Bicyclic heterocyclic derivative having viral growth inhibitory activity and pharmaceutical composition containing same

Abstract

The present invention provides: a compound having coronavirus 3CL protease inhibitory activity or a pharmaceutically acceptable salt thereof; and a pharmaceutical composition containing same. Provided is a compound represented by formula (I) (in the formula, each of carbon atom a and carbon atom b is a carbon atom constituting ring A, ring A is a substituted aromatic carbon ring or the like, R1 is a substituted or unsubstituted aromatic heterocyclic group or the like, R2 is a substituted or unsubstituted 6-membered aromatic carbon ring group or the like, m is 1 or the like, R5a is each independently a hydrogen atom or the like, R5b is each independently a hydrogen atom or the like, n is 1 or the like, R4a is a hydrogen atom or the like, and R4b is a hydrogen atom or the like), or a pharmaceutically acceptable salt thereof.

Description

Bicyclic heterocyclic derivatives having virus growth inhibitory activity and pharmaceutical compositions containing them

[0001] The present invention relates to compounds that exhibit coronavirus 3 CL protease inhibitory activity, and pharmaceutical compositions containing compounds that exhibit coronavirus 3 CL protease inhibitory activity.

[0002] Coronaviruses, which belong to the Orthocoronavirus subfamily of the Coronaviridae family of the Nidovirales order, have a genome size of approximately 30 kilobases and are among the largest single-stranded positive-strand RNA viruses known. Coronaviruses are classified into four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. Seven types of coronaviruses that infect humans are known: two types in the Alphacoronavirus genus (HCoV-229E and HCoV-NL63) and five types in the Betacoronavirus genus (HCoV-HKU1, HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2). Of these, four (HCoV-229E, HCoV-NL63, HCoV-HKU1, and HCoV-OC43) are pathogens that cause the common cold, while the remaining three are severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV), and novel coronavirus (SARS-CoV-2), which cause severe pneumonia.

[0003] The novel coronavirus disease (COVID-19) that broke out in Wuhan, China in December 2019, rapidly spread internationally, and on March 11, 2020, the WHO declared it a pandemic. As of September 6, 2022, the number of confirmed cases had reached over 600 million, with over 6.5 million deaths (Non-Patent Document 1). The main routes of SARS-CoV-2 transmission have been reported to be droplet transmission, contact transmission, and aerosol transmission. SARS-CoV-2 has been confirmed to remain airborne with aerosols for approximately three hours, maintaining its infectiousness (Non-Patent Document 2). The incubation period is approximately 2 to 14 days, and typical cold-like symptoms include fever (87.9%), dry cough (67.7%), fatigue (38.1%), and phlegm (33.4%) (Non-Patent Document 3). In severe cases, respiratory failure due to acute respiratory distress syndrome, acute lung injury, interstitial pneumonia, etc. occurs. Multiple organ failure, including renal and hepatic failure, has also been reported.

[0004] In Japan, through drug repositioning of existing drugs, the antiviral drug remdesivir, the anti-inflammatory drug dexamethasone, and the rheumatism drug baricitinib have been approved as treatments for COVID-19, with the anti-IL-6 receptor antibody tocilizumab receiving additional approval in January 2022. Additionally, the antibody cocktail therapy Lonaprive (casirivimab / imdevimab) received special approval in July 2021, sotrolvimab in September 2021, molnupiravir in December 2021, and Evasheld (tixagevimab / silgavimab) in August 2022. However, some of these drugs are not clinically used in some cases due to drug interactions or contraindications for pregnant women, and the development of new therapeutic options is eagerly awaited.

[0005] Upon infecting cells, coronaviruses synthesize two polyproteins. These polyproteins contain the replication complex that creates the viral genome and two proteases. Proteases cleave the polyproteins synthesized by the virus, playing an essential role in enabling each protein to function. Of the two proteases, the 3CL protease (main protease) is responsible for most of the polyprotein cleavage (Non-Patent Document 4). In June 2021, the completion of a Phase 1b trial of Pfizer's Lufotrelvir (PF-07304814), a prodrug of PF-00835231, a COVID-19 treatment targeting 3CL protease, was published in ClinicalTrials.gov (NCT04535167). In addition, in March 2021, Pfizer announced the initiation of Phase 1 trials for PF-07321332, a therapeutic drug for COVID-19. The structural formulas of PF-00835231, Lufotrelvir, and PF-07321332 are shown below, and have different chemical structures from the compounds of the present invention (Non-Patent Documents 5, 10, and 11, and Patent Documents 1 and 2). PF-00835231: Lufotrelvir (PF-07304814): PF-07321332: In December 2021, PAXLOVID™ was granted emergency use authorization in the United States, and on February 10, 2022, PAXLOVID® Pak was granted special approval in Japan.

[0006] Additionally, in August 2021, the start of Phase 1 trials of PBI-0451 by Pardes Biosciences, a COVID-19 treatment targeting 3CL protease, was published in ClinicalTrials.gov (NCT05011812). The structural formula of PBI-0451 is shown below, and its chemical structure is different from that of the compound of the present invention (Non-Patent Document 12).

[0007] There is insufficient evidence regarding resistance mutations to COVID-19 drugs targeting 3CL proteases.

[0008] Compounds having 3CL protease inhibitory activity are disclosed in Non-Patent Documents 5 to 8 and 13 to 16, but none of these documents describe or suggest compounds related to the present invention. ３ Derivatives having receptor inhibitory activity are disclosed in Patent Document 1, but 3CL protease inhibitory activity and antiviral effects are neither described nor suggested. Furthermore, Non-Patent Document 9 and Patent Documents 2 and 5 to 8 describe compounds having a similar structure to the compound of the present invention, but 3CL protease inhibitory activity and antiviral effects are neither described nor suggested.

[0009] International Publication No. 2012 / 020742 International Publication No. 2018 / 107112 International Publication No. 2021 / 205298 International Publication No. 2021 / 250648 International Publication No. 2015 / 003879 International Publication No. 2020 / 261114 U.S. Patent No. 6,242,452 Specification JP 2002-308774 A

[0010] “COVID-19 Dashboard by the Center for Systems Science and Engineering at Johns Hopkins University,” [online], Johns Hopkins University, [Retrieved September 6, 2022], Internet<URL:https: / / coronavirus.jhu.edu / map.html> The New England Journal of Medicine (2020), Vol. 382, ​​pp. 1564-1567, "Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19)", [online], February 28, 2020, WHO, [Retrieved February 8, 2021], Internet <URL:https: / / www.who.int / docs / default-source / coronaviruse / who-china-joint-mission-on-covid-19-final-report.pdf> Science (2003), Vol. 300, pp. 1763-1767, "A comparative analysis of SARS-CoV-2 antivirals characterizes 3CLpro inhibitor PF-00835231 as a potential new treatment for COVID-19," Journal of Virology, [online], April 26, 2021, [retrieved February 15, 2022], Internet <URL: https: / / journals.asm.org / doi / 10.1128 / JVI.01819-20><doi: 10.1128 / JVI.01819-20>Cell Research (2020), Vol. 30, pp. 678-692 Science (2020), Vol. 368, pp. 409-412 ACS Central Science (2021), Vol. 7, No. 3, pp. 467-475 European Journal of Medicinal Chemistry (2019), Vol. 172, pp. 109-130 261st Am Chem Soc (ACS) Natl Meet ・ 2021-04-05 / 2021-04-16 Virtual, Abst 243Science (2021), Vol. 374, pp. 1586-1593 "Discovery and Development of PBI-0451", [online], March 24, 2022, 35th International Conference on Antiviral Research (ICAR), [Retrieved April 5, 2022], Internet <URL: https: / / ir.pardesbio.com / static-files / fc7c4f8c-e0bd-4b97-8c9c-eff09bafd4db> Molecules (2020), Vol. 25, p. 3193 Molecules (2020), Vol. 25, p. 3920 European Journal of Medicinal Chemistry (2020), Vol. 206, p. 112711 Journal of the American Chemical Society (2022), Vol. 144, pp. 2905-2920.

[0011] An object of the present invention is to provide a compound having coronavirus 3CL protease inhibitory activity. Preferably, the present invention provides a compound having antiviral activity, particularly an activity of inhibiting coronavirus proliferation, and a pharmaceutical containing the compound.

[0012] The present invention relates to: (1''') a compound of formula (I): (In the formula, carbon atom a and carbon atom b are carbon atoms constituting ring A; ring A is (Wherein, carbon atom a represents carbon atom a in formula (I); carbon atom b represents carbon atom b in formula (I); R３ａ is a hydrogen atom, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted alkyloxy, a substituted amino, a halogen atom, a substituted or unsubstituted carbamoyl, a substituted or unsubstituted sulfamoyl, a substituted or unsubstituted non-aromatic carbocyclic oxy or a substituted or unsubstituted non-aromatic heterocyclic oxy; R ３ｂ and R ３ｂ’ are each independently a hydrogen atom, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted alkyloxy, a substituted amino, a halogen atom, a cyano, a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted carbamoyl, a substituted or unsubstituted sulfamoyl, a substituted or unsubstituted non-aromatic carbocyclic oxy, or a substituted or unsubstituted non-aromatic heterocyclic oxy; R ８ and R ８’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; or ３ａ and R ８ and R ３ｂ and R ８ may form, together with the carbon atom to which they are attached, a substituted or unsubstituted aromatic carbocyclic ring or a substituted or unsubstituted aromatic heterocyclic ring; R ６ is a hydrogen atom, halogen, substituted or unsubstituted alkyloxy, hydroxy or cyano; R ７ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted amino, substituted or unsubstituted alkylsulfoxy, substituted or unsubstituted carbamoyl, hydroxy, carboxy, formyl or cyano; R ７’ and R ９’are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３ｂ and R ７’ may be taken together with the atom to which they are attached to form a substituted or unsubstituted non-aromatic heterocycle; R ９ are each independently halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; s is 0, 1, or 2; and p is 1, 2, or 3; R １ is a substituted or unsubstituted nitrogen-containing aromatic heterocyclic group, a substituted or unsubstituted nitrogen-containing non-aromatic heterocyclic group, or a substituted or unsubstituted carbamoyl; R ２ is a substituted or unsubstituted 6-membered aromatic carbocyclic group or a substituted or unsubstituted 6-membered aromatic heterocyclic group; n is 0 or 1; R ４ａ is a hydrogen atom or a substituted or unsubstituted alkyl; R ４ｂ is a hydrogen atom or a substituted or unsubstituted alkyl; or R ４ａ and R ４ｂ may be taken together with the carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; m is 0, 1 or 2; R ５ａ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ５ｂ are each independently a hydrogen atom or a substituted or unsubstituted alkyl) １ is a substituted or unsubstituted carbamoyl, and R ３ａ and R ３ｂ (2''') a compound in which ring A is: (Wherein, carbon atom a, carbon atom b, R ３ａ , R ３ｂ , R ６ , R ７ , R ７’ , R ８ , R ９ , R ９’, s and p are as defined in the above item (1'"), or a pharmaceutically acceptable salt thereof. ３ａ and R ３ｂ are each independently (Wherein, Y is CR １０ｈ R １０ｈ’ or O; t is an integer from 0 to 5; R １０ａ are each independently halogen, cyano, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted sulfoximino, or substituted or unsubstituted iminosulfino; or two R bonded to adjacent carbon atoms １０ａ may be taken together to form a substituted or unsubstituted aromatic heterocycle or a substituted or unsubstituted non-aromatic heterocycle; R １０ｂ , R １０ｂ’ , R １０ｃ , R １０ｃ’ , R １０ｄ , R １０ｄ’ , R １０ｅ , R １０ｅ’ , R １０ｆ , R １０ｆ’ , R １０ｇ , R １０ｇ’ , R １０ｈ , R １０ｈ’ , R １０ｉ , R １０ｉ’ , R １０ｊ and R １０ｊ’ are each independently a hydrogen atom, hydroxy, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyloxycarbonyl, or substituted or unsubstituted aromatic heterocyclic group; R １０ｂ and R１０ｂ’ , R １０ｃ and R １０ｃ’ , R １０ｄ and R １０ｄ’ , R １０ｅ and R １０ｅ’ , R １０ｆ and R １０ｆ’ , R １０ｇ and R １０ｇ’ , R １０ｈ and R １０ｈ’ , R １０ｉ and R １０ｉ’ , and R １０ｊ and R １０ｊ’ may each independently form, together with the carbon atom to which it is attached, oxo, a substituted or unsubstituted non-aromatic carbocyclic ring, or a substituted or unsubstituted non-aromatic heterocyclic ring; R １０ｂ and R １０ｃ , R １０ｃ and R １０ｄ , R １０ｄ and R １０ｅ , R １０ｆ and R １０ｇ , R １０ｇ and R １０ｈ , R １０ｈ and R １０ｉ , and R １０ｉ and R １０ｊ may each independently form, together with the carbon atom to which it is attached, a substituted or unsubstituted non-aromatic heterocycle, a substituted or unsubstituted aromatic carbocycle, or a substituted or unsubstituted non-aromatic carbocycle; R １０ｂ and R １０ｄ , R １０ｂ and R １０ｅ , R １０ｃ and R １０ｅ , R １０ｆ and R １０ｈ , R １０ｆ and R １０ｉ , R １０ｆ and R １０ｊ , R １０ｇ and R １０ｉ , R １０ｇ and R １０ｊare each independently taken together to form a (C1-C4) bridge, one of the carbon atoms constituting the bridge may be replaced by an oxygen atom or a nitrogen atom; and the carbon atoms constituting the bridge are each independently R ａ and the nitrogen atom constituting the bridge is substituted with a substituent selected from R ｂ and R is substituted with a substituent selected from ａ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ｂ (4''') R is a group represented by the formula (I) or (II), or a pharmaceutically acceptable salt thereof. ２ is a 6-membered aromatic carbocyclic group substituted with one halogen and further substituted with 1, 2, 3 or 4 substituents selected from substituent group G, or a 6-membered aromatic heterocyclic group substituted with one halogen and further substituted with 1 or 2 substituents selected from substituent group G; and substituent group G is the group consisting of halogen, cyano, alkyl, alkenyl, alkynyl, haloalkyl, alkyloxy, alkenyloxy, alkynyloxy and haloalkyloxy, or a pharmaceutically acceptable salt thereof. (5''') R ２ is a 6-membered aromatic carbocyclic group substituted with one halogen and further substituted with 1, 2, 3 or 4 substituents selected from Substituent Group G (same as in item (4''') above), or a pharmaceutically acceptable salt thereof. １ (7''') The compound according to any one of the above items (1''') to (5'''), wherein is a substituted or unsubstituted nitrogen-containing aromatic heterocyclic group or a substituted or unsubstituted nitrogen-containing non-aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. (Wherein, carbon atom a, carbon atom b, R ３ａ , R ３ｂ , R ６ , R ７ , R ７’, R ８ , R ９ and s is the same as defined in the above item (1'")), or a pharmaceutically acceptable salt thereof. (8'") The compound according to any one of the above items (1'") to (6'"), wherein ring A is (Wherein, carbon atom a, carbon atom b, R ３ａ , R ６ and R ８ is the same as in item (1'''); R ７ (9''') The compound according to any one of the above items (1''') to (7'''), wherein ring A is a ring represented by the formula: (Wherein, carbon atom a, carbon atom b, R ３ｂ , R ６ , R ７ , R ７’ and R ８ is the same as the ring represented by the above item (1'")), or a pharmaceutically acceptable salt thereof. (10''') The compound according to any one of the above items (1''') to (9'''), or a pharmaceutically acceptable salt thereof, wherein m is 0 or 1. (11''') R ５ａ are each independently a hydrogen atom, and R ５ｂ (12'") R is a compound according to any one of the above items (1'") to (10'", or a pharmaceutically acceptable salt thereof, wherein R ６ (13'") R is a halogen atom, a substituted or unsubstituted alkyloxy atom, or a pharmaceutically acceptable salt thereof. ４ａ is a hydrogen atom, and R ４ｂis a hydrogen atom. (14''') The compound according to the above item (1''') or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of compounds I-0174, I-0414, I-0417, I-0437, I-0699, I-0934, I-0955, I-0957, I-0978, I-0990 and I-1005. (15''') A pharmaceutical composition comprising a compound according to any one of the above items (1''') to (14''') or a pharmaceutically acceptable salt thereof. (16''') A coronavirus 3CL protease inhibitor comprising a compound according to any one of the above items (1''') to (14''') or a pharmaceutically acceptable salt thereof. (17''') A coronavirus proliferation inhibitor comprising the compound according to any one of the above items (1''') to (14''') or a pharmaceutically acceptable salt thereof. (18''') A coronavirus proliferation inhibitor according to the above item (17'''), wherein the coronavirus is an alphacoronavirus and / or a betacoronavirus. (19''') A coronavirus proliferation inhibitor according to the above item (17'''), wherein the coronavirus is SARS-CoV-2.

[0013] The present invention also relates to the following: (1'') Formula (I): (In the formula, carbon atom a and carbon atom b are carbon atoms constituting ring A; ring A is (Wherein, carbon atom a represents carbon atom a in formula (I); carbon atom b represents carbon atom b in formula (I); R ３ａ is a hydrogen atom, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted alkyloxy, a substituted amino, a halogen atom, a substituted or unsubstituted carbamoyl, a substituted or unsubstituted sulfamoyl, a substituted or unsubstituted non-aromatic carbocyclic oxy or a substituted or unsubstituted non-aromatic heterocyclic oxy; R ３ｂ and R ３ｂ’are each independently a hydrogen atom, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted alkyloxy, a substituted amino, a halogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted carbamoyl, a substituted or unsubstituted sulfamoyl, a substituted or unsubstituted non-aromatic carbocyclic oxy, or a substituted or unsubstituted non-aromatic heterocyclic oxy; R ８ and R ８’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; or ３ａ and R ８ and R ３ｂ and R ８ may form, together with the carbon atom to which they are attached, a substituted or unsubstituted aromatic carbocyclic ring or a substituted or unsubstituted aromatic heterocyclic ring; R ６ is a hydrogen atom, halogen, substituted or unsubstituted alkyloxy, hydroxy or cyano; R ７ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted non-aromatic carbocycle, substituted or unsubstituted non-aromatic heterocycle, substituted or unsubstituted non-aromatic carbocycleoxy, substituted or unsubstituted amino, substituted or unsubstituted alkylsulfoxy, substituted or unsubstituted carbamoyl, hydroxy, carboxy, formyl or cyano; R ７’ and R ９’ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３ｂ and R ７’ may be taken together with the atom to which they are attached to form a substituted or unsubstituted non-aromatic heterocycle; R ９ is halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; s is 0, 1, or 2; p is 1, 2, or 3) of the ring represented by the formula; R １is a substituted or unsubstituted nitrogen-containing aromatic heterocyclic group, a substituted or unsubstituted nitrogen-containing non-aromatic heterocyclic group, or a substituted or unsubstituted carbamoyl; R ２ is a substituted or unsubstituted 6-membered aromatic carbocyclic group or a substituted or unsubstituted 6-membered aromatic heterocyclic group; n is 0 or 1; R ４ａ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ４ｂ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; or R ４ａ and R ４ｂ may be taken together with the carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; m is 0, 1 or 2; R ５ａ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ５ｂ are each independently a hydrogen atom or a substituted or unsubstituted alkyl) (wherein R １ is a substituted or unsubstituted carbamoyl, and R ３ａ and R ３ｂ (2'') A compound in which ring A is: (Wherein, carbon atom a, carbon atom b, R ３ａ , R ３ｂ , R ６ , R ７ , R ７’ , R ８ , R ９ , R ９’ (3'') R is a ring represented by the formula (1'', or a pharmaceutically acceptable salt thereof. ３ａ and R ３ｂ are each independently (Wherein, t is an integer from 0 to 5, and R １０ａare each independently halogen, cyano, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted sulfoximino, or substituted or unsubstituted iminosulfino; or two R bonded to adjacent carbon atoms １０ａ may be taken together to form a substituted or unsubstituted aromatic heterocycle or a substituted or unsubstituted non-aromatic heterocycle; R １０ｂ , R １０ｂ’ , R １０ｃ , R １０ｃ’ , R １０ｄ , R １０ｄ’ , R １０ｅ , R １０ｅ’ , R １０ｆ , R １０ｆ’ , R １０ｇ , R １０ｇ’ , R １０ｈ , R １０ｈ’ , R １０ｉ , R １０ｉ’ , R １０ｊ and R １０ｊ’ are each independently a hydrogen atom, hydroxy, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyloxycarbonyl, or substituted or unsubstituted aromatic heterocyclic group; R １０ｂ and R １０ｂ’ , R １０ｃ and R １０ｃ’ , R １０ｄ and R １０ｄ’ , R １０ｅ and R １０ｅ’ , R １０ｆ and R １０ｆ’ , R １０ｇ and R １０ｇ’ , R １０ｈ and R １０ｈ’ , R１０ｉ and R １０ｉ’ , and R １０ｊ and R １０ｊ’ may each independently form, together with the carbon atom to which it is attached, oxo, a substituted or unsubstituted non-aromatic carbocyclic ring, or a substituted or unsubstituted non-aromatic heterocyclic ring; R １０ｂ and R １０ｃ , R １０ｃ and R １０ｄ , R １０ｄ and R １０ｅ , R １０ｆ and R １０ｇ , R １０ｇ and R １０ｈ , R １０ｈ and R １０ｉ , and R １０ｉ and R １０ｊ may each independently form, together with the carbon atom to which it is attached, a substituted or unsubstituted non-aromatic heterocycle, a substituted or unsubstituted aromatic carbocycle, or a substituted or unsubstituted non-aromatic carbocycle; R １０ｂ and R １０ｄ , R １０ｂ and R １０ｅ , R １０ｃ and R １０ｅ , R １０ｆ and R １０ｈ , R １０ｆ and R １０ｉ , R １０ｆ and R １０ｊ , R １０ｇ and R １０ｉ , R １０ｇ and R １０ｊ are each independently taken together to form a (C1-C4) bridge, one of the carbon atoms constituting the bridge may be replaced by an oxygen atom or a nitrogen atom; and the carbon atoms constituting the bridge are each independently R ａ and the nitrogen atom constituting the bridge is substituted with a substituent selected from R ｂ and R is substituted with a substituent selected from ａ represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ｂ(4'') R is a hydrogen atom or a group represented by the formula (I) or (II), or a pharmaceutically acceptable salt thereof. ２ is a 6-membered aromatic carbocyclic group substituted with one halogen and further substituted with 1, 2, 3 or 4 substituents selected from substituent group G, or a 6-membered aromatic heterocyclic group substituted with one halogen and further substituted with 1 or 2 substituents selected from substituent group G; and substituent group G is the group consisting of halogen, cyano, alkyl, alkenyl, alkynyl, haloalkyl, alkyloxy, alkenyloxy, alkynyloxy and haloalkyloxy, or a pharmaceutically acceptable salt thereof. (5'') A compound according to any one of the above items (1'') to (3''), wherein R ２ is a 6-membered aromatic carbocyclic group substituted with one halogen and further substituted with 1, 2, 3 or 4 substituents selected from Substituent Group G (same as in the above item (4'')), or a pharmaceutically acceptable salt thereof. (6'') R １ (7'') The compound according to any one of the above items (1'') to (5''), wherein ring A is a substituted or unsubstituted nitrogen-containing aromatic heterocyclic group or a substituted or unsubstituted nitrogen-containing non-aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. (Wherein, carbon atom a, carbon atom b, R ３ａ , R ６ and R ８ is the same as in the above item (1''); R ７ (8'') The compound according to any one of the above items (1'') to (6''), wherein ring A is a ring represented by the formula: (Wherein, carbon atom a, carbon atom b, R ３ｂ , R ６ , R ７ , R ７’ and R ８is the ring represented by the same meaning as in the above item (1")), or a pharmaceutically acceptable salt thereof. (9") The compound according to any one of the above items (1") to (8"), or a pharmaceutically acceptable salt thereof, wherein m is 0 or 1. (10") R ５ａ are each independently a hydrogen atom, and R ５ｂ (11'') A compound according to any one of the above items (1'') to (9'') or a pharmaceutically acceptable salt thereof, wherein R ６ (12'') The compound according to any one of the above items (1'') to (10'') or a pharmaceutically acceptable salt thereof, wherein R is halogen, substituted or unsubstituted alkyloxy, or hydroxy. ４ａ are each independently a hydrogen atom, and R ４ｂ are each independently a hydrogen atom, or a pharmaceutically acceptable salt thereof. (13'') A pharmaceutical composition comprising a compound according to any one of items (1'') to (12'') above or a pharmaceutically acceptable salt thereof. (14'') A coronavirus 3CL protease inhibitor comprising a compound according to any one of items (1'') to (12'') above or a pharmaceutically acceptable salt thereof. (15'') A coronavirus proliferation inhibitor comprising a compound according to any one of items (1'') to (12'') above or a pharmaceutically acceptable salt thereof. (16'') A coronavirus proliferation inhibitor according to item (15'') above, wherein the coronavirus is an alphacoronavirus and / or a betacoronavirus. (17'') A coronavirus proliferation inhibitor according to item (15'') above, wherein the coronavirus is SARS-CoV-2.

[0014] The present invention also relates to the following: (1') Formula (I): (Wherein, ring A is (In the formula, R ３is a hydrogen atom, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted alkyloxy, a substituted or unsubstituted amino, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted non-aromatic heterocyclic oxy; R ８ is a hydrogen atom or a halogen; or R ３ and R ８ may form, together with the carbon atom to which they are attached, a substituted or unsubstituted aromatic carbocyclic ring or a substituted or unsubstituted aromatic heterocyclic ring; R ６ is a hydrogen atom, halogen, substituted or unsubstituted alkyloxy or hydroxy; R ７ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted amino or hydroxy; R ７’ is a hydrogen atom or a substituted or unsubstituted alkyl; R ９ is halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; s is 0, 1, or 2; p is 1, 2, or 3) of the ring represented by the formula; R １ is a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted carbamoyl or a substituted or unsubstituted amino; R ２ is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, or a substituted or unsubstituted alkyl; n is 0, 1, or 2; R ４ａ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ４ｂ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; or R ４ａ and R ４ｂmay be taken together with the carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; m is 0, 1 or 2; R ５ａ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ５ｂ are each independently a hydrogen atom or a substituted or unsubstituted alkyl) (provided that the following compounds: (2') Ring A is excluding the following), or a pharmaceutically acceptable salt thereof. (In the formula, R ６ , R ７ , R ９ and s are the same as those in the above item (1'), R ８ is a hydrogen atom or a halogen; R ３ but, (Wherein, t is an integer from 0 to 5, and R １０ａ are each independently halogen, cyano, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted sulfoximino, or substituted or unsubstituted iminosulfino; or two R bonded to adjacent carbon atoms １０ａ may be taken together to form a substituted or unsubstituted aromatic heterocycle or a substituted or unsubstituted non-aromatic heterocycle; R １０ｂ , R １０ｂ’ , R １０ｃ , R １０ｃ’ , R １０ｄ , R １０ｄ’ , R １０ｅ , R １０ｅ’ , R １０ｆ , R １０ｆ’ , R １０ｇ , R １０ｇ’ , R １０ｈ , R １０ｈ’, R １０ｉ , R １０ｉ’ , R １０ｊ and R １０ｊ’ are each independently a hydrogen atom, hydroxy, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyloxycarbonyl, or substituted or unsubstituted aromatic heterocyclic group; R １０ｂ and R １０ｂ’ , R １０ｃ and R １０ｃ’ , R １０ｄ and R １０ｄ’ , R １０ｅ and R １０ｅ’ , R １０ｆ and R １０ｆ’ , R １０ｇ and R １０ｇ’ , R １０ｈ and R １０ｈ’ , R １０ｉ and R １０ｉ’ , and R １０ｊ and R １０ｊ’ may each independently form, together with the carbon atom to which it is attached, oxo, a substituted or unsubstituted non-aromatic carbocyclic ring, or a substituted or unsubstituted non-aromatic heterocyclic ring; R １０ｂ and R １０ｃ , R １０ｃ and R １０ｄ , R １０ｄ and R １０ｅ , R １０ｆ and R １０ｇ , R １０ｇ and R １０ｈ , R １０ｈ and R １０ｉ , and R １０ｉ and R １０ｊ may each independently form, together with the carbon atom to which it is attached, a substituted or unsubstituted non-aromatic heterocycle, a substituted or unsubstituted aromatic carbocycle, or a substituted or unsubstituted non-aromatic carbocycle; R １０ｂ and R １０ｄ , R １０ｂ and R １０ｅ , R １０ｃ and R １０ｅ , R１０ｆ and R １０ｈ , R １０ｆ and R １０ｉ , R １０ｆ and R １０ｊ , R １０ｇ and R １０ｉ , R １０ｇ and R １０ｊ are each independently taken together to form a (C1-C4) bridge, one of the carbon atoms constituting the bridge may be replaced by an oxygen atom or a nitrogen atom; and the carbon atoms constituting the bridge are each independently R ａ and the nitrogen atom constituting the bridge is substituted with a substituent selected from R ｂ and R is substituted with a substituent selected from ａ represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ｂ is a hydrogen atom or a cyclic group represented by the group represented by substituted or unsubstituted alkyl) or a substituted or unsubstituted alkyloxy; R １ is a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, or a substituted or unsubstituted amino; R ２ (3') The compound according to the above item (1'), wherein R is a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. ２ is a 6-membered aromatic carbocyclic group substituted with one halogen and further substituted with 1, 2, 3 or 4 substituents selected from substituent group G, or a 6-membered aromatic heterocyclic group substituted with one halogen and further substituted with 1 or 2 substituents selected from substituent group G; and substituent group G is the group consisting of halogen, cyano, alkyl, alkenyl, alkynyl, haloalkyl, alkyloxy, alkenyloxy, alkynyloxy and haloalkyloxy, or a pharmaceutically acceptable salt thereof. (4') R ２is a 6-membered aromatic carbocyclic group substituted with one halogen and further substituted with 1, 2, 3 or 4 substituents selected from Substituent Group G (same as in the above item (3')), or a pharmaceutically acceptable salt thereof. １ (6') The compound according to any one of the above items (1') to (4'), wherein ring A is a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. (In the formula, R ６ and R ８ is the same as the above item (1'); R ３ is the same as the above item (2'); R ７ (7') The compound according to any one of the above items (1') to (5'), wherein ring A is a ring represented by the formula: (In the formula, R ６ , R ７ and R ８ is the same as the above item (1'); R ３ (8') The compound according to any one of the above items (1') to (7'), wherein R is a ring represented by the formula (1), or a pharmaceutically acceptable salt thereof. (9') The compound according to any one of the above items (1') to (7'), wherein R is a ring represented by the formula (1), or a pharmaceutically acceptable salt thereof. ５ａ are each independently a hydrogen atom, and R ５ｂ are each independently a hydrogen atom. (10') The compound according to any one of the above items (1') to (9') or a pharmaceutically acceptable salt thereof, wherein n is 0 or 1. (11') R ４ａ are each independently a hydrogen atom, and R ４ｂare each independently a hydrogen atom, or a pharmaceutically acceptable salt thereof. (12') A pharmaceutical composition comprising a compound according to any one of items (1') to (11') above or a pharmaceutically acceptable salt thereof. (13') A coronavirus 3CL protease inhibitor comprising a compound according to any one of items (1') to (11') above or a pharmaceutically acceptable salt thereof. (14') A coronavirus proliferation inhibitor comprising a compound according to any one of items (1') to (11') above or a pharmaceutically acceptable salt thereof. (15') A coronavirus proliferation inhibitor according to item (14') above, wherein the coronavirus is an alphacoronavirus and / or a betacoronavirus. (16') A coronavirus proliferation inhibitor according to item (14') above, wherein the coronavirus is SARS-CoV-2.

[0015] The present invention also relates to the following: (1) Formula (I): (Wherein, ring A is (In the formula, R ３ is a hydrogen atom, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted alkyloxy, or a substituted or unsubstituted amino; R ８ is a hydrogen atom or a halogen; or R ３ and R ８ may form, together with the carbon atom to which they are attached, a substituted or unsubstituted aromatic carbocyclic ring or a substituted or unsubstituted aromatic heterocyclic ring; R ６ is a hydrogen atom, halogen, or substituted or unsubstituted alkyloxy; R ７ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, or substituted or unsubstituted amino; R ７’ is a hydrogen atom or a substituted or unsubstituted alkyl; R ９is halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; s is 0, 1, or 2; p is 1, 2, or 3) of the ring represented by the formula; R １ is a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted carbamoyl or a substituted or unsubstituted amino; R ２ is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, or a substituted or unsubstituted alkyl; n is 0, 1, or 2; R ４ａ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ４ｂ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; or R ４ａ and R ４ｂ may be taken together with the carbon atom to which they are attached to form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; m is 0, 1 or 2; R ５ａ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ５ｂ are each independently a hydrogen atom or a substituted or unsubstituted alkyl) (provided that the following compounds: (2) A compound in which ring A is (In the formula, R ６ , R ７ , R ９ and s are the same as those in the above item (1), R ８ is a hydrogen atom or a halogen; R ３ but, (Wherein, t is an integer from 0 to 5, and R １０ａare each independently halogen, cyano, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted sulfoximino, or substituted or unsubstituted iminosulfino; or two R bonded to adjacent carbon atoms １０ａ may be taken together to form a substituted or unsubstituted aromatic heterocycle or a substituted or unsubstituted non-aromatic heterocycle; R １０ｂ , R １０ｂ’ , R １０ｃ , R １０ｃ’ , R １０ｄ , R １０ｄ’ , R １０ｅ , R １０ｅ’ , R １０ｆ , R １０ｆ’ , R １０ｇ , R １０ｇ’ , R １０ｈ , R １０ｈ’ , R １０ｉ , R １０ｉ’ , R １０ｊ and R １０ｊ’ are each independently a hydrogen atom, hydroxy, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyloxycarbonyl, or substituted or unsubstituted aromatic heterocyclic group; R １０ｂ and R １０ｂ’ , R １０ｃ and R １０ｃ’ , R １０ｄ and R １０ｄ’ , R １０ｅ and R １０ｅ’ , R １０ｆ and R １０ｆ’ , R １０ｇ and R １０ｇ’ , R １０ｈ and R １０ｈ’ , R１０ｉ and R １０ｉ’ , and R １０ｊ and R １０ｊ’ may each independently form, together with the carbon atom to which it is attached, oxo, a substituted or unsubstituted non-aromatic carbocyclic ring, or a substituted or unsubstituted non-aromatic heterocyclic ring; R １０ｂ and R １０ｃ , R １０ｃ and R １０ｄ , R １０ｄ and R １０ｅ , R １０ｆ and R １０ｇ , R １０ｇ and R １０ｈ , R １０ｈ and R １０ｉ , and R １０ｉ and R １０ｊ may each independently form, together with the carbon atom to which it is attached, a substituted or unsubstituted non-aromatic heterocycle, a substituted or unsubstituted aromatic carbocycle, or a substituted or unsubstituted non-aromatic carbocycle; R １０ｂ and R １０ｄ , R １０ｂ and R １０ｅ , R １０ｃ and R １０ｅ , R １０ｆ and R １０ｈ , R １０ｆ and R １０ｉ , R １０ｆ and R １０ｊ , R １０ｇ and R １０ｉ , R １０ｇ and R １０ｊ are each independently taken together to form a (C1-C4) bridge, one of the carbon atoms constituting the bridge may be replaced by an oxygen atom or a nitrogen atom; and the carbon atoms constituting the bridge are each independently R ａ and the nitrogen atom constituting the bridge is substituted with a substituent selected from R ｂ and R is substituted with a substituent selected from ａ represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ｂis a hydrogen atom or a cyclic group represented by the group represented by substituted or unsubstituted alkyl) or a substituted or unsubstituted alkyloxy; R １ is a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, or a substituted or unsubstituted amino; R ２ (3) The compound according to the above item (1), wherein R is a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. ２ is a 6-membered aromatic carbocyclic group substituted with one halogen and further substituted with 1, 2, 3 or 4 substituents selected from substituent group G, or a 6-membered aromatic heterocyclic group substituted with one halogen and further substituted with 1 or 2 substituents selected from substituent group G; and substituent group G is the group consisting of halogen, cyano, alkyl, alkenyl, alkynyl, haloalkyl, alkyloxy, alkenyloxy, alkynyloxy and haloalkyloxy, or a pharmaceutically acceptable salt thereof. (4) A compound according to the above item (1) or (2), wherein R ２ is a 6-membered aromatic carbocyclic group substituted with one halogen and further substituted with 1, 2, 3 or 4 substituents selected from Substituent Group G (same as in item (3) above), or a pharmaceutically acceptable salt thereof. (5) A compound according to any one of items (1) to (3), wherein R １ (6) The compound according to any one of the above items (1) to (4), wherein ring A is a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. (In the formula, R ６ and R ８ is the same as the above item (1); R ３ is the same as the above item (2); R ７ (7) The compound according to any one of the above items (1) to (6), wherein R is a ring represented by the formula (I), or a pharmaceutically acceptable salt thereof. (8) The compound according to any one of the above items (1) to (6), wherein R is a ring represented by the formula (I), or a pharmaceutically acceptable salt thereof.５ａ are each independently a hydrogen atom, and R ５ｂ (9) The compound according to any one of the above items (1) to (8), or a pharmaceutically acceptable salt thereof, wherein R is independently a hydrogen atom. (10) The compound according to any one of the above items (1) to (8), or a pharmaceutically acceptable salt thereof, wherein R is 0 or 1. ４ａ are each independently a hydrogen atom, and R ４ｂare each independently a hydrogen atom, or a pharmaceutically acceptable salt thereof. (11) A pharmaceutical composition comprising a compound according to any one of items (1) to (10) above or a pharmaceutically acceptable salt thereof. (12) A coronavirus 3CL protease inhibitor comprising a compound according to any one of items (1) to (10) above or a pharmaceutically acceptable salt thereof. (13) A coronavirus proliferation inhibitor comprising a compound according to any one of items (1) to (10) above or a pharmaceutically acceptable salt thereof. (14) The coronavirus proliferation inhibitor according to item (13) above, wherein the coronavirus is an alphacoronavirus and / or a betacoronavirus. (15) The coronavirus proliferation inhibitor according to item (13) above, wherein the coronavirus is SARS-CoV-2. (16) A pharmaceutical composition for preventing and / or treating coronavirus infection, comprising the compound according to any one of items (1) to (10), (1') to (11'), (1") to (12"), and (1'") to (14'") above, or a pharmaceutically acceptable salt thereof. (17) The pharmaceutical composition according to item (16) above, for preventing and / or treating novel coronavirus infection (COVID-19). (18) The pharmaceutical composition according to item (16) above, for preventing and / or treating infection caused by SARS-CoV-2. (19) A method for inhibiting coronavirus proliferation, comprising administering a compound according to any one of items (1) to (10), (1') to (11'), (1") to (12"), and (1'") to (14'") above, or a pharmaceutically acceptable salt thereof. (20) The method for inhibiting proliferation according to item (19), wherein the coronavirus is an alphacoronavirus and / or a betacoronavirus. (21) The growth inhibition method according to the above item (19), wherein the coronavirus is SARS-CoV-2. (22) A method for treating and / or preventing a disease associated with coronavirus 3CL protease, comprising administering a compound according to any one of the above items (1) to (10), (1') to (11'), (1") to (12"), and (1'") to (14'"), or a pharmaceutically acceptable salt thereof.(23) A method for treating and / or preventing a coronavirus infection, comprising administering a compound according to any one of the above items (1) to (10), (1') to (11'), (1") to (12"), and (1'") to (14'"), or a pharmaceutically acceptable salt thereof. (24) The method for preventing and / or treating a coronavirus infection according to the above item (23), wherein the coronavirus infection is novel coronavirus infection (COVID-19). (25) The method for preventing and / or treating a coronavirus infection according to the above item (23), wherein the coronavirus infection is infection caused by SARS-CoV-2. (26) Use of a compound according to any one of the above items (1) to (10), (1') to (11'), (1") to (12"), and (1'") to (14'"), or a pharmaceutically acceptable salt thereof, for the manufacture of an agent for treating and / or preventing a disease involving coronavirus 3CL protease. (27) Use of the compound according to any one of the above items (1) to (10), (1') to (11'), (1") to (12"), and (1'") to (14'") or a pharmaceutically acceptable salt thereof for the manufacture of an inhibitor of coronavirus proliferation. (28) The use according to the above item (27), wherein the coronavirus is an alphacoronavirus and / or a betacoronavirus. (29) The use according to the above item (27), wherein the coronavirus is SARS-CoV-2. (30) Use of the compound according to any one of the above items (1) to (10), (1') to (11'), (1") to (12"), and (1'") to (14'") or a pharmaceutically acceptable salt thereof for the manufacture of an agent for the treatment and / or prevention of coronavirus infection. (31) The use according to the above item (30), wherein the coronavirus infection is novel coronavirus infection (COVID-19). (32) The use according to the above item (30), wherein the coronavirus infection is an infection caused by SARS-CoV-2. (33) The compound or a pharmaceutically acceptable salt thereof according to any of the above items (1) to (10), (1') to (11'), (1") to (12"), and (1'") to (14'"), for use in the treatment and / or prevention of a disease involving coronavirus 3CL protease.(34) The compound according to any one of the above items (1) to (10), (1') to (11'), (1") to (12"), and (1'") to (14'") or a pharmaceutically acceptable salt thereof, for use in inhibiting the growth of coronavirus. (35) The compound according to the above item (34) or a pharmaceutically acceptable salt thereof, wherein the coronavirus is an alphacoronavirus and / or a betacoronavirus. (36) The compound according to the above item (34) or a pharmaceutically acceptable salt thereof, wherein the coronavirus is SARS-CoV-2. (37) The compound according to any one of the above items (1) to (10), (1') to (11'), (1") to (12"), and (1'") to (14'") or a pharmaceutically acceptable salt thereof, for use in treating and / or preventing coronavirus infection. (38) The compound according to the above item (37) or a pharmaceutically acceptable salt thereof, wherein the coronavirus infection is novel coronavirus infection (COVID-19). (39) The compound or a pharmaceutically acceptable salt thereof according to the above item (37), wherein the coronavirus infection is an infection caused by SARS-CoV-2.

[0016] The compounds according to the present invention have inhibitory activity against coronavirus 3CL protease and are useful as therapeutic and / or preventive agents for coronavirus infections.

[0017] The meaning of each term used in this specification is explained below. Unless otherwise specified, each term has the same meaning whether used alone or in combination with other terms. The term "consisting of" means having only the constituent elements. The term "comprises" means not being limited to the constituent elements and does not exclude unrecited elements. The present invention will be explained below with reference to exemplary embodiments. Throughout this specification, singular expressions should be understood to include the plural concept unless otherwise specified. Therefore, singular articles (e.g., "a," "an," "the," etc. in English) should be understood to include the plural concept unless otherwise specified. Furthermore, terms used in this specification should be understood to have the meaning commonly used in the art unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In the event of conflict, the present specification (including definitions) will prevail.

[0018] The term "halogen" includes fluorine, chlorine, bromine, and iodine atoms. Particularly, fluorine and chlorine atoms are preferred.

[0019] The term "alkyl" encompasses straight-chain or branched hydrocarbon groups having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, and even more preferably 1 to 4 carbon atoms. Examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, n-heptyl, isoheptyl, n-octyl, isooctyl, n-nonyl, and n-decyl. Preferred embodiments of "alkyl" include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, and n-pentyl. More preferred embodiments include methyl, ethyl, n-propyl, isopropyl, and tert-butyl.

[0020] The term "alkenyl" encompasses straight-chain or branched hydrocarbon groups having 2 to 15 carbon atoms, preferably 2 to 10 carbon atoms, more preferably 2 to 6 carbon atoms, and even more preferably 2 to 4 carbon atoms, and having one or more double bonds at any position. Examples include vinyl, allyl, propenyl, isopropenyl, butenyl, isobutenyl, prenyl, butadienyl, pentenyl, isopentenyl, pentadienyl, hexenyl, isohexenyl, hexadienyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, and pentadecenyl. Preferred embodiments of "alkenyl" include vinyl, allyl, propenyl, isopropenyl, and butenyl. More preferred embodiments include ethenyl and n-propenyl.

[0021] "Alkynyl" includes a straight-chain or branched hydrocarbon group having 2 to 10 carbon atoms, preferably 2 to 8 carbon atoms, more preferably 2 to 6 carbon atoms, and even more preferably 2 to 4 carbon atoms, and having one or more triple bonds at any position. It may further have a double bond at any position. Examples include ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, and the like. Preferred embodiments of "alkynyl" include ethynyl, propynyl, butynyl, and pentynyl. More preferred embodiments include ethynyl, propynyl, and the like.

[0022] The term "aromatic carbocyclic group" refers to a cyclic aromatic hydrocarbon group having one ring or two or more rings. Examples include phenyl, naphthyl, anthryl, and phenanthryl. An example of a six-membered aromatic carbocyclic group is phenyl. A preferred embodiment of the "aromatic carbocyclic group" is phenyl.

[0023] The term "aromatic carbocyclic ring" refers to a ring derived from the above-mentioned "aromatic carbocyclic group".

[0024] In the above formula (I), "R ３ and R ８ "R" and "R" are substituted or unsubstituted aromatic carbocyclic rings formed together with the carbon atoms to which they are attached. ３ａ and R８ and R ３ｂ and R ８ Examples of the "substituted or unsubstituted aromatic carbocyclic ring formed by combining each of the carbon atoms to which they are bonded with each other" include the following rings.

[0025] In the above formula (I), "R １０ｂ and R １０ｃ , R １０ｃ and R １０ｄ , R １０ｄ and R １０ｅ , R １０ｆ and R １０ｇ , R １０ｇ and R １０ｈ , R １０ｈ and R １０ｉ , and R １０ｉ and R １０ｊ are each independently formed together with the carbon atom to which they are attached, and a substituted or unsubstituted aromatic carbocyclic ring is exemplified by the following rings.

[0026] The term "non-aromatic carbocyclic group" refers to a monocyclic or bicyclic or multicyclic saturated or non-aromatic unsaturated hydrocarbon group. A bicyclic or multicyclic "non-aromatic carbocyclic group" also includes a monocyclic or bicyclic or multicyclic non-aromatic carbocyclic group to which the ring of the above-mentioned "aromatic carbocyclic group" is fused. Furthermore, the term "non-aromatic carbocyclic group" also includes bridged groups or groups that form spiro rings as shown below. The monocyclic non-aromatic carbocyclic group preferably has 3 to 16 carbon atoms, more preferably 3 to 12 carbon atoms, and even more preferably 4 to 8 carbon atoms. Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclohexadienyl. The bicyclic or higher non-aromatic carbocyclic group preferably has 8 to 20 carbon atoms, more preferably 8 to 16 carbon atoms. Examples include indanyl, indenyl, acenaphthyl, tetrahydronaphthyl, and fluorenyl.

[0027] The term "non-aromatic carbocyclic ring" refers to a ring derived from the above-mentioned "non-aromatic carbocyclic group".

[0028] In the above formula (I), when n is 1, "R ４ａ and R ４ｂ Examples of the "substituted or unsubstituted non-aromatic carbocyclic ring formed by combining each of the carbon atoms to which they are bonded with each other" include the following rings.

[0029] In the above formula (I), "R １０ｂ and R １０ｂ’ , R １０ｃ and R １０ｃ’ , R １０ｄ and R １０ｄ’ , R １０ｅ and R １０ｅ’ , R １０ｆ and R １０ｆ’ , R １０ｇ and R １０ｇ’ , R １０ｈ and R １０ｈ’ , R １０ｉ and R １０ｉ’ , and R １０ｊ and R １０ｊ’ are each independently formed together with the carbon atom to which it is attached, and a substituted or unsubstituted non-aromatic carbocyclic ring is exemplified by the following rings.

[0030] In the above formula (I), "R １０ｂ and R １０ｃ , R １０ｃ and R １０ｄ , R １０ｄ and R １０ｅ , R １０ｆ and R １０ｇ , R １０ｇ and R １０ｈ , R １０ｈ and R １０ｉ , and R １０ｉ and R １０ｊ are each independently formed together with the carbon atom to which they are attached, and examples of the "substituted or unsubstituted non-aromatic carbocyclic ring" include the following rings.

[0031] The term "aromatic heterocyclic group" refers to a monocyclic or bicyclic or multicyclic aromatic cyclic group having one or more identical or different heteroatoms selected from O, S, and N in the ring. Bicyclic or multicyclic aromatic heterocyclic groups also include those in which the rings in the "aromatic carbocyclic group" are fused to a monocyclic or bicyclic or multicyclic aromatic heterocyclic group, and the bond may be on any of the rings. Monocyclic aromatic heterocyclic groups are preferably 5- to 8-membered, and more preferably 5- or 6-membered. Examples of 5-membered aromatic heterocyclic groups include pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, thiadiazolyl, etc. Examples of 6-membered aromatic heterocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, etc. The bicyclic aromatic heterocyclic group is preferably 8- to 10-membered, more preferably 9- or 10-membered. Examples thereof include indolyl, isoindolyl, indazolyl, indolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, naphthyridinyl, quinoxalinyl, purinyl, pteridinyl, benzimidazolyl, benzisoxazolyl, benzoxazolyl, benzoxadiazolyl, benzisothiazolyl, benzothiazolyl, benzothiadiazolyl, benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, imidazopyridyl, triazolopyridyl, imidazothiazolyl, pyrazinopyridazinyl, oxazolopyridyl, and thiazolopyridyl. Examples of the 9-membered aromatic heterocyclic group include indolyl, isoindolyl, indazolyl, indolizinyl, purinyl, benzimidazolyl, benzisoxazolyl, benzoxazolyl, benzoxadiazolyl, benzisothiazolyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyl, benzofuranyl, imidazopyridyl, triazolopyridyl, oxazolopyridyl, thiazolopyridyl, etc. Examples of the 10-membered aromatic heterocyclic group include quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, naphthyridinyl, quinoxalinyl, pteridinyl, pyrazinopyridazinyl, etc.The aromatic heterocyclic group having three or more rings is preferably 13 to 15-membered, and examples thereof include carbazolyl, acridinyl, xanthenyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, and dibenzofuryl.

[0032] The term "nitrogen-containing aromatic heterocyclic group" refers to a monocyclic or bicyclic or more aromatic heterocyclic group having one or more nitrogen atoms in the ring.

[0033] The term "aromatic heterocycle" refers to a ring derived from the above-mentioned "aromatic heterocyclic group".

[0034] In the above formula (I), "R ３ and R ８ "R" and "R" are substituted or unsubstituted aromatic heterocyclic rings formed together with the carbon atoms to which they are attached. ３ａ and R ８ and R ３ｂ and R ８ are taken together with the carbon atoms to which they are bonded to form a substituted or unsubstituted aromatic heterocycle, for example, the following rings.

[0035] In the above formula (I), "two R bonds to adjacent carbon atoms" １０ａ Examples of the "substituted or unsubstituted aromatic heterocycle formed by combining these rings together" include the following rings. (In the formula, R Y represents a hydrogen atom, substituted or unsubstituted alkyl, etc.)

[0036] The term "non-aromatic heterocyclic group" refers to a monocyclic or bicyclic or more non-aromatic cyclic group having one or more identical or different heteroatoms selected from O, S, and N in the ring. Bicyclic or more non-aromatic heterocyclic groups include monocyclic or bicyclic or more non-aromatic heterocyclic groups fused with the respective rings of the above-mentioned "aromatic carbocyclic group," "non-aromatic carbocyclic group," and / or "aromatic heterocyclic group," as well as monocyclic or bicyclic or more non-aromatic carbocyclic groups fused with the rings of the above-mentioned "aromatic heterocyclic group," and the bond may be on any of the rings. Furthermore, the term "non-aromatic heterocyclic group" also includes bridged groups or groups forming spiro rings as described below. The monocyclic non-aromatic heterocyclic group is preferably 3 to 8 members, more preferably 5 or 6 members. Examples of 3-membered non-aromatic heterocyclic groups include thiiranyl, oxiranyl, and aziridinyl. Examples of 4-membered non-aromatic heterocyclic groups include oxetanyl and azetidinyl. Examples of 5-membered non-aromatic heterocyclic groups include oxathiolanyl, thiazolidinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, tetrahydrofuryl, dihydrothiazolyl, tetrahydroisothiazolyl, dioxolanyl, dioxolyl, and thiolanyl. Examples of 6-membered non-aromatic heterocyclic groups include dioxanyl, thianyl, piperidyl, piperazinyl, morpholinyl, morpholino, thiomorpholinyl, thiomorpholino, dihydropyridyl, tetrahydropyridyl, tetrahydropyranyl, dihydrooxazinyl, tetrahydropyridazinyl, hexahydropyrimidinyl, dioxazinyl, thiinyl, and thiazinyl. Examples of 7-membered non-aromatic heterocyclic groups include hexahydroazepinyl, tetrahydrodiazepinyl, and oxepanyl. Non-aromatic heterocyclic groups having two or more rings preferably have 8 to 20 members, more preferably 8 to 13 members, and even more preferably 8 to 10 members. Examples include indolinyl, isoindolinyl, chromanyl, and isochromanyl.

[0037] The term "nitrogen-containing non-aromatic heterocyclic group" refers to a monocyclic or bicyclic or more non-aromatic heterocyclic group having one or more nitrogen atoms in the ring. Bicyclic or more non-aromatic heterocyclic groups include monocyclic or bicyclic or more non-aromatic nitrogen-containing non-aromatic heterocyclic groups fused with the rings of the above-mentioned "aromatic carbocyclic groups," "non-aromatic carbocyclic groups," and / or "aromatic heterocyclic groups," and the bond may be on any of the rings. Bicyclic or more non-aromatic heterocyclic groups also include monocyclic or bicyclic or more non-aromatic carbocyclic groups fused with the rings of the above-mentioned "nitrogen-containing aromatic heterocyclic groups," and the bond may be on any of the rings. For example, the following groups are shown. Furthermore, the term "nitrogen-containing non-aromatic heterocyclic group" also includes bridged groups or groups that form spiro rings, as shown below.

[0038] The term "non-aromatic heterocycle" refers to a ring derived from the above-mentioned "non-aromatic heterocyclic group".

[0039] In the above formula (I), when n is 1, "R ４ａ and R ４ｂ are taken together with the carbon atoms to which they are bonded to form a substituted or unsubstituted non-aromatic heterocycle, for example, the following rings. (In the formula, R ｘ is substituted or unsubstituted alkyl, etc.)

[0040] In the above formula (I), "two R bonds to adjacent carbon atoms" １０ａ Examples of the "substituted or unsubstituted non-aromatic heterocycle formed by combining the following rings" include the following rings:

[0041] In the above formula (I), "R １０ｂ and R １０ｂ’ , R １０ｃ and R １０ｃ’ , R １０ｄ and R １０ｄ’ , R １０ｅ and R １０ｅ’ , R １０ｆ and R １０ｆ’ , R １０ｇ and R １０ｇ’ , R１０ｈ and R １０ｈ’ , R １０ｉ and R １０ｉ’ , and R １０ｊ and R １０ｊ’ are each independently formed together with the carbon atom to which they are attached, a substituted or unsubstituted non-aromatic heterocycle, for example, includes the following rings.

[0042] In the above formula (I), "R １０ｂ and R １０ｃ , R １０ｃ and R １０ｄ , R １０ｄ and R １０ｅ , R １０ｆ and R １０ｇ , R １０ｇ and R １０ｈ , R １０ｈ and R １０ｉ , and R １０ｉ and R １０ｊ and each independently form a substituted or unsubstituted non-aromatic heterocycle together with the carbon atom to which it is bonded, includes, for example, the following rings.

[0043] In the above formula (I), "R ３ｂ and R ７’ are taken together with the atoms to which they are attached to form a substituted or unsubstituted non-aromatic heterocycle, for example, the following rings. (wherein the nitrogen atom c is R ７’ represents a nitrogen atom to which R is bonded; and carbon atom d represents a nitrogen atom to which R is bonded in the above formula (I). ３ｂ indicates the carbon atom to which

[0044] "Trialkylsilyl" refers to a group in which three of the above-mentioned "alkyl" groups are bonded to a silicon atom. The three alkyl groups may be the same or different. Examples include trimethylsilyl, triethylsilyl, and tert-butyldimethylsilyl.

[0045] "Iminosulfino" refers to a group having the following formula: One or two hydrogen atoms may be substituted at any position. Substituents of "substituted iminosulfino" include alkyl and the like.

[0046] In this specification, "optionally substituted with substituent group α" means "optionally substituted with one or more groups selected from substituent group α." The same applies to substituent groups β, γ, and γ'.

[0047] Examples of substituents such as "substituted alkyl," "substituted alkenyl," "substituted alkynyl," "substituted alkyloxy," "substituted alkenyloxy," "substituted alkynyloxy," "substituted alkylcarbonyloxy," "substituted alkenylcarbonyloxy," "substituted alkynylcarbonyloxy," "substituted alkylcarbonyl," "substituted alkenylcarbonyl," "substituted alkynylcarbonyl," "substituted alkyloxycarbonyl," "substituted alkenyloxycarbonyl," "substituted alkynyloxycarbonyl," "substituted alkylsulfanyl," "substituted alkenylsulfanyl," "substituted alkynylsulfanyl," "substituted alkylsulfinyl," "substituted alkenylsulfinyl," "substituted alkynylsulfinyl," "substituted alkylsulfonyl," "substituted alkenylsulfonyl," and "substituted alkynylsulfonyl" include the following Substituent Group A. A carbon atom at any position may be bonded to one or more groups selected from the following Substituent Group A. Substituent group A: halogen, hydroxy, carboxy, formyl, formyloxy, sulfanyl, sulfino, sulfo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, cyano, nitro, nitroso, azido, hydrazino, ureido, amidino, guanidino, pentafluorothio, trialkylsilyl, alkyloxy optionally substituted with substituent group α, alkenyloxy optionally substituted with substituent group α, alkynyloxy optionally substituted with substituent group α, alkylcarbonyloxy optionally substituted with substituent group α, alkenylcarbonyloxy optionally substituted with substituent group α, alkynylcarbonyloxy optionally substituted with substituent group α, alkylcarbonyl optionally substituted with substituent group α, alkenylcarbonyl optionally substituted with substituent group α, alkynylcarbonyl optionally substituted with substituent group α, alkyloxycarbonyl optionally substituted with substituent group α, alkenyloxycarbonyl optionally substituted with substituent group α, alkynyloxycarbonyl optionally substituted with substituent group α, alkylsulfanyl optionally substituted with substituent group α, alkenylsulfanyl optionally substituted with substituent group α, alkynylsulfanyl optionally substituted with substituent group α,alkylsulfinyl optionally substituted with substituent group α, alkenylsulfinyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, alkylsulfonyl optionally substituted with substituent group α, alkenylsulfonyl optionally substituted with substituent group α, alkynylsulfonyl optionally substituted with substituent group α, amino optionally substituted with substituent group β, imino optionally substituted with substituent group β, carbamoyl optionally substituted with substituent group β, sulfamoyl optionally substituted with substituent group β, Aromatic carbocyclic group optionally substituted with substituent group γ, non-aromatic carbocyclic group optionally substituted with substituent group γ', aromatic heterocyclic group optionally substituted with substituent group γ, non-aromatic heterocyclic group optionally substituted with substituent group γ', aromatic carbocyclic oxy optionally substituted with substituent group γ, non-aromatic carbocyclic oxy optionally substituted with substituent group γ', aromatic heterocyclic oxy optionally substituted with substituent group γ, non-aromatic heterocyclic oxy optionally substituted with substituent group γ', aromatic carbocyclic carbonyloxy optionally substituted with substituent group γ, non-aromatic carbocyclic carbonyloxy optionally substituted with substituent group γ', aromatic heterocyclic carbonyloxy optionally substituted with substituent group γ, non-aromatic heterocyclic carbonyloxy optionally substituted with substituent group γ', aromatic carbocyclic carbonyl optionally substituted with substituent group γ, non-aromatic carbocyclic carbonyl optionally substituted by group γ', aromatic heterocyclic carbonyl optionally substituted by substituent group γ, non-aromatic heterocyclic carbonyl optionally substituted by substituent group γ', aromatic carbocyclic oxycarbonyl optionally substituted by substituent group γ, non-aromatic carbocyclic oxycarbonyl optionally substituted by substituent group γ', aromatic heterocyclic oxycarbonyl optionally substituted by substituent group γ, non-aromatic heterocyclic oxycarbonyl optionally substituted by substituent group γ', aromatic carbocyclic alkyloxy optionally substituted by substituent group γ, non-aromatic carbocyclic alkyloxy optionally substituted by substituent group γ', aromatic heterocyclic alkyloxy optionally substituted by substituent group γ, non-aromatic heterocyclic alkyloxy optionally substituted by substituent group γ', aromatic carbocyclic alkyloxycarbonyl optionally substituted by substituent group γ,Non-aromatic carbocyclic alkyloxycarbonyl optionally substituted with substituent group γ', aromatic heterocyclic alkyloxycarbonyl optionally substituted with substituent group γ, non-aromatic heterocyclic alkyloxycarbonyl optionally substituted with substituent group γ', aromatic carbocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfanyl optionally substituted with substituent group γ', aromatic heterocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfanyl optionally substituted with substituent group γ', aromatic carbocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfinyl optionally substituted with substituent group γ', aromatic heterocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfinyl optionally substituted with substituent group γ', aromatic carbocyclic sulfonyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfonyl optionally substituted with substituent group γ', aromatic heterocyclic sulfonyl optionally substituted with substituent group γ and non-aromatic heterocyclic sulfonyl optionally substituted with substituent group γ'.

[0048] Substituent group α: halogen, hydroxy, carboxy, alkyloxy, haloalkyloxy, alkenyloxy, alkynyloxy, sulfanyl, and cyano.

[0049] Substituent group β: halogen, hydroxy, carboxy, cyano, alkyl optionally substituted with substituent group α, alkenyl optionally substituted with substituent group α, alkynyl optionally substituted with substituent group α, alkylcarbonyl optionally substituted with substituent group α, alkenylcarbonyl optionally substituted with substituent group α, alkynylcarbonyl optionally substituted with substituent group α, alkylsulfanyl optionally substituted with substituent group α, alkenylsulfanyl optionally substituted with substituent group α, alkynylsulfanyl optionally substituted with substituent group α, alkylsulfinyl optionally substituted with substituent group α, alkenylsulfinyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, alkylsulfonyl optionally substituted with substituent group α, alkenylsulfonyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, alkylsulfonyl optionally substituted with substituent group α, alkenylsulfonyl optionally substituted with substituent group α, alkynylsulfonyl optionally substituted with substituent group α,Aromatic carbocyclic group optionally substituted with substituent group γ, non-aromatic carbocyclic group optionally substituted with substituent group γ', aromatic heterocyclic group optionally substituted with substituent group γ, non-aromatic heterocyclic group optionally substituted with substituent group γ', aromatic carbocyclic alkyl optionally substituted with substituent group γ, non-aromatic carbocyclic alkyl optionally substituted with substituent group γ', aromatic heterocyclic alkyl optionally substituted with substituent group γ, non-aromatic heterocyclic alkyl optionally substituted with substituent group γ', aromatic carbocyclic carbonyl optionally substituted with substituent group γ, non-aromatic carbocyclic carbonyl optionally substituted with substituent group γ', aromatic heterocyclic carbonyl optionally substituted with substituent group γ, non-aromatic heterocyclic carbonyl optionally substituted with substituent group γ', aromatic carbocyclic oxycarbonyl optionally substituted with substituent group γ, non-aromatic carbocyclic oxycarbonyl optionally substituted with substituent group γ', aromatic heterocyclic oxycarbonyl optionally substituted with substituent group γ', non-aromatic heterocyclic oxycarbonyl optionally substituted with substituent group γ', aromatic carbocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfanyl optionally substituted with substituent group γ', aromatic heterocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfanyl optionally substituted with substituent group γ', aromatic carbocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfinyl optionally substituted with substituent group γ', aromatic heterocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfinyl optionally substituted with substituent group γ', aromatic carbocyclic sulfonyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfonyl optionally substituted with substituent group γ', aromatic heterocyclic sulfonyl optionally substituted with substituent group γ and non-aromatic heterocyclic sulfonyl optionally substituted with substituent group γ'.

[0050] Substituent group γ: Substituent group α, alkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, alkylcarbonyl, haloalkylcarbonyl, alkenylcarbonyl and alkynylcarbonyl.

[0051] Substituent group γ': Substituent group γ and oxo.

[0052] Substituents on the ring of an "aromatic carbocycle" and "aromatic heterocycle", such as a "substituted aromatic carbocyclic group", "substituted aromatic heterocyclic group", "substituted aromatic carbocycleoxy", "substituted aromatic heterocyclicoxy", "substituted aromatic carbocyclecarbonyloxy", "substituted aromatic heterocycliccarbonyloxy", "substituted aromatic carbocyclecarbonyl", "substituted aromatic heterocycliccarbonyl", "substituted aromatic carbocycleoxycarbonyl", "substituted aromatic heterocyclicoxycarbonyl", "substituted aromatic carbocyclesulfanyl", "substituted aromatic heterocyclicsulfanyl", "substituted aromatic carbocyclesulfinyl", "substituted aromatic heterocyclicsulfinyl", "substituted aromatic carbocyclesulfonyl", "substituted aromatic heterocyclicsulfonyl" and "substituted nitrogen-containing aromatic heterocyclic group", include the following substituent group B. An atom at any position on the ring may be bonded to one or more groups selected from the following substituent group B. Substituent group B: halogen, hydroxy, carboxy, formyl, formyloxy, sulfanyl, sulfino, sulfo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, cyano, nitro, nitroso, azido, hydrazino, ureido, amidino, guanidino, pentafluorothio, trialkylsilyl, alkyl optionally substituted with substituent group α, alkenyl optionally substituted with substituent group α, alkynyl optionally substituted with substituent group α, alkyloxy optionally substituted with substituent group α, alkenyloxy optionally substituted with substituent group α, alkynyloxy optionally substituted with substituent group α, alkylcarbonyloxy optionally substituted with substituent group α, alkenylcarbonyloxy optionally substituted with substituent group α, alkynylcarbonyloxy optionally substituted with substituent group α, alkylcarbonyl optionally substituted with substituent group α, alkenylcarbonyl optionally substituted with substituent group α, alkynylcarbonyl optionally substituted with substituent group α, alkyloxycarbonyl optionally substituted with substituent group α, alkenyloxycarbonyl optionally substituted with substituent group α, alkynyloxycarbonyl optionally substituted with substituent group α, alkylsulfanyl optionally substituted with substituent group α, alkenylsulfanyl optionally substituted with substituent group α, alkynylsulfanyl optionally substituted with substituent group α,alkylsulfinyl optionally substituted with substituent group α, alkenylsulfinyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, alkylsulfonyl optionally substituted with substituent group α, alkenylsulfonyl optionally substituted with substituent group α, alkynylsulfonyl optionally substituted with substituent group α, amino optionally substituted with substituent group β, imino optionally substituted with substituent group β, carbamoyl optionally substituted with substituent group β, sulfamoyl optionally substituted with substituent group β, Aromatic carbocyclic group optionally substituted with substituent group γ, non-aromatic carbocyclic group optionally substituted with substituent group γ', aromatic heterocyclic group optionally substituted with substituent group γ, non-aromatic heterocyclic group optionally substituted with substituent group γ', aromatic carbocyclic oxy optionally substituted with substituent group γ, non-aromatic carbocyclic oxy optionally substituted with substituent group γ', aromatic heterocyclic oxy optionally substituted with substituent group γ, non-aromatic heterocyclic oxy optionally substituted with substituent group γ', aromatic carbocyclic carbonyloxy optionally substituted with substituent group γ, non-aromatic carbocyclic carbonyloxy optionally substituted with substituent group γ', aromatic heterocyclic carbonyloxy optionally substituted with substituent group γ, non-aromatic heterocyclic carbonyloxy optionally substituted with substituent group γ', aromatic carbocyclic carbonyloxy optionally substituted with substituent group γ, carbonyl, non-aromatic carbocyclic carbonyl optionally substituted by substituent group γ', aromatic heterocyclic carbonyl optionally substituted by substituent group γ, non-aromatic heterocyclic carbonyl optionally substituted by substituent group γ', aromatic carbocyclic oxycarbonyl optionally substituted by substituent group γ', non-aromatic carbocyclic oxycarbonyl optionally substituted by substituent group γ, aromatic heterocyclic oxycarbonyl optionally substituted by substituent group γ, non-aromatic heterocyclic oxycarbonyl optionally substituted by substituent group γ', aromatic carbocyclic alkyl optionally substituted by substituent group γ, non-aromatic carbocyclic alkyl optionally substituted by substituent group γ', aromatic heterocyclic alkyl optionally substituted by substituent group γ, non-aromatic heterocyclic alkyl optionally substituted by substituent group γ', aromatic carbocyclic alkyloxy optionally substituted by substituent group γ,Non-aromatic carbocyclic alkyloxy optionally substituted with substituent group γ', aromatic heterocyclic alkyloxy optionally substituted with substituent group γ, non-aromatic heterocyclic alkyloxy optionally substituted with substituent group γ', aromatic carbocyclic alkyloxycarbonyl optionally substituted with substituent group γ', non-aromatic carbocyclic alkyloxycarbonyl optionally substituted with substituent group γ, aromatic heterocyclic alkyloxycarbonyl optionally substituted with substituent group γ, non-aromatic heterocyclic alkyloxycarbonyl optionally substituted with substituent group γ', aromatic carbocyclic alkyloxyalkyl optionally substituted with substituent group γ', non-aromatic carbocyclic alkyloxyalkyl optionally substituted with substituent group γ', aromatic heterocyclic alkyloxyalkyl optionally substituted with substituent group γ, non-aromatic heterocyclic alkyloxyalkyl optionally substituted with substituent group γ, non-aromatic heterocyclic alkyloxyalkyl optionally substituted with substituent group γ' alkyloxyalkyl, aromatic carbocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfanyl optionally substituted with substituent group γ', aromatic heterocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfanyl optionally substituted with substituent group γ', aromatic carbocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfinyl optionally substituted with substituent group γ', aromatic heterocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfinyl optionally substituted with substituent group γ', aromatic carbocyclic sulfonyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfonyl optionally substituted with substituent group γ', aromatic heterocyclic sulfonyl optionally substituted with substituent group γ and non-aromatic heterocyclic sulfonyl optionally substituted with substituent group γ'.

[0053]

[0049] Substituents on the ring of a "non-aromatic carbocyclic group" and a "non-aromatic heterocyclic group", such as a "substituted non-aromatic carbocyclic group", a "substituted non-aromatic carbocyclic groupoxy", a "substituted non-aromatic heterocyclic groupoxy", a "substituted non-aromatic carbocyclic groupcarbonyloxy", a "substituted non-aromatic heterocyclic groupcarbonyloxy", a "substituted non-aromatic carbocyclic groupcarbonyl", a "substituted non-aromatic heterocyclic groupcarbonyl", a "substituted non-aromatic carbocyclic groupoxycarbonyl", a "substituted non-aromatic heterocyclic groupoxycarbonyl", a "substituted non-aromatic carbocyclic groupsulfanyl", a "substituted non-aromatic heterocyclic groupsulfinyl", a "substituted non-aromatic heterocyclic group sulfinyl", a "substituted non-aromatic carbocyclic group sulfonyl", a "substituted non-aromatic heterocyclic group sulfonyl", and a "substituted nitrogen-containing non-aromatic heterocyclic group" include the following substituent group C. An atom at any position on the ring may be bonded to one or more groups selected from the following substituent group C. Substituent group C: Substituent group B and oxo.

[0054] When a "non-aromatic carbocycle" or a "non-aromatic heterocycle" is substituted with "oxo", it means a ring in which two hydrogen atoms on a carbon atom are replaced as follows:

[0055] Substituents for "substituted amino", "substituted imino", "substituted carbamoyl" and "substituted sulfamoyl" include the following Substituent Group D. Each group may be substituted with 1 or 2 groups selected from Substituent Group D. Substituent group D: halogen, hydroxy, carboxy, cyano, alkyl optionally substituted with substituent group α, alkenyl optionally substituted with substituent group α, alkynyl optionally substituted with substituent group α, alkylcarbonyl optionally substituted with substituent group α, alkenylcarbonyl optionally substituted with substituent group α, alkynylcarbonyl optionally substituted with substituent group α, alkylsulfanyl optionally substituted with substituent group α, alkenylsulfanyl optionally substituted with substituent group α, alkynylsulfanyl optionally substituted with substituent group α, alkylsulfinyl optionally substituted with substituent group α, alkenylsulfinyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, alkylsulfonyl optionally substituted with substituent group α, alkenylsulfonyl optionally substituted with substituent group α, alkynylsulfinyl optionally substituted with substituent group α, alkylsulfonyl optionally substituted with substituent group α, alkenylsulfonyl optionally substituted with substituent group α, alkynylsulfonyl optionally substituted with substituent group α, amino optionally substituted with substituent group β, imino optionally substituted with substituent group β, carbamoyl optionally substituted with substituent group β, sulfamoyl optionally substituted with substituent group β,Aromatic carbocyclic group optionally substituted with substituent group γ, non-aromatic carbocyclic group optionally substituted with substituent group γ', aromatic heterocyclic group optionally substituted with substituent group γ, non-aromatic heterocyclic group optionally substituted with substituent group γ', aromatic carbocyclic alkyl optionally substituted with substituent group γ, non-aromatic carbocyclic alkyl optionally substituted with substituent group γ', aromatic heterocyclic alkyl optionally substituted with substituent group γ, non-aromatic heterocyclic alkyl optionally substituted with substituent group γ', aromatic carbocyclic carbonyl optionally substituted with substituent group γ, non-aromatic carbocyclic carbonyl optionally substituted with substituent group γ', aromatic heterocyclic carbonyl optionally substituted with substituent group γ, non-aromatic heterocyclic carbonyl optionally substituted with substituent group γ', aromatic carbocyclic oxycarbonyl optionally substituted with substituent group γ, non-aromatic carbocyclic oxycarbonyl optionally substituted with substituent group γ', aromatic heterocyclic oxycarbonyl optionally substituted with substituent group γ', non-aromatic heterocyclic oxycarbonyl optionally substituted with substituent group γ', aromatic carbocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfanyl optionally substituted with substituent group γ', aromatic heterocyclic sulfanyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfanyl optionally substituted with substituent group γ', aromatic carbocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfinyl optionally substituted with substituent group γ', aromatic heterocyclic sulfinyl optionally substituted with substituent group γ, non-aromatic heterocyclic sulfinyl optionally substituted with substituent group γ', aromatic carbocyclic sulfonyl optionally substituted with substituent group γ, non-aromatic carbocyclic sulfonyl optionally substituted with substituent group γ', aromatic heterocyclic sulfonyl optionally substituted with substituent group γ and non-aromatic heterocyclic sulfonyl optionally substituted with substituent group γ'.

[0056] R １Examples of substituents for the "substituted or unsubstituted non-aromatic heterocyclic group" and "substituted or unsubstituted nitrogen-containing non-aromatic heterocyclic group" in the above formula include oxo; thioxo; halogen; cyano; nitro; carboxy; substituted or unsubstituted carbamoyl; substituted or unsubstituted alkyl; substituted or unsubstituted alkyloxy; substituted or unsubstituted alkylcarbonyl; substituted or unsubstituted alkyloxycarbonyl; substituted or unsubstituted alkylsulfanyl; substituted or unsubstituted amino; substituted or unsubstituted aromatic carbocyclic group; substituted or unsubstituted aromatic heterocyclic group; substituted or unsubstituted non-aromatic carbocyclic group; substituted or unsubstituted non-aromatic heterocyclic group; substituted or unsubstituted non-aromatic heterocyclic carbonyl; and may be substituted with one or more groups selected from these.

[0057] R １ Examples of the substituents of the "substituted or unsubstituted non-aromatic heterocyclic group" and the "substituted or unsubstituted nitrogen-containing non-aromatic heterocyclic group" in the above formula include oxo; halogen; and may be substituted with one or more groups selected from these.

[0058] R １ Examples of the substituents of the "substituted or unsubstituted aromatic heterocyclic group" and "substituted or unsubstituted nitrogen-containing aromatic heterocyclic group" in the above formula include halogen, cyano, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted amino, and substituted or unsubstituted aromatic carbocyclic group. They may be substituted with one or more groups selected from these.

[0059] R １ Examples of the substituents of the "substituted or unsubstituted aromatic heterocyclic group" and "substituted or unsubstituted nitrogen-containing aromatic heterocyclic group" in the above formula include halogen, cyano, hydroxy, substituted or unsubstituted alkyl, and substituted or unsubstituted alkyloxy. They may be substituted with one or more groups selected from these.

[0060] R １Examples of the substituents of the "substituted or unsubstituted aromatic heterocyclic group" and "substituted or unsubstituted nitrogen-containing aromatic heterocyclic group" in the above formula include halogen; cyano; hydroxy; substituted alkyl (substituents include halogen; which may be substituted with one or more groups selected from these); unsubstituted alkyl; and unsubstituted alkyloxy. These may be substituted with one or more groups selected from these.

[0061] R １ Examples of the substituents of the "substituted or unsubstituted aromatic heterocyclic group" and "substituted or unsubstituted nitrogen-containing aromatic heterocyclic group" in the above include halogen; cyano; substituted alkyl (substituents include halogen; which may be substituted with one or more groups selected from these); unsubstituted alkyl; substituted alkyloxy (substituents include halogen; which may be substituted with one or more groups selected from these); and unsubstituted alkyloxy. They may be substituted with one or more groups selected from these.

[0062] R １ In the above formula, examples of the substituents of the "substituted or unsubstituted carbamoyl" include: a substituted or unsubstituted alkyl; a substituted or unsubstituted non-aromatic carbocyclic group; and it may be substituted with one or more groups selected from these.

[0063] R １ In the above formula, examples of the substituents of the "substituted or unsubstituted carbamoyl" include: substituted or unsubstituted alkyl; and it may be substituted with one or more groups selected from these.

[0064] R １ In the above, examples of the substituents of the "substituted or unsubstituted carbamoyl" include: substituted alkyl (the substituents are halogen and non-aromatic carbocyclic groups; which may be substituted with one or more groups selected from these); unsubstituted alkyl; and unsubstituted non-aromatic carbocyclic groups; which may be substituted with one or more groups selected from these.

[0065] R １In the above formula, examples of the substituents of the "substituted or unsubstituted carbamoyl" include alkyl. It may be substituted with one or more groups selected from these.

[0066] R ２ Examples of the substituents of the "substituted or unsubstituted aromatic carbocyclic group" in the formula (I) include: halogen; cyano; substituted or unsubstituted alkyl; substituted or unsubstituted alkynyl; substituted or unsubstituted alkyloxy; and may be substituted with one or more groups selected from these.

[0067] R ２ Examples of the substituents of the "substituted or unsubstituted 6-membered aromatic carbocyclic group" in the above formula include: halogen; cyano; substituted or unsubstituted alkyl; substituted or unsubstituted alkyloxy; substituted or unsubstituted alkyloxycarbonyl; and it may be substituted with one or more groups selected from these.

[0068] R ２ Examples of the substituent of the "substituted or unsubstituted 6-membered aromatic carbocyclic group" in the formula (I) include: halogen; cyano; substituted alkyl (substituents include halogen and alkyloxy; which may be substituted with one or more groups selected from these); unsubstituted alkyl; substituted alkyloxy (substituents include aromatic carbocyclic groups; which may be substituted with one or more groups selected from these); unsubstituted alkyloxy; and unsubstituted alkyloxycarbonyl. It may be substituted with one or more groups selected from these.

[0069] R ２ Examples of the substituents of the "substituted or unsubstituted aromatic heterocyclic group" in the above formula include: halogen; cyano; substituted or unsubstituted alkyl; substituted or unsubstituted alkynyl; substituted or unsubstituted alkyloxy; and it may be substituted with one or more groups selected from these.

[0070] R ２Examples of the substituents of the "substituted or unsubstituted 6-membered aromatic heterocyclic group" in the above formula include: halogen; and it may be substituted with one or more groups selected from these.

[0071] R ３ , R ３ａ , R ３ｂ and R ３ｂ’ Examples of the substituents of the "substituted or unsubstituted aromatic carbocyclic group" in the formula (I) include halogen, cyano, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted amino, substituted or unsubstituted imino, substituted or unsubstituted iminosulfino, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, and substituted or unsubstituted non-aromatic heterocyclic group. It may be substituted with one or more groups selected from these. R ３ , R ３ａ , R ３ｂ and R ３ｂ’ Examples of the substituents of the "substituted or unsubstituted aromatic carbocyclic group" in the formula (I) include: halogen; cyano; substituted or unsubstituted alkyl; substituted or unsubstituted carbamoyl; substituted or unsubstituted imino; substituted or unsubstituted iminosulfino; and it may be substituted with one or more groups selected from these.

[0072] R ３ , R ３ａ , R ３ｂ and R ３ｂ’Substituents for the "substituted or unsubstituted aromatic carbocyclic group" in the above formula (I) include, for example, halogen; cyano; hydroxy; carboxy; substituted or unsubstituted alkyl; substituted or unsubstituted alkyloxy; substituted or unsubstituted alkylcarbonyl; substituted or unsubstituted alkyloxycarbonyl; substituted or unsubstituted alkylsulfinyl; substituted or unsubstituted alkylsulfonyl; substituted or unsubstituted sulfoximino; substituted or unsubstituted iminosulfino; substituted or unsubstituted amino; substituted or unsubstituted carbamoyl; substituted or unsubstituted N-(bis(dialkylamino)methylene)carbamoyl; substituted or unsubstituted sulfamoyl; substituted or unsubstituted dialkylphosphoryl; substituted or unsubstituted non-aromatic carbocyclic group; substituted or unsubstituted aromatic heterocyclic group; substituted or unsubstituted non-aromatic heterocyclic group; substituted or unsubstituted non-aromatic heterocyclic carbonyl; It may be substituted with one or more groups selected from these.

[0073] R ３ , R ３ａ , R ３ｂ and R ３ｂ’Examples of the substituents of the "substituted or unsubstituted aromatic carbocyclic group" in the above formula include halogen; cyano; hydroxy; carboxy; substituted alkyl (substituents include halogen, hydroxy, carboxy, carbamoyl, dialkylcarbamoyl, alkylsulfonylalkylcarbamoyl, dialkylaminoalkylcarbamoyl, alkyl non-aromatic heterocyclic group carbamoyl, alkyloxy, alkyloxycarbonyl, dialkylsulfoximinyl, non-aromatic heterocyclic group, alkyl non-aromatic heterocyclic group, amino non-aromatic heterocyclic group carbonyl; which may be substituted with one or more groups selected from these); unsubstituted alkyl; substituted alkyloxy (substituents include alkyloxy; which may be substituted with one or more groups selected from these); unsubstituted alkyloxy; unsubstituted alkylcarbonyl; unsubstituted alkyloxycarbonyl; substituted alkylsulfinyl (substituents include imino and alkylimino; which may be substituted with one or more groups selected from these); unsubstituted alkylsulfonyl; Substituted sulfoximino (substituents include alkyl; optionally substituted with one or more groups selected from these); substituted iminosulfino (substituents include alkyl; optionally substituted with one or more groups selected from these); substituted amino (substituents include alkylcarbonyl and alkylsulfonyl; optionally substituted with one or more groups selected from these); unsubstituted amino; substituted carbamoyl (substituents include alkyl, hydroxyalkyl, dialkylaminoalkyl, hydroxyalkylaminoalkyl, non-aromatic heterocyclic alkyl, alkyloxy, hydroxyalkyloxy, alkyl non-aromatic heterocyclic, alkyloxy aromatic heterocyclic amino non-aromatic carbocyclic; optionally substituted with one or more groups selected from these); unsubstituted carbamoyl; unsubstituted N-(bis(dialkylamino)methylene)carbamoyl; substituted sulfamoyl (substituents include alkyl; optionally substituted with one or more groups selected from these); unsubstituted sulfamoyl; unsubstituted dialkylphosphoryl; a substituted non-aromatic carbocyclic group (the substituent may be hydroxy; the group may be optionally substituted with one or more groups selected from these);Examples of the heterocyclic group include a substituted aromatic heterocyclic group (substituents include amino and alkyl; the group may be substituted with one or more groups selected from these); an unsubstituted aromatic heterocyclic group; an unsubstituted non-aromatic heterocyclic group; a substituted non-aromatic heterocyclic carbonyl (substituents include alkyl, alkyloxyalkyl, and dialkylcarbamoyl; the group may be substituted with one or more groups selected from these); and an unsubstituted non-aromatic heterocyclic carbonyl. The group may be substituted with one or more groups selected from these.

[0074] R ３ , R ３ａ , R ３ｂ and R ３ｂ’Examples of the substituent of the "substituted or unsubstituted aromatic carbocyclic group" in the formula (I) include halogen, cyano, substituted or unsubstituted alkyl (substituents include halogen, cyano, hydroxy, carboxy, carbamoyl, dialkylcarbamoyl, alkylsulfonylalkylcarbamoyl, dialkylaminoalkylcarbamoyl, (alkyl non-aromatic heterocyclic group)carbamoyl, alkyloxy, dialkylsulfoximino, amino non-aromatic heterocyclic group carbonyl; which may be substituted with one or more groups selected from these), unsubstituted alkyloxy, unsubstituted alkylcarbonyl, unsubstituted alkylsulfonyl, substituted sulfoximino (substituents include alkyl; which may be substituted with one or more groups selected from these), substituted iminosulfino (substituents include alkyl; which may be substituted with one or more groups selected from these), substituted or unsubstituted amino (substituents include alkylcarbonyl, alkylsulfonyl; which may be substituted with one or more groups selected from these), substituted or unsubstituted carbamoyl (substituents include alkyl, Hydroxyalkyl, dialkylaminoalkyl, hydroxyalkylaminoalkyl, non-aromatic heterocyclic alkyl, alkyloxy, alkyloxyalkyl, hydroxyalkyloxyalkyl, alkyl non-aromatic heterocyclic, ((alkyloxy aromatic heterocyclic) amino) non-aromatic carbocyclic group; optionally substituted with one or more groups selected from these), substituted or unsubstituted sulfamoyl (substituents include alkyl; optionally substituted with one or more groups selected from these), unsubstituted dialkylphosphoryl, substituted or unsubstituted non-aromatic carbocyclic group (substituents include hydroxy; optionally substituted with one or more groups selected from these), substituted or unsubstituted aromatic heterocyclic group (substituents include amino, alkyl; optionally substituted with one or more groups selected from these), unsubstituted non-aromatic heterocyclic group or substituted or unsubstituted non-aromatic heterocyclic carbonyl (substituents include alkyl; optionally substituted with one or more groups selected from these). Optionally substituted with one or more groups selected from these.

[0075] R ３ , R３ａ , R ３ｂ and R ３ｂ’ Examples of the substituents of the "substituted or unsubstituted aromatic heterocyclic group" in the formula (I) include halogen, cyano, carboxy, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted amino, substituted or unsubstituted imino, substituted or unsubstituted iminosulfino, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, and substituted or unsubstituted non-aromatic heterocyclic group. It may be substituted with one or more groups selected from these. R ３ Examples of the substituents of the "substituted or unsubstituted aromatic heterocyclic group" in the formula (I) include: halogen; cyano; hydroxy; substituted or unsubstituted alkyl; substituted or unsubstituted carbamoyl; substituted or unsubstituted imino; substituted or unsubstituted iminosulfino; and it may be substituted with one or more groups selected from these.

[0076] R ３ , R ３ａ , R ３ｂ and R ３ｂ’ Examples of the substituents of the "substituted or unsubstituted aromatic heterocyclic group" in the formula (I) include: halogen; cyano; hydroxy; substituted or unsubstituted alkyl; substituted or unsubstituted alkyloxy; substituted or unsubstituted amino; substituted or unsubstituted carbamoyl; and may be substituted with one or more groups selected from these.

[0077] R ３ , R ３ａ , R ３ｂ and R ３ｂ’Examples of the substituents of the "substituted or unsubstituted aromatic heterocyclic group" in the above formula include halogen, cyano, hydroxy, substituted alkyl (substituents include halogen and hydroxy; which may be substituted with one or more groups selected from these), unsubstituted alkyl, substituted alkyloxy (substituents include halogen; which may be substituted with one or more groups selected from these), unsubstituted alkyloxy, substituted amino (substituents include alkyl, carbamoyl, alkylcarbonyl, alkylsulfinyl, alkylsulfonyl; which may be substituted with one or more groups selected from these), unsubstituted amino, substituted carbamoyl (substituents include alkyl, unsubstituted non-aromatic heterocyclic alkyl, unsubstituted non-aromatic heterocyclic group; which may be substituted with one or more groups selected from these), and unsubstituted carbamoyl. It may be substituted with one or more groups selected from these.

[0078] R ３ , R ３ａ , R ３ｂ and R ３ｂ’ Examples of the substituents of the "substituted or unsubstituted non-aromatic heterocyclic group" in the formula (I) include halogen, carboxy, hydroxy, oxo, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted aromatic carbocyclic group, and substituted or unsubstituted aromatic heterocyclic group. R may be substituted with one or more groups selected from these. ３ , R ３ａ , R ３ｂ and R ３ｂ’ Examples of the substituents of the "substituted or unsubstituted non-aromatic heterocyclic group" in the formula (I) include halogen, hydroxy, substituted or unsubstituted alkyl, substituted alkyloxy, substituted or unsubstituted amino, and substituted or unsubstituted carbamoyl. The group may be substituted with one or more groups selected from these.

[0079] R ３ , R３ａ , R ３ｂ and R ３ｂ’ Examples of substituents for the "substituted or unsubstituted non-aromatic heterocyclic group" in the above formula include oxo; halogen; cyano; hydroxy; carboxy; substituted or unsubstituted alkyl; substituted or unsubstituted alkyloxy; substituted or unsubstituted alkyloxycarbonyl; substituted or unsubstituted amino; substituted or unsubstituted carbamoyl; substituted or unsubstituted alkylsulfonyl; substituted or unsubstituted aromatic heterocyclic group; substituted or unsubstituted non-aromatic heterocyclic carbonyl; and it may be substituted with one or more groups selected from these.

[0080] R ３ , R ３ａ , R ３ｂ and R ３ｂ’ Examples of the substituents of the "substituted or unsubstituted non-aromatic heterocyclic group" in the above formula include oxo; halogen; cyano; hydroxy; carboxy; substituted alkyl (substituents include halogen, hydroxy, carboxy, alkyloxy, amino, alkylamino, and unsubstituted non-aromatic heterocyclic groups; which may be substituted with one or more groups selected from these); unsubstituted alkyl; substituted alkyloxy (substituents include halogen; which may be substituted with one or more groups selected from these); unsubstituted alkyloxy; unsubstituted alkyloxycarbonyl; substituted amino (substituents include alkyl, alkylcarbonyl, and alkyloxycarbonyl; which may be substituted with one or more groups selected from these); unsubstituted amino; substituted carbamoyl (substituents include alkyl; which may be substituted with one or more groups selected from these); unsubstituted carbamoyl; unsubstituted alkylsulfonyl; unsubstituted aromatic heterocyclic groups; and unsubstituted non-aromatic heterocyclic carbonyl. Optionally substituted with one or more groups selected from these.

[0081] R ３ , R ３ａ , R ３ｂ and R ３ｂ’Examples of the substituents of the "substituted or unsubstituted non-aromatic heterocyclic group" in the above formula include a hydrogen atom, halogen, cyano, hydroxy, carboxy, substituted or unsubstituted alkyl (substituents include halogen, hydroxy, and alkyloxy; which may be substituted with one or more groups selected from these), substituted or unsubstituted alkyloxy (substituents include halogen; which may be substituted with one or more groups selected from these), unsubstituted alkyloxycarbonyl, substituted or unsubstituted amino (substituents include alkyl and alkylcarbonyl; which may be substituted with one or more groups selected from these), substituted or unsubstituted carbamoyl (substituents include alkyl; which may be substituted with one or more groups selected from these), unsubstituted alkylsulfonyl, unsubstituted aromatic heterocyclic group, and unsubstituted non-aromatic heterocyclic carbonyl; which may be substituted with one or more groups selected from these.

[0082] R ３ "Substituted or unsubstituted amino" in R ３ａ , R ３ｂ and R ３ｂ’ Substituents for the "substituted amino" in the above formula include, for example, substituted or unsubstituted alkyl; substituted or unsubstituted alkylcarbonyl; substituted or unsubstituted alkylsulfonyl; substituted or unsubstituted aromatic carbocyclic groups; substituted or unsubstituted non-aromatic carbocyclic groups; and substituted or unsubstituted non-aromatic heterocyclic groups. The amino group may be substituted with one or more groups selected from these.

[0083] R ３ "Substituted or unsubstituted amino" in R ３ａ , R ３ｂ and R ３ｂ’Examples of the substituents of the "substituted amino" in the above formula include: substituted alkyl (substituents include halogen, hydroxy, alkyloxy, non-aromatic carbocyclic group; optionally substituted with one or more groups selected from these); unsubstituted alkyl; substituted alkylcarbonyl (substituents include halogen, carbamoyl; optionally substituted with one or more groups selected from these); unsubstituted alkylcarbonyl; unsubstituted alkylsulfonyl; substituted aromatic carbocyclic group (substituents include haloalkyl, alkyloxy; optionally substituted with one or more groups selected from these); unsubstituted aromatic carbocyclic group; substituted non-aromatic carbocyclic group (substituents include halogen, hydroxy, alkyloxycarbonyl; optionally substituted with one or more groups selected from these); unsubstituted non-aromatic carbocyclic group; substituted non-aromatic heterocyclic group (substituents include halogen, alkyl; optionally substituted with one or more groups selected from these); optionally substituted with one or more groups selected from these.

[0084] R ３ "Substituted or unsubstituted amino" in R ３ａ , R ３ｂ and R ３ｂ’ Substituents of the "substituted amino" in the above formula (I) include, for example, a substituted or unsubstituted alkyl; a substituted or unsubstituted non-aromatic carbocyclic group; and it may be substituted with one or more groups selected from these.

[0085] R ３ "Substituted or unsubstituted amino" in R ３ａ , R ３ｂ and R ３ｂ’ In the above, examples of the substituents of the "substituted amino" include: substituted alkyl (the substituents are halogen and alkyloxy; which may be substituted with one or more groups selected from these); unsubstituted alkyl; unsubstituted non-aromatic carbocyclic group; which may be substituted with one or more groups selected from these.

[0086] R ３ , R ３ａ , R ３ｂ and R ３ｂ’In the formula (I), examples of the substituents of the "substituted or unsubstituted alkyloxy" include: halogen; hydroxy; sulfothio; substituted or unsubstituted non-aromatic carbocyclic ring; substituted or unsubstituted non-aromatic heterocyclic group; and it may be substituted with one or more groups selected from these.

[0087] R ３ , R ３ａ , R ３ｂ and R ３ｂ’ In the above, examples of the substituents of the "substituted or unsubstituted alkyloxy" include: halogen; hydroxy; sulfothio; substituted non-aromatic carbocyclic ring (substituents include halogen; which may be substituted with one or more groups selected from these); and unsubstituted non-aromatic heterocyclic group. It may be substituted with one or more groups selected from these.

[0088] R ３ , R ３ａ , R ３ｂ and R ３ｂ’ In the above, examples of the substituents of the "substituted or unsubstituted carbamoyl" and "substituted or unsubstituted sulfamoyl" include: substituted or unsubstituted alkyl; and may be substituted with one or more groups selected from these.

[0089] R ３ , R ３ａ , R ３ｂ and R ３ｂ’ In the above, examples of the substituents of the "substituted or unsubstituted carbamoyl" and "substituted or unsubstituted sulfamoyl" include: unsubstituted alkyl; and may be substituted with one or more groups selected from these.

[0090] R ３ , R ３ａ , R ３ｂ and R ３ｂ’ In the above formula, examples of the substituents of the "substituted or unsubstituted non-aromatic carbocyclic oxy" include: halogen; and it may be substituted with one or more groups selected from these.

[0091] R ３ , R ３ｂ and R ３ｂ’In the above, examples of the substituents of the "substituted or unsubstituted alkyl" include: a substituted or unsubstituted aromatic carbocyclic group; and it may be substituted with one or more groups selected from these.

[0092] R ３ , R ３ｂ and R ３ｂ’ In the formula (I), examples of the substituents for the "substituted or unsubstituted alkyl" include: a substituted or unsubstituted alkyloxy; a substituted or unsubstituted aromatic carbocyclic group; and it may be substituted with one or more groups selected from these.

[0093] R ３ , R ３ｂ and R ３ｂ’ In the above, examples of the substituents of the "substituted or unsubstituted alkyl" include: an unsubstituted aromatic carbocyclic group; and it may be substituted with one or more groups selected from these.

[0094] R ３ , R ３ｂ and R ３ｂ’ In the formula (I), examples of the substituents for the "substituted or unsubstituted alkyl" include: unsubstituted alkyloxy; unsubstituted aromatic carbocyclic group; and it may be substituted with one or more groups selected from these.

[0095] R ６ In the above formula, examples of the substituents of the "substituted or unsubstituted alkyloxy" include: halogen; and it may be substituted with one or more groups selected from these.

[0096] R ７ In the above, examples of the substituents of "substituted or unsubstituted alkyl", "substituted or unsubstituted alkenyl" and "substituted or unsubstituted alkynyl" include halogen, hydroxy, and may be substituted with one or more groups selected from these.

[0097] R ７In the formula (I), examples of the substituents of the "substituted or unsubstituted alkyloxy" include: halogen; cyano; substituted or unsubstituted alkyloxy; substituted or unsubstituted aromatic carbocyclic groups; and it may be substituted with one or more groups selected from these.

[0098] R ７ In the formula (I), examples of the substituents of the "substituted or unsubstituted alkyloxy" include: halogen; cyano; unsubstituted alkyloxy; unsubstituted aromatic carbocyclic group; and it may be substituted with one or more groups selected from these.

[0099] R ７ In the above formula, examples of the substituents of the "substituted or unsubstituted alkylsulfoxy" include: halogen; and may be substituted with one or more groups selected from these.

[0100] R ７ In the above formula, examples of the substituents of the "substituted or unsubstituted carbamoyl" include: substituted or unsubstituted alkyl; and it may be substituted with one or more groups selected from these.

[0101] R ７ In the above, examples of the substituents of the "substituted or unsubstituted carbamoyl" include: unsubstituted alkyl; and It may be substituted with one or more groups selected from these.

[0102] Formula (I): (Wherein, ring A is ) in the compound represented by the formula: １ , R ２ , R ３ , R ４ａ , R ４ｂ , R ５ａ , R ５ｂ , R ６ , R ７ , R ８ , R ９ , m, n, p, s, R ３ａ , R ３ｂ , R ３ｂ’ , R ７’ , R ８’ , R ９’Preferred embodiments of the formula (I) are shown below: The compounds represented by formula (I) include all combinations of the specific examples shown below.

[0103] R １ R may be a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted carbamoyl, or a substituted or unsubstituted amino (hereinafter referred to as A-1). １ R may be a substituted or unsubstituted nitrogen-containing aromatic heterocyclic group, a substituted or unsubstituted nitrogen-containing non-aromatic heterocyclic group, or a substituted or unsubstituted carbamoyl (hereinafter referred to as A-6). １ R may be a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, or a substituted or unsubstituted amino (hereinafter referred to as A-2). １ R may be a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as A-3). １ R is a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as A-4). １ R is a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as A-5). １ R may be a substituted or unsubstituted nitrogen-containing aromatic heterocyclic group or a substituted or unsubstituted nitrogen-containing non-aromatic heterocyclic group (hereinafter referred to as A-7). １ R is a substituted or unsubstituted nitrogen-containing aromatic heterocyclic group (hereinafter referred to as A-8). １ R is a substituted or unsubstituted nitrogen-containing non-aromatic heterocyclic group (hereinafter referred to as A-9). １ R is a substituted or unsubstituted 5- to 9-membered nitrogen-containing aromatic heterocyclic group or a substituted or unsubstituted 6-membered nitrogen-containing non-aromatic heterocyclic group (hereinafter referred to as A-10). １ R is a substituted or unsubstituted 5- to 9-membered nitrogen-containing aromatic heterocyclic group (hereinafter referred to as A-11). １ R is a substituted or unsubstituted 6-membered nitrogen-containing non-aromatic heterocyclic group (hereinafter referred to as A-12). １Examples of the group include substituted or unsubstituted triazolyl, substituted or unsubstituted pyridyl, substituted or unsubstituted dihydropyridyl, and substituted or unsubstituted imidazopyridyl (hereinafter referred to as A-12).

[0104] R ２ R may be a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, or a substituted or unsubstituted alkyl (hereinafter referred to as B-1). ２ R may be a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as B-2). ２ R is a substituted or unsubstituted aromatic carbocyclic group (hereinafter referred to as B-3). ２ R is a substituted or unsubstituted aromatic heterocyclic group (hereinafter referred to as B-4). ２ R is a substituted or unsubstituted 6-membered aromatic carbocyclic group or a substituted or unsubstituted 6-membered aromatic heterocyclic group (hereinafter referred to as B-7). ２ R is a substituted or unsubstituted 6-membered aromatic carbocyclic group (hereinafter referred to as B-8). ２ R is a substituted or unsubstituted 6-membered aromatic heterocyclic group (hereinafter referred to as B-9). ２ R is a 6-membered aromatic carbocyclic group substituted with 1, 2, 3, 4, or 5 substituents selected from Substituent Group G (Substituent Group G: halogen, cyano, alkyl, alkenyl, alkynyl, haloalkyl, alkyloxy, alkenyloxy, alkynyloxy, and haloalkyloxy), or a 6-membered aromatic heterocyclic group substituted with 1 or 2 substituents selected from Substituent Group G (hereinafter referred to as B-10). ２is a 6-membered aromatic carbocyclic group substituted with one halogen and further substituted with 1, 2, 3 or 4 substituents selected from Substituent Group G (Substituent Group G: halogen, cyano, alkyl, alkenyl, alkynyl, haloalkyl, alkyloxy, alkenyloxy, alkynyloxy and haloalkyloxy), or a 6-membered aromatic heterocyclic group substituted with one halogen and further substituted with 1 or 2 substituents selected from Substituent Group G (hereinafter referred to as B-5). ２ represents a 6-membered aromatic carbocyclic group substituted with one halogen and further substituted with 1, 2, 3, or 4 substituents selected from Substituent Group G (Substituent Group G: halogen, cyano, alkyl, alkenyl, alkynyl, haloalkyl, alkyloxy, alkenyloxy, alkynyloxy, and haloalkyloxy) (hereinafter, referred to as B-6).

[0105] R ３ R is a hydrogen atom, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted alkyloxy, or a substituted or unsubstituted amino (hereinafter referred to as C-1). ３ R is a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted alkyloxy, or a substituted or unsubstituted amino (hereinafter referred to as C-2). ３ R may be a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as C-3). ３ R is a substituted or unsubstituted aromatic carbocyclic group (hereinafter referred to as C-4). ３ R is a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as C-5). ３ teeth, (Wherein, t is an integer from 0 to 5, and R １０ａare each independently halogen, cyano, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted sulfoximino, or substituted or unsubstituted iminosulfino; or two R bonded to adjacent carbon atoms １０ａ may be taken together to form a substituted or unsubstituted aromatic heterocycle or a substituted or unsubstituted non-aromatic heterocycle; R １０ｂ , R １０ｂ’ , R １０ｃ , R １０ｃ’ , R １０ｄ , R １０ｄ’ , R １０ｅ , R １０ｅ’ , R １０ｆ , R １０ｆ’ , R １０ｇ , R １０ｇ’ , R １０ｈ , R １０ｈ’ , R １０ｉ , R １０ｉ’ , R １０ｊ and R １０ｊ’ are each independently a hydrogen atom, hydroxy, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyloxycarbonyl, or substituted or unsubstituted aromatic heterocyclic group; R １０ｂ and R １０ｂ’ , R １０ｃ and R １０ｃ’ , R １０ｄ and R １０ｄ’ , R １０ｅ and R １０ｅ’ , R １０ｆ and R １０ｆ’ , R １０ｇ and R １０ｇ’ , R １０ｈ and R １０ｈ’ , R１０ｉ and R １０ｉ’ , and R １０ｊ and R １０ｊ’ may each independently form, together with the carbon atom to which it is attached, oxo, a substituted or unsubstituted non-aromatic carbocyclic ring, or a substituted or unsubstituted non-aromatic heterocyclic ring; R １０ｂ and R １０ｃ , R １０ｃ and R １０ｄ , R １０ｄ and R １０ｅ , R １０ｆ and R １０ｇ , R １０ｇ and R １０ｈ , R １０ｈ and R １０ｉ , and R １０ｉ and R １０ｊ may each independently form, together with the carbon atom to which it is attached, a substituted or unsubstituted non-aromatic heterocycle or a substituted or unsubstituted non-aromatic carbocycle; R １０ｂ and R １０ｄ , R １０ｂ and R １０ｅ , R １０ｃ and R １０ｅ , R １０ｆ and R １０ｈ , R １０ｆ and R １０ｉ , R １０ｆ and R １０ｊ , R １０ｇ and R １０ｉ , R １０ｇ and R １０ｊ are each independently taken together to form a (C1-C4) bridge, one of the carbon atoms constituting the bridge may be replaced by an oxygen atom or a nitrogen atom; and the carbon atoms constituting the bridge are each independently R ａ and the nitrogen atom constituting the bridge is substituted with a substituent selected from R ｂ and R is substituted with a substituent selected from ａ represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ｂis a hydrogen atom or a substituted or unsubstituted alkyl) (hereinafter referred to as C-6). ３ａ R is a hydrogen atom, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted alkyloxy, a substituted amino, a halogen atom, a substituted or unsubstituted carbamoyl, a substituted or unsubstituted sulfamoyl, a substituted or unsubstituted non-aromatic carbocyclic oxy, or a substituted or unsubstituted non-aromatic heterocyclic oxy (hereinafter referred to as C-7). ３ｂ and R ３ｂ’ are each independently a hydrogen atom, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted alkyloxy, a substituted amino, a halogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted carbamoyl, a substituted or unsubstituted sulfamoyl, a substituted or unsubstituted non-aromatic carbocyclic oxy, or a substituted or unsubstituted non-aromatic heterocyclic oxy (hereinafter referred to as C-8). ３ａ , R ３ｂ and R ３ｂ’ are each independently a hydrogen atom, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted alkyloxy, a substituted amino, a halogen atom, a substituted or unsubstituted carbamoyl, a substituted or unsubstituted sulfamoyl, a substituted or unsubstituted non-aromatic carbocyclic oxy, or a substituted or unsubstituted non-aromatic heterocyclic oxy (hereinafter referred to as C-9). ３ａ , R ３ｂ and R ３ｂ’ R each independently represents a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as C-10). ３ａ , R ３ｂ and R ３ｂ’ R each independently represents a substituted or unsubstituted aromatic carbocyclic group (hereinafter referred to as C-11). ３ａ , R ３ｂ and R３ｂ’ R each independently represents a substituted or unsubstituted non-aromatic heterocyclic group (hereinafter referred to as C-12). ３ａ , R ３ｂ and R ３ｂ’ are each independently (Wherein, t is an integer from 0 to 5, and R １０ａ are each independently halogen, cyano, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted sulfoximino, or substituted or unsubstituted iminosulfino; or two R bonded to adjacent carbon atoms １０ａ may be taken together to form a substituted or unsubstituted aromatic heterocycle or a substituted or unsubstituted non-aromatic heterocycle; R １０ｂ , R １０ｂ’ , R １０ｃ , R １０ｃ’ , R １０ｄ , R １０ｄ’ , R １０ｅ , R １０ｅ’ , R １０ｆ , R １０ｆ’ , R １０ｇ , R １０ｇ’ , R １０ｈ , R １０ｈ’ , R １０ｉ , R １０ｉ’ , R １０ｊ and R １０ｊ’ are each independently a hydrogen atom, hydroxy, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyloxycarbonyl, or substituted or unsubstituted aromatic heterocyclic group; R １０ｂ and R １０ｂ’ , R １０ｃ and R １０ｃ’, R １０ｄ and R １０ｄ’ , R １０ｅ and R １０ｅ’ , R １０ｆ and R １０ｆ’ , R １０ｇ and R １０ｇ’ , R １０ｈ and R １０ｈ’ , R １０ｉ and R １０ｉ’ , and R １０ｊ and R １０ｊ’ may each independently form, together with the carbon atom to which it is attached, oxo, a substituted or unsubstituted non-aromatic carbocyclic ring, or a substituted or unsubstituted non-aromatic heterocyclic ring; R １０ｂ and R １０ｃ , R １０ｃ and R １０ｄ , R １０ｄ and R １０ｅ , R １０ｆ and R １０ｇ , R １０ｇ and R １０ｈ , R １０ｈ and R １０ｉ , and R １０ｉ and R １０ｊ may each independently form, together with the carbon atom to which it is attached, a substituted or unsubstituted non-aromatic heterocycle or a substituted or unsubstituted non-aromatic carbocycle; R １０ｂ and R １０ｄ , R １０ｂ and R １０ｅ , R １０ｃ and R １０ｅ , R １０ｆ and R １０ｈ , R １０ｆ and R １０ｉ , R １０ｆ and R １０ｊ , R １０ｇ and R １０ｉ , R １０ｇ and R １０ｊ are each independently taken together to form a (C1-C4) bridge, one of the carbon atoms constituting the bridge may be replaced by an oxygen atom or a nitrogen atom; and the carbon atoms constituting the bridge are each independently R ａand the nitrogen atom constituting the bridge is substituted with a substituent selected from R ｂ and R is substituted with a substituent selected from ａ represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; R ｂ is a hydrogen atom or a substituted or unsubstituted alkyl) (hereinafter referred to as C-13). ３ａ and R ３ｂ are each independently (wherein each symbol has the same meaning as C-13 above) (hereinafter referred to as C-14). ３ａ , R ３ｂ and R ３ｂ’ are each independently (wherein each symbol has the same meaning as C-13 above) or a substituted amino (hereinafter referred to as C-15). ３ａ and R ３ｂ are each independently (wherein each symbol has the same meaning as C-13 above) or a substituted amino (hereinafter referred to as C-16). ３ and R ８ The ring formed by combining with the carbon atoms to which each of R is bonded includes a substituted or unsubstituted aromatic carbocyclic ring or a substituted or unsubstituted aromatic heterocyclic ring (hereinafter referred to as C'-1). ３ａ and R ８ and R ３ｂ and R ８ The ring formed by combining with the carbon atom to which each of these is attached includes a substituted or unsubstituted aromatic carbocyclic ring (hereinafter referred to as C'-2).

[0106] R ４ａ is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as D-1). ４ａ is a hydrogen atom or an unsubstituted alkyl (hereinafter referred to as D-3). ４ａ is a hydrogen atom (hereinafter referred to as D-2).

[0107] R ４ｂR is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as E-1). ４ｂ is a hydrogen atom (hereinafter referred to as E-2).

[0108] R ５ａ R is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as F-1). ５ａ is a hydrogen atom (hereinafter referred to as F-2).

[0109] R ５ｂ is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as G-1). ５ｂ is a hydrogen atom (hereinafter referred to as G-2).

[0110] R ６ R is a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyloxy, a hydroxyl group, or a cyano group (hereinafter referred to as H-2). ６ R is exemplified by halogen, substituted or unsubstituted alkyloxy, hydroxy, or cyano (hereinafter referred to as H-3). ６ R is exemplified by halogen, alkyloxy, and hydroxy (hereinafter referred to as H-4). ６ represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyloxy (hereinafter referred to as H-1).

[0111] R ７ R includes a hydrogen atom, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted non-aromatic carbocyclic ring, substituted or unsubstituted non-aromatic heterocyclic ring, substituted or unsubstituted non-aromatic carbocyclic ring-oxy, substituted or unsubstituted amino, substituted or unsubstituted alkylsulfoxy, substituted or unsubstituted carbamoyl, hydroxy, carboxy, formyl, or cyano (hereinafter referred to as I-2). ７ R is a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted alkyloxy, or a substituted or unsubstituted amino (hereinafter referred to as I-1). ７R is a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy (hereinafter referred to as I-3). ７’ is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as I'-1). ９’ R is a hydrogen atom or a substituted or unsubstituted alkyl (hereinafter referred to as I'-2). ３ｂ and R ７’ The ring formed by combining with the atoms to which they are bonded includes a substituted or unsubstituted non-aromatic heterocycle (hereinafter referred to as I''-1).

[0112] R ８ and R ８’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy (hereinafter referred to as J-2). ８ and R ８’ are each independently a hydrogen atom or a halogen (hereinafter referred to as J-3). ８ is a hydrogen atom or a halogen (hereinafter referred to as J-1). ８ is a hydrogen atom (hereinafter referred to as J-4). ８ Examples of the halogen include halogen (hereinafter referred to as J-5).

[0113] R ９ R is exemplified by halogen, hydroxy, substituted or unsubstituted alkyl, and substituted or unsubstituted alkyloxy (hereinafter referred to as O-2). ９ R is halogen, hydroxy or alkyl (hereinafter referred to as O-2). ９ is substituted or unsubstituted alkyl (hereinafter referred to as O-1).

[0114] Examples of m include 0, 1, or 2 (hereinafter referred to as K-1). Examples of m include 0 or 1 (hereinafter referred to as K-2). Examples of m include 0 (hereinafter referred to as K-3). Examples of m include 1 (hereinafter referred to as K-4).

[0115] n may be 0, 1 or 2 (hereinafter referred to as L-1). n may be 0 or 1 (hereinafter referred to as L-2). n may be 0 (hereinafter referred to as L-4). n may be 1 (hereinafter referred to as L-3).

[0116] p may be 1, 2 or 3 (hereinafter referred to as M-1), or 1 (hereinafter referred to as M-2).

[0117] s may be 0, 1 or 2 (hereinafter referred to as N-1), s may be 0 or 1 (hereinafter referred to as N-3), or s may be 0 (hereinafter referred to as N-2).

[0118] Also, the formula (I): (Wherein, ring A is ) in the compound represented by the formula: １ , R ２ , R ３ , R ４ａ , R ４ｂ , R ５ａ , R ５ｂ , R ６ , R ７ , R ８ Preferred embodiments of m and n are shown below: As the compound represented by formula (I), embodiments of all combinations of the specific examples shown below are exemplified.

[0119] R １ Examples of R include A-1, A-2, A-3, A-4, and A-5. ２ Examples of R include B-1, B-2, B-3, B-4, B-5, and B-6. ３ R can be C-1, C-2, C-3, C-4, C-5, C-6, or C'-1. ４ａ Examples of R include D-1 and D-2. ４ｂ can be E-1 or E-2. ５ａ Examples of the R include F-1 and F-2. ５ｂ Examples of R include G-1 and G-2. ６ Examples of the compound include H-1. ７ Examples of the compound include I-1. ８Examples of n include J-1, m includes K-1, K-2, K-3, and K-4, and n includes L-1, L-2, and L-3.

[0120] Also, the formula (I): (Wherein, ring A is ) in the compound represented by the formula: １ , R ２ , R ３ａ , R ３ｂ , R ４ａ , R ４ｂ , R ５ａ , R ５ｂ , R ６ , R ７ , R ７’ , R ８ Preferred embodiments of m and n are shown below: As the compound represented by formula (I), embodiments of all combinations of the specific examples shown below are exemplified.

[0121] R １ Examples of R include A-6, A-7, A-8, and A-9. ２ Examples of R include B-5, B-6, B-7, B-8, and B-9. ３ａ R is C-7, C-10, C-11, C-12 or C-14. ３ｂ R is C-8, C-9, C-10, C-11, C-12 or C-14. ４ａ Examples of R include D-2 and D-3. ４ｂ Examples of the compound include E-2. ５ａ Examples of the F-2 include: ５ｂ Examples of the compound include G-2. ６ can be H-1, H-2 or H-3. ７ Examples of R include I-1 and I-2. ７’ is I'-1, or R ３ｂ and R ７’ Examples of R include I″-1. ８ is J-1 or J-2. m is K-2, K-3 or K-4. n is L-2, L-3 or L-4.

[0122] Another embodiment of the compound of formula (I) or a pharmaceutically acceptable salt thereof is exemplified below. Formula (I): In the formula, ring A is wherein R ３ａ and R ３ｂ are each independently (Wherein, Y is CR １０ｈ R １０ｈ’ or O; t is an integer from 1 to 5; R １０ａare each independently halogen, cyano, substituted or unsubstituted alkyl (substituents include halogen, cyano, hydroxy, carboxy, carbamoyl, dialkylcarbamoyl, alkylsulfonylalkylcarbamoyl, dialkylaminoalkylcarbamoyl, alkyl non-aromatic heterocyclic group carbamoyl, alkyloxy, dialkylsulfoximino, amino non-aromatic heterocyclic group carbonyl; which may be substituted with one or more groups selected from these), unsubstituted alkyloxy, unsubstituted alkylcarbonyl, unsubstituted alkylsulfonyl, substituted sulfoximino (substituents include alkyl; which may be substituted with one or more groups selected from these), substituted iminosulfino (substituents include alkyl; which may be substituted with one or more groups selected from these), substituted or unsubstituted amino (substituents include alkylcarbonyl, alkylsulfonyl; which may be substituted with one or more groups selected from these), substituted or unsubstituted carbamo yl (substituents include alkyl, hydroxyalkyl, dialkylaminoalkyl, hydroxyalkylaminoalkyl, non-aromatic heterocyclic alkyl, alkyloxy, alkyloxyalkyl, hydroxyalkyloxyalkyl, and alkyl non-aromatic heterocyclic groups; optionally substituted with one or more groups selected from these), substituted or unsubstituted sulfamoyl (substituents include alkyl; optionally substituted with one or more groups selected from these), unsubstituted dialkylphosphoryl, substituted or unsubstituted non-aromatic carbocyclic groups (substituents include hydroxy; optionally substituted with one or more groups selected from these), substituted or unsubstituted aromatic heterocyclic groups (substituents include amino and alkyl; optionally substituted with one or more groups selected from these), unsubstituted non-aromatic heterocyclic groups, or substituted or unsubstituted non-aromatic heterocyclic carbonyl (substituents include alkyl; optionally substituted with one or more groups selected from these); or １０ａ may be joined together to form a substituted or unsubstituted aromatic heterocycle or a substituted or unsubstituted non-aromatic heterocycle; １０ａThe substituents on the ring of "a substituted or unsubstituted aromatic heterocycle formed by two R bonded to adjacent carbon atoms" are groups selected from cyano, alkyl, haloalkyl and alkyloxy; and may be substituted with one or more groups selected from these; １０ａ The substituents on the ring of the "substituted or unsubstituted non-aromatic heterocycle" formed by combining R are groups selected from oxo, alkyl, haloalkyl and non-aromatic carbocycles; R may be substituted with one or more groups selected from these; １０ｂ , R １０ｂ’ , R １０ｃ , R １０ｃ’ , R １０ｄ , R １０ｄ’ , R １０ｅ , R １０ｅ’ , R １０ｆ , R １０ｆ’ , R １０ｇ , R １０ｇ’ , R １０ｈ , R １０ｈ’ , R １０ｉ , R １０ｉ’ , R １０ｊ and R １０ｊ’ are each independently a hydrogen atom, halogen, cyano, hydroxy, carboxy, substituted or unsubstituted alkyl (substituents include halogen, hydroxy, and alkyloxy; which may be substituted with one or more groups selected from these), substituted or unsubstituted alkyloxy (substituents include halogen; which may be substituted with one or more groups selected from these), substituted or unsubstituted amino (substituents include alkyl and alkylcarbonyl; which may be substituted with one or more groups selected from these), substituted or unsubstituted carbamoyl (substituents include alkyl; which may be substituted with one or more groups selected from these), unsubstituted alkylsulfonyl, unsubstituted aromatic heterocyclic group, or unsubstituted non-aromatic heterocyclic carbonyl; R １０ｂ and R １０ｂ’ , R １０ｃ and R １０ｃ’ , R １０ｄ and R １０ｄ’ , R １０ｅ and R １０ｅ’ , R １０ｆ and R１０ｆ’ , R １０ｇ and R １０ｇ’ , R １０ｈ and R １０ｈ’ , R １０ｉ and R １０ｉ’ , and R １０ｊ and R １０ｊ’ may each independently form, together with the carbon atom to which it is attached, an oxo or non-aromatic heterocycle; R １０ｂ and R １０ｃ , R １０ｃ and R １０ｄ , R １０ｄ and R １０ｅ , R １０ｆ and R １０ｇ , R １０ｇ and R １０ｈ , R １０ｈ and R １０ｉ , and R １０ｉ and R １０ｊ may each independently form, together with the carbon atom to which it is bonded, a substituted or unsubstituted non-aromatic heterocycle (which may be substituted with a halogen atom or one or more groups selected therefrom) or a substituted or unsubstituted non-aromatic carbocycle (which may be substituted with a halogen atom or one or more groups selected therefrom); R １０ｂ and R １０ｄ , R １０ｂ and R １０ｅ , R １０ｃ and R １０ｅ , R １０ｆ and R １０ｈ , R １０ｆ and R １０ｉ , R １０ｆ and R １０ｊ , R １０ｇ and R １０ｉ , R １０ｇ and R １０ｊ are each independently taken together to form a (C1-C4) bridge, one of the carbon atoms constituting the bridge may be replaced by an oxygen atom or a nitrogen atom; and the carbon atoms constituting the bridge are each independently R ａ and the nitrogen atom constituting the bridge is substituted with a substituent selected from R ｂand R is substituted with a substituent selected from ａ is a hydrogen atom and hydroxy; R ｂ is a hydrogen atom) or a substituted amino; ３ａ and R ３ｂ The substituent of the "substituted amino" in R is a group selected from substituted alkyl (the substituents are halogen and alkyloxy; it may be substituted with one or more groups selected from these), unsubstituted alkyl, and unsubstituted non-aromatic carbocyclic group; it may be substituted with one or more groups selected from these; ８ is a hydrogen atom or a halogen; R ６ is halogen, alkyloxy or hydroxy; R ７ is a hydrogen atom, halogen, alkyl, alkyloxy or cyanoalkyloxy; R ７’ is a hydrogen atom or alkyl; R ３ｂ and R ７’ may form a non-aromatic heterocyclic ring together with the carbon atom to which each is attached; R ９ are each independently halogen, hydroxy, or alkyl; s is 0 or 1; R １ is a substituted or unsubstituted 5- to 9-membered nitrogen-containing aromatic heterocyclic group or a substituted or unsubstituted 6-membered nitrogen-containing non-aromatic heterocyclic group; R １ The substituents on the ring of the "substituted or unsubstituted 5- to 9-membered nitrogen-containing aromatic heterocyclic group" in the formula (I) are groups selected from halogen, cyano, alkyl, haloalkyl, alkyloxy, and haloalkyloxy; and may be substituted with one or more groups selected from these; １ The substituents on the ring of the "substituted or unsubstituted 6-membered nitrogen-containing non-aromatic heterocyclic group" in R are groups selected from oxo and halogen; and may be substituted with one or more groups selected from these; ２is a 6-membered aromatic carbocyclic group substituted with 1, 2, 3, 4, or 5 substituents selected from the substituent group G (substituent group G: halogen, cyano, alkyl, alkenyl, alkynyl, haloalkyl, alkyloxy, alkenyloxy, alkynyloxy, and haloalkyloxy), or a 6-membered aromatic heterocyclic group substituted with 1 or 2 substituents selected from the substituent group G; n is 0 or 1; R ４ａ and R ４ｂ are each independently a hydrogen atom or alkyl; m is 0 or 1; R ５ａ and R ５ｂ are each independently a hydrogen atom.

[0123] The compound represented by formula (I) is not limited to a particular isomer, and includes all possible isomers (e.g., keto-enol isomers, imine-enamine isomers, diastereoisomers, optical isomers, rotamers, etc.), racemates, or mixtures thereof.

[0124] One or more hydrogen, carbon and / or other atoms of the compounds of formula (I) may be replaced by isotopes of the respective hydrogen, carbon and / or other atoms. Examples of such isotopes include: ２ H. ３ H. １１ C. １３ C. １４ C. １５ N. １８ O. １７ O. ３１ P. ３２ P. ３５ S. １８ F. 123 I and ３６The isotopes of the compounds of formula (I) include hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, iodine, and chlorine, such as Cl. The compounds of formula (I) also include compounds substituted with such isotopes. The isotope-substituted compounds are also useful as pharmaceuticals, and include all radiolabeled compounds of formula (I). Also included in the present invention is a "radiolabeling method" for producing the "radiolabeled compounds," which are useful as research and / or diagnostic tools in metabolism pharmacokinetic studies and binding assays.

[0125] Radiolabeled compounds of formula (I) can be prepared by methods well known in the art. For example, tritium-labeled compounds of formula (I) can be prepared by introducing tritium into a specific compound of formula (I) via catalytic dehalogenation using tritium. This method involves reacting a suitable halogen-substituted precursor of formula (I) with tritium gas in the presence of a suitable catalyst, such as Pd / C, in the presence or absence of a base. Other suitable methods for preparing tritium-labeled 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 are １４ It can be prepared by using a raw material having C carbon.

[0126] Pharmaceutically acceptable salts of the compound represented by formula (I) include, for example, salts of the compound represented by formula (I) with alkali metals (e.g., lithium, sodium, potassium, etc.), alkaline earth metals (e.g., calcium, barium, etc.), magnesium, transition metals (e.g., zinc, iron, etc.), ammonia, organic bases (e.g., trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, meglumine, ethylenediamine, pyridine, picolinic acid, methylparaben ... Examples of suitable salts include salts with carboxylic acids (e.g., carboxylic acids such as carboxylic acids, ...

[0127] The compound of formula (I) of the present invention or a pharmaceutically acceptable salt thereof may form a solvate (e.g., hydrate, etc.), a co-crystal, and / or a crystalline polymorph, and the present invention also encompasses such various solvates, co-crystals, and crystalline polymorphs. A "solvate" may be coordinated with the compound of formula (I) with any number of solvent molecules (e.g., water molecules, etc.). When the compound of formula (I) or a pharmaceutically acceptable salt thereof is left in the atmosphere, it may absorb moisture, resulting in the adsorbed water adsorbing, or may form a hydrate. Furthermore, a crystalline polymorph may be formed by recrystallization of the compound of formula (I) or a pharmaceutically acceptable salt thereof. A "co-crystal" means that the compound of formula (I) or a salt thereof and a counter molecule exist in the same crystal lattice, and may contain any number of counter molecules.

[0128] The compound of the present invention represented by formula (I) or a pharmaceutically acceptable salt thereof may form a prodrug, and the present invention also encompasses such various prodrugs. A prodrug is a derivative of the compound of the present invention having a chemically or metabolically decomposable group, and is a compound that becomes a pharmaceutically active compound of the present invention in vivo by solvolysis or under physiological conditions. Prodrugs include compounds that are converted to the compound of formula (I) by enzymatic oxidation, reduction, hydrolysis, etc. under physiological conditions in vivo, and compounds that are converted to the compound of formula (I) by hydrolysis with gastric acid, etc. Methods for selecting and preparing appropriate prodrug derivatives are described, for example, in "Design of Prodrugs, Elsevier, Amsterdam, 1985." Prodrugs may themselves be active.

[0129] When the compound represented by formula (I) or a pharmaceutically acceptable salt thereof has a hydroxyl group, examples of the prodrug include acyloxy derivatives and sulfonyloxy derivatives produced by reacting the compound having a hydroxyl group with an appropriate acyl halide, an appropriate acid anhydride, an appropriate sulfonyl chloride, an appropriate sulfonyl anhydride, and a mixed anhydride, or by reacting the compound using a condensing agent. For example, CH ３ COO-, C ２ H ５ COO-, tert-BuCOO-, C １５ H ３１ COO-, PhCOO-, (m-NaOOCPh)COO-, NaOOCCH ２ CH ２ COO-, CH ３ CH(NH ２ ) COO-, CH ２ N (CH ３ ) ２ COO-, CH ３ SO ３ -, CH ３ CH ２ SO ３ -, CF ３ SO ３ -, CH ２ FSO３ -, CF ３ CH ２ SO ３ -, p-CH ３ O-PhSO ３ -, PhSO ３ -, p-CH ３ PhSO ３ - are some examples.

[0130] The compounds of the present invention have inhibitory activity against coronavirus 3CL protease and are therefore useful as therapeutic and / or preventive agents for diseases associated with coronavirus 3CL protease. In the present invention, the term "therapeutic and / or preventive agent" also encompasses symptom-ameliorating agents. Diseases associated with coronavirus 3CL protease include viral infections, preferably coronavirus infections. In one embodiment, the coronavirus includes a coronavirus that infects humans. Examples of coronaviruses that infect humans include HCoV-229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43, SARS-CoV, MERS-CoV, and / or SARS-CoV-2. In one embodiment, the coronavirus includes an alphacoronavirus and / or a betacoronavirus, more preferably a betacoronavirus, and even more preferably a sarbecovirus. In one embodiment, the alphacoronavirus includes HCoV-229E and HCoV-NL63. Particularly preferred is HCoV-229E. In one embodiment, betacoronaviruses include HCoV-HKU1, HCoV-OC43, SARS-CoV, MERS-CoV, and / or SARS-CoV-2. Preferably, HCoV-OC43 or SARS-CoV-2 is used, and particularly preferably SARS-CoV-2. In one embodiment, betacoronaviruses include betacoronavirus lineage A (β-coronavirus lineage A), betacoronavirus lineage B (β-coronavirus lineage B), and betacoronavirus lineage C (β-coronavirus lineage C). More preferred are beta coronavirus lineage A and beta coronavirus lineage B, with beta coronavirus lineage B being particularly preferred.Examples of betacoronavirus lineage A include HCoV-HKU1 and HCoV-OC43, preferably HCoV-OC43. Examples of betacoronavirus lineage B include SARS-CoV and SARS-CoV-2, preferably SARS-CoV-2. Examples of betacoronavirus lineage C include MERS-CoV. In one embodiment, the coronavirus includes HCoV-229E, HCoV-OC43, and / or SARS-CoV-2, particularly preferably SARS-CoV-2. Examples of coronavirus infections include infections caused by HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and / or SARS-CoV-2. Preferably, infections caused by HCoV-229E, HCoV-OC43, and / or SARS-CoV-2 are included, and particularly preferably infections caused by SARS-CoV-2. Particularly preferably, examples of coronavirus infections include novel coronavirus disease (COVID-19).

[0131] (Method for producing the compound of the present invention) The compound represented by formula (I) according to the present invention can be produced, for example, by the general synthesis method shown below. Extraction, purification, etc. can be carried out by the same procedures as those performed in ordinary organic chemistry experiments. The compound of the present invention can be produced by referring to methods known in the art. For example, it can be produced by referring to WO2013 / 184806, US4731106, WO2013 / 064083, and WO2020 / 261114.

[0132] (Method A) When Ring A is an aromatic carbocyclic ring or aromatic heterocyclic ring (In the formula, Lg is a leaving group, and the other symbols are as defined above.)

[0133] (Step 1) Compound (A-3) can be obtained by adding HATU, WSC.HCl, and a condensing agent such as HOBt or PyBOP to compound (A-1) in the presence of a solvent such as DMF, DMA, NMP, or THF, or in a mixed solvent thereof, and then adding an amine (A-2) corresponding to the target compound and, if necessary, a tertiary amine such as triethylamine, N-methylmorpholine, or N,N-diisopropylethylamine, and reacting the mixture at 0° C. to 60° C., preferably 20° C. to 40° C., for 0.1 to 24 hours, preferably 0.5 to 12 hours.

[0134] (Step 2) Compound (A-4) can be obtained by adding a carbonylating agent such as triphosgene, CDI, di-tert-butyl dicarbonate, urea, 4-nitrophenyl chloroformate, or methyl chloroformate to compound (A-3) in the presence of a solvent such as DMF, DMA, NMP, THF, toluene, acetonitrile, dimethyl sulfoxide, dioxane, or dichloromethane, or in a mixed solvent thereof, and reacting the mixture at 0° C. to 140° C., preferably 20° C. to 100° C., for 0.1 to 24 hours, preferably 0.5 to 12 hours.

[0135] (Step 3) Compound (A-5) corresponding to the target compound is added to compound (A-4) in the presence of acetonitrile, acetone, DMF, DMSO, NMP, etc. or a mixed solvent thereof, in the presence of a base such as potassium carbonate, sodium carbonate, or cesium carbonate, and the reaction is carried out at 0°C to 100°C, preferably 20°C to 60°C, for 0.1 to 24 hours, preferably 0.5 to 12 hours, to produce compound (I). Examples of leaving groups include halogen and -OSO ２ (C ｔ F ２ｔ＋１ ) (wherein t is an integer of 1 to 4). Preferred halogens are chlorine, iodine and bromine, and -OSO ２ (C ｔ F ２ｔ＋１ ) group is preferably an -OTf group (trifluoromethanesulfonate ester).

[0136] (Method B) When Ring A is an aromatic carbocyclic ring or aromatic heterocyclic ring (In the formula, Lg is a leaving group, and the other symbols are as defined above.)

[0137] (Step 1) Compound (B-3) can be obtained by adding compound (B-2) corresponding to the target compound and a tertiary amine such as triethylamine, N-methylmorpholine, N,N-diisopropylethylamine, etc., and optionally DMAP to compound (B-1) in the presence of a solvent such as DMF, DMA, NMP, THF, toluene, etc., or in a mixed solvent thereof, and reacting the resulting mixture at 0° C. to 140° C., preferably 20° C. to 100° C., for 0.1 to 24 hours, preferably 0.5 to 12 hours. Examples of the leaving group include halogen and alkoxy.

[0138] (Step 2) Compound (B-4) can be produced by adding an acid such as hydrochloric acid or sulfuric acid to compound (B-3) and reacting the mixture at 0°C to 160°C, preferably 40°C to 120°C, for 0.1 to 24 hours, preferably 0.5 to 12 hours.

[0139] (Step 3) Compound (B-4) is added with compound (B-5) corresponding to the target compound in the presence of acetonitrile, acetone, DMF, DMSO, NMP, or a mixed solvent thereof, in the presence of a base such as potassium carbonate, sodium carbonate, or cesium carbonate, and the reaction is carried out at 0°C to 100°C, preferably 20°C to 60°C, for 0.1 to 24 hours, preferably 0.5 to 12 hours, to produce compound (B-6). Examples of leaving groups include halogen and -OSO ２ (C ｔ F ２ｔ＋１ ) (wherein t is an integer of 1 to 4). Preferred halogens are chlorine, iodine and bromine, and -OSO ２ (C ｔ F ２ｔ＋１ ) group is preferably an -OTf group (trifluoromethanesulfonate ester).

[0140] (Method C) When Ring A is a non-aromatic carbocyclic ring or a non-aromatic heterocyclic ring (In the formula, Lg is a leaving group, and the other symbols are as defined above.)

[0141] (Step 1) Compound (C-2) can be obtained by adding urea and a base such as sodium methoxide or sodium ethoxide to compound (C-1) in a solvent such as methanol or ethanol, and reacting the mixture at 0°C to 140°C, preferably 20°C to 100°C, for 0.1 to 48 hours, preferably 0.5 to 18 hours.

[0142] (Step 2) Compound (C-4) can be produced by adding N,O-bis(trimethylsilyl)acetamide and the corresponding compound (C-3), and, if necessary, a quaternary ammonium salt such as tetrabutylammonium bromide, to compound (C-2) in the presence of acetonitrile, acetone, DMF, DMSO, NMP, or the like, or in a mixed solvent thereof, and reacting at 0°C to 140°C, preferably 40°C to 100°C, for 0.1 to 48 hours, preferably 0.5 to 18 hours. Alternatively, compound (C-4) can be produced by adding compound (C-3) corresponding to the target compound to compound (C-2) in the presence of DMF, DMSO, NMP, or the like, or in a mixed solvent thereof, in the presence of a base such as potassium carbonate, sodium carbonate, cesium carbonate, or sodium hydride, and reacting at 0°C to 100°C, preferably 20°C to 60°C, for 0.1 to 24 hours, preferably 0.5 to 12 hours. Examples of leaving groups include halogen and -OSO ２ (C ｔ F ２ｔ＋１ ) (wherein t is an integer of 1 to 4). Preferred halogens are chlorine, iodine and bromine, and -OSO ２ (C ｔ F ２ｔ＋１ ) group is preferably an -OTf group (trifluoromethanesulfonate ester).

[0143] (Step 3) Compound (C-4) is added with compound (C-5) corresponding to the target compound in the presence of DMF, DMSO, NMP, or a mixed solvent thereof, in the presence of a base such as potassium carbonate, sodium carbonate, cesium carbonate, or sodium hydride, and the reaction is carried out at 0°C to 100°C, preferably 20°C to 60°C, for 0.1 to 24 hours, preferably 0.5 to 12 hours, to produce compound (C-6). Examples of leaving groups include halogen and -OSO ２ (C ｔ F ２ｔ＋１ ) (wherein t is an integer of 1 to 4). Preferred halogens are chlorine, iodine and bromine, and -OSO ２ (C ｔ F ２ｔ＋１ ) group is preferably an -OTf group (trifluoromethanesulfonate ester).

[0144] The compounds of the present invention have inhibitory activity against coronavirus 3CL protease and are therefore useful as therapeutic and / or preventive agents for viral infections. Furthermore, the compounds of the present invention are useful as pharmaceuticals and preferably have one or more of the following excellent characteristics: a) weak inhibitory activity against CYP enzymes (e.g., CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, etc.); b) good pharmacokinetics, such as high bioavailability and moderate clearance; c) high metabolic stability; d) no irreversible inhibitory activity against CYP enzymes (e.g., CYP3A4) within the concentration range of the measurement conditions described herein; e) no mutagenicity; f) low cardiovascular risk; g) high solubility; h) high protein unbound rate (fu value); i) high selectivity for coronavirus 3CL protease; and j) high coronavirus growth inhibitory activity. For example, it has high coronavirus growth inhibitory activity when human serum (HS) or human serum albumin (HSA) is added. k) It has high growth inhibitory activity against 3CL protease inhibitor-resistant viruses. As a coronavirus growth inhibitor, for example, in the CPE suppression effect confirmation test (SARS-CoV-2) described below, it is possible to use a compound having high growth inhibitory activity against EC ５０is 10 μM or less, preferably 1 μM or less, and more preferably 100 nM or less.

[0145] The pharmaceutical composition of the present invention can be administered orally or parenterally, including transdermal, subcutaneous, intravenous, intraarterial, intramuscular, intraperitoneal, transmucosal, inhalation, nasal, ophthalmic, otic, and vaginal administration.

[0146] For oral administration, the composition may be prepared and administered in any of the commonly used dosage forms, such as solid preparations for internal use (e.g., tablets, powders, granules, capsules, pills, films, etc.) and liquid preparations for internal use (e.g., suspensions, emulsions, elixirs, syrups, lemonades, spirits, perfumes, extracts, decoctions, tinctures, etc.), according to conventional methods. Tablets may be sugar-coated tablets, film-coated tablets, enteric-coated tablets, sustained-release tablets, troches, sublingual tablets, buccal tablets, chewable tablets, or orally disintegrating tablets; powders and granules may be dry syrups; and capsules may be soft capsules, microcapsules, or sustained-release capsules.

[0147] In the case of parenteral administration, the compound can be suitably administered in any of the commonly used dosage forms, such as injections, infusions, and topical preparations (e.g., eye drops, nasal drops, ear drops, aerosols, inhalants, lotions, infusions, liniments, mouthwashes, enemas, ointments, plasters, jellies, creams, patches, poultices, powders for topical use, suppositories, etc.). Injections may be emulsions such as O / W, W / O, O / W / O, and W / O / W types.

[0148] Pharmaceutical compositions can be prepared by mixing an effective amount of the compound of the present invention with various pharmaceutical additives, such as excipients, binders, disintegrants, and lubricants, appropriate for the dosage form, as needed. Furthermore, by appropriately modifying the effective amount of the compound of the present invention, the dosage form, and / or the various pharmaceutical additives, the pharmaceutical composition can also be prepared as a pharmaceutical composition for pediatrics, the elderly, critically ill patients, or surgical patients. For example, pediatric pharmaceutical compositions can be administered to newborns (less than 4 weeks old), infants (4 weeks old to less than 1 year old), toddlers (1 year old to less than 7 years old), children (7 years old to less than 15 years old), or patients aged 15 to 18 years. For example, pharmaceutical compositions for the elderly can be administered to patients aged 65 years or older.

[0149] The dosage of the pharmaceutical composition of the present invention is desirably determined taking into consideration the patient's age, body weight, type and severity of the disease, route of administration, etc., but when administered orally, it is usually 0.05 to 200 mg / kg / day, preferably 0.1 to 100 mg / kg / day. When administered parenterally, it varies greatly depending on the route of administration, but is usually 0.005 to 200 mg / kg / day, preferably 0.01 to 100 mg / kg / day. This dosage may be administered once or in divided doses per day.

[0150] The compound of the present invention may be used in combination with, for example, another therapeutic agent for novel coronavirus disease (COVID-19) (such therapeutic agents include approved agents and agents under development or to be developed in the future) (hereinafter referred to as a concomitant drug) for the purpose of enhancing the effect of the compound or reducing the dosage of the compound. In this case, the administration timing of the compound of the present invention and the concomitant drug is not limited, and they may be administered to the subject simultaneously or at staggered times. Furthermore, the compound of the present invention and the concomitant drug may be administered as two or more types of preparations containing the respective active ingredients, or as a single preparation containing those active ingredients.

[0151] The dose of the concomitant drug can be appropriately selected based on the clinically used dose. The compounding ratio of the compound of the present invention to the concomitant drug can be appropriately selected depending on the administration subject, administration route, target disease, symptoms, combination, etc. For example, when the administration subject is a human, 0.01 to 100 parts by weight of the concomitant drug may be used per 1 part by weight of the compound of the present invention.

[0152] The present invention will be explained in more detail below with reference to Examples, Reference Examples and Test Examples, but the present invention is not limited to these.

[0153] The abbreviations used in this specification have the following meanings: CDI: carbonyldiimidazole, DMA: dimethylacetamide, DMAP: 4-dimethylaminopyridine, DMF: N,N-dimethylformamide, ESI: electrospray ionization, FBS: fetal bovine serum, NMP: N-methylpyrrolidone, PdCl２ (dppf): [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct PyBOP: (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate RT: retention time RuPhos Pd G3: (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate mM: mmol / L μM: μmol / L nM: nmol / L

[0154] (Method for identifying compounds) NMR analysis obtained in each example was carried out at 400 MHz, and DMSO-d ６ , CDCl ３Measurement was performed using a NMR spectrometer. Furthermore, when NMR data is presented, not all measured peaks may be listed. In the specification, RT represents the retention time in LC / MS (liquid chromatography / mass spectrometry), and was measured under the following conditions. (Measurement Condition 1) Column: ACQUITY UPLC (registered trademark) BEH C18 (1.7 μm i.d. 2.1 x 50 mm) (Waters) Flow rate: 0.8 mL / min UV detection wavelength: 254 nm Mobile phase: [A] is an aqueous solution containing 0.1% formic acid, [B] is an acetonitrile solution containing 0.1% formic acid Gradient: A linear gradient of 5%-100% solvent [B] was performed over 3.5 minutes, followed by maintaining 100% solvent [B] for 0.5 minutes. (Measurement Condition 2) Column: Shim-pack XR-ODS (2.2 μm, i.d. 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: A linear gradient of 10%-100% solvent [B] was performed over 3 minutes, and 100% solvent [B] was maintained for 0.5 minutes. (Measurement Condition 3) Column: ACQUITY UPLC (registered trademark) BEH C18 (1.7 μm i.d. 2.1 x 50 mm) (Waters) Flow rate: 0.8 mL / min UV detection wavelength: 254 nm Mobile phase: [A] is an aqueous solution containing 10 mM ammonium carbonate, [B] is acetonitrile Gradient: A linear gradient of 5%-100% solvent [B] was performed over 3.5 minutes, followed by maintaining 100% solvent [B] for 0.5 minutes. In the specification, the term MS (m / z) refers to a value observed by mass spectrometry.

[0155] (Compound separation method) (Reverse-phase separation) Column: Gemini (registered trademark) 5 μm NX-C18 110 A, LC Column 100 x 30 mm, AXIA (trademark) Packed (Phenomenex) Flow rate: 25 mL / min UV detection wavelength: 254 nm Mobile phase: [A] is 10 mmol / L ammonium carbonate aqueous solution, [B] is acetonitrile Gradient: Yes Start (0 min) [A]:[B] = 40:60 End (8 min) [A]:[B] = 20:80 Wash (8-10 min) [A]:[B] = 0:100

[0156] Synthesis of compound (I-0299) Step 1: Synthesis of Compound 1 2-Amino-4-bromo-6-fluorobenzoic acid (1.00 g, 4.27 mmol) was dissolved in dichloromethane (20 ml), and PyBOP (2.67 g, 5.13 mmol) and diisopropylethylamine (2.24 ml, 12.8 mmol) were added, followed by stirring at room temperature for 18 hours. Water (50 ml) was added to the reaction mixture, followed by separation, and the aqueous layer was extracted with dichloromethane. The organic layer was washed with water and then dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate / methanol) to obtain Compound 1 (1.63 g, 4.97 mmol, 100% yield). LC / MS (ESI): m / z = 328, RT = 1.41 min, LC / MS measurement condition 1

[0157] Step 2: Synthesis of Compound 2 A mixture of Compound 1 (1.34 g, 4.08 mmol), THF (13 ml), and CDI (1.32 g, 8.17 mmol) was stirred at 70° C. for 4 hours. The reaction mixture was cooled to room temperature, water was added, and the precipitated solid was collected by filtration to obtain Compound 2 (906 mg, 2.56 mmol, yield 63%). LC / MS (ESI): m / z = 354, RT = 1.35 min, LC / MS measurement condition 1

[0158] Step 3 Synthesis of Compound 3 Compound 2 (50.0 mg, 0.141 mmol) was dissolved in DMF (1 ml), and 28% sodium methoxide-methanol solution (0.103 ml, 0.424 mmol) was added, followed by stirring at 60°C for 1 hour. The reaction solution was cooled to room temperature, neutralized with 10% aqueous citric acid, and the precipitated solid was collected by filtration to obtain Compound 3 (51.0 mg, 0.139 mmol, yield 99%). LC / MS (ESI): m / z = 366, RT = 1.23 min, LC / MS measurement condition 1

[0159] Step 4 Synthesis of Compound 4 Compound 3 (50.0 mg, 0.137 mmol), DMF (1.0 ml), and potassium carbonate (37.7 g, 0.273 mmol) were mixed and stirred at room temperature for 10 minutes. 1-(Bromomethyl)-2,4,5-trifluorobenzene (32.3 mg, 0.143 mmol) was added at 0°C, and the mixture was warmed to room temperature and stirred for 2 hours. Water was added to the reaction mixture, and the precipitated solid was dissolved in chloroform, washed with water, and then dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting crude product was crystallized from ethyl acetate-diisopropyl ether to obtain Compound 4 (51 mg, 0.10 mmol, yield 73%). LC / MS (ESI): m / z = 510, RT = 2.00 min, LC / MS measurement condition 1

[0160] Step 5 Synthesis of Compound 5 Compound 4 (48.0 mg, 0.0940 mmol), (5-carbamoyl-2-chlorophenyl)boronic acid (24.4 mg, 0.122 mmol), dioxane (0.7 ml), 2 mol / L aqueous potassium carbonate solution (0.0940 ml, 0.188 mmol), PdCl ２(dppf) (6.88 mg, 0.00941 mmol) was mixed with the resulting solution and stirred at 90°C for 4 hours under a nitrogen atmosphere. The reaction solution was cooled, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate / methanol) to obtain compound (I-0299) (22.0 mg, 0.0380 mmol, yield 40%). LC / MS (ESI): m / z = 585, RT = 1.89 min, LC / MS measurement conditions 1 1H-NMR (DMSO-d6) δ: 8.34 (s, 1H), 8.09 (s, 1H), 7.91 (m, 2H), 7.66 (d, J = 8.8 Hz, 1H), 7.63-7.58 (s, 1H), 7.55 (s, 1H), 7.29 (m, 1H), 6.98 (s, 1H), 6.88 (s, 1H), 5.40 (s, 2H), 5.17 (s, 2H), 3.92 (s, 3H), 3.79 (s, 3H).

[0161] Synthesis of compound (I-0067) Step 1 Synthesis of Compound 6 2-Amino-4-bromo-6-fluorobenzoic acid (2.00 g, 8.55 mmol) was dissolved in DMA (2.0 ml), and phenyl N-(5-methyl-3-pyridyl)carbamate (2.71 g, 10.3 mmol) (see WO2009127948, WO2009127949, and WO2002048152 for synthesis methods), DMAP (0.104 g, 0.855 mmol), and triethylamine (2.84 ml, 20.5 mmol) were added, followed by stirring at 100°C for 2 hours. The reaction solution was cooled to room temperature, water (60 ml) was added, and the mixture was neutralized with 2 mol / L hydrochloric acid. The precipitated solid was collected by filtration and washed with water to obtain compound 5 (2.48 g, 6.74 mmol, yield 79%). LC / MS (ESI): m / z = 508, RT = 2.17 min, LC / MS measurement conditions 1

[0162] Step 2: Synthesis of Compound 6 Compound 5 (2.48 g, 6.74 mmol) was suspended in 2 mol / L hydrochloric acid (25 ml, 50.0 mmol) and stirred at 100° C. for 2 hours. The reaction solution was cooled to room temperature and neutralized with a saturated aqueous solution of sodium bicarbonate. The precipitated solid was collected by filtration and washed with water to obtain Compound 6 (2.05 g, 5.85 mmol, yield 87%). LC / MS (ESI): m / z = 352, RT = 1.45 min, LC / MS measurement condition 1

[0163] Step 3: Synthesis of Compound 7 Compound 7 (79.5 mg, 0.220 mmol, yield 77%) was obtained in the same manner as in Step 3 of Example 1. LC / MS (ESI): m / z = 569, RT = 2.07 min, LC / MS measurement condition 1

[0164] Step 4 Synthesis of Compound 8 Compound 8 (99.5 mg, 0.197 mmol, yield 90%) was obtained in the same manner as in Step 4 of Example 1. LC / MS (ESI): m / z = 508, RT = 2.17 min, LC / MS measurement condition 1

[0165] Step 5 Synthesis of Compound (I-0067) Compound (I-0067) was obtained in the same manner as in Step 5 of Example 1 (24.0 mg, 0.0410 mmol, yield 42%). LC / MS (ESI): m / z = 581, RT = 1.94 min, LC / MS measurement conditions 1 1H-NMR (DMSO-d6) δ: 8.46 (d, J = 1.4 Hz, 1H), 8.42 (d, J = 2.0 Hz, 1H), 8.11 (br s, 1H), 7.90 (dt, J = 6.7, 2.2 Hz, 2H), 7.70 (br s, 1H), 7.67-7.65 (m, 1H), 7.57 (br s, 1H), 7.45-7.42 (m, 2H), 6.98 (s, 1H), 6.85 (s, 1H), 5.37 (br s, 2H), 3.91 (s, 3H), 2.38 (s, 3H).

[0166] Synthesis of Compound (I-0176), Compound (I-0177) and Compound (I-0169) Step 1: Synthesis of Compound 9 Compound 9 (3.52 g, 22.2 mmol, yield 75%) was synthesized by a known method (see WO2017066742 and WO2010093849). LC / MS (ESI): m / z = 159, RT = 1.19 min, LC / MS measurement condition 1

[0167] Step 2: Synthesis of Compound 10 Compound 11 (3.32 g, 20.9 mmol) was dissolved in acetic acid (33 ml), sodium iodide (3.76 g, 25.1 mmol), and chloramine T (7.07 g, 25.1 mmol) were added, and the mixture was stirred at room temperature for 30 minutes. To the reaction mixture, 10 mol / L aqueous sodium hydroxide solution (61.2 ml, 612 mmol), ethyl acetate (30 ml), sodium thiosulfate (3.31 g, 20.9 mmol), and water (30 ml) were added and the mixture was separated. The aqueous layer was extracted with ethyl acetate, and the organic layer was washed with water and dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain compound 10 (5.01 g, 17.6 mmol, 84% yield). LC / MS (ESI): m / z = 285, RT = 2.02 min, LC / MS measurement condition 1

[0168] Step 3: Synthesis of Compound 11 Compound 10 (4.62 g, 16.2 mmol), methanol (46 ml), triethylamine (4.50 ml, 32.5 mmol), and PdCl(dppf) (1.19 g, 1.62 mmol) were mixed and stirred under a carbon monoxide atmosphere at 60° C. for 4.5 hours. The reaction mixture was cooled to room temperature and concentrated. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain Compound 11 (3.06 g, 14.1 mmol, 87% yield). LC / MS (ESI): m / z = 217, RT = 1.76 min, LC / MS measurement condition 1

[0169] Step 4: Synthesis of Compound 12 Compound 11 (2.86 g, 13.2 mmol) was dissolved in methanol (30 ml) and tetrahydrofuran (15 ml), and 2 mol / L aqueous sodium hydroxide solution (33.0 ml, 66.0 mmol) was added and stirred at 60° C. for 45 minutes. After cooling to room temperature, the mixture was neutralized with 2 mol / L hydrochloric acid. The precipitated solid was collected by filtration and washed with water to obtain Compound 12 (1.47 g, 7.28 mmol, 55% yield). LC / MS (ESI): m / z = 203, RT = 1.49 min, LC / MS measurement condition 1

[0170] Step 5: Synthesis of Compound 13 Compound 13 (691 mg, 2.33 mmol, yield 94%) was obtained in the same manner as in Step 1 of Example 1. LC / MS (ESI): m / z = 297, RT = 1.34 min, LC / MS measurement condition 1

[0171] Step 6: Synthesis of Compound 14 Compound 13 (610 mg, 2.06 mmol) was added to tetrahydrofuran (60 ml), and 60% sodium hydride (247 mg, 6.17 mmol) and CDI (667 mg, 4.11 mmol) were added at 0°C, followed by stirring at room temperature for 40 minutes. Further, 60% sodium hydride (247 mg, 6.17 mmol) and CDI (667 mg, 4.11 mmol) were added at 0°C, followed by stirring at 70°C for 30 minutes. Water (30 ml) was added, and the mixture was neutralized with 2 mol / L hydrochloric acid. The precipitated solid was collected by filtration to obtain Compound 14 (470 mg, 1.46 mmol, 71% yield). LC / MS (ESI): m / z = 323, RT = 1.21 min, LC / MS measurement condition 1

[0172] Step 7 Synthesis of Compound 15 Compound 15 (265 mg, 0.568 mmol, yield 92%) was obtained in the same manner as in Step 4 of Example 1. LC / MS (ESI): m / z = 467, RT = 2.03 min, LC / MS measurement condition 1

[0173] Step 8 Synthesis of Compound (I-0176) Compound (I-0176) (126 mg, 0.222 mmol, 69% yield) was obtained in a similar manner to Step 5 of Example 1. LC / MS (ESI): m / z = 568, RT = 2.24 min, LC / MS measurement condition 1. 1H-NMR (DMSO-d6) δ: 8.36 (s, 1H), 8.17 (d, J = 1.9 Hz, 1H), 7.98 (dd, J = 8.4, 1.9 Hz, 1H), 7.83 (d, J = 8.4 Hz), 5.41 (s, 2H), 5.18 (s, 2H), 4.00 (s, 3H), 3.79 (s, 3H).

[0174] Step 9 Synthesis of Compound (I-0177) Compound 18 (111 mg, 0.195 mmol), chlorotrimethylsilane (63.7 mg, 0.586 mmol), sodium iodide (88.0 mg, 0.586 mmol), and acetonitrile (1.1 ml) were mixed and stirred for 30 minutes at 70° C. The reaction solution was cooled to room temperature, and saturated aqueous sodium bicarbonate solution was added. The precipitated solid was collected by filtration and washed with water to obtain compound 19 (85.7 mg, 0.155 mmol, yield 79%). LC / MS (ESI): m / z = 554, RT = 1.87 min, LC / MS measurement conditions 1 1H-NMR (DMSO-d6) δ: 8.37 (s, 1H), 7.92-7.87 (m, 2H), 7.74-7.72 (m, 1H), 7.30-7.26 (m, 2H), 6.13 (br s, 1H), 5.23 (s, 2H), 5.13 (s, 2H), 3.79 (s, 3H).

[0175] Step 10: Synthesis of Compound (I-0169) Compound (I-0177) (76.4 mg, 0.138 mmol) was dissolved in DMF (1.5 ml), and cesium carbonate (225 mg, 0.690 mmol) and iodomethane (98.0 mg, 0.690 mmol) were added, followed by stirring at room temperature for 45 minutes. Water (5 ml) and ethyl acetate (5 ml) were added to the reaction solution, followed by phase separation, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulfate. The solvent was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (chloroform / methanol) to obtain compound (I-0169) (49.0 mg, 0.0860 mmol, yield 63%). LC / MS (ESI): m / z = 568, RT = 1.86 min, LC / MS measurement conditions 1 1H-NMR (DMSO-d6) δ: 8.35 (s, 1H), 8.10-8.07 (m, 2H), 7.92 (d, J = 8.3 Hz, 1H), 7.27-7.23 (m, 2H), 6.44 (s, 1H), 5.37-5.23 (m, 2H), 5.12 (s, 3H), 3.79 (s, 3H), 3.08 (s, 3H).

[0176] Synthesis of compound (I-0353) Step 1: Synthesis of Compound 16 Compound 16 (1.26 g, 2.47 mmol, yield 95%) was obtained in the same manner as in Step 4 of Example 1. LC / MS (ESI): m / z = 510, RT = 2.05 min, LC / MS measurement condition 1

[0177] Step 2: Synthesis of Compound 17 Dichloromethane (2.0 ml) was added to compound 16 (200 mg, 0.392 mmol), and a 1.0 mol / L boron tribromide-dichloromethane solution (0.862 ml, 0.862 mmol) was added at 0°C, followed by stirring for 2 hours. Methanol (2.0 ml) and a 2.0 mol / L aqueous sodium hydroxide solution (1.5 ml) were added to the reaction solution, followed by stirring at 50°C for 1 hour. The reaction solution was cooled to room temperature, and the precipitated solid was collected by filtration and washed with water to obtain compound 17 (181 mg, 0.349 mmol, yield 89%).

[0178] Step 3: Synthesis of Compound 18 Compound 17 (192 mg, 0.370 mmol) was dissolved in DMF (1.0 ml), and potassium carbonate (51.1 mg, 0.370 mmol) and allyl bromide (0.0680 ml, 0.740 mmol) were added, followed by stirring for 5 hours at 60° C. The reaction solution was cooled to room temperature, and water was added. The precipitated solid was collected by filtration to obtain Compound 18 (175 mg, 0.326 mmol, yield 88%).

[0179] Step 4: Synthesis of Compound 19 Compound 18 (175 mg, 0.326 mmol) was dissolved in NMP (1.3 ml) and stirred at 240° C. for 1 hour. The reaction solution was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulfate, and the solvent was then evaporated under reduced pressure to obtain Compound 19 (175 mg, 0.326 mmol, yield 100%). LC / MS (ESI): m / z = 536, RT = 2.77 min, LC / MS measurement condition 1

[0180] Step 5: Synthesis of Compound 20 Compound 19 (175 mg, 0.326 mmol) was dissolved in tetrahydrofuran (1.5 ml) and water (0.5 ml), and 2,6-lutidine (0.0760 ml, 0.653 mmol), sodium periodate (209 mg, 0.979 mmol), and potassium osmate(VI) dihydrate (3.61 mg, 0.00979 mmol) were added. The mixture was stirred at room temperature for 1.5 hours. Water (3 ml) and ethyl acetate (5 ml) were added to the reaction mixture, and the layers were separated. The aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulfate. The solvent was concentrated, and the resulting residue was purified by silica gel column chromatography (chloroform / methanol) to give compound 20 (116 mg, 0.216 mmol, 66% yield). LC / MS (ESI): m / z = 538, RT = 2.19 min, LC / MS measurement condition 1

[0181] Step 6: Synthesis of Compound 21 Compound 20 (116 mg, 0.216 mmol) was dissolved in methanol (1.2 ml), sodium borohydride (8.15 mg, 0.216 mmol) was added, and the mixture was stirred for 2 hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the precipitated solid was collected by filtration to obtain Compound 21 (85.3 mg, 0.158 mmol, yield 73%). LC / MS (ESI): m / z = 540, RT = 2.41 min, LC / MS measurement condition 1

[0182] Step 7 Synthesis of Compound 22 To a solution of compound 21 (85.3 mg, 0.158 mmol) in tetrahydrofuran (1.0 ml), triphenylphosphine (49.7 mg, 0.189 mmol) and diisopropyl azodicarboxylate (47.9 mg, 0.237 mmol) were added at 0° C., and the mixture was stirred at room temperature for 2.5 hours. The reaction mixture was concentrated, and the crude product was washed with methanol to obtain compound 22 (33.2 mg, 0.0640 mmol, 40% yield). LC / MS (ESI): m / z = 522, RT = 2.07 min, LC / MS measurement condition 1

[0183] Step 8 Synthesis of Compound (I-0353) Compound (I-0353) was synthesized in the same manner as in Step 5 of Example 1 using compound 22 (33.2 mg, 0.0640 mmol) to give compound (I-0353) (25.4 mg, 0.0420 mmol, yield: 66%). LC / MS (ESI): m / z = 609, RT = 1.83 min, LC / MS measurement conditions 1 1H-NMR (DMSO-d6) δ: 10.62 (s, 1H), 8.35 (s, 1H), 7.28 (m, 2H), 7.20 (s, 1H), 6.93 (s, 1H), 6.57 (s, 1H), 5.34 (br s, 2 H), 5.17 (s, 2H), 4.70 (t, J = 8.4 Hz, 2H), 3.79 (s, 3H), 3.51 (s, 2H), 2.98 (br t, J = 8.4Hz, 2H).

[0184] Synthesis of compound (I-0325) Step 1: Synthesis of Compound 23 A mixture of 5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione (200 mg, 1.20 mmol), acetonitrile (2.0 ml), and N,O-bis(trimethylsilyl)acetamide (367 mg, 1.81 mmol) was stirred at room temperature for 40 minutes. 1-(Bromomethyl)-3,4,5-trifluorobenzene (406 mg, 1.81 mmol) was added to the reaction mixture, and the mixture was stirred at 80°C for 18 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with water and dried over sodium sulfate. The solvent was concentrated to give a crude product, which was solidified with dichloromethane-diisopropyl ether to give Compound 23 (283 mg, 0.912 mmol, 76% yield). LC / MS (ESI): m / z = 311, RT = 1.90 min, LC / MS measurement condition 1

[0185] Step 2: Synthesis of Compound 24 Compound 23 (50.0 mg, 0.161 mmol) was dissolved in DMF (0.75 ml), potassium carbonate (44.5 mg, 0.322 mmol) and 3-(chloromethyl)-2-methoxypyridine (33.0 mg, 0.209 mmol) were added, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulfate. The solvent was concentrated, and the resulting residue was purified by silica gel column chromatography (chloroform / methanol) to obtain compound 24 (58.0 mg, 0.134 mmol, 83% yield). LC / MS (ESI): m / z = 432, RT = 2.45 min, LC / MS measurement condition 1

[0186] Step 3: Synthesis of Compound (I-0325) Compound 24 (55.0 mg, 0.127 mmol), chlorotrimethylsilane (41.6 mg, 0.382 mmol), sodium iodide (57.3 mg, 0.382 mmol), and acetonitrile (2.2 ml) were mixed and stirred at 70°C for 2 hours. The reaction solution was cooled to room temperature, and an aqueous sodium thiosulfate solution was added, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was concentrated to obtain a residue, which was purified by silica gel column chromatography (ethyl acetate / methanol) to obtain compound (I-0325) (12.0 mg, 0.0290 mmol, yield 23%). LC / MS (ESI): m / z = 418, RT = 1.84 min, LC / MS measurement conditions 1 1H-NMR (CDCl3) δ: 11.41 (s, 1H), 7.26-7.19 (m, 2H), 6.83 (t, J = 6.9 Hz, 2H), 6.20 (t, J = 6.7 Hz, 1H), 5.13 (s, 2H), 5.06 (s, 2H), 2.43 (m, 4H), 1.76 (m, 2H), 1.66 (m, 2H).

[0187] Synthesis of compound (I-0140) Step 1 Synthesis of Compound 25 Compound 25 (24.0 g, 71.4 mmol, yield 77%) was obtained in the same manner as in Step 1 of Example 1.

[0188] Step 2: Synthesis of Compound 26 Compound 26 (20.0 g, 55.2 mmol, yield 77%) was obtained in the same manner as in Step 2 of Example 1.

[0189] Step 3 Synthesis of Compound 27 Compound 27 (19.4 g, 38.1 mmol, yield 93%) was obtained in the same manner as in Step 4 of Example 1.

[0190] Step 4 Synthesis of Compound 28 Compound 27 (30.0 mg, 0.0590 mmol), (1R,4R)-TERT-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate hydrochloride (24.0 mg, 0.119 mmol), DMF (0.30 ml), cesium carbonate (57.9 mg, 0.178 mmol), and RuPhos Pd G3 (4.96 mg, 0.00593 mmol) were mixed and stirred at 100°C for 18 hours. The reaction solution was cooled to room temperature, and chloroform and water were added to separate the layers. The aqueous layer was extracted with chloroform, and the combined organic layers were concentrated. The resulting residue was purified by PLCMS to obtain Compound 28 (34.4 mg, 0.0552 mmol, yield 94%). LC / MS (ESI): m / z = 624, RT = 2.79 min, LC / MS measurement condition 1

[0191] Step 4 Synthesis of Compound (I-0140) Compound (I-0140) was obtained in the same manner as in Step 3 of Example 5 (8.10 mg, 0.0159 mmol, yield 29%). LC / MS (ESI): m / z = 512, RT = 1.41 min, LC / MS measurement conditions 1 1H-NMR (CDCl3) δ: 11.6 (s, 1H), 8.62 (s, 1H), 7.86 (d, J = 8.8 Hz, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 7.28 (d, J = 6.4 Hz, 1H), 6.99 (d, J = 4.8 Hz, 1H), 6.62 (d, J = 8.4 Hz, 1H), 6.16 (s, 1H), 6.10 (dd, J = 6.8 Hz, 1H), 5.41-5.31 (m, 2H), 4.90 (s, 2H), 4.78 (s, 1H), 4.50 (s, 1H), 3.63 (d, J = 9.2 Hz, 1H), 3.27-3.16 (m, 4H), 2.97 (d, J = 10.4 Hz, 1H), 2.15 (d, J = 11.2 Hz, 1H), 1.95 (d, J = 10.8 Hz, 1H).

[0192] Synthesis of Compound (I-0978) and Compound (I-1065) Step 1: Synthesis of Compound 29 Compound 11 (5.00 g, 23.1 mmol) was dissolved in 1,4-dioxane (25 mL), and potassium phosphate (14.7 g, 69.2 mmol), 1,2-difluoro-4-iodobenzene (8.31 g, 34.6 mmol), trans-N,N-dimethylcyclohexane-1,2-diamine (1.31 g, 9.23 mmol), and copper(I) iodide (1.76 g, 9.23 mmol) were added. The mixture was stirred at 110°C for 7 hours under a nitrogen atmosphere. The reaction mixture was cooled, diluted with chloroform, and then filtered through Celite (registered trademark). The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography (n-hexane / ethyl acetate) to obtain compound 29 (3.04 g, 9.25 mol, yield 40%). LC / MS (ESI): m / z = 329, RT = 2.74 min, LC / MS measurement conditions 1

[0193] Step 2: Synthesis of Compound 30 Compound 29 (3.04 g, 9.25 mmol) was dissolved in methanol (15 mL) and tetrahydrofuran (15 mL), and 2 mol / L aqueous sodium hydroxide solution (23.1 mL, 46.2 mmol) was added and stirred at 60° C. for 1 hour. After cooling to room temperature, the mixture was neutralized with 2 mol / L hydrochloric acid. The precipitated solid was collected by filtration and washed with water to obtain Compound 30 (2.53 g, 8.04 mmol, 87% yield). LC / MS (ESI): m / z = 315, RT = 2.42 min, LC / MS measurement condition 1

[0194] Step 3: Synthesis of Compound 31 Compound 30 (1.10 g, 3.50 mmol) was dissolved in DMF (11 mL), and 7-fluoroimidazo[1,2-a]pyridin-3-amine (634 mg, 4.19 mmol), PyBOP (2.37 g, 4.54 mmol), and diisopropylethylamine (1.53 mL, 8.74 mmol) were added, followed by stirring at room temperature for 3 hours. Water (50 mL) was added to the reaction mixture, followed by separation, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and then dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate / methanol) to give compound 31 (1.20 g, 2.68 mmol, 77% yield). LC / MS (ESI): m / z = 448, RT = 2.23 min, LC / MS measurement condition 1

[0195] Step 4: Synthesis of Compound (I-1065) Compound 31 (1.20 g, 2.68 mmol), 1,3,5-trifluoro-2-nitrobenzene (949 mg, 5.36 mmol), and CDI (1.74 g, 10.7 mmol) were dissolved in DMA (24 mL), and 60% sodium hydride (322 mg, 8.04 mmol) was added at 0°C, followed by stirring at the same temperature for 30 minutes. The reaction solution was added to a mixture of water (50 mL) and 2 mol / L hydrochloric acid (2 mL), and extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by amino column chromatography (n-hexane / ethyl acetate) to obtain compound (I-1065) (283 mg, 0.597 mmol, yield 22%). LC / MS (ESI): m / z = 474, RT = 1.91 min, LC / MS measurement condition 1

[0196] Step 5: Synthesis of Compound (I-0978) Compound (I-1065) (47.0 mg, 0.0990 mmol), (1S,4S)-2-oxa-5-azabicyclo[2,2,1]heptane hydrochloride (14.8 mg, 0.109 mmol), and diisopropylethylamine (0.0518 mL, 0.298 mmol) were dissolved in DMA (0.47 mL) and stirred at 110°C for 2 hours. Water (20 ml) was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform / methanol) to obtain compound (I-0978) (27.0 mg, 0.0500 mmol, 51% yield). LC / MS (ESI): m / z = 537, RT = 1.75 min, LC / MS measurement condition 1 1 H-NMR (CDCl3) δ: 7.69 (m, 1H), 7.64 (d, J = 2.5 Hz, 1H), 7.43-7.12 (m, 5H), 6.72 (m, 1H), 4.80 (m, 1H), 4.69 (s, 1H), 4.03 (s, 3H), 3.90-3.80 (m, 2H), 3.28-3.04 (m, 2H), 2.02-1.88 (m, 2H).

[0197] Synthesis of compound (I-0957) Compound (I-0957) was synthesized in the same manner as in Example 7. LC / MS (ESI): m / z = 509, RT = 1.96 min, LC / MS measurement condition 1 1 H-NMR (CDCl3) δ: 8.86 (d, J = 1.9 Hz, 1H), 8.77 (d, J = 2.3 Hz, 1H), 7.97 (t, J = 2.1 Hz, 1H), 7.46 (d, J = 6.3 Hz, 1H), 7.35 (t, J = 8.5 Hz, 1H), 7.26 (m, 2H), 4.84 (br s, 1H), 4.60 (br s, 1H), 4.05 (s, 3H), 3.91-3.00 (m, 4H), 2.08 (m, 2H).

[0198] The following compounds were synthesized according to the general synthesis methods and those described in the Examples. The structures and physical properties (LC / MS data) are shown in the table below. In the structural formulas, the "wedge shape" and "dashed line" indicate the configuration.

[0199]

[0200]

[0201]

[0202]

[0203]

[0204]

[0205]

[0206]

[0207]

[0208]

[0209]

[0210]

[0211]

[0212]

[0213]

[0214]

[0215]

[0216]

[0217]

[0218]

[0219]

[0220]

[0221]

[0222]

[0223]

[0224]

[0225]

[0226]

[0227]

[0228]

[0229]

[0230]

[0231]

[0232]

[0233]

[0234]

[0235]

[0236]

[0237]

[0238]

[0239]

[0240]

[0241]

[0242]

[0243]

[0244]

[0245]

[0246]

[0247]

[0248]

[0249]

[0250]

[0251]

[0252]

[0253]

[0254]

[0255]

[0256]

[0257]

[0258]

[0259]

[0260]

[0261]

[0262]

[0263]

[0264]

[0265]

[0266]

[0267]

[0268]

[0269]

[0270]

[0271]

[0272]

[0273]

[0274]

[0275]

[0276]

[0277]

[0278]

[0279]

[0280]

[0281]

[0282]

[0283]

[0284]

[0285]

[0286]

[0287] The following compounds (I-0543), (I-0544) and (I-0545) are for reference purposes only.

[0288]

[0289] Biological test examples of the compound of the present invention are described below. The compound represented by formula (I) according to the present invention has a coronavirus 3 CL protease inhibitory activity and may be any compound that inhibits coronavirus 3 CL protease. Specifically, in the evaluation method described below, the IC50 is preferably 50 μM or less, more preferably 1 μM or less, and even more preferably 100 nM or less.

[0290] Test Example 1-1: Cytopathic effect (CPE) inhibitory effect confirmation test using human TMPRSS2-expressing Vero E6 cells (Vero E6 / TMPRSS2 cells) <Procedure> - Dilution and dispensing of test sample: The test sample is diluted to an appropriate concentration with DMSO in advance, and a 2- to 5-fold serial dilution series is prepared, and then dispensed into a 384-well plate. - Dilution and dispensing of cells and SARS-CoV-2: Vero E6 / TMPRSS2 cells (JCRB1819, 5 x 10 ３ cells / well) and SARS-CoV-2 (100TCID ５０ / well) was mixed with a medium (MEM, 2% FBS, penicillin-streptomycin), and the mixture was dispensed into the wells containing the test samples. ２ Culture in an incubator for 3 days. Dispensing of CellTiter-Glo® 2.0 and measurement of luminescence signal After the 3-day culture plate is returned to room temperature, CellTiter-Glo® 2.0 is dispensed into each well and mixed using a plate mixer. After leaving for a certain period of time, the luminescence signal (Lum) is measured using a plate reader.

[0291] <Calculation of each measurement item value> 50% SARS-CoV-2 infected cell death inhibitory concentration (EC ５０ ) Calculation When x is the logarithm of the compound concentration and y is % efficacy, the inhibition curve is approximated by the following logistic regression equation, and the value of x when y = 50 (%) is substituted is the EC ５０ Calculated as follows: y = min + (max - min) / {1 + (X50 / x) ^Hill} %Efficacy = {(Sample - virus control) / (cell control - virus control)} * 100% cell control: the average of Lum of cell control wells virus control: the average of Lum of virus control wells min: lower limit of y-axis, max: upper limit of y-axis, X50: x-coordinate of inflection point, Hill: slope of the curve at the midpoint between min and max

[0292] The compounds of the present invention were tested essentially as described above, and the results are shown in the table below. ５０ Values ​​below 1 μM are categorized as "A," and values ​​between 1 μM and 10 μM are categorized as "B." (Results)

[0293]

[0294]

[0295] Test Example 1-2: Cytopathic effect (CPE) inhibitory effect confirmation test using human TMPRSS2 and ACE2-expressing HEK293T cells (HEK293T / ACE2-TMPRSS2 cells) <Procedure> - Dilution and dispensing of test sample: The test sample is diluted to an appropriate concentration with DMSO in advance, and a 2- to 5-fold serial dilution series is prepared, and then dispensed into a 384-well plate. - Dilution and dispensing of cells and SARS-CoV-2: HEK293T / ACE2-TMPRSS2 cells (GCP-SL222, 5 x 10 ３ cells / well) and SARS-CoV-2 (200-300TCID ５０ / well) was mixed with a medium (MEM, 2% FBS, penicillin-streptomycin), and the mixture was dispensed into the wells containing the test samples. ２ Culture in an incubator for 3 days. Dispensing CellTiter-Glo® 2.0 and measuring luminescence signals After 3 days of culture, return the plate to room temperature, dispense CellTiter-Glo® 2.0 into each well, and mix using a plate mixer. After a certain period of time, measure the luminescence signal (Lum) using a plate reader. <Calculation of values ​​for each measurement item> 50% SARS-CoV-2-infected cell death inhibitory concentration (EC ５０ ) Calculation When x is the logarithm of the compound concentration and y is % efficacy, the inhibition curve is approximated by the following logistic regression equation, and the value of x when y = 50 (%) is substituted is the EC ５０Calculated as follows: y = min + (max - min) / {1 + (X50 / x) ^Hill} %Efficacy = {(Sample - virus control) / (cell control - virus control)} * 100% cell control: the average of Lum of cell control wells virus control: the average of Lum of virus control wells min: lower limit of y-axis, max: upper limit of y-axis, X50: x-coordinate of inflection point, Hill: slope of the curve at the midpoint between min and max

[0296] The compounds of the present invention were tested essentially as described above. The results are shown below. ５０ The values ​​are "A" for less than 0.1 μM, "B" for 0.1 μM or more and less than 1 μM, and "C" for 1 μM or more and less than 10 μM.

[0297]

[0298]

[0299]

[0300] Test Example 2: Inhibitory activity test against SARS-CoV-2 3CL protease <Materials> Commercially available recombinant SARS-CoV-2 3CL protease Commercially available substrate peptide Dabcyl-Lys-Thr-Ser-Ala-Val-Leu-Gln-Ser-Gly-Phe-Arg-Lys-Met-Glu(Edans)-NH2 (SEQ ID NO: 1) Internal standard peptide Dabcyl-Lys-Thr-Ser-Ala-Val-Leu(13C6,15N)-Gln (SEQ ID NO: 2) Dabcyl-Lys-Thr-Ser-Ala-Val-Leu(13C6,15N)-Gln can be synthesized with reference to literature (Atherton, E.; Sheppard, RC, "In Solid Phase Peptide Synthesis, A Practical Approach", IRL Press at Oxford University Press, 1989, and Bioorg. Med. Chem., Vol. 5, No. 9, 1997, pp. 1883-1891, etc.). An example is shown below. H-Lys-Thr-Ser-Ala-Val-Leu(13C6,15N)-Glu(resin)-OαOtBu (Lys side chain is Boc-protected, Thr side chain is protected with a tert-butyl group, Ser side chain is protected with a tert-butyl group, the C-terminal OH of Glu is protected with a tert-butyl group, and the carboxylic acid of the Glu side chain is condensed to the resin) was synthesized by Fmoc solid-phase synthesis using Rink amide resin. The N-terminal Dabcyl group was modified by on-resin condensation with 4-dimethylaminoazobenzene-4'-carboxylic acid (Dabcyl-OH) using EDC / HOBT. Final deprotection and cleavage from the resin were performed by treatment with TFA / EDT = 95:5. The product was then purified by reverse-phase HPLC. RapidFire Cartridge C4 type A <Procedure> Preparation of assay buffer In this test, an assay buffer consisting of 20 mM Tris-HCl, 100 mM sodium chloride, 1 mM EDTA, 10 mM DTT, and 0.01% BSA is used. ５０For compounds with a concentration of 10 nM or less, use an assay buffer consisting of 20 mM Tris-HCl, 1 mM EDTA, 10 mM DTT, and 0.01% BSA. - Dilution and dispensing of test samples: Dilute the test samples to the appropriate concentration with DMSO in advance, prepare a 2- to 5-fold serial dilution series, and dispense them into a 384-well plate. - Addition of enzyme and substrate: Enzyme reaction: Add 8 μM substrate and 6 or 0.6 nM enzyme solution to the prepared compound plate and incubate at room temperature for 3 to 5 hours. Then, add a reaction stop solution (0.067 μM internal standard, 0.1% formic acid, 10 or 25% acetonitrile) to stop the enzyme reaction. Measurement of reaction products The plate after the reaction is completed is measured using a RapidFire System 360 and a mass spectrometer (Agilent, 6550 iFunnel Q-TOF) or a RapidFire System 365 and a mass spectrometer (Agilent, 6495C Triple Quadruple). Solution A (75% isopropanol, 15% acetonitrile, 5 mM ammonium formate) and solution B (0.01% trifluoroacetic acid, 0.09% formic acid) are used as the mobile phase during measurement. The reaction products detected by the mass spectrometer are calculated using RapidFire Integrator or an equivalent analysis program to obtain the product area value. The internal standard detected at the same time is also calculated and used as the internal standard area value. <Calculation of each measurement item value> Calculation of P / IS The area value obtained in the previous item is calculated using the following formula to calculate P / IS. P / IS = Product area value / Internal standard area value 50% SARS-CoV-2 3CL protease inhibitory concentration (IC ５０ ) Calculation When x is the logarithm of the compound concentration and y is % Inhibition, the inhibition curve is approximated by the following logistic regression equation, and the value of x when y = 50 (%) is substituted is used to calculate the IC ５０Calculated as follows: y = min + (max - min) / {1 + (X50 / x) ^Hill} %Inhibition = {1-(Sample - Control(-)) / Control(+)-Control(-))} * 100 Control(-): the average of P / IS of enzyme inhibited condition wells Control(+): the average of P / IS of DMSO control wells min: lower limit of y-axis, max: upper limit of y-axis, X50: x-coordinate of inflection point, Hill: slope of the curve at the midpoint between min and max

[0301] The compounds of the present invention were tested essentially as described above. The results are shown in the table below. ５０ The values ​​are categorized as "A" for less than 0.1 μM, "B" for 0.1 μM or more and less than 1 μM, and "C" for 1 μM or more and less than 10 μM. (Results)

[0302]

[0303]

[0304]

[0305]

[0306]

[0307] Test Example 3: CYP inhibition test Using commercially available pooled human liver microsomes, the extent to which the production of each metabolite is inhibited by the compound of the present invention is evaluated using as indicators the typical substrate metabolic reactions of human major CYP5 molecular species (CYP1A2, 2C9, 2C19, 2D6, 3A4), namely, O-deethylation of 7-ethoxyresorufin (CYP1A2), methyl-hydroxylation of tolbutamide (CYP2C9), 4'-hydroxylation of mephenytoin (CYP2C19), O-demethylation of dextromethorphan (CYP2D6), and hydroxylation of terfenadine (CYP3A4).

[0308] The reaction conditions were as follows: substrates, 0.5 μmol / L ethoxyresorufin (CYP1A2), 100 μmol / L tolbutamide (CYP2C9), 50 μmol / L S-mephenytoin (CYP2C19), 5 μmol / L dextromethorphan (CYP2D6), 1 μmol / L terfenadine (CYP3A4); reaction time, 15 minutes; reaction temperature, 37°C; enzyme, pooled human liver microsomes, 0.2 mg protein / mL; concentration of the compound of the present invention, 1, 5, 10, 20 μmol / L (4 points).

[0309] Five substrates, human liver microsomes, and the compound of the present invention were added to a 96-well plate in the above-mentioned composition in 50 mmol / L HEPES buffer, and the coenzyme NADPH was added to initiate the metabolic reaction. After 15 minutes of reaction at 37°C, the reaction was stopped by adding a 1:1 (V / V) methanol / acetonitrile solution. After 15 minutes of centrifugation at 3000 rpm, resorufin (a CYP1A2 metabolite) in the supernatant was quantified by a fluorescent multilabel counter or LC / MS / MS, and tolbutamide hydroxylate (a CYP2C9 metabolite), mephenytoin 4'-hydroxylate (a CYP2C19 metabolite), dextrorphan (a CYP2D6 metabolite), and terfenadine alcohol (a CYP3A4 metabolite) were quantified by LC / MS / MS. The dilution concentration and solvent were adjusted as needed.

[0310] The control (100%) was a reaction solution in which only DMSO, the solvent in which the compound was dissolved, was added instead of the compound of the present invention. The remaining activity (%) was calculated, and the IC was calculated by inverse estimation using a logistic model using the concentration and inhibition rate. ５０ Calculate.

[0311] Compounds of the invention were tested essentially as described above.

[0312] Test Example 4: CYP3A4 (MDZ) MBI Test This test evaluates the mechanism-based inhibition (MBI) ability of the compounds of the present invention in terms of the CYP3A4 inhibition, based on the enhancement of the inhibitory effect caused by the metabolic reaction of the compounds of the present invention. CYP3A4 inhibition is evaluated using pooled human liver microsomes and the 1-hydroxylation reaction of midazolam (MDZ) as an index.

[0313] The reaction conditions were as follows: substrate, 10 μmol / L MDZ; pre-reaction time, 0 or 30 minutes; substrate metabolic reaction time, 2 minutes; reaction temperature, 37°C; pooled human liver microsomes, 0.5 mg / mL during pre-reaction and 0.05 mg / mL (10-fold dilution) during reaction; concentration of the compound of the present invention during pre-reaction, 1, 5, 10, 20 μmol / L (4 points) or 0.83, 5, 10, 20 μmol / L (4 points).

[0314] Pooled human liver microsomes and a solution of the compound of the present invention were added to a 96-well plate as a pre-reaction solution in K-Pi buffer (pH 7.4) at the pre-reaction composition described above. A portion of this solution was transferred to another 96-well plate so that it was diluted 1 / 10 with K-Pi buffer containing the substrate, and the coenzyme NADPH was added to initiate the reaction (pre-incubation 0 min). After the predetermined reaction time, the reaction was stopped by adding a 1 / 1 (V / V) methanol / acetonitrile solution. NADPH was also added to the remaining pre-reaction solution to initiate the pre-reaction (pre-incubation 30 min). After the predetermined reaction time, a portion of this solution was transferred to another plate so that it was diluted 1 / 10 with K-Pi buffer containing the substrate, and the reaction was started. After the predetermined reaction time, the reaction was stopped by adding a 1 / 1 (V / V) methanol / acetonitrile solution. After centrifuging the plates where the indicator reactions were performed at 3000 rpm for 15 minutes, the amount of 1-hydroxymidazolam in the supernatant was quantified by LC / MS / MS. The dilution concentration and dilution solvent were changed as necessary.

[0315] A control (100%) was prepared by adding only DMSO, the solvent in which the compound was dissolved, to the reaction solution instead of the compound of the present invention. The residual activity (%) was calculated when the compound of the present invention was added at each concentration, and the IC was calculated by inverse estimation using a logistic model using the concentration and inhibition rate. The Shifted IC value was calculated as the IC at 0 min preincubation / IC at 30 min preincubation. If the Shifted IC was 1.5 or higher, it was considered positive, and if the Shifted IC was 1.0 or lower, it was considered negative.

[0316] Compounds of the invention were tested essentially as described above.

[0317] Test Example 5: BA Test Materials and Methods for Experiment to Examine Oral Absorbability (1) Animals Used: SD rats are used. (2) Breeding Conditions: SD rats are allowed free access to solid feed and sterilized tap water. (3) Dosage and Grouping: Predetermined dosages are administered orally and intravenously. Groups are set up as follows. (Dosages vary depending on the compound) Oral Administration: 1-60 μmol / kg or 0.5-30 mg / kg (n=2-3) Intravenous Administration: 0.5-20 μmol / kg or 0.1-10 mg / kg (n=2-3) (4) Preparation of Dosage Solution: Oral administration is administered as a solution or suspension. Intravenous administration is administered after solubilization. (5) Administration Method: Oral administration is administered by forced administration into the stomach using an oral probe. Intravenous administration is administered via the tail vein using a syringe with an injection needle attached. (6) Evaluation item: Blood samples are collected over time, and the plasma concentration of the compound of the present invention is measured using LC / MS / MS. (7) Statistical analysis: The area under the plasma concentration-time curve (AUC) of the compound of the present invention over time is calculated using moment analysis, and the bioavailability (BA) of the compound of the present invention is calculated from the dose ratio and AUC ratio between the oral and intravenous administration groups. The dilution concentration and dilution solvent are changed as necessary.

[0318] Compounds of the invention were tested essentially as described above.

[0319] Test Example 6: Clearance Evaluation Test Experimental Materials and Methods (1) Animals: SD rats were used. (2) Breeding Conditions: SD rats were allowed free access to solid feed and sterilized tap water. (3) Dose and Grouping: Intravenous administration was performed at a predetermined dose. Groups were set up as follows: Intravenous administration: 0.5 or 1 μmol / kg (n=2) (4) Preparation of Dosage Solution: Solubilized and administered using a dimethyl sulfoxide / propylene glycol = 1 / 1 solvent. (5) Administration Method: Administered via the tail vein using a syringe with an injection needle. (6) Evaluation Items: Blood was collected over time, and the plasma concentration of the compound of the present invention was measured using LC / MS / MS. (7) Statistical Analysis: The total body clearance (CLtot) was calculated using moment analysis of the plasma concentration of the compound of the present invention. The dilution concentration and dilution solvent were changed as necessary.

[0320] Compounds of the invention were tested essentially as described above.

[0321] Test Example 7: Metabolic stability test Pooled human liver microsomes or pooled rat liver microsomes are reacted with the compound of the present invention for a certain period of time, and the residual rate is calculated by comparing the reacted sample with the unreacted sample to evaluate the extent to which the compound of the present invention is metabolized in the liver.

[0322] Human or rat liver microsomes (0.5 mg protein / mL) were incubated in 0.2 mL of buffer (50 mmol / L Tris-HCl pH 7.4, 150 mmol / L potassium chloride, 10 mmol / L magnesium chloride) at 37°C for 0 or 30 minutes in the presence of 1 mmol / L NADPH (oxidation reaction). After the reaction, 50 μL of the reaction mixture was added to 100 μL of a 1 / 1 (v / v) methanol / acetonitrile solution, mixed, and centrifuged at 3000 rpm for 15 minutes. The amount of the compound of the present invention in the supernatant was quantified by LC / MS / MS or solid-phase extraction (SPE) / MS. The ratio of the amount of the compound of the present invention at 0 minutes of reaction to the amount of compound after the reaction was expressed as the residual percentage. Note that the hydrolysis reaction was performed in the absence of NADPH, and the glucuronidation reaction was performed in the presence of 5 mmol / L UDP-glucuronic acid instead of NADPH, and the same procedures were then repeated. The dilution concentration and dilution solvent may be changed as necessary.

[0323] Compounds of the invention were tested essentially as described above.

[0324] Test Example 8: Solubility Test The solubility of the compound of the present invention is determined under conditions where 1% DMSO is added. A 10 mmol / L compound solution is prepared in DMSO. 2 μL of the compound solution of the present invention is added to 198 μL of JP-1 solution and JP-2 solution, respectively. After shaking at room temperature for at least 1 hour, the mixture is filtered under suction. The filtrate is diluted 10-fold with methanol / water = 1 / 1 (V / V), and the concentration in the filtrate is measured using LC / MS / MS or solid phase extraction (SPE) / MS according to the absolute calibration curve method. The dilution concentration and dilution solvent may be changed as necessary.

[0325] The composition of JP-1 solution is as follows: 2.0 g of sodium chloride, 7.0 mL of hydrochloric acid, and water are added to make 1000 mL. The composition of JP-2 solution is as follows: 3.40 g of potassium dihydrogen phosphate and 3.55 g of anhydrous disodium hydrogen phosphate are dissolved in water to make 1000 mL, and one volume of water is added.

[0326] Compounds of the invention were tested essentially as described above.

[0327] The following formulation examples are illustrative only and are not intended to limit the scope of the invention. The compounds of the present invention can be administered as pharmaceutical compositions by any conventional route, particularly enterally, e.g., orally, e.g., in the form of tablets or capsules, or parenterally, e.g., in the form of injection solutions or suspensions, topically, e.g., in the form of lotions, gels, ointments, or creams, or intranasally or in the form of suppositories. Pharmaceutical compositions containing the compounds of the present invention in free form or in the form of a pharmaceutically acceptable salt together with at least one pharmaceutically acceptable carrier or diluent can be prepared by conventional mixing, granulation, or coating methods. For example, oral compositions can be in the form of tablets, granules, or capsules containing excipients, disintegrants, binders, lubricants, etc., and active ingredients, etc. Injectable compositions can be in the form of solutions or suspensions, which may be sterilized and may contain preservatives, stabilizers, buffers, etc.

[0328] The compounds according to the present invention have an inhibitory effect on coronavirus 3 CL protease and are considered to be useful as therapeutic and / or preventive agents for diseases or conditions associated with coronavirus 3 CL protease.

Claims

1. Formula (I): 【Chemical 1】 (In the formula, carbon atom a and carbon atom b are carbon atoms constituting ring A; Ring A is 【Chemistry 2】 (wherein carbon atom a represents carbon atom a in formula (I); Carbon atom b represents carbon atom b in formula (I); R ３ａ is a hydrogen atom, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted alkyloxy, a substituted amino, a halogen atom, a substituted or unsubstituted carbamoyl, a substituted or unsubstituted sulfamoyl, a substituted or unsubstituted non-aromatic carbocyclic oxy, or a substituted or unsubstituted non-aromatic heterocyclic oxy; R ３ｂ and R ３ｂ’ are each independently a hydrogen atom, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted alkyloxy, a substituted amino, a halogen atom, a cyano, a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted carbamoyl, a substituted or unsubstituted sulfamoyl, a substituted or unsubstituted non-aromatic carbocyclic oxy, or a substituted or unsubstituted non-aromatic heterocyclic oxy; R ８ and R ８’ are each independently a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, or a substituted or unsubstituted alkyloxy; or R ３ａ and R ８ and R ３ｂ and R ８ may, together with the carbon atom to which they are attached, form a substituted or unsubstituted aromatic carbocyclic ring or a substituted or unsubstituted aromatic heterocyclic ring; R ６ is a hydrogen atom, halogen, substituted or unsubstituted alkyloxy, hydroxy, or cyano; R ７ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted amino, substituted or unsubstituted alkylsulfoxy, substituted or unsubstituted carbamoyl, hydroxy, carboxy, formyl, or cyano; R ７’ and R ９’ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ３ｂ and R ７’ may, together with the atom to which each is attached, form a substituted or unsubstituted non-aromatic heterocycle; R ９ are each independently halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; s is 0, 1 or 2; p is 1, 2 or 3; R １ is a substituted or unsubstituted nitrogen-containing aromatic heterocyclic group, a substituted or unsubstituted nitrogen-containing non-aromatic heterocyclic group, or a substituted or unsubstituted carbamoyl; R ２ is a substituted or unsubstituted 6-membered aromatic carbocyclic group or a substituted or unsubstituted 6-membered aromatic heterocyclic group; n is 0 or 1; R ４ａ is a hydrogen atom or substituted or unsubstituted alkyl; R ４ｂ is a hydrogen atom or a substituted or unsubstituted alkyl; or R ４ａ and R ４ｂ may, together with the carbon atom to which they are attached, form a substituted or unsubstituted non-aromatic carbocyclic ring or a substituted or unsubstituted non-aromatic heterocyclic ring; m is 0, 1 or 2; R ５ａ are each independently a hydrogen atom or a substituted or unsubstituted alkyl; R ５ｂ are each independently a hydrogen atom or a substituted or unsubstituted alkyl) １ is a substituted or unsubstituted carbamoyl, and R ３ａ and R ３ｂ is substituted or unsubstituted oxazolyl or substituted or unsubstituted thiazolyl), or a pharmaceutically acceptable salt thereof.

2. Ring A is 【Chemistry 3】 (Wherein, carbon atom a, carbon atom b, R ３ａ , R ３ｂ , R ６ , R ７ , R ７’ , R ８ , R ９ , R ９’ 2. The compound according to claim 1, wherein s and p are rings represented by the formula:

3. R ３ａ and R ３ｂ are each independently 【Chemistry 4】 (Wherein, Y is CR １０ｈ R １０ｈ’ or O; t is an integer from 0 to 5; R １０ａ are each independently halogen, cyano, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted sulfoximino, or substituted or unsubstituted iminosulfino; or Two R bonds to adjacent carbon atoms １０ａ may be taken together to form a substituted or unsubstituted aromatic heterocycle or a substituted or unsubstituted non-aromatic heterocycle; R １０ｂ , R １０ｂ’ , R １０ｃ , R １０ｃ’ , R １０ｄ , R １０ｄ’ , R １０ｅ , R １０ｅ’ , R １０ｆ , R １０ｆ’ , R １０ｇ , R １０ｇ’ , R １０ｈ , R １０ｈ’ , R １０ｉ , R １０ｉ’ , R １０ｊ and R １０ｊ’ are each independently a hydrogen atom, hydroxy, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyloxycarbonyl, or substituted or unsubstituted aromatic heterocyclic group; R １０ｂ and R １０ｂ’ , R １０ｃ and R １０ｃ’ , R １０ｄ and R １０ｄ’ , R １０ｅ and R １０ｅ’ , R １０ｆ and R １０ｆ’ , R １０ｇ and R １０ｇ’ , R １０ｈ and R １０ｈ’ , R １０ｉ and R １０ｉ’ , and R １０ｊ and R １０ｊ’ may each independently, together with the carbon atom to which it is attached, form oxo, a substituted or unsubstituted non-aromatic carbocyclic ring, or a substituted or unsubstituted non-aromatic heterocyclic ring; R １０ｂ and R １０ｃ , R １０ｃ and R １０ｄ , R １０ｄ and R １０ｅ , R １０ｆ and R １０ｇ , R １０ｇ and R １０ｈ , R １０ｈ and R １０ｉ , and R １０ｉ and R １０ｊ may each independently, together with the carbon atom to which they are attached, form a substituted or unsubstituted non-aromatic heterocycle, a substituted or unsubstituted aromatic carbocycle, or a substituted or unsubstituted non-aromatic carbocycle; R １０ｂ and R １０ｄ , R １０ｂ and R １０ｅ , R １０ｃ and R １０ｅ , R １０ｆ and R １０ｈ , R １０ｆ and R １０ｉ , R １０ｆ and R １０ｊ , R １０ｇ and R １０ｉ , R １０ｇ and R １０ｊ are each independently taken together to form a (C1-C4) bridge, one of the carbon atoms constituting the bridge may be replaced by an oxygen atom or a nitrogen atom; and the carbon atoms constituting the bridge are each independently R ａ and the nitrogen atom constituting the bridge is substituted with a substituent selected from R ｂ substituted with a substituent selected from R ａ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; R ｂ is a hydrogen atom or a substituted or unsubstituted alkyl.

3. The compound according to claim 1 or 2, wherein the compound is a group represented by the formula: or a substituted amino, or a pharmaceutically acceptable salt thereof.

4. R ２ is a 6-membered aromatic carbocyclic group substituted with one halogen and further substituted with 1, 2, 3 or 4 substituents selected from substituent group G, or a 6-membered aromatic heterocyclic group substituted with one halogen and further substituted with 1 or 2 substituents selected from substituent group G; 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the substituent group G is the group consisting of halogen, cyano, alkyl, alkenyl, alkynyl, haloalkyl, alkyloxy, alkenyloxy, alkynyloxy, and haloalkyloxy.

5. R ２ is a 6-membered aromatic carbocyclic group substituted with one halogen and further substituted with 1, 2, 3 or 4 substituents selected from Substituent Group G (same meaning as in Claim 4), or a pharmaceutically acceptable salt thereof.

6. R １ The compound according to claim 1, wherein is a substituted or unsubstituted nitrogen-containing aromatic heterocyclic group or a substituted or unsubstituted nitrogen-containing non-aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof.

7. Ring A is 【Chemistry 5】 (Wherein, carbon atom a, carbon atom b, R ３ａ , R ６ and R ８ is the same as in claim 1; R ７ 2. The compound of claim 1, wherein R is a ring represented by the formula: wherein R is a hydrogen atom, halogen, or substituted or unsubstituted alkyl, or a pharmaceutically acceptable salt thereof.

8. Ring A is 【Chemistry 6】 (Wherein, carbon atom a, carbon atom b, R ３ｂ , R ６ , R ７ , R ７’ and R ８ 2. The compound according to claim 1, wherein R is a ring represented by the formula: R is the same as R in claim 1, or a pharmaceutically acceptable salt thereof.

9. 2. The compound of claim 1, wherein m is 0 or 1, or a pharmaceutically acceptable salt thereof.

10. R ５ａ are each independently a hydrogen atom, and R ５ｂ 3. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein each of the following is independently a hydrogen atom:

11. R ６ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein is halogen, substituted or unsubstituted alkyloxy, or hydroxy.

12. R ４ａ is a hydrogen atom, and R ４ｂ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein is a hydrogen atom.

13. 2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of compounds I-0174, I-0414, I-0417, I-0437, I-0699, I-0934, I-0955, I-0957, I-0978, I-0990, and I-1005.

14. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof.

15. A coronavirus 3CL protease inhibitor comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

16. A coronavirus proliferation inhibitor comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

17. The coronavirus proliferation inhibitor according to claim 16, wherein the coronavirus is an alphacoronavirus and / or a betacoronavirus.

18. The coronavirus proliferation inhibitor according to claim 16, wherein the coronavirus is SARS-CoV-2.

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