JP2023045359A - Pharmaceutical composition containing heteroaromatic ring derivative having serotonin receptor bonding activity - Google Patents

Abstract

To provide a composition for serotonin 5-HT2A receptor antagonism and/or inverse agonism, containing a compound having serotonin 5-HT2A receptor antagonism and/or inverse agonism or a pharmaceutically acceptable salt thereof, and to provide a pharmaceutical composition containing a compound having serotonin 5-HT2A receptor antagonism and/or inverse agonism or a pharmaceutically acceptable salt thereof.SOLUTION: A composition for serotonin 5-HT2A receptor antagonism and/or inverse agonism contains a compound represented by a formula (I), where R7 is illustrated by the formula below, or a pharmaceutically acceptable salt thereof.SELECTED DRAWING: None

Description

The present invention provides a compound or a pharmaceutically acceptable salt thereof that has serotonin 5-HT2A receptor antagonistic and/or inverse agonistic activity and is useful in the treatment and/or prevention of diseases caused by the serotonin 5-HT2A receptor; and pharmaceutical compositions containing them.

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

Despite considerable progress in understanding the genetic causes underlying these disparate disorders, the biochemical mechanisms underlying the selective neuronal degeneration common to all of them remain largely unknown. relatively few Also, for the most common of these disorders, including Parkinson's disease and Alzheimer's disease, a large number of sporadic cases have been identified, although genetic factors have been discovered that cause rare familial forms of these disorders. For parts, the pathophysiological basis is not yet known. Therefore, there is currently no specific therapeutic agent that can directly alter disease progression. Instead, clinicians are taking advantage of a variety of existing agents to achieve symptomatic relief of the motor, cognitive and neuropsychiatric manifestations that characterize these disorders. , 3).

Among the various neurological symptoms that characterize ND, motor dysfunction including bradykinesia, dyskinesias and chorea, and the emergence of neuropsychiatric symptoms including psychosis and affective symptoms such as anxiety and depression are common symptoms. , severely affect the functional status and quality of life of patients (Non-Patent Documents 4, 5). Most existing therapeutic agents, including antipsychotics and antidepressants, are often efficacious in these patients but are remarkably poorly tolerated (Non-Patent Document 6). In addition, available Parkinson's disease therapeutic agents, including L-dopa and dopamine agonists, although generally effective, cause the emergence of treatment-limiting side effects severe enough to be currently unaddressed by drug therapy.

For a long time, there was no approved drug specifically for ND, but in 2016, the 5-HT2A receptor inverse agonist pimavanserin was approved for the first time in the United States for hallucinogenic delusions associated with Parkinson's disease (Non-Patent Document 7). . Unlike existing antipsychotic drugs, this drug has not been reported to cause side effects such as worsening of motor symptoms or deterioration of cognitive function. The main pharmacological action of pimavanserin is serotonin 5-HT2A receptor inverse agonism/antagonism, but it also has serotonin 5-HT2C receptor inverse agonism (Non-Patent Document 8). The results of 5-HT2A occupancy measured in PET studies of pimavanserin in humans and the results of clinical trials of pimavanserin suggest that pimavanserin exerts its efficacy through 5-HT2A and 2C ( Non-Patent Document 9). In addition, pimavanserin has a significant adverse effect on the cardiovascular system, which limits its use.

These findings highlight the need to develop new therapeutic agents specifically designed to not only show efficacy against these specific disabling conditions, but also to be well-tolerated in these specific patient populations. reveals sexuality. 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 targets 5-HT2A and 2C and reducing adverse effects on the cardiovascular system.

Compounds having serotonin 5-HT2A receptor antagonistic and/or inverse agonistic action are described in Patent Documents 3 to 14 and 16 to 21, but none of these documents describe or suggest compounds related to the present invention. not
Quinuclidine derivatives having muscarinic _M3 receptor inhibitory activity are disclosed in Patent Document 15, but serotonin 5-HT2A receptor antagonistic and/or inverse agonistic action and hallucinatory delusional therapeutic effects are not described, and No compounds related to the present invention are described or suggested.

WO2018/131672 U.S. Pat. No. 8,377,959 WO2001/066521 WO2004/064738 WO2019/040104 WO2019/040105 WO2019/040106 WO2019/040107 WO2010/111353 WO2004/000808 WO2003/057698 China Publication No. 109111385 WO2009/039461 WO2007/124136 WO2004/000840 WO2021/147818 WO2021/147909 China Publication No. 109111385 China Publication No. 113214141 China Publication No. 113214231 China Publication No. 113214289

Nature Reviews Neurology volume 10, pages 620-633 (2014) Progress in Neurology and Psychiatry I Vol.22 Issue.1 2018 Movement Disorders, Vol. 24, No. 11, 2009, pp. 1641-1649 Parkisonism and related disorder 155.2009. S 105-110 Neurology. 2004; 63(2):293-300. JAMA Neurol. 2016; 73(5):535-541. Lancet; 383:533-40 (2014) Journal of Pharmacology and Experimental Therapeutics May 2006, 317 (2) 910-918 CNS Spectrum (2016), 21, 271-275

An object of the present invention is to provide novel compounds having serotonin 5-HT2A receptor antagonistic and/or inverse agonistic activity and compositions for serotonin 5-HT2A receptor antagonistic and/or inverse agonistic activity. More preferably, the present invention exhibits effects on serotonin-related diseases such as hallucinations and delusions associated with Parkinson's disease and/or dementia by having serotonin 5-HT2A receptor antagonistic and/or inverse agonistic action. and novel compounds containing them and pharmaceuticals containing them.

（式中、
Ｒ^１は、置換もしくは非置換の芳香族複素環式基または置換もしくは非置換の非芳香族複素環式基であり；
Ｒ^２はそれぞれ独立して、水素原子、ハロゲン、ヒドロキシ、置換もしくは非置換のアルキルまたは置換もしくは非置換のアルキルオキシであり；
Ｒ^３はそれぞれ独立して、水素原子、ハロゲン、ヒドロキシ、置換もしくは非置換のアルキルまたは置換もしくは非置換のアルキルオキシであり；
ｎは、１または２であり；
Ｒ^４は、置換もしくは非置換の非芳香族含窒素複素環式基であり；
Ｌは、－ＮＲ^８－、－Ｏ－または単結合であり；
Ｒ^８は、水素原子または置換もしくは非置換のアルキルであり；
Ｒ^５はそれぞれ独立して、水素原子、ハロゲン、ヒドロキシ、置換もしくは非置換のアルキルまたは置換もしくは非置換のアルキルオキシであり；
Ｒ^６はそれぞれ独立して、水素原子、ハロゲン、ヒドロキシ、置換もしくは非置換のアルキルまたは置換もしくは非置換のアルキルオキシであり；
ｐは、１または２であり；
Ｒ^７は、式：

（式中、
Ｒ^９は、水素原子、ハロゲン、置換もしくは非置換のアルキルオキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換のアミノ、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換のアルケニルまたは置換もしくは非置換のアルキルであり；
Ｒ^１０は、水素原子、ヒドロキシ、ハロゲンまたは置換もしくは非置換のアルキルであり；または、
Ｒ^９およびＲ^１０が一緒になって、置換もしくは非置換の非芳香族複素環を形成し；
Ｒ^１１は、ハロゲン、ヒドロキシ、置換もしくは非置換のアルキルまたは置換もしくは非置換のアルキルオキシであり；
ｍは、０または１である）で示される基である）で示される化合物（ただし、以下の（ｉ）および（ｉｉ）の化合物を除く：
（ｉ）Ｌが単結合であり、かつＲ^１が置換もしくは非置換のフリルまたは置換もしくは非置換のチエニルである化合物；
（ｉｉ）Ｌが－ＮＲ^８－であり、かつＲ^１が置換もしくは非置換の２、３－ジヒドロベンゾフリルである化合物）またはその製薬上許容される塩を含有する、セロトニン５－ＨＴ２Ａ受容体拮抗および／または逆作動用組成物。
（２）Ｒ^１が置換もしくは非置換の芳香族複素環式基であり；
Ｌが－ＮＲ^８－または－Ｏ－である、化合物またはその製薬上許容される塩を含有する、上記項目（１）記載のセロトニン５－ＨＴ２Ａ受容体拮抗および／または逆作動用組成物。
（３）医薬組成物である、上記項目（１）または（２）記載のセロトニン５－ＨＴ２Ａ受容体拮抗および／または逆作動用組成物。
（４）式（ＩＩ）：

（式中、
Ｒ^１は、置換もしくは非置換の芳香族複素環式基であり；
Ｒ^２はそれぞれ独立して、水素原子、ハロゲン、ヒドロキシ、置換もしくは非置換のアルキルまたは置換もしくは非置換のアルキルオキシであり；
Ｒ^３はそれぞれ独立して、水素原子、ハロゲン、ヒドロキシ、置換もしくは非置換のアルキルまたは置換もしくは非置換のアルキルオキシであり；
ｎは、１または２であり；
Ｒ^４は、置換もしくは非置換の非芳香族含窒素複素環式基であり；
Ｒ^８は、水素原子または置換もしくは非置換のアルキルであり；
Ｒ^５は、水素原子、ハロゲン、ヒドロキシ、置換もしくは非置換のアルキルまたは置換もしくは非置換のアルキルオキシであり；
Ｒ^６は、水素原子、ハロゲン、ヒドロキシ、置換もしくは非置換のアルキルまたは置換もしくは非置換のアルキルオキシであり；
Ｒ^７は、式：

（式中、
Ｒ^９は、置換もしくは非置換のアルキルオキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換のアミノ、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換のアルケニルまたは置換もしくは非置換のアルキルであり；
Ｒ^１０は、水素原子、ハロゲンまたは置換もしくは非置換のアルキルであり；または、
Ｒ^９およびＲ^１０が一緒になって、置換もしくは非置換の非芳香族複素環を形成し；
Ｒ^１１は、ハロゲン、ヒドロキシ、置換もしくは非置換のアルキルまたは置換もしくは非置換のアルキルオキシであり；
ｍは、０または１である）で示される基である）で示される化合物（ただし、以下に示される化合物：

を除く）またはその製薬上許容される塩、を含有する医薬組成物。
（５）Ｒ^１が置換もしくは非置換の芳香族含窒素複素環式基である、上記項目（４）記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
（６）Ｒ^１が置換もしくは非置換の６員芳香族含窒素複素環式基または置換もしくは非置換の５員芳香族含窒素複素環式基である、上記項目（４）記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
（７）Ｒ^２およびＲ^３が水素原子である、上記項目（４）～（６）のいずれかに記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
（８）ｎが１である、上記項目（４）～（７）のいずれかに記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
（９）Ｒ^４が置換もしくは非置換の４～７員非芳香族含窒素複素環式基である、上記項目（４）～（８）のいずれかに記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
（１０）Ｒ^４が置換もしくは非置換のピペリジニルである、上記項目（４）～（９）のいずれかに記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
（１１）Ｒ^４が式：

（式中、
Ｒ^２１は、水素原子または置換もしくは非置換のアルキルであり；
Ｒ^２２は、水素原子、ハロゲンまたは置換もしくは非置換のアルキルであり；
Ｒ^２３は、水素原子、ハロゲンまたは置換もしくは非置換のアルキルであり；または、
Ｒ^２２およびＲ^２３が結合する炭素原子と一緒になって、置換もしくは非置換の非芳香族炭素環を形成する）で示される基である、上記項目（４）～（１０）のいずれかに記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
（１２）Ｒ^４が式：

（式中、Ｒ^２１、Ｒ^２２およびＲ^２３は上記項目（１１）と同義）で示される基である、上記項目（１１）記載の化合物またはその製薬上許容される塩。
（１３）Ｒ^２２がハロゲンまたは置換もしくは非置換のアルキルであり；
Ｒ^２３が水素原子、ハロゲンまたは置換もしくは非置換のアルキルであり；または、
Ｒ^２２およびＲ^２３が結合する炭素原子と一緒になって、置換もしくは非置換の非芳香族炭素環を形成する、上記項目（１１）または（１２）記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
（１４）Ｒ^８が水素原子である、上記項目（４）～（１３）のいずれかに記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
（１５）Ｒ^５およびＲ^６が水素原子である、上記項目（４）～（１４）のいずれかに記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
（１６）Ｒ^７が式：

（式中、Ｒ^９は置換もしくは非置換のアルキルオキシである）で示される基である、上記項目（４）～（１５）のいずれかに記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
（１７）化合物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およびＩ－１４５からなる群から選択される、上記項目（４）記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
（１８）セロトニン５－ＨＴ２Ａ受容体拮抗および／または逆作動薬である、上記項目（４）～（１７）のいずれかに記載の医薬組成物。
The present invention relates to the following items (1) to (18) (1) Formula (I):

(In the formula,
R ¹ is a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group;
each R ² is independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
each R ³ is independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
n is 1 or 2;
R ⁴ is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group;
L is -NR ⁸ -, -O- or a single bond;
R ⁸ is a hydrogen atom or substituted or unsubstituted alkyl;
each ^R5 is independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
each R ⁶ is independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
p is 1 or 2;
R ⁷ has the formula:

(In the formula,
R ⁹ is a hydrogen atom, halogen, substituted or unsubstituted alkyloxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted amino, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted alkenyl or substituted or unsubstituted alkyl;
R ¹⁰ is a hydrogen atom, hydroxy, halogen or substituted or unsubstituted alkyl; or
R ⁹ and R ¹⁰ together form a substituted or unsubstituted non-aromatic heterocyclic ring;
R ¹¹ is halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
m is a group represented by 0 or 1) (excluding the following compounds (i) and (ii):
(i) compounds wherein L is a single bond and R ¹ is substituted or unsubstituted furyl or substituted or unsubstituted thienyl;
(ii) a compound wherein L is —NR ⁸ — and R ¹ is a substituted or unsubstituted 2,3-dihydrobenzofuryl) or a pharmaceutically acceptable salt thereof. Antagonistic and/or inverse agonist compositions.
(2) R ¹ is a substituted or unsubstituted aromatic heterocyclic group;
The composition for serotonin 5-HT2A receptor antagonistic and/or inverse agonistic action according to item (1) above, containing a compound or a pharmaceutically acceptable salt thereof, wherein L is -NR ⁸ - or -O-.
(3) The composition for serotonin 5-HT2A receptor antagonistic and/or inverse agonistic action according to item (1) or (2) above, which is a pharmaceutical composition.
(4) Formula (II):

(In the formula,
R ¹ is a substituted or unsubstituted aromatic heterocyclic group;
each R ² is independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
each R ³ is independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
n is 1 or 2;
R ⁴ is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group;
R ⁸ is a hydrogen atom or substituted or unsubstituted alkyl;
^R5 is a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
R ⁶ is a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
R ⁷ has the formula:

(In the formula,
R ⁹ is substituted or unsubstituted alkyloxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted amino, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted alkenyl or substituted or unsubstituted alkyl;
R ¹⁰ is a hydrogen atom, halogen or substituted or unsubstituted alkyl; or
R ⁹ and R ¹⁰ together form a substituted or unsubstituted non-aromatic heterocyclic ring;
R ¹¹ is halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
m is a group represented by 0 or 1) (provided that the compounds shown below:

) or a pharmaceutically acceptable salt thereof.
(5) A pharmaceutical composition containing the compound or a pharmaceutically acceptable salt thereof according to item (4) above, wherein ^R1 is a substituted or unsubstituted aromatic nitrogen-containing heterocyclic group.
(6) The compound according to item (4) above, wherein R ¹ is a substituted or unsubstituted 6-membered aromatic nitrogen-containing heterocyclic group or a substituted or unsubstituted 5-membered aromatic nitrogen-containing heterocyclic group, or A pharmaceutical composition containing a pharmaceutically acceptable salt.
(7) A pharmaceutical composition containing the compound or a pharmaceutically acceptable salt thereof according to any one of items (4) to (6) above, wherein R ² and R ³ are hydrogen atoms.
(8) A pharmaceutical composition containing the compound or a pharmaceutically acceptable salt thereof according to any one of items (4) to (7), wherein n is 1.
(9) The compound or a pharmaceutically acceptable compound according to any one of the above items (4) to (8), wherein R ⁴ is a substituted or unsubstituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic group. A pharmaceutical composition containing a salt.
(10) A pharmaceutical composition containing the compound or a pharmaceutically acceptable salt thereof according to any one of the above items (4) to (9), wherein R ⁴ is substituted or unsubstituted piperidinyl.
(11) ^R4 has the formula:

(In the formula,
R ²¹ is a hydrogen atom or substituted or unsubstituted alkyl;
R ²² is a hydrogen atom, halogen or substituted or unsubstituted alkyl;
R ²³ is a hydrogen atom, halogen or substituted or unsubstituted alkyl; or
together with the carbon atoms to which R ²² and R ²³ are attached form a substituted or unsubstituted non-aromatic carbocyclic ring), any of the above items (4) to (10) A pharmaceutical composition containing the described compound or a pharmaceutically acceptable salt thereof.
(12) ^R4 has the formula:

(wherein R ²¹ , R ²² and R ²³ have the same meanings as in item (11)), the compound or a pharmaceutically acceptable salt thereof according to item (11) above.
(13) R ²² is halogen or substituted or unsubstituted alkyl;
R ²³ is a hydrogen atom, halogen or substituted or unsubstituted alkyl; or
The compound according to item (11) or (12) above, or a pharmaceutically acceptable salt thereof, which together with the carbon atoms to which R ²² and R ²³ are attached form a substituted or unsubstituted non-aromatic carbocyclic ring A pharmaceutical composition containing
(14) A pharmaceutical composition containing the compound or a pharmaceutically acceptable salt thereof according to any one of the above items (4) to (13), wherein R ⁸ is a hydrogen atom.
(15) A pharmaceutical composition containing the compound or a pharmaceutically acceptable salt thereof according to any one of the above items (4) to (14), wherein R ⁵ and R ⁶ are hydrogen atoms.
(16) ^R7 has the formula:

(wherein R ⁹ is a substituted or unsubstituted alkyloxy), the compound according to any one of the above items (4) to (15) or a pharmaceutically acceptable salt thereof; Pharmaceutical composition containing.
(17) 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, the compound or a pharmaceutically acceptable salt thereof according to item (4) above, A pharmaceutical composition containing
(18) The pharmaceutical composition according to any one of items (4) to (17) above, which is a serotonin 5-HT2A receptor antagonist and/or inverse agonist.

Compounds of the present invention (in the present specification, "compounds of the present invention" refer to compounds of the present invention, 5-HT2A receptor antagonists and/or inverse agonist compounds of the present invention, 5- HT2A receptor antagonistic and/or inverse agonistic action of the composition or the compound of the pharmaceutical composition of the present invention) has serotonin 5-HT2A receptor antagonistic and/or inverse agonistic action, It is useful as a therapeutic and/or prophylactic agent for hallucinogenic delusions associated with Parkinson's disease and/or dementia.

FIG. 1 shows the results of an inhibitory effect test on rat MK801-induced hyperlocomotion when vehicle and Example compound I-008 were administered. FIG. 2 shows the results of an inhibitory effect test on rat MK801-induced hyperlocomotion when vehicle and example compound I-102 were administered. FIG. 3 shows the results of an inhibitory effect test on rat MK801-induced hyperlocomotion when Vehicle and Example compound I-126 were administered. FIG. 4 shows the results of an inhibitory effect test on rat MK801-induced hyperlocomotion when Vehicle and Example compound I-139 were administered.

The meaning of each term used in this specification will be explained below. Unless otherwise specified, each term has the same meaning whether it is used alone or in combination with other terms.
The term "consisting of" means having only constituent elements.
The term "comprising" is meant to be open to the elements and does not exclude elements not listed.
Hereinafter, the present invention will be described while showing embodiments. It should be understood that throughout this specification, expressions in the singular also include the concept of the plural unless specifically stated otherwise. Thus, articles in the singular (eg, “a,” “an,” “the,” etc. in the English language) should be understood to include their plural concepts as well, unless specifically stated otherwise.
In addition, it should be understood that the terms used in this specification have the meanings commonly used in the art unless otherwise specified. Thus, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification (including definitions) will control.

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

"Alkyl" includes a linear or branched hydrocarbon group having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, still more preferably 1 to 4 carbon atoms. do. For example, 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.
The alkyl moiety of alkyloxy in R ⁹ is preferably C2-C4 alkyl. Examples include ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl and the like.

"Haloalkyl" means the above alkyl substituted with one or more halogens. When substituted with 2 or more halogens, the halogens may be the same or different. Examples include fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl and the like.

The term “alkenyl” refers to a group having 2 to 15 carbon atoms, preferably 2 to 10 carbon atoms, more preferably 2 to 6 carbon atoms, still more preferably 2 to 4 carbon atoms, having one or more double bonds at any position. straight chain or branched hydrocarbon groups. For example, vinyl, allyl, propenyl, isopropenyl, butenyl, isobutenyl, prenyl, butadienyl, pentenyl, isopentenyl, pentadienyl, hexenyl, isohexenyl, hexadienyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl. etc.
Preferred embodiments of "alkenyl" include vinyl, allyl, propenyl, isopropenyl and butenyl. More preferred embodiments include vinyl, n-propenyl, and the like.

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

"Aromatic carbocyclic group" means a monocyclic or bicyclic or more cyclic aromatic hydrocarbon group. Examples include phenyl, naphthyl, anthryl, phenanthryl and the like.
A preferred embodiment of the "aromatic carbocyclic group" is phenyl.

"Aromatic carbocyclic ring" means a ring derived from the above "aromatic carbocyclic group".

単環の非芳香族炭素環式基としては、炭素数３～１６が好ましく、より好ましくは炭素数３～１２、さらに好ましくは炭素数４～８である。例えば、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシル、シクロヘプチル、シクロオクチル、シクロノニル、シクロデシル、シクロプロペニル、シクロブテニル、シクロペンテニル、シクロヘキセニル、シクロヘプテニル、シクロヘキサジエニル等が挙げられる。
２環以上の非芳香族炭素環式基としては、炭素数８～２０が好ましく、より好ましくは炭素数８～１６である。例えば、インダニル、インデニル、アセナフチル、テトラヒドロナフチル、フルオレニル等が挙げられる。 "Non-aromatic carbocyclic group" means a monocyclic or bicyclic or more ring saturated cyclic hydrocarbon group or cyclic non-aromatic unsaturated hydrocarbon group. The "non-aromatic carbocyclic group" having two or more rings also includes a monocyclic or non-aromatic carbocyclic group having two or more rings condensed with the above "aromatic carbocyclic group".
Furthermore, the “non-aromatic carbocyclic group” also includes a group that forms a bridge or a spiro ring as shown below.

The monocyclic non-aromatic carbocyclic group preferably has 3 to 16 carbon atoms, more preferably 3 to 12 carbon atoms, and still more preferably 4 to 8 carbon atoms. Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclohexadienyl and the like.
The bicyclic or more non-aromatic carbocyclic group preferably has 8 to 20 carbon atoms, more preferably 8 to 16 carbon atoms. Examples include indanyl, indenyl, acenaphthyl, tetrahydronaphthyl, fluorenyl and the like.

"Non-aromatic carbocyclic ring" means a ring derived from the above "non-aromatic carbocyclic group".

“Aromatic heterocyclic group” means a monocyclic or bicyclic or more aromatic cyclic group having one or more heteroatoms which are the same or different and are arbitrarily selected from O, S and N in the ring. do.
An aromatic heterocyclic group with two or more rings includes a monocyclic or an aromatic heterocyclic group with two or more rings condensed with the ring in the above "aromatic carbocyclic group", and the bond is Either ring may have it.
The monocyclic aromatic heterocyclic group is preferably 5- to 8-membered, more preferably 5- or 6-membered. Five-membered aromatic heterocyclic groups include, for example, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, thiadiazolyl and the like. Examples of 6-membered aromatic heterocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and the like.
The bicyclic aromatic heterocyclic group is preferably 8- to 10-membered, more preferably 9- or 10-membered. For example, indolyl, isoindolyl, indazolyl, indolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, naphthyridinyl, quinoxalinyl, purinyl, pteridinyl, benzimidazolyl, benzisoxazolyl, benzoxazolyl, benzoxadiazolyl, benzisothiazolyl. Ryl, benzothiazolyl, benzothiadiazolyl, benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, imidazopyridyl, triazolopyridyl, imidazothiazolyl, pyrazinopyridazinyl, oxazolopyridyl, thiazolopyridyl, etc. are mentioned.
The aromatic heterocyclic group having 3 or more rings is preferably 13- to 15-membered. Examples include carbazolyl, acridinyl, xanthenyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, dibenzofuryl and the like.

"Heteroaromatic ring" means a ring derived from the above "heteroaromatic group".

The "aromatic nitrogen-containing heterocyclic group" includes one or more N in the ring, and may have one or more identical or different heteroatoms arbitrarily selected from O or S in the ring, It means a monocyclic or bicyclic or more aromatic heterocyclic group. The bicyclic or more aromatic nitrogen-containing heterocyclic group includes a monocyclic or bicyclic or more aromatic nitrogen-containing heterocyclic group in which the ring in the above "aromatic carbocyclic group" is condensed, The bond may be present in any ring.

The monocyclic aromatic nitrogen-containing heterocyclic group is preferably 5- to 8-membered, more preferably 5- or 6-membered. Five-membered aromatic nitrogen-containing heterocyclic groups include, for example, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, thiadiazolyl and the like. Examples of 6-membered aromatic nitrogen-containing heterocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and the like.
The bicyclic aromatic nitrogen-containing heterocyclic group is preferably 8- to 10-membered, more preferably 9- or 10-membered. For example, indolyl, isoindolyl, indazolyl, indolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, naphthyridinyl, quinoxalinyl, purinyl, pteridinyl, benzimidazolyl, benzisoxazolyl, benzoxazolyl, benzoxadiazolyl, benzisothiazolyl. lyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyl, imidazopyridyl, triazolopyridyl, imidazothiazolyl, pyrazinopyridazinyl, oxazolopyridyl, thiazolopyridyl and the like.
The aromatic nitrogen-containing heterocyclic group having 3 or more rings is preferably 13- to 15-membered. Examples include carbazolyl, acridinyl, phenothiazinyl and the like.

単環の非芳香族複素環式基としては、３～８員が好ましく、より好ましくは５員または６員である。
３員非芳香族複素環式基としては、例えば、チイラニル、オキシラニル、アジリジニルが挙げられる。４員非芳香族複素環式基としては、例えば、オキセタニル、アゼチジニルが挙げられる。５員非芳香族複素環式基としては、例えば、オキサチオラニル、チアゾリジニル、ピロリジニル、ピロリニル、イミダゾリジニル、イミダゾリニル、ピラゾリジニル、ピラゾリニル、テトラヒドロフリル、ジヒドロチアゾリル、テトラヒドロイソチアゾリル、ジオキソラニル、ジオキソリル、チオラニル等が挙げられる。６員非芳香族複素環式基としては、例えば、ジオキサニル、チアニル、ピペリジル、ピペラジニル、モルホリニル、モルホリノ、チオモルホリニル、チオモルホリノ、ジヒドロピリジル、テトラヒドロピリジル、テトラヒドロピラニル、ジヒドロオキサジニル、テトラヒドロピリダジニル、ヘキサヒドロピリミジニル、ジオキサジニル、チイニル、チアジニル等が挙げられる。７員非芳香族複素環式基としては、例えば、ヘキサヒドロアゼピニル、テトラヒドロジアゼピニル、オキセパニルが挙げられる。８員非芳香族複素環式基としては、例えば、アゾカン、チオカン、オキソカン等が挙げられる。
２環以上の非芳香族複素環式基としては、８～２０員が好ましく、より好ましくは８～１０員である。例えば、インドリニル、イソインドリニル、クロマニル、イソクロマニル等が挙げられる。 "Non-aromatic heterocyclic group" means a monocyclic or bicyclic or more non-aromatic cyclic group having one or more heteroatoms in the ring that are the same or different and arbitrarily selected from O, S and N. means A bicyclic or more non-aromatic heterocyclic group is a monocyclic or bicyclic or more non-aromatic heterocyclic group, the above "aromatic carbocyclic group", "non-aromatic carbocyclic group", and / Or each ring in the "aromatic heterocyclic group" is condensed, furthermore, the ring in the above "aromatic heterocyclic group" is condensed to a monocyclic or bicyclic or more non-aromatic carbocyclic group and the bond may be in any ring.
Furthermore, the “non-aromatic heterocyclic group” also includes a group that forms a bridge or a spiro ring as shown below.

The monocyclic non-aromatic heterocyclic group is preferably 3- to 8-membered, more preferably 5- or 6-membered.
Three-membered non-aromatic heterocyclic groups include, for example, thiiranyl, oxiranyl, aziridinyl. Examples of 4-membered non-aromatic heterocyclic groups include oxetanyl and azetidinyl. Five-membered non-aromatic heterocyclic groups include, for example, oxathiolanyl, thiazolidinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, tetrahydrofuryl, dihydrothiazolyl, tetrahydroisothiazolyl, dioxolanyl, dioxolyl, thiolanyl, and the like. mentioned. 6-membered non-aromatic heterocyclic groups include, for example, dioxanyl, thianyl, piperidyl, piperazinyl, morpholinyl, morpholino, thiomorpholinyl, thiomorpholino, dihydropyridyl, tetrahydropyridyl, tetrahydropyranyl, dihydrooxazinyl, tetrahydropyridazinyl hexahydropyrimidinyl, dioxazinyl, thiinyl, thiazinyl and the like. Seven-membered non-aromatic heterocyclic groups include, for example, hexahydroazepinyl, tetrahydrodiazepinyl, oxepanyl. Examples of 8-membered non-aromatic heterocyclic groups include azocane, thiocane, oxocane and the like.
The non-aromatic heterocyclic group having two or more rings is preferably 8- to 20-membered, more preferably 8- to 10-membered. Examples include indolinyl, isoindolinyl, chromanyl, isochromanyl and the like.

さらに、「非芳香族含窒素複素環式基」は、以下のように架橋している基、またはスピロ環を形成する基も包含する。

“Non-aromatic nitrogen-containing heterocyclic group” means a monocyclic or bicyclic or more non-aromatic heterocyclic group having one or more nitrogen atoms in the ring. A non-aromatic heterocyclic group having two or more rings is a monocyclic or non-aromatic nitrogen-containing heterocyclic group having two or more rings, and the above "aromatic carbocyclic group" and "non-aromatic carbocyclic group" and/or condensed rings in the "aromatic heterocyclic group", and the bond may be present in any ring.
For example, the following rings are shown.

Furthermore, the “non-aromatic nitrogen-containing heterocyclic group” also includes a group that forms a bridge or a spiro ring as shown below.

"Non-aromatic heterocyclic ring" means a ring derived from the above "non-aromatic heterocyclic group".

Examples of the non-aromatic heterocyclic ring formed by R ⁹ and R ¹⁰ together include the following rings.

The non-aromatic carbocyclic ring formed together with the carbon atoms to which R ²² and R ²³ are bonded includes, for example, the following rings.

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

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

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

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

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

Substituent Group γ: Substituent Group α, alkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, alkylcarbonyl, haloalkylcarbonyl, alkenylcarbonyl, and alkynylcarbonyl.

Substituent group γ': Substituent group γ and oxo.

"substituted aromatic carbocyclic group", "substituted aromatic heterocyclic group", "substituted aromatic nitrogen-containing heterocyclic group", "substituted aromatic carbocyclic oxy", "substituted aromatic heterocyclic oxy", "substituted aromatic carbocyclic carbonyloxy", "substituted aromatic heterocyclic carbonyloxy", "substituted aromatic carbocyclic carbonyl", "substituted aromatic heterocyclic carbonyl", "substituted aromatic carbocyclic oxycarbonyl", "substituted Aromatic heterocycle oxycarbonyl", "Substituted aromatic carbocycle sulfanyl", "Substituted aromatic heterocycle sulfanyl", "Substituted aromatic carbocycle sulfinyl", "Substituted aromatic heterocycle sulfinyl", "Substituted aromatic carbocycle Substituents on the ring of "aromatic carbocyclic ring" and "aromatic heterocyclic ring" such as "sulfonyl" and "substituted aromatic heterocyclic sulfonyl" include the following substituent group B. Any atom on the ring may be bonded to one or more groups selected from Substituent Group B below.
Substituent group B: halogen, hydroxy, carboxy, formyl, formyloxy, sulfanyl, sulfino, sulfo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, cyano, nitro, nitroso, azide, hydrazino, ureido, amidino, guanidino, penta fluorothio, trialkylsilyl,
alkyl optionally substituted with substituent group α, alkenyl optionally substituted with substituent group α, alkynyl optionally substituted with substituent group α, optionally substituted with substituent group α alkyloxy, alkenyloxy optionally substituted with substituent group α, alkynyloxy optionally substituted with substituent group α, alkylcarbonyloxy optionally substituted with substituent group α, substituent group α alkenylcarbonyloxy optionally substituted with, alkynylcarbonyloxy optionally substituted with substituent group α, alkylcarbonyl optionally substituted with substituent group α, even if substituted with substituent group α alkenylcarbonyl optionally substituted with substituent group α, alkynylcarbonyl optionally substituted with substituent group α, alkyloxycarbonyl optionally substituted with substituent group α, alkenyloxycarbonyl optionally substituted with substituent group α, substituent alkynyloxycarbonyl optionally substituted with group α, alkylsulfanyl optionally substituted with substituent group α, alkenylsulfanyl optionally substituted with substituent group α, substituted with substituent group α alkynylsulfanyl optionally substituted with substituent group α, alkylsulfinyl optionally substituted with substituent group α, alkenylsulfinyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, substituent group alkylsulfonyl optionally substituted with α, alkenylsulfonyl optionally substituted with substituent group α, alkynylsulfonyl optionally substituted with substituent group α,
amino optionally substituted with substituent group β, imino optionally substituted with substituent group β, carbamoyl optionally substituted with substituent group β, optionally substituted with substituent group β sulfamoyl,
Aromatic carbocyclic group optionally substituted with substituent group γ, non-aromatic carbocyclic group optionally substituted with substituent group γ', aromatic optionally substituted with substituent group γ heterocyclic group, non-aromatic heterocyclic group optionally substituted with substituent group γ', aromatic carbocyclic oxy optionally substituted with substituent group γ, substituted with substituent group γ' optionally substituted non-aromatic carbocyclic oxy, optionally substituted with substituent group γ, non-aromatic heterocyclic oxy optionally substituted with substituent group γ', “substituted Aromatic carbocyclic carbonyloxy optionally substituted with group γ", "Non-aromatic carbocyclic carbonyloxy optionally substituted with substituent group γ'", "Substituted with substituent group γ aromatic heterocyclic carbonyloxy optionally substituted with substituent group γ', and “non-aromatic heterocyclic carbonyloxy optionally substituted with substituent group γ′”, aromatic carbocyclic carbonyl optionally substituted with substituent group γ, non-aromatic carbocyclic carbonyl optionally substituted with substituent group γ', aromatic heterocyclic carbonyl optionally substituted with substituent group γ, non-aromatic optionally substituted with substituent group γ' heterocyclic carbonyl, aromatic carbocyclic oxycarbonyl optionally substituted with substituent group γ, non-aromatic carbocyclic oxycarbonyl optionally substituted with substituent group γ', substituted with substituent group γ optionally substituted aromatic heterocyclic oxycarbonyl, non-aromatic heterocyclic oxycarbonyl optionally substituted with substituent group γ', aromatic carbocyclic alkyl optionally substituted with substituent group γ, substituent non-aromatic carbocyclic alkyl optionally substituted with substituent group γ', aromatic heterocyclic alkyl optionally substituted with substituent group γ', non-aromatic heterocyclic alkyl optionally substituted with substituent group γ' ring alkyl, aromatic carbocyclic alkyloxy optionally substituted with substituent group γ, non-aromatic carbocyclic alkyloxy optionally substituted with substituent group γ', substituted with substituent group γ aromatic heterocyclic alkyloxy optionally substituted with substituent group γ', non-aromatic heterocyclic alkyloxy optionally substituted with substituent group γ', aromatic carbocyclic alkyloxycarbonyl optionally substituted with substituent group γ, substituent non-aromatic carbocyclic alkyloxycarbonyl optionally substituted by group γ', aromatic heterocyclic alkyloxycarbonyl optionally substituted by substituent group γ, optionally substituted by substituent group γ' non-aromatic heterocyclic alkyloxycarbonyl, aromatic carbocyclic alkyloxyalkyl optionally substituted with substituent group γ, non-aromatic carbocyclic alkyloxyalkyl optionally substituted with substituent group γ', substituted aromatic heterocyclic alkyloxyalkyl optionally substituted with group γ, non-aromatic heterocyclic alkyloxyalkyl optionally substituted with substituent group γ', optionally substituted with substituent group γ aromatic carbocyclic sulfanyl, non-aromatic carbocyclic sulfanyl optionally substituted with substituent group γ', aromatic heterocyclic sulfanyl optionally substituted with substituent group γ, substituted with substituent group γ' non-aromatic heterocyclic sulfanyl optionally substituted with substituent group γ, aromatic carbocyclic sulfinyl optionally substituted with substituent group γ', non-aromatic carbocyclic sulfinyl optionally substituted with substituent group γ', substituent group aromatic heterocyclic sulfinyl optionally substituted with γ, non-aromatic heterocyclic sulfinyl optionally substituted with substituent group γ', aromatic carbocyclic sulfonyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfonyl optionally substituted with substituent group γ', aromatic heterocyclic sulfonyl optionally substituted with substituent group γ and non-aromatic optionally substituted with substituent group γ' heterocyclic sulfonyl group.

“substituted non-aromatic carbocyclic group”, “substituted non-aromatic heterocyclic group”, “substituted non-aromatic nitrogen-containing heterocyclic group”, “substituted non-aromatic group formed by ^R9 and ^R10 together” aromatic heterocyclic ring", "substituted non-aromatic carbocyclic ring formed together with the carbon atoms to which ^R22 and ^R23 are attached", "substituted non-aromatic carbocyclic ring-oxy", "substituted non-aromatic heterocyclic ring-oxy ", "substituted non-aromatic carbocyclic carbonyloxy", "substituted non-aromatic heterocyclic carbonyloxy", "substituted non-aromatic carbocyclic carbonyl", "substituted non-aromatic heterocyclic carbonyl", "substituted non-aromatic carbon ring oxycarbonyl", "substituted non-aromatic heterocycle oxycarbonyl", "substituted non-aromatic carbocycle sulfanyl", "substituted non-aromatic heterocycle sulfanyl", "substituted non-aromatic carbocycle sulfinyl", "substituted non-aromatic As a substituent on the ring of the "non-aromatic carbocycle" and "non-aromatic heterocycle" of "substituted non-aromatic carbocycle sulfonyl", "substituted non-aromatic heterocycle sulfonyl", and "substituted non-aromatic heterocycle sulfonyl" , and the following substituent group C. An atom at any position on the ring may be bonded to one or more groups selected from Substituent Group C below.
Substituent Group C: Substituent Group B and oxo.

When "non-aromatic carbocyclic ring", "non-aromatic heterocyclic ring" and "non-aromatic nitrogen-containing heterocyclic ring" are substituted with "oxo", two hydrogen atoms on the carbon atoms are It refers to a ring that is substituted.

Substituents of “substituted amino”, “substituted imino”, “substituted carbamoyl” and “substituted sulfamoyl” include Substituent Group D below. It may be substituted with one or two groups selected from Substituent Group D.
Substituent group D: halogen, hydroxy, carboxy, cyano, alkyl optionally substituted with substituent group α, alkenyl optionally substituted with substituent group α, optionally substituted with substituent group α alkynyl, alkylcarbonyl optionally substituted with substituent group α, alkenylcarbonyl optionally substituted with substituent group α, alkynylcarbonyl optionally substituted with substituent group α, substituted with substituent group α alkylsulfanyl optionally substituted with substituent group α, alkenylsulfanyl optionally substituted with substituent group α, alkynylsulfanyl optionally substituted with substituent group α, alkylsulfinyl optionally substituted with substituent group α, alkenylsulfinyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, alkylsulfonyl optionally substituted with substituent group α, substituted with substituent group α alkenylsulfonyl which may be substituted, alkynylsulfonyl which may be substituted with substituent group α,
amino optionally substituted with substituent group β, imino optionally substituted with substituent group β, carbamoyl optionally substituted with substituent group β, optionally substituted with substituent group β sulfamoyl,
Aromatic carbocyclic group optionally substituted with substituent group γ, non-aromatic carbocyclic group optionally substituted with substituent group γ', aromatic optionally substituted with substituent group γ heterocyclic group, non-aromatic heterocyclic group optionally substituted with substituent group γ', aromatic carbocyclic alkyl optionally substituted with substituent group γ, substituted with substituent group γ' non-aromatic carbocyclic alkyl optionally substituted with substituent group γ, aromatic heterocyclic alkyl optionally substituted with substituent group γ', non-aromatic heterocyclic alkyl optionally substituted with substituent group γ', substituent aromatic carbocyclic carbonyl optionally substituted with substituent group γ, non-aromatic carbocyclic carbonyl optionally substituted with substituent group γ', aromatic heterocyclic carbonyl optionally substituted with substituent group γ , non-aromatic heterocyclic carbonyl optionally substituted with substituent group γ', aromatic carbocyclic oxycarbonyl optionally substituted with substituent group γ, optionally substituted with substituent group γ' non-aromatic carbocyclic oxycarbonyl, aromatic heterocyclic oxycarbonyl optionally substituted with substituent group γ, non-aromatic heterocyclic oxycarbonyl optionally substituted with substituent group γ', substituent group γ aromatic carbocyclic sulfanyl optionally substituted with, non-aromatic carbocyclic sulfanyl optionally substituted with substituent group γ', aromatic heterocyclic sulfanyl optionally substituted with substituent group γ, substituted non-aromatic heterocyclic sulfanyl optionally substituted with group γ', aromatic carbocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic optionally substituted with substituent group γ' carbocyclic sulfinyl, aromatic heterocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfinyl optionally substituted with substituent group γ', optionally substituted with substituent group γ good aromatic carbocyclic sulfonyl, non-aromatic carbocyclic sulfonyl optionally substituted with substituent group γ', aromatic heterocyclic sulfonyl optionally substituted with substituent group γ, and substituted with substituent group γ' non-aromatic heterocyclic sulfonyl which may be

R ¹ , R ² , R ^{3 , n, R 4 ,} L, R ⁸ , R ⁵ , R ⁶ , p, R ⁷ , R ⁹ , R ¹⁰ in the compounds represented by formula (I) or formula (II) , R ¹¹ , R ²¹ , R ²² , R ²³ and m are shown below. As the compound represented by formula (I) or formula (II), all combinations of specific examples shown below are exemplified.
R ¹ includes a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as A-1).
R ¹ includes a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as A-2).
R ¹ includes a substituted or unsubstituted aromatic nitrogen-containing heterocyclic group (hereinafter referred to as A-3).
R ¹ includes a substituted or unsubstituted 5-membered aromatic heterocyclic group, a substituted or unsubstituted 6-membered aromatic heterocyclic group, or a substituted or unsubstituted 10-membered aromatic heterocyclic group (hereinafter , A-4).
R ¹ includes a substituted or unsubstituted 6-membered aromatic heterocyclic group or a substituted or unsubstituted 5-membered aromatic heterocyclic group (hereinafter referred to as A-5).
R ¹ is an alkyl-substituted 5-membered aromatic heterocyclic group; an unsubstituted 5-membered aromatic heterocyclic group; one or more selected from the group consisting of halogen, alkyloxy, cyano, haloalkyl and alkyl A 6-membered aromatic heterocyclic group substituted with a group or an unsubstituted 6-membered aromatic heterocyclic group (hereinafter referred to as A-6).
R ¹ includes a substituted or unsubstituted 5-membered aromatic heterocyclic group (hereinafter referred to as A-7).
R ¹ includes an alkyl-substituted 5-membered aromatic heterocyclic group or an unsubstituted 5-membered aromatic heterocyclic group (hereinafter referred to as A-8).
R ¹ includes a substituted or unsubstituted 6-membered aromatic heterocyclic group (hereinafter referred to as A-9).
R ¹ is a 6-membered aromatic heterocyclic group substituted with one or more groups selected from the group consisting of halogen, alkyloxy, cyano, haloalkyl and alkyl or an unsubstituted 6-membered aromatic heterocyclic group (hereinafter referred to as A-10).
R ¹ includes a substituted or unsubstituted 10-membered aromatic heterocyclic group (hereinafter referred to as A-11).
R ¹ includes an unsubstituted 10-membered aromatic heterocyclic group (hereinafter referred to as A-12).
R ¹ is substituted or unsubstituted pyridyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted pyrazinyl, 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 includes 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 , A-14).
R ¹ includes substituted or unsubstituted pyridyl, substituted or unsubstituted pyrrolyl or substituted or unsubstituted pyrazolyl (hereinafter referred to as A-15).
R ¹ includes substituted or unsubstituted pyrrolyl or substituted or unsubstituted pyrazolyl (hereinafter referred to as A-16).
R ¹ includes substituted or unsubstituted pyridyl (hereinafter referred to as A-17).
R ¹ includes pyridyl or unsubstituted pyridyl substituted with one or more groups selected from the group consisting of halogen, alkyloxy, cyano, haloalkyl and alkyl (hereinafter referred to as A-18).
R ¹ includes pyridyl substituted with halogen and/or haloalkyl or unsubstituted pyridyl (hereinafter referred to as A-19).
R ¹ includes halogen-substituted pyridyl or unsubstituted pyridyl (hereinafter referred to as A-20).
R ¹ includes halogen-substituted pyridyl (hereinafter referred to as A-21).
R ¹ includes haloalkyl-substituted pyridyl or unsubstituted pyridyl (hereinafter referred to as A-22).
R ¹ includes haloalkyl-substituted pyridyl (hereinafter referred to as A-23).
R ¹ includes substituted or unsubstituted pyrazolyl (hereinafter referred to as A-24).
R ¹ includes pyrazolyl substituted with haloalkyl and/or alkyl or unsubstituted pyrazolyl (hereinafter referred to as A-25).
R ¹ includes pyrazolyl substituted with alkyl or unsubstituted pyrazolyl (hereinafter referred to as A-26).
R ¹ includes alkyl-substituted pyrazolyl (hereinafter referred to as A-27).
R ¹ includes substituted or unsubstituted pyrrolyl (hereinafter referred to as A-28).
R ¹ includes pyrrolyl substituted with haloalkyl and/or alkyl or unsubstituted pyrrolyl (hereinafter referred to as A-29).
R ¹ includes alkyl-substituted pyrazolyl or unsubstituted pyrrolyl (hereinafter referred to as A-30).
R ¹ includes alkyl-substituted pyrrolyl (hereinafter referred to as A-31).

Each R ² independently includes a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy (hereinafter referred to as B-1).
Each R ² independently includes a hydrogen atom (hereinafter referred to as B-2).
Each R ³ independently includes a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy (hereinafter referred to as C-1).
Each R ³ independently includes a hydrogen atom (hereinafter referred to as C-2).
n includes 1 or 2 (hereinafter referred to as D-1).
n includes 1 (hereinafter referred to as D-2).

（式中、
Ｒ^２１は、水素原子または置換もしくは非置換のアルキルであり；
Ｒ^２２は、水素原子、ハロゲンまたは置換もしくは非置換のアルキルであり；
Ｒ^２３は、水素原子、ハロゲンまたは置換もしくは非置換のアルキルであり；または、
Ｒ^２２およびＲ^２３が結合する炭素原子と一緒になって、置換もしくは非置換の非芳香族炭素環を形成する）が挙げられる（以下、Ｅ－５とする）。
R^４は、式：

（式中、
Ｒ^２１は、水素原子または置換もしくは非置換のアルキルであり；
Ｒ^２２は、ハロゲンまたは置換もしくは非置換のアルキルであり；
Ｒ^２３は、水素原子、ハロゲンまたは置換もしくは非置換のアルキルであり；または、
Ｒ^２２およびＲ^２３が結合する炭素原子と一緒になって、置換もしくは非置換の非芳香族炭素環を形成する）で示される基が挙げられる（以下、Ｅ－６とする）。
Ｒ^４は、式：

（式中、Ｒ^２１は、水素原子または置換もしくは非置換のアルキルである）が挙げられる（以下、Ｅ－７とする）。
R^４は、式：

（式中、Ｒ^２１、Ｒ^２２およびＲ^２３はＥ－５と同義）で示される基が挙げられる（以下、Ｅ－８とする）。
R^４は、式：

（式中、式中、Ｒ^２１、Ｒ^２２およびＲ^２３はＥ－６と同義）で示される基が挙げられる（以下、Ｅ－９とする）。
R^４は、式：

（式中、Ｒ^２１は、水素原子または置換もしくは非置換のアルキルである）で示される基が挙げられる（以下、Ｅ－１０とする）。

（式中、
Ｒ^２１は、水素原子または置換もしくは非置換のアルキルであり；
Ｒ^２２は、ハロゲンである）で示される基が挙げられる（以下、Ｅ－１１とする）。 R ⁴ includes a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group (hereinafter referred to as E-1).
R ⁴ includes a substituted or unsubstituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic group (hereinafter referred to as E-2).
R ⁴ includes a substituted or unsubstituted 6-membered non-aromatic nitrogen-containing heterocyclic group (hereinafter referred to as E-3).
R ⁴ includes substituted or unsubstituted piperidinyl (hereinafter referred to as E-4).
^R4 has the formula:

(In the formula,
R ²¹ is a hydrogen atom or substituted or unsubstituted alkyl;
R ²² is a hydrogen atom, halogen or substituted or unsubstituted alkyl;
R ²³ is a hydrogen atom, halogen or substituted or unsubstituted alkyl; or
together with the carbon atoms to which R ²² and R ²³ are attached form a substituted or unsubstituted non-aromatic carbocyclic ring) (hereinafter referred to as E-5).
^R4 has the formula:

(In the formula,
R ²¹ is a hydrogen atom or substituted or unsubstituted alkyl;
R ²² is halogen or substituted or unsubstituted alkyl;
R ²³ is a hydrogen atom, halogen or substituted or unsubstituted alkyl; or
forming a substituted or unsubstituted non-aromatic carbocyclic ring together with the carbon atoms to which R ²² and R ²³ are bonded (hereinafter referred to as E-6).
^R4 has the formula:

(wherein R ²¹ is a hydrogen atom or substituted or unsubstituted alkyl) (hereinafter referred to as E-7).
^R4 has the formula:

(wherein R ²¹ , R ²² and R ²³ have the same meanings as E-5) (hereinafter referred to as E-8).
^R4 has the formula:

(wherein R ²¹ , R ²² and R ²³ have the same definitions as E-6) (hereinafter referred to as E-9).
^R4 has the formula:

(wherein R ²¹ is a hydrogen atom or substituted or unsubstituted alkyl) (hereinafter referred to as E-10).

(In the formula,
R ²¹ is a hydrogen atom or substituted or unsubstituted alkyl;
R ²² is a halogen) (hereinafter referred to as E-11).

L includes -NR ⁸ -, -O-, or a single bond (hereinafter referred to as F-1).
L includes -NR ⁸ - (hereinafter referred to as F-2).
L includes -O- (hereinafter referred to as F-3).
L includes a single bond (hereinafter referred to as F-4).
R ⁸ includes a hydrogen atom or substituted or unsubstituted alkyl (hereinafter referred to as G-1).
R ⁸ includes a hydrogen atom (hereinafter referred to as G-2).

Each R ⁵ independently includes a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy (hereinafter referred to as H-1).
Each R ⁵ independently includes a hydrogen atom (hereinafter referred to as H-2).
Each R ⁶ independently includes a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy (hereinafter referred to as J-1).
Each R ⁶ independently includes a hydrogen atom (hereinafter referred to as J-2).
p is 1 or 2 (hereinafter referred to as K-1).
p can be 1 (hereinafter referred to as K-2).

（式中、
Ｒ^９は、水素原子、ハロゲン、置換もしくは非置換のアルキルオキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換のアミノ、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換のアルケニルまたは置換もしくは非置換のアルキルであり；
Ｒ^１０は、水素原子、ヒドロキシ、ハロゲンまたは置換もしくは非置換のアルキルであり；または、
Ｒ^９およびＲ^１０が一緒になって、置換もしくは非置換の非芳香族複素環を形成し；
Ｒ^１１は、ハロゲン、ヒドロキシ、置換もしくは非置換のアルキルまたは置換もしくは非置換のアルキルオキシであり；
ｍは、０または１である）で示される基が挙げられる（以下、Ｌ－１とする）。
Ｒ^７は、式：

（式中、
Ｒ^９は、置換もしくは非置換のアルキルオキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換のアミノ、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換のアルケニルまたは置換もしくは非置換のアルキルであり；
Ｒ^１０は、水素原子、ハロゲンまたは置換もしくは非置換のアルキルであり；または、
Ｒ^９およびＲ^１０が一緒になって、置換もしくは非置換の非芳香族複素環を形成し；
Ｒ^１１は、ハロゲン、ヒドロキシ、置換もしくは非置換のアルキルまたは置換もしくは非置換のアルキルオキシであり；
ｍは、０または１である）で示される基が挙げられる（以下、Ｌ－２とする）。
Ｒ^７は、式：

（式中、
Ｒ^９は、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアミノまたは置換もしくは非置換のアルキルであり；
Ｒ^１０は、水素原子、ハロゲンまたは置換もしくは非置換のアルキル；または、
Ｒ^９およびＲ^１０が一緒になって、置換もしくは非置換の非芳香族複素環を形成し；
Ｒ^１１は、ハロゲン、ヒドロキシ、置換もしくは非置換のアルキルまたは置換もしくは非置換のアルキルオキシであり；
ｍは、０または１である）で示される基が挙げられる（以下、Ｌ－３とする）。
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のアルキルオキシ、Ｒ^１０は、水素原子、ｍは、０である）で示される基、または式：

（式中、Ｒ^９およびＲ^１０が一緒になって、置換もしくは非置換の非芳香族複素環を形成し、ｍは、０である）で示される基が挙げられる（以下、Ｌ－４とする）。
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のアルキルオキシ、Ｒ^１０は、水素原子、ｍは、０である）で示される基が挙げられる（以下、Ｌ－５とする）。
Ｒ^７は、式：

（式中、Ｒ^９は、ハロゲンで置換されたアルキルオキシまたは非置換のアルキルオキシ、Ｒ^１０は水素原子、ｍは、０である）で示される基が挙げられる（以下、Ｌ－６とする）。
Ｒ^７は、式：

（式中、Ｒ^９およびＲ^１０が一緒になって、置換もしくは非置換の非芳香族複素環を形成し、ｍは、０である）で示される基が挙げられる（以下、Ｌ－７とする）。
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のアルキルオキシである）で示される基が挙げられる（以下、Ｌ－８とする）。
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のＣ２－Ｃ４アルキルオキシである）で示される基が挙げられる。（以下、Ｌ－９とする）。
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のアルキルで置換されたアミノである）で示される基が挙げられる。（以下、Ｌ－１０とする）。

（式中、Ｒ^９は、置換もしくは非置換のＣ２－Ｃ４アルキルオキシまたは置換もしくは非置換のアミノである）で示される基が挙げられる。（以下、Ｌ－１１とする）。
R ⁷ has the formula:

(In the formula,
R ⁹ is a hydrogen atom, halogen, substituted or unsubstituted alkyloxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted amino, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted alkenyl or substituted or unsubstituted alkyl;
R ¹⁰ is a hydrogen atom, hydroxy, halogen or substituted or unsubstituted alkyl; or
R ⁹ and R ¹⁰ together form a substituted or unsubstituted non-aromatic heterocyclic ring;
R ¹¹ is halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
m is 0 or 1) (hereinafter referred to as L-1).
R ⁷ has the formula:

(In the formula,
R ⁹ is substituted or unsubstituted alkyloxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted amino, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted alkenyl or substituted or unsubstituted alkyl;
R ¹⁰ is a hydrogen atom, halogen or substituted or unsubstituted alkyl; or
R ⁹ and R ¹⁰ together form a substituted or unsubstituted non-aromatic heterocyclic ring;
R ¹¹ is halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
m is 0 or 1) (hereinafter referred to as L-2).
R ⁷ has the formula:

(In the formula,
R ⁹ is substituted or unsubstituted alkyloxy, substituted or unsubstituted amino or substituted or unsubstituted alkyl;
R ¹⁰ is a hydrogen atom, halogen or substituted or unsubstituted alkyl; or
R ⁹ and R ¹⁰ together form a substituted or unsubstituted non-aromatic heterocyclic ring;
R ¹¹ is halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
m is 0 or 1) (hereinafter referred to as L-3).
R ⁷ has the formula:

(wherein R ⁹ is a substituted or unsubstituted alkyloxy, R ¹⁰ is a hydrogen atom, m is 0) or a group represented by the formula:

(wherein R ⁹ and R ¹⁰ together form a substituted or unsubstituted non-aromatic heterocyclic ring, and m is 0) (hereinafter L-4 and do).
R ⁷ has the formula:

(wherein R ⁹ is a substituted or unsubstituted alkyloxy, R ¹⁰ is a hydrogen atom, and m is 0) (hereinafter referred to as L-5).
R ⁷ has the formula:

(wherein R ⁹ is a halogen-substituted alkyloxy or unsubstituted alkyloxy, R ¹⁰ is a hydrogen atom, and m is 0) (hereinafter referred to as L-6 ).
R ⁷ has the formula:

(wherein R ⁹ and R ¹⁰ together form a substituted or unsubstituted non-aromatic heterocyclic ring, and m is 0) (hereinafter L-7 and do).
R ⁷ has the formula:

(wherein R ⁹ is a substituted or unsubstituted alkyloxy) (hereinafter referred to as L-8).
R ⁷ has the formula:

(wherein R ⁹ is a substituted or unsubstituted C2-C4 alkyloxy). (hereinafter referred to as L-9).
R ⁷ has the formula:

(wherein R ⁹ is amino substituted with substituted or unsubstituted alkyl). (hereinafter referred to as L-10).

(wherein R ⁹ is substituted or unsubstituted C2-C4 alkyloxy or substituted or unsubstituted amino). (hereinafter referred to as L-11).

（式中、
Ｒ^１は、Ａ－１７であり；
Ｒ^２は、水素原子であり；
Ｒ^３は、水素原子であり；
ｎは、１であり；
Ｒ^４は、Ｅ－４であり；
Ｌは、－ＮＲ^８－であり；
Ｒ^８は、水素原子であり；
Ｒ^５は、水素原子であり；
Ｒ^６は、水素原子であり；
ｐは、１であり；
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のアルキルオキシである）で示される基である）で示される化合物またはその製薬上許容される塩を含有する、セロトニン５－ＨＴ２Ａ受容体拮抗および／または逆作動薬。
（ｉｉ）式（Ｉ）：

（式中、
Ｒ^１は、Ａ－２４であり；
Ｒ^２は、水素原子であり；
Ｒ^３は、水素原子であり；
ｎは、１であり；
Ｒ^４は、Ｅ－４であり；
Ｌは、－ＮＲ^８－であり；
Ｒ^８は、水素原子であり；
Ｒ^５は、水素原子であり；
Ｒ^６は、水素原子であり；
ｐは、１であり；
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のアルキルオキシである）で示される基である）で示される化合物またはその製薬上許容される塩を含有する、セロトニン５－ＨＴ２Ａ受容体拮抗および／または逆作動薬。
（ｉｉｉ）式（Ｉ）：

（式中、
Ｒ^１は、Ａ－２８であり；
Ｒ^２は、水素原子であり；
Ｒ^３は、水素原子であり；
ｎは、１であり；
Ｒ^４は、Ｅ－４であり；
Ｌは、－ＮＲ^８－であり；
Ｒ^８は、水素原子であり；
Ｒ^５は、水素原子であり；
Ｒ^６は、水素原子であり；
ｐは、１であり；
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のアルキルオキシである）で示される基である）で示される化合物またはその製薬上許容される塩を含有する、セロトニン５－ＨＴ２Ａ受容体拮抗および／または逆作動薬。
（ｉｖ）式（Ｉ）：

（式中、
Ｒ^１は、Ａ－１７であり；
Ｒ^２は、水素原子であり；
Ｒ^３は、水素原子であり；
ｎは、１であり；
Ｒ^４は、Ｅ－４であり；
Ｌは、－ＮＲ^８－であり；
Ｒ^８は、水素原子であり；
Ｒ^５は、水素原子であり；
Ｒ^６は、水素原子であり；
ｐは、１であり；
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のアルキルオキシである）で示される基である）で示される化合物またはその製薬上許容される塩を含有する、セロトニン５－ＨＴ２Ａ受容体拮抗および／または逆作動用組成物。
（ｖ）式（Ｉ）：

（式中、
Ｒ^１は、Ａ－２４であり；
Ｒ^２は、水素原子であり；
Ｒ^３は、水素原子であり；
ｎは、１であり；
Ｒ^４は、Ｅ－４であり；
Ｌは、－ＮＲ^８－であり；
Ｒ^８は、水素原子であり；
Ｒ^５は、水素原子であり；
Ｒ^６は、水素原子であり；
ｐは、１であり；
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のアルキルオキシである）で示される基である）で示される化合物またはその製薬上許容される塩を含有する、セロトニン５－ＨＴ２Ａ受容体拮抗および／または逆作動用組成物。
（ｖｉ）式（Ｉ）：

（式中、
Ｒ^１は、Ａ－２８であり；
Ｒ^２は、水素原子であり；
Ｒ^３は、水素原子であり；
ｎは、１であり；
Ｒ^４は、Ｅ－４であり；
Ｌは、－ＮＲ^８－であり；
Ｒ^８は、水素原子であり；
Ｒ^５は、水素原子であり；
Ｒ^６は、水素原子であり；
ｐは、１であり；
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のアルキルオキシである）で示される基である）で示される化合物またはその製薬上許容される塩を含有する、セロトニン５－ＨＴ２Ａ受容体拮抗および／または逆作動用組成物。

（ｖｉｉ）式（ＩＩ）：

（式中、
Ｒ^１は、置換もしくは非置換の芳香族含窒素複素環式基であり；
Ｒ^２は、水素原子であり；
Ｒ^３は、水素原子であり；
ｎは、１であり；
Ｒ^４は、置換もしくは非置換の非芳香族含窒素複素環式基であり；
Ｒ^８は、水素原子であり；
Ｒ^５は、水素原子であり；
Ｒ^６は、水素原子であり；
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のＣ２－Ｃ４アルキルオキシまたは置換もしくは非置換のアミノである）で示される基である）で示される化合物またはその製薬上許容される塩、を含有する医薬組成物。

（ｖｉｉｉ）式（ＩＩ）：

（式中、
Ｒ^１は、Ａ－１７であり；
Ｒ^２は、水素原子であり；
Ｒ^３は、水素原子であり；
ｎは、１であり；
Ｒ^４は、置換もしくは非置換の非芳香族含窒素複素環式基であり；
Ｒ^８は、水素原子であり；
Ｒ^５は、水素原子であり；
Ｒ^６は、水素原子であり；
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のアルキルオキシである）で示される基である）で示される化合物またはその製薬上許容される塩、を含有する医薬組成物。
（ｉｘ）式（ＩＩ）：

（式中、
Ｒ^１は、Ａ－２４であり；
Ｒ^２は、水素原子であり；
Ｒ^３は、水素原子であり；
ｎは、１であり；
Ｒ^４は、置換もしくは非置換の非芳香族含窒素複素環式基であり；
Ｒ^８は、水素原子であり；
Ｒ^５は、水素原子であり；
Ｒ^６は、水素原子であり；
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のアルキルオキシである）で示される基である）で示される化合物またはその製薬上許容される塩、を含有する医薬組成物。
（ｘ）式（ＩＩ）：

（式中、
Ｒ^１は、Ａ－２８であり；
Ｒ^２は、水素原子であり；
Ｒ^３は、水素原子であり；
ｎは、１であり；
Ｒ^４は、置換もしくは非置換の非芳香族含窒素複素環式基であり；
Ｒ^８は、水素原子であり；
Ｒ^５は、水素原子であり；
Ｒ^６は、水素原子であり；
Ｒ^７は、式：

（式中、Ｒ^９は、置換もしくは非置換のアルキルオキシである）で示される基である）で示される化合物またはその製薬上許容される塩、を含有する医薬組成物。
（ｘｉ）式（ＩＩＩ）：

（式中、
Ｒ^１は、置換もしくは非置換の６員芳香族含窒素複素環式基または置換もしくは非置換の５員芳香族含窒素複素環式基であり；
Ｒ^４は式：

（式中、Ｒ^２１は、水素原子または置換もしくは非置換のアルキルであり；
Ｒ^２２およびＲ^２３は結合する炭素原子と一緒になって、置換もしくは非置換の非芳香族炭素環を形成する）で示される基であり；
Ｒ^７は、式：

（式中、
Ｒ^９は、置換もしくは非置換のＣ２－Ｃ４アルキルオキシまたは置換もしくは非置換のアミノである）で示される基である）で示される化合物またはその製薬上許容される塩、を含有する医薬組成物。
In particular, the following aspects are preferred (i) formula (I):

(In the formula,
R ¹ is A-17;
R ² is a hydrogen atom;
R ³ is a hydrogen atom;
n is 1;
R ⁴ is E-4;
L is -NR ⁸ -;
R ⁸ is a hydrogen atom;
R ⁵ is a hydrogen atom;
R ⁶ is a hydrogen atom;
p is 1;
R ⁷ has the formula:

(Wherein R ⁹ is a substituted or unsubstituted alkyloxy group) or a pharmaceutically acceptable salt thereof, a serotonin 5-HT2A receptor antagonist and/or or inverse agonists.
(ii) Formula (I):

(In the formula,
R ¹ is A-24;
R ² is a hydrogen atom;
R ³ is a hydrogen atom;
n is 1;
R ⁴ is E-4;
L is -NR ⁸ -;
R ⁸ is a hydrogen atom;
R ⁵ is a hydrogen atom;
R ⁶ is a hydrogen atom;
p is 1;
R ⁷ has the formula:

(Wherein R ⁹ is a substituted or unsubstituted alkyloxy group) or a pharmaceutically acceptable salt thereof, a serotonin 5-HT2A receptor antagonist and/or or inverse agonists.
(iii) Formula (I):

(In the formula,
R ¹ is A-28;
R ² is a hydrogen atom;
R ³ is a hydrogen atom;
n is 1;
R ⁴ is E-4;
L is -NR ⁸ -;
R ⁸ is a hydrogen atom;
R ⁵ is a hydrogen atom;
R ⁶ is a hydrogen atom;
p is 1;
R ⁷ has the formula:

(Wherein R ⁹ is a substituted or unsubstituted alkyloxy group) or a pharmaceutically acceptable salt thereof, a serotonin 5-HT2A receptor antagonist and/or or inverse agonists.
(iv) Formula (I):

(In the formula,
R ¹ is A-17;
R ² is a hydrogen atom;
R ³ is a hydrogen atom;
n is 1;
R ⁴ is E-4;
L is -NR ⁸ -;
R ⁸ is a hydrogen atom;
R ⁵ is a hydrogen atom;
R ⁶ is a hydrogen atom;
p is 1;
R ⁷ has the formula:

(Wherein R ⁹ is a substituted or unsubstituted alkyloxy group) or a pharmaceutically acceptable salt thereof, a serotonin 5-HT2A receptor antagonist and/or Or a composition for reverse action.
(v) Formula (I):

(In the formula,
R ¹ is A-24;
R ² is a hydrogen atom;
R ³ is a hydrogen atom;
n is 1;
R ⁴ is E-4;
L is -NR ⁸ -;
R ⁸ is a hydrogen atom;
R ⁵ is a hydrogen atom;
R ⁶ is a hydrogen atom;
p is 1;
R ⁷ has the formula:

(Wherein R ⁹ is a substituted or unsubstituted alkyloxy group) or a pharmaceutically acceptable salt thereof, a serotonin 5-HT2A receptor antagonist and/or Or a composition for reverse action.
(vi) Formula (I):

(In the formula,
R ¹ is A-28;
R ² is a hydrogen atom;
R ³ is a hydrogen atom;
n is 1;
R ⁴ is E-4;
L is -NR ⁸ -;
R ⁸ is a hydrogen atom;
R ⁵ is a hydrogen atom;
R ⁶ is a hydrogen atom;
p is 1;
R ⁷ has the formula:

(Wherein R ⁹ is a substituted or unsubstituted alkyloxy group) or a pharmaceutically acceptable salt thereof, a serotonin 5-HT2A receptor antagonist and/or Or a composition for reverse action.

(vii) Formula (II):

(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 has the formula:

(wherein R ⁹ is a substituted or unsubstituted C2-C4 alkyloxy or substituted or unsubstituted amino) or a pharmaceutically acceptable salt thereof. A pharmaceutical composition for

(viii) Formula (II):

(In the formula,
R ¹ is 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 has the formula:

(wherein R ⁹ is a substituted or unsubstituted alkyloxy) or a pharmaceutically acceptable salt thereof.
(ix) Formula (II):

(In the formula,
R ¹ is A-24;
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 has the formula:

(wherein R ⁹ is a substituted or unsubstituted alkyloxy) or a pharmaceutically acceptable salt thereof.
(x) Formula (II):

(In the formula,
R ¹ is 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 has the formula:

(wherein R ⁹ is a substituted or unsubstituted alkyloxy) or a pharmaceutically acceptable salt thereof.
(xi) Formula (III):

(In the formula,
R ¹ is a substituted or unsubstituted 6-membered aromatic nitrogen-containing heterocyclic group or a substituted or unsubstituted 5-membered aromatic nitrogen-containing heterocyclic group;
^R4 has the formula:

(wherein R ²¹ is a hydrogen atom or substituted or unsubstituted alkyl;
R ²² and R ²³ together with the attached carbon atoms form a substituted or unsubstituted non-aromatic carbocyclic ring;
R ⁷ has the formula:

(In the formula,
R ⁹ is a substituted or unsubstituted C2-C4 alkyloxy or substituted or unsubstituted amino) or a pharmaceutically acceptable salt thereof. .

Compounds of formula (I) or formula (II) are not limited to any particular isomer, but include all possible isomers (e.g. keto-enol isomers, imine-enamine isomers, diastereoisomers isomers, optical isomers, rotational isomers, etc.), racemates or mixtures thereof.

One or more hydrogen, carbon and/or other atoms of the compounds of Formula (I) or Formula (II) may be replaced with isotopes of hydrogen, carbon and/or other atoms, respectively. Examples of such isotopes include ² H, ³ H, ¹¹ C, ¹³ C, ¹⁴ C, ¹⁵ N, ¹⁸ O, ¹⁷ O ^, 31 P, ³² P, ³⁵ S, ¹⁸ F, ¹²³ I and Hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, iodine and chlorine are included, as is ³⁶ Cl. A compound of formula (I) or formula (II) also includes such isotopically substituted compounds. The isotopically substituted compounds are also useful as pharmaceuticals, and include all radiolabeled compounds of formula (I) or formula (II). A "radiolabeling method" for producing the "radiolabel" is also encompassed by the present invention, and the "radiolabel" is useful as a research and/or diagnostic tool in metabolic pharmacokinetic studies, binding assays. is.

Radiolabeled compounds of formula (I) or formula (II) can be prepared by methods well known in the art. For example, a tritium-labeled compound represented by formula (I) or formula (II) introduces tritium into a specific compound represented by formula (I) or formula (II) by a catalytic dehalogenation reaction using tritium. It can be prepared by This method comprises the reaction of a compound of formula (I) or formula (II) with an appropriately halogenated precursor and tritium in the presence or absence of a base in the presence of a suitable catalyst such as Pd/C. Including reacting with gas. Other suitable methods for preparing tritiated compounds can be found in "Isotopes in the Physical and Biomedical Sciences, Vol. 1, Labeled Compounds (Part A), Chapter 6 (1987)". ¹⁴ C-labeled compounds can be prepared by using starting materials with a ¹⁴ C carbon.

Pharmaceutically acceptable salts of compounds represented by formula (I) or formula (II) include, for example, compounds 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, triethanol amine, meglumine, ethylenediamine, pyridine, picoline, quinoline, etc.) and salts with amino acids, or 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) acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, trifluoroacetic acid, etc.). These salts can be formed by a commonly used method.

When the compound represented by formula (I) or formula (II) of the present invention or a pharmaceutically acceptable salt thereof forms a solvate (e.g., hydrate, etc.), co-crystal and/or crystal polymorph and the invention also includes such various solvates, co-crystals and polymorphs. A "solvate" may be coordinated with any number of solvent molecules (eg, water molecules, etc.) to a compound of formula (I) or formula (II). When the compound represented by formula (I) or formula (II) or a pharmaceutically acceptable salt thereof is left in the atmosphere, it absorbs water and adheres to the adsorbed water or forms a hydrate. Sometimes. Also, the compound represented by formula (I) or formula (II) or a pharmaceutically acceptable salt thereof may be recrystallized to form a crystal polymorph. "Co-crystal" means that a compound or salt of formula (I) or formula (II) and a counter molecule are present in the same crystal lattice, and may contain any number of counter molecules.

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 includes such various prodrugs. A prodrug is a derivative of a compound according to the invention which possesses chemically or metabolically degradable groups which, upon solvolysis or under physiological conditions, result in a compound according to the invention which is pharmaceutically active in vivo. is. A prodrug is a compound that undergoes enzymatic oxidation, reduction, hydrolysis, etc. under physiological conditions in vivo and is converted into a compound represented by formula (I) or formula (II), or hydrolyzed by gastric acid, etc. Compounds that are converted to compounds represented by formula (I) or formula (II) are included. Methods for selecting and preparing suitable prodrug derivatives are described, for example, in "Design of Prodrugs, Elsevier, Amsterdam, 1985". A prodrug may itself have activity.

When the compound represented by formula (I) or formula (II) or a pharmaceutically acceptable salt thereof has a hydroxyl group, for example, a compound having a hydroxyl group and a suitable acyl halide, a suitable acid anhydride, a suitable Prodrugs such as acyloxy derivatives and sulfonyloxy derivatives prepared by reacting with sulfonyl chlorides, appropriate sulfonyl anhydrides and mixed anhydrides or by using condensing agents are exemplified. For example, CH ₃ COO-, C ₂ H ₅ COO-, tert-BuCOO-, C ₁₅ H ₃₁ COO-, PhCOO-, (m-NaOOCPh)COO-, NaOOCCH ₂ CH ₂ COO-, CH ₃ CH(NH ₂ ) COO—, CH ₂ N(CH ₃ ) ₂ COO—, CH ₃ SO ₃ —, CH ₃ CH ₂ SO ₃ —, CF ₃ SO ₃ —, CH ₂ FSO ₃ —, CF ₃ CH ₂ SO ₃ —, p -CH ₃ O-PhSO ₃ -, PhSO ₃ -, p-CH ₃ PhSO ₃ -.

The compounds according to the present invention have serotonin 5-HT2A receptor antagonistic and/or inverse agonistic activity, and are therefore useful as therapeutic and/or prophylactic agents for diseases involving serotonin 5-HT2A receptors. Diseases involving serotonin 5-HT2A receptors include delusions associated with Parkinson's disease, delusions associated with dementia, delusions associated with schizophrenia, delusions associated with depression, delusions associated with neurodegenerative diseases, and depression. , schizophrenia, autism, dependence, dyskinesia, sleep disorders, irritability associated with Parkinson's disease, irritability associated with dementia, irritability associated with schizophrenia, sexual dysfunction, etc., mediated by serotonin diseases that cause Preferably, hallucinatory delusions associated with Parkinson's disease, hallucinatory delusions associated with dementia, hallucinatory delusions associated with schizophrenia, hallucinatory delusions associated with depression, irritability associated with Parkinson's disease, irritability associated with dementia, schizophrenia irritability associated with More preferably, hallucinogenic delusions associated with Parkinson's disease, hallucinogenic delusions associated with dementia, and the like are included.
"Serotonin 5-HT2A receptor antagonist and/or inverse agonist" means a pharmaceutical agent having serotonin 5-HT2A receptor antagonist and/or inverse agonist action.
A “composition for serotonin 5-HT2A receptor antagonistic and/or inverse agonistic action” means a composition having serotonin 5-HT2A receptor antagonistic and/or inverse agonistic action, and is not limited to medical use.

(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 synthetic methods shown below. Extraction, purification, and the like may be carried out as in ordinary organic chemistry experiments.
The compounds of the present invention can be synthesized with reference to methods known in the art.

（式中、各記号は上記（１）と同義であり、Ｒ^１A－は、Ｒ^１－またはＲ^１Ｒ^２ＣＨ－である。）
工程１
化合物（ａ－１）およびＣＤＩを、適当な溶媒中で反応させることにより化合物（ａ－２）を得ることができる。
ＣＤＩは、化合物（ａ－１）に対して１．０モル当量またはそれ以上、好ましくは１．２モル等量使用することができる。
反応溶媒としては、アルコール類（例、メタノール、エタノール、ｔｅｒｔ－ブタノール、イソプロパノールなど）、芳香族炭化水素類（例、トルエン、ベンゼン、キシレンなど）、飽和炭化水素類（例、シクロヘキサン、ヘキサンなど）、エーテル類（例、テトラヒドロフラン、ジエチルエーテル、ジオキサン、ジメトキシエタンなど）、ハロゲン化炭化水素類（例、クロロホルム、ジクロロメタンなど）、ＤＭＦ、ＤＭＳＯ、ＮＭＰ、アセトニトリル、ピリジン等が挙げられ、単独または混合して用いることができる。
反応温度は、０～８０℃、好ましくは０～２０℃である。
反応時間は、０．１～２４時間、好ましくは０．５～６時間である。
得られた所望の化合物（ａ－２）は、要すれば常法（例、カラムクロマトグラフィー、再結晶など）により精製することができる。

工程２
化合物（ａ－３）および化合物（ａ－４）を、適切な還元剤、酢酸と適当な溶媒中で反応させることにより化合物（ａ－５）を得ることができる。
還元剤としては、例えば、水素化トリアセトキシホウ素ナトリウム、シアノ水素化ホウ素ナトリウム等が挙げられ、化合物（ａ－３）に対して１．０モル当量またはそれ以上、好ましくは１．０～２．０モル当量使用することができる。
酢酸は、化合物（ａ－３）に対して１．０モル当量またはそれ以上、好ましくは１．０～２．０モル当量使用することができる。
反応溶媒としては、アルコール類（例、メタノール、エタノール、ｔｅｒｔ－ブタノール、イソプロパノールなど）、芳香族炭化水素類（例、トルエン、ベンゼン、キシレンなど）、飽和炭化水素類（例、シクロヘキサン、ヘキサンなど）、エーテル類（例、テトラヒドロフラン、ジエチルエーテル、ジオキサン、ジメトキシエタンなど）、ハロゲン化炭化水素類（例、クロロホルム、ジクロロメタンなど）、ＤＭＦ、ＤＭＳＯ、ＮＭＰ、アセトニトリル、ピリジン等が挙げられ、単独または混合して用いることができる。
反応温度は、０～８０℃、好ましくは０～２０℃である。
反応時間は、０．１～４８時間、好ましくは０．５～２４時間である。
得られた所望の化合物（ａ－５）は、要すれば常法（例、カラムクロマトグラフィー、再結晶など）により精製することができる。

工程３
化合物（ａ－５）および化合物（ａ－２）を、適当な溶媒中で反応させることにより化合物（Ｉ－ａ）を得ることができる。
反応溶媒としては、アルコール類（例、メタノール、エタノール、ｔｅｒｔ－ブタノール、イソプロパノールなど）、芳香族炭化水素類（例、トルエン、ベンゼン、キシレンなど）、飽和炭化水素類（例、シクロヘキサン、ヘキサンなど）、エーテル類（例、テトラヒドロフラン、ジエチルエーテル、ジオキサン、ジメトキシエタンなど）、ハロゲン化炭化水素類（例、クロロホルム、ジクロロメタンなど）、ＤＭＦ、ＤＭＳＯ、ＮＭＰ、アセトニトリル、ピリジン等が挙げられ、単独または混合して用いることができる。
反応温度は、０～１００℃、好ましくは０～８０℃である。
反応時間は、０．１～２４時間、好ましくは０．５～６時間である。
得られた所望の化合物（Ｉ－ａ）は、要すれば常法（例、カラムクロマトグラフィー、再結晶など）により精製することができる。 (When R ³ is a hydrogen atom and L is -NH-)

(In the formula, each symbol has the same meaning as in (1) above, and R ^1A — is R ¹ — or R ¹ R ² 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).
Reaction solvents include alcohols (eg, methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.), saturated hydrocarbons (eg, 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., alone or in combination. can be used for
The reaction temperature is 0-80°C, preferably 0-20°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 a conventional method (eg, column chromatography, recrystallization, etc.), if necessary.

Process 2
Compound (a-5) can be obtained by reacting compound (a-3) and compound (a-4) with a suitable reducing agent and acetic acid in a suitable solvent.
Examples of the reducing agent include sodium triacetoxyborohydride, sodium cyanoborohydride and the like, and the amount thereof is 1.0 molar equivalent or more, preferably 1.0 to 2.0 molar equivalents relative to compound (a-3). 0 molar equivalents can be used.
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).
Reaction solvents include alcohols (eg, methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.), saturated hydrocarbons (eg, 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., alone or in combination. can be used for
The reaction temperature is 0-80°C, preferably 0-20°C.
The reaction time is 0.1 to 48 hours, preferably 0.5 to 24 hours.
The resulting desired compound (a-5) can be purified by conventional methods (eg, 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.
Reaction solvents include alcohols (eg, methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.), saturated hydrocarbons (eg, 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., alone or in combination. can be used for
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 (Ia) can be purified by a conventional method (eg, column chromatography, recrystallization, etc.), if necessary.

（式中、各記号は上記（１）と同義であり、ＰＧはアミノ基の適切な保護基であり、環Ａは置換もしくは非置換の非芳香族含窒素複素環式基であり、Ｒ^ａは置換もしくは非置換のアルキルである。）

工程１
化合物（ｂ－１）および化合物（ｂ－２）を、適切な還元剤、必要に応じて酢酸と適当な溶媒中で反応させることにより、化合物（ｂ－３）を得ることができる。
還元剤としては、例えば、水素化トリアセトキシホウ素ナトリウム、シアノ水素化ホウ素ナトリウム等が挙げられ、化合物（ｂ－１）に対して１．０モル当量またはそれ以上、好ましくは１．０～２．０モル当量使用することができる。
酢酸は、化合物（ｂ－３）に対して１．０モル当量またはそれ以上、好ましくは１．０～２．０モル当量使用することができる。
反応溶媒としては、アルコール類（例、メタノール、エタノール、ｔｅｒｔ－ブタノール、イソプロパノールなど）、芳香族炭化水素類（例、トルエン、ベンゼン、キシレンなど）、飽和炭化水素類（例、シクロヘキサン、ヘキサンなど）、エーテル類（例、テトラヒドロフラン、ジエチルエーテル、ジオキサン、ジメトキシエタンなど）、ハロゲン化炭化水素類（例、クロロホルム、ジクロロメタンなど）、ＤＭＦ、ＤＭＳＯ、ＮＭＰ、アセトニトリル、ピリジン等が挙げられ、単独または混合して用いることができる。
反応温度は、０～８０℃、好ましくは０～２０℃である。
反応時間は、０．１～４８時間、好ましくは０．５～２４時間である。
得られた所望の化合物（ｂ－３）は、要すれば常法（例、カラムクロマトグラフィー、再結晶など）により精製することができる。

工程２
化合物（ｂ－３）および化合物（ａ－２）を、適当な溶媒中で反応させることにより化合物（ｂ－４）を得ることができる。
反応溶媒としては、アルコール類（例、メタノール、エタノール、ｔｅｒｔ－ブタノール、イソプロパノールなど）、芳香族炭化水素類（例、トルエン、ベンゼン、キシレンなど）、飽和炭化水素類（例、シクロヘキサン、ヘキサンなど）、エーテル類（例、テトラヒドロフラン、ジエチルエーテル、ジオキサン、ジメトキシエタンなど）、ハロゲン化炭化水素類（例、クロロホルム、ジクロロメタンなど）、ＤＭＦ、ＤＭＳＯ、ＮＭＰ、アセトニトリル、ピリジン等が挙げられ、単独または混合して用いることができる。
反応温度は、０～１００℃、好ましくは０～８０℃である。
反応時間は、０．１～２４時間、好ましくは０．５～６時間である。
得られた所望の化合物（ｂ－４）は、要すれば常法（例、カラムクロマトグラフィー、再結晶など）により精製することができる。

工程３
化合物（ｂ－４）を酸存在下、無溶媒または適当な溶媒中で反応させることにより化合物（ｂ－５）を得ることができる。
酸としては、例えば、塩酸、硫酸、ＴＦＡ、ギ酸などが挙げられ、化合物（ｂ－４）に対して１．０モル当量またはそれ以上、好ましくは１．０～３０モル当量使用することができる。
反応溶媒としては、アルコール類（例、メタノール、エタノール、ｔｅｒｔ－ブタノール、イソプロパノールなど）、芳香族炭化水素類（例、トルエン、ベンゼン、キシレンなど）、飽和炭化水素類（例、シクロヘキサン、ヘキサンなど）、エーテル類（例、テトラヒドロフラン、ジエチルエーテル、ジオキサン、ジメトキシエタンなど）、ハロゲン化炭化水素類（例、クロロホルム、ジクロロメタンなど）、ＤＭＦ、ＤＭＳＯ、ＮＭＰ、アセトニトリル、ピリジン等が挙げられ、単独または混合して用いることができる。
反応温度は、０～８０℃、好ましくは０～２０℃である。
反応時間は、０．１～２４時間、好ましくは０．５～６時間である。
得られた所望の化合物（ｂ－５）は、要すれば常法（例、カラムクロマトグラフィー、再結晶など）により精製することができる。

工程４
化合物（ｂ－５）および化合物（ｂ－６）を、適切な還元剤、必要に応じて酢酸と適当な溶媒中で反応させることにより化合物（Ｉ－ｂ）を得ることができる。
還元剤としては、例えば、水素化トリアセトキシホウ素ナトリウム、シアノ水素化ホウ素ナトリウム等が挙げられ、化合物（ｂ－５）に対して１．０モル当量またはそれ以上、好ましくは１．０～２．０モル当量使用することができる。
酢酸は、化合物（ｂ－５）に対して１．０モル当量またはそれ以上、好ましくは１．０～２．０モル当量使用することができる。
反応溶媒としては、アルコール類（例、メタノール、エタノール、ｔｅｒｔ－ブタノール、イソプロパノールなど）、芳香族炭化水素類（例、トルエン、ベンゼン、キシレンなど）、飽和炭化水素類（例、シクロヘキサン、ヘキサンなど）、エーテル類（例、テトラヒドロフラン、ジエチルエーテル、ジオキサン、ジメトキシエタンなど）、ハロゲン化炭化水素類（例、クロロホルム、ジクロロメタンなど）、ＤＭＦ、ＤＭＳＯ、ＮＭＰ、アセトニトリル、ピリジン等が挙げられ、単独または混合して用いることができる。
反応温度は、０～８０℃、好ましくは０～２０℃である。
反応時間は、０．１～２４時間、好ましくは０．５～６時間である。
得られた所望の化合物（Ｉ－ｂ）は、要すれば常法（例、カラムクロマトグラフィー、再結晶など）により精製することができる。

(wherein each symbol has the same meaning as in (1) above, 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 is a substituted or unsubstituted alkyl.)

Process 1
Compound (b-3) can be obtained by reacting compound (b-1) and compound (b-2) with a suitable reducing agent and, if necessary, acetic acid in a suitable solvent.
Examples of the reducing agent include sodium triacetoxyborohydride, sodium cyanoborohydride and the like, and the amount thereof is 1.0 molar equivalent or more, preferably 1.0 to 2.0 molar equivalents relative to compound (b-1). 0 molar equivalents can be used.
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).
Reaction solvents include alcohols (eg, methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.), saturated hydrocarbons (eg, 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., alone or in combination. can be used
The reaction temperature is 0-80°C, preferably 0-20°C.
The reaction time is 0.1 to 48 hours, preferably 0.5 to 24 hours.
The resulting desired compound (b-3) can be purified by a conventional method (eg, column chromatography, recrystallization, etc.), if desired.

Process 2
Compound (b-4) can be obtained by reacting compound (b-3) and compound (a-2) in a suitable solvent.
Reaction solvents include alcohols (eg, methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.), saturated hydrocarbons (eg, 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., alone or in combination. can be used
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 (b-4) thus obtained can be purified by a conventional method (eg, column chromatography, recrystallization, etc.), if necessary.

Step 3
Compound (b-5) can be obtained by reacting compound (b-4) in the presence of an acid in the absence of solvent or in a suitable solvent.
Examples of the acid include hydrochloric acid, sulfuric acid, TFA, and formic acid, which 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). .
Reaction solvents include alcohols (eg, methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.), saturated hydrocarbons (eg, 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., alone or in combination. can be used
The reaction temperature is 0-80°C, preferably 0-20°C.
The reaction time is 0.1 to 24 hours, preferably 0.5 to 6 hours.
The resulting desired compound (b-5) can be purified by conventional methods (eg, column chromatography, recrystallization, etc.), if necessary.

Step 4
Compound (Ib) can be obtained by reacting compound (b-5) and compound (b-6) with a suitable reducing agent and, if necessary, acetic acid in a suitable solvent.
Examples of the reducing agent include sodium triacetoxyborohydride, sodium cyanoborohydride and the like, and the amount thereof is 1.0 molar equivalent or more, preferably 1.0 to 2.0 molar equivalents relative to compound (b-5). 0 molar equivalents can be used.
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).
Reaction solvents include alcohols (eg, methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.), saturated hydrocarbons (eg, 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., alone or in combination. can be used
The reaction temperature is 0-80°C, preferably 0-20°C.
The reaction time is 0.1 to 24 hours, preferably 0.5 to 6 hours.
The resulting desired compound (Ib) can be purified by conventional methods (eg, column chromatography, recrystallization, etc.), if necessary.

（式中、各記号は上記（１）と同義である。）
工程１
化合物（ａ－５）および化合物（ｃ－１）を、適切な縮合剤、必要に応じて塩基と適当な溶媒中で反応させることにより化合物（Ｉ－ｃ）を得ることができる。
縮合剤としては、例えば、ＨＯＢｔ、ＨＯＡｔ、ＤＣＣ、ＤＩＣ、ＥＤＣ ＨＣｌ、ＨＡＴＵ、ＰｙＢＯＰ等が挙げられ、化合物（ｂ－５）に対して１．０モル当量またはそれ以上、好ましくは１．０～２．０モル当量使用することができる。
塩基は、トリエチルアミン、ＤＩＥＡ等が挙げられる。化合物（ａ－５）に対して１．０モル当量またはそれ以上、好ましくは１．０～２．０モル当量使用することができる。
反応溶媒としては、アルコール類（例、メタノール、エタノール、ｔｅｒｔ－ブタノール、イソプロパノールなど）、芳香族炭化水素類（例、トルエン、ベンゼン、キシレンなど）、飽和炭化水素類（例、シクロヘキサン、ヘキサンなど）、エーテル類（例、テトラヒドロフラン、ジエチルエーテル、ジオキサン、ジメトキシエタンなど）、ハロゲン化炭化水素類（例、クロロホルム、ジクロロメタンなど）、ＤＭＦ、ＤＭＳＯ、ＮＭＰ、アセトニトリル、ピリジン等が挙げられ、単独または混合して用いることができる。
反応温度は、０～８０℃、好ましくは０～２０℃である。
反応時間は、０．１～２４時間、好ましくは０．５～６時間である。
得られた所望の化合物（Ｉ－ｃ）は、要すれば常法（例、カラムクロマトグラフィー、再結晶など）により精製することができる。

(In the formula, each symbol has the same meaning as in (1) above.)
Process 1
Compound (Ic) can be obtained by reacting compound (a-5) and compound (c-1) with a suitable condensing agent and, if necessary, a base in a suitable solvent.
Examples of the condensing agent include HOBt, HOAt, DCC, DIC, EDC HCl, HATU, PyBOP and the like, and the amount is 1.0 molar equivalent or more, preferably 1.0 to 1.0 molar equivalent, relative to compound (b-5). 2.0 molar equivalents can be used.
Bases include triethylamine, DIEA and the like. It 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-5).
Reaction solvents include alcohols (eg, methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.), saturated hydrocarbons (eg, 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., alone or in combination. can be used for
The reaction temperature is 0-80°C, preferably 0-20°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 a conventional method (eg, column chromatography, recrystallization, etc.), if necessary.

（式中、各記号は上記（１）と同義である。）
工程１
化合物（ａ－５）および化合物（ｄ－１）を、塩基と適当な溶媒中で反応させることにより化合物（Ｉ－ｃ）を得ることができる。
塩基は、トリエチルアミン、ＤＩＥＡ、ピリジン等が挙げられる。化合物（ａ－５）に対して１．０モル当量またはそれ以上、好ましくは１．０～５．０モル当量使用することができる。
反応溶媒としては、アルコール類（例、メタノール、エタノール、ｔｅｒｔ－ブタノール、イソプロパノールなど）、芳香族炭化水素類（例、トルエン、ベンゼン、キシレンなど）、飽和炭化水素類（例、シクロヘキサン、ヘキサンなど）、エーテル類（例、テトラヒドロフラン、ジエチルエーテル、ジオキサン、ジメトキシエタンなど）、ハロゲン化炭化水素類（例、クロロホルム、ジクロロメタンなど）、ＤＭＦ、ＤＭＳＯ、ＮＭＰ、アセトニトリル、ピリジン等が挙げられ、単独または混合して用いることができる。
反応温度は、０～１２０℃、好ましくは０～８０℃である。
反応時間は、０．１～２４時間、好ましくは０．５～１２時間である。
得られた所望の化合物（Ｉ－ｄ）は、要すれば常法（例、カラムクロマトグラフィー、再結晶など）により精製することができる。

(In the formula, each symbol has the same meaning as in (1) above.)
Process 1
Compound (Ic) can be obtained by reacting compound (a-5) and compound (d-1) with a base in a suitable solvent.
Bases include triethylamine, DIEA, pyridine and the like. It can be used in an amount of 1.0 molar equivalent or more, preferably 1.0 to 5.0 molar equivalents, relative to compound (a-5).
Reaction solvents include alcohols (eg, methanol, ethanol, tert-butanol, isopropanol, etc.), aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.), saturated hydrocarbons (eg, 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., alone or in combination. can be used
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 obtained desired compound (Id) can be purified by a conventional method (eg, column chromatography, recrystallization, etc.), if desired.

Since the compound according to the present invention has serotonin 5-HT2A receptor antagonistic and/or inverse agonistic action, it is useful as a therapeutic and/or prophylactic agent for hallucinogenic delusions associated with Parkinson's disease and/or dementia.
Furthermore, the compounds according to the present invention are useful as pharmaceuticals, and preferably have one or more of the following excellent characteristics.
a) It has a weak inhibitory effect on CYP enzymes (eg, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, etc.).
b) shows good pharmacokinetics such as high bioavailability and moderate clearance;
c) high metabolic stability;
d) Does not exhibit irreversible inhibitory action on CYP enzymes (eg, CYP3A4) within the concentration range of the measurement conditions described herein.
e) not mutagenic;
f) low cardiovascular risk;
g) exhibit high solubility;
h) have high serotonin 5-HT2A receptor binding capacity;
i) have high serotonin 5-HT2C receptor binding ability;
j) high brain transferability;
k) Poor P-gp substrate.

The pharmaceutical composition of the present invention can be administered orally or parenterally. Examples of parenteral administration methods include transdermal, subcutaneous, intravenous, intraarterial, intramuscular, intraperitoneal, transmucosal, inhalation, nasal, ocular, ear and intravaginal administration.

For oral administration, internal solid preparations (e.g., tablets, powders, granules, capsules, pills, films, etc.), internal liquid preparations (e.g., suspensions, emulsions, elixirs, syrups, etc.) It may be prepared and administered in any commonly used dosage form such as a drug, limonade, alcohol, aromatic water, extract, decoction, tincture, and the like. Tablets may be sugar-coated tablets, film-coated tablets, enteric-coated tablets, sustained-release tablets, troches, sublingual tablets, buccal tablets, chewable tablets or orally disintegrating tablets, and powders and granules may be dry syrups. Alternatively, the capsules may be soft capsules, microcapsules or sustained release capsules.

In the case of parenteral administration, injections, drops, external preparations (e.g., eye drops, nasal drops, ear drops, aerosols, inhalants, lotions, injections, coatings, gargles, enemas, Any commonly used dosage form such as ointments, plasters, jellies, creams, patches, poultices, powders for external use, suppositories, etc.) can be suitably administered. Injections may be emulsions such as O/W, W/O, O/W/O and W/O/W types.

An effective amount of the compound according to the present invention can be mixed, if necessary, with various pharmaceutical additives such as excipients, binders, disintegrants, and lubricants suitable for the dosage form to prepare a pharmaceutical composition. can. Furthermore, the pharmaceutical composition can be used for children, the elderly, critically ill patients, or surgery by appropriately changing the effective amount of the compound according to the present invention, the dosage form and/or various pharmaceutical additives. It can also be an object. For example, a pediatric pharmaceutical composition can be used for neonates (less than 4 weeks after birth), infants (4 weeks after birth to less than 1 year old) infants (1 to 7 years old), children (7 to 15 years old) or 15 Patients between the ages of 18 and 18 can be administered. For example, geriatric pharmaceutical compositions may be administered to patients 65 years of age or older.

The dosage of the pharmaceutical composition of the present invention is preferably set in consideration of the patient's age, body weight, type and degree of disease, administration route, etc., but 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. In the case of parenteral administration, it is generally 0.005 to 10 mg/kg/day, preferably 0.01 to 1 mg/kg/day, although it varies greatly depending on the route of administration. It may be administered once to several times a day.

The compounds according to the present invention are anti-Parkinson's drugs, anti-Alzheimer's drugs, antipsychotics, antidepressants (hereinafter referred to as concomitant drug) for the purpose of enhancing the action of the compound or reducing the dose of the compound. can be used in combination with In this case, the timing of administration of the compound of the present invention and the concomitant drug are not limited, and they may be administered to the subject at the same time or at different times. Furthermore, the compound of the present invention and the concomitant drug may be administered as two or more formulations containing each active ingredient, or may be administered as a single formulation containing those active ingredients.

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

Antiparkinsonian drugs include, for example, levodopa preparations and the like.
Anti-Alzheimer's drugs include, for example, donepezil and the like.
Antipsychotic drugs include, for example, quetiapine and the like.
Examples of antidepressants include escitalopram and the like.

EXAMPLES 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.

Abbreviations used in this specification have the following meanings.
AcOH: acetic acid CDCl ₃ : 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®: hexafluorophosphoric acid ( benzotriazol-1-yloxy)tripyrrolidinophosphonium

(Compound identification method)
NMR analyzes obtained in each example were performed at 400 MHz and measured using DMSO-d ₆ , CDCl ₃ . Moreover, when NMR data are shown, there are cases where not all measured peaks are shown.
RT in the specification represents retention time in LC/MS: liquid chromatography/mass spectrometry, and was measured under the following conditions.
(Measurement condition 1)
Column: Shim-pack XR-ODS (2.2 μm id 3.0×50 mm) (Shimadzu)
Flow rate: 1.6 mL/min UV detection wavelength: 254 nm
Mobile phase: [A] is an aqueous solution containing 0.1% formic acid, [B] is an acetonitrile solution containing 0.1% formic acid Gradient: 10%-100% solvent [B] linear gradient over 3 minutes, then 0 Maintain 100% solvent [B] for .5 minutes.
(Measurement condition 2)
Column: ACQUITY UPLC® BEH C18 (1.7 μm id 2.1×50 mm) (Waters)
Flow rate: 0.8 mL/min UV detection wavelength: 254 nm
Mobile phase: [A] is an aqueous solution containing 0.1% formic acid, [B] is an acetonitrile solution containing 0.1% formic acid Gradient: After performing a linear gradient of 5%-100% solvent [B] in 3.5 minutes , 100% solvent [B] was maintained for 0.5 min.
In the specification, the description of MS (m/z) indicates the value observed by mass spectrometry.

工程１ 化合物１の合成
４－イソブトキシフェニルメタンアミン（６．００ｇ、３３．５ｍｍｏｌ）とＣＤＩ（６５１ｍｇ、４０．２ｍｍｏｌ）をアセトニトリル（６０ｍＬ）に溶解し、室温で１時間撹拌した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物１（７．９２ｇ、収率８７％）を得た。
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).

工程２ 化合物２の合成
５－フルオロピコリンアルデヒド（１．００ｇ、７．９９ｍｍｏｌ）と１－メチルピペリジン４－アミン（９１３ｍｇ、７．９９ｍｍｏｌ）をジクロロメタン（２０ｍＬ）に溶解し、水素化トリアセトキシボロヒドリド（３．３９ｇ、１６．０ｍｍｏｌ）、酢酸（０．９１４ｍＬ、１６．０ｍｍｏｌ）を加え、室温で終夜撹拌した。飽和炭酸水素ナトリウム水溶液を加え、クロロホルムで抽出した。有機層を無水硫酸マグネシウムで乾燥した。溶媒を減圧留去し、化合物２（９７０ｍｇ、収率５５％）を得た。
¹H-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).

工程３ 化合物（Ｉ－００８）の合成
化合物１（６７３ｍｇ、２．４６ｍｍｏｌ）と化合物２（５００ｍｇ、２．２４ｍｍｏｌ）をトルエン（５ｍＬ）に溶解し、８０℃で１時間撹拌した。放冷後、溶媒を減圧留去し、得られた残渣をアミノカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物（Ｉ－００８）（５２５ｍｇ、収率５５％）を得た。 Synthesis of compound (I-008)

Step 1 Synthesis of Compound 1 4-Isobutoxyphenylmethanamine (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 distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 1 (7.92 g, yield 87%).
¹ H-NMR (CDCl ₃ ) 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 Dissolve 5-fluoropicolinaldehyde (1.00 g, 7.99 mmol) and 1-methylpiperidin 4-amine (913 mg, 7.99 mmol) in dichloromethane (20 mL) and convert to hydrogenated triacetoxyborohydride. (3.39 g, 16.0 mmol), acetic acid (0.914 mL, 16.0 mmol) were added and stirred overnight at room temperature. A saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with chloroform. The organic layer was dried with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain compound 2 (970 mg, yield 55%).
¹ H-NMR (CDCl ₃ ) 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 allowing to cool, the solvent was distilled off under reduced pressure, and the obtained residue was purified by amino column chromatography (hexane-ethyl acetate) to obtain compound (I-008) (525 mg, yield 55%).

工程１ 化合物（Ｉ－０４２）の合成
化合物２（７４．４ｍｇ、０．３３３ｍｍｏｌ）をＮ，Ｎ－ジメチルホルムアミド（１．１５ｍＬ）に溶解し、４－イソブトキシベンジル（４－ニトロフェニル）カーボネート（７４．４ｍｇ、０．３３３ｍｍｏｌ）、及びトリエチルアミン（０．１４ｍＬ、１．００ｍｍｏｌ）を加え、７０℃で８時間撹拌した。水を加え、酢酸エチルで抽出した。有機層を水洗した後、溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（酢酸エチル－ヘキサン）により精製して化合物（Ｉ－０４２）（４０ｍｇ、収率２８％）を得た。 Synthesis of compound (I-042)

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 and stirred at 70° C. for 8 hours. Water was added and extracted with ethyl acetate. After the organic layer was washed with water, the solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate-hexane) to obtain compound (I-042) (40 mg, yield 28%). .

工程１ 化合物５の合成
化合物４（３００ｍｇ、１．３３ｍｍｏｌ）にジクロロメタン（５ｍＬ）、（５－フルオロピリジン－２－イル）メタンアミン（２０２ｍｇ、１．６０ｍｍｏｌ）、ＡｃＯＨ（０．０７ｍＬ、１．３３ｍｍｏｌ）、およびナトリウムトリアセトキシボロヒドリド（４２３ｍｇ、２．００ｍｍｏｌ）を加え、室温で６時間撹拌した。飽和重曹水（５ｍＬ）を加え、室温で攪拌した。水を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄した後、無水硫酸マグネシウムで乾燥した。溶媒を減圧留去し、得られた残渣をアミノシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物５（４０２ｍｇ、収率９０％）を得た。
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).

工程２ 化合物６の合成
化合物５（１５０ｍｇ、０．４５ｍｍｏｌ）にアセトニトリル（２ｍＬ）、およびＮ－（４－イソブトキシベンジル）－１Ｈ－イミダゾール－１－カルボキサミド（１４７ｍｇ、０．５４ｍｍｏｌ）を加え、８０℃で８時間撹拌した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物６（１９５ｍｇ、収率８１％）を得た。
¹H-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).

工程３ 化合物（Ｉ－０５１）の合成
化合物６（１９５ｍｇ、０．３６ｍｍｏｌ）にジクロロメタン（２ｍＬ）、およびＴＦＡ（０．５ｍＬ、６．４９ｍｍｏｌ）を加え、室温で３時間撹拌した。２０％炭酸カリウム水溶液（４ｍＬ）を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄した後、無水硫酸マグネシウムで乾燥した。溶媒を減圧留去し化合物（Ｉ－０５１）（１５２ｍｇ、収率９６％）を得た。
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).

工程４ 化合物（Ｉ－０５０）の合成
化合物（Ｉ－０５１）（８５ｍｇ、０．１９ｍｍｏｌ）にエタノール（２ｍＬ）、３７％ホルムアルデヒド液（０．０３ｍＬ、０．３９ｍｍｏｌ）、およびナトリウムトリアセトキシボロヒドリド（６１ｍｇ、０．２９ｍｍｏｌ）を加え、室温で２時間撹拌した。飽和重曹水（５ｍＬ）を加え、室温で攪拌した。水を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄した後、無水硫酸マグネシウムで乾燥した。溶媒を減圧留去し、得られた残渣をアミノシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物（Ｉ－０５０）（８０ｍｇ、収率９１％）を得た。 Synthesis of compound (I-050)

Step 1 Synthesis of compound 5 To compound 4 (300 mg, 1.33 mmol), dichloromethane (5 mL), (5-fluoropyridin-2-yl)methanamine (202 mg, 1.60 mmol), AcOH (0.07 mL, 1.33 mmol) , and sodium triacetoxyborohydride (423 mg, 2.00 mmol) were added and stirred at room temperature for 6 hours. Saturated sodium bicarbonate water (5 mL) was added, and the mixture was stirred at room temperature. Water was added and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by amino silica gel column chromatography (hexane-ethyl acetate) to obtain compound 5 (402 mg, yield 90%).
¹ H-NMR (CDCl ₃ ) 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 To compound 5 (150 mg, 0.45 mmol) was added acetonitrile (2 mL) and N-(4-isobutoxybenzyl)-1H-imidazole-1-carboxamide (147 mg, 0.54 mmol). C. for 8 hours. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 6 (195 mg, yield 81%).
¹ H-NMR (CDCl ₃ ) 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) Dichloromethane (2 mL) and TFA (0.5 mL, 6.49 mmol) were added to compound 6 (195 mg, 0.36 mmol) and stirred at room temperature for 3 hours. A 20% aqueous potassium carbonate solution (4 mL) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain compound (I-051) (152 mg, yield 96%).
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) Ethanol (2 mL), 37% formaldehyde solution (0.03 mL, 0.39 mmol), and sodium triacetoxyborohydride (I-051) (85 mg, 0.19 mmol) 61 mg, 0.29 mmol) was added and stirred at room temperature for 2 hours. Saturated sodium bicarbonate water (5 mL) was added, and the mixture was stirred at room temperature. Water was added and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by amino silica gel column chromatography (hexane-ethyl acetate) to obtain compound (I-050) (80 mg, yield 91%).

工程１ 化合物（Ｉ－０６８）の合成
化合物２（７５．０ｍｇ、０．３３６ｍｍｏｌ）をＮ，Ｎ－ジメチルホルムアミド（０．７５ｍＬ）に溶解し、２－（４－イソブトキシフェニル）酢酸（８４．０ｍｇ、０．４０３ｍｍｏｌ）（合成法はＷＯ２０１９／４０１０４に記載）、ＨＯＢｔ（５４．５ｍｇ、０．４０３ｍｍｏｌ）及び１－エチル－３－（３－ジメチルアミノプロピル）カルボジイミド塩酸塩（７７．０ｍｇ、０．４０３ｍｍｏｌ）を加え、室温で１．５時間撹拌した。炭酸カリウム水溶液を加え、酢酸エチルで抽出した。有機層を水洗した後、溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（酢酸エチル－ヘキサン）により精製して化合物（Ｉ－０６８）（１０４ｍｇ、収率７５％）を得た。
参考例１ Synthesis of compound (I-068)

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) (the synthetic method is 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) was added and stirred at room temperature for 1.5 hours. An aqueous potassium carbonate solution was added, and the mixture was extracted with ethyl acetate. After the organic layer was washed with water, the solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate-hexane) to obtain compound (I-068) (104 mg, yield 75%). .
Reference example 1

工程１ 化合物８の合成
ｐ－トリルメタンアミン（０．６ｇ、５．００ｍｍｏｌ）のテトラヒドロフラン（１４ｍｌ）溶液に、ＣＤＩ（０．９７ｇ、６．００ｍｍｏｌ）を加え、４５度で３時間撹拌した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物８（０．６６ｇ、収率６１％）を得た。
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). Synthesis of compound 8

Step 1 Synthesis of Compound 8 CDI (0.97 g, 6.00 mmol) was added to a solution of p-tolylmethanamine (0.6 g, 5.00 mmol) in tetrahydrofuran (14 ml) and stirred at 45 degrees for 3 hours. The solvent was distilled off under reduced pressure, and the obtained 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).

工程１ 化合物９の合成
氷冷下、（Ｓ）－１－フェネチル－１－アミン（１．２９ｇ、１０．７ｍｍｏｌ）にジクロロメタン（３０ｍＬ）、トリエチルアミン（５．３９ｇ、５３．３ｍｍｏｌ）、四塩化チタン（４．４４ｍｌ、４．４４ｍｍｏｌ）および化合物４（２ｇ、８．８８ｍｍｏｌ）を加え、室温で１８時間攪拌した。ジエチルエーテル（６０ｍｌ）を加え、室温で３０分間攪拌した。生じた固体をろ過で除去した後、溶媒を減圧除去し、化合物９（２．８ｇ、収率９６％）を得た。

工程２ 化合物１０の合成
－７８度の化合物９（２．８ｇ、８．５２ｍｍｏｌ）のエタノール（２８ｍｌ）溶液に、水素化ホウ素ナトリウム（０．１６ｇ、４．２６ｍｍｏｌ）を加え、－７８度で２時間撹拌した。飽和重曹水（２０ｍＬ）を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄した後、無水硫酸マグネシウムで乾燥した。溶媒を減圧留去し、得られた残渣をアミノシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物１０（２．１ｇ、収率７５％）を得た。
¹H-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).

工程３ 化合物１１の合成
化合物１０（１５７ｍｇ、０．４８ｍｍｏｌ）にメタノール（１．６ｍＬ）、ギ酸アンモニウム（１５０ｍｇ、２．３８ｍｍｏｌ）、および水酸化パラジウム炭素（４０ｍｇ、０．１４ｍｍｏｌ）を加え、６０度で１時間撹拌した。反応液をろ過して水酸化パラジウム炭素を除去した後、溶媒を減圧除去し、化合物１１（１０２ｍｇ、収率９５％）を得た。
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).

工程４ 化合物１２の合成
実施例１の工程２における１－メチルピペリジン４－アミンの代わりに、化合物１１（４９ｍｇ、０．２２ｍｍｏｌ）を用いることによって、化合物１２を得た。

工程５ 化合物１３の合成
実施例３の工程２における化合物５の代わりに化合物１２を用い、Ｎ－（４－イソブトキシベンジル）－１Ｈ－イミダゾール－１－カルボキサミドの代わりに化合物８を用いることによって化合物１３を得た。

工程６ 化合物１４の合成
実施例３の工程３における化合物６の代わりに化合物１３を用いることによって化合物１４を得た。

工程７ Ｉ－１２０の合成
実施例３の工程４における化合物（Ｉ－０５１）の代わりに化合物１４を用いることによって化合物（Ｉ－１２０）（３８ｍｇ、４工程総収率５３％）を得た。 Synthesis of compound (I-120)

Step 1 Synthesis of Compound 9 Under ice-cooling, (S)-1-phenethyl-1-amine (1.29 g, 10.7 mmol), 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) were added and stirred at room temperature for 18 hours. Diethyl ether (60 ml) was added and stirred at room temperature for 30 minutes. After removing the resulting solid by filtration, the solvent was removed under reduced pressure to give compound 9 (2.8 g, 96% yield).

Step 2 Synthesis of compound 10 Sodium borohydride (0.16 g, 4.26 mmol) was added to an ethanol (28 ml) solution of compound 9 (2.8 g, 8.52 mmol) at -78 degrees, and Stirred for an hour. Saturated sodium bicarbonate water (20 mL) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by amino silica gel column chromatography (hexane-ethyl acetate) to obtain compound 10 (2.1 g, yield 75%).
¹ H-NMR (CDCl ₃ ) 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 = 4.3Hz, 4H).

Step 3 Synthesis of compound 11 Methanol (1.6 mL), ammonium formate (150 mg, 2.38 mmol), and palladium hydroxide on carbon (40 mg, 0.14 mmol) were added to compound 10 (157 mg, 0.48 mmol), and the mixture was heated to 60°C. and stirred for 1 hour. After removing the palladium hydroxide carbon by filtering the reaction solution, the solvent was removed under reduced pressure to obtain compound 11 (102 mg, yield 95%).
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 substituting Compound 11 (49 mg, 0.22 mmol) for 1-methylpiperidin-4-amine in Step 2 of Example 1.

Step 5 Synthesis of Compound 13 Compound 13 was synthesized by substituting compound 12 for compound 5 and compound 8 for N-(4-isobutoxybenzyl)-1H-imidazole-1-carboxamide in step 2 of Example 3. 13 was obtained.

Step 6 Synthesis of Compound 14 Compound 14 was obtained by substituting compound 13 for compound 6 in step 3 of example 3.

Step 7 Synthesis of I-120 Compound (I-120) (38 mg, 53% overall yield for 4 steps) was obtained by substituting compound 14 for compound (I-051) in step 4 of Example 3.

工程１ 化合物１６の合成
化合物１５（５００ｍｇ、３．０２ｍｍｏｌ）にエタノール（５ｍＬ）、アクリル酸メチル（０．０３ｍＬ、３．０２ｍｍｏｌ）およびトリエチルアミン（０．４２ｍＬ、３．０２ｍｍｏｌ）を加え、室温で４８時間撹拌した。溶媒を減圧留去し、化合物１６（６５４ｍｇ、収率１０１％）を粗生成物として得た。

工程２ 化合物１７の合成
化合物１６（６５４ｍｇ、３．０２ｍｍｏｌ）にメタノール（５ｍＬ）、３７％ホルムアルデヒド溶液（０．６７ｍＬ、９．０６ｍｍｏｌ）およびＮａＢＨ（ＯＡｃ）３（６１ｍｇ、０．２９ｍｍｏｌ）を加え、室温で１時間撹拌した。 飽和重曹水（５ｍＬ）を加え、室温で攪拌した。水を加え、クロロホルムで抽出した。有機層を飽和食塩水で洗浄した後、無水硫酸マグネシウムで乾燥した。溶媒を減圧留去し、化合物１７（６８７ｍｇ、収率９９％）を粗生成物として得た。

工程３ 化合物１８の合成
化合物１７（１９５ｍｇ、０．３６ｍｍｏｌ）にトルエン（７ｍＬ）、および２８％ナトリウムメトキシド溶液（２．２ｍＬ、８．８７ｍｍｏｌ）を加え、加熱還流で４時間撹拌した。溶媒を減圧留去した後、メタノール（３ｍＬ）および水（３ｍＬ）を加え、加熱還流で４時間撹拌した。反応液を水で希釈し、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄した後、無水硫酸マグネシウムで乾燥した。溶媒を減圧留去し化合物１８（４３２ｍｇ、収率１０５％）を粗生成物として得た。

工程４ 化合物１９の合成
化合物１８（１３２ｍｇ、０．９５ｍｍｏｌ）にジクロロメタン（５ｍＬ）、（５－フルオロピリジン－２－イル）メタンアミン（１２０ｍｇ、０．９５ｍｍｏｌ）、ＡｃＯＨ（０．０７ｍＬ、１．１４ｍｍｏｌ）、および ＮａＢＨ（ＯＡｃ）３（２４１ｍｇ、１．１４ｍｍｏｌ）を加え、室温で１時間撹拌した。飽和重曹水（５ｍＬ）を加え、室温で攪拌した。水を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄した後、無水硫酸マグネシウムで乾燥した。溶媒を減圧留去し、化合物１９（１５７ｍｇ、収率６７％）を粗生成物として得た。

工程５ 化合物（Ｉ－１３６）の合成
化合物１９（１８ｍｇ、０．０７ｍｍｏｌ）にアセトニトリル（０．２ｍＬ）、およびＮ－（４－イソブトキシベンジル）－１Ｈ－イミダゾール－１－カルボキサミド（２２ｍｇ、０．０８ｍｍｏｌ）を加え、８０度で１時間撹拌した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物（Ｉ－１３６）（２２ｍｇ、収率６７％）を得た。

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). Synthesis of compound (I-136)

Step 1 Synthesis of compound 16 Ethanol (5 mL), methyl acrylate (0.03 mL, 3.02 mmol) and triethylamine (0.42 mL, 3.02 mmol) were added to compound 15 (500 mg, 3.02 mmol) and Stirred for an hour. The solvent was distilled off under reduced pressure to obtain compound 16 (654 mg, yield 101%) as a crude product.

Step 2 Synthesis of compound 17 To compound 16 (654 mg, 3.02 mmol) was added methanol (5 mL), 37% formaldehyde solution (0.67 mL, 9.06 mmol) and NaBH(OAc)3 (61 mg, 0.29 mmol), Stir at room temperature for 1 hour. Saturated sodium bicarbonate water (5 mL) was added, and the mixture was stirred at room temperature. Water was added and extracted with chloroform. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain compound 17 (687 mg, yield 99%) as a crude product.

Step 3 Synthesis of compound 18 Toluene (7 mL) and 28% sodium methoxide solution (2.2 mL, 8.87 mmol) were added to compound 17 (195 mg, 0.36 mmol), and the mixture was heated under reflux with stirring for 4 hours. After distilling off the solvent under reduced pressure, methanol (3 mL) and water (3 mL) were added, and the mixture was stirred under reflux for 4 hours. The reaction was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain compound 18 (432 mg, yield 105%) as a crude product.

Step 4 Synthesis of compound 19 To compound 18 (132 mg, 0.95 mmol) was added dichloromethane (5 mL), (5-fluoropyridin-2-yl)methanamine (120 mg, 0.95 mmol), AcOH (0.07 mL, 1.14 mmol). , and NaBH(OAc)3 (241 mg, 1.14 mmol) were added and stirred at room temperature for 1 hour. Saturated sodium bicarbonate water (5 mL) was added, and the mixture was stirred at room temperature. Water was added and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain compound 19 (157 mg, yield 67%) as a crude product.

Step 5 Synthesis of Compound (I-136) Compound 19 (18 mg, 0.07 mmol) was treated with acetonitrile (0.2 mL) and N-(4-isobutoxybenzyl)-1H-imidazole-1-carboxamide (22 mg, 0.07 mmol). 08 mmol) was added and stirred at 80 degrees for 1 hour. The solvent was distilled off under reduced pressure, and the obtained 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).

工程１ 化合物２１の合成
化合物２０（３００ｍｇ、１．３７ｍｍｏｌ）にジクロロメタン（５ｍＬ）、１、５－ジメチルー１Ｈーピラゾールカルボアルデヒド（１７１ｍｇ、１．３７ｍｍｏｌ）、ＡｃＯＨ（０．３９ｍＬ、６．８７ｍｍｏｌ）、および ＮａＢＨ（ＯＡｃ）３（５８３ｍｇ、２．７５ｍｍｏｌ）を加え、室温で２時間撹拌した。飽和重曹水を加え、室温で攪拌した。水を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄した後、無水硫酸マグネシウムで乾燥した。溶媒を減圧留去し、得られた残渣をアミノシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物２１（３５９ｍｇ、収率８０％）を得た。
¹H-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).

工程２ 化合物２２の合成
化合物２１（１４２ｍｇ、０．４４ｍｍｏｌ）にアセトニトリル（３ｍＬ）、およびＮ－（４－ノルマルプロポキシベンジル）－１Ｈ－イミダゾール－１－カルボキサミド（１１３ｍｇ、０．４４ｍｍｏｌ）を加え、８０度で４時間撹拌した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物２２（１９５ｍｇ、収率８１％）を得た。
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).

工程３ 化合物２３の合成
化合物２２（８０ｍｇ、０．３６ｍｍｏｌ）にジクロロメタン（１ｍＬ）、２、６－ルチジン（０．０８ｍＬ、０．６９５ｍｍｏｌ）、およびトリメチルシリルトリフラート（０．０８ｍＬ、０．６９５ｍｍｏｌ）を加え、室温で１０分撹拌した。２０％炭酸カリウム水溶液（４ｍＬ）を加え、酢酸エチルで抽出した。溶媒を減圧留去し、得られた残渣をアミノシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物２３（５２ｍｇ、収率８０％）を得た。
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).

工程４ 化合物（Ｉ－１３９）の合成
化合物２３（３０ｍｇ、０．１９ｍｍｏｌ）にメタノール（１ｍＬ）、３７％ホルムアルデヒド液（０．０３ｍＬ、０．３６ｍｍｏｌ）、およびＮａＢＨ（ＯＡｃ）３（４５ｍｇ、０．２２ｍｍｏｌ）を加え、室温で１時間撹拌した。飽和重曹水を加え、室温で攪拌した。水を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄した後、無水硫酸マグネシウムで乾燥した。溶媒を減圧留去し、得られた残渣をアミノシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物（Ｉ－１３９）（２０ｍｇ、収率６６％）を得た。
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). Synthesis of compound (I-139)

Step 1 Synthesis of compound 21 To compound 20 (300 mg, 1.37 mmol) was added dichloromethane (5 mL), 1,5-dimethyl-1H-pyrazolecarbaldehyde (171 mg, 1.37 mmol), AcOH (0.39 mL, 6.87 mmol), and NaBH(OAc)3 (583 mg, 2.75 mmol) were added and stirred at room temperature for 2 hours. Saturated sodium bicarbonate water was added, and the mixture was stirred at room temperature. Water was added and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by amino silica gel column chromatography (hexane-ethyl acetate) to obtain compound 21 (359 mg, yield 80%).
¹ H-NMR (CDCl ₃ ) 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 Acetonitrile (3 mL) and N-(4-normal-propoxybenzyl)-1H-imidazole-1-carboxamide (113 mg, 0.44 mmol) were added to compound 21 (142 mg, 0.44 mmol). and stirred for 4 hours. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 22 (195 mg, yield 81%).
¹ H-NMR (CDCl ₃ ) 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 To compound 22 (80 mg, 0.36 mmol) was added 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. A 20% aqueous potassium carbonate solution (4 mL) was added, and the mixture was extracted with ethyl acetate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by amino silica gel column chromatography (hexane-ethyl acetate) to obtain compound 23 (52 mg, yield 80%).
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 = 8.5Hz).

Step 4 Synthesis of compound (I-139) To compound 23 (30 mg, 0.19 mmol) was added methanol (1 mL), 37% formaldehyde solution (0.03 mL, 0.36 mmol), and NaBH(OAc)3 (45 mg, 0.36 mmol). 22 mmol) was added and stirred at room temperature for 1 hour. Saturated sodium bicarbonate water was added, and the mixture was stirred at room temperature. Water was added and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by amino silica 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).

The following compounds were synthesized according to the above general synthetic method and the methods described in the examples. Structures and physical properties (LC/MS data) are shown in the table below.
In the structural formulas, "wedge" and "broken line" indicate the configuration. In particular, among compounds whose steric configuration is described, a compound whose steric configuration is described as "racemate" is a racemic compound whose relative steric configuration is specified.
In addition, among the compounds in which the bond forming the asymmetric carbon is indicated by a solid line, the compound in which "racemate" is indicated in the "steric" item is a racemic compound.
A compound described as "diastereo mixture" in the item "Stereo" is a diastereomeric mixture.

Biological test examples 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 has a serotonin 5-HT2A receptor antagonistic and/or inverse agonistic action and antagonizes the human serotonin 5-HT2A receptor. good.
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.

Test Example 1: 5-HT2A Receptor Binding Inhibition Test
(each experimental condition)
Cell membranes: 15 μg Jump-In HEK cell membranes (expressing human recombinant 5-HT2A receptor) per well
Assay buffer: NaCl 120 mmol/L, MgCl 2.6H ₂ O ₁ mmol/L, KCl 5 mmol/L, Tris-HCl 50 mmol/L containing 0.1% BSA and CaCl _{2 2} mmol/L (pH 7.4).
Radioactive ligand: [ ³ H]-Ketanserin at a final concentration of 3 nmol/L
Non-specific ligand: Serotonin HCl at a final concentration of 500 μmol/L
Kd values were calculated at different lots of cell membranes. 0.5 μL of 1 mmol/L of a compound for non-specific binding calculation dissolved in DMSO or DMSO was dispensed into a microplate in advance, and the cell membrane was diluted with an assay buffer. The radioactive ligand solution was serially diluted from 16 nM to 2-fold, and counts were confirmed with a liquid scintillator. 50 μL/well of the assay buffer containing the diluted cell membrane was dispensed into a microplate. After that, 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/LTris-HCl (pH 7.4) was dispensed onto the GF/B UniFilter plate and allowed to stand at 4° C. for 1 hour or longer. Filtration was then performed in a Cell harvester (PerkinElmer). 10 μL/well of the radioactive ligand solution was dispensed into empty wells of the GF/B UniFilter plate. After drying the GF/B UniFilter plate at room temperature, 50 μL/well of MicroScinti20 was dispensed onto the GF/B UniFilter plate and the plate was sealed. The GF/B UniFilter plate was left overnight at room temperature. The radioactivity of [ ³ H]-Ketanserin bound to the 5-HT2A receptor was measured using Microbeta2 (PerkinElmer) at a measurement time of 1 min/well. A saturation curve was drawn from the measured values, and the Kd value was calculated from the slope of the Scatchard plot.
(Binding test of compound according to the present invention)
0.5 μL of a compound solution dissolved in DMSO was previously dispensed into a microplate, and cell membranes and hot ligands were each diluted with an Assay buffer. After that, 50 μL/well of the assay buffer containing the diluted cell membrane was dispensed into the microplate. After that, 50 μL/well of the radioactive ligand solution was dispensed into the microplate, and the plate was sealed. After that, 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 the GF/B UniFilter plate and allowed to stand at 4° C. for 1 hour or longer. Filtration was then performed in a Cell harvester (PerkinElmer). After drying the GF/B UniFilter plate at room temperature, 50 μL/well of MicroScinti20 was dispensed onto the GF/B UniFilter plate and the plate was sealed. The GF/B UniFilter plate was left overnight at room temperature. The radioactivity of [ ³ H]-Ketanserin bound to 5-HT2A receptors was measured using Microbeta2 (PerkinElmer) at a measurement time of 1 min/well. Non-specific binding was calculated from the radioactivity of [ 3 H]-ketanserin in the presence of 500 μmol/L serotonin HCl without ligand labeling, and total binding was calculated from the radioactivity of [ ³ H]-Ketanserin in the absence of the compound of the present invention (vehicle). Ki values were finally calculated from the dose-response curves.
(The binding activity of the compound according to the present invention was calculated from the binding inhibition rate (%) below.)
Inhibition rate (%) = [1-(c-a)/(b-a)] x 100
a; Average cpm of non-specific binding
b; mean cpm of total binding
c; cpm in the presence of test compound
(result)
Evaluation results of the human serotonin 5-HT2A receptor binding activity of the compounds of the present invention are shown below. The Ki value is "A" when less than 10 nM, "B" when 10 nM or more and less than 100 nM, and "C" when 100 nM or more.
Compound I-009: 0.291 nM
Compound I-021: 0.858 nM
Compound I-037: 0.654 nM
Compound I-042: 1.15 nM
Compound I-043: 2.52 nM
Compound I-068: 6.52 nM
Compound I-071: 13.3 nM
Compound I-072: 219 nM
Compound I-075: 130 nM
Compound I-076: 62 nM
Compound I-082: 3.74 nM
Compound I-084: 5.61 nM
Compound I-085: 23.8 nM
Compound I-088: 25.7 nM
Compound I-102: 0.919 nM
Compound I-116: 1.45 nM
Compound I-124: 0.690 nM
Compound I-126: 1.92 nM
Compound I-129: 0.85 nM
Compound I-130: 15.3 nM
Compound I-134: 0.475 nM
Compound I-136: 8.02 nM
Compound I-139: 2.93 nM
Compound I-146: 1.94 nM
Compound I-147: 0.758 nM

Test Example 2: 5-HT2C Receptor Binding Inhibition Test
(each experimental condition)
Cell membranes: 0.5 μg Jump-In HEK cell membranes per well (expressing human recombinant 5-HT2C receptor)
Assay buffer: NaCl 120 mmol/L, MgCl 2.6H ₂ O ₁ mmol/L, KCl 5 mmol/L, Tris-HCl 50 mmol/L containing 0.1% BSA and CaCl _{2 2} mmol/L (pH 7.4).
Radioactive ligand: [ ³ H]-Mesulergine at a final concentration of 1 nmol/L
Non-specific ligand: final concentration 500 μmol Serotonin HCl
Kd values were calculated at different lots of cell membranes. 0.5 μL of 1 mmol/L of a compound for non-specific binding calculation dissolved in DMSO or DMSO was dispensed into a microplate in advance, and the cell membrane was diluted with an assay buffer. The radioactive ligand solution was serially diluted from 16 nM to 2-fold, and counts were confirmed with a liquid scintillator. 50 μL/well of the assay buffer containing the diluted cell membrane was dispensed into a microplate. After that, 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 the GF/B UniFilter plate and allowed to stand at 4° C. for 1 hour or longer. Filtration was then performed in a Cell harvester (PerkinElmer). 10 μL/well of the radioactive ligand solution was dispensed into empty wells of the GF/B UniFilter plate. After drying the GF/B UniFilter plate at room temperature, 50 μL/well of MicroScinti20 was dispensed onto the GF/B UniFilter plate and the plate was sealed. The GF/B UniFilter plate was left overnight at room temperature. The radioactivity of [ ³ H]-Ketanserin bound to the 5-HT2A receptor was measured using Microbeta2 (PerkinElmer) at a measurement time of 1 min/well. A saturation curve was drawn from the measured values, and the Kd value was calculated from the slope of the Scatchard plot.
(Binding test of compound according to the present invention)
0.5 μL of a compound solution dissolved in DMSO was previously dispensed into a microplate, and cell membranes and hot ligands were each diluted with an Assay buffer. After that, 50 μL/well of the assay buffer containing the diluted cell membrane was dispensed into the microplate. After that, 50 μL/well of the radioactive ligand solution was dispensed into the microplate, and the plate was sealed. After that, it was allowed 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 onto the GF/B UniFilter plate and allowed to stand at 4° C. for 1 hour or more. Filtration was then performed in a Cell harvester (PerkinElmer). After drying the GF/B UniFilter plate at room temperature, 50 μL/well of MicroScinti20 was dispensed onto the GF/B UniFilter plate and sealed. The GF/B UniFilter plate was left overnight at room temperature. The radioactivity of [ ³ H]-Mesulergine bound to the 5-HT2A receptor was measured using Microbeta2 (PerkinElmer) at a measurement time of 1 min/well. Non-specific binding was calculated from the radioactivity of [ 3 H]-Mesulergine in the presence of 500 μmol/L serotonin HCl without ligand labeling, and total binding was calculated from the radioactivity of [ ³ H]-Mesulergine in the absence of the compound of the present invention (vehicle). Ki values were finally calculated from the dose-response curves.
(The binding activity of the compound according to the present invention was calculated from the binding inhibition rate (%) below.)
Inhibition rate (%) = [1-(c-a)/(b-a)] x 100
a; Average cpm of non-specific binding
b; mean cpm of total binding
c; cpm in presence of test compound
(result)
Evaluation results of the human serotonin 5-HT2C receptor binding inhibitory activity of the compounds of the present invention are shown below. The Ki value is defined as "A" when less than 10 nM, "B" when 10 nM or more and less than 100 nM, and "C" when 100 nM or more.
Compound I-009: 7.92 nM
Compound I-021: 50.7 nM
Compound I-037: 28.2 nM
Compound I-042: 2.31 nM
Compound I-043: 55.7 nM
Compound I-068: 49.9 nM
Compound I-071: 60.7 nM
Compound I-072: 617 nM
Compound I-075: 1310 nM
Compound I-076: 263 nM
Compound I-082: 28.8 nM
Compound I-084: 65.2 nM
Compound I-085: 96.2 nM
Compound I-088: 134 nM
Compound I-102: 4.01 nM
Compound I-116: 12.2 nM
Compound I-124: 2.22 nM
Compound I-126: 1.09 nM
Compound I-129: 1.51 nM
Compound I-130: 348 nM
Compound I-134: 3.2 nM
Compound I-136: 148 nM
Compound I-139: 11.1 nM
Compound I-146: 4.96 nM
Compound I-147: 2.12 nM

Test Example 3: hERG test For the purpose of evaluating the electrocardiographic QT interval prolongation risk of the compounds according to the present invention, CHO cells expressing human ether-a-go-go related gene (hERG) channels were used to test the ventricular repolarization process. The effects of compounds according to the present invention on the delayed rectifier K ⁺ current (I _Kr ), which plays an important role in
Using a fully automated patch clamp system (QPatch; Sophion Bioscience A/S), cells were held at a membrane potential of −80 mV by the whole-cell patch clamp method, and a leak potential of −50 mV was applied, followed by +20 mV depolarization stimulation. was applied for 2 seconds, and the I _Kr evoked when a repolarizing stimulus of -50 mV was applied for 2 seconds was recorded. Extracellular solution adjusted to 0.1% dimethyl sulfoxide (NaCl: 145 mmol/L, KCl: 4 mmol/L, CaCl ₂ : 2 mmol/L, MgCl ₂ : 1 mmol/L, glucose: 10 mmol/L , HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid): 10 mmol/L, pH = 7.4), and Each extracellular solution in which the compound according to the invention was dissolved at a desired concentration was applied to the cells for 15 minutes or more under room temperature conditions. From the obtained _IKr , analysis software (QPatch Assay software; Sophion Bioscience A/S) was used to measure the absolute value of the maximum tail current based on the current value at the retained membrane potential. By calculating the maximum tail current after application of the compound of the present invention relative to the maximum tail current after application of the vehicle as the inhibition rate, and further correcting using the inhibition rate result of the negative control, the I _Kr of the compound of the present invention evaluated the impact on
(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%

Test Example 4: BA test Examination of oral absorbability Experimental materials and methods (1) Animal used: Mice or rats are used.
(2) Breeding conditions: Mice or rats are given solid feed and sterilized tap water ad libitum.
(3) Dose and setting of grouping: Oral and intravenous administration at a predetermined dose. Set up the group as follows. (Dosage may be changed for each 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 liquid: Oral administration is administered as a solution or suspension. Intravenous administration is administered after solubilization.
(5) Administration method: Oral administration is forcibly administered into the stomach using an oral probe. Intravenous administration is administered through the tail vein using a syringe with an injection needle.
(6) Evaluation item: Blood is collected over time, and the plasma concentration of the compound according to the present invention is measured using LC/MS/MS.
(7) Statistical analysis: For the transition of the concentration of the compound according to the present invention in plasma, the plasma concentration-area under the time curve (AUC) was calculated by the moment analysis method, and the dose ratio and AUC of the oral administration group and the intravenous administration group were calculated. The bioavailability (BA) of the compounds according to the invention is calculated from the ratio.
Note that the dilution concentration and dilution solvent are changed as necessary.

Test Example 5: Clearance Evaluation Test Experimental Materials and Methods (1) Animal used: SD rats are used.
(2) Breeding conditions: SD rats are given solid food and sterilized tap water ad libitum.
(3) Dose and setting of grouping: Intravenous administration was administered at a predetermined dose. Set up the group as follows.
Intravenous administration 1 μmol/kg (n=2)
(4) Preparation of administration solution: Solubilize with a solvent of dimethyl sulfoxide/propylene glycol = 1/1 and administer.
(5) Administration method: Administer through the tail vein using a syringe with an injection needle.
(6) Evaluation item: Blood is collected over time, and the plasma concentration of the compound according to the present invention is measured using LC/MS/MS.
(7) Statistical analysis: The total body clearance (CLtot) is calculated by the moment analysis method for the transition of the concentration of the compound of the present invention in plasma. Note that the dilution concentration and dilution solvent are changed as necessary.

Test Example 6: Metabolic Stability Test Commercially available pooled human liver microsomes and the compound according to the present invention were reacted for a certain period of time, the residual rate was calculated by comparing the reacted sample and the unreacted sample, and the compound according to the present invention was metabolized in the liver. Evaluate the extent to which

In 0.2 mL of buffer (50 mmol/L Tris-HCl pH 7.4, 150 mmol/L potassium chloride, 10 mmol/L magnesium chloride) containing 0.5 mg protein/mL human liver microsomes, in the presence of 1 mmol/L NADPH. React at 37° C. for 0 or 30 minutes (oxidative reaction). 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 centrifugal supernatant is quantified by LC/MS/MS or solid phase extraction (SPE)/MS, and the compound according to the present invention after reaction is taken as 100% at the time of 0 minute reaction. Calculate the remaining amount of

Test Example 7: P-gp Substrate Test A compound of the present invention is added to one side of Transwell (registered trademark, CORNING) in which human MDR1-expressing cells or parental cells are monolayer-cultured, and allowed to react for a certain period of time. For the MDR1-expressing cells and the parent cells, the membrane permeability coefficients in the Apical side to the Basolateral direction (A → B) and the Basolateral side to the Apical direction (B → A) were calculated, and the Efflux Ratio (ER; Calculate the ratio of the membrane permeability coefficients of B→A and A→B. Efflux ratios (ER values) of MDR1-expressing cells and parental cells are compared to determine whether compounds of the present invention are P-gp substrates.

Test Example 8: MK801-induced Hyperlocomotion Suppression Test Male Wistar rats aged 6-10 weeks were used. 30 mmol/L HCl was used as a solvent to prepare the administration solution of the test compound, and physiological saline was used as the solvent to prepare the administration solution of MK801. Suppression test of MK801-induced hyperlocomotion SCANET manufactured by Melquest, data acquisition program SCL-40, and transparent plastic cages were used as follows.
In the breeding room, the compound administration solution (solvent or test compound solution) was administered subcutaneously and returned to the breeding cage. Thirty minutes later, animals were brought into the laboratory and laboratory habituation was performed. After 15 minutes, the rat was gently taken out, an MK801 administration solution (solvent or MK801 solution) was administered intraperitoneally, and returned to the breeding cage. Fifteen minutes after intraperitoneal administration, the rats were taken out and gently placed in the SCANET to start the locomotion measurement. The measurement was terminated 30 minutes after the start of the measurement, and the exercise amount of each individual for 30 minutes was totaled.
Analysis of the test results was performed as follows.
A Student-T Test (significance level: 5% on both sides) was performed on the test compound-administered group and the solvent-administered group. When the test compound-administered group showed significant suppression of locomotion compared to the vehicle-administered group, it was judged to have an antipsychotic effect.
The results of the above tests when Example compounds I-008, I-102, I-126, and I-139 were administered are shown in Figures 1-4. ● in the figure indicates the total locomotor activity of rats administered with a solvent, and ▪ indicates the total locomotor activity of rats administered with the compound of the present invention.

The formulation examples shown below are merely illustrative and are not intended to limit the scope of the invention in any way.
The compounds of the invention can be administered topically by any conventional route, especially enterally, e.g. orally, e.g. in the form of tablets or capsules, or parenterally, e.g. in the form of injection solutions or suspensions. For example, it can be administered as a pharmaceutical composition in the form of lotions, gels, ointments or creams, or in nasal or suppository form. A pharmaceutical composition comprising a compound of the invention in free form or in pharmaceutically acceptable salt form together with at least one pharmaceutically acceptable carrier or diluent can be prepared by mixing, mixing, It can be manufactured by a granulation or coating method. For example, oral compositions can be tablets, granules, capsules containing excipients, disintegrants, binders, lubricants, etc. and active ingredients. Injectable compositions may be in the form of solutions or suspensions, may be sterilized, and may contain preservatives, stabilizers, buffers and the like.

The compounds according to the present invention have serotonin 5-HT2A receptor antagonistic and/or inverse agonistic activity and are considered to be useful as therapeutic and/or prophylactic agents for diseases or conditions involving serotonin 5-HT2A receptors. be done.

Claims (18)

Formula (I):

(In the formula,
R ¹ is a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group;
each R ² is independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
each R ³ is independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
n is 1 or 2;
R ⁴ is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group;
L is -NR ⁸ -, -O- or a single bond;
R ⁸ is a hydrogen atom or substituted or unsubstituted alkyl;
each ^R5 is independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
each R ⁶ is independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
p is 1 or 2;
R ⁷ has the formula:

(In the formula,
R ⁹ is a hydrogen atom, halogen, substituted or unsubstituted alkyloxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted amino, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted alkenyl or substituted or unsubstituted alkyl;
R ¹⁰ is a hydrogen atom, hydroxy, halogen or substituted or unsubstituted alkyl; or
R ⁹ and R ¹⁰ together form a substituted or unsubstituted non-aromatic heterocyclic ring;
R ¹¹ is halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
m is a group represented by 0 or 1) (excluding the following compounds (i) and (ii):
(i) compounds wherein L is a single bond and R ¹ is substituted or unsubstituted furyl or substituted or unsubstituted thienyl;
(ii) a compound wherein L is —NR ⁸ — and R ¹ is a substituted or unsubstituted 2,3-dihydrobenzofuryl) or a pharmaceutically acceptable salt thereof. Antagonistic and/or inverse agonist compositions. R ¹ is a substituted or unsubstituted aromatic heterocyclic group;
The composition for serotonin 5-HT2A receptor antagonistic and/or inverse agonistic action according to claim 1, comprising a compound or a pharmaceutically acceptable salt thereof, wherein L is -NR ⁸ - or -O-. 3. The composition for serotonin 5-HT2A receptor antagonistic and/or inverse agonistic action according to claim 1 or 2, which is a pharmaceutical composition. Formula (II):

(In the formula,
R ¹ is a substituted or unsubstituted aromatic heterocyclic group;
each R ² is independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
each R ³ is independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
n is 1 or 2;
R ⁴ is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group;
R ⁸ is a hydrogen atom or substituted or unsubstituted alkyl;
^R5 is a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
R ⁶ is a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
R ⁷ has the formula:

(In the formula,
R ⁹ is substituted or unsubstituted alkyloxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted amino, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted alkenyl or substituted or unsubstituted alkyl;
R ¹⁰ is a hydrogen atom, halogen or substituted or unsubstituted alkyl; or
R ⁹ and R ¹⁰ together form a substituted or unsubstituted non-aromatic heterocyclic ring;
R ¹¹ is halogen, hydroxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy;
m is a group represented by 0 or 1) (provided that the compounds shown below:

) or a pharmaceutically acceptable salt thereof. 5. A pharmaceutical composition containing the compound or a pharmaceutically acceptable salt thereof according to claim 4, wherein ^R1 is a substituted or unsubstituted aromatic nitrogen-containing heterocyclic group. The compound according to claim 4, wherein R ¹ is a substituted or unsubstituted 6-membered aromatic nitrogen-containing heterocyclic group or a substituted or unsubstituted 5-membered aromatic nitrogen-containing heterocyclic group, or a pharmaceutically acceptable compound thereof A pharmaceutical composition containing a salt. A pharmaceutical composition containing the compound or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 6, wherein R ² and R ³ are hydrogen atoms. A pharmaceutical composition comprising the compound according to any one of claims 4 to 7, wherein n is 1, or a pharmaceutically acceptable salt thereof. A pharmaceutical composition containing the compound or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 8, wherein R ⁴ is a substituted or unsubstituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic group. thing. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 9, wherein ^R4 is substituted or unsubstituted piperidinyl. ^R4 is of the formula:

(In the formula,
R ²¹ is a hydrogen atom or substituted or unsubstituted alkyl;
R ²² is a hydrogen atom, halogen or substituted or unsubstituted alkyl;
R ²³ is a hydrogen atom, halogen or substituted or unsubstituted alkyl; or
together with the carbon atoms to which R ²² and R ²³ are attached form a substituted or unsubstituted non-aromatic carbocyclic ring), or A pharmaceutical composition containing a pharmaceutically acceptable salt thereof. ^R4 is of the formula:

(wherein R ²¹ , R ²² and R ²³ are as defined in claim 11), or a pharmaceutically acceptable salt thereof according to claim 11. R ²² is halogen or substituted or unsubstituted alkyl;
R ²³ is a hydrogen atom, halogen or substituted or unsubstituted alkyl; or
13. The compound or a pharmaceutically acceptable salt thereof according to claim 11 or 12, which together with the carbon atoms to which ^R22 and ^R23 are attached form a substituted or unsubstituted non-aromatic carbocyclic ring. pharmaceutical composition. A pharmaceutical composition containing the compound or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 13, wherein R ⁸ is a hydrogen atom. A pharmaceutical composition containing the compound or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 14, wherein R ⁵ and R ⁶ are hydrogen atoms. R ⁷ has the formula:

A pharmaceutical composition containing the compound of any one of claims 4 to 15 or a pharmaceutically acceptable salt thereof, which is a group represented by (wherein R ⁹ is substituted or unsubstituted alkyloxy) thing. 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, a pharmaceutical composition containing the compound according to claim 4 or a pharmaceutically acceptable salt thereof, thing. The pharmaceutical composition according to any one of claims 4 to 17, which is a serotonin 5-HT2A receptor antagonist and/or inverse agonist.

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