Aromatic heterocyclic derivatives having serotonin receptor binding activity

Abstract

The present invention provides a compound which has a serotonin 5-HT2A receptor inverse agonist effect, a pharmaceutically acceptable salt thereof, and a composition which is for serotonin 5-HT2A receptor inverse agonism and which contains the compound or the salt. Provided is a composition which is for serotonin 5-HT2A receptor inverse agonism and which contains a compound represented by formula (I) or a pharmaceutically acceptable salt thereof. (I) (In formula (I), R1 is a substituted or unsubstituted aromatic heterocyclic group or the like, each R2 is independently a hydrogen atom or the like, each R3 is independently a hydrogen atom or the like, n is 1 or 2, R4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group, L is -NR8- or the like, R8 is a hydrogen atom or the like, each R5 is independently a hydrogen atom or the like, each R6 is independently a hydrogen atom or the like, p is 1 or 2, and R7 is a group represented by the other formula shown.) (In the other formula shown, R9 is substituted or unsubstituted alkyloxy or the like, R10 is a hydrogen atom or the like, R11 is halogen or the like, and m is 0 or 1.)

Description

[Technical Field]

[0001] The present invention relates to compounds having serotonin 5-HT2A receptor inverse agonism and useful in the treatment and / or prevention of diseases caused by serotonin 5-HT2A receptors, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions containing them. [Background technology]

[0002] Neurodegenerative disorders (NDs) are a group of related human diseases that share common pathophysiological characteristics, namely the progressive degeneration of selective neuronal populations over time. These neurodegenerative disorders include, but are not limited to, Alzheimer's disease and related dementia, Parkinson's disease, Huntington's disease, Lewy body dementia and related motor disorders. Each of these disorders has its own 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 specific to each disease (Non-Patent Literature 1).

[0003] Although considerable progress has been made in elucidating the genetic causes underlying these fundamentally different disorders, relatively little is known about the biochemical mechanisms that cause the selective neuronal degeneration common to all of them. Furthermore, while genetic factors causing rare familial forms of these disorders have been identified for the most common ones, including Parkinson's disease and Alzheimer's disease, the pathophysiological basis for the majority of sporadic cases remains unknown. Therefore, there are currently no specific therapeutic agents that can directly alter the progression of these disorders. Instead, clinicians utilize a variety of existing drugs to achieve symptom relief for 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 appearance of motor dysfunction, including bradykinesia, dyskinesia, and chorea, as well as neuropsychiatric symptoms, including psychosis and emotional symptoms such as anxiety and depression, are common symptoms that have a serious impact on the patient's functional status and quality of life (Non-Patent Literature 4, 5). Although most existing treatments, including antipsychotics and antidepressants, are often effective in these patients, their tolerability is remarkably low (Non-Patent Literature 6). Furthermore, while available Parkinson's disease treatments, including L-dopa and dopamine agonists, are generally effective, they currently cause severe treatment-limiting side effects that cannot be managed with pharmacotherapy.

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

[0006] These findings highlight the need to develop novel therapeutic agents that are not only effective against these specific symptoms causing physical impairment, but also specifically designed to be tolerable in these particular patient populations. This can be achieved by improving the selectivity of drug target interactions of new therapeutic agents. Specifically, this is achieved by having strong activity and selectivity for the target 5-HT2A and 2C, while reducing adverse cardiovascular effects.

[0007] Although compounds having serotonin 5-HT2A receptor inverse agonism are described in Patent Documents 3 to 14, none of these documents describe or suggest compounds related to the present invention. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] International Publication No. 2018 / 131672 [Patent Document 2] U.S. Patent No. 8377959 [Patent Document 3] International Publication No. 2001 / 066521 [Patent Document 4] International Publication No. 2004 / 064738 [Patent Document 5] International Publication No. 2019 / 040104 [Patent Document 6] International Publication No. 2019 / 040105 [Patent Document 7] International Publication No. 2019 / 040106 [Patent Document 8] International Publication No. 2019 / 040107 [Patent Document 9] International Publication No. 2010 / 111353 [Patent Document 10] International Publication No. 2004 / 000808 [Patent Document 11] International Publication No. 2003 / 057698 [Patent Document 12] China Publication No. 109111385 [Patent Document 13] International Publication No. 2009 / 039461 [Patent Document 14] International Publication No. 2007 / 124136 [Non-patent literature]

[0009] [Non-Patent Document 1] Nature Reviews Neurology volume 10, pages 620-633(2014) [Non-Patent Document 2] Progress in Neurology and Psychiatry I Vol. 22 Iss. 1 2018 [Non-Patent Document 3] Movement Disorders Vol. 24, No. 11, 2009, pp. 1641-1649 [Non-Patent Document 4] Parkisonism and related disorders 155.200 9.S 105-110 [Non-Patent Document 5] Neurology. 2004; 63(2):293-300. [Non-Patent Document 6] JAMA Neurol. 2016; 73(5):535-541. [Non-Patent Document 7] Lancet; 383:533-40(2014) [Non-Patent Document 8] Journal of Pharmacology and Experimental Therapeutics May 2006, 317 (2) 910-918 [Non-Patent Document 9] CNS Spectrum (2016), 21, 271-275 [Overview of the project] [Problems that the invention aims to solve]

[0010] The object of the present invention is to provide novel compounds having serotonin 5-HT2A receptor inverse agonism and compositions for serotonin 5-HT2A receptor inverse agonism. More preferably, the present invention provides novel compounds having an effect on serotonin-related diseases, including hallucinations and delusions associated with Parkinson's disease and / or dementia, by having serotonin 5-HT2A receptor inverse agonism, and pharmaceuticals containing these.

Means for Solving the Problem

[0011] The present invention relates to the following items (1α) to (20α), (1) to (17), (1'), (3'), (7'), (9'), (7'') and (7''') (1α) Formula (II):<00?0766>

Chem.

Chem.

Chem.

Chem.

Chem.

Chemical formula

[0012] Furthermore, the present invention relates to the following items (1αA)~(22αA), (1A)~(15A), (1'A)~(7'A), (9'A), (10'A), (12'A), (1''A), (7''A), (1'''A), (7'''A), and (7''''A). Equation (1αA)(I): [ka] (In the formula, R 1 is a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group; R 2 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 3 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; n is either 1 or 2; R 4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; L is -NR 8 -, -O-, or single bond; R 8 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 5 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 6 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; p is either 1 or 2; R 7 The formula is: [ka] (In the formula, R 9 is a hydrogen atom, a halogen, a substituted or unsubstituted alkyloxy, a substituted or unsubstituted non-aromatic carbocyclic oxy, a substituted or unsubstituted amino, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkyl; R 10 is a hydrogen atom, hydroxyl, halogen or substituted or unsubstituted alkyl; or, R 9 and R 10 These combine to form substituted or unsubstituted non-aromatic heterocycles; R 11 is a halogen, hydroxyl, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; The compound represented by (m is a group represented by 0 or 1) (except for the compounds in (i) and (ii) below: (i) L is a single bond, and R 1 Compounds in which furyl or thienyl is substituted or unsubstituted; (ii) L is -NR 8 - and R 1A serotonin 5-HT2A receptor inverse agonist containing a compound in which 2,3-dihydrobenzofuryl is substituted or unsubstituted, or a pharmaceutically acceptable salt thereof. (2αA)R 1 is a substituted or unsubstituted aromatic heterocyclic group; L is -NR 8 A serotonin 5-HT2A receptor inverse agonist according to item (1αA) above, comprising a compound or a pharmaceutically acceptable salt thereof that is - or -O-. (3αA) Formula (II): [ka] (In the formula, R 1 is a substituted or unsubstituted aromatic heterocyclic group; R 2 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 3 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; n is either 1 or 2; R 4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; R 8 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 5 is a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 6 is a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 7 The formula is: [ka] (In the formula, R9 is a substituted or unsubstituted alkyloxy, a substituted or unsubstituted non-aromatic carbocyclic oxy, a substituted or unsubstituted amino, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkyl; R 10 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 9 and R 10 These combine to form substituted or unsubstituted non-aromatic heterocycles; R 11 is a halogen, hydroxyl, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; m is a group represented by (where m is 0 or 1) (however, the compounds represented by (where m is a groupm is a group represented by [ka] A serotonin 5-HT2A receptor inverse agonist containing (excluding) or a pharmaceutically acceptable salt thereof. (4αA)R 1 A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1αA) to (3αA), wherein is a substituted or unsubstituted aromatic nitrogen-containing heterocyclic group. (5αA)R 1 A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1αA) to (4αA), wherein is a substituted or unsubstituted 6-membered aromatic nitrogen-containing heterocyclic group or a substituted or unsubstituted 5-membered aromatic nitrogen-containing heterocyclic group. (6αA)R 2 and R 3 A serotonin 5-HT2A receptor inverse agonist described in any of the above items (1αA) to (5αA), wherein the atom is a hydrogen atom. A serotonin 5-HT2A receptor inverse agonist described in any of the above items (1αA) to (6αA), wherein (7αA)n is 1. (8αA)R 4A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1αA) to (7αA), wherein is a substituted or unsubstituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic group. (9αA)R 4 A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1αA) to (8αA), wherein piperidinil is either substituted or unsubstituted. (10αA)R 4 The formula is: [ka] (In the formula, R 21 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 22 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; R 23 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 22 and R 23 A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1αA) to (9αA), which is a group represented by (together with the carbon atom to which it is bonded, forming a substituted or unsubstituted non-aromatic carbocyclic ring). (11αA)R 4 The formula is: [ka] (In the formula, R 21 , R 22 and R 23 A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1αA) to (10αA), which is a group indicated by the above item (10αA) (synonymous with the above item (10αA)). (12αA)R 22 is a halogen or a substituted or unsubstituted alkyl group; R 23 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 22 and R23 A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1αA) to (11αA), wherein the bonded carbon atom forms a substituted or unsubstituted non-aromatic carbon ring together with the bonded carbon atom. (13αA)R 8 A serotonin 5-HT2A receptor inverse agonist described in any of the above items (1αA) to (12αA), wherein the atom is a hydrogen atom. (14αA)R 5 and R 6 A serotonin 5-HT2A receptor inverse agonist described in any of the above items (1αA) to (13αA), wherein the atom is a hydrogen atom. (15αA)R 7 The formula is: [ka] (In the formula, R 9 A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1αA) to (14αA), wherein the group is represented by (which is a substituted or unsubstituted alkyloxy). (16αA) Formula (III): [ka] (In the formula, R 1 is a substituted or unsubstituted six-membered aromatic nitrogen-containing heterocyclic group or a substituted or unsubstituted five-membered aromatic nitrogen-containing heterocyclic group; R 4 The formula is: [ka] (In the formula, R 21 This is a group represented by a hydrogen atom or a substituted or unsubstituted alkyl group. R 7 The formula is: [ka] (In the formula, R 9A serotonin 5-HT2A receptor inverse agonist as described in item (3αA) above, which is a group represented by (a substituted or unsubstituted C2-C4 alkyloxy or a substituted or unsubstituted amino). (17αA)R 1 However, the serotonin 5-HT2A receptor inverse agonist described in item (16αA) above is a substituted or unsubstituted 5-membered aromatic nitrogen-containing heterocyclic group. (18αA) A serotonin 5-HT2A receptor inverse agonist as described in item (3αA) above, selected from the group consisting of compounds I-008, I-027, I-047, I-102, I-112, I-114, I-115, I-124, I-126, I-129, I-133, I-134, I-138, I-139, I-140, I-141, I-144, and I-145. (19αA) A method for treating and / or preventing a disease involving the serotonin 5-HT2A receptor, characterized by administering a serotonin 5-HT2A receptor inverse agonist described in any of the above items (1αA) to (18αA). (20αA) A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1αA) to (18αA), for use in the treatment and / or prevention of diseases involving the serotonin 5-HT2A receptor. (21αA) Use of any of the serotonin 5-HT2A receptor inverse agonists described in any of the above items (1αA) to (18αA) for the manufacture of agents for the treatment and / or prophylactic of diseases involving the serotonin 5-HT2A receptor. (1A) Formula (I): [ka] (In the formula, R 1 is a substituted or unsubstituted aromatic heterocyclic group; R 2 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 3Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; n is either 1 or 2; R 4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; L is -NR 8 -, -O-, or single bond; R 8 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 5 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 6 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; p is either 1 or 2; R 7 The formula is: [ka] (In the formula, R 9 is a substituted or unsubstituted alkyloxy, a substituted or unsubstituted amino, or a substituted or unsubstituted alkyl; R 10 is a hydrogen atom, a halogen or a substituted or unsubstituted alkyl; or, R 9 and R 10 These combine to form substituted or unsubstituted non-aromatic heterocycles; R 11 is a halogen, hydroxyl, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; A serotonin 5-HT2A receptor inverse agonist containing a compound represented by (where m is a group represented by 0 or 1) or a pharmaceutically acceptable salt thereof. (1'A) Equation (I): [ka] (In the formula, R 1 is a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group; R 2 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 3 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; n is either 1 or 2; R 4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; L is -NR 8 -, -O-, or single bond; R 8 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 5 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 6 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; p is either 1 or 2; R 7 The formula is: [ka] (In the formula, R 9 is a hydrogen atom, a halogen, a substituted or unsubstituted alkyloxy, a substituted or unsubstituted non-aromatic carbocyclic oxy, a substituted or unsubstituted amino, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkyl; R 10is a hydrogen atom, hydroxyl, halogen or substituted or unsubstituted alkyl; or, R 9 and R 10 These combine to form substituted or unsubstituted non-aromatic heterocycles; R 11 is a halogen, hydroxyl, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; The compound represented by (m is a group represented by 0 or 1) (except for the compounds in (i) and (ii) below: (i) L is a single bond, and R 1 Compounds in which furyl or thienyl is substituted or unsubstituted; (ii) L is -NR 8 - and R 1 A serotonin 5-HT2A receptor inverse agonist containing a compound in which 2,3-dihydrobenzofuryl is substituted or unsubstituted, or a pharmaceutically acceptable salt thereof. (1''A)R 1 is a substituted or unsubstituted aromatic heterocyclic group; L is -NR 8 A serotonin 5-HT2A receptor inverse agonist as described in item (1'A) above, comprising a compound or a pharmaceutically acceptable salt thereof that is - or -O-. (1'''A) Equation (II): [ka] (In the formula, R 1 is a substituted or unsubstituted aromatic heterocyclic group; R 2 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 3 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; n is either 1 or 2; R 4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; R 8 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 5 is a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 6 is a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 7 The formula is: [ka] (In the formula, R 9 is a substituted or unsubstituted alkyloxy, a substituted or unsubstituted non-aromatic carbocyclic oxy, a substituted or unsubstituted amino, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkyl; R 10 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 9 and R 10 These combine to form substituted or unsubstituted non-aromatic heterocycles; R 11 is a halogen, hydroxyl, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; The compound is a group represented by (where m is 0 or 1) (however, the compounds shown below: [ka] A serotonin 5-HT2A receptor inverse agonist containing (excluding) or a pharmaceutically acceptable salt thereof. (2A)R 1 A serotonin 5-HT2A receptor inverse agonist as described in item (1A) above, wherein is a substituted or unsubstituted aromatic nitrogen-containing heterocyclic group. (2'A)R 1 A serotonin 5-HT2A receptor inverse agonist according to any one of the above items (1'A), (1''A), and (1''''A), comprising a compound or a pharmaceutically acceptable salt thereof, wherein is a substituted or unsubstituted aromatic nitrogen-containing heterocyclic group. (3A)R 1 A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1A), (2A), (1'A), (1''A), and (1'''A), wherein is a substituted or unsubstituted 6-membered aromatic heterocyclic group or a substituted or unsubstituted 5-membered aromatic heterocyclic group. (3'A)R 1 A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1A), (2A), (1'A), (1''A), and (1'''A), comprising a compound or a pharmaceutically acceptable salt thereof, wherein is a substituted or unsubstituted 6-membered aromatic nitrogen-containing heterocyclic group or a substituted or unsubstituted 5-membered aromatic nitrogen-containing heterocyclic group. (4A)R 2 and R 3 A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1A) to (3A), wherein the atom is a hydrogen atom. (4'A)R 2 and R 3 A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1'A) to (3'A), (1''A), and (1'''A), comprising a compound or a pharmaceutically acceptable salt thereof in which is a hydrogen atom. A serotonin 5-HT2A receptor inverse agonist described in any of the above items (1A) to (4A), wherein (5A)n is 1. A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1'A) to (4'A), (1''A), and (1'''A), comprising a compound or a pharmaceutically acceptable salt thereof in which (5'A)n is 1. (6A)R 4 A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1A) to (5A), wherein is a substituted or unsubstituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic group. (6'A)R 4A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1'A) to (5'A), (1''A), and (1'''A), comprising a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a substituted or unsubstituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic group. (7A)R 4 A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1A) to (6A), wherein piperidinil is either substituted or unsubstituted. (7'A)R 4 A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1'A) to (6'A), (1''A), and (1'''A), comprising a compound or a pharmaceutically acceptable salt thereof, wherein piperidinil is substituted or unsubstituted. (7''A)R 4 The formula is: [ka] (In the formula, R 21 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 22 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; R 23 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 22 and R 23 A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1A) to (7A), (1'A) to (7'A), (1''A), and (1'''A), comprising a compound or a pharmaceutically acceptable salt thereof, which is a group represented by (together with the carbon atom to which it is bonded, to form a substituted or unsubstituted non-aromatic carbon ring). (7'''A)R 4 The formula is: [ka] (In the formula, R 21 , R 22 and R23 A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1A) to (7A), (1'A) to (7'A), (1''A), (7''A), and (1'''A), comprising a compound or a pharmaceutically acceptable salt thereof, wherein (1'''A) is a group indicated in item (7''A) above. (7''''A)R 22 is a halogen or a substituted or unsubstituted alkyl group; R 23 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 22 and R 23 A serotonin 5-HT2A receptor inverse agonist according to item (7''A) or (7'''A), comprising a compound or a pharmaceutically acceptable salt thereof, which together with a carbon atom to which it is bonded, form a substituted or unsubstituted non-aromatic carbon ring. (8A)L is -NR 8 A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1A) to (7A), which is - or -O-. (9A)L is -NH-, and is a serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1A) to (8A). (9'A)R 8 A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1'A) to (7'A), (1''A), (7''A), (1'''A), (7'''), and (7''''A), comprising a compound or a pharmaceutically acceptable salt thereof in which is a hydrogen atom. (10A)R 5 and R 6 A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1A) to (9A), wherein the atom is a hydrogen atom. (10'A)R 5 and R 6 A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1'A) to (7'A), (9'A), (1''A), (7''A), (1'''A), (7'''A), and (7''''A), comprising a compound or a pharmaceutically acceptable salt thereof in which is a hydrogen atom. (11A) A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1A) to (10A), wherein p is 1. (12A)R 7 The formula is: [ka] (In the formula, R 9 A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1A) to (11A), wherein the group is represented by (which is a substituted or unsubstituted alkyloxy). (12A')R 7 The formula is: [ka] (In the formula, R 9 A serotonin 5-HT2A receptor inverse agonist according to any of the above items (1'A) to (7'A), (9'A), (10'A), (1''A), (7''A), (1'''A), (7'''A), and (7''''A), comprising a compound or a pharmaceutically acceptable salt thereof, wherein the group is represented by (a) is a substituted or unsubstituted alkyloxy. (13A) A method for treating and / or preventing a disease involving the serotonin 5-HT2A receptor, characterized by administering a serotonin 5-HT2A receptor inverse agonist described in any of the above items (1A) to (12A), (1'A) to (7'A), (9'A), (10'A), (12'A), (1''A), (7''A), (1'''A), (7'''A), and (7''''A). (14A) A serotonin 5-HT2A receptor inverse agonist as described in any of the above items (1A) to (12A), (1'A) to (7'A), (9'A), (10'A), (12'A), (1''A), (7''A), (1'''A), (7'''A), and (7''''A), for use in the treatment and / or prevention of diseases involving the serotonin 5-HT2A receptor. (15A) Use of any of the serotonin 5-HT2A receptor inverse agonists described in items (1A) to (12A), (1'A) to (7'A), (9'A), (10'A), (12'A), (1''A), (7''A), (1'''A), (7'''A), and (7''''A) above for the manufacture of agents for the treatment and / or prophylaxis of diseases involving the serotonin 5-HT2A receptor.

[0013] Furthermore, the present invention relates to the following items (1αB)~(22αB), (1B)~(15B), (1'B)~(7'B), (9'B), (10'B), (12'B), (1''B), (7''B), (1'''B), (7'''B), and (7''''B). (1αB) Equation (I): [ka] (In the formula, R 1 is a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group; R 2 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 3 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; n is either 1 or 2; R 4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; L is -NR 8 -, -O-, or single bond; R 8 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 5 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 6Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; p is either 1 or 2; R 7 The formula is: [ka] (In the formula, R 9 is a hydrogen atom, a halogen, a substituted or unsubstituted alkyloxy, a substituted or unsubstituted non-aromatic carbocyclic oxy, a substituted or unsubstituted amino, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkyl; R 10 is a hydrogen atom, hydroxyl, halogen or substituted or unsubstituted alkyl; or, R 9 and R 10 These combine to form substituted or unsubstituted non-aromatic heterocycles; R 11 is a halogen, hydroxyl, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; The compound represented by (m is a group represented by 0 or 1) (except for the compounds in (i) and (ii) below: (i) L is a single bond, and R 1 Compounds in which furyl or thienyl is substituted or unsubstituted; (ii) L is -NR 8 - and R 1 A serotonin 5-HT2A receptor inverse agonist composition containing a compound in which is substituted or unsubstituted 2,3-dihydrobenzofuryl or a pharmaceutically acceptable salt thereof. (2αB)R 1 is a substituted or unsubstituted aromatic heterocyclic group; L is -NR 8A serotonin 5-HT2A receptor inverse agonist composition according to item (1αB) above, comprising a compound that is - or -O- or a pharmaceutically acceptable salt thereof. (3αB) Formula (II): [ka] (In the formula, R 1 is a substituted or unsubstituted aromatic heterocyclic group; R 2 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 3 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; n is either 1 or 2; R 4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; R 8 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 5 is a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 6 is a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 7 The formula is: [ka] (In the formula, R 9 is a substituted or unsubstituted alkyloxy, a substituted or unsubstituted non-aromatic carbocyclic oxy, a substituted or unsubstituted amino, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkyl; R 10is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 9 and R 10 These combine to form substituted or unsubstituted non-aromatic heterocycles; R 11 is a halogen, hydroxyl, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; m is a group represented by (where m is 0 or 1) (however, the compounds represented by (where m is a group [ka] A composition for serotonin 5-HT2A receptor inverse agonism, comprising (excluding) or a pharmaceutically acceptable salt thereof. (4αB)R 1 A serotonin 5-HT2A receptor reverse agonist composition according to any of the above items (1αB) to (3αB), wherein is a substituted or unsubstituted aromatic nitrogen-containing heterocyclic group. (5αB)R 1 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1αB) to (4αB), wherein is a substituted or unsubstituted 6-membered aromatic nitrogen-containing heterocyclic group or a substituted or unsubstituted 5-membered aromatic nitrogen-containing heterocyclic group. (6αB)R 2 and R 3 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1αB) to (5αB), wherein the atom is a hydrogen atom. A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1αB) to (6αB), wherein (7αB)n is 1. (8αB)R 4 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1αB) to (7αB), wherein is a substituted or unsubstituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic group. (9αB)R 4 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1αB) to (8αB), wherein is substituted or unsubstituted piperidinyl. (10αB)R 4 The formula is: [ka] (In the formula, R 21 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 22 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; R 23 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 22 and R 23 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1αB) to (9αB), wherein the group is represented by (which together with the carbon atom to which it is bonded to form a substituted or unsubstituted non-aromatic carbocyclic ring). (11αB)R 4 The formula is: [ka] (In the formula, R 21 , R 22 and R 23 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1αB) to (10αB), wherein the group is the same as item (10αB) above. (12αB)R 22 is a halogen or a substituted or unsubstituted alkyl group; R 23 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 22 and R 23 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1αB) to (11αB), wherein the carbon atom to which the agonist is bonded forms a substituted or unsubstituted non-aromatic carbocyclic ring. (13αB)R 8A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1αB) to (12αB), wherein the atom is a hydrogen atom. (14αB)R 5 and R 6 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1αB) to (13αB), wherein the atom is a hydrogen atom. (15αB)R 7 The formula is: [ka] (In the formula, R 9 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1αB) to (14αB), wherein the group is represented by (which is a substituted or unsubstituted alkyloxy). (16αB) Formula (III): [ka] (In the formula, R 1 is a substituted or unsubstituted six-membered aromatic nitrogen-containing heterocyclic group or a substituted or unsubstituted five-membered aromatic nitrogen-containing heterocyclic group; R 4 The formula is: [ka] (In the formula, R 21 This is a group represented by a hydrogen atom or a substituted or unsubstituted alkyl group. R 7 The formula is: [ka] (In the formula, R 9 A serotonin 5-HT2A receptor inverse agonist composition according to item (3αB) above, wherein the group is represented by (a substituted or unsubstituted C2-C4 alkyloxy or a substituted or unsubstituted amino). (17αB)R1 The serotonin 5-HT2A receptor reverse agonist composition described in item (16αB) above, wherein the group is a substituted or unsubstituted 5-membered aromatic nitrogen-containing heterocyclic group. A serotonin 5-HT2A receptor inverse agonist composition according to item (3αB) above, selected from the group consisting of compounds I-008, I-027, I-047, I-102, I-112, I-114, I-115, I-124, I-126, I-129, I-133, I-134, I-138, I-139, I-140, I-141, I-144, and I-145. (19αB) A method for treating and / or preventing a disease involving the serotonin 5-HT2A receptor, characterized by administering a serotonin 5-HT2A receptor inverse agonist composition described in any of the above items (1αB) to (18αB). (20αB) A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1αB) to (18αB), for use in the treatment and / or prevention of diseases involving the serotonin 5-HT2A receptor. (21αB) Use of a serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1αB) to (18αB) for the manufacture of a therapeutic and / or prophylactic agent for diseases involving the serotonin 5-HT2A receptor. (1B) Formula (I): [ka] (In the formula, R 1 is a substituted or unsubstituted aromatic heterocyclic group; R 2 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 3 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; n is either 1 or 2; R 4is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; L is -NR 8 -, -O-, or single bond; R 8 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 5 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 6 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; p is either 1 or 2; R 7 The formula is: [ka] (In the formula, R 9 is a substituted or unsubstituted alkyloxy, a substituted or unsubstituted amino, or a substituted or unsubstituted alkyl; R 10 is a hydrogen atom, a halogen or a substituted or unsubstituted alkyl; or, R 9 and R 10 These combine to form substituted or unsubstituted non-aromatic heterocycles; R 11 is a halogen, hydroxyl, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; A serotonin 5-HT2A receptor inverse agonist composition comprising a compound represented by (where m is a group represented by 0 or 1) or a pharmaceutically acceptable salt thereof. (1'B) Formula (I): [ka] (In the formula, R 1is a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group; R 2 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 3 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; n is either 1 or 2; R 4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; L is -NR 8 -, -O-, or single bond; R 8 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 5 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 6 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; p is either 1 or 2; R 7 The formula is: [ka] (In the formula, R 9 is a hydrogen atom, a halogen, a substituted or unsubstituted alkyloxy, a substituted or unsubstituted non-aromatic carbocyclic oxy, a substituted or unsubstituted amino, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkyl; R 10 is a hydrogen atom, hydroxyl, halogen or substituted or unsubstituted alkyl; or, R 9 and R 10These combine to form substituted or unsubstituted non-aromatic heterocycles; R 11 is a halogen, hydroxyl, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; The compound represented by (m is a group represented by 0 or 1) (except for the compounds in (i) and (ii) below: (i) L is a single bond, and R 1 Compounds in which furyl or thienyl is substituted or unsubstituted; (ii) L is -NR 8 - and R 1 A serotonin 5-HT2A receptor inverse agonist composition containing a compound in which is substituted or unsubstituted 2,3-dihydrobenzofuryl or a pharmaceutically acceptable salt thereof. (1''B)R 1 is a substituted or unsubstituted aromatic heterocyclic group; L is -NR 8 A serotonin 5-HT2A receptor inverse agonist composition according to item (1'B) above, comprising a compound that is - or -O- or a pharmaceutically acceptable salt thereof. (1'''B) Formula (II): [ka] (In the formula, R 1 is a substituted or unsubstituted aromatic heterocyclic group; R 2 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 3 Each of these is independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; n is either 1 or 2; R 4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; R 8is a hydrogen atom or a substituted or unsubstituted alkyl group; R 5 is a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 6 is a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group; R 7 The formula is: [ka] (In the formula, R 9 is a substituted or unsubstituted alkyloxy, a substituted or unsubstituted non-aromatic carbocyclic oxy, a substituted or unsubstituted amino, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkyl; R 10 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 9 and R 10 These combine to form substituted or unsubstituted non-aromatic heterocycles; R 11 is a halogen, hydroxyl, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; The compound is a group represented by (where m is 0 or 1) (however, the compounds shown below: [ka] A serotonin 5-HT2A receptor inverse agonist composition containing (excluding) or a pharmaceutically acceptable salt thereof. (2B)R 1 A serotonin 5-HT2A receptor reverse agonist composition according to item (1B) above, wherein is a substituted or unsubstituted aromatic nitrogen-containing heterocyclic group. (2'B)R 1A serotonin 5-HT2A receptor inverse agonist composition according to any one of the above items (1'B), (1''B), and (1'''B), comprising a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a substituted or unsubstituted aromatic nitrogen-containing heterocyclic group. (3B)R 1 A serotonin 5-HT2A receptor inverse agonist composition according to any one of the above items (1B), (2B), (1'B), (1''B), and (1'''B), wherein is a substituted or unsubstituted 6-membered aromatic heterocyclic group or a substituted or unsubstituted 5-membered aromatic heterocyclic group. (3'B)R 1 A serotonin 5-HT2A receptor inverse agonist composition according to any one of the above items (1B), (2B), (1'B), (1''B), and (1'''B), comprising a compound or a pharmaceutically acceptable salt thereof, wherein is a substituted or unsubstituted 6-membered aromatic nitrogen-containing heterocyclic group or a substituted or unsubstituted 5-membered aromatic nitrogen-containing heterocyclic group. (4B)R 2 and R 3 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1B) to (3B), wherein is a hydrogen atom. (4'B)R 2 and R 3 A serotonin 5-HT2A receptor inverse agonist composition according to any one of the above items (1'B) to (3'B), (1''B), and (1'''B), comprising a compound or a pharmaceutically acceptable salt thereof in which is a hydrogen atom. A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1B) to (4B), wherein (5B)n is 1. A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1'B) to (4'B), (1''B), and (1'''B), comprising a compound or a pharmaceutically acceptable salt thereof, wherein (5'B)n is 1. (6B)R 4 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1B) to (5B), wherein is a substituted or unsubstituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic group. (6'B)R 4A serotonin 5-HT2A receptor inverse agonist composition according to any one of the above items (1'B) to (5'B), (1''B), and (1'''B), comprising a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a substituted or unsubstituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic group. (7B)R 4 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1B) to (6B), wherein is substituted or unsubstituted piperidinil. (7'B)R 4 A serotonin 5-HT2A receptor inverse agonist composition according to any one of the above items (1'B) to (6'B), (1''B), and (1'''B), comprising a compound or a pharmaceutically acceptable salt thereof, wherein the compound is substituted or unsubstituted piperidinyl. (7''B)R 4 The formula is: [ka] (In the formula, R 21 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 22 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; R 23 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 22 and R 23 A serotonin 5-HT2A receptor inverse agonist composition according to any one of the above items (1B) to (7B), (1'B) to (7'B), (1''B) and (1'''B), comprising a compound or a pharmaceutically acceptable salt thereof, which is a group represented by (together with a carbon atom to which it is bonded, to form a substituted or unsubstituted non-aromatic carbon ring). (7'''B)R 4 The formula is: [ka] (In the formula, R 21 , R 22and R 23 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1B) to (7B), (1'B) to (7'B), (1''B), (7''B), and (1'''B), comprising a compound or a pharmaceutically acceptable salt thereof, wherein (1'''B) is a group indicated in item (7''B) above. (7''''B)R 22 is a halogen or a substituted or unsubstituted alkyl group; R 23 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 22 and R 23 A serotonin 5-HT2A receptor inverse agonist composition according to item (7''B) or (7'''B), comprising a compound or a pharmaceutically acceptable salt thereof, which together with a carbon atom to which it is bonded, form a substituted or unsubstituted non-aromatic carbon ring. (8B)L is -NR 8 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1B) to (7B), wherein the composition is - or -O-. A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1B) to (8B), wherein (9B)L is -NH-. (9'B)R 8 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1'B) to (7'B), (1''B), (7''B), (1'''B), (7'''), and (7''''B), comprising a compound or a pharmaceutically acceptable salt thereof in which is a hydrogen atom. (10B)R 5 and R 6 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1B) to (9B), wherein the atom is a hydrogen atom. (10'B)R 5 and R 6A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1'B) to (7'B), (9'B), (1''B), (7''B), (1'''B), (7'''B), and (7''''B), comprising a compound or a pharmaceutically acceptable salt thereof in which is a hydrogen atom. (11B) A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1B) to (10B), wherein p is 1. (12B)R 7 The formula is: [ka] (In the formula, R 9 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1B) to (11B), wherein the group is represented by (which is a substituted or unsubstituted alkyloxy). (12B')R 7 The formula is: [ka] (In the formula, R 9 A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1'B) to (7'B), (9'B), (10'B), (1''B), (7''B), (1'''B), (7'''B), and (7''''B), comprising a compound or a pharmaceutically acceptable salt thereof, wherein the group is represented by (a) is a substituted or unsubstituted alkyloxy. (13B) A method for treating and / or preventing a disease involving the serotonin 5-HT2A receptor, characterized by administering a serotonin 5-HT2A receptor inverse agonist composition described in any of the above items (1B) to (12B), (1'B) to (7'B), (9'B), (10'B), (12'B), (1''B), (7''B), (1'''B), (7'''B), and (7''''B). (14B) A serotonin 5-HT2A receptor inverse agonist composition according to any of the above items (1B) to (12B), (1'B) to (7'B), (9'B), (10'B), (12'B), (1''B), (7''B), (1'''B), (7'''B), and (7''''B), for use in the treatment and / or prevention of diseases involving the serotonin 5-HT2A receptor. (15B) Use of any of the serotonin 5-HT2A receptor inverse agonists described in items (1B) to (12B), (1'B) to (7'B), (9'B), (10'B), (12'B), (1''B), (7''B), (1'''B), (7'''B), and (7''''B) above for the manufacture of therapeutic and / or prophylactic agents for diseases involving the serotonin 5-HT2A receptor. [Effects of the Invention]

[0014] The compounds according to the present invention (in this specification, "compounds according to the present invention" means the compounds of the present invention, the compounds relating to the 5-HT2A receptor inverse agonist of the present invention, the compounds relating to the composition for 5-HT2A receptor inverse agonism of the present invention, or the compounds relating to the pharmaceutical composition of the present invention) have serotonin 5-HT2A receptor inverse agonism and are useful as therapeutic and / or prophylactic agents for hallucinations and delusions associated with Parkinson's disease and / or dementia. [Modes for carrying out the invention]

[0015] The meanings of the terms used in this specification are 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 "includes" means that it is not limited to constituent elements and does not exclude any elements that are not listed. The present invention will now be described with reference to embodiments. Throughout this specification, singular expressions should be understood to include the concept of their plural form unless otherwise specified. Therefore, singular articles (for example, "a," "an," and "the" in English) should be understood to include the concept of their plural form unless otherwise specified. Furthermore, unless otherwise specified, terms used herein should be understood to have the meaning commonly used in the art described above. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention pertains. In case of any conflict, this specification (including definitions) shall prevail.

[0016] "Halogen" includes fluorine atoms, chlorine atoms, bromine atoms, and iodine atoms. Fluorine atoms and chlorine atoms are particularly preferred.

[0017] "Alkyl" refers to linear 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, n-decyl, and the like. 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 9 In the alkyloxy, C2-C4 alkyl is preferred as the alkyl portion. Examples include ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, and the like.

[0018] "Haloalkyl" refers to the alkyl group 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, and chlorofluoromethyl.

[0019] "Alkenyl" refers to a linear or branched hydrocarbon group 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, 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, pentadecenyl, and the like. Preferred embodiments of "alkenyl" include vinyl, allyl, propenyl, isopropenyl, and butenyl. More preferred embodiments include vinyl, n-propenyl, and the like.

[0020] "Alkynyl" refers to a linear 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, having one or more triple bonds at any position. It may also have double bonds at any position. Examples include ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octinyl, noninyl, desynyl, etc. Preferred embodiments of "alkynyl" include ethynyl, propynyl, butynyl, and pentynyl. More preferred embodiments include ethynyl, propynyl, and the like.

[0021] An "aromatic carbocyclic group" refers to a cyclic aromatic hydrocarbon group consisting of one or more rings. Examples include phenyl, naphthyl, anthryl, and phenanthryl. A preferred embodiment of the "aromatic carbocyclic group" is phenyl.

[0022] "Aromatic carbocyclic ring" refers to a ring derived from the "aromatic carbocyclic group" described above.

[0023] "Non-aromatic carbocyclic group" refers to a monocyclic or bicyclic or multicyclic cyclic saturated hydrocarbon group or a cyclic non-aromatic unsaturated hydrocarbon group. A "non-aromatic carbocyclic group" with two or more rings also includes a monocyclic or bicyclic or multicyclic non-aromatic carbocyclic group to which the rings in the above-mentioned "aromatic carbocyclic group" are fused. Furthermore, "non-aromatic carbocyclic groups" also include groups that are bridging or that form a spiro ring, as described below. [ka] 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 non-aromatic carbocyclic group with two or more rings preferably has 8 to 20 carbon atoms, and more preferably 8 to 16 carbon atoms. Examples include indanyl, indenyl, acenaphthyl, tetrahydronaphthyl, and fluorenyl.

[0024] "Non-aromatic carbon ring" refers to a ring derived from the "non-aromatic carbon ring group" described above.

[0025] An "aromatic heterocyclic group" refers to an aromatic cyclic group, whether monocyclic or bicyclic, that has one or more identical or different heteroatoms arbitrarily selected from O, S, and N within the ring. The aromatic heterocyclic group with two or more rings includes a monocyclic or aromatic heterocyclic group with two or more rings fused with the rings in the above-mentioned "aromatic carbocyclic group," and the bond may be located on any of the rings. The monocyclic aromatic heterocyclic group is 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, and thiadiazolyl. Examples of 6-membered aromatic heterocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl. The bicyclic aromatic heterocyclic group is preferably 8 to 10 members, more preferably 9 or 10 members. Examples include indolyl, isoindolyl, indazolyl, indolidinyl, quinolinyl, isoquinolinyl, synnolinyl, phthalazinyl, quinazolinyl, naphthylidinyl, quinoxalinyl, purinyl, pteridinyl, benzimidazolyl, benzisoxazolyl, benzoxazolyl, benzoxadiazolyl, benzisothiazolyl, benzothiazolyl, benzothiadiazolyl, benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, imidazopyridyl, triazolopyridyl, imidazothiazolyl, pyrazinopyridazinyl, oxazolopyridyl, thiazolopyridyl, and the like. As for aromatic heterocyclic groups with three or more rings, 13 to 15 members are preferred. Examples include carbazolyl, acridinyl, xanthenyl, phenothiazinyl, phenoxadinyl, phenoxadinyl, and dibenzofuryl.

[0026] The term "aromatic heterocyclic ring" refers to a ring derived from the "aromatic heterocyclic group" described above.

[0027] "Aromatic nitrogen-containing heterocyclic group" means a monocyclic or bicyclic or multicyclic aromatic heterocyclic group that contains one or more N atoms in the ring and may also have one or more identical or different heteroatoms arbitrarily selected from O or S in the ring. A bicyclic or multicyclic aromatic nitrogen-containing heterocyclic group also includes a monocyclic or bicyclic or multicyclic aromatic nitrogen-containing heterocyclic group to which the rings in the above-mentioned "aromatic carbocyclic group" are fused, and the bonds may be located on any of the rings.

[0028] The monocyclic aromatic nitrogen-containing heterocyclic group is preferably 5 to 8-membered, and 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, pyridadinyl, pyrimidinyl, pyrazinyl, and triazinyl. The bicyclic aromatic nitrogen-containing heterocyclic group is preferably 8 to 10 members, more preferably 9 or 10 members. Examples include indolyl, isoindolyl, indazolyl, indolidinyl, quinolinyl, isoquinolinyl, sinnolinyl, phthalazinyl, quinazolinyl, naphthylidinyl, quinoxalinyl, purinyl, pteridinyl, benzimidazolyl, benzisoxazolyl, benzoxazolyl, benzoxadiazolyl, benzisothiazolyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyl, imidazopyridyl, triazolopyridyl, imidazothiazolyl, pyrazinopyridazinyl, oxazolopyridyl, thiazolopyridyl, and the like. As for aromatic nitrogen-containing heterocyclic groups with three or more rings, 13 to 15 members are preferred. Examples include carbazolyl, acridinyl, and phenothiazinyl.

[0029] "Non-aromatic heterocyclic group" means a monocyclic or bicyclic or multicyclic non-aromatic cyclic group having one or more identical or different heteroatoms arbitrarily selected from O, S, and N within the ring. A bicyclic or multicyclic non-aromatic heterocyclic group includes a monocyclic or bicyclic or multicyclic non-aromatic heterocyclic group fused with the respective rings of the "aromatic carbocyclic group," "non-aromatic carbocyclic group," and / or "aromatic heterocyclic group," as well as a monocyclic or bicyclic or multicyclic non-aromatic carbocyclic group fused with the rings of the "aromatic heterocyclic group," and the bonds may be present on any of the rings. Furthermore, "non-aromatic heterocyclic groups" also include groups that form bridges or spiro rings, as described below. [ka] The monocyclic non-aromatic heterocyclic group is preferably 3 to 8-membered, and more preferably 5 or 6-membered. Examples of 3-membered non-aromatic heterocyclic groups include thyranyl, oxyranyl, and azilidinyl. 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, pyrazolidinyl, 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 thiadinyl. 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. The non-aromatic heterocyclic group with two or more rings preferably has 8 to 20 members, and more preferably 8 to 10 members. Examples include indolinyl, isoindolinyl, chromanyl, and isochromanyl.

[0030] "Non-aromatic nitrogen-containing heterocyclic group" means a monocyclic or bicyclic or bicyclic non-aromatic heterocyclic group having one or more nitrogen atoms in the ring. A bicyclic or bicyclic non-aromatic heterocyclic group includes a monocyclic or bicyclic or bicyclic non-aromatic nitrogen-containing heterocyclic group to which the rings in the above-mentioned "aromatic carbocyclic group," "non-aromatic carbocyclic group," and / or "aromatic heterocyclic group" are fused, and the bond may be present in any of the rings. For example, the following ring is shown. [ka] Furthermore, "non-aromatic nitrogen-containing heterocyclic groups" also include groups that are bridging or forming spiro rings, as described below. [ka]

[0031] A "non-aromatic heterocyclic ring" refers to a ring derived from the "non-aromatic heterocyclic group" described above.

[0032] R 9 and R 10 Examples of non-aromatic heterocycles formed by the combination of these elements include the following rings. [ka]

[0033] R 22 and R 23 Non-aromatic carbon rings formed by the bonded carbon atoms include, for example, the following rings. [ka]

[0034] "Trialkylsilyl" refers to a group in which three 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.

[0035] In this specification, "may be substituted with substituent group α" means "may be substituted with one or more groups selected from substituent group α." The same applies to substituent groups β, γ, and γ'.

[0036] 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, azide, hydrazino, ureido, amidino, guanidino, pentafluorothio, trialkylsilyl, alkyloxy which may be substituted with substituent group α, alkenyloxy which may be substituted with substituent group α, alkynyloxy which may be substituted with substituent group α, alkylcarbonyloxy which may be substituted with substituent group α, alkenylcarbonyloxy which may be substituted with substituent group α, alkynylcarbonyloxy which may be substituted with substituent group α, alkylcarbonyl which may be substituted with substituent group α, alkenylcarbonyl which may be substituted with substituent group α, alkynylcarbonyl which may be substituted with substituent group α, alkyloxycarbonyl which may be substituted with substituent group α, A which may be substituted with substituent group α Lukenyloxycarbonyl, alkynyloxycarbonyl which may be substituted with substituent group α, alkylsulfanyl which may be substituted with substituent group α, alkenylsulfanyl which may be substituted with substituent group α, alkynylsulfanyl which may be substituted with substituent group α, alkylsulfinyl which may be substituted with substituent group α, alkenylsulfinyl which may be substituted with substituent group α, alkynylsulfinyl which may be substituted with substituent group α, alkylsulfonyl which may be substituted with substituent group α, alkenylsulfonyl which may be substituted with substituent group α, alkynylsulfonyl which may be substituted with substituent group α, aminos which may be substituted with substituent group β, iminos which may be substituted with substituent group β, carbamoyls which may be substituted with substituent group β, sulfamoyls which may be substituted with substituent group β, Aromatic carbocyclic groups which may be substituted with substituent group γ, non-aromatic carbocyclic groups which may be substituted with substituent group γ', aromatic heterocyclic groups which may be substituted with substituent group γ, non-aromatic heterocyclic groups which may be substituted with substituent group γ', aromatic carbocyclic oxy which may be substituted with substituent group γ, non-aromatic carbocyclic oxy which may be substituted with substituent group γ', aromatic heterocyclic oxy which may be substituted with substituent group γ, non-aromatic heterocyclic oxy which may be substituted with substituent group γ', aromatic carbocyclic carbonyl oxy which may be substituted with substituent group γ, with substituent group γ' substituted non-aromatic carbocyclic carbonyloxy, aromatic heterocyclic carbonyloxy which may be substituted with substituent group γ, non-aromatic heterocyclic carbonyloxy which may be substituted with substituent group γ', aromatic carbocyclic carbonyl which may be substituted with substituent group γ, non-aromatic carbocyclic carbonyl which may be substituted with substituent group γ', aromatic heterocyclic carbonyl which may be substituted with substituent group γ, non-aromatic heterocyclic carbonyl which may be substituted with substituent group γ', aromatic carbocyclic oxycarbonyl which may be substituted with substituent group γ, substituted with substituent group γ' A non-aromatic carbocyclic oxycarbonyl which may be substituted with substituent group γ, an aromatic heterocyclic oxycarbonyl which may be substituted with substituent group γ', an aromatic carbocyclic alkyloxy which may be substituted with substituent group γ, a non-aromatic carbocyclic alkyloxy which may be substituted with substituent group γ', an aromatic heterocyclic alkyloxy which may be substituted with substituent group γ, a non-aromatic heterocyclic alkyloxy which may be substituted with substituent group γ', an aromatic carbocyclic alkyloxycarbonyl which may be substituted with substituent group γ, with substituent group γ' substituted non-aromatic carbocyclic alkyloxycarbonyl, aromatic heterocyclic alkyloxycarbonyl which may be substituted with substituent group γ, non-aromatic heterocyclic alkyloxycarbonyl which may be substituted with substituent group γ', aromatic carbocyclic sulfanyl which may be substituted with substituent group γ, non-aromatic carbocyclic sulfanyl which may be substituted with substituent group γ', aromatic heterocyclic sulfanyl which may be substituted with substituent group γ, non-aromatic heterocyclic sulfanyl which may be substituted with substituent group γ', aromatic carbocyclic sulfinyl which may be substituted with substituent group γNon-aromatic carbon ring sulfinyls which may be substituted with substituent group γ', aromatic heterocyclic sulfinyls which may be substituted with substituent group γ, non-aromatic heterocyclic sulfinyls which may be substituted with substituent group γ', aromatic carbon ring sulfonyls which may be substituted with substituent group γ, non-aromatic carbon ring sulfonyls which may be substituted with substituent group γ', aromatic heterocyclic sulfonyls which may be substituted with substituent group γ, and non-aromatic heterocyclic sulfonyls which may be substituted with substituent group γ'.

[0037] Substituent group α: halogen, hydroxy, carboxy, alkyloxy, haloalkyloxy, alkenyloxy, alkynyloxy, sulfanyl, and cyano.

[0038] Substituent group β: halogen, hydroxy, carboxy, cyano, alkyl which may be substituted with substituent group α, alkenyl which may be substituted with substituent group α, alkynyl which may be substituted with substituent group α, alkylcarbonyl which may be substituted with substituent group α, alkenylcarbonyl which may be substituted with substituent group α, alkynylcarbonyl which may be substituted with substituent group α, alkylsulfanyl which may be substituted with substituent group α, alkenylsulfanyl which may be substituted with substituent group α, alkynylsulfanyl which may be substituted with substituent group α, alkylsulfonyl which may be substituted with substituent group α, alkenylsulfinyl which may be substituted with substituent group α, alkynylsulfinyl which may be substituted with substituent group α, alkylsulfonyl which may be substituted with substituent group α, alkenylsulfonyl which may be substituted with substituent group α, alkynylsulfonyl which may be substituted with substituent group α, Aromatic carbocyclic groups which may be substituted with substituent group γ, non-aromatic carbocyclic groups which may be substituted with substituent group γ', aromatic heterocyclic groups which may be substituted with substituent group γ, non-aromatic heterocyclic groups which may be substituted with substituent group γ', aromatic carbocyclic alkyl groups which may be substituted with substituent group γ, non-aromatic carbocyclic alkyl groups which may be substituted with substituent group γ', aromatic heterocyclic alkyl groups which may be substituted with substituent group γ, non-aromatic heterocyclic alkyl groups which may be substituted with substituent group γ', aromatic carbocyclic carbonyl groups which may be substituted with substituent group γ, non-aromatic carbocyclic carbonyl groups which may be substituted with substituent group γ', aromatic carbocyclic oxycarbonyl groups which may be substituted with substituent group γ', non-aromatic carbocyclic oxycarbonyl groups which may be substituted with substituent group γ Aromatic heterocyclic oxycarbonyls may be substituted with substituent group γ', non-aromatic heterocyclic oxycarbonyls may be substituted with substituent group γ', aromatic carbocyclic sulfanyls may be substituted with substituent group γ, non-aromatic carbocyclic sulfanyls may be substituted with substituent group γ', aromatic heterocyclic sulfanyls may be substituted with substituent group γ, non-aromatic heterocyclic sulfanyls may be substituted with substituent group γ', aromatic carbocyclic sulfinyls may be substituted with substituent group γ, non-aromatic carbocyclic sulfinyls may be substituted with substituent group γ', aromatic carbocyclic sulfonyls may be substituted with substituent group γ, non-aromatic carbocyclic sulfonyls may be substituted with substituent group γ', aromatic carbocyclic sulfonyls may be substituted with substituent group γ, non-aromatic carbocyclic sulfonyls may be substituted with substituent group γ', aromatic heterocyclic sulfonyls may be substituted with substituent group γ, and non-aromatic heterocyclic sulfonyls may be substituted with substituent group γ'.

[0039] Substituent group γ: Substituent group α, alkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, alkylcarbonyl, haloalkylcarbonyl, alkenylcarbonyl, and alkynylcarbonyl.

[0040] Substituent group γ': Substituent group γ and oxo.

[0041] Examples of substituents on the rings of "aromatic carbocyclic" and "aromatic heterocyclic" groups include "substituted aromatic carbocyclic groups", "substituted aromatic heterocyclic groups", "substituted aromatic nitrogen-containing heterocyclic groups", "substituted aromatic carbocyclic oxy", "substituted aromatic heterocyclic oxy", "substituted aromatic carbocyclic carbonyl oxy", "substituted aromatic heterocyclic carbonyl oxy", "substituted aromatic carbocyclic carbonyl", "substituted aromatic heterocyclic carbonyl", "substituted aromatic carbocyclic oxycarbonyl", "substituted aromatic heterocyclic oxycarbonyl", "substituted aromatic carbocyclic sulfanyl", "substituted aromatic heterocyclic sulfanyl", "substituted aromatic carbocyclic sulfinyl", "substituted aromatic heterocyclic sulfinyl", "substituted aromatic carbocyclic sulfonyl", and "substituted aromatic heterocyclic sulfonyl", and 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, azide, hydrazino, ureido, amidino, guanidino, pentafluorothio, trialkylsilyl, alkyl which may be substituted with substituent group α, alkenyl which may be substituted with substituent group α, alkynyl which may be substituted with substituent group α, alkyloxy which may be substituted with substituent group α, alkenyloxy which may be substituted with substituent group α, alkynyloxy which may be substituted with substituent group α, alkylcarbonyloxy which may be substituted with substituent group α, alkenylcarbonyloxy which may be substituted with substituent group α, alkynylcarbonyloxy which may be substituted with substituent group α, alkylcarbonyl which may be substituted with substituent group α, alkenylcarbonyl which may be substituted with substituent group α, alkynylcarbonyl which may be substituted with substituent group α, substituted with substituent group α A good alkyloxycarbonyl, an alkenyloxycarbonyl which may be substituted with substituent group α, an alkynyloxycarbonyl which may be substituted with substituent group α, an alkylsulfanyl which may be substituted with substituent group α, an alkenylsulfanyl which may be substituted with substituent group α, an alkynylsulfanyl which may be substituted with substituent group α, an alkylsulfinyl which may be substituted with substituent group α, an alkenylsulfinyl which may be substituted with substituent group α, an alkynylsulfinyl which may be substituted with substituent group α, an alkylsulfonyl which may be substituted with substituent group α, an alkenylsulfonyl which may be substituted with substituent group α, an alkynylsulfonyl which may be substituted with substituent group α, aminos which may be substituted with substituent group β, iminos which may be substituted with substituent group β, carbamoyls which may be substituted with substituent group β, sulfamoyls which may be substituted with substituent group β, Aromatic carbocyclic groups which may be substituted with substituent group γ, non-aromatic carbocyclic groups which may be substituted with substituent group γ', aromatic heterocyclic groups which may be substituted with substituent group γ, non-aromatic heterocyclic groups which may be substituted with substituent group γ', aromatic carbocyclic oxy which may be substituted with substituent group γ, non-aromatic carbocyclic oxy which may be substituted with substituent group γ', aromatic heterocyclic oxy which may be substituted with substituent group γ, non-aromatic heterocyclic oxy which may be substituted with substituent group γ', "aromatic carbocyclic carbonyl oxy which may be substituted with substituent group γ "Non-aromatic carbonyloxy which may be substituted with substituent group γ'", "Aromatic heterocyclic carbonyloxy which may be substituted with substituent group γ", and "Non-aromatic heterocyclic carbonyloxy which may be substituted with substituent group γ'", aromatic carbonyl which may be substituted with substituent group γ, non-aromatic carbonyl which may be substituted with substituent group γ', aromatic heterocyclic carbonyl which may be substituted with substituent group γ, non-aromatic heterocyclic carbonyl which may be substituted with substituent group γ', aromatic carbon which may be substituted with substituent group γ Cyclocyclic oxycarbonyl, non-aromatic carbocyclic oxycarbonyl which may be substituted with substituent group γ', aromatic heterocyclic oxycarbonyl which may be substituted with substituent group γ, non-aromatic heterocyclic oxycarbonyl which may be substituted with substituent group γ', aromatic carbocyclic alkyl which may be substituted with substituent group γ, non-aromatic carbocyclic alkyl which may be substituted with substituent group γ', aromatic heterocyclic alkyl which may be substituted with substituent group γ, non-aromatic heterocyclic alkyl which may be substituted with substituent group γ', aromatic carbocyclic alkyloxy which may be substituted with substituent group γ, non-aromatic carbocyclic alkyloxy which may be substituted with substituent group γ', aromatic carbocyclic alkyloxycarbonyl which may be substituted with substituent group γ, non-aromatic carbocyclic alkyloxycarbonyl which may be substituted with substituent group γ', aromatic heterocyclic alkyloxycarbonyl which may be substituted with substituent group γ, non-aromatic heterocyclic alkyloxycarbonyl which may be substituted with substituent group γ'Aromatic carbocyclic alkyloxyalkyl which may be substituted with substituent group γ, non-aromatic carbocyclic alkyloxyalkyl which may be substituted with substituent group γ', aromatic heterocyclic alkyloxyalkyl which may be substituted with substituent group γ, non-aromatic heterocyclic alkyloxyalkyl which may be substituted with substituent group γ', aromatic carbocyclic sulfanyl which may be substituted with substituent group γ, non-aromatic carbocyclic sulfanyl which may be substituted with substituent group γ', aromatic heterocyclic sulfanyl which may be substituted with substituent group γ, non-aromatic heterocyclic sulfanyl which may be substituted with substituent group γ', aromatic carbocyclic sulfinyl which may be substituted with substituent group γ, non-aromatic carbocyclic sulfinyl which may be substituted with substituent group γ', aromatic carbocyclic sulfonyl which may be substituted with substituent group γ, non-aromatic carbocyclic sulfonyl which may be substituted with substituent group γ', aromatic carbocyclic sulfonyl which may be substituted with substituent group γ, non-aromatic carbocyclic sulfonyl which may be substituted with substituent group γ', aromatic heterocyclic sulfonyl which may be substituted with substituent group γ, and non-aromatic heterocyclic sulfonyl which may be substituted with substituent group γ'. ,

[0042] "Substituted non-aromatic carbocyclic group", "Substituted non-aromatic heterocyclic group", "Substituted non-aromatic nitrogen-containing heterocyclic group", "R 9 and R 10 "A substituted non-aromatic heterocycle formed by the combination of these elements", "R 22 and R 23The following substituent group C is a list of substituents on the "non-aromatic carbocycle" and "non-aromatic heterocycle" of "substituted non-aromatic carbocycles" and "non-aromatic heterocycles" that are formed together with the carbon atom to which they are bonded: "substituted non-aromatic carbocycle oxy", "substituted non-aromatic heterocycle oxy", "substituted non-aromatic carbocycle carbonyl oxy", "substituted non-aromatic heterocycle carbonyl", "substituted non-aromatic heterocycle carbonyl", "substituted non-aromatic carbocycle oxycarbonyl", "substituted non-aromatic heterocycle oxycarbonyl", "substituted non-aromatic carbocycle sulfanyl", "substituted non-aromatic heterocycle sulfanyl", "substituted non-aromatic carbocycle sulfinyl", "substituted non-aromatic heterocycle sulfinyl", "substituted non-aromatic carbocycle sulfonyl", and "substituted non-aromatic heterocycle sulfonyl". 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.

[0043] When "non-aromatic carbon ring," "non-aromatic heterocycle," and "non-aromatic nitrogen-containing heterocycle" are substituted with "oxo," it means a ring in which two hydrogen atoms on a carbon atom are substituted, as follows: [ka]

[0044] Examples of substituents for "substituted amino," "substituted imino," "substituted carbamoyl," and "substituted sulfamoyl" include the following substituent group D. They may be substituted with one or two groups selected from substituent group D. Substituent group D: halogen, hydroxy, carboxy, cyano, alkyl which may be substituted with substituent group α, alkenyl which may be substituted with substituent group α, alkynyl which may be substituted with substituent group α, alkylcarbonyl which may be substituted with substituent group α, alkenylcarbonyl which may be substituted with substituent group α, alkynylcarbonyl which may be substituted with substituent group α, alkylsulfanyl which may be substituted with substituent group α, alkenylsulfanyl which may be substituted with substituent group α, alkynylsulfanyl which may be substituted with substituent group α, alkylsulfonyl which may be substituted with substituent group α, alkenylsulfonyl which may be substituted with substituent group α, alkynylsulfonyl which may be substituted with substituent group α, aminos which may be substituted with substituent group β, iminos which may be substituted with substituent group β, carbamoyls which may be substituted with substituent group β, sulfamoyls which may be substituted with substituent group β, Aromatic carbocyclic groups which may be substituted with substituent group γ, non-aromatic carbocyclic groups which may be substituted with substituent group γ', aromatic heterocyclic groups which may be substituted with substituent group γ, non-aromatic heterocyclic groups which may be substituted with substituent group γ', aromatic carbocyclic alkyl groups which may be substituted with substituent group γ, non-aromatic carbocyclic alkyl groups which may be substituted with substituent group γ', aromatic heterocyclic alkyl groups which may be substituted with substituent group γ, non-aromatic heterocyclic alkyl groups which may be substituted with substituent group γ', aromatic carbocyclic carbonyl groups which may be substituted with substituent group γ, non-aromatic carbocyclic carbonyl groups which may be substituted with substituent group γ', aromatic carbocyclic oxycarbonyl groups which may be substituted with substituent group γ', non-aromatic carbocyclic oxycarbonyl groups which may be substituted with substituent group γ Aromatic heterocyclic oxycarbonyls may be substituted with substituent group γ', non-aromatic heterocyclic oxycarbonyls may be substituted with substituent group γ', aromatic carbocyclic sulfanyls may be substituted with substituent group γ, non-aromatic carbocyclic sulfanyls may be substituted with substituent group γ', aromatic heterocyclic sulfanyls may be substituted with substituent group γ, non-aromatic heterocyclic sulfanyls may be substituted with substituent group γ', aromatic carbocyclic sulfinyls may be substituted with substituent group γ, non-aromatic carbocyclic sulfinyls may be substituted with substituent group γ', aromatic carbocyclic sulfonyls may be substituted with substituent group γ, non-aromatic carbocyclic sulfonyls may be substituted with substituent group γ', aromatic carbocyclic sulfonyls may be substituted with substituent group γ, non-aromatic carbocyclic sulfonyls may be substituted with substituent group γ', aromatic heterocyclic sulfonyls may be substituted with substituent group γ, and non-aromatic heterocyclic sulfonyls may be substituted with substituent group γ'.

[0045] In the compound represented by formula (I) or formula (II), R 1 , R 2 , R 3 , n, R 4 , L, R 8 , R 5 , R 6 , p, R7 , R 9 , R 10 , R 11 , R 21 ,R 22 ,R 23 Preferred embodiments of and m are shown below. As compounds represented by formula (I) or formula (II), all combinations of the specific examples shown below are illustrated. R 1 This includes substituted or unsubstituted aromatic heterocyclic groups or substituted or unsubstituted non-aromatic heterocyclic groups (hereinafter referred to as A-1). R 1 Examples include substituted or unsubstituted aromatic heterocyclic groups (hereinafter referred to as A-2). R 1 Examples include substituted or unsubstituted aromatic nitrogen-containing heterocyclic groups (hereinafter referred to as A-3). R 1 Examples include substituted or unsubstituted 5-membered aromatic heterocyclic groups, substituted or unsubstituted 6-membered aromatic heterocyclic groups, or substituted or unsubstituted 10-membered aromatic heterocyclic groups (hereinafter referred to as A-4). R 1 This includes substituted or unsubstituted 6-membered aromatic heterocyclic groups or substituted or unsubstituted 5-membered aromatic heterocyclic groups (hereinafter referred to as A-5). R 1 Examples include alkyl-substituted five-membered aromatic heterocyclic groups; unsubstituted five-membered aromatic heterocyclic groups; and six-membered aromatic heterocyclic groups substituted with one or more groups selected from the group consisting of halogens, alkyloxys, cyanos, haloalkyls, and alkyls, or unsubstituted six-membered aromatic heterocyclic groups (hereinafter referred to as A-6). R 1 Examples include substituted or unsubstituted five-membered aromatic heterocyclic groups (hereinafter referred to as A-7). R 1 Examples include alkyl-substituted five-membered aromatic heterocyclic groups or unsubstituted five-membered aromatic heterocyclic groups (hereinafter referred to as A-8). R 1 Examples include substituted or unsubstituted 6-membered aromatic heterocyclic groups (hereinafter referred to as A-9). R 1Examples include a six-membered aromatic heterocyclic group substituted with one or more groups selected from the group consisting of halogens, alkyloxys, cyanos, haloalkyls, and alkyls, or an unsubstituted six-membered aromatic heterocyclic group (hereinafter referred to as A-10). R 1 Examples include substituted or unsubstituted 10-membered aromatic heterocyclic groups (hereinafter referred to as A-11). R 1 Examples include unsubstituted 10-membered aromatic heterocyclic groups (hereinafter referred to as A-12). R 1 Examples include substituted or unsubstituted pyridyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted pyridadinyl, substituted or unsubstituted pyrazolyl, substituted or unsubstituted imidazolyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted thiophenyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted isothiazolyl, substituted or unsubstituted isoxazolyl, substituted or unsubstituted oxadiazolyl, substituted or unsubstituted isoquinolinyl, substituted or unsubstituted quinolinyl, or substituted or unsubstituted indolyl (hereinafter referred to as A-13). R 1 These include substituted or unsubstituted pyridyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyrrolyl, or substituted or unsubstituted pyrazolyl (hereinafter referred to as A-14). R 1 These include substituted or unsubstituted pyridyl, substituted or unsubstituted pyrrolyl, or substituted or unsubstituted pyrazolyl (hereinafter referred to as A-15). R 1 This includes substituted or unsubstituted pyrrolyl or substituted or unsubstituted pyrazolyl (hereinafter referred to as A-16). R 1 This includes substituted or unsubstituted pyridyls (hereinafter referred to as A-17). R 1This includes pyridyls substituted with one or more groups selected from the group consisting of halogens, alkyloxys, cyanos, haloalkyls, and alkyls, or unsubstituted pyridyls (hereinafter referred to as A-18). R 1 Examples include pyridyls substituted with halogens and / or haloalkyls or unsubstituted pyridyls (hereinafter referred to as A-19). R 1 Examples include halogen-substituted or unsubstituted pyridyls (hereinafter referred to as A-20). R 1 Examples include pyridyls substituted with halogens (hereinafter referred to as A-21). R 1 Examples include haloalkyl-substituted or unsubstituted pyridyls (hereinafter referred to as A-22). R 1 Examples include pyridyls substituted with haloalkyl groups (hereinafter referred to as A-23). R 1 Examples include substituted or unsubstituted pyrazolyl (hereinafter referred to as A-24). R 1 Examples include haloalkyl and / or alkyl-substituted pyrazolyl or unsubstituted pyrazolyl (hereinafter referred to as A-25). R 1 Examples include alkyl-substituted or unsubstituted pyrazolyl compounds (hereinafter referred to as A-26). R 1 Examples include alkyl-substituted pyrazolyl compounds (hereinafter referred to as A-27). R 1 Examples include substituted or unsubstituted pyrrolyl compounds (hereinafter referred to as A-28). R 1 Examples include haloalkyl and / or alkyl-substituted pyrrolyl or unsubstituted pyrrolyl (hereinafter referred to as A-29). R 1 Examples include alkyl-substituted pyrazolyl or unsubstituted pyrrolyl (hereinafter referred to as A-30). R 1Examples include alkyl-substituted pyrrolyl compounds (hereinafter referred to as A-31).

[0046] R 2 Each of these can be independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group (hereinafter referred to as B-1). R 2 Each of these can be independently identified as a hydrogen atom (hereinafter referred to as B-2). R 3 Each of these can be independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group (hereinafter referred to as C-1). R 3 Each of these can be independently identified as a hydrogen atom (hereinafter referred to as C-2). n can be either 1 or 2 (hereinafter referred to as D-1). n can be 1 (hereinafter referred to as D-2).

[0047] R 4 Examples include substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic groups (hereinafter referred to as E-1). R 4 Examples include substituted or unsubstituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic groups (hereinafter referred to as E-2). R 4 This includes substituted or unsubstituted 6-membered non-aromatic nitrogen-containing heterocyclic groups (hereinafter referred to as E-3). R 4 Examples include substituted or unsubstituted piperidinyl compounds (hereinafter referred to as E-4). R 4 The formula is: [ka] (In the formula, R 21 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 22 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; R 23 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 22 and R 23 This includes (hereinafter referred to as E-5) which, together with the carbon atom to which it is bonded, forms a substituted or unsubstituted non-aromatic carbocyclic ring. R 4 The formula is: [ka] (In the formula, R 21 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 22 is a halogen or a substituted or unsubstituted alkyl; R 23 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 22 and R 23 Examples of groups include those represented by (hereinafter referred to as E-6), which, together with the carbon atom to which they are bonded, form a substituted or unsubstituted non-aromatic carbon ring. R 4 The formula is: [ka] (In the formula, R 21 Examples include a hydrogen atom or a substituted or unsubstituted alkyl group (hereinafter referred to as E-7). R 4 The formula is: [ka] (In the formula, R 21 , R 22 and R 23 The group shown by (which is synonymous with E-5) is an example (hereinafter referred to as E-8). R 4 The formula is: [ka] (In the formula, in the formula, R 21 , R 22 and R 23 The group shown by (which is synonymous with E-6) is an example (hereinafter referred to as E-9). R 4 The formula is: [ka] (In the formula, R 21 Examples of groups represented by a hydrogen atom or a substituted or unsubstituted alkyl group include (hereinafter referred to as E-10). [ka] (In the formula, R 21 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 22 Examples of groups include those represented by (which are halogens) (hereinafter referred to as E-11).

[0048] L is -NR 8 Examples include -, -O-, or single bonds (hereinafter referred to as F-1). L is -NR 8 - is one example (hereinafter referred to as F-2). L can be represented by -O- (hereinafter referred to as F-3). L is a single bond (hereinafter referred to as F-4). R 8 This includes hydrogen atoms or substituted or unsubstituted alkyl groups (hereinafter referred to as G-1). R 8 A hydrogen atom is an example of this (hereinafter referred to as G-2).

[0049] R 5 Each of these can be independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group (hereinafter referred to as H-1). R5 Each of these can be independently identified as a hydrogen atom (hereinafter referred to as H-2). R 6 Each of these can be independently a hydrogen atom, a halogen, a hydroxyl group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted alkyloxy group (hereinafter referred to as J-1). R 6 Each of these can be independently identified as a hydrogen atom (hereinafter referred to as J-2). p can be either 1 or 2 (hereinafter referred to as K-1). p is 1 (hereinafter referred to as K-2).

[0050] R 7 The formula is: [ka] (In the formula, R 9 is a hydrogen atom, a halogen, a substituted or unsubstituted alkyloxy, a substituted or unsubstituted non-aromatic carbocyclic oxy, a substituted or unsubstituted amino, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkyl; R 10 is a hydrogen atom, hydroxyl, halogen or substituted or unsubstituted alkyl; or, R 9 and R 10 These combine to form substituted or unsubstituted non-aromatic heterocycles; R 11 is a halogen, hydroxyl, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; Examples of groups include those represented by (where m is 0 or 1) (hereinafter referred to as L-1). R 7 The formula is: [ka] (In the formula, R 9is a substituted or unsubstituted alkyloxy, a substituted or unsubstituted non-aromatic carbocyclic oxy, a substituted or unsubstituted amino, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkyl; R 10 is a hydrogen atom, a halogen, or a substituted or unsubstituted alkyl group; or, R 9 and R 10 These combine to form substituted or unsubstituted non-aromatic heterocycles; R 11 is a halogen, hydroxyl, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; Examples of groups include those represented by (where m is 0 or 1) (hereinafter referred to as L-2). R 7 The formula is: [ka] (In the formula, R 9 is a substituted or unsubstituted alkyloxy, a substituted or unsubstituted amino, or a substituted or unsubstituted alkyl; R 10 is a hydrogen atom, a halogen or a substituted or unsubstituted alkyl; or, R 9 and R 10 These combine to form substituted or unsubstituted non-aromatic heterocycles; R 11 is a halogen, hydroxyl, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; Examples of groups include those represented by (where m is 0 or 1) (hereinafter referred to as L-3). R 7 The formula is: [ka] (In the formula, R 9 R is a substituted or unsubstituted alkyloxy. 10A group represented by (where m is a hydrogen atom, and m is 0), or formula: [ka] (In the formula, R 9 and R 10 The group shown is (hereinafter referred to as L-4) (where m is 0) and these groups combine to form a substituted or unsubstituted non-aromatic heterocycle. R 7 The formula is: [ka] (In the formula, R 9 R is a substituted or unsubstituted alkyloxy. 10 Examples of groups include those represented by (where is a hydrogen atom and m is 0) (hereinafter referred to as L-5). R 7 The formula is: [ka] (In the formula, R 9 R is a halogen-substituted alkyloxy or an unsubstituted alkyloxy. 10 Examples of groups include those represented by (where is a hydrogen atom and m is 0) (hereinafter referred to as L-6). R 7 The formula is: [ka] (In the formula, R 9 and R 10 The group shown is (hereinafter referred to as L-7) (where m is 0) and these groups combine to form a substituted or unsubstituted non-aromatic heterocycle. R 7 The formula is: [ka] (In the formula, R 9Examples of groups represented by (which are substituted or unsubstituted alkyloxy groups) are (hereinafter referred to as L-8). R 7 The formula is: [ka] (In the formula, R 9 Examples of groups represented by (which are substituted or unsubstituted C2-C4 alkyloxy groups) include (hereinafter referred to as L-9). R 7 The formula is: [ka] (In the formula, R 9 Examples of groups include those represented by (which are aminos substituted with or unsubstituted alkyl groups). (Hereinafter referred to as L-10). [ka] (In the formula, R 9 Examples of groups include those represented by (which are substituted or unsubstituted C2-C4 alkyloxy or substituted or unsubstituted amino). (Hereinafter referred to as L-11).

[0051] The following embodiments are particularly preferred. (i) Equation (I): [ka] (In the formula, R 1 It is an A-17; R 2 is a hydrogen atom; R 3 is a hydrogen atom; n is 1; R 4 It is E-4; L is -NR 8 -and; R 8is a hydrogen atom; R 5 is a hydrogen atom; R 6 is a hydrogen atom; p is 1; R 7 The formula is: [ka] (In the formula, R 9 A serotonin 5-HT2A receptor inverse agonist containing a compound represented by (which is a substituted or unsubstituted alkyloxy group) or a pharmaceutically acceptable salt thereof. (ii) Equation (I): [ka] (In the formula, R 1 It is an A-24; R 2 is a hydrogen atom; R 3 is a hydrogen atom; n is 1; R 4 It is E-4; L is -NR 8 -and; R 8 is a hydrogen atom; R 5 is a hydrogen atom; R 6 is a hydrogen atom; p is 1; R 7 The formula is: [ka] (In the formula, R 9 A serotonin 5-HT2A receptor inverse agonist containing a compound represented by (which is a substituted or unsubstituted alkyloxy group) or a pharmaceutically acceptable salt thereof. (iii) Equation (I): [ka] (In the formula, R 1 It is an A-28; R 2 is a hydrogen atom; R 3 is a hydrogen atom; n is 1; R 4 It is E-4; L is -NR 8 -and; R 8 is a hydrogen atom; R 5 is a hydrogen atom; R 6 is a hydrogen atom; p is 1; R 7 The formula is: [ka] (In the formula, R 9 A serotonin 5-HT2A receptor inverse agonist containing a compound represented by (which is a substituted or unsubstituted alkyloxy group) or a pharmaceutically acceptable salt thereof. (iv) Equation (I): [ka] (In the formula, R 1 It is an A-17; R 2 is a hydrogen atom; R 3 is a hydrogen atom; n is 1; R 4 It is E-4; L is -NR 8 -and; R 8 is a hydrogen atom; R 5is a hydrogen atom; R 6 is a hydrogen atom; p is 1; R 7 The formula is: [ka] (In the formula, R 9 A serotonin 5-HT2A receptor inverse agonist composition containing a compound represented by (which is a group represented by substituted or unsubstituted alkyloxy) or a pharmaceutically acceptable salt thereof. (v) Formula (I): [ka] (In the formula, R 1 It is an A-24; R 2 is a hydrogen atom; R 3 is a hydrogen atom; n is 1; R 4 It is E-4; L is -NR 8 -and; R 8 is a hydrogen atom; R 5 is a hydrogen atom; R 6 is a hydrogen atom; p is 1; R 7 The formula is: [ka] (In the formula, R 9 A serotonin 5-HT2A receptor inverse agonist composition containing a compound represented by (which is a group represented by substituted or unsubstituted alkyloxy) or a pharmaceutically acceptable salt thereof. (vi) Equation (I): [ka] (In the formula, R 1 It is an A-28; R 2 is a hydrogen atom; R 3 is a hydrogen atom; n is 1; R 4 It is E-4; L is -NR 8 -and; R 8 is a hydrogen atom; R 5 is a hydrogen atom; R 6 is a hydrogen atom; p is 1; R 7 The formula is: [ka] (In the formula, R 9 A serotonin 5-HT2A receptor inverse agonist composition containing a compound represented by (which is a group represented by substituted or unsubstituted alkyloxy) or a pharmaceutically acceptable salt thereof. (vii) Formula (II): [ka] (In the formula, R 1 is a substituted or unsubstituted aromatic nitrogen-containing heterocyclic group; R 2 is a hydrogen atom; R 3 is a hydrogen atom; n is 1; R 4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; R 8 is a hydrogen atom; R 5 is a hydrogen atom; R 6 is a hydrogen atom; R 7 The formula is: [ka] (In the formula, R 9 Compounds represented by (a group represented by ) (which is a substituted or unsubstituted C2-C4 alkyloxy or a substituted or unsubstituted amino) or pharmaceutically acceptable salts thereof. (viii) Equation (II): [ka] (In the formula, R 1 It is an A-17; R 2 is a hydrogen atom; R 3 is a hydrogen atom; n is 1; R 4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; R 8 is a hydrogen atom; R 5 is a hydrogen atom; R 6 is a hydrogen atom; R 7 The formula is: [ka] (In the formula, R 9 Compounds represented by (where (is a substituted or unsubstituted alkyloxy)) or pharmaceutically acceptable salts thereof. (ix) Formula (II): [ka] (In the formula, R 1 It is an A-24; R2 is a hydrogen atom; R 3 is a hydrogen atom; n is 1; R 4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; R 8 is a hydrogen atom; R 5 is a hydrogen atom; R 6 is a hydrogen atom; R 7 The formula is: [ka] (In the formula, R 9 Compounds represented by (where (is a substituted or unsubstituted alkyloxy)) or pharmaceutically acceptable salts thereof. (x) Formula (II): [ka] (In the formula, R 1 It is an A-28; R 2 is a hydrogen atom; R 3 is a hydrogen atom; n is 1; R 4 is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group; R 8 is a hydrogen atom; R 5 is a hydrogen atom; R 6 is a hydrogen atom; R 7 The formula is: [ka] (In the formula, R 9Compounds represented by (where (is a substituted or unsubstituted alkyloxy)) or pharmaceutically acceptable salts thereof. (xi) Formula (III): [ka] (In the formula, R 1 is a substituted or unsubstituted six-membered aromatic nitrogen-containing heterocyclic group or a substituted or unsubstituted five-membered aromatic nitrogen-containing heterocyclic group; R 4 The formula is: [ka] (In the formula, R 21 is a hydrogen atom or a substituted or unsubstituted alkyl group; R 22 and R 23 (together with the bonded carbon atom, it forms a substituted or unsubstituted non-aromatic carbon ring) is a group represented by; R 7 The formula is: [ka] (In the formula, R 9 Compounds represented by (a group represented by ) (which is a substituted or unsubstituted C2-C4 alkyloxy or a substituted or unsubstituted amino) or pharmaceutically acceptable salts thereof.

[0052] The compounds represented by formula (I) or formula (II) are not limited to specific isomers, but include all possible isomers (e.g., keto-enol isomers, imine-enamine isomers, diastereoisomers, optical isomers, rotational isomers, etc.), racemates, or mixtures thereof.

[0053] In the compounds represented by formula (I) or formula (II), one or more hydrogen, carbon, and / or other atoms may be substituted with isotopes of hydrogen, carbon, and / or other atoms, respectively. Examples of such isotopes are, 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 36 Like Cl, hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, iodine, and chlorine are included. Compounds represented by formula (I) or formula (II) also include compounds substituted with such isotopes. These isotope-substituted compounds are also useful as pharmaceuticals and include all radiolabeled compounds of the compounds represented by formula (I) or formula (II). The present invention also includes a "radiolabeling method" for producing these "radiolabeled compounds," which are useful as tools for metabolic pharmacokinetic studies, binding assays, and / or diagnostics.

[0054] Radiolabeled compounds of the compounds represented by formula (I) or formula (II) can be prepared by methods well known in the art. For example, tritium-labeled compounds represented by formula (I) or formula (II) can be prepared by introducing tritium into a specific compound represented by formula (I) or formula (II) by a catalytic dehalogenation reaction using tritium. This method involves reacting a appropriately halogenated precursor of the compound represented by formula (I) or formula (II) with tritium gas in the presence or absence of a suitable catalyst, such as Pd / C, or 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 are14 It can be prepared by using a raw material containing carbon.

[0055] Examples of pharmaceutically acceptable salts of the compound represented by formula (I) or formula (II) include the compound represented by formula (I) or formula (II) and alkali metals (e.g., lithium, sodium, potassium, etc.), alkaline earth metals (e.g., calcium, barium, etc.), magnesium, transition metals (e.g., zinc, iron, etc.), ammonia, organic bases (e.g., trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, meglumine, ethylenediamine, etc.). Examples include salts of pyridine, picoline, quinoline, etc., with amino acids, or salts of 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 commonly used methods.

[0056] The compounds represented by formula (I) or formula (II) of the present invention, or their pharmaceutically acceptable salts, may form solvates (e.g., hydrates), cocrystals, and / or polymorphs, and the present invention also encompasses such various solvates, cocrystals, and polymorphs. A "solvate" may be coordinated with any number of solvent molecules (e.g., water molecules) to the compound represented by formula (I) or formula (II). When the compound represented by formula (I) or formula (II) or its pharmaceutically acceptable salt is left in the air, it may absorb moisture, resulting in adsorbed water adhering to it, or it may form a hydrate. Furthermore, the compound represented by formula (I) or formula (II) or its pharmaceutically acceptable salt may form polymorphs by recrystallization. A "cocrystal" means that the compound or salt represented by formula (I) or formula (II) and a counter molecule exist in the same crystal lattice, and may contain any number of counter molecules.

[0057] The compounds represented by formula (I) or formula (II) of the present invention or pharmaceutically acceptable salts thereof may form prodrugs, and the present invention also encompasses various such prodrugs. A prodrug is a derivative of the compound according to the present invention having a group that can be chemically or metabolically degraded, and is a compound that becomes a pharmaceutically active compound according to the present invention in vivo by solvolysis or under physiological conditions. Prodrugs include compounds that are enzymatically oxidized, reduced, hydrolyzed, etc., under physiological conditions in vivo to be converted to the compound represented by formula (I) or formula (II), compounds that are hydrolyzed by gastric acid, etc., to be converted to the compound represented by formula (I) or formula (II), etc. Methods for selecting and producing a suitable prodrug derivative are described, for example, in “Design of Prodrugs, Elsevier, Amsterdam, 1985”. Prodrugs may be active themselves.

[0058] If the compound represented by formula (I) or formula (II) or a pharmaceutically acceptable salt thereof has a hydroxyl group, examples of prodrugs include acyloxy derivatives and sulfonyloxy derivatives produced by reacting the compound having a hydroxyl group with a suitable acyl halide, a suitable acid anhydride, a suitable sulfonyl chloride, a suitable sulfonyl anhydride, and a mixed anhydride, or by reacting them with a condensing agent. For example, CH3COO-, C2H5COO-, tert-BuCOO-, C 15 H 31 Examples include COO-, PhCOO-, (m-NaOOCPh)COO-, NaOOCCH2CH2COO-, CH3CH(NH2)COO-, CH2N(CH3)2COO-, CH3SO3-, CH3CH2SO3-, CF3SO3-, CH2FSO3-, CF3CH2SO3-, p-CH3O-PhSO3-, PhSO3-, and p-CH3PhSO3-.

[0059] The compounds according to the present invention have a serotonin 5-HT2A receptor inverse agonist effect and are therefore useful as therapeutic and / or prophylactic agents for diseases involving the serotonin 5-HT2A receptor. Diseases involving the serotonin 5-HT2A receptor 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, 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, sexual dysfunction, and other diseases mediated by serotonin. Preferably, 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 preferably, hallucinations and delusions associated with Parkinson's disease and hallucinations and delusions associated with dementia are included. "Serotonin 5-HT2A receptor inverse agonist" refers to a drug that has an inverse agonistic effect on the serotonin 5-HT2A receptor. "Composition for serotonin 5-HT2A receptor inverse agonism" refers to a composition having serotonin 5-HT2A receptor inverse agonism, and is not limited to pharmaceutical applications.

[0060] (Method for producing the compound of the present invention) The compounds represented by formula (I) or formula (II) according to the present invention can be produced, for example, by the general synthesis method shown below. Extraction, purification, etc., can be carried out using the same procedures as those performed in ordinary organic chemistry experiments. The compounds of the present invention can be synthesized with reference to methods known in the art.

[0061] (R 3 (When L is a hydrogen atom and L is -NH-) [ka] (In the formula, each symbol is equivalent to (1) above, R 1A - is R 1 - or R 1 R 2 It is CH-. Process 1 Compound (a-2) can be obtained by reacting compound (a-1) and CDI in a suitable solvent. CDI can be used in an amount of 1.0 molar equivalent or more, preferably 1.2 molar equivalents, relative to compound (a-1). Examples of reaction solvents include alcohols (e.g., methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane, etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.), DMF, DMSO, NMP, acetonitrile, pyridine, etc., which can be used individually 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. The obtained desired compound (a-2) can be purified by conventional methods (e.g., column chromatography, recrystallization, etc.) if necessary. Process 2 Compound (a-5) can be obtained by reacting compounds (a-3) and (a-4) with a suitable reducing agent, acetic acid, and a suitable solvent. Examples of reducing agents include sodium triacetoxyborohydride and sodium cyanoborohydride, which 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-3). 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-3). Examples of reaction solvents include alcohols (e.g., methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane, etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.), DMF, DMSO, NMP, acetonitrile, pyridine, etc., which can be used individually or in combination. The reaction temperature is 0 to 80°C, preferably 0 to 20°C. The reaction time is 0.1 to 48 hours, preferably 0.5 to 24 hours. The obtained desired compounds (a-5) can be purified by conventional methods (e.g., column chromatography, recrystallization, etc.) if necessary. Process 3 Compound (Ia) can be obtained by reacting compound (a-5) and compound (a-2) in a suitable solvent. Examples of reaction solvents include alcohols (e.g., methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane, etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.), DMF, DMSO, NMP, acetonitrile, pyridine, etc., which can be used individually or in combination. The reaction temperature is 0 to 100°C, preferably 0 to 80°C. The reaction time is 0.1 to 24 hours, preferably 0.5 to 6 hours. The desired compound (Ia) obtained can be purified by conventional methods (e.g., column chromatography, recrystallization, etc.) if necessary.

[0062] [ka] (wherein PG is a suitable protecting group for an amino group, ring A is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group, R a (This is a substituted or unsubstituted alkyl group.) Process 1 Compound (b-3) can be obtained by reacting compounds (b-1) and (b-2) with a suitable reducing agent, and optionally acetic acid, in a suitable solvent. Examples of reducing agents include sodium triacetoxyborohydride and sodium cyanoborohydride, which can be used in an amount of 1.0 molar equivalent or more, preferably 1.0 to 2.0 molar equivalents, relative to compound (b-1). 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 (b-3). Examples of reaction solvents include alcohols (e.g., methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane, etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.), DMF, DMSO, NMP, acetonitrile, pyridine, etc., which can be used individually or in combination. The reaction temperature is 0 to 80°C, preferably 0 to 20°C. The reaction time is 0.1 to 48 hours, preferably 0.5 to 24 hours. The obtained desired compound (b-3) can be purified by conventional methods (e.g., column chromatography, recrystallization, etc.) if necessary. Process 2 Compound (b-4) can be obtained by reacting compound (b-3) and compound (a-2) in a suitable solvent. Examples of reaction solvents include alcohols (e.g., methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane, etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.), DMF, DMSO, NMP, acetonitrile, pyridine, etc., which can be used individually or in combination. The reaction temperature is 0 to 100°C, preferably 0 to 80°C. The reaction time is 0.1 to 24 hours, preferably 0.5 to 6 hours. The obtained desired compound (b-4) can be purified by conventional methods (e.g., column chromatography, recrystallization, etc.) if necessary. Process 3 Compound (b-4) can be reacted with compound (b-4) in the presence of an acid, in a solvent-free environment or in a suitable solvent to obtain compound (b-5). Examples of acids include hydrochloric acid, sulfuric acid, TFA, and formic acid, and can be used in an amount of 1.0 molar equivalent or more, preferably 1.0 to 30 molar equivalents, relative to compound (b-4). Examples of reaction solvents include alcohols (e.g., methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane, etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.), DMF, DMSO, NMP, acetonitrile, pyridine, etc., which can be used individually 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. The obtained desired compound (b-5) can be purified by conventional methods (e.g., column chromatography, recrystallization, etc.) if necessary. Process 4 Compound (Ib) can be obtained by reacting compounds (b-5) and (b-6) in a suitable solvent with a suitable reducing agent, and optionally with acetic acid. Examples of reducing agents include sodium triacetoxyborohydride and sodium cyanoborohydride, which can be used in an amount of 1.0 molar equivalent or more, preferably 1.0 to 2.0 molar equivalents, relative to compound (b-5). 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 (b-5). Examples of reaction solvents include alcohols (e.g., methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane, etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.), DMF, DMSO, NMP, acetonitrile, pyridine, etc., which can be used individually 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. The desired compound (Ib) obtained can be purified by conventional methods (e.g., column chromatography, recrystallization, etc.) if necessary.

[0063] [ka] Process 1 Compound (Ic) can be obtained by reacting compounds (a-5) and (c-1) in a suitable solvent with a suitable coupling agent and, if necessary, a base. Examples of condensing agents include HOBt, HOAt, DCC, DIC, EDC HCl, HATU, and PyBOP, which can be used in an amount of 1.0 molar equivalent or more, preferably 1.0 to 2.0 molar equivalents, relative to compound (b-5). Examples of bases include triethylamine and DIEA. A molar equivalent of 1.0 molar equivalent or more, preferably 1.0 to 2.0 molar equivalents, can be used relative to compound (a-5). Examples of reaction solvents include alcohols (e.g., methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane, etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.), DMF, DMSO, NMP, acetonitrile, pyridine, etc., which can be used individually 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. The obtained desired compound (Ic) can be purified by conventional methods (e.g., column chromatography, recrystallization, etc.) if necessary.

[0064] [ka] Process 1 Compound (a-5) and compound (d-1) are reacted with a base in a suitable solvent to form compound (I- d ) can be obtained. Examples of bases include triethylamine, DIEA, and pyridine. A molar equivalent of 1.0 molar equivalent or more, preferably 1.0 to 5.0 molar equivalents, can be used relative to compound (a-5). Examples of reaction solvents include alcohols (e.g., methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane, etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.), DMF, DMSO, NMP, acetonitrile, pyridine, etc., which can be used individually or in combination. The reaction temperature is 0 to 120°C, preferably 0 to 80°C. The reaction time is 0.1 to 24 hours, preferably 0.5 to 12 hours. The desired compound (Id) obtained can be purified by conventional methods (e.g., column chromatography, recrystallization) if necessary.

[0065] The compounds according to the present invention have a serotonin 5-HT2A receptor inverse agonist effect and are therefore useful as therapeutic and / or prophylactic agents for hallucinations and delusions associated with Parkinson's disease and / or dementia. Furthermore, the compounds according to the present invention possess pharmaceutical utility and preferably have one or more of the following excellent characteristics. a) It has a weak inhibitory effect on CYP enzymes (e.g., CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, etc.). b) It exhibits good pharmacokinetics, including high bioavailability and moderate clearance. c) High metabolic stability. d) It does not exhibit irreversible inhibitory activity against CYP enzymes (e.g., CYP3A4) within the concentration range of the measurement conditions described herein. e) It does not possess mutagenic properties. f) Low cardiovascular risk. g) It exhibits high solubility. h) It has high serotonin 5-HT2A receptor binding ability. i) It has high serotonin 5-HT2C receptor binding ability. j) High brain permeability. k) Low P-gp substrate activity

[0066] The pharmaceutical composition of the present invention can be administered orally or parenterally. Parenteral administration methods include transdermal, subcutaneous, intravenous, intra-arterial, intramuscular, intraperitoneal, transmucosal, inhalation, nasal, ophthalmic, ophthalmic, ophthalmic, and vaginal administration.

[0067] For oral administration, the drug may be prepared and administered in any of the commonly used dosage forms, such as oral solid preparations (e.g., tablets, powders, granules, capsules, pills, films, etc.) or oral liquid preparations (e.g., suspensions, emulsions, elixirs, syrups, lemonades, alcoholic preparations, aromatic water preparations, extracts, decoctions, tinctures, etc.), according to conventional methods. Tablets may be sugar-coated tablets, film-coated tablets, enteric-coated tablets, sustained-release tablets, lozenges, 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.

[0068] For parenteral administration, any commonly used dosage form such as injections, infusions, or topical preparations (e.g., eye drops, nasal drops, ear drops, aerosols, inhalants, lotions, injectables, ointments, gargles, enemas, ointments, plasters, jellies, creams, patches, poultices, topical powders, suppositories, etc.) can be suitably administered. Injectable preparations may also be emulsions of O / W, W / O, O / W / O, W / O / W type, etc.

[0069] A pharmaceutical composition can be prepared by mixing an effective amount of the compound according to the present invention with various pharmaceutical additives such as excipients, binders, disintegrants, and lubricants suitable for the dosage form, as needed. Furthermore, by appropriately changing the effective amount of the compound according to the present invention, the dosage form, and / or the various pharmaceutical additives, the pharmaceutical composition can be prepared for use in children, the elderly, critically ill patients, or for surgical use. For example, a pharmaceutical composition for children can be administered to neonates (less than 4 weeks after birth), infants (4 weeks after birth to less than 1 year), toddlers (1 year to less than 7 years), children (7 years to less than 15 years), or patients aged 15 to 18 years. For example, a pharmaceutical composition for the elderly can be administered to patients aged 65 years or older.

[0070] The dosage of the pharmaceutical composition of the present invention should preferably be determined considering the patient's age, weight, type and severity of the disease, route of administration, etc. However, when administered orally, it is usually 0.05 to 100 mg / kg / day, preferably within the range of 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 within the range of 0.01 to 1 mg / kg / day. This can be administered once or several times a day.

[0071] The compound according to the present invention can be used in combination with anti-Parkinson's disease drugs, anti-Alzheimer's disease drugs, antipsychotic drugs, and antidepressants (hereinafter referred to as "combination drugs") for the purpose of enhancing the effect of the compound or reducing the dosage of the compound. In this case, the timing of administration of the compound according to the present invention and the combination drugs is not limited; they may be administered to the target patient simultaneously or with a time difference. Furthermore, the compound according to the present invention and the combination drugs may be administered as two or more formulations containing their respective active ingredients, or as a single formulation containing those active ingredients.

[0072] The dosage of the concomitant drug can be appropriately selected based on clinically used doses. Furthermore, the mixing ratio of the compound according to the present invention and the concomitant drug can be appropriately selected depending on the target recipient, route of administration, target disease, symptoms, combination, etc. For example, when the target recipient is a human, 0.01 to 100 parts by weight of the concomitant drug may be used for every 1 part by weight of the compound according to the present invention.

[0073] Examples of antiparkinson's disease drugs include levodopa preparations. Examples of anti-Alzheimer's drugs include donepezil. Examples of antipsychotic drugs include quetiapine. Examples of antidepressants include escitalopram. [Examples]

[0074] The present invention will be described in more detail below with reference to examples, reference examples, and test examples, but the present invention is not limited thereto.

[0075] Furthermore, the abbreviations used in this specification have the following meanings. Acetic acid (ATOH) CDCl3: Deuterated chloroform CDI: Carbonyldiimidazole DCC:N,N'-Dicyclohexylcarbodiimide DIC: N,N'-Diisopropylcarbodiimide DIEA: N,N-diisopropylethylamine DMF: N,N-dimethylformamide DMSO: Dimethyl sulfoxide EDC: 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide HATU:O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate HOAt: 1-Hydroxy-7-Azabenzotriazole HOBt: 1-hydroxybenzotriazole NaBH(OAc)3: Sodium triacetoxyborohydride NMP: N-methylpyrrolidone TFA: Trifluoroacetic acid PyBOP®: Hexafluorophosphate (benzotriazole-1-yloxy)tripyrrolidinophosphonium

[0076] (Method for identifying compounds) NMR analysis of the results obtained in each example was performed at 400 MHz using DMSO-d6 and CDCl3. Note that when presenting NMR data, not all measured peaks may be listed. In the specification, RT 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 (2.2μm id3.0x50mm) (Shimadzu) Flow rate: 1.6mL / min UV detection wavelength: 254nm 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 was applied from 10% to 100% solvent [B] over 3 minutes, followed by maintaining 100% solvent [B] for 0.5 minutes. (Measurement condition 2) Column: ACQUITY UPLC(registered trademark) BEH C18 (1.7μm id2.1x50mm) (Waters) Flow rate: 0.8mL / min UV detection wavelength: 254nm 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 was applied from 5% to 100% solvent [B] over 3.5 minutes, followed by maintaining 100% solvent [B] for 0.5 minutes. In the specification, MS(m / z) refers to the value observed by mass spectrometry. [Examples]

[0077] Synthesis of compound (I-008) [ka] Step 1: Synthesis of Compound 1 4-Isobutoxyphenylmethaneamine (6.00 g, 33.5 mmol) and CDI (651 mg, 40.2 mmol) were dissolved in acetonitrile (60 mL) and stirred at room temperature for 1 hour. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 1 (7.92 g, yield 87%). 1H-NMR(CDCl3)δ:1.02 (d, J = 6.5 Hz, 6H), 2.00-2.14 (m, 1H), 3.68-3.77 (m, 2H), 4.49-4.59 (m, 2H), 6.03 (brs, 1H), 6.90 (d, J = 7.3 Hz, 2H), 7.07 (s, 1H), 7.22-7.35 (m, 3H), 8.10 (s, 1H). Step 2: Synthesis of Compound 2 5-Fluoropicolinealdehyde (1.00 g, 7.99 mmol) and 1-methylpiperidine 4-amine (913 mg, 7.99 mmol) were dissolved in dichloromethane (20 mL), and hydrogenated triacetoxyborohydride (3.39 g, 16.0 mmol) and acetic acid (0.914 mL, 16.0 mmol) were added. The mixture was stirred overnight at room temperature. Saturated sodium bicarbonate aqueous solution was added, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain compound 2 (970 mg, yield 55%). 1 H-NMR(CDCl3)δ:1.42-1.53 ​​(m, 2H), 1.81-2.03 (m, 4H), 2.27 (s, 3H), 2.45-2.54 (m, 1H), 2.83 (d, J = 11.8 Hz, 2H), 3.92 (s, 2H), 7.31-7.40 (m, 2H), 8.40 (d, J = 2.5 Hz, 1H). Step 3 Synthesis of compound (I-008) Compound 1 (673 mg, 2.46 mmol) and Compound 2 (500 mg, 2.24 mmol) were dissolved in toluene (5 mL) and stirred at 80°C for 1 hour. After cooling, the solvent was removed by distillation under reduced pressure, and the resulting residue was purified by amino column chromatography (hexane-ethyl acetate) to obtain Compound (I-008) (525 mg, yield 55%). [Examples]

[0078] Synthesis of compound (I-042) [ka] Step 1: Synthesis of compound (I-042) Compound 2 (74.4 mg, 0.333 mmol) was dissolved in N,N-dimethylformamide (1.15 mL), and 4-isobutoxybenzyl (4-nitrophenyl) carbonate (74.4 mg, 0.333 mmol) and triethylamine (0.14 mL, 1.00 mmol) were added. The mixture was stirred at 70°C for 8 hours. Water was added, and the mixture was extracted with ethyl acetate. After washing the organic layer with water, the solvent was removed by reduced pressure, and the resulting residue was purified by silica gel column chromatography (ethyl acetate-hexane) to obtain compound (I-042) (40 mg, yield 28%). [Examples]

[0079] Synthesis of compound (I-050) [ka] Step 1: Synthesis of Compound 5 Compound 4 (300 mg, 1.33 mmol) was mixed with dichloromethane (5 mL), (5-fluoropyridine-2-yl)methaneamine (202 mg, 1.60 mmol), AcOH (0.07 mL, 1.33 mmol), and sodium triacetoxyborohydride (423 mg, 2.00 mmol) and stirred at room temperature for 6 hours. Saturated sodium bicarbonate solution (5 mL) was added and stirred at room temperature. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the resulting residue was purified by aminosilica gel column chromatography (hexane-ethyl acetate) to obtain compound 5 (402 mg, 90% yield). 1H-NMR (CDCl3) δ: 0.28-0.33 (m, 1H), 0.40-0.48 (m, 3H), 1.44 (s, 9H), 1.62-1.68 (m, 1H), 1.75-1.82 (m, 1H), 2.15 (t, J = 3.6 Hz, 1H), 2.94-3.10 (m, 1H), 3.33-3.42 (m, 1H), 3.46-3.53(m, 1H), 3.65-3.82 (m, 1H), 3.84 (d, J = 14.4 Hz, 1H), 3.90 (d, J = 14.4 Hz, 1H), 7.31-7.39 (m, 2H), 8.40 (d, J = 2.6 Hz, 1H). Step 2: Synthesis of Compound 6 Compound 5 (150 mg, 0.45 mmol) was mixed with acetonitrile (2 mL) and N-(4-isobutoxybenzyl)-1H-imidazole-1-carboxamide (147 mg, 0.54 mmol) and stirred at 80°C for 8 hours. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 6 (195 mg, yield 81%). 1 H-NMR (CDCl3) δ: 0.32-0.50 (m, 3H), 0.52-0.58 (m, 1H), 1.02 (d, J = 6.8 Hz, 6H), 1.44 (9H, s), 1.56-1.62 (m, 1H), 1.69-1.76 (m, 1H), 1.80-1.91 (m, 1H), 2.04-2.11 (m, 1H), 2.80-3.01 (m, 1H), 3.06-3.48 (m, 2H), 3.70 (d, J = 6.7 Hz, 2H), 5.80-6.18 (m, 1H), 6.82 (d, J = 8.5 Hz, 2H), 7.13 (d, J = 8.7 Hz, 2H), 7.21-7.25 (m, 1H), 7.35 (td, J = 8.3, 2.8 Hz, 1H), 8.28 (s, 1H). Step 3 Synthesis of compound (I-051) Compound 6 (195 mg, 0.36 mmol) was mixed with dichloromethane (2 mL) and TFA (0.5 mL, 6.49 mmol) and stirred at room temperature for 3 hours. 20% potassium carbonate aqueous solution (4 mL) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain compound (I-051) (152 mg, 96% yield). 1H-NMR (CDCl3) δ: 0.28-0.32 (m, 1H), 0.39-0.42 (m, 1H), 0.42-0.48 (m, 1H), 0.57-0.62 (m, 1H), 1.01 (d, J = 6.7 Hz, 6H), 1.95-2.10 (m, 3H), 2.35 (d, J = 13.6 Hz, 1H), 2.87 (t, J = 10.8 Hz, 1H), 3.17 (d, J = 12.2 Hz, 1H), 3.28 (d, J = 12.9 Hz, 1H), 3.70 (d, J = 6.5 Hz, 2H), 4.24-4.57 (m, 6H), 6.05 (s, 1H), 6.82 (d, J = 8.5 Hz, 2H), 7.13 (d, J = 8.5 Hz, 2H), 7.22-7.26 (m, 1H), 7.35 (td, J = 8.3, 2.9 Hz, 1H), 8.27 (d, J = 2.8 Hz, 1H). Step 4 Synthesis of compound (I-050) Compound (I-051) (85 mg, 0.19 mmol) was mixed with ethanol (2 mL), 37% formaldehyde solution (0.03 mL, 0.39 mmol), and sodium triacetoxyborohydride (61 mg, 0.29 mmol), and the mixture was stirred at room temperature for 2 hours. Saturated sodium bicarbonate solution (5 mL) was added, and the mixture was stirred at room temperature. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was removed by vacuum distillation, and the resulting residue was purified by aminosilica gel column chromatography (hexane-ethyl acetate) to obtain compound (I-050) (80 mg, yield 91%). [Examples]

[0080] Synthesis of compound (I-068) [ka] Step 1: Synthesis of compound (I-068) Compound 2 (75.0 mg, 0.336 mmol) was dissolved in N,N-dimethylformamide (0.75 mL), and 2-(4-isobutoxyphenyl)acetic acid (84.0 mg, 0.403 mmol) (synthesis method described in WO2019 / 40104), HOBt (54.5 mg, 0.403 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (77.0 mg, 0.403 mmol) were added. The mixture was stirred at room temperature for 1.5 hours. Aqueous potassium carbonate solution was added, and the mixture was extracted with ethyl acetate. After washing the organic layer with water, the solvent was removed by vacuum distillation, and the resulting residue was purified by silica gel column chromatography (ethyl acetate-hexane) to obtain compound (I-068) (104 mg, yield 75%). Reference example 1

[0081] Synthesis of compound 8 [ka] Step 1: Synthesis of Compound 8 To a solution of p-tolylmethaneamine (0.6 g, 5.00 mmol) in tetrahydrofuran (14 ml), CDI (0.97 g, 6.00 mmol) was added and the mixture was stirred at 45°C for 3 hours. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 8 (0.66 g, yield 61%). 1H-NMR (400 MHz, CDCl3) δ: 1.60 (s, 3H), 2.34 (s, 3H), 4.56 (d, J = 5.5 Hz, 2H), 6.06 (s, 1H), 7.07 (s, 1H), 7.19 (d, J = 7.9 Hz, 2H), 7.22-7.26 (m, 2H), 7.31 (s, 1H), 8.09 (s, 1H). [Examples]

[0082] Synthesis of compound (I-120) [ka] Step 1: Synthesis of Compound 9 Under ice cooling, (S)-1-phenethyl-1-amine (1.29 g, 10.7 mmol) was mixed with dichloromethane (30 mL), triethylamine (5.39 g, 53.3 mmol), titanium tetrachloride (4.44 mL, 4.44 mmol), and compound 4 (2 g, 8.88 mmol), and the mixture was stirred at room temperature for 18 hours. Diethyl ether (60 mL) was added, and the mixture was stirred at room temperature for 30 minutes. After removing the resulting solid by filtration, the solvent was removed under reduced pressure to obtain compound 9 (2.8 g, 96% yield). Step 2 Synthesis of compound 10 To a solution of compound 9 (2.8 g, 8.52 mmol) at -78°C in ethanol (28 ml), sodium borohydride (0.16 g, 4.26 mmol) was added and the mixture was stirred at -78°C for 2 hours. Saturated sodium bicarbonate solution (20 mL) was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was removed by vacuum distillation, and the resulting residue was purified by aminosilica gel column chromatography (hexane-ethyl acetate) to obtain compound 10 (2.1 g, yield 75%). 1 H-NMR (CDCl3) δ: 0.29-0.50 (m, 4H), 1.30 (d, J = 6.4 Hz, 2H), 1.42 (s, 9H), 1.45-1.70 (m, 2H), 2.18 (s, 1H), 2.92-3.06 (s, 1H), 3.28-3.49 (m, 3H), 3.83 (q, J = 6.6 Hz, 1H), 7.22 (dd, J = 8.7, 4.5 Hz, 1H), 7.30 (d, J = 4.3 Hz, 4H). Step 3 Synthesis of Compound 11 Compound 10 (157 mg, 0.48 mmol) was mixed with methanol (1.6 mL), ammonium formate (150 mg, 2.38 mmol), and palladium carbon hydroxide (40 mg, 0.14 mmol), and the mixture was stirred at 60°C for 1 hour. The reaction mixture was filtered to remove the palladium carbon hydroxide, and then the solvent was removed under reduced pressure to obtain compound 11 (102 mg, 95% yield). 1H-NMR (CDCl3) δ: 0.32-0.50 (m, 4H), 1.45 (s, 9H), 1.50-1.62 (m, 1H), 1.80-1.88 (m, 1H), 2.62 (dd, J = 10.0, 6.4 Hz, 1H), 3.05 (d, J = 12.2 Hz, 1H), 3.41 (d, J = 13.6 Hz, 1H), 3.45-3.62 (m, 2H). Step 4 Synthesis of Compound 12 Compound 12 was obtained by using compound 11 (49 mg, 0.22 mmol) instead of 1-methylpiperidine 4-amine in step 2 of Example 1. Step 5 Synthesis of Compound 13 Compound 13 was obtained by using compound 12 instead of compound 5 in step 2 of Example 3, and by using compound 8 instead of N-(4-isobutoxybenzyl)-1H-imidazole-1-carboxamide. Step 6 Synthesis of Compound 14 Compound 14 was obtained by using compound 13 instead of compound 6 in step 3 of Example 3. Step 7 Synthesis of I-120 Compound (I-120) (38 mg, 53% total yield in 4 steps) was obtained by using compound 14 instead of compound (I-051) in step 4 of Example 3. [Examples]

[0083] Synthesis of compound (I-136) [ka] Step 1: Synthesis of Compound 16 Compound 15 (500 mg, 3.02 mmol) was mixed with ethanol (5 mL), methyl acrylate (0.03 mL, 3.02 mmol), and triethylamine (0.42 mL, 3.02 mmol), and the mixture was stirred at room temperature for 48 hours. The solvent was removed by distillation under reduced pressure to obtain compound 16 (654 mg, 101% yield) as the crude product. Step 2 Synthesis of Compound 17 Compound 16 (654 mg, 3.02 mmol) was mixed with methanol (5 mL), 37% formaldehyde solution (0.67 mL, 9.06 mmol), and NaBH(OAc)3 (61 mg, 0.29 mmol) and stirred at room temperature for 1 hour. Saturated sodium bicarbonate solution (5 mL) was added and stirred at room temperature. Water was added and the mixture was extracted with chloroform. The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain compound 17 (687 mg, 99% yield) as the crude product. Step 3 Synthesis of Compound 18 Compound 17 (195 mg, 0.36 mmol) was mixed with toluene (7 mL) and 28% sodium methoxide solution (2.2 mL, 8.87 mmol) and stirred under reflux for 4 hours. After removing the solvent under reduced pressure, methanol (3 mL) and water (3 mL) were added and stirred under reflux for 4 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After removing the solvent under reduced pressure, compound 18 (432 mg, yield 105%) was obtained as the crude product. Step 4 Synthesis of Compound 19 Compound 18 (132 mg, 0.95 mmol) was mixed with dichloromethane (5 mL), (5-fluoropyridine-2-yl)methaneamine (120 mg, 0.95 mmol), AcOH (0.07 mL, 1.14 mmol), and NaBH(OAc)3 (241 mg, 1.14 mmol) and stirred at room temperature for 1 hour. Saturated sodium bicarbonate solution (5 mL) was added and stirred at room temperature. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain compound 19 (157 mg, 67% yield) as the crude product. Step 5 Synthesis of compound (I-136) Compound 19 (18 mg, 0.07 mmol) was mixed with acetonitrile (0.2 mL) and N-(4-isobutoxybenzyl)-1H-imidazole-1-carboxamide (22 mg, 0.08 mmol) and stirred at 80°C for 1 hour. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound (I-136) (22 mg, yield 67%). 1H-NMR (CDCl3) δ: 0.30-0.36 (m, 1H), 0.43-0.48 (m, 1H), 0.58-0.71 (m, 2H), 1.02 (d, 6H, J = 6.5 Hz), 1.37-1.47 (m, 1H), 1.86-1.97 (m, 1H), 2.03-2.10 (m, 1H), 2.21-2.37 (m, 4H), 2.85-2.99 (m, 2H), 3.70 (d, 2H, J = 5.0 Hz), 4.33 (t, 2H, J = 4.5 Hz), 4.42 (s, 3H), 6.20 (br s, 1H), 6.82 (d, 2H, J = 8.0 Hz), 7.15 (d, 2H, J = 8.0 Hz), 7.28-7.40 (m, 2H), 8.29 (s, 1H). [Examples]

[0084] Synthesis of compound (I-139) [ka] Step 1: Synthesis of Compound 21 Compound 20 (300 mg, 1.37 mmol) was mixed with dichloromethane (5 mL), 1,5-dimethyl-1H-pyrazolecarbolide (171 mg, 1.37 mmol), AcOH (0.39 mL, 6.87 mmol), and NaBH(OAc)3 (583 mg, 2.75 mmol) and stirred at room temperature for 2 hours. Saturated sodium bicarbonate solution was added and stirred at room temperature. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was removed by reduced pressure distillation, and the resulting residue was purified by aminosilica gel column chromatography (hexane-ethyl acetate) to obtain compound 21 (359 mg, yield 80%). 1 H-NMR (CDCl3) δ: 1.45 (s, 9H), 1.59-1.81 (m, 2H), 2.24 (s, 3H), 2.69-3.02 (m, 2H), 3.72 (s, 3H), 3.72 (s, 3H), 3.80 (s, 2H), 3.69-4.20 (m, 1H), 4.23-4.42 (m, 1H), 4.69-4.81 (m, 1H), 5.96 (s, 1H). Step 2: Synthesis of Compound 22 Compound 21 (142 mg, 0.44 mmol) was mixed with acetonitrile (3 mL) and N-(4-n-propoxybenzyl)-1H-imidazole-1-carboxamide (113 mg, 0.44 mmol) and stirred at 80°C for 4 hours. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 22 (195 mg, yield 81%). 1H-NMR (CDCl3) δ: 1.03 (t, 3H, J = 7.4 Hz), 1.47 (s, 9H), 1.56-1.65 (m, 1H), 1.75-1.84 (m, 1H), 2.15-2.24 (m, 4H), 2.75-3.10 (m, 2H), 3.56 (s, 3H), 3.90 (t, 2H, J = 6.6 Hz), 4.25-4.42 (m, 5H), 4.74-4.63 (m, 1H), 4.76-4.89 (m, 1H), 5.92 (s, 1H), 5.92 (s, 1H), 6.82 (d, J = 8.5 Hz, 2H), 7.15 (d, J = 8.5 Hz, 2H). Step 3 Synthesis of Compound 23 Compound 22 (80 mg, 0.36 mmol) was mixed with dichloromethane (1 mL), 2,6-lutidine (0.08 mL, 0.695 mmol), and trimethylsilyl triflate (0.08 mL, 0.695 mmol) and stirred at room temperature for 10 minutes. 20% aqueous potassium carbonate solution (4 mL) was added, and the mixture was extracted with ethyl acetate. The solvent was removed by reduced pressure, and the resulting residue was purified by aminosilica gel column chromatography (hexane-ethyl acetate) to obtain compound 23 (52 mg, 80% yield). 1H-NMR (CDCl3) δ: 1.01 (6H, d, J = 6.8 Hz), 1.62 (1H, br s), 2.02-2.12 (2H, m), 2.21 (3H, s), 2.74-2.92 (2H, m), 3.24 (2H, dd, J = 29.7, 14.9 Hz), 3.57 (3H, s), 3.69 (2H, d, J = 6.5 Hz), 4.30-4.34 (4H, m), 4.57 (1H, dt, J = 35.4, 6.4 Hz), 4.78 (1H, d, J = 50.8 Hz), 5.92 (1H, s), 6.82 (1H, br s), 6.81 (2H, d, J = 8.5 Hz), 7.14 (2H, d, J = 8.5 Hz). Step 4 Synthesis of compound (I-139) Compound 23 (30 mg, 0.19 mmol) was mixed with methanol (1 mL), 37% formaldehyde solution (0.03 mL, 0.36 mmol), and NaBH(OAc)3 (45 mg, 0.22 mmol) and stirred at room temperature for 1 hour. Saturated sodium bicarbonate solution was added and stirred at room temperature. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was removed by vacuum distillation, and the resulting residue was purified by aminosilica gel column chromatography (hexane-ethyl acetate) to obtain compound (I-139) (20 mg, yield 66%). 1H-NMR (CDCl3) δ: 1.03 (t, 3H, J = 7.5 Hz), 1.61-1.68 (m, 1H), 1.75-1.84 (m, 2H), 2.15-2.37 (m, 9H), 3.00 (d, 1H, J = 10.8 Hz), 3.14 (t, 1H, J = 11.9 Hz), 3.56 (s, 3H), 3.90 (t, 2H, J = 6.7 Hz), 4.26-4.51 (m, 5H), 4.79-4.91 (m, 1H), 5.93 (br s, 1H), 6.70 (br s, 1H), 6.81(d, 2H, J = 8.5 Hz), 7.15 (d, 2H, J = 8.5 Hz).

[0085] The following compounds were synthesized according to the general synthesis methods and the methods described in the examples above. Their structures and properties (LC / MS data) are shown in the table below. In the structural formula, the "wedge shape" and "dashed line" indicate the stereochemistry. In particular, among compounds where the stereochemistry is described, compounds with "racemate" listed under the "stereochemistry" section are racemates whose relative stereochemistry has been determined. Furthermore, in compounds where the bond forming the chiral carbon is indicated by a solid line, compounds with "racemate" listed under the "stereotype" section are racemic compounds. Compounds listed as "diastereo mixture" under the "stereotype" section are diastereomer mixtures.

[0086] Table 1

[0087] Table 2

[0088] Table 3

[0089] Table 4

[0090] Table 5

[0091] Table 6

[0092] Table 7 Table 8

[0093] Table 9

[0094] Table 10

[0095] Table 11

[0096] Table 12

[0097] Table 13

[0098] Table 14

[0099] Table 15

[0100] Table 16

[0101] Table 17

[0102] Table 18

[0103] Table 19

[0104] Table 20

[0105] Table 21

[0106] Table 22

[0107] Table 23

[0108] Table 24

[0109] Table 25

[0110] Table 26

[0111] Table 27

[0112] Table 28

[0113] Table 29

[0114] Table 30

[0115] Table 31

[0116] Table 32

[0117] [Table 33]

[0118] [Table 34]

[0119] [Table 35]

[0120] [Table 36]

[0121] [Table 37]

[0122] [Table 38]

[0123] [Table 39]

[0124] [Table 40]

[0125] Examples of biological tests of the compounds according to the present invention are described below. The compound represented by formula (I) or formula (II) according to the present invention may have serotonin 5-HT2A receptor inverse agonism and antagonize human serotonin 5-HT2A receptors. Specifically, in the evaluation method 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.

[0126] Test Example 1: 5-HT2A receptor binding inhibition test (Each experimental condition) Cell membrane: 15 μg of Jump-In HEK cell membrane (expressing human recombinant 5-HT2A receptor) per well Assay buffer: 50 mmol / L (pH 7.4) containing NaCl 120 mmol / L, MgCl2·6H2O 1 mmol / L, KCl 5 mmol / L, 0.1% BSA, and CaCl2 2 mmol / L, along with Tris-HCl. Radioactive ligand: Final concentration of 3 nmol / L [ 3 H]-Ketanserin Nonspecific ligand: Serotonin HCl at a final concentration of 500 μmol / L Kd values ​​were calculated when the cell membrane lot was changed. Prior to this, 0.5 μL of a 1 mmol / L non-specific binding calculation compound dissolved in DMSO or DMSO was dispensed into a microplate, and the cell membrane was diluted with Assay buffer. The radioactive ligand solution was serially diluted from 16 nM at a 2-fold common ratio, and the count was confirmed using a liquid scintillator. 50 μL / well of Assay buffer containing the diluted cell membrane was dispensed into a microplate. Then, 50 μL / well of the radioactive ligand solution was dispensed into the microplate, and the plate was sealed. It was allowed 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) was dispensed into a GF / B UniFilter plate, and it was allowed to stand at 4°C for at least 1 hour. Then, filtration was performed using a cell harvester (PerkinElmer). 10 μL / well of the radioactive ligand solution was dispensed into the empty wells of the GF / B UniFilter plate. After drying the GF / B UniFilter plate at room temperature, MicroScinti20 was dispensed into the GF / B UniFilter plate at 50 μL / well and the plate was sealed. The GF / B UniFilter plate was left to stand overnight at room temperature. [ 5-HT2A receptor bound [ 3 The radioactivity of [H]-Ketanserin was measured using Microbeta2 (PerkinElmer) at a measurement time of 1 min / well. A saturation curve was plotted from the measured values, and the Kd value was calculated from the slope of the Scatchard plot. (Compound binding test according to the present invention) First, 0.5 μL of the compound solution dissolved in DMSO was dispensed into a microplate, and the cell membrane and hot ligand were diluted in Assay buffer. Then, 50 μL / well of the Assay buffer containing the diluted cell membrane was dispensed into the microplate. Next, 50 μL / well of the radioactive ligand solution was dispensed into the microplate, and the plate was sealed. Then, it was 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) was dispensed into a GF / B UniFilter plate, and it was left to stand at 4°C for more than 1 hour. Then, filtration was performed with a cell harvester (PerkinElmer). After drying the GF / B UniFilter plate at room temperature, 50 μL / well of MicroScinti20 was dispensed into the GF / B UniFilter plate, and the plate was sealed. The GF / B UniFilter plate was left to stand overnight at room temperature. [ ] 3 The radioactivity of [H]-Ketanserin was measured using Microbeta2 (PerkinElmer) at a measurement time of 1 min / well. Nonspecific binding was measured in the presence of ligand-free 500 μmol / L Serotonin HCl, and total binding was measured in the absence of the compound according to the present invention (Vehicle). 3 The Ki value was calculated from the radioactivity of [H]-Ketanserin. Finally, the Ki value was calculated from the dose-response curve. (The binding activity of the compound according to the present invention was calculated from the following binding inhibition rate (%).) Inhibition rate (%) = [1 - (ca) / (ba)] × 100 a; Average cpm of non-singular coupling b; average cpm of total connections c; cpm in the presence of the test compound (result) The evaluation results regarding the human serotonin 5-HT2A receptor binding activity of the compounds according to the present invention are shown below. The Ki value is defined as follows: less than 10 nM is "A", 10 nM or more and less than 100 nM is "B", and 100 nM or more is "C". Compound I-009:0.291nM Compound I-021:0.858nM Compound I-037:0.654nM Compound I-042: 1.15nM Compound I-043:2.52nM Compound I-068:6.52nM Compound I-071: 13.3nM Compound I-072:219nM Compound I-075: 130nM Compound I-076:62nM Compound I-082: 3.74nM Compound I-084:5.61nM Compound I-085:23.8nM Compound I-088:25.7nM Compound I-102: 0.919nM Compound I-116: 1.45nM Compound I-124: 0.690nM Compound I-126: 1.92nM Compound I-129: 0.85nM Compound I-130: 15.3nM Compound I-134: 0.475nM Compound I-136:8.02nM Compound I-139: 2.93nM Compound I-146: 1.94nM Compound I-147: 0.758nM [Table 41] [Table 42] [Table 43]

[0127] Test Example 2: 5-HT2C Receptor Binding Inhibition Test (Each experimental condition) Cell membrane: 0.5 μg of Jump-In HEK cell membrane (expressing human recombinant 5-HT2C receptor) per well Assay buffer: 50 mmol / L (pH 7.4) containing NaCl 120 mmol / L, MgCl2·6H2O 1 mmol / L, KCl 5 mmol / L, 0.1% BSA, and CaCl2 2 mmol / L, along with Tris-HCl. Radioactive ligand: Final concentration of 1 nmol / L [ 3 H]-Mesulergine Non-specific ligand: Final concentration 500 μmol / L Serotonin HCl Kd values ​​were calculated when the cell membrane lot was changed. Prior to this, 0.5 μL of a 1 mmol / L non-specific binding calculation compound dissolved in DMSO or DMSO was dispensed into a microplate, and the cell membrane was diluted with Assay buffer. The radioactive ligand solution was serially diluted from 16 nM at a 2-fold common ratio, and the count was confirmed using a liquid scintillator. 50 μL / well of Assay buffer containing the diluted cell membrane was dispensed into a microplate. Then, 50 μL / well of the radioactive ligand solution was dispensed into the microplate, and the plate was sealed. It was 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) was dispensed into a GF / B UniFilter plate, and it was left to stand at 4°C for at least 1 hour. Then, filtration was performed using a cell harvester (PerkinElmer). 10 μL / well of the radioactive ligand solution was dispensed into the empty wells of the GF / B UniFilter plate. After drying the GF / B UniFilter plate at room temperature, MicroScinti20 was dispensed into the GF / B UniFilter plate at a rate of 50 μL / well, and the plate was sealed. The GF / B UniFilter plate was left to stand overnight at room temperature. 5-HT2 C Binding to the receptor [ 3 H]- MesulergineThe radioactivity was measured using Microbeta2 (PerkinElmer) at a measurement time of 1 min / well. A saturation curve was plotted from the measured values, and the Kd value was calculated from the slope of the Scatchard plot. (Compound binding test according to the present invention) First, 0.5 μL of the compound solution dissolved in DMSO was dispensed into a microplate, and the cell membrane and hot ligand were diluted in Assay buffer. Then, 50 μL / well of the Assay buffer containing the diluted cell membrane was dispensed into the microplate. Next, 50 μL / well of the radioactive ligand solution was dispensed into the microplate, and the plate was sealed. The plate was then left to stand at 37°C for 2 hours. During this time, 50 μL / well of 50 mmol / L Tris-HCl (pH 7.4) was dispensed into a GF / B UniFilter plate, and it was left to stand at 4°C for at least 1 hour. After that, filtration was performed using a cell harvester (PerkinElmer). After drying the GF / B UniFilter plate at room temperature, 50 μL / well of MicroScinti20 was dispensed into the GF / B UniFilter plate, and it was sealed. The GF / B UniFilter plate was left to stand overnight at room temperature. 5-HT2 C Binding to the receptor [ 3 The radioactivity of [H]-Mesulergine was measured using Microbeta2 (PerkinElmer) at a measurement time of 1 min / well. Nonspecific binding was measured in the presence of ligand-free 500 μmol / L Serotonin HCl, and total binding was measured in the absence of the compound according to the present invention (Vehicle) [ 3 The Ki value was calculated from the radioactivity of [H]-Mesulergine. Finally, the Ki value was calculated from the dose-response curve. (The binding activity of the compound according to the present invention was calculated from the following binding inhibition rate (%).) Inhibition rate (%) = [1 - (ca) / (ba)] × 100 a; Average cpm of non-singular coupling b; average cpm of total connections c; cpm in the presence of the test compound (result) The evaluation results regarding the human serotonin 5-HT2C receptor binding inhibitory activity of the compounds according to the present invention are shown below. The Ki value is defined as follows: less than 10 nM is "A", 10 nM or more and less than 100 nM is "B", and 100 nM or more is "C". Compound I-009:7.92nM Compound I-021:50.7nM Compound I-037:28.2nM Compound I-042:2.31nM Compound I-043:55.7nM Compound I-068:49.9nM Compound I-071:60.7nM Compound I-072:617nM Compound I-075:1310nM Compound I-076:263nM Compound I-082:28.8nM Compound I-084:65.2nM Compound I-085:96.2nM Compound I-088: 134nM Compound I-102:4.01nM Compound I-116: 12.2nM Compound I-124: 2.22nM Compound I-126: 1.09nM Compound I-129: 1.51nM Compound I-130: 348nM Compound I-134: 3.2nM Compound I-136: 148nM Compound I-139: 11.1nM Compound I-146:4.96nM Compound I-147: 2.12nM [Table 44] [Table 45] [Table 46]

[0128] Test Example 3: hERG Test To evaluate the risk of QT interval prolongation on an electrocardiogram using compounds according to the present invention, CHO cells expressing human ether-a-go-go related gene (hERG) channels were used to evaluate delayed rectification K, which plays an important role in the ventricular repolarization process. + Current (I Kr The effects of the compounds according to the present invention on ) were investigated. Using a fully automated patch clamp system (QPatch; Sophion Bioscience A / S), the whole-cell patch clamp method was used to maintain cells at a membrane potential of -80mV, apply a leakage potential of -50mV, then apply a depolarizing stimulus of +20mV for 2 seconds, followed by a repolarizing stimulus of -50mV for 2 seconds, which induced I Kr The results were recorded. An extracellular solution of dimethyl sulfoxide adjusted to 0.1% (NaCl: 145 mmol / L, KCl: 4 mmol / L, CaCl2: 2 mmol / L, MgCl2: 1 mmol / L, glucose: 10 mmol / L, HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid): 10 mmol / L, pH=7.4) was used as the medium, and the extracellular solution in which the medium and the compound according to the present invention were dissolved at the desired concentration was applied to cells at room temperature for 15 minutes or more. Kr Therefore, using analysis software (QPatch Assay software; Sophion Bioscience A / S), the absolute value of the maximum tail current was measured based on the current value at the retained membrane potential. The maximum tail current after application of the compound according to the present invention was calculated as the inhibition rate relative to the maximum tail current after application of the medium, and further correction was performed using the inhibition rate results of the negative control to determine the I of the compound according to the present invention. Kr The impact was evaluated. (Results) The inhibition rate at a compound concentration of 3 μmol / L is shown. Compound I-129:31.4% Compound I-133:6.60% Compound I-134:31.2% Compound I-139:14.2% Compound I-141:49.3%

[0129] Test Example 4: BA Test Materials and methods for the study of oral absorption (1) Animals used: Mice or rats will be used. (2) Rearing conditions: Mice or rats will be given free access to solid feed and sterilized tap water. (3) Dosage and group setting: Administer orally and intravenously at the prescribed dosage. Groups are set as follows: (Dosage may vary depending on the compound) Oral administration: 2-60 μmol / kg or 1-30 mg / kg (n=2-3) Intravenous administration: 1-20 μmol / kg or 0.5-10 mg / kg (n=2-3) (4) Preparation of administration solution: Oral administration should be given as a solution or suspension. Intravenous administration should be given after solubilization. (5) Method of administration: Oral administration is performed by forcibly administering the drug into the stomach using an oral tube. Intravenous administration is performed by administering the drug into the tail vein using a syringe fitted with a needle. (6) Evaluation items: Blood samples are collected over time, and the concentration of the compound according to the present invention in the plasma is measured using LC / MS / MS. (7) Statistical analysis: The area under the plasma concentration-time curve (AUC) is calculated for the plasma concentration profile of the compound according to the present invention using moment analysis, and the bioavailability (BA) of the compound according to the present invention is calculated from the dose ratio and AUC ratio of the oral administration group and the intravenous administration group. Note that the dilution concentration and dilution solvent may be changed as needed.

[0130] Test Example 5: Clearance Evaluation Test Experimental materials and methods (1) Animals used: SD rats will be used. (2) Rearing conditions: SD rats are given free access to solid feed and sterilized tap water. (3) Dosage and group setting: Intravenous administration was performed at the prescribed dosage. The groups were set up as follows. Intravenous administration: 1 μmol / kg (n=2) (4) Preparation of the administration solution: Solubilize with dimethyl sulfoxide / propylene glycol = 1 / 1 solvent and administer. (5) Method of administration: Administer via the tail vein using a syringe fitted with a needle. (6) Evaluation items: Blood samples are collected over time, and the concentration of the compound according to the present invention in the plasma is measured using LC / MS / MS. (7) Statistical analysis: The systemic clearance (CLtot) of the plasma concentration profile of the compound according to the present invention is calculated using moment analysis. The dilution concentration and dilution solvent may be changed as necessary.

[0131] Test Example 6: Metabolic Stability Test The compound according to the present invention is reacted with commercially available pooled human liver microsomes for a certain period of time, and the residual rate is calculated by comparing the reacted sample with the unreacted sample to evaluate the extent to which the compound according to the present invention is metabolized in the liver.

[0132] The reaction is carried out at 37°C for 0 or 30 minutes (oxidative reaction) 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 human liver microsome protein / mL in the presence of 1 mmol / L NADPH. After the reaction, 50 μL of the reaction solution is added to 100 μL of methanol / acetonitrile = 1 / 1 (v / v) solution, mixed, and centrifuged at 3000 rpm for 15 minutes. The compound according to the present invention in the supernatant is quantified by LC / MS / MS or solid-phase extraction (SPE) / MS, and the amount of the compound according to the present invention remaining after the reaction is calculated, with the amount of the compound at 0 minutes of reaction set to 100%.

[0133] Test Example 7: P-gp Substrate Test The compound according to the present invention is added to one side of a Transwell (registered trademark, CORNING) containing a monolayer culture of human MDR1-expressing cells or parental cells, and the mixture is allowed to react for a certain period of time. The membrane permeability coefficients are calculated for the MDR1-expressing cells and parental cells in the direction from apical to basolateral (A→B) and from basolateral to apical (B→A), and the Efflux Ratio (ER; ratio of membrane permeability coefficients from B→A to A→B) is calculated for the MDR1-expressing cells and parental cells. The Efflux Ratio (ER value) of the MDR1-expressing cells and parental cells is compared to determine whether the compound according to the present invention is a P-gp substrate.

[0134] The formulation examples shown below are for illustrative purposes only and are not intended to limit the scope of the invention in any way. The compounds of the present invention can be administered as pharmaceutical compositions by any conventional route, particularly enterally, for example, orally, for example, in the form of tablets or capsules; parenterally, for example, in the form of injection solutions or suspensions; topically, for example, 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 pharmaceutically acceptable salts, together with at least one pharmaceutically acceptable carrier or diluent, can be produced by conventional methods such as mixing, granulation or coating. For example, oral compositions may be tablets, granules, or capsules containing excipients, disintegrants, binders, lubricants, etc., and the active ingredient, etc. Injectable compositions may be solutions or suspensions, which may be sterile, and may also contain preservatives, stabilizers, buffers, etc. [Industrial applicability]

[0135] The compounds according to the present invention have serotonin 5-HT2A receptor inverse agonism and are considered useful as therapeutic and / or prophylactic agents for diseases or conditions involving the serotonin 5-HT2A receptor.

Claims

1. Formula (II): 【Chemistry 1】 (In the formula, R １ These are halogen- and / or haloalkyl-substituted pyridyl, unsubstituted pyridyl, haloalkyl and / or alkyl-substituted pyrazolyl, unsubstituted pyrazolyl, haloalkyl and / or alkyl-substituted pyrrolyl, or unsubstituted pyrrolyl; R ２ is a hydrogen atom; R ３ is a hydrogen atom; n is 1; R ４ The formula is: 【Chemistry 2】 (In the formula, R ２１ is a hydrogen atom or an unsubstituted alkyl group; R ２２ is a hydrogen atom, a halogen, or an unsubstituted alkyl group; R ２３ is a hydrogen atom, a halogen or an unsubstituted alkyl group; or, R ２２ and R ２３ together with the carbon atom to which they are attached form an unsubstituted non-aromatic carbocyclic ring); a group represented by R ８ is a hydrogen atom; R ５ is a hydrogen atom; R ６ is a hydrogen atom; R ７ The formula is: 【Transformation 3】 (In the formula, R ９ Compounds represented by (where is a halogen-substituted alkyloxy or unsubstituted alkyloxy group) (however, the compounds shown below: 【Chemistry 4】 (excluding) or its pharmaceutically acceptable salts.

2. R １ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein is a halogen-substituted pyridyl, an alkyl-substituted pyrazolyl, or an alkyl-substituted pyrrolyl.

3. R ４ The formula is: 【Transformation 5】 (In the formula, R ２１ , R ２２ and R ２３ A compound according to claim 1 or 2 or a pharmaceutically acceptable salt thereof, wherein the group is as defined in claim 1.

4. R ２２ is a halogen or an unsubstituted alkyl group; R ２３ is a hydrogen atom, a halogen or an unsubstituted alkyl group; or, R ２２ and R ２３ A compound according to any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof, wherein the compound, together with the bonded carbon atom, forms an unsubstituted, non-aromatic carbon ring.

5. The following compounds: 【Transformation 6】 【Transformation 7】 A compound or a pharmaceutically acceptable salt thereof, selected from the group consisting of the following.

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