen atom; R １４’ is a hydrogen atom; q and r are each 1; R １０ is a phenyl substituted with a halogen, a phenyl, a 5-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω (substituent group ω: alkyl, haloalkyl, and non-aromatic carbocyclic group), or a 6-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ω′ (substituent group ω′: alkyl and halogen); R １１ is the formula: 【Chemistry 11】 (In the formula, R １８ is a hydrogen atom or a halogen; R １９ is alkyl, haloalkyl, alkyl substituted with an aromatic carbocyclic group, alkyloxy, alkyloxy substituted with a non-aromatic carbocyclic group, alkyloxy or haloalkyloxy substituted with a non-aromatic carbocyclic group substituted with a halogen), a bicyclic 9-membered aromatic heterocyclic group, or a bicyclic 9-membered aromatic heterocyclic group substituted with one or more substituents selected from the substituent group ψ (substituent group ψ: halogen, alkyl, and alkyloxy); R ８ 2. The compound according to claim 1, wherein R is a ring represented by the formula: wherein R is a hydrogen atom, or a pharmaceutically acceptable salt thereof.

13. Formula (III): 【Chemistry 12】 (In the formula, R ３１ is a hydrogen atom or C1-C3 alkyl; R ３２ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３３ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３４ are each independently a hydrogen atom, halogen, or substituted or unsubstituted alkyl; R ３５ are each independently a hydrogen atom, halogen, or substituted or unsubstituted alkyl; R ３２ and R ３３ and R ３４ and R ３５ may, together with the same carbon atom to which it is attached, form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; Ring B' is a group represented by the formula: 【Chemistry 13】 (In the formula, R ６ is the formula: 【Chemistry 14】 (In the formula, A ６ are each independently, CR ２５ R ２５’ and R ２５ are each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２５’ are each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; s is 0 or 1; s' is 0, 1 or 2; R ２４ is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ５ is a hydrogen atom or a substituted or unsubstituted alkyl; R ６ ' is the formula: 【Chemistry 15】 (In the formula, A ７ is CR ２７ R ２７’ and R ２７ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２７’ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; t is 0 or 1; R ２６ is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group; R ７ is the formula: 【Chemistry 16】 (In the formula, A ５ are each independently, CR ２８ R ２８’ and R ２８ are each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ２８’ are each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; u is 0, 1 or 2; R ２３ is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group), R ２１ is a hydrogen atom or substituted or unsubstituted alkyl; R ２２ are each independently halogen or substituted or unsubstituted alkyl; and v is 0, 1 or 2), or a pharmaceutically acceptable salt thereof.

14. Ring B' is a group represented by the formula: 【Chemistry 17】 14. The compound according to claim 13, wherein the ring is represented by the formula: wherein the symbols have the same meanings as in claim 13, or a pharmaceutically acceptable salt thereof.

15. R ６ But the formula: 【Chemistry 18】 14. The compound according to claim 13, which is a group represented by the formula: wherein the symbols have the same meanings as in claim 13, or a pharmaceutically acceptable salt thereof.

16. 14. The compound of claim 13, wherein s' is 1, or a pharmaceutically acceptable salt thereof.

17. R ２４ 14. The compound of claim 13, or a pharmaceutically acceptable salt thereof, wherein is a substituted or unsubstituted aromatic carbocyclic group.

18. 14. The compound of claim 13, wherein u is 1, or a pharmaceutically acceptable salt thereof.

19. R ２３ 14. The compound according to claim 13, or a pharmaceutically acceptable salt thereof, wherein is a substituted or unsubstituted aromatic heterocyclic group.

20. R ３２ and R ３３ The compound according to claim 13 or a pharmaceutically acceptable salt thereof, wherein is a hydrogen atom.

21. 2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of compounds I-067, I-080, I-104, I-105, I-113, I-114, I-115, I-125 and I-128.

22. A pharmaceutical composition comprising the compound according to any one of claims 1 to 21 or a pharmaceutically acceptable salt thereof.

23. 23. The pharmaceutical composition according to claim 22, which is a serotonin 5-HT2A receptor antagonist and / or inverse agonist.

24. 23. The pharmaceutical composition of claim 22, which is a serotonin 5-HT2A and 5-HT2C receptor antagonist and / or inverse agonist.

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