WO2013157622A1

WO2013157622A1 - Hiv replication inhibitor

Info

Publication number: WO2013157622A1
Application number: PCT/JP2013/061575
Authority: WO
Inventors: 杉山　修一; 俊行秋山; 善之垰田
Original assignee: 塩野義製薬株式会社
Priority date: 2012-04-19
Filing date: 2013-04-19
Publication date: 2013-10-24

Abstract

Provided are: a novel compound represented by formula (I) (wherein a dashed line represents the presence or absence of a bond; R¹ represents a substituted or unsubstituted alkyl group or the like;R² represents a substituted or unsubstituted alkyloxy group or the like; n represents 1 or 2; R³ represents a substituted or unsubstituted aromatic carbocyclic group or the like; R⁴ represents a hydrogen atom or the like; R⁵ is not present, or the like; R⁶ represents a substituted or unsubstituted alkyl group or the like; R⁷ represents -Z⁷-R⁷¹ or the like; Z⁷ represents -NR⁷³-CO-NR⁷²- or the like; R⁷¹ represents a substituted or unsubstituted aromatic carbocyclic group or the like; R⁷² represents a hydrogen atom or the like; and R⁷³ represents a hydrogen atom or the like), which has an anti-viral activity, particularly an HIV replication-inhibiting activity; and a medicinal agent, particularly an anti-HIV drug, which comprises the compound.

Description

HIV replication inhibitor

The present invention relates to a novel compound having an antiviral action, and more particularly to an anti-HIV drug.

Among viruses, human immunodeficiency virus (hereinafter abbreviated as HIV), which is a type of retrovirus, is the cause of acquired immunodeficiency syndrome (hereinafter abbreviated as AIDS). It has been known. So far, reverse transcriptase inhibitors (AZT, 3TC, etc.), protease inhibitors (indinavir, etc.), and integrase inhibitors (raltegravir, etc.) have been mainstream as therapeutic agents for AIDS. Problems such as side effects such as disability and the emergence of resistant viruses have been found, and the development of anti-HIV drugs having a different mechanism of action is expected.

In addition, in the treatment of AIDS, multidrug therapy is currently reported to be effective because resistant viruses easily appear. As anti-HIV drugs, reverse transcriptase inhibitors, protease inhibitors, and integrase inhibitors are clinically used, but drugs having the same mechanism of action often show cross-resistance or have additional effects. However, development of anti-HIV drugs having different mechanisms of action is desired.

Patent Document 1 reports a compound having a carboxymethylbenzene skeleton as an HIV reverse transcriptase inhibitor. Further, as an HIV replication inhibitor having a structure relatively similar to that of the present invention, carboxymethylpyridine derivatives (Patent Documents 2 to 8, 14, 19), carboxymethylpyrimidine derivatives (Patent Documents 8 to 11), phenylacetic acid derivatives (patents) Documents 12 to 13), tricyclic carboxymethylpyridine derivatives (Patent Document 15), carboxymethylpyridone derivatives (Patent Document 16), substituted five-membered ring compounds (Patent Document 17) and substituted six-membered ring compounds (Patent Document 18) Has been reported. Patent Document 18 widely discloses six-membered ring compounds, and Patent Documents 2 to 8, 14, and 19 widely disclose pyridine derivatives, but any of the pyridine derivatives having a carboxymethyl structure at the 4-position. It is not described in the literature.

Patent Document 20 describes a compound having a structure relatively similar to that of the present invention, but is a document relating to an anticancer drug. Non-Patent Documents 1 and 2 describe compounds that are relatively similar in structure to the present invention, but are related to synthesis techniques.

Furthermore, the applicants have filed patent applications for HIV replication inhibitors (Patent Document 21, International Application PCT / JP2012 / 0775544, Japanese Patent Application No. 2013-016433, Japanese Patent Application No. 2013-071415). .

International Publication No. 2008/071587 Pamphlet International Publication No. 2007/131350 Pamphlet International Publication No. 2009/062285 Pamphlet International Publication No. 2009/062288 Pamphlet International Publication No. 2009/062289 Pamphlet International Publication No. 2009/062308 Pamphlet International Publication 2010/130034 Pamphlet International Publication 2010/130842 Pamphlet International publication 2011/015641 pamphlet International Publication No. 2011-077665 Pamphlet

International Publication 2012/033735 Pamphlet International Publication 2012/003497 Pamphlet International Publication 2012/003498 Pamphlet International Publication No. 2012/065963 Pamphlet International Publication 2012/066642 Pamphlet International Publication 2012/102985 Pamphlet International Publication 2012/137181 Pamphlet International Publication 2012/140243 Pamphlet International publication 2013/012649 pamphlet Japanese Application Publication No. 2001-151777

International Publication 2013/002357 Pamphlet

An object of the present invention is to provide a novel compound having antiviral activity. The present invention more preferably provides an anti-HIV drug having an HIV replication inhibitory action.

As a result of intensive studies, the present inventors have found a novel HIV replication inhibitor. In addition, the compounds of the present invention and medicaments containing them are antiviral drugs (eg, antiretroviral drugs, anti-HIV drugs, anti-HTLV-1 (Human T cell leukemia virus type 1: human T cell leukemia virus type 1) , Anti-FIV (Feline immunodefectivity virus: feline AIDS virus) drug, anti-SIV (Simian immunodefectivity virus: salid AIDS virus) drug, particularly anti-HIV drug, anti-AIDS drug, or related diseases The present invention shown below has been completed.

(1) Formula (I):

(In the formula, a broken line indicates the presence or absence of a bond, provided that adjacent broken lines do not indicate the presence of a bond at the same time,
R ¹ is a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted A non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
Each R ² is independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted Alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, or substituted or unsubstituted alkynylsulfanyl,
n is 1 or 2,
R ³ represents a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic group. A heterocyclic group,
R ⁴ represents a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle A formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R ⁵ is absent, hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted unsubstituted An aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R ⁶ is halogen, cyano, nitro, or —Z ⁶ —R ⁶¹ ,
Here, Z ⁶ is a single bond, —O—, —S—, —NR ⁶² —, —CO—, —CS—, —SO ₂ —, —O—CO—, —CO—O—, —NR. ⁶² —CO—, —CO—NR ⁶² —, —CH ₂ —CO—NR ⁶² —, —NR ⁶³ —CO—NR ⁶² —, —NR ⁶² —CS—, —CS—NR ⁶² —, —NR ⁶³ — CS—NR ⁶² —, —NR ⁶² —SO ₂ —, —SO ₂ —NR ⁶² —, or —NR ⁶³ —SO ₂ —NR ⁶² —,
R ⁶¹ is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle A formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R ⁶² and R ⁶³ are each independently a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
Z ⁶ is ^{^{_{^{-NR 62 -, - CO-NR}}}} 62 -, - CH 2 -CO-NR 62 -, - NR 63 -CO-NR 62 -, - CS-NR 62 -, - NR 63 -CS-NR 62 In the case of —, —SO ₂ —NR ⁶² —, or —NR ⁶³ —SO ₂ —NR ⁶² —, R ⁶¹ and R ⁶² together with the adjacent nitrogen atom are substituted or unsubstituted aromatic heterocyclic A group or a substituted or unsubstituted non-aromatic heterocyclic group, and R ⁷ is halogen, cyano, nitro, or —Z ⁷ —R ⁷¹ ,
Here, Z ⁷ is a single bond, —O—, —S—, —NR ⁷² —, —CO—, —CS—, —SO ₂ —, —O—CO—, —CO—O—, —NR. ⁷² —CO—, —CO—NR ⁷² —, —CH ₂ —CO—NR ⁷² —, —NR ⁷³ —CO—NR ⁷² —, —NR ⁷² —CS—, —CS—NR ⁷² —, —NR ⁷³ — CS—NR ⁷² —, —NR ⁷² —SO ₂ —, —SO ₂ —NR ⁷² —, or —NR ⁷³ —SO ₂ —NR ⁷² —,
R ⁷¹ is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle A formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R ⁷² and R ⁷³ are each independently a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
Z ⁷ is ^{^{_{^{-NR 72 -, - CO-NR}}}} 72 -, - CH 2 -CO-NR 72 -, - NR 73 -CO-NR 72 -, - CS-NR 72 -, - NR 73 -CS-NR 72 In the case of —, —SO ₂ —NR ⁷² —, or —NR ⁷³ —SO ₂ —NR ⁷² —, R ⁷¹ and R ⁷² together with the adjacent nitrogen atom are substituted or unsubstituted aromatic heterocyclic May form a group or a substituted or unsubstituted non-aromatic heterocyclic group,
Here, R ¹ and R ⁷ together with adjacent carbon atoms are substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted May form an aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R ⁵ and R ⁷ together with the adjacent nitrogen and carbon atoms may form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group ,
R ⁵ and R ⁶ may be combined with adjacent nitrogen and carbon atoms to form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group. . )
Or a pharmaceutically acceptable salt thereof (excluding the following compounds):

(2) The compound according to (1) or a pharmaceutically acceptable salt thereof, wherein R ⁵ is not present,
(3) The compound of the above (2) represented by formula (II) or a pharmaceutically acceptable salt thereof,

(4) The compound according to any one of (1) to (3) above, wherein R ⁴ is a hydrogen atom, or a pharmaceutically acceptable salt thereof,
(5) The compound according to any one of the above (1) to (4), wherein n is 1, or a pharmaceutically acceptable salt thereof,
(6) The compound according to any one of the above (1) to (5), wherein R ² is substituted or unsubstituted alkyloxy, or a pharmaceutically acceptable salt thereof,
(7) The compound according to any one of the above (1) to (6), wherein R ⁶ is substituted or unsubstituted alkyl, or a pharmaceutically acceptable salt thereof,
(8) The compound or a pharmaceutically acceptable salt thereof according to any one of the above (1) to (7), wherein R ¹ is substituted or unsubstituted alkyl,
(9) R ⁷ is —Z ⁷ —R ⁷¹ and Z ⁷ is a single bond, —O—, —NR ⁷² —, —NR ⁷² —CO—, —CO—NR ⁷² —, —CH ₂ —CO—. ^{^{^{^{NR 72 -, - NR 73 -CO}}}} -NR 72 -, - NR 72 -CS -, - CS-NR 72 -, - NR 73 -CS-NR 72 -, - NR 72 -SO 2 -, - SO 2 - NR ⁷² -, or ^{^-NR} 73 _-SO 2 ^-NR ⁷² - is a compound or a pharmaceutically acceptable salt thereof according to any one of the above (1) to (8),
(10) R ⁷ is —Z ⁷ —R ⁷¹ , Z ⁷ is a single bond, —NR ⁷² —, —NR ⁷² —CO—, —CO—NR ⁷² —, —CH ₂ —CO—NR ⁷² —, The compound according to the above (9), which is —NR ⁷³ —CO—NR ⁷² —, —NR ⁷³ —CS—NR ⁷² —, —NR ⁷² —SO ₂ —, or —NR ⁷³ —SO ₂ —NR ⁷² — Its pharmaceutically acceptable salt,
(11) R ⁷¹ is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic ring The compound of the above (9) or (10) or a pharmaceutically acceptable salt thereof, which is a formula group, or a substituted or unsubstituted non-aromatic heterocyclic group,
(12) R ⁷ is —Z ⁷ —R ⁷¹ , Z ⁷ is —NR ⁷³ —CO—NR ⁷² —, and R ⁷¹ is a substituted or unsubstituted non-aromatic carbocyclic group, 9) to (11) or a pharmaceutically acceptable salt thereof,
(13) The above ( ¹ ), wherein R ¹ and R ⁷ together with adjacent carbon atoms form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group. A compound or a pharmaceutically acceptable salt thereof according to any one of to (7),
(14) Formula (III):

Indicated by
X is —C (R ¹⁰ ) ₂ —, —NR ⁹ —, or —O—,
Y is —C (R ¹⁰ ) ₂ —, —CO—, or —SO ₂ —,
W is —C (R ¹⁰ ) ₂ —, —NR ¹⁰ —, or —O—,
R ⁹ is halogen, cyano, nitro, or —Z ⁹ —R ⁹¹ ,
Here, Z ⁹ is a single bond, —O—, —S—, —NR ⁹² —, —CO—, —CS—, —SO ₂ —, —O—CO—, —CO—O—, —NR. ⁹² —CO—, —CO—NR ⁹² —, —CH ₂ —CO—NR ⁹² —, —NR ⁹³ —CO—NR ⁹² —, —NR ⁹² —CS—, —CS—NR ⁹² —, —NR ⁹³ — CS—NR ⁹² —, —NR ⁹² —SO ₂ —, —SO ₂ —NR ⁹² —, or —NR ⁹³ —SO ₂ —NR ⁹² —,
R ⁹¹ is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle A formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R ⁹² and R ⁹³ are each independently a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
Z ⁹ is ^{^{_{^{-NR 92 -, - CO-NR}}}} 92 -, - CH 2 -CO-NR 92 -, - NR 93 -CO-NR 92 -, - CS-NR 92 -, - NR 93 -CS-NR 92 In the case of —, —SO ₂ —NR ⁹² —, or —NR ⁹³ —SO ₂ —NR ⁹² —, R ⁹¹ and R ⁹² together with the adjacent nitrogen atom are substituted or unsubstituted aromatic heterocyclic May form a group or a substituted or unsubstituted non-aromatic heterocyclic group, and
R ¹⁰ each independently represents a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted A non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
The compound of the above (13) or a pharmaceutically acceptable salt thereof,
(15) X is —NR ⁹ —, R ⁹ is —Z ⁹ —R ⁹¹ , Z ⁹ is —CO—NR ⁹² —, and R ⁹¹ is a substituted or unsubstituted non-aromatic carbocyclic group. The compound or a pharmaceutically acceptable salt thereof according to (14), which is a group,
(16) R ⁵ and R ⁷ together with the adjacent nitrogen and carbon atoms form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group, (1) The compound described in the above or a pharmaceutically acceptable salt thereof,
(17) Formulas (IV) to (VI):

Indicated by one of the
R ⁸ is halogen, cyano, nitro, or —Z ⁸ —R ⁸¹ ;
Here, Z ⁸ is a single bond, —O—, —S—, —NR ⁸² —, —CO—, —CS—, —SO ₂ —, —O—CO—, —CO—O—, —NR. ⁸² —CO—, —CO—NR ⁸² —, —CH ₂ —CO—NR ⁸² —, —NR ⁸³ —CO—NR ⁸² —, —NR ⁸² —CS—, —CS—NR ⁸² —, —NR ⁸³ — CS—NR ⁸² —, —NR ⁸² —SO ₂ —, —SO ₂ —NR ⁸² —, or —NR ⁸³ —SO ₂ —NR ⁸² —,
R ⁸¹ is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle A formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R ⁸² and R ⁸³ are each independently a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
Z ⁸ is ^{^{_{^{-NR 82 -, - CO-NR}}}} 82 -, - CH 2 -CO-NR 82 -, - NR 83 -CO-NR 82 -, - CS-NR 82 -, - NR 83 -CS-NR 82 In the case of —, —SO ₂ —NR ⁸² —, or —NR ⁸³ —SO ₂ —NR ⁸² —, R ⁸¹ and R ⁸² together with the adjacent nitrogen atom are substituted or unsubstituted aromatic heterocyclic May form a group or a substituted or unsubstituted non-aromatic heterocyclic group,
The compound of the above (16) or a pharmaceutically acceptable salt thereof,
(18) In the above (1) to (17), R ³ is substituted or unsubstituted phenyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted chromanyl, or substituted or unsubstituted benzomorpholinyl Any of the compounds or pharmaceutically acceptable salts thereof,
(19) R ¹ is substituted or unsubstituted alkyl, R ² is substituted or unsubstituted alkyloxy, n is 1, and R ³ is substituted or unsubstituted phenyl, substituted or unsubstituted cyclo Alkenyl, substituted or unsubstituted chromanyl, or substituted or unsubstituted benzomorpholinyl, R ⁴ is a hydrogen atom, R ⁵ is absent, and R ⁶ is substituted or unsubstituted alkyl. (1) to the compound according to any one of (11) or a pharmaceutically acceptable salt thereof,
(20) R ¹ and R ⁷ together with the adjacent carbon atom form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group, and R ² is substituted Or unsubstituted alkyloxy, n is 1, and R ³ is substituted or unsubstituted phenyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted chromanyl, or substituted or unsubstituted benzomorpholinyl Wherein R ⁴ is a hydrogen atom, R ⁵ is absent, and R ⁶ is a substituted or unsubstituted alkyl, or a pharmaceutically acceptable salt thereof Salt,
(21) R ¹ is substituted or unsubstituted alkyl, R ² is substituted or unsubstituted alkyloxy, n is 1, and R ³ is substituted or unsubstituted phenyl, substituted or unsubstituted cyclo Alkenyl, substituted or unsubstituted chromanyl, or substituted or unsubstituted benzomorpholinyl, R ⁴ is a hydrogen atom, and R ⁵ and R ⁷ are substituted with adjacent nitrogen and carbon atoms or The compound according to the above (1), which forms an unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group, and R ⁶ is substituted or unsubstituted alkyl, or a pharmaceutically acceptable salt thereof Salt,
(22) A pharmaceutical composition comprising the compound according to any one of (1) to (21) above or a pharmaceutically acceptable salt thereof,
(23) The pharmaceutical composition according to the above (22), which has an anti-HIV action,
(24) A method for treating a viral infection, comprising administering to a human an antivirally effective amount of the compound according to any one of (1) to (21) above,
(25) The treatment method according to (24) above for HIV infection,
(26) The compound according to any one of (1) to (21) or a pharmaceutically acceptable salt thereof for the treatment of a viral infection,
(27) The compound according to the above (26) or a pharmaceutically acceptable salt thereof for the treatment of HIV infection,
(28) Use of the compound according to any one of (1) to (21) above or a pharmaceutically acceptable salt thereof for the manufacture of a therapeutic agent for viral infections,
(29) Use of the above (28) for the manufacture of a therapeutic agent for HIV infection.

The compound of the present invention has replication inhibitory activity against viruses, particularly HIV (eg, HIV-1) and its resistant viruses. Therefore, it is useful for prevention or treatment of viral infections (eg AIDS).

The meaning of each term used in this specification is explained below. Unless otherwise specified, each term is used in the same meaning when used alone or in combination with other terms.

“Halogen” includes fluorine atom, chlorine atom, bromine atom, and iodine atom. In particular, a fluorine atom and a chlorine atom are preferable.

“Alkyl” includes straight or branched hydrocarbon groups having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, and still more preferably 1 to 4 carbon atoms. To do. For example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, n-heptyl, isoheptyl, n-octyl , Isooctyl, n-nonyl, n-decyl and the like.
Preferred embodiments of “alkyl” include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl and n-pentyl. Further preferred examples include methyl, ethyl, n-propyl, isopropyl and tert-butyl.

“Alkenyl” has 2 to 15 carbon atoms, preferably 2 to 10 carbon atoms, more preferably 2 to 6 carbon atoms, and further preferably 2 to 4 carbon atoms, having one or more double bonds at any position. These linear or branched hydrocarbon groups are included. For example, vinyl, allyl, propenyl, isopropenyl, butenyl, isobutenyl, prenyl, butadienyl, pentenyl, isopentenyl, pentadienyl, hexenyl, isohexenyl, hexadienyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, decenyl, tridecenyl, decenyl Etc.
Preferred embodiments of “alkenyl” include vinyl, allyl, propenyl, isopropenyl and butenyl.

“Alkynyl” has 2 to 10 carbon atoms, preferably 2 to 8 carbon atoms, more preferably 2 to 6 carbon atoms, and more preferably 2 to 4 carbon atoms, having one or more triple bonds at any position. Includes straight chain or branched hydrocarbon groups. Examples include ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl and the like. These may further have a double bond at an arbitrary position.
Preferred embodiments of “alkynyl” include ethynyl, propynyl, butynyl and pentynyl.

“Alkylene” is a straight or branched divalent hydrocarbon having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, and still more preferably 1 to 4 carbon atoms. Includes groups. Examples include methylene, ethylene, trimethylene, propylene, tetramethylene, pentamethylene, hexamethylene and the like.

The term “alkenylene” refers to a carbon number of 2 to 15, preferably 2 to 10, more preferably 2 to 6 and even more preferably 2 to 4 having one or more double bonds at an arbitrary position. And a linear or branched divalent hydrocarbon group. For example, vinylene, propenylene, butenylene, pentenylene and the like can be mentioned.

“Alkynylene” refers to carbon atoms of 2 to 15, preferably 2 to 10, more preferably 2 to 6, more preferably 2 to 4 carbon atoms having one or more triple bonds at any position. A linear or branched divalent hydrocarbon group is included. These may further have a double bond at an arbitrary position. For example, ethynylene, propynylene, butynylene, pentynylene, hexynylene and the like can be mentioned.

“Aromatic carbocyclic group” means a monocyclic or bicyclic or more aromatic hydrocarbon group. For example, phenyl, naphthyl, anthryl, phenanthryl and the like can be mentioned.
A preferred embodiment of the “aromatic carbocyclic group” includes phenyl.

The “non-aromatic carbocyclic group” means a non-aromatic saturated hydrocarbon group or non-aromatic unsaturated hydrocarbon group having one or more rings. The non-aromatic carbocyclic group having 2 or more rings also includes those in which the ring in the above “aromatic carbocyclic group” is condensed with a monocyclic or 2 or more non-aromatic carbocyclic groups.
Furthermore, the “non-aromatic carbocyclic group” includes a group that forms a bridge or a spiro ring as described below.

The monocyclic non-aromatic carbocyclic group preferably has 3 to 16 carbon atoms, more preferably 3 to 12 carbon atoms, and still more preferably 4 to 8 carbon atoms. For example, cycloalkyl, cycloalkenyl and the like can be mentioned.
“Cycloalkyl” includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl and the like.
“Cycloalkenyl” includes cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclohexadienyl and the like.
Examples of the two or more non-aromatic carbocyclic groups include indanyl, indenyl, acenaphthyl, tetrahydronaphthyl, fluorenyl, dihydroindenyl and the like.

“Aromatic heterocyclic group” means a monocyclic or bicyclic or more aromatic cyclic group having one or more heteroatoms arbitrarily selected from O, S and N in the ring To do.
The aromatic heterocyclic group having two or more rings includes those obtained by condensing a ring in the above “aromatic carbocyclic group” to a monocyclic or two or more aromatic heterocyclic group.
The monocyclic aromatic heterocyclic group is preferably 5 to 8 members, more preferably 5 or 6 members. Examples include pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazolyl, triazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, thiadiazolyl, and the like.
Examples of the bicyclic aromatic heterocyclic group include indolyl, isoindolyl, indazolyl, indolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, naphthyridinyl, quinoxalinyl, purinyl, pteridinyl, benzimidazolyl, benzisoxazolyl, benzisoxazolyl, Oxazolyl, benzoxiazolyl, benzisothiazolyl, benzothiazolyl, benzothiadiazolyl, benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, imidazopyridyl, triazolopyridyl, imidazothiazolyl, pyrazinopyr Dazinyl, oxazolopyridyl, thiazolopyridyl and the like can be mentioned.
Examples of the aromatic heterocyclic group having 3 or more rings include carbazolyl, acridinyl, xanthenyl, phenothiazinyl, phenoxathinyl, phenoxazinyl, dibenzofuryl and the like.

"Non-aromatic heterocyclic group" means a monocyclic or bicyclic or more non-aromatic cyclic group having one or more of the same or different heteroatoms arbitrarily selected from O, S and N in the ring Means.
The non-aromatic heterocyclic group having 2 or more rings is a monocyclic or 2 or more non-aromatic heterocyclic group, the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group”, and Also included are those in which each ring in the “aromatic heterocyclic group” is condensed.
Furthermore, the “non-aromatic heterocyclic group” includes a group which forms a bridge or a spiro ring as described below.

The monocyclic non-aromatic heterocyclic group is preferably 3 to 8 members, more preferably 5 or 6 members. For example, dioxanyl, thiranyl, oxiranyl, oxetanyl, oxathiolanyl, azetidinyl, thianyl, thiazolidinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl, morpholinyl, morpholino, thiomorpholinyl, morpholino, thiomorpholinyl, morpholino, thiomorpholinyl Furyl, tetrahydropyranyl, dihydrothiazolyl, tetrahydrothiazolyl, tetrahydroisothiazolyl, dihydrooxazinyl, hexahydroazepinyl, tetrahydrodiazepinyl, tetrahydropyridazinyl, hexahydropyrimidinyl, dioxolanyl, dioxazinyl Aziridinyl, dioxolinyl, oxepanyl, thiolanyl, thii Le, triazinyl, and the like.
Examples of the non-aromatic heterocyclic group having two or more rings include indolinyl, isoindolinyl, chromanyl, isochromanyl, dihydrobenzofuryl, benzodioxolyl, benzodioxanyl, benzomorpholinyl and the like.

“Hydroxyalkyl” means a group in which one or more hydroxy groups are replaced with a hydrogen atom bonded to a carbon atom of the “alkyl”. Examples thereof include hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxypropyl, 2-hydroxypropyl, 1,2-hydroxyethyl and the like.
A preferred embodiment of “hydroxyalkyl” includes hydroxymethyl.

“Alkyloxy” means a group in which the above “alkyl” is bonded to an oxygen atom. Examples thereof include methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, tert-butyloxy, isobutyloxy, sec-butyloxy, pentyloxy, isopentyloxy, hexyloxy and the like.
Preferable embodiments of “alkyloxy” include methoxy, ethoxy, n-propyloxy, isopropyloxy, tert-butyloxy.

“Alkenyloxy” means a group in which the above “alkenyl” is bonded to an oxygen atom.
For example, vinyloxy, allyloxy, 1-propenyloxy, 2-butenyloxy, 2-pentenyloxy, 2-hexenyloxy, 2-heptenyloxy, 2-octenyloxy and the like can be mentioned.

“Alkynyloxy” means a group in which the above “alkynyl” is bonded to an oxygen atom.
Examples include ethynyloxy, 1-propynyloxy, 2-propynyloxy, 2-butynyloxy, 2-pentynyloxy, 2-hexynyloxy, 2-heptynyloxy, 2-octynyloxy and the like.

“Haloalkyl” means a group in which one or more of the above “halogens” are bonded to the above “alkyl”. For example, monofluoromethyl, monofluoroethyl, monofluoropropyl, 2,2,3,3,3-pentafluoropropyl, monochloromethyl, trifluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2, Examples include 2,2-trichloroethyl, 1,2-dibromoethyl, 1,1,1-trifluoropropan-2-yl and the like.
Preferable embodiments of “haloalkyl” include trifluoromethyl and trichloromethyl.

“Haloalkyloxy” means a group in which the above “haloalkyl” is bonded to an oxygen atom. Examples thereof include monofluoromethoxy, monofluoroethoxy, trifluoromethoxy, trichloromethoxy, trifluoroethoxy, trichloroethoxy and the like.
Preferable embodiments of “haloalkyloxy” include trifluoromethoxy and trichloromethoxy.

“Alkyloxyalkyl” means a group in which the above “alkyloxy” is bonded to the above “alkyl”. For example, methoxymethyl, methoxyethyl, ethoxymethyl and the like can be mentioned.

“Alkyloxyalkyloxy” means a group in which the “alkyloxy” is bonded to the “alkyloxy”. Examples thereof include methoxymethoxy, methoxyethoxy, ethoxymethoxy, ethoxyethoxy and the like.

“Alkylcarbonyl” means a group in which the above “alkyl” is bonded to a carbonyl group. Examples thereof include methylcarbonyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, tert-butylcarbonyl, isobutylcarbonyl, sec-butylcarbonyl, pentylcarbonyl, isopentylcarbonyl, hexylcarbonyl and the like.
Preferable embodiments of “alkylcarbonyl” include methylcarbonyl, ethylcarbonyl, and n-propylcarbonyl.

“Alkenylcarbonyl” means a group in which the above “alkenyl” is bonded to a carbonyl group. For example, ethylenylcarbonyl, propenylcarbonyl and the like can be mentioned.

“Alkynylcarbonyl” means a group in which the above “alkynyl” is bonded to a carbonyl group. For example, ethynylcarbonyl, propynylcarbonyl and the like can be mentioned.

“Monoalkylamino” means a group in which the above “alkyl” is replaced with one hydrogen atom bonded to the nitrogen atom of the amino group. For example, methylamino, ethylamino, isopropylamino and the like can be mentioned.
Preferable embodiments of “monoalkylamino” include methylamino and ethylamino.

“Dialkylamino” means a group in which the above “alkyl” is replaced with two hydrogen atoms bonded to the nitrogen atom of the amino group. Two alkyl groups may be the same or different. Examples include dimethylamino, diethylamino, N, N-diisopropylamino, N-methyl-N-ethylamino, N-isopropyl-N-ethylamino and the like.
Preferred embodiments of “dialkylamino” include dimethylamino and diethylamino.

“Alkylsulfonyl” means a group in which the above “alkyl” is bonded to a sulfonyl group. For example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, tert-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl and the like can be mentioned.
Preferable embodiments of “alkylsulfonyl” include methylsulfonyl and ethylsulfonyl.

“Alkenylsulfonyl” means a group in which the above “alkenyl” is bonded to a sulfonyl group. For example, ethylenylsulfonyl, propenylsulfonyl and the like can be mentioned.

“Alkynylsulfonyl” means a group in which the above “alkynyl” is bonded to a sulfonyl group. For example, ethynylsulfonyl, propynylsulfonyl and the like can be mentioned.

“Monoalkylcarbonylamino” means a group in which the above “alkylcarbonyl” is replaced with one hydrogen atom bonded to the nitrogen atom of the amino group. For example, methylcarbonylamino, ethylcarbonylamino, propylcarbonylamino, isopropylcarbonylamino, tert-butylcarbonylamino, isobutylcarbonylamino, sec-butylcarbonylamino and the like can be mentioned.
Preferable embodiments of “monoalkylcarbonylamino” include methylcarbonylamino and ethylcarbonylamino.

“Dialkylcarbonylamino” means a group in which the above “alkylcarbonyl” is replaced with two hydrogen atoms bonded to the nitrogen atom of the amino group. Two alkylcarbonyl groups may be the same or different. For example, dimethylcarbonylamino, diethylcarbonylamino, N, N-diisopropylcarbonylamino and the like can be mentioned.
Preferred embodiments of “dialkylcarbonylamino” include dimethylcarbonylamino and diethylcarbonylamino.

“Monoalkylsulfonylamino” means a group in which the above “alkylsulfonyl” is replaced with one hydrogen atom bonded to the nitrogen atom of the amino group. Examples include methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, isopropylsulfonylamino, tert-butylsulfonylamino, isobutylsulfonylamino, sec-butylsulfonylamino and the like.
Preferable embodiments of “monoalkylsulfonylamino” include methylsulfonylamino and ethylsulfonylamino.

“Dialkylsulfonylamino” means a group in which the above “alkylsulfonyl” is replaced with two hydrogen atoms bonded to the nitrogen atom of the amino group. Two alkylsulfonyl groups may be the same or different. For example, dimethylsulfonylamino, diethylsulfonylamino, N, N-diisopropylsulfonylamino and the like can be mentioned.
Preferred embodiments of “dialkylcarbonylamino” include dimethylsulfonylamino and diethylsulfonylamino.

“Alkylimino” means a group in which the above “alkyl” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group. For example, methylimino, ethylimino, n-propylimino, isopropylimino and the like can be mentioned.

“Alkenylimino” means a group in which the above “alkenyl” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group. Examples thereof include ethylenylimino and propenylimino.

“Alkynylimino” means a group in which the above “alkynyl” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group. For example, ethynylimino, propynylimino and the like can be mentioned.

“Alkylcarbonylimino” means a group in which the above “alkylcarbonyl” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group. For example, methylcarbonylimino, ethylcarbonylimino, n-propylcarbonylimino, isopropylcarbonylimino and the like can be mentioned.

“Alkenylcarbonylimino” means a group in which the above “alkenylcarbonyl” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group. For example, ethylenylcarbonylimino, propenylcarbonylimino and the like can be mentioned.

“Alkynylcarbonylimino” means a group in which the above “alkynylcarbonyl” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group. For example, ethynylcarbonylimino, propynylcarbonylimino and the like can be mentioned.

“Alkyloxyimino” means a group in which the above “alkyloxy” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group. Examples thereof include methyloxyimino, ethyloxyimino, n-propyloxyimino, isopropyloxyimino and the like.

“Alkenyloxyimino” means a group in which the above “alkenyloxy” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group. For example, ethylenyloxyimino, propenyloxyimino and the like can be mentioned.

“Alkynyloxyimino” means a group in which the above “alkynyloxy” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group. For example, ethynyloxyimino, propynyloxyimino and the like can be mentioned.

“Alkylcarbonyloxy” means a group in which the above “alkylcarbonyl” is bonded to an oxygen atom. For example, methylcarbonyloxy, ethylcarbonyloxy, propylcarbonyloxy, isopropylcarbonyloxy, tert-butylcarbonyloxy, isobutylcarbonyloxy, sec-butylcarbonyloxy and the like can be mentioned.
Preferable embodiments of “alkylcarbonyloxy” include methylcarbonyloxy and ethylcarbonyloxy.

“Alkenylcarbonyloxy” means a group in which the above “alkenylcarbonyl” is bonded to an oxygen atom. For example, ethylenylcarbonyloxy, propenylcarbonyloxy and the like can be mentioned.

“Alkynylcarbonyloxy” means a group in which the above “alkynylcarbonyl” is bonded to an oxygen atom. For example, ethynylcarbonyloxy, propynylcarbonyloxy and the like can be mentioned.

“Alkyloxycarbonyl” means a group in which the above “alkyloxy” is bonded to a carbonyl group. For example, methyloxycarbonyl, ethyloxycarbonyl, propyloxycarbonyl, isopropyloxycarbonyl, tert-butyloxycarbonyl, isobutyloxycarbonyl, sec-butyloxycarbonyl, pentyloxycarbonyl, isopentyloxycarbonyl, hexyloxycarbonyl, etc. It is done.
Preferable embodiments of “alkyloxycarbonyl” include methyloxycarbonyl, ethyloxycarbonyl, and propyloxycarbonyl.

“Alkenyloxycarbonyl” means a group in which the above “alkenyloxy” is bonded to a carbonyl group. For example, ethylenyloxycarbonyl, propenyloxycarbonyl and the like can be mentioned.

“Alkynyloxycarbonyl” means a group in which the above “alkynyloxy” is bonded to a carbonyl group. For example, ethynyloxycarbonyl, propynyloxycarbonyl and the like can be mentioned.

“Alkylsulfanyl” means a group in which the above “alkyl” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group. For example, methylsulfanyl, ethylsulfanyl, n-propylsulfanyl, isopropylsulfanyl and the like can be mentioned.

“Alkenylsulfanyl” means a group in which the above “alkenyl” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group. For example, ethylenylsulfanyl, propenylsulfanyl and the like can be mentioned.

“Alkynylsulfanyl” means a group in which the above “alkynyl” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group. For example, ethynylsulfanyl, propynylsulfanyl and the like can be mentioned.

“Alkylsulfinyl” means a group in which the above “alkyl” is bonded to a sulfinyl group. Examples thereof include methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl and the like.

“Alkenylsulfinyl” means a group in which the above “alkenyl” is bonded to a sulfinyl group. For example, ethylenylsulfinyl, propenylsulfinyl and the like can be mentioned.

“Alkynylsulfinyl” means a group in which the above “alkynyl” is bonded to a sulfinyl group. For example, ethynylsulfinyl, propynylsulfinyl and the like can be mentioned.

“Monoalkylcarbamoyl” means a group in which the above “alkyl” is replaced with one hydrogen atom bonded to the nitrogen atom of the carbamoyl group. Examples thereof include methylcarbamoyl and ethylcarbamoyl.

“Dialkylcarbamoyl” means a group in which the above “alkyl” is replaced with two hydrogen atoms bonded to the nitrogen atom of the carbamoyl group. Two alkyl groups may be the same or different. Examples thereof include dimethylcarbamoyl, diethylcarbamoyl and the like.

“Monoalkylsulfamoyl” means a group in which the above “alkyl” is replaced with one hydrogen atom bonded to the nitrogen atom of the sulfamoyl group. For example, methylsulfamoyl, dimethylsulfamoylmoyl, etc. are mentioned.

“Dialkylsulfamoyl” means a group in which the above “alkyl” is replaced with two hydrogen atoms bonded to the nitrogen atom of the sulfamoyl group. Two alkyl groups may be the same or different. Examples thereof include dimethylcarbamoyl, diethylcarbamoyl and the like.

“Trialkylsilyl” means a group in which three of the above “alkyl” are bonded to a silicon atom. The three alkyls may be the same or different. For example, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl and the like can be mentioned.

“Aromatic carbocyclic alkyl”, “non-aromatic carbocyclic alkyl”, “aromatic heterocyclic alkyl”, and “non-aromatic heterocyclic alkyl”,
“Aromatic carbocyclic alkyloxy”, “non-aromatic carbocyclic alkyloxy”, “aromatic heterocyclic alkyloxy”, and “non-aromatic heterocyclic alkyloxy”,
“Aromatic carbocyclic alkylsulfanyl”, “non-aromatic carbocyclic alkylsulfanyl”, “aromatic heterocyclic alkylsulfanyl”, and “non-aromatic heterocyclic alkylsulfanyl”,
“Aromatic carbocyclic alkyloxycarbonyl”, “non-aromatic carbocyclic alkyloxycarbonyl”, “aromatic heterocyclic alkyloxycarbonyl”, and “non-aromatic heterocyclic alkyloxycarbonyl”,
“Aromatic carbocyclic alkyloxyalkyl”, “non-aromatic carbocyclic alkyloxyalkyl”, “aromatic heterocyclic alkyloxyalkyl”, and “non-aromatic heterocyclic alkyloxyalkyl”, and “aromatic carbocyclic alkyl” The alkyl part of “amino”, “non-aromatic carbocyclic alkylamino”, “aromatic heterocyclic alkylamino”, and “nonaromatic heterocyclic alkylamino” is the same as the above “alkyl”.

“Aromatic carbocyclic alkyl” means an alkyl substituted with one or more of the above “aromatic carbocyclic groups”. For example, benzyl, phenethyl, phenylpropynyl, benzhydryl, trityl, naphthylmethyl, groups shown below

Etc.
Preferable embodiments of “aromatic carbocyclic alkyl” include benzyl, phenethyl and benzhydryl.

“Non-aromatic carbocyclic alkyl” means alkyl substituted with one or more of the above “non-aromatic carbocyclic groups”. The “non-aromatic carbocyclic alkyl” also includes “non-aromatic carbocyclic alkyl” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group”. For example, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, groups shown below

Etc.

“Aromatic heterocyclic alkyl” means alkyl substituted with one or more of the above “aromatic heterocyclic groups”. “Aromatic heterocyclic alkyl” also includes “aromatic heterocyclic alkyl” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group” and / or “non-aromatic carbocyclic group”. . For example, pyridylmethyl, furanylmethyl, imidazolylmethyl, indolylmethyl, benzothiophenylmethyl, oxazolylmethyl, isoxazolylmethyl, thiazolylmethyl, isothiazolylmethyl, pyrazolylmethyl, isopyrazolylmethyl, pyrrolidinylmethyl, benz Oxazolylmethyl, group shown below

Etc.

“Non-aromatic heterocyclic alkyl” means alkyl substituted with one or more of the above “non-aromatic heterocyclic groups”. In the “non-aromatic heterocyclic alkyl”, the alkyl portion is substituted with the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group” and / or “aromatic heterocyclic group”. Also included are “non-aromatic heterocyclic alkyl”. For example, tetrahydropyranylmethyl, morpholinylethyl, piperidinylmethyl, piperazinylmethyl, groups shown below

Etc.

“Aromatic carbocyclic alkyloxy” means alkyloxy substituted with one or more of the above “aromatic carbocyclic groups”. For example, benzyloxy, phenethyloxy, phenylpropynyloxy, benzhydryloxy, trityloxy, naphthylmethyloxy, groups shown below

Etc.

“Non-aromatic carbocyclic alkyloxy” means alkyloxy substituted with one or more of the above “non-aromatic carbocyclic groups”. The “non-aromatic carbocyclic alkyloxy” also includes “non-aromatic carbocyclic alkyloxy” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group”. For example, cyclopropylmethyloxy, cyclobutylmethyloxy, cyclopentylmethyloxy, cyclohexylmethyloxy, groups shown below

Etc.

“Aromatic heterocyclic alkyloxy” means alkyloxy substituted with one or more of the above “aromatic heterocyclic groups”. “Aromatic heterocyclic alkyloxy” also includes “aromatic heterocyclic alkyloxy” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group” and / or “non-aromatic carbocyclic group”. Include. For example, pyridylmethyloxy, furanylmethyloxy, imidazolylmethyloxy, indolylmethyloxy, benzothiophenylmethyloxy, oxazolylmethyloxy, isoxazolylmethyloxy, thiazolylmethyloxy, isothiazolylmethyloxy , Pyrazolylmethyloxy, isopyrazolylmethyloxy, pyrrolidinylmethyloxy, benzoxazolylmethyloxy, groups shown below

Etc.

“Non-aromatic heterocyclic alkyloxy” means alkyloxy substituted with one or more of the above “non-aromatic heterocyclic groups”. In the “non-aromatic heterocyclic alkyloxy”, the alkyl moiety is substituted with the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group” and / or “aromatic heterocyclic group”. It also includes “non-aromatic heterocyclic alkyloxy”. For example, tetrahydropyranylmethyloxy, morpholinylethyloxy, piperidinylmethyloxy, piperazinylmethyloxy, groups shown below

Etc.

“Aromatic carbocyclic alkylsulfanyl” means alkylsulfanyl substituted with one or more of the above “aromatic carbocyclic groups”. Examples include benzylsulfanyl, phenethylsulfanyl, phenylpropynylsulfanyl, benzhydrylsulfanyl, tritylsulfanyl, naphthylmethylsulfanyl and the like.

“Non-aromatic carbocyclic alkylsulfanyl” means alkylsulfanyl substituted with one or more of the above “non-aromatic carbocyclic groups”. The “non-aromatic carbocyclic alkylsulfanyl” also includes “non-aromatic carbocyclic alkylsulfanyl” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group”. Examples thereof include cyclopropylmethylsulfanyl, cyclobutylmethylsulfanyl, cyclopentylmethylsulfanyl, cyclohexylmethylsulfanyl and the like.

“Aromatic heterocyclic alkylsulfanyl” means alkylsulfanyl substituted with one or more of the above “aromatic heterocyclic groups”. In addition, “aromatic heterocyclic alkylsulfanyl” includes “aromatic heterocyclic alkylsulfanyl” in which an alkyl moiety is substituted with the above “aromatic carbocyclic group” and / or “non-aromatic carbocyclic group”. Include. For example, pyridylmethylsulfanyl, furanylmethylsulfanyl, imidazolylmethylsulfanyl, indolylmethylsulfanyl, benzothiophenylmethylsulfanyl, oxazolylmethylsulfanyl, isoxazolylmethylsulfanyl, thiazolylmethylsulfanyl, isothiazolylmethylsulfanyl , Pyrazolylmethylsulfanyl, isopyrazolylmethylsulfanyl, pyrrolidinylmethylsulfanyl, benzoxazolylmethylsulfanyl and the like.

“Non-aromatic heterocyclic alkylsulfanyl” means alkylsulfanyl substituted with one or more of the above “non-aromatic heterocyclic groups”. In the “non-aromatic heterocyclic alkylsulfanyl”, the alkyl moiety is substituted with the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group” and / or “aromatic heterocyclic group”. Also included are “non-aromatic heterocyclic alkylsulfanyl”. Examples thereof include tetrahydropyranylmethylsulfanyl, morpholinylethylsulfanyl, piperidinylmethylsulfanyl, piperazinylmethylsulfanyl and the like.

“Aromatic carbocyclic alkyloxycarbonyl” means alkyloxycarbonyl substituted with one or more of the above “aromatic carbocyclic groups”. For example, benzyloxycarbonyl, phenethyloxycarbonyl, phenylpropynyloxycarbonyl, benzohydryloxycarbonyl, trityloxycarbonyl, naphthylmethyloxycarbonyl, groups shown below

Etc.

“Non-aromatic carbocyclic alkyloxycarbonyl” means alkyloxycarbonyl substituted with one or more of the above “non-aromatic carbocyclic groups”. The “non-aromatic carbocyclic alkyloxycarbonyl” also includes “non-aromatic carbocyclic alkyloxycarbonyl” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group”. For example, cyclopropylmethyloxycarbonyl, cyclobutylmethyloxycarbonyl, cyclopentylmethyloxycarbonyl, cyclohexylmethyloxycarbonyl, groups shown below

Etc.

“Aromatic heterocyclic alkyloxycarbonyl” means alkyloxycarbonyl substituted with one or more of the above “aromatic heterocyclic groups”. The “aromatic heterocyclic alkyloxycarbonyl” is an “aromatic heterocyclic alkyloxycarbonyl” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group” and / or “non-aromatic carbocyclic group”. Is also included. For example, pyridylmethyloxycarbonyl, furanylmethyloxycarbonyl, imidazolylmethyloxycarbonyl, indolylmethyloxycarbonyl, benzothiophenylmethyloxycarbonyl, oxazolylmethyloxycarbonyl, isoxazolylmethyloxycarbonyl, thiazolylmethyl Oxycarbonyl, isothiazolylmethyloxycarbonyl, pyrazolylmethyloxycarbonyl, isopyrazolylmethyloxycarbonyl, pyrrolidinylmethyloxycarbonyl, benzoxazolylmethyloxycarbonyl, groups shown below

Etc.

“Non-aromatic heterocyclic alkyloxycarbonyl” means alkyloxycarbonyl substituted with one or more of the above “non-aromatic heterocyclic groups”. In the “non-aromatic heterocyclic alkyloxycarbonyl”, the alkyl moiety is substituted with the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group” and / or “aromatic heterocyclic group”. And “non-aromatic heterocyclic alkyloxycarbonyl”. For example, tetrahydropyranylmethyloxy, morpholinylethyloxy, piperidinylmethyloxy, piperazinylmethyloxy, groups shown below

Etc.

“Aromatic carbocyclic alkyloxyalkyl” means alkyloxyalkyl substituted with one or more of the above “aromatic carbocyclic groups”. For example, benzyloxymethyl, phenethyloxymethyl, phenylpropynyloxymethyl, benzohydryloxymethyl, trityloxymethyl, naphthylmethyloxymethyl, groups shown below

Etc.

“Non-aromatic carbocyclic alkyloxyalkyl” means alkyloxyalkyl substituted with one or more of the above “non-aromatic carbocyclic groups”. In addition, “non-aromatic carbocyclic alkyloxyalkyl” means “non-aromatic carbocyclic alkyloxyalkyl” in which the alkyl moiety to which the non-aromatic carbocycle is bonded is substituted with the above “aromatic carbocyclic group”. Is also included. For example, cyclopropylmethyloxymethyl, cyclobutylmethyloxymethyl, cyclopentylmethyloxymethyl, cyclohexylmethyloxymethyl, groups shown below

Etc.

“Aromatic heterocyclic alkyloxyalkyl” means alkyloxyalkyl substituted with one or more of the above “aromatic heterocyclic groups”. In addition, the “aromatic heterocyclic alkyloxyalkyl” is obtained by replacing the alkyl moiety to which the aromatic heterocyclic ring is bonded with the above “aromatic carbocyclic group” and / or “non-aromatic carbocyclic group”. Also included are “aromatic heterocyclic alkyloxyalkyl”. For example, pyridylmethyloxymethyl, furanylmethyloxymethyl, imidazolylmethyloxymethyl, indolylmethyloxymethyl, benzothiophenylmethyloxymethyl, oxazolylmethyloxymethyl, isoxazolylmethyloxymethyl, thiazolylmethyl Oxymethyl, isothiazolylmethyloxymethyl, pyrazolylmethyloxymethyl, isopyrazolylmethyloxymethyl, pyrrolidinylmethyloxymethyl, benzoxazolylmethyloxymethyl, groups shown below

Etc.

“Non-aromatic heterocyclic alkyloxyalkyl” means alkyloxyalkyl substituted with one or more of the above “non-aromatic heterocyclic groups”. In addition, “non-aromatic heterocyclic alkyloxy” means that the alkyl moiety to which the non-aromatic heterocyclic ring is bonded is the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group” and / or “aromatic”. Also included are “non-aromatic heterocyclic alkyloxyalkyl” substituted with “aromatic heterocyclic group”. For example, tetrahydropyranylmethyloxymethyl, morpholinylethyloxymethyl, piperidinylmethyloxymethyl, piperazinylmethyloxymethyl, groups shown below

Etc.

“Aromatic carbocyclic alkylamino” means a group in which the above “aromatic carbocyclic alkyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. Examples include benzylamino, phenethylamino, phenylpropynylamino, benzohydrylamino, tritylamino, naphthylmethylamino, dibenzylamino and the like.

“Non-aromatic carbocyclic alkylamino” means a group in which the above “non-aromatic carbocyclic alkyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. For example, cyclopropylmethylamino, cyclobutylmethylamino, cyclopentylmethylamino, cyclohexylmethylamino and the like can be mentioned.

“Aromatic heterocyclic alkylamino” means a group in which the above “aromatic heterocyclic alkyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. For example, pyridylmethylamino, furanylmethylamino, imidazolylmethylamino, indolylmethylamino, benzothiophenylmethylamino, oxazolylmethylamino, isoxazolylmethylamino, thiazolylmethylamino, isothiazolylmethylamino , Pyrazolylmethylamino, isopyrazolylmethylamino, pyrrolidinylmethylamino, benzoxazolylmethylamino and the like.

“Non-aromatic heterocyclic alkylamino” means a group in which the above “non-aromatic heterocyclic alkyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. For example, tetrahydropyranylmethylamino, morpholinylethylamino, piperidinylmethylamino, piperazinylmethylamino and the like can be mentioned.

"Aromatic carbocyclic oxy", "aromatic carbocyclic amino", "aromatic carbocyclic carbonyl", "aromatic carbocyclic oxycarbonyl", "aromatic carbocyclic carbonylamino", "aromatic carbocyclic sulfanyl", The “aromatic carbocyclic” portion of “aromatic carbocyclic sulfonyl” is the same as the above “aromatic carbocyclic group”.
“Aromatic carbocyclic oxy” means a group in which an “aromatic carbocycle” is bonded to an oxygen atom. For example, phenyloxy, naphthyloxy and the like can be mentioned.
“Aromatic carbocyclic amino” means a group in which “aromatic carbocycle” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. For example, phenylamino, naphthylamino and the like can be mentioned.
“Aromatic carbocyclic carbonyl” means a group in which an “aromatic carbocycle” is bonded to a carbonyl group. For example, phenylcarbonyl, naphthylcarbonyl and the like can be mentioned.
“Aromatic carbocyclic oxycarbonyl” means a group in which the above “aromatic carbocyclic oxy” is bonded to a carbonyl group. For example, phenyloxycarbonyl, naphthyloxycarbonyl and the like can be mentioned.
“Aromatic carbocyclic carbonylamino” means a group in which the above “aromatic carbocyclic carbonyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. For example, phenylcarbonylamino, naphthylcarbonylamino and the like can be mentioned.
“Aromatic carbocyclic sulfanyl” means a group in which an “aromatic carbocyclic ring” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group. Examples thereof include phenylsulfanyl and naphthylsulfanyl.
“Aromatic carbocyclic sulfonyl” means a group in which “aromatic carbocycle” is bonded to a sulfonyl group. For example, phenylsulfonyl, naphthylsulfonyl and the like can be mentioned.

"Non-aromatic carbocyclic oxy", "non-aromatic carbocyclic amino", "non-aromatic carbocyclic carbonyl", "non-aromatic carbocyclic oxycarbonyl", "non-aromatic carbocyclic carbonylamino", "non-aromatic The “non-aromatic carbocyclic group” of “Aromatic carbocyclic sulfanyl” and “non-aromatic carbocyclic sulfonyl” is the same as the above “non-aromatic carbocyclic group”.
“Non-aromatic carbocyclic oxy” means a group in which “non-aromatic carbocycle” is bonded to an oxygen atom. For example, cyclopropyloxy, cyclohexyloxy, cyclohexenyloxy and the like can be mentioned.
“Non-aromatic carbocyclic amino” means a group in which “non-aromatic carbocycle” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. For example, cyclopropylamino, cyclohexylamino, cyclohexenylamino and the like can be mentioned.
“Non-aromatic carbocycle carbonyl” means a group in which “non-aromatic carbocycle” is bonded to a carbonyl group. For example, cyclopropylcarbonyl, cyclohexylcarbonyl, cyclohexenylcarbonyl and the like can be mentioned.
The “non-aromatic carbocyclic oxycarbonyl” means a group in which the above “non-aromatic carbocyclic oxy” is bonded to a carbonyl group. For example, cyclopropyloxycarbonyl, cyclohexyloxycarbonyl, cyclohexenyloxycarbonyl and the like can be mentioned.
The “non-aromatic carbocyclic carbonylamino” means a group in which the above “non-aromatic carbocyclic carbonyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. Examples thereof include cyclopropylcarbonylamino, cyclohexylcarbonylamino, cyclohexenylcarbonylamino and the like.
“Non-aromatic carbocyclic sulfanyl” means a group in which a “non-aromatic carbocyclic ring” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group. For example, cyclopropylsulfanyl, cyclohexylsulfanyl, cyclohexenylsulfanyl and the like can be mentioned.
“Non-aromatic carbocycle sulfonyl” means a group in which “non-aromatic carbocycle” is bonded to a sulfonyl group. Examples include cyclopropylsulfonyl, cyclohexylsulfonyl, cyclohexenylsulfonyl and the like.

“Aromatic heterocyclic oxy”, “aromatic heterocyclic amino”, “aromatic heterocyclic carbonyl”, “aromatic heterocyclic oxycarbonyl”, “aromatic heterocyclic carbonylamino”, “aromatic heterocyclic sulfanyl”, The “aromatic heterocycle” part of “aromatic heterocycle sulfonyl” is the same as the above “aromatic heterocycle”.
“Aromatic heterocycle oxy” means a group in which “aromatic heterocycle” is bonded to an oxygen atom. For example, pyridyloxy, oxazolyloxy and the like can be mentioned.
“Aromatic heterocycle amino” means a group in which “aromatic heterocycle” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. For example, pyridylamino, oxazolylamino and the like can be mentioned.
“Aromatic heterocycle carbonyl” means a group in which “aromatic heterocycle” is bonded to a carbonyl group. For example, pyridylcarbonyl, oxazolylcarbonyl, etc. are mentioned.
“Aromatic heterocyclic oxycarbonyl” means a group in which the above “aromatic heterocyclic oxy” is bonded to a carbonyl group. For example, pyridyloxycarbonyl, oxazolyloxycarbonyl and the like can be mentioned.
“Aromatic heterocyclic carbonylamino” means a group in which the above “aromatic heterocyclic carbonyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. For example, pyridylcarbonylamino, oxazolylcarbonylamino and the like can be mentioned.
“Aromatic heterocycle sulfanyl” means a group in which an “aromatic heterocycle” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group. For example, pyridylsulfanyl, oxazolylsulfanyl and the like can be mentioned.
“Aromatic heterocycle sulfonyl” means a group in which “aromatic heterocycle” is bonded to a sulfonyl group. For example, pyridylsulfonyl, oxazolylsulfonyl and the like can be mentioned.

“Non-aromatic heterocyclic oxy”, “Non-aromatic heterocyclic amino”, “Non-aromatic heterocyclic carbonyl”, “Non-aromatic heterocyclic oxycarbonyl”, “Non-aromatic heterocyclic carbonyl amino”, “Non-aromatic” The “non-aromatic heterocyclic” part of the “aromatic heterocyclic sulfanyl” and “non-aromatic heterocyclic sulfonyl” is the same as the above “non-aromatic heterocyclic group”.
“Non-aromatic heterocyclic oxy” means a group in which “non-aromatic heterocyclic” is bonded to an oxygen atom. For example, piperidinyloxy, tetrahydrofuryloxy and the like can be mentioned.
“Non-aromatic heterocyclic amino” means a group in which “non-aromatic heterocyclic” is replaced with one hydrogen atom bonded to the nitrogen atom of the amino group. For example, piperidinylamino, tetrahydrofurylamino and the like can be mentioned.
“Non-aromatic heterocyclic carbonyl” means a group in which “non-aromatic heterocyclic” is bonded to a carbonyl group. For example, piperidinylcarbonyl, tetrahydrofurylcarbonyl and the like can be mentioned.
The “non-aromatic heterocyclic oxycarbonyl” means a group in which the above “non-aromatic heterocyclic oxy” is bonded to a carbonyl group. For example, piperidinyloxycarbonyl, tetrahydrofuryloxycarbonyl and the like can be mentioned.
The “non-aromatic heterocyclic carbonylamino” means a group in which the above “non-aromatic heterocyclic carbonyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. For example, piperidinylcarbonylamino, tetrahydrofurylcarbonylamino and the like can be mentioned.
“Non-aromatic heterocyclic sulfanyl” means a group in which a “non-aromatic heterocyclic ring” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group. For example, piperidinylsulfanyl, tetrahydrofurylsulfanyl and the like can be mentioned.
“Non-aromatic heterocyclic sulfonyl” means a group in which “non-aromatic heterocyclic” is bonded to a sulfonyl group. For example, piperidinylsulfonyl, tetrahydrofurylsulfonyl and the like can be mentioned.

"Substituted or unsubstituted alkyl", "substituted or unsubstituted alkenyl", "substituted or unsubstituted alkynyl", "substituted or unsubstituted haloalkyl", "substituted or unsubstituted alkyloxy", "substituted or unsubstituted "Substituted alkenyloxy", "substituted or unsubstituted alkynyloxy", "substituted or unsubstituted haloalkyloxy", "substituted or unsubstituted alkylcarbonyl", "substituted or unsubstituted alkenylcarbonyl", "substituted or unsubstituted "Substituted alkynylcarbonyl", "substituted or unsubstituted monoalkylamino", "substituted or unsubstituted dialkylamino", "substituted or unsubstituted alkylsulfonyl", "substituted or unsubstituted alkenylsulfonyl", "substituted or Unsubstituted alkynylsulfonyl , "Substituted or unsubstituted monoalkylcarbonylamino", "substituted or unsubstituted dialkylcarbonylamino", "substituted or unsubstituted monoalkylsulfonylamino", "substituted or unsubstituted dialkylsulfonylamino", "substituted or "Unsubstituted alkylimino", "substituted or unsubstituted alkenylimino", "substituted or unsubstituted alkynylimino", "substituted or unsubstituted alkylcarbonylimino", "substituted or unsubstituted alkenylcarbonylimino", " Substituted or unsubstituted alkynylcarbonylimino, substituted or unsubstituted alkyloxyimino, substituted or unsubstituted alkenyloxyimino, substituted or unsubstituted alkynyloxyimino, substituted or unsubstituted alkyl "Lubonyloxy", "Substituted or unsubstituted alkenylcarbonyloxy", "Substituted or unsubstituted alkynylcarbonyloxy", "Substituted or unsubstituted alkyloxycarbonyl", "Substituted or unsubstituted alkenyloxycarbonyl", "Substituted Or “substituted alkynyloxycarbonyl”, “substituted or unsubstituted alkylsulfanyl”, “substituted or unsubstituted alkenylsulfanyl”, “substituted or unsubstituted alkynylsulfanyl”, “substituted or unsubstituted alkylsulfinyl”, “ Substituted or unsubstituted alkenylsulfinyl, substituted or unsubstituted alkynylsulfinyl, substituted or unsubstituted monoalkylcarbamoyl, substituted or unsubstituted dialkylcarbamoyl, substituted Examples of the substituent of “unsubstituted monoalkylsulfamoyl” and “substituted or unsubstituted dialkylsulfamoyl” include the following substituents. The carbon atom at any position may be bonded to one or more groups selected from the following substituents.
Substituents: halogen, hydroxy, carboxy, amino, imino, hydroxyamino, hydroxyimino, formyl, formyloxy, carbamoyl, sulfamoyl, sulfanyl, sulfino, sulfo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, cyano, nitro, nitroso , Azide, hydrazino, ureido, amidino, guanidino, trialkylsilyl, alkyloxy, alkenyloxy, alkynyloxy, haloalkyloxy, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, monoalkylamino, dialkylamino, alkylsulfonyl, alkenylsulfonyl, alkynyl Sulfonyl, monoalkylcarbonylamino, dialkylcarbonylamino, monoalkylsulfonyl Mino, dialkylsulfonylamino, alkylimino, alkenylimino, alkynylimino, alkylcarbonylimino, alkenylcarbonylimino, alkynylcarbonylimino, alkyloxyimino, alkenyloxyimino, alkynyloxyimino, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy , Alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylsulfanyl, alkenylsulfanyl, alkynylsulfanyl, alkylsulfinyl, alkenylsulfinyl, alkynylsulfinyl, monoalkylcarbamoyl, dialkylcarbamoyl, monoalkylsulfamoyl, dialkylsulfamoyl, aromatic Group carbocyclic group, Aromatic carbocyclic group, aromatic heterocyclic group, non-aromatic heterocyclic group, aromatic carbocyclic oxy, non-aromatic carbocyclic oxy, aromatic heterocyclic oxy, non-aromatic heterocyclic oxy, aromatic Carbocyclic amino, non-aromatic carbocyclic amino, aromatic heterocyclic amino, non-aromatic heterocyclic amino, aromatic carbocyclic carbonyl, non-aromatic carbocyclic carbonyl, aromatic heterocyclic carbonyl, non-aromatic heterocyclic carbonyl, Aromatic carbocyclic oxycarbonyl, non-aromatic carbocyclic oxycarbonyl, aromatic heterocyclic oxycarbonyl, non-aromatic heterocyclic oxycarbonyl, aromatic carbocyclic carbonylamino, non-aromatic carbocyclic carbonylamino, aromatic heterocyclic carbonyl Amino, non-aromatic heterocyclic carbonylamino, aromatic carbocyclic alkyloxy, non-aromatic carbocyclic alkyloxy, aromatic heterocyclic alkyloxy, non-aromatic Heterocyclic alkyloxy, aromatic carbocyclic alkylsulfanyl, nonaromatic carbocyclic alkylsulfanyl, aromatic heterocyclic alkylsulfanyl, nonaromatic heterocyclic alkylsulfanyl, aromatic carbocyclic alkyloxycarbonyl, nonaromatic carbocyclic alkyloxy Carbonyl, aromatic heterocyclic alkyloxycarbonyl, non-aromatic heterocyclic alkyloxycarbonyl, aromatic carbocyclic alkylamino, non-aromatic carbocyclic alkylamino, aromatic heterocyclic alkylamino, non-aromatic heterocyclic alkylamino, aromatic Aromatic carbocyclic sulfanyl, non-aromatic carbocyclic sulfanyl, aromatic heterocyclic sulfanyl, non-aromatic heterocyclic sulfanyl, non-aromatic carbocyclic sulfonyl, aromatic carbocyclic sulfonyl, aromatic heterocyclic sulfonyl, and non-aromatic heterocyclic ring Sulfonyl.

“Substituted or unsubstituted aromatic carbocyclic group”, “Substituted or unsubstituted nonaromatic carbocyclic group”, “Substituted or unsubstituted aromatic heterocyclic group”, and “Substituted or unsubstituted aromatic carbocyclic group” Non-aromatic heterocyclic group ",
"Substituted or unsubstituted aromatic carbocyclic oxy", "Substituted or unsubstituted non-aromatic carbocyclic oxy", "Substituted or unsubstituted aromatic heterocyclic oxy", and "Substituted or unsubstituted non-aromatic Heterocyclic oxy ",
"Substituted or unsubstituted aromatic carbocyclic amino", "Substituted or unsubstituted non-aromatic carbocyclic amino", "Substituted or unsubstituted aromatic heterocyclic amino", and "Substituted or unsubstituted non-aromatic Heterocyclic amino ",
"Substituted or unsubstituted aromatic carbocyclic carbonyl", "Substituted or unsubstituted non-aromatic carbocyclic carbonyl", "Substituted or unsubstituted aromatic heterocyclic carbonyl", and "Substituted or unsubstituted non-aromatic Heterocyclic carbonyl ",
“Substituted or unsubstituted aromatic carbocyclic oxycarbonyl”, “substituted or unsubstituted nonaromatic carbocyclic oxycarbonyl”, “substituted or unsubstituted aromatic heterocyclic oxycarbonyl”, and “substituted or unsubstituted Non-aromatic heterocyclic oxycarbonyl ",
"Substituted or unsubstituted aromatic carbocyclic sulfanyl", "Substituted or unsubstituted non-aromatic carbocyclic sulfanyl", "Substituted or unsubstituted aromatic heterocyclic sulfanyl", and "Substituted or unsubstituted non-aromatic "Heterocyclic sulfanyl", and "substituted or unsubstituted aromatic carbocyclic sulfonyl", "substituted or unsubstituted non-aromatic carbocyclic sulfonyl", "substituted or unsubstituted aromatic heterocyclic sulfonyl", and "substituted or Substituents on the rings of “aromatic carbocycle”, “non-aromatic carbocycle”, “aromatic heterocycle”, and “non-aromatic heterocycle” of “unsubstituted non-aromatic heterocycle sulfonyl” include The following substituents are mentioned. An atom at any position on the ring may be bonded to one or more groups selected from the following substituents.
Substituents: halogen, hydroxy, carboxy, amino, imino, hydroxyamino, hydroxyimino, formyl, formyloxy, carbamoyl, sulfamoyl, sulfanyl, sulfino, sulfo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, cyano, nitro, nitroso , Azide, hydrazino, ureido, amidino, guanidino, trialkylsilyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkyloxy, alkenyloxy, alkynyloxy, haloalkyloxy, alkyloxyalkyl, alkyloxyalkyloxy, alkylcarbonyl, Alkenylcarbonyl, alkynylcarbonyl, monoalkylamino, dialkylamino, alkylsulfonyl, Kenylsulfonyl, alkynylsulfonyl, monoalkylcarbonylamino, dialkylcarbonylamino, monoalkylsulfonylamino, dialkylsulfonylamino, alkylimino, alkenylimino, alkynylimino, alkylcarbonylimino, alkenylcarbonylimino, alkynylcarbonylimino, alkyloxyimino, Alkenyloxyimino, alkynyloxyimino, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylsulfanyl, alkenylsulfanyl, alkynylsulfanyl, alkylsulfinyl, alkenylsulfinyl, alkynylsulfinyl, Noalkylcarbamoyl, dialkylcarbamoyl, monoalkylsulfamoyl, dialkylsulfamoyl, aromatic carbocyclic group, non-aromatic carbocyclic group, aromatic heterocyclic group, non-aromatic heterocyclic group, aromatic Carbocyclic oxy, non-aromatic carbocyclic oxy, aromatic heterocyclic oxy, non-aromatic heterocyclic oxy, aromatic carbocyclic amino, non-aromatic carbocyclic amino, aromatic heterocyclic amino, non-aromatic heterocyclic amino, Aromatic carbocyclic carbonyl, non-aromatic carbocyclic carbonyl, aromatic heterocyclic carbonyl, non-aromatic heterocyclic carbonyl, aromatic carbocyclic oxycarbonyl, non-aromatic carbocyclic oxycarbonyl, aromatic heterocyclic oxycarbonyl, non-aromatic Aromatic heterocyclic oxycarbonyl, non-aromatic heterocyclic oxycarbonyl, aromatic carbocyclic carbonylamino, non-aromatic carbocyclic carbonylamino, aromatic Aromatic heterocyclic carbonylamino, non-aromatic heterocyclic carbonylamino, aromatic carbocyclic alkyl, non-aromatic carbocyclic alkyl, aromatic heterocyclic alkyl, non-aromatic heterocyclic alkyl, aromatic carbocyclic alkyloxy, non-aromatic Aromatic carbocyclic alkyloxy, aromatic heterocyclic alkyloxy, nonaromatic heterocyclic alkyloxy, aromatic carbocyclic alkylsulfanyl, nonaromatic carbocyclic alkylsulfanyl, aromatic heterocyclic alkylsulfanyl, nonaromatic heterocyclic alkylsulfanyl , Aromatic carbocyclic alkyloxycarbonyl, non-aromatic carbocyclic alkyloxycarbonyl, aromatic heterocyclic alkyloxycarbonyl, non-aromatic heterocyclic alkyloxycarbonyl, aromatic carbocyclic alkyloxyalkyl, non-aromatic carbocyclic alkyloxy Alkyl, aromatic heterocyclic alkyloxya Kill, non-aromatic heterocyclic alkyloxyalkyl, aromatic carbocyclic alkylamino, non-aromatic carbocyclic alkylamino, aromatic heterocyclic alkylamino, non-aromatic heterocyclic alkylamino, aromatic carbocyclic sulfanyl, non-aromatic Carbocyclic sulfanyl, aromatic heterocyclic sulfanyl, non-aromatic heterocyclic sulfanyl, non-aromatic carbocyclic sulfonyl, aromatic carbocyclic sulfonyl, aromatic heterocyclic sulfonyl, and non-aromatic heterocyclic sulfonyl.

In addition, “substituted or unsubstituted non-aromatic carbocyclic group” and “substituted or unsubstituted non-aromatic heterocyclic group” may be substituted with “oxo”. In this case, it means a group in which two hydrogen atoms on a carbon atom are substituted as follows.

Furthermore, “substituted or unsubstituted non-aromatic carbocyclic group” and “substituted or unsubstituted non-aromatic heterocyclic group” are bridged by alkylene, alkenylene, or alkynylene, or other ring For example, a spiro ring may be formed together with cycloalkane, cycloalkene, cycloalkyne, oxirane, oxetane, thiirane and the like.

"Substituted or unsubstituted non-aromatic carbocyclic oxy", "substituted or unsubstituted non-aromatic heterocyclic oxy", "substituted or unsubstituted non-aromatic carbocyclic amino", "substituted or unsubstituted “Non-aromatic heterocyclic amino”, “substituted or unsubstituted non-aromatic carbocyclic carbonyl”, “substituted or unsubstituted non-aromatic heterocyclic carbonyl”, “substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl” , “Substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl”, “substituted or unsubstituted non-aromatic carbocyclic carbonylamino”, “substituted or unsubstituted non-aromatic heterocyclic carbonylamino”, “substituted or unsubstituted "Substituted non-aromatic carbocyclic sulfanyl", "Substituted or unsubstituted non-aromatic heterocyclic sulfanyl", "Substituted or unsubstituted non-aromatic carbocyclic sulfonyl" , And it may be substituted with non-aromatic carbocyclic ring "substituted or unsubstituted non-aromatic heterocyclic sulfonyl", and non-aromatic heterocyclic moiety also similarly to the "oxo".

Preferred embodiments of the compound represented by the formula (I) are shown below.

R ¹ is preferably a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted Or an unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, more preferably a substituted or unsubstituted alkyl , Substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, more preferably substituted or unsubstituted alkyl, particularly preferably alkyl having 1 to 4 carbon atoms, most preferably methyl. It is.

R ² is each independently preferably substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted Or an unsubstituted alkynyloxy, a substituted or unsubstituted alkylsulfanyl, a substituted or unsubstituted alkenylsulfanyl, or a substituted or unsubstituted alkynylsulfanyl, more preferably a substituted or unsubstituted alkyloxy, substituted or unsubstituted Alkenyloxy, or substituted or unsubstituted alkynyloxy, more preferably substituted or unsubstituted alkyloxy, particularly preferably alkyloxy having 1 to 4 carbon atoms, and most preferably tert- The Tiloxy.

N is preferably 1 or 2, particularly preferably 1.

R ³ is preferably a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted A non-aromatic heterocyclic group, more preferably a substituted or unsubstituted phenyl, a substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted chromanyl, or a substituted or unsubstituted benzomorpholinyl; Preferred is substituted or unsubstituted phenyl or substituted or unsubstituted chromanyl.

When R ³ has a substituent, preferred substituents are halogen, hydroxy, amino, cyano, oxo, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkyloxy, alkenyloxy, alkynyloxy, alkyloxyalkyl, monoalkyl Amino, dialkylamino, alkylsulfanyl, alkenylsulfanyl, or alkynylsulfanyl, more preferred substituents are halogen, alkyl, haloalkyl or alkyloxy, and more preferred substituents are fluoro, chloro, bromo, iodo, methyl, Ethyl, propyl, isopropyl, methyloxy, ethyloxy, propyloxy, isopropyloxy, trifluoromethyl, trichloromethyl, tribromomethyl or triio Particularly preferred substituents are fluoro, chloro, methyl, methyloxy, isopropyloxy or trifluoromethyl.

R ³ is more preferably a group shown below.

R ⁴ is preferably a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic An aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, and most preferably a hydrogen atom.

R ⁵ is preferably absent, hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted A substituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, particularly preferably absent.

In the absence of R ^{5, the} compound of formula (I) is

Any one of the above, preferably has a structure represented by the formula (II).

R ⁶ is preferably halogen, cyano, nitro, or —Z ⁶ —R ⁶¹ (Z ⁶ is a single bond, —O—, —S—, —NR ⁶² —, —CO—, —CS—, — SO ₂ —, —O—CO—, —CO—O—, —NR ⁶² —CO—, —CO—NR ⁶² —, —CH ₂ —CO—NR ⁶² —, —NR ⁶³ —CO—NR ⁶² —, —NR ⁶² —CS—, —CS—NR ⁶² —, —NR ⁶³ —CS—NR ⁶² —, —NR ⁶² —SO ₂ —, —SO ₂ —NR ⁶² —, or —NR ⁶³ —SO ₂ —NR ⁶² -; R ⁶¹ represents a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic Carbocyclic group, substituted or unsubstituted Aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group,; R ⁶² and R ⁶³ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkynyl wherein, ^{Z 6} is ^{^{_{^{-NR 62 -., - CO-}}}} NR 62 -, - CH 2 -CO-NR 62 -, - NR 63 -CO-NR 62 -, - CS-NR ^{^{^{62 -, - NR 63 -CS-}}} NR 62 -, - SO 2 -NR 62 -, or ^{^-NR} 63 _-SO 2 ^-NR ⁶² - in the case ^of, together with the nitrogen atom to ^{which R 61} and ^{R 62} are adjacent A substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group may be formed), and —Z ⁶ —R ⁶¹ is more preferable.
Here, Z ⁶ is more preferably a single bond, —NR ⁶² —, —NR ⁶² —CO—, —CO—NR ⁶² —, —CH ₂ —CO—NR ⁶² —, —NR ⁶³ —CO—NR. ^{^{^{^{62 -, - NR 62 -CS -}}}} , - CS-NR 62 -, - NR 63 -CS-NR 62 -, - NR 62 -SO 2 -, - SO 2 -NR 62 -, or ^-NR 63 -SO ₂ —NR ⁶² —, more preferably a single bond, —NR ⁶² —, —NR ⁶² —CO—, —CO—NR ⁶² —, —CH ₂ —CO—NR ⁶² —, —NR ⁶³ —CO—NR ^{^{^{62 -, - NR 63 -CS-}}} NR 62 -, - NR 62 -SO 2 -, or ^{^-NR} 63 _-SO 2 ^-NR ⁶² -, and particularly preferably a single bond. R ⁶¹ is preferably a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group. Or a substituted or unsubstituted non-aromatic heterocyclic group, more preferably alkyl, and still more preferably methyl. R ⁶² is preferably a hydrogen atom or substituted or unsubstituted alkyl, more preferably a hydrogen atom or alkyl, and still more preferably a hydrogen atom. R ⁶³ is preferably a hydrogen atom or substituted or unsubstituted alkyl, more preferably a hydrogen atom or alkyl, and still more preferably a hydrogen atom.
When R ⁶¹ is substituted alkyl, substituted alkenyl, or substituted alkynyl, the substituent is an aromatic carbocyclic group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic group Heterocyclic groups are preferred. When R ⁶¹ is a substituted aromatic carbocyclic group, a substituted non-aromatic carbocyclic group, a substituted aromatic heterocyclic group, or a substituted non-aromatic heterocyclic group, the substituent Is preferably an alkyl, alkenyl, alkynyl, aromatic carbocyclic group, non-aromatic carbocyclic group, aromatic heterocyclic group, or non-aromatic heterocyclic group.
R ⁶ is more preferably a hydrogen atom, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted non-aromatic carbocyclic group. More preferably a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, more preferably substituted or unsubstituted alkyl, and particularly preferably carbon. It is an alkyl having a number of 1 to 4, and most preferably methyl.

R ⁷ is preferably halogen, cyano, nitro, or —Z ⁷ —R ⁷¹ (Z ⁷ is a single bond, —O—, —S—, —NR ⁷² —, —CO—, —CS—, — SO ₂ —, —O—CO—, —CO—O—, —NR ⁷² —CO—, —CO—NR ⁷² —, —CH ₂ —CO—NR ⁷² —, —NR ⁷³ —CO—NR ⁷² —, ^{^{^{-NR 72 -CS -, - CS-}}} NR 72 -, - NR 73 -CS-NR 72 -, - NR 72 -SO 2 -, - SO 2 -NR 72 - or ^{^-NR} 73 _-SO 2 ^-NR ^72, -; R ⁷¹ is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic Carbocyclic group, substituted or unsubstituted Aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group,; R ⁷² and R ⁷³ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkynyl wherein, ^{Z 7} is ^{^{_{^{-NR 72 -., - CO-}}}} NR 72 -, - CH 2 -CO-NR 72 -, - NR 73 -CO-NR 72 -, - CS-NR ^{^{^{72 -, - NR 73 -CS-}}} NR 72 -, - SO 2 -NR 72 -, or ^{^-NR} 73 _-SO 2 ^-NR ⁷² - in the case ^of, together with the nitrogen atom to ^{which R 71} and ^{R 72} are adjacent Or a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group), and more preferably —Z ⁷ —R ⁷¹ .
Here, Z ⁷ is more preferably a single bond, —O—, —NR ⁷² —, —NR ⁷² —CO—, —CO—NR ⁷² —, —CH ₂ —CO—NR ⁷² —, —NR ^73. —CO—NR ⁷² —, —NR ⁷² —CS—, —CS—NR ⁷² —, —NR ⁷³ —CS—NR ⁷² —, —NR ⁷² —SO ₂ —, —SO ₂ —NR ⁷² —, or —NR ⁷³ —SO ₂ —NR ⁷² —, and more preferably a single bond, —NR ⁷² —, —NR ⁷² —CO—, —CO—NR ⁷² —, —CH ₂ —CO—NR ⁷² —, —NR ⁷³ —CO—NR ⁷² —, —NR ⁷³ —CS—NR ⁷² —, —NR ⁷² —SO ₂ —, or —NR ⁷³ —SO ₂ —NR ⁷² —, more preferably —NR ⁷² — or —NR ⁷³ ^{-CO-NR 72} - in Ri, particularly ^preferably, -NR 73 ^{-CO-NR 72} - a, and most preferably, a -NH-CO-NH-. R ⁷¹ is preferably a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group. Or a substituted or unsubstituted non-aromatic heterocyclic group, more preferably aromatic carbocyclic alkyl, non-aromatic carbocyclic alkyl, aromatic heterocyclic alkyl, non-aromatic heterocyclic alkyl, aromatic carbon A cyclic group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic heterocyclic group, more preferably benzyl, phenethyl, cyclohexyl, dihydroindenyl, phenyl, naphthyl, pyridyl, Pyrimidinyl or cycloalkyl, particularly preferably 4-8 membered cycloalkyl. R ⁷² is preferably a hydrogen atom or substituted or unsubstituted alkyl, more preferably a hydrogen atom or alkyl, and still more preferably a hydrogen atom or methyl. R ⁷³ is preferably a hydrogen atom or substituted or unsubstituted alkyl, more preferably a hydrogen atom or alkyl, still more preferably a hydrogen atom or methyl, and particularly preferably a hydrogen atom. R ⁷¹ is more preferably a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted non-aromatic carbocyclic group, and further preferably substituted or unsubstituted cycloalkyl or substituted or unsubstituted phenyl.
When R ⁷¹ is substituted alkyl, substituted alkenyl, or substituted alkynyl, the substituent is an aromatic carbocyclic group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic group Heterocyclic groups are preferred, and aromatic carbocyclic groups are more preferred. When R ⁷¹ is a substituted aromatic carbocyclic group, a substituted non-aromatic carbocyclic group, a substituted aromatic heterocyclic group, or a substituted non-aromatic heterocyclic group, the substituent Is preferably an alkyl, alkenyl, alkynyl, aromatic carbocyclic group, non-aromatic carbocyclic group, aromatic heterocyclic group, or non-aromatic heterocyclic group.
R ⁷ is more preferably —Z ⁷ —R ⁷¹ (Z ⁷ is a single bond, —O—, —NR ⁷² —, —NR ⁷² —CO—, —CO—NR ⁷² —, —CH ₂ —CO ^{^{^{^{-NR 72 -, - NR 73 -CO}}}} -NR 72 -, - NR 73 -CS-NR 72 -, - NR 72 -SO 2 -, or ^{_{^{^{-NR 73 -SO 2 -NR 72 -;}}}} R 71 is substituted Or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, or substituted or unsubstituted non-substituted Aromatic heterocyclic group; R ⁷² and R ⁷³ are each independently a hydrogen atom or substituted or unsubstituted alkyl, and particularly preferably —Z ⁷ —R ⁷¹ (Z ⁷ is a single bond, -NR ^⁷² -, - ^NR ⁷² - ^{_{^{^{CO -, - CO-NR 72}}}} -, - CH 2 -CO-NR 72 -, - NR 73 -CO-NR 72 -, - NR 73 -CS-NR 72 -, - NR 72 -SO 2 -, or - NR ⁷³ —SO ₂ —NR ⁷² —; R ⁷¹ represents aromatic carbocyclic alkyl, non-aromatic carbocyclic alkyl, aromatic heterocyclic alkyl, non-aromatic heterocyclic alkyl, aromatic carbocyclic group, non-aromatic A carbocyclic group, an aromatic heterocyclic group, or a non-aromatic heterocyclic group; R ⁷² is a hydrogen atom or substituted or unsubstituted alkyl; R ⁷³ is a hydrogen atom, or Z ⁷ is —NR ⁷³ —CO—. NR ^72- ; R ⁷¹ is a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted non-aromatic carbocyclic group; R ⁷² and R ⁷³ are each independently a hydrogen atom or Non-replaced A kill), and most ^preferably, -Z ^{⁷ -R} 71 ^(Z ⁷ is ^{-NH-CO-NH-; R 71} is cycloalkyl).

R ⁷ is more preferably a group shown below.

R ¹ and R ⁷ together with adjacent carbon atoms are substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocycles, and A cyclic group or a substituted or unsubstituted non-aromatic heterocyclic group may be formed, and a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group is formed. More preferably, the cyclic group formed by R ¹ and R ⁷ together with adjacent carbon atoms is preferably a 5- to 8-membered non-aromatic heterocyclic group, more preferably a 6-membered ring, The cyclic group may be substituted with a plurality of ^RA . Here, each R ^A is preferably independently halogen, cyano, nitro, oxo, or —Z ^A —R ^A1 (Z ^A is a single bond, —O—, —S—, —NR ^A2 —). , —CO—, —CS—, —SO ₂ —, —O—CO—, —CO—O—, —NR ^A2 —CO—, —CO—NR ^A2 —, —CH ₂ —CO—NR ^A2 —, —NR ^A3 —CO—NR ^A2 —, —NR ^A2 —CS—, —CS—NR ^A2 —, —NR ^A3 —CS—NR ^A2 —, —NR ^A2 —SO ₂ —, —SO ₂ —NR ^A2 —, Or —NR ^A3 —SO ₂ —NR ^A2 —; R ^A1 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted Or unsubstituted non-aromatic carbocyclic , Substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,; R ^A2 and R ^A3 each independently represent a hydrogen atom, a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted alkynyl, where,, ^{Z a} is ^{^{_{-NR A2 -., - CO-}}} NR A2 -, - CH 2 -CO-NR A2 -, - NR A3 -CO-NR A2 ^{^{-, - CS-NR A2 -}} , - NR A3 -CS-NR A2 -, - SO 2 -NR A2 -, or ^{^-NR} A3 _-SO 2 ^-NR ^A2 - ^{for, R A1} and ^{R A2} are adjacent May be combined with a nitrogen atom to form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted nonaromatic heterocyclic group), more preferably oxo or — A ^A -R ^A1. The number of R ^{A to be} substituted is preferably 5 or less.

When R ¹ and R ⁷ together with adjacent carbon atoms form a substituted or unsubstituted non-aromatic heterocyclic group, the compound of formula (I) is preferably represented by formula (III) Having the structure shown.

Here, X is preferably —C (R ¹⁰ ) ₂ —, —NR ⁹ —, or —O—, and more preferably —NR ⁹ —. Y is preferably —C (R ¹⁰ ) ₂ —, —CO—, or —SO ₂ —, more preferably —CH ₂ — or —CO—. W is preferably —C (R ¹⁰ ) ₂ —, —NR ¹⁰ —, or —O—, and more preferably —CH ₂ —. Particularly preferably, X is —NR ⁹ —, Y is —CH ₂ — or —CO—, and W is —CH ₂ —.
R ⁹ is preferably halogen, cyano, nitro, or —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond, —O—, —S—, —NR ⁹² —, —CO—, —CS—, — SO ₂ —, —O—CO—, —CO—O—, —NR ⁹² —CO—, —CO—NR ⁹² —, —CH ₂ —CO—NR ⁹² —, —NR ⁹³ —CO—NR ⁹² —, —NR ⁹² —CS—, —CS—NR ⁹² —, —NR ⁹³ —CS—NR ⁹² —, —NR ⁹² —SO ₂ —, —SO ₂ —NR ⁹² —, or —NR ⁹³ —SO ₂ —NR ⁹² -; R ⁹¹ represents a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic Carbocyclic group, substituted or unsubstituted Aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group,; R ⁹² and R ⁹³ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkynyl wherein, ^{Z 9} is ^{^{_{^{-NR 92 -., - CO-}}}} NR 92 -, - CH 2 -CO-NR 92 -, - NR 93 -CO-NR 92 -, - CS-NR ^{In the case of 92} −, —NR ⁹³ —CS—NR ⁹² —, —SO ₂ —NR ⁹² —, or —NR ⁹³ —SO ₂ —NR ⁹² —, R ⁹¹ and R ⁹² are combined with the adjacent nitrogen atom. A substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group may be formed, and more preferably —Z ⁹ —R ⁹¹ .
Here, Z ⁹ is more preferably a single bond, —CO—, —CS—, —SO ₂ —, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —. More preferably a single bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —, particularly preferably —CO—NR ⁹² —. Most preferably, it is —CO—NH—.
R ⁹¹ is preferably a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, or a substituted or unsubstituted non-aromatic carbocyclic group, more preferably a substituted Or an unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group or a substituted or substituted or unsubstituted non-aromatic carbocyclic group, more preferably methyl, benzyl, phenyl or cycloalkyl, Most preferred is 4-8 membered cycloalkyl.
R ⁹² is preferably a hydrogen atom or substituted or unsubstituted alkyl, more preferably a hydrogen atom or methyl, and particularly preferably a hydrogen atom. R ⁹³ is preferably a hydrogen atom or substituted or unsubstituted alkyl, more preferably a hydrogen atom or methyl, and particularly preferably a hydrogen atom.
When R ⁹¹ is substituted alkyl, substituted alkenyl, or substituted alkynyl, the substituent is an aromatic carbocyclic group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic group Heterocyclic groups are preferred, and aromatic carbocyclic groups are more preferred. When R ⁹¹ is a substituted aromatic carbocyclic group, a substituted non-aromatic carbocyclic group, a substituted aromatic heterocyclic group, or a substituted non-aromatic heterocyclic group, the substituent Is preferably an alkyl, alkenyl, alkynyl, aromatic carbocyclic group, non-aromatic carbocyclic group, aromatic heterocyclic group, or non-aromatic heterocyclic group.
R ⁹ is more preferably —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, or substituted or unsubstituted non-aromatic carbocyclic group; R ⁹² is hydrogen atom or substituted or unsubstituted -Z ⁹ -R ⁹¹ (Z ⁹ is a single bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —). R ⁹¹ is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, or substituted or unsubstituted non-aromatic heterocyclic group; R ⁹² is a hydrogen atom), most preferably ^is, -Z 9 ^{-R 91} Z ⁹ is ^{-CO-NH-; R 91} is cycloalkyl).

R ⁹ is more preferably a group shown below.

R ⁹ particularly preferably has a cyclic group such as cycloalkyl or phenyl at the terminal. The cyclic group may have a crosslinked structure such as adamantyl.
R ¹⁰ is each independently preferably a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted An unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, more preferably a hydrogen atom or a substituted or unsubstituted Alkyl, more preferably a hydrogen atom.
When R ¹⁰ is substituted alkyl, substituted alkenyl, or substituted alkynyl, the substituent is an aromatic carbocyclic group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic group Heterocyclic groups are preferred. When R ¹⁰ is a substituted aromatic carbocyclic group, a substituted non-aromatic carbocyclic group, a substituted aromatic heterocyclic group, or a substituted non-aromatic heterocyclic group, the substituent Is preferably an alkyl, alkenyl, alkynyl, aromatic carbocyclic group, non-aromatic carbocyclic group, aromatic heterocyclic group, or non-aromatic heterocyclic group.

R ⁵ and R ⁷ together with the adjacent nitrogen and carbon atoms may form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group. .
The cyclic group formed by R ⁵ and R ⁷ together with the adjacent nitrogen and carbon atoms is preferably a 5- to 8-membered ring, more preferably a 5- to 6-membered ring, still more preferably a 5-membered ring, , Each may be substituted with a plurality of independent R ⁸ . The number of R ^{8 to be} substituted is preferably 2 or less, and more preferably 1 or less. The cyclic group preferably contains 1 to 4 nitrogen atoms, and more preferably has one of the following structures (in the formula, the broken line indicates the presence or absence of a bond, provided that the adjacent broken line) Does not indicate the presence of a bond at the same time).

When R ⁵ and R ⁷ together with the adjacent nitrogen and carbon atoms form a substituted or unsubstituted aromatic heterocyclic group, the compound of formula (I) is preferably of formula (IV ) To (VI).

Here, R ⁸ is preferably halogen, cyano, nitro, or —Z ⁸ —R ⁸¹ (Z ⁸ is a single bond, —O—, —S—, —NR ⁸² —, —CO—, —CS —, —SO ₂ —, —O—CO—, —CO—O—, —NR ⁸² —CO—, —CO—NR ⁸² —, —CH ₂ —CO—NR ⁸² —, —NR ⁸³ —CO—NR ^{^{^{^{82 -, - NR 82 -CS -}}}} , - CS-NR 82 -, - NR 83 -CS-NR 82 -, - NR 82 -SO 2 -, - SO 2 -NR 82 -, or ^-NR 83 -SO ₂ —NR ⁸² —; R ⁸¹ is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted Non-aromatic carbocyclic group, substituted or Substituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,; R ⁸² and R ⁸³ are each independently a hydrogen atom, a substituted or unsubstituted alkyl, substituted or unsubstituted . alkenyl or substituted or unsubstituted alkynyl, where,, ^{Z 8} is ^{^{_{-NR 82 -, - CO-NR}}} 82 -, - CH 2 -CO-NR 82 -, - NR 83 -CO-NR 82 -, - CS In the case of —NR ⁸² —, —NR ⁸³ —CS—NR ⁸² —, —SO ₂ —NR ⁸² —, or —NR ⁸³ —SO ₂ —NR ⁸² —, R ⁸¹ and R ⁸² together with the adjacent nitrogen atom And a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group may be formed, and more preferably a hydrogen atom or a substituted or unsubstituted An aromatic carbocyclic group, more preferably a substituted or unsubstituted aromatic carbocyclic group, particularly preferably a substituted or unsubstituted phenyl, most preferably phenyl. When the phenyl is substituted, preferred substituents are exemplified by halogen, alkyl, haloalkyl, alkoxy and the like.
When R ⁸¹ is substituted alkyl, substituted alkenyl, or substituted alkynyl, the substituent is an aromatic carbocyclic group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic group Heterocyclic groups are preferred. When R ⁸¹ is a substituted aromatic carbocyclic group, a substituted non-aromatic carbocyclic group, a substituted aromatic heterocyclic group, or a substituted non-aromatic heterocyclic group, the substituent Is preferably an alkyl, alkenyl, alkynyl, aromatic carbocyclic group, non-aromatic carbocyclic group, aromatic heterocyclic group, or non-aromatic heterocyclic group.

R ⁵ and R ⁶ may be combined with adjacent nitrogen and carbon atoms to form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group. .
For example, Formula (I) may take the structure shown below.

Preferred embodiments of the compound represented by the formula (I) include the following 1) to 4) in the formula (II).

1) R ¹ is substituted or unsubstituted alkyl, R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic carbocyclic group, R ⁴ is a hydrogen atom, R ⁶ is substituted or unsubstituted alkyl, R ⁷ is —Z ⁷ —R ⁷¹ (Z ⁷ is a single bond, —NR ⁷² —, —NR ⁷² —CO—, — CO—NR ⁷² —, —CH ₂ —CO—NR ⁷² —, —NR ⁷³ —CO—NR ⁷² —, —NR ⁷³ —CS—NR ⁷² —, —NR ⁷² —SO ₂ —, or —NR ⁷³ —SO ₂ -NR 72 ^-; R ⁷¹ is a substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic A cyclic group, or substituted or non-substituted A compound having a substituted non-aromatic heterocyclic group; R ⁷² is a hydrogen atom or substituted or unsubstituted alkyl; R ⁷³ is a hydrogen atom).
2) R ¹ is substituted or unsubstituted alkyl, R ² is substituted or unsubstituted alkyloxy, n is 1, and R ³ is a substituted or unsubstituted non-aromatic carbocyclic group , R ⁴ is a hydrogen atom, R ⁶ is substituted or unsubstituted alkyl, and R ⁷ is —Z ⁷ —R ⁷¹ (Z ⁷ is a single bond, —NR ⁷² —, —NR ⁷² —CO—, —CO—NR ⁷² —, —CH ₂ —CO—NR ⁷² —, —NR ⁷³ —CO—NR ⁷² —, —NR ⁷³ —CS—NR ⁷² —, —NR ⁷² —SO ₂ —, or —NR ⁷³ — SO ₂ —NR ⁷² —; R ⁷¹ is substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic A heterocyclic group, or substituted or non- A substituted non-aromatic heterocyclic group; R ⁷² is a hydrogen atom or substituted or unsubstituted alkyl; R ⁷³ is a hydrogen atom).
3) R ¹ is substituted or unsubstituted alkyl, R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic heterocyclic group, R ⁴ is a hydrogen atom, R ⁶ is substituted or unsubstituted alkyl, R ⁷ is —Z ⁷ —R ⁷¹ (Z ⁷ is a single bond, —NR ⁷² —, —NR ⁷² —CO—, — CO—NR ⁷² —, —CH ₂ —CO—NR ⁷² —, —NR ⁷³ —CO—NR ⁷² —, —NR ⁷³ —CS—NR ⁷² —, —NR ⁷² —SO ₂ —, or —NR ⁷³ —SO ₂ -NR 72 ^-; R ⁷¹ is a substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic A cyclic group, or substituted or non-substituted A compound having a substituted non-aromatic heterocyclic group; R ⁷² is a hydrogen atom or substituted or unsubstituted alkyl; R ⁷³ is a hydrogen atom).
4) R ¹ is substituted or unsubstituted alkyl, R ² is substituted or unsubstituted alkyloxy, n is 1, and R ³ is a substituted or unsubstituted non-aromatic heterocyclic group , R ⁴ is a hydrogen atom, R ⁶ is substituted or unsubstituted alkyl, and R ⁷ is —Z ⁷ —R ⁷¹ (Z ⁷ is a single bond, —NR ⁷² —, —NR ⁷² —CO—, —CO—NR ⁷² —, —CH ₂ —CO—NR ⁷² —, —NR ⁷³ —CO—NR ⁷² —, —NR ⁷³ —CS—NR ⁷² —, —NR ⁷² —SO ₂ —, or —NR ⁷³ — SO ₂ —NR ⁷² —; R ⁷¹ is substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic A heterocyclic group, or substituted or non- A substituted non-aromatic heterocyclic group; R ⁷² is a hydrogen atom or substituted or unsubstituted alkyl; R ⁷³ is a hydrogen atom).

As another preferred embodiment of the compound represented by the formula (I), the following 5) to 28) in the formula (III) may be mentioned.

5) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y is —CO—, W is —CH ₂ —, and R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond) , —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R ⁹² is a hydrogen atom).
6) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted non-aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is Substituted or unsubstituted alkyl, X is —NR ⁹ —, Y is —CO—, W is —CH ₂ —, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single atom) A bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R ⁹² is a hydrogen atom).
7) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y is —CO—, W is —CH ₂ —, and R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond) , —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R ⁹² is a hydrogen atom).
8) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted non-aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is Substituted or unsubstituted alkyl, X is —NR ⁹ —, Y is —CO—, W is —CH ₂ —, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single atom) A bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R ⁹² is a hydrogen atom).
9) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y is —CH ₂ —, W is —CH ₂ —, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single atom) A bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R ⁹² is a hydrogen atom).
10) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted non-aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is Substituted or unsubstituted alkyl, X is —NR ⁹ —, Y is —CH ₂ —, W is —CH ₂ —, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is Single bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocycle A compound of the formula: R ⁹² is a hydrogen atom).
11) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y is —CH ₂ —, W is —CH ₂ —, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single atom) A bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R ⁹² is a hydrogen atom).
12) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted non-aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is Substituted or unsubstituted alkyl, X is —NR ⁹ —, Y is —CH ₂ —, W is —CH ₂ —, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is Single bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocycle A compound of the formula: R ⁹² is a hydrogen atom).
13) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y is —CO—, W is —NH—, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group; R ⁹² is a hydrogen atom).
14) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted non-aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is Substituted or unsubstituted alkyl, X is —NR ⁹ —, Y is —CO—, W is —NH—, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond) , —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R ⁹² is a hydrogen atom).
15) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y is —CO—, W is —NH—, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group; R ⁹² is a hydrogen atom).
16) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted non-aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is Substituted or unsubstituted alkyl, X is —NR ⁹ —, Y is —CO—, W is —NH—, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond) , —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R ⁹² is a hydrogen atom).
17) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y is —SO ₂ —, W is —NH—, and R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond) , —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R ⁹² is a hydrogen atom).
18) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted non-aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is Substituted or unsubstituted alkyl, X is —NR ⁹ —, Y is —SO ₂ —, W is —NH—, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single atom) A bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R ⁹² is a hydrogen atom).
19) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y is —SO ₂ —, W is —NH—, and R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond) , —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R ⁹² is a hydrogen atom).
20) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted non-aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is Substituted or unsubstituted alkyl, X is —NR ⁹ —, Y is —SO ₂ —, W is —NH—, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single atom) A bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R ⁹² is a hydrogen atom).
21) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y is —CO—, W is —O—, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group; R ⁹² is a hydrogen atom).
22) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted non-aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is Substituted or unsubstituted alkyl, X is —NR ⁹ —, Y is —CO—, W is —O—, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond) , —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R ⁹² is a hydrogen atom).
23) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y is —CO—, W is —O—, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group; R ⁹² is a hydrogen atom).
24) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted non-aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is Substituted or unsubstituted alkyl, X is —NR ⁹ —, Y is —CO—, W is —O—, R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond) , —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R ⁹² is a hydrogen atom).
25) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y is —SO ₂ —, W is —O—, and R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond) , —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R ⁹² is a hydrogen atom).
26) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted non-aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is Substituted or unsubstituted alkyl, X is —NR ⁹ —, Y is —SO ₂ —, W is —O—, and R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single atom) A bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R ⁹² is a hydrogen atom).
27) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y is —SO ₂ —, W is —O—, and R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single bond) , —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R ⁹² is a hydrogen atom).
28) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted non-aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is Substituted or unsubstituted alkyl, X is —NR ⁹ —, Y is —SO ₂ —, W is —O—, and R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is a single atom) A bond, —CO—, —CO—NR ⁹² —, —CS—NR ⁹² —, or —SO ₂ —NR ⁹² —; R ⁹¹ is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R ⁹² is a hydrogen atom).

As another preferred embodiment of the compound represented by the formula (I), the following 29) to 32) in any one of the formulas (IV) to (VI) may be mentioned.

29) R ¹ is substituted or unsubstituted alkyl, R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic carbocyclic group, A compound in which R ⁴ is a hydrogen atom, R ⁶ is substituted or unsubstituted alkyl, and R ⁸ is a substituted or unsubstituted aromatic carbocyclic group.
30) R ¹ is substituted or unsubstituted alkyl, R ² is substituted or unsubstituted alkyloxy, n is 1, and R ³ is a substituted or unsubstituted non-aromatic carbocyclic group , R ⁴ is a hydrogen atom, R ⁶ is substituted or unsubstituted alkyl, and R ⁸ is a substituted or unsubstituted aromatic carbocyclic group.
31) R ¹ is substituted or unsubstituted alkyl, R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic heterocyclic group, A compound in which R ⁴ is a hydrogen atom, R ⁶ is substituted or unsubstituted alkyl, and R ⁸ is a substituted or unsubstituted aromatic carbocyclic group.
32) R ¹ is substituted or unsubstituted alkyl, R ² is substituted or unsubstituted alkyloxy, n is 1, and R ³ is a substituted or unsubstituted non-aromatic heterocyclic group , R ⁴ is a hydrogen atom, R ⁶ is substituted or unsubstituted alkyl, and R ⁸ is a substituted or unsubstituted aromatic carbocyclic group.
In 29) to 32), R ⁸ does not exist for the compound of the formula (VI).

Other preferred embodiments of the compound represented by the formula (I) include the following 51) to 52) in the formula (II) and the following 53) to 54) in the formula (III).

51) R ¹ is substituted or unsubstituted alkyl, R ² is substituted or unsubstituted alkyloxy, n is 1, and R ³ is substituted or unsubstituted aromatic carbocyclic group, substituted or An unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is A compound that is substituted or unsubstituted alkyl, and R ⁷ is —Z ⁷ —R ⁷¹ (Z ⁷ is —NH—CO—NH—; R ⁷¹ is a substituted or unsubstituted aromatic carbocyclic group) .
52) R ¹ is substituted or unsubstituted alkyl, R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic carbocyclic group, substituted or An unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is A substituted or unsubstituted alkyl, and R ⁷ is —Z ⁷ —R ⁷¹ (Z ⁷ is —NH—CO—NH—; R ⁷¹ is a substituted or unsubstituted non-aromatic carbocyclic group). Compound.

53) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y and W are both —CH ₂ —, and R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is —CO—NH—; R ⁹¹ is a compound which is a substituted or unsubstituted aromatic carbocyclic group).
54) R ² is substituted or unsubstituted alkyloxy, n is 1, R ³ is a substituted or unsubstituted aromatic carbocyclic group, R ⁴ is a hydrogen atom, and R ⁶ is substituted Or unsubstituted alkyl, X is —NR ⁹ —, Y and W are both —CH ₂ —, and R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is —CO—NH—; R ⁹¹ is a compound which is a substituted or unsubstituted non-aromatic carbocyclic group).

A feature of the compound according to the present invention is that in the formula (I):
(1) A cyclic group (R ³ ) is substituted on the pyridine ring as the main skeleton,
(2) By having a side chain represented by -C (R ² ) nCOOR ⁴ (n = 1, ² ) at the 4-position of the pyridine ring,
It has a HIV replication inhibitory effect.

Another feature of the compound according to the present invention is that a substituted or unsubstituted alkyloxy group is preferably introduced as R ^{2 in} the formula (I), and R ⁴ is a hydrogen atom. It is a point to have.

The compound according to the present invention exhibits a strong HIV replication inhibitory action against resistant viruses. In particular, R ⁷ is represented by the formula (II) in which —Z ⁷ —R ⁷¹ (Z ⁷ is —NR ⁷³ —CO—NR ⁷² —; R ⁷¹ is a substituted or unsubstituted non-aromatic carbocyclic group) The compound, and X is —NR ⁹ — and R ⁹ is —Z ⁹ —R ⁹¹ (Z ⁹ is —CO—NR ⁹² —; R ⁹¹ is a substituted or unsubstituted non-aromatic carbocyclic group). The compound represented by the formula (III) exhibits a strong HIV replication inhibitory action against resistant viruses. That is, as a preferred embodiment of the compound of the present invention, the presence of a urea structure at R ⁷ in the formula (II) and X in the formula (III) is important for showing a strong medicinal effect.

The compound of formula (I) is not limited to a particular isomer, but all possible isomers (eg keto-enol isomer, imine-enamine isomer, diastereoisomer, atropisomer) , Optical isomers, rotational isomers, etc.), racemates or mixtures thereof.

One or more hydrogen, carbon and / or other atoms of the compound of formula (I) may be replaced with isotopes of hydrogen, carbon and / or other atoms, respectively. Examples of such isotopes are ² H, ³ H, ¹¹ C, ¹³ C, ¹⁴ C, ¹⁵ N, ¹⁸ O, ¹⁷ O, ³¹ P, ³² P, ³⁵ S, ¹⁸ F, ¹²³ I and ^{Like 36} Cl, hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, iodine and chlorine are included. The compound represented by the formula (I) also includes a compound substituted with such an isotope. The compound substituted with the isotope is useful as a pharmaceutical, and includes all radiolabeled compounds of the compound represented by the formula (I). A “radiolabeling method” for producing the “radiolabeled product” is also encompassed in the present invention, and is useful as a metabolic pharmacokinetic study, a study in a binding assay, and / or a diagnostic tool.

The radioactive label of the compound represented by the formula (I) can be prepared by a method well known in the art. For example, the tritium-labeled compound represented by the formula (I) can be prepared by introducing tritium into the specific compound represented by the formula (I) by, for example, catalytic dehalogenation reaction using tritium. In this method, a tritium gas is reacted with a precursor in which the compound of formula (I) is appropriately halogen-substituted in the presence of a suitable catalyst such as Pd / C, in the presence or absence of a base. Including that. Suitable methods for preparing other tritium labeled compounds include the document Isotopes in the Physical and Biomedical Sciences, Vol. 1, Labeled Compounds (Part A), Chapter 6 (1987). ¹⁴ C-labeled compounds can be prepared by using raw materials having ¹⁴ C carbon.

As the pharmaceutically acceptable salt of the compound represented by the formula (I), for example, a compound represented by the formula (I), an alkali metal (for example, lithium, sodium, potassium, etc.), an alkaline earth metal (for example, Calcium, barium, etc.), magnesium, transition metals (eg, zinc, iron, etc.), ammonia, organic bases (eg, trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, meglumine, diethanolamine, ethylenediamine, pyridine, Picolin, quinoline etc.) and salts with amino acids, or inorganic acids (eg hydrochloric acid, sulfuric acid, nitric acid, carbonic acid, hydrobromic acid, phosphoric acid, hydroiodic acid etc.) and organic acids (eg formic acid, acetic acid, Propionic acid, trifluoroacetic acid, citric acid, lactic acid Tartaric acid, oxalic acid, maleic acid, fumaric acid, mandelic acid, glutaric acid, malic acid, benzoic acid, phthalic acid, ascorbic acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, etc.) Salt. Particularly, salts with hydrochloric acid, sulfuric acid, phosphoric acid, tartaric acid, methanesulfonic acid and the like can be mentioned. These salts can be formed by a commonly performed method.

The compound represented by the formula (I) of the present invention or a pharmaceutically acceptable salt thereof may form a solvate (for example, a hydrate etc.) and / or a crystalline polymorph. Various solvates and crystalline polymorphs. The “solvate” may be coordinated with an arbitrary number of solvent molecules (for example, water molecules) with respect to the compound represented by the formula (I). When the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof is left in the air, it may absorb moisture and adsorbed water may adhere or form a hydrate. In some cases, the compound represented by formula (I) or a pharmaceutically acceptable salt thereof may be recrystallized to form a crystalline polymorph thereof.

The compound represented by the formula (I) of the present invention or a pharmaceutically acceptable salt thereof may form a prodrug, and the present invention includes such various prodrugs. A prodrug is a derivative of a compound of the invention that has a group that can be chemically or metabolically degraded and is a compound that becomes a pharmaceutically active compound of the invention in vivo by solvolysis or under physiological conditions. A prodrug is a compound that is enzymatically oxidized, reduced, hydrolyzed, etc. under physiological conditions in vivo to be converted into a compound represented by formula (I), hydrolyzed by gastric acid, etc. The compound etc. which are converted into the compound shown are included. Methods for selecting and producing suitable prodrug derivatives are described, for example, in Design of Prodrugs, Elsevier, Amsterdam 1985. Prodrugs may themselves have activity.

When the compound represented by formula (I) or a pharmaceutically acceptable salt thereof has a hydroxyl group, for example, the compound having a hydroxyl group and a suitable acyl halide, a suitable acid anhydride, a suitable sulfonyl chloride, a suitable Examples thereof include prodrugs such as acyloxy derivatives and sulfonyloxy derivatives produced by reacting sulfonyl anhydride and mixed anhydride or by reacting with a condensing agent. For example, CH ₃ COO—, C ₂ H ₅ COO—, t-BuCOO—, C ₁₅ H ₃₁ COO—, PhCOO—, (m-NaOOCPh) COO—, NaOOCCH ₂ CH ₂ COO—, CH ₃ CH (NH ₂ ) COO—, CH ₂ N (CH ₃ ) ₂ COO—, CH ₃ SO ₃ —, CH ₃ CH ₂ SO ₃ —, CF ₃ SO ₃ —, CH ₂ FSO ₃ —, CF ₃ CH ₂ SO ₃ —, p —CH ₃ —O—PhSO ₃ —, PhSO ₃ —, and p—CH ₃ PhSO ₃ — can be mentioned.

(Method for producing the compound of the present invention)
The compound represented by the formula (I) according to the present invention can be produced, for example, by the general synthesis method shown below. Extraction, purification, and the like may be performed in a normal organic chemistry experiment.
The synthesis of the compound of the present invention can be carried out in consideration of techniques known in the art.

1) Synthesis of compounds A-1 and A-2

(Wherein R ³ , R ⁴ and R ⁷¹ are as defined above. R ^{2 ′} is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, etc.)

Step 1 Benzylamine is added to compound a1 in an aqueous solvent and reacted at 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 8 hours, preferably 0.5 hour to 2 hours. Thus, compound a2 can be obtained.

Second Step In a solvent such as dichloromethane, THF, dichloroethane, or a mixed solvent thereof, a base such as pyridine, lutidine, triethylamine and a triflating agent such as trifluoromethanesulfonic anhydride and comin's reagent are added to compound a2. Compound a3 can be obtained by reacting at −50 ° C. to 50 ° C., preferably −30 ° C. to 30 ° C. for 0.1 hour to 4 hours, preferably 0.5 hour to 1 hour.

Third Step In a solvent such as DMF, DMA, THF, dioxane, or a mixed solvent thereof, compound a3 is added with a phosphine such as tritert-butylphosphine, tricyclohexylphosphine, triphenylphosphine, and dibenzylideneacetone palladium, palladium acetate, A catalyst such as dichlorobistriphenylphosphine palladium and silyl enol ether a4 prepared separately from zinc fluoride are added, and the temperature is 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 8 hours, preferably 0. Compound a5 can be obtained by reacting in 5 to 2 hours.

Fourth Step In a solvent such as dichloromethane, chloroform, dichloroethane, or a mixed solvent thereof, a brominating agent such as bromine or NBS is added to compound a5, and the temperature is −50 ° C. to 50 ° C., preferably −30 ° C. to 30 ° C. The compound a6 can be obtained by reacting for 0.1 to 4 hours, preferably 0.5 to 1 hour.

Step 5 In a solvent such as DMF, DMA, THF, dioxane, water, or a mixed solvent thereof, an aqueous solution of a base such as potassium carbonate, sodium carbonate, potassium phosphate and boronic acid a7, or boronic ester in compound a6 a8 and a catalyst such as dibenzylideneacetone palladium, palladium acetate, dichlorobistriphenylphosphine palladium and the like are added, and the temperature is 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 8 hours, preferably 0.5 to Compound a9 can be obtained by reacting for 2 hours.

Step 6 In a solvent such as methanol, ethyl acetate, acetic acid, or a mixed solvent thereof, a catalyst such as palladium carbon, palladium hydroxide, Raney nickel is added to compound a9, and a hydrogen atmosphere is used at 30 ° C. to 130 ° C., preferably Compound a10 can be obtained by reacting at 50 to 110 ° C. for 0.1 to 8 hours, preferably 0.5 to 2 hours.

Seventh Step From compound a10, compound a11 can be obtained in the same manner as in the second step.

8th step
In a solvent such as DMF, DMA, THF, or dioxane, or in a mixed solvent thereof, a compound such as triethylamine, lutidine, or pyridine, a base such as triethylamine, benzylamine, and dibenzylideneacetone palladium, palladium acetate, or dichlorobistriphenylphosphine palladium. And a ligand such as xanthophos, tri-tert-butylphosphine and the like, and reacted at 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 8 hours, preferably 0.5 to 2 hours. To give compound a12.

Ninth Step From compound a12, compound a13 can be obtained in the same manner as in the second step.

Step 10 In a solvent such as dichloroethane, benzene, dioxane or the like or a mixed solvent thereof, a base such as triethylamine, lutidine, pyridine and the isocyanate a14 are added to compound a13, and 50 ° C to 150 ° C, preferably 70 ° C to 130 ° C. The compound A-1 can be obtained by reacting for 0.1 to 8 hours, preferably 0.5 to 2 hours.

Step 11 In a solvent such as methanol, THF, dioxane, or a mixed solvent thereof, a base such as an aqueous sodium hydroxide solution, an aqueous potassium hydroxide solution, or an aqueous lithium hydroxide solution is added to compound A-1 at 10 ° C to 110 ° C. Compound A-2 can be obtained by reacting at 30 ° C. to 90 ° C. for 0.1 hour to 8 hours, preferably 0.5 hour to 1 hour.

Here, a4 can be synthesized by the following method.

Step 12 In a solvent such as THF, diethyl ether, dioxane, or a mixed solvent thereof, compound a15 and an alcohol such as tert-butanol, isopropanol, or methanol, and a metal such as sodium hydride, lithium hydride, or potassium hydride Compound a16 can be obtained by adding a reagent and reacting at 20 ° C. to 120 ° C., preferably 40 ° C. to 100 ° C., for 0.1 hour to 12 hours, preferably 0.5 hour to 6 hours.

Step 13 In a solvent such as DMF, DMA, THF, dioxane, or a mixed solvent thereof, compound a16 is mixed with a base such as potassium carbonate, calcium carbonate, potassium phosphate and the like and R ⁴ -I, R ⁴ -Br, R ^4. By adding -OSO ₃ H and the like, and reacting at −30 ° C. to 70 ° C., preferably −10 ° C. to 50 ° C. for 0.1 hour to 5 hours, preferably 0.5 hour to 1 hour, compound a17 Can be obtained.

Step 14 In a solvent such as THF, diethyl ether, dioxane, or a mixed solvent thereof, compound a17 is subjected to silylation with a base such as potassium hexamethyldisilazide, lithium hexamethyldisilazide, or lithium diisopropylamide and TMSCl, TMSOTf or the like. The compound a4 is obtained by adding an agent and reacting at −130 ° C. to −20 ° C., preferably −110 ° C. to −50 ° C. for 0.1 hour to 5 hours, preferably 0.5 hour to 1 hour. be able to.

2) Synthesis of compounds B-1 and B-2

(In the formula, each definition is as defined above.)

Step 1 In a solvent such as DMF, DMA, THF, dioxane, or a mixed solvent thereof, compound a11 includes a base such as triethylamine or pyridine, an amine b1, dibenzylideneacetone palladium, palladium acetate, dichlorobistriphenylphosphine palladium, and the like. A catalyst and an inorganic salt such as lithium bromide, sodium bromide and potassium bromide are added, and a carbon monoxide atmosphere is used at 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C. for 0.1 hour to 8 hours, preferably Can be obtained by reacting for 0.5 to 2 hours.

Second Step From compound B-1, compound B-2 can be obtained in the same manner as in the eleventh step in 1) above.

3) Synthesis of compounds C-1 and C-2

(In the formula, each definition is as defined above.)

First Step From compound a11, compound C-1 can be obtained in the same manner as in the fifth step in 1) above.

Second Step From compound C-1, compound C-2 can be obtained in the same manner as in the eleventh step in 1) above.

4) Synthesis of compounds D-1 and D-2

(In the formula, each definition is as defined above.)

First Step In a solvent such as dichloromethane, THF, dichloroethane, or a mixed solvent thereof, a base such as pyridine, lutidine, triethylamine and acid chloride d1 are added to compound a13, and -50 ° C to 50 ° C, preferably -30 ° C. Compound D-1 can be obtained by reacting at 0.1 to 4 hours, preferably 0.5 to 1 hour at from 30 to 30 ° C.

Second Step From compound D-1, compound D-2 can be obtained in the same manner as in the eleventh step in 1) above.

5) Synthesis of compounds E-1 and E-2

(In the formula, each definition is as defined above.)

First Step In a solvent such as dichloromethane, THF, dichloroethane, or a mixed solvent thereof, a base such as pyridine, lutidine, triethylamine and a sulfonic acid chloride e1 are added to compound a13, and -50 ° C. to 50 ° C., preferably − Compound E-1 can be obtained by reacting at 30 to 30 ° C. for 0.1 to 4 hours, preferably 0.5 to 1 hour.

Second Step From compound E-1, compound E-2 can be obtained in the same manner as in the eleventh step in 1) above.

6) Synthesis of compounds F-1 and F-2

(In the formula, R ^{2 ′} , R ³ , R ⁴ and R ⁹¹ are as defined above. L ¹ is substituted or unsubstituted alkyl, etc.)

First Step From compound f1, compound f2 can be obtained in the same manner as in the first step in 1) above.

Second Step From compound f2, compound f3 can be obtained in the same manner as in the second step in 1) above.

Third Step From compound f3, compound f4 can be obtained in the same manner as in the third step in 1) above.

Fourth Step From compound f4, compound f5 can be obtained in the same manner as in the fourth step in 1) above.

Fifth Step From compound f5, compound f8 can be obtained in the same manner as in the fifth step in 1) above.

Sixth Step From compound f8, compound f9 can be obtained in the same manner as in the sixth step in 1) above.

Seventh Step From compound f9, compound f10 can be obtained in the same manner as in the seventh step in 1) above.

Eighth Step From compound f10, compound f11 can be obtained in the same manner as in the eighth step in 1) above.

9th process
From compound f11, compound f12 can be obtained in the same manner as in the fourth step in 1) above.

Tenth Step From compound f12, compound f13 can be obtained in the same manner as in the fifth step in 1) above.

Eleventh Step From compound f13, compound f14 can be obtained in the same manner as in the sixth step in 1) above.

Twelfth Step From compound f14, compound F-1 can be obtained in the same manner as in the first step in 4) above.

Thirteenth Step From compound F-1, compound F-2 can be obtained in the same manner as in the eleventh step in 1) above.

7) Synthesis of compounds G-1 and G-2

(In the formula, each definition is as defined above.)

First Step In a solvent such as dioxane, THF, diethyl ether, or a mixed solvent thereof, a base such as sodium hydride, potassium hydride, lithium hydride and the like and phenyl g1 chloroformate are added to compound f14, and -50 ° C to Compound g2 can be obtained by reacting at 50 ° C., preferably −30 ° C. to 30 ° C., for 0.1 hour to 4 hours, preferably 0.5 hour to 1 hour.

Second Step In a solvent such as dichloromethane, chloroform, dichloroethane, or a mixed solvent thereof, a base such as pyridine, lutidine, triethylamine and the amine g3 are added to the compound g2, and -30 ° C to 70 ° C, preferably -10 ° C to By reacting at 50 ° C. for 0.1 to 8 hours, preferably 0.5 to 2 hours, compound G-1 can be obtained.

Third Step From compound G-1, compound G-2 can be obtained in the same manner as in the eleventh step in 1) above.

8) Synthesis of compounds H-1 and H-2

(In the formula, each definition is as defined above.)

First Step From compound f10, compound h1 can be obtained in the same manner as in the eighth step in 1) above.

Second Step From compound h1, compound h2 can be obtained in the same manner as in the fourth step in 1) above.

Third Step From compound h2, compound H-1 can be obtained in the same manner as in the fifth step in 1) above.

Fourth Step From compound H-1, compound H-2 can be obtained in the same manner as in the eleventh step in 1) above.

9) Synthesis of compounds I-1 and I-2

(In the formula, each definition is as defined above.)

First Step In a solvent such as dioxane, THF, diethyl ether or the like or a mixed solvent thereof, a reducing agent such as borane-THF, borane-diethyl ether, borane-dimethylsulfane is added to compound f14, and -30 ° C. to 70 ° C. Compound i1 can be obtained by reacting at 0.1 ° C. to 50 ° C., preferably 0.1 to 8 hours, preferably 0.5 to 2 hours.

Second Step From compound i1, compound H-1 can be obtained in the same manner as in the first step in 4) above.

Third Step From compound I-1, compound I-2 can be obtained in the same manner as in the eleventh step in 1) above.

10) Synthesis of compounds J-1 and J-2

(In the formula, each definition is as defined above.)

First Step From compound i1, compound j1 can be obtained in the same manner as in the first step in 7) above.

Second Step From compound j1, compound J-1 can be obtained in the same manner as in the second step in 7) above.

Third Step From compound J-1, compound J-2 can be obtained in the same manner as in the eleventh step in 1) above.

11) Synthesis of compounds K-1 and K-2

(In the formula, each definition is as defined above.)

First Step From compound H-1, compound K-1 can be obtained in the same manner as in the first step in 9) above.

Second Step From compound K-1, compound K-2 can be obtained in the same manner as in the eleventh step in 1) above.

12) Synthesis of compounds L-1 and L-2

(In the formula, each definition is as defined above.)

First Step From compound f14, compound L-1 can be obtained in the same manner as in the first step in 4) above.

Second Step From compound L-1, compound L-2 can be obtained in the same manner as in the eleventh step in 1) above.

13) Synthesis of compounds M-1 and M-2

(In the formula, each definition is as defined above.)

First Step From compound i1, compound M-1 can be obtained in the same manner as in the first step in 4) above.

Second Step From compound M-1, compound M-2 can be obtained in the same manner as in the eleventh step in 1) above.

14) Synthesis of compounds N-1 and N-2

(In the formula, each definition is as defined above.)

First Step From compound f4, compound n1 can be obtained in the same manner as in the sixth step in 1) above.

Second Step From compound n1, compound n2 can be obtained in the same manner as in the fourth step in 1) above.

Third Step From compound n2, compound n3 can be obtained in the same manner as in the first step in 2) above.

Fourth Step From compound n3, compound n4 can be obtained in the same manner as in the seventh step in 1) above.

Fifth Step From compound n4, compound n6 can be obtained in the same manner as in the eighth step in 1) above.

Sixth Step From compound n6, compound n7 can be obtained in the same manner as in the sixth step in 1) above.

Seventh Step From compound n7, compound n8 can be obtained in the same manner as in the first step in 9) above.

Step 8 In a solvent such as dichloromethane, THF, dichloroethane, or a mixed solvent thereof, a base such as pyridine, lutidine, triethylamine and a reagent such as triphosgene, carbonyldiimidazole, diethyl carbonate, etc. are added to compound n8, and -50 ° C to Compound n9 can be obtained by reacting at 50 ° C., preferably −30 ° C. to 30 ° C., for 0.1 hour to 4 hours, preferably 0.5 hour to 1 hour.

Ninth Step From compound n9, compound n10 can be obtained in the same manner as in the fourth step in 1) above.

Tenth Step From compound n10, compound N-1 can be obtained in the same manner as in the fifth step in 1) above.

Eleventh Step From compound N-1, compound N-2 can be obtained in the same manner as in the eleventh step in 1) above.

15) Synthesis of compounds O-1 and O-2

(In the formula, each definition is as defined above.)

Step 1 Amide sulfuric acid is added to compound n8 in a pyridine solvent and reacted at 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 4 hours, preferably 0.5 hour to 1 hour. Thus, compound o1 can be obtained.

Second Step From compound o1, compound o2 can be obtained in the same manner as in the fourth step in 1) above.

Third Step From compound o2, compound O-2 can be obtained in the same manner as in the fifth step in 1) above.

Fourth Step From compound O-1, compound O-2 can be obtained in the same manner as in the eleventh step in 1) above.

16) Synthesis of compounds P-1 and P-2

(In the formula, each definition is as defined above.)

First Step From compound f5, compound p1 can be obtained in the same manner as in the fifth step in 1) above.

Second Step From compound p1, compound p2 can be obtained in the same manner as in the seventh step in 1) above.

Third Step From compound p2, compound p3 can be obtained in the same manner as in the eighth step in 1) above.

Fourth Step In a mixed solvent of water and acetone, osmium tetroxide and N-methylmorpholine N-oxide are added to compound p3, and the temperature is −50 ° C. to 50 ° C., preferably −30 ° C. to 30 ° C. for 0.1 hour to The reaction is performed for 4 hours, preferably 0.5 to 1 hour. Subsequently, sodium periodate is added to a mixed solvent of THF and water at −50 ° C. to 50 ° C., preferably −30 ° C. to 30 ° C., for 0.1 hour to 4 hours, preferably 0.5 hour to 1 hour. To give compound p4.

Fifth Step From compound p4, compound p5 can be obtained in the same manner as in the eighth step in 14) above.

Sixth Step From compound p5, compound p6 can be obtained in the same manner as in the fourth step in 1) above.

Seventh Step From compound p6, compound P-1 can be obtained in the same manner as in the fifth step in 1) above.

Eighth Step From compound P-1, compound P-2 can be obtained in the same manner as in the eleventh step in 1) above.

17) Synthesis of compounds Q-1 and Q-2

(In the formula, each definition is as defined above.)

First Step In a solvent such as dichloromethane, THF, dichloroethane, or a mixed solvent thereof, a base such as pyridine, lutidine, triethylamine and thionyl chloride are added to compound n8, and -50 ° C to 50 ° C, preferably -30 ° C to By reacting at 30 ° C. for 0.1 hour to 4 hours, preferably 0.5 hour to 1 hour, compound q1 can be obtained.

Second Step Ruthenium tetroxide and sodium periodate are added to compound q1 in a mixed solvent such as acetonitrile and water, and the temperature is −50 ° C. to 50 ° C., preferably −30 ° C. to 30 ° C., for 0.1 hour to 4 hours. The compound q2 can be obtained by reacting preferably for 0.5 to 1 hour.

Third Step From compound q2, compound q3 can be obtained in the same manner as in the fourth step in 1) above.

Fourth Step From compound q3, compound Q-1 can be obtained in the same manner as in the fifth step in 1) above.

Fifth Step From compound Q-1, compound Q-2 can be obtained in the same manner as in the eleventh step in 1) above.

18) Synthesis of compounds R-1 and R-2

(In the formula, each definition is as defined above.)

First Step In a solvent such as dioxane, THF, ethanol, or a mixed solvent thereof, a base such as potassium carbonate, sodium carbonate, potassium phosphate and bromoketone r1 are added to compound a13, and 50 ° C. to 150 ° C., preferably 70 ° C. Compound R-1 can be obtained by reacting at a temperature of from 120 ° C. to 120 ° C. for 1 to 24 hours, preferably 0.5 to 6 hours.

Second Step From compound R-1, compound R-2 can be obtained in the same manner as in the eleventh step in 1) above.

19) Synthesis of compounds S-1 and S-2

(In the formula, each definition is as defined above.)

First Step In a solvent such as dioxane, THF, DMF, or a mixed solvent thereof, a base such as potassium carbonate, sodium carbonate, sodium bicarbonate and bromoalkyne s1 are added to compound a13, and 50 ° C. to 150 ° C., preferably Compound S-1 can be obtained by reacting at 70 to 120 ° C. for 1 to 24 hours, preferably 0.5 to 6 hours.

Second Step From compound S-1, compound S-2 can be obtained in the same manner as in the eleventh step in 1) above.

20) Synthesis of compounds T-1 and T-2

(In the formula, each definition is as defined above.)

First Step 1,10-phenanthroline, copper bromide, zinc iodide, and nitrile t1 are added to compound a13 in a solvent such as 1,2-dichlorobenzene, toluene, DMSO, or a mixed solvent thereof. Compound T-1 can be obtained by reacting at 180 ° C., preferably 100 ° C. to 160 ° C., for 0.1 hour to 48 hours, preferably 1 hour to 24 hours.

Second Step From compound T-1, compound T-2 can be obtained in the same manner as in the eleventh step in 1) above.

21) Synthesis of compounds U-1 and U-2

(In the formula, each definition is as defined above.)

First Step In a solvent such as THF, diethyl ether, toluene, or a mixed solvent thereof, a base such as n-butyllithium, sodium hydride, lithium diisopropylamide, azidotris (diethylamino) phosphonium bromide is added to compound a13, Compound U-1 can be obtained by reacting at 130 ° C. to −30 ° C., preferably −110 ° C. to −50 ° C. for 0.1 hour to 5 hours, preferably 0.5 hour to 1 hour. .

Second Step From compound U-1, compound U-2 can be obtained in the same manner as in the eleventh step in 1) above.

22) Synthesis of compounds V-1 and V-2

(In the formula, each definition is as defined above.)

First Step In a solvent such as DMF, DMA, THF, dioxane, or a mixed solvent thereof, compound a11 is mixed with a base such as triethylamine, lutidine, pyridine, alcohol (R ⁷¹ OH), dibenzylideneacetone palladium, palladium acetate, Add a catalyst such as dichlorobistriphenylphosphine palladium and a ligand such as xanthophos, P (t-Bu) ₃ and at 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C. for 0.1 to 8 hours, Compound V-1 can be obtained by reacting preferably in 0.5 to 2 hours.

Second Step From compound V-1, compound V-2 can be obtained in the same manner as in the eleventh step in 1) above.

23) Synthesis of compounds W-1, W-2, W-3 and W-4

(In the formula, each definition is as defined above.)

Step 1 In a solvent such as DMF, DMA, THF, dioxane, or a mixed solvent thereof, compound w1 is added with a phosphine such as tritert-butylphosphine, tricyclohexylphosphine, triphenylphosphine, dibenzylideneacetone palladium, palladium acetate. In addition, a catalyst such as dichlorobistriphenylphosphine palladium, zinc fluoride, and compound a4 are added, and the temperature is 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 8 hours, preferably 0.5 hour to Compound w2 can be obtained by reacting in 2 hours.

Second Step In a solvent such as methanol, ethyl acetate, acetic acid, or a mixed solvent thereof, a catalyst such as palladium carbon, palladium hydroxide, Raney nickel catalyst is added to compound w2, and 30 ° C. to 130 ° C. in a hydrogen atmosphere, preferably Can be obtained by reacting at 50 ° C. to 110 ° C. for 0.1 to 8 hours, preferably 0.5 to 2 hours.

Third Step A brominating agent such as bromine or NBS is added to compound w3 in a solvent such as dichloromethane, chloroform, dichloroethane, or a mixed solvent thereof, and -50 ° C to 50 ° C, preferably -30 ° C to 30 ° C. The compound w4 can be obtained by reacting for 0.1 to 4 hours, preferably 0.5 to 1 hour.

Fourth Step In a solvent such as DMF, DMA, THF, dioxane, water, or a mixed solvent thereof, compound w4 is added with an aqueous solution of a base such as potassium carbonate, sodium carbonate, potassium phosphate, boronic acid or boronic acid ester, And a catalyst such as dibenzylideneacetone palladium, palladium acetate, dichlorobistriphenylphosphine palladium and the like at 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 8 hours, preferably 0.5 to 2 Compound W-1 can be obtained by reacting with time.

Step 5 Acetic acid and potassium permanganate are added to Compound W-1 in a tert-butanol aqueous solution, and the temperature is −50 ° C. to 50 ° C., preferably −30 ° C. to 30 ° C., for 0.1 hour to 4 hours, preferably Compound W-3 can be obtained by reacting in 0.5 hour to 1 hour.

Sixth Step From compound W-1, compound W-2 can be obtained in the same manner as in the eleventh step in 1) above. Compound W-4 can be obtained from compound W-3 by the same method.

24) Synthesis of compounds X-1 and X-2

(In the formula, each definition is as defined above.)

First Step In a solvent such as DMF, DMA, THF, dioxane, toluene, or a mixed solvent thereof, compound a11 is mixed with a base such as cesium carbonate, potassium carbonate, sodium carbonate, triethylamine, lutidine, pyridine, amine (R ⁷¹ NH ₂ ), a catalyst such as dibenzylideneacetone palladium, palladium acetate, dichlorobistriphenylphosphine palladium, and a ligand such as xanthophos, P (t-Bu) ₃ are added, and 50 ° C. to 150 ° C., preferably 70 ° C. to Compound X-1 can be obtained by reacting at 130 ° C. for 0.1 to 8 hours, preferably 0.5 to 2 hours.

Second Step From compound X-1, compound X-2 can be obtained in the same manner as in the eleventh step in 1) above.

Since the compound of the present invention has an HIV replication inhibitory action, it is useful as a therapeutic and / or prophylactic agent for viral infections such as AIDS.
The compound of the present invention has not only an HIV replication inhibitory action but also a usefulness as a medicine, and preferably has any or all of the following excellent features.
a) The inhibitory effect on CYP enzymes (eg, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, etc.) is weak.
b) Good pharmacokinetics such as high bioavailability and moderate clearance.
c) High metabolic stability.
d) Does not exhibit irreversible inhibitory action on CYP enzymes (eg CYP3A4) within the concentration range of the measurement conditions described herein.
e) Not mutagenic.
f) Low cardiovascular risk.
g) High solubility.
h) It shows a strong medicinal effect against resistant viruses.
i) It is difficult to express resistant viruses.

When administering the pharmaceutical composition of the present invention, it can be administered either orally or parenterally. Oral administration may be carried out by preparing a commonly used dosage form such as tablets, granules, powders, capsules and the like according to conventional methods. For parenteral administration, any commonly used dosage form such as an injection can be suitably administered. Since the compound of the present invention preferably has high oral absorbability, it can be suitably used as an oral preparation.

Various pharmaceutical additives such as excipients, binders, disintegrants, lubricants and the like suitable for the dosage form can be mixed with the effective amount of the compound of the present invention as necessary to obtain a pharmaceutical composition.

The dosage of the pharmaceutical composition of the present invention is preferably set in consideration of the age, weight, type and degree of disease, route of administration, etc. of the patient. 100 mg / kg / day, preferably in the range of 0.1 to 10 mg / kg / day. In the case of parenteral administration, although it varies greatly depending on the administration route, it is usually 0.005 to 10 mg / kg / day, preferably 0.01 to 1 mg / kg / day. This may be administered once to several times a day.

The compound of the present invention is combined with a reverse transcriptase inhibitor, a protease inhibitor, an integrase inhibitor, etc. (hereinafter abbreviated as a concomitant drug) for the purpose of enhancing the action of the compound or reducing the dose of the compound. Can be used. In this case, the administration time of the compound of the present invention and the concomitant drug is not limited, and these may be administered to the administration subject at the same time or may be administered with a time difference. Furthermore, the compound of the present invention and the concomitant drug may be administered as two types of preparations containing each active ingredient, or may be administered as a single preparation containing both active ingredients. *

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 and the concomitant drug can be appropriately selected depending on the administration subject, administration route, target disease, symptom, combination and the like. 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.

In addition, the compound of the present invention should be used in the field of gene therapy to prevent the spread of retroviral vector infection beyond the target tissue when using a retroviral vector based on HIV or MLV. Can do. In particular, when the compound of the present invention is administered in advance in the case where the vector is infected with cells in a test tube and then returned to the body, unnecessary infection in the body can be prevented.

Examples of the reverse transcriptase inhibitor include AZT, 3TC, didanosine, sarcitabine, sanylvudine, abacavir, tenofovir, emtricitabine, nevirabin, efavirenz, coupleravirin, etravirin, delavirdine and the like.

Examples of protease inhibitors include indinavir, ritonavir, saquinavir, nelfinavir, amprenavir, atanazavir, lopinavir, fosamprenavir, darunavir, atazanavir, branavir, tipranavir and the like.

Examples of the integrase inhibitor include raltegravir, elvitegravir, JTK-656, dolutegravir, S-265744 and the like.

Other anti-HIV drugs include, for example, invasion inhibitors such as maraviroc and bicrivirok, and fusion inhibitors such as enfuvirtide, sifuvirtide, and albuvirtide.

Hereinafter, the present invention will be described in more detail with reference to Examples, Reference Examples, and Test Examples of the present invention, but the present invention is not limited thereto.

Moreover, the abbreviation used in this specification represents the following meaning.
Ac: acetyl n-Bu: n-butyl t-Bu: tert-butyl Bn: benzyl Et: ethyl DME: dimethoxyethane DMF: N, N-dimethylformamide DCM: dichloromethane DMSO: dimethyl sulfoxide dppf: 1,1'-bis (Diphenylphosphino) ferrocene Me: methyl MsOH: methanesulfonic acid NBS: N-bromosuccinimide NCS: N-chlorosuccinimide NIS: N-iodosuccinimide Ph: phenyl TBS: tert-butyldimethylsilyl THF: tetrahydrofuran Tf: trifluoromethanesulfonyl TFA: trifluoroacetic acid TMS: trimethylsilyl Ts: p-toluenesulfonyl

The NMR analysis obtained in each example was performed at 300 MHz and measured using DMSO-d ₆ and CDCl ₃ .
RT in the table represents the retention time in LC / MS: liquid chromatography / mass spectrometry, and was measured under the following conditions. In addition, about the compound which can exist as two types of isomers in a mobile phase, a measurement peak can become two.
(Measurement condition)
Column: Shim-pack XR-ODS (2.2 μm, id 50 × 3.0 mm) (Shimadzu Corporation)
Flow rate: 1.6 mL / min UV detection wavelength: 254 nm
Mobile phase: [A] is a 0.1% formic acid-containing aqueous solution, [B] is a 0.1% formic acid-containing acetonitrile solution. 100% solvent [B] was maintained for minutes.

Example 1 Synthesis of Compound 5

First Step To a solution of compound (1) (25 g, 178 mmol) in water (250 mL) was added benzylamine (19.49 ml, 178 mmol), and the mixture was stirred with heating under reflux for 5 hours. The precipitated solid was filtered and recrystallized with methanol to obtain an orange solid compound (2) (21 g, yield 51.3%).
MS (ESI) m / z: 230.05 (M + H ^< + ^> )

Second Step To a solution of compound (2) (22 g, 96 mmol) in dichloromethane (200 mL) was added pyridine (10.09 mL, 125 mmol) and trifluoromethanesulfonic anhydride (17.83 mL, 106 mmol) under ice cooling in a nitrogen atmosphere. Added and stirred. After 30 minutes, 2 mol / L hydrochloric acid was added, and the mixture was extracted with dichloromethane (100 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated, and purified by column chromatography to give yellow oily compound (3) (32 g, yield 92.3%).
MS (ESI) m / z: 362.40 (M + H ^< + ^> )

Third Step To a solution of compound (3) in DMF (300 mL) under a nitrogen atmosphere, zinc fluoride (13.73 g, 133 mmol), dibenzylideneacetone palladium (5.09 g, 8.86 mmol), tritert-butylphosphine ( 4.16 mL, 17.71 mmol) and silyl enol ether (58.3 g, 267 mmol) were added and stirred at 100 degrees. After 1 hour, water (300 mL) was added, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give a yellow solid compound (4) (16 g, yield 50.5%).
MS (ESI) m / z: 358.65 (M + H ^< + ^> )

Fourth Step To a solution of compound (4) (9 g, 25.2 mmol) in acetonitrile (100 mL), NBS (4.48 g, 25.2 mmol) was added and stirred under ice cooling. After 30 minutes, saturated aqueous sodium hydrogen carbonate (100 mL) was added, and the mixture was extracted with dichloromethane (100 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated, and purified by column chromatography to give white solid compound (5) (9.02 g, yield 82.1%). It was.
MS (ESI) m / z: 436.05 (M + H ^< + ^> )

Step 5 To a solution of compound (5) (1 g, 2.292 mmol) in DMF (10 mL) under nitrogen atmosphere, water (3.5 mL), boronic acid (687 mg, 4.58 mmol), triphenylphosphine palladium (265 mg, 0.229 mmol) and potassium carbonate (951 mg, 6.88 mmol) were added and stirred at 140 degrees. After 1 hour, 2 mol / L hydrochloric acid (100 mL) was added, and the mixture was extracted with ethyl acetate (10 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give a yellow liquid compound (6) (800 mg, yield 75.6%).
MS (ESI) m / z: 462.60 (M + H ^< + ^> )

Step 6 To a solution of compound (6) (800 mg, 1.733 mmol) in acetic acid (10 ml) was added palladium carbon (80 mg), and the mixture was stirred at 80 ° C. in a hydrogen atmosphere. After 2 hours, the mixture was filtered through Celite, and the filtrate was concentrated and purified by column chromatography to obtain a white solid compound (7) (270 mg, yield 41.9%).
MS (ESI) m / z: 372.10 (M + H ⁺ )

Seventh Step To a solution of compound (7) (240 mg, 0.646 mmol) in dichloromethane (2 mL) under a nitrogen atmosphere, pyridine (0.068 mL, 0.84 mmol) and trifluoromethanesulfonic anhydride (0.12 mL, .0. 711 mmol) was added under ice-cooling and stirred. After 30 minutes, 2 mol / L hydrochloric acid was added, and the mixture was extracted with dichloromethane (2 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give a transparent liquid compound (8) (280 mg, yield 86.1%).
MS (ESI) m / z: 504.15 (M + H ^< + ^> )

Step 8 To a 1,4-dioxane solution (3 mL) of compound (8) (300 mg, 0.596 mmol) under a nitrogen atmosphere, cesium carbonate (582 mg, 1.787 mmol), benzylamine (0.13 mL, 1.192 mmol) , Dibenzylideneacetone palladium (34.3 mg, 0.06 mmol) and xanthophos (68.9 mg, 0.119 mmol) were added, and the mixture was stirred with heating under reflux. After 2 hours, water was added and extracted with ethyl acetate (3 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give a yellow solid compound (9) (270 mg, yield 98.4%).
MS (ESI) m / z: 461.70 (M + H ^< + ^> )

Step 9 To a solution of compound (9) (260 mg, 0.564 mmol) in methanol (3 ml) was added palladium carbon (26 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere. After 5 hours, the mixture was filtered through Celite, and the filtrate was concentrated and purified by column chromatography to obtain a white solid compound (10) (170 mg, 81.3% yield).
MS (ESI) m / z: 371.55 (M + H ^< + ^> )

Step 10 To a solution of compound (10) (30 mg, 0.081 mmol) in dichloroethane (1 mL) was added triethylamine (0.034 mL, 0.243 mmol) and phenyl isocyanate (0.018 mL, 0.162 mmol) under a nitrogen atmosphere. , And stirred at 60 degrees. After 30 minutes, 2 mol / L hydrochloric acid (1 mL) was added, and the mixture was extracted with ethyl acetate (1 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give a yellow liquid compound (11).
MS (ESI) m / z: 490.25 (M + H ^< + ^> )

Step 11 To a solution of compound (11) (39.6 mg, 0.081 mmol) in methanol (1 mL) was added 2 mol / L aqueous sodium hydroxide solution (0.121 mL, 0.243 mmol), and the mixture was stirred with heating under reflux. After 1 hour, 2 mol / L hydrochloric acid (1 mL) was added, and the mixture was extracted with ethyl acetate (1 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give compound 5 (25 mg, yield 65.0% (10th to 11th steps) as a white solid. )
MS (ESI) m / z: 476.20 (M + H ^< + ^> )
¹ H-NMR (400 MHz, CDCl ₃ ): δ12.5 (1H, s), 7.60-6.94 (9H, m), 5.12 (1H, s), 2.34-2.24 (12H, m), 1.01 (9H, s )

Example 2 Synthesis of Compound 1

First Step To a solution of compound (8) (200 mg, 0.397 mmol) in DMF (2 mL), triethylamine (0.11 mL, 0.794 mmol), benzylamine (0.13 mL, 1.192 mmol), lithium bromide (103 mg) 1.192 mmol) and triphenylphosphine palladium (45.9 mg, 0.04 mmol) were added, and the mixture was stirred with heating under reflux in a carbon monoxide atmosphere. After 30 minutes, 2 mol / L hydrochloric acid (2 mL) was added, and the mixture was extracted with ethyl acetate (2 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated, and purified by column chromatography to give white solid compound (12) (178 mg, yield 91.7%).
MS (ESI) m / z: 489.20 (M + H ^< + ^> )

Second Step To a solution of compound (12) (178 mg, 0.364 mmol) in methanol (2 mL) was added 2 mol / L aqueous sodium hydroxide solution (0.546 mL, 1.093 mmol), and the mixture was stirred with heating under reflux. After 30 minutes, 2 mol / L hydrochloric acid (2 mL) was added, and the mixture was extracted with ethyl acetate (2 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give Compound 1 (145 mg, yield 83.9%) as a white solid.
MS (ESI) m / z: 475.20 (M + H ^< + ^> )
¹ H-NMR (400 MHz, CDCl ₃ ): δ8.43 (1H, s), 7.57-6.91 (8H, m), 5.18 (1H, s), 4.61 (2H, d), 2.74 (3H, s), 2.33-2.18 (9H, m), 1.00 (9H, s)

Example 3 Synthesis of Compound 4

First Step To a solution of compound (12) (100 mg, 0.205 mmol) in THF (1 mL) under a nitrogen atmosphere, sodium hydride (9.82 mg, 0.409 mmol), methyl iodide (0.032 mL, 0.512 mmol). ) And stirred under ice cooling. After 3 hours, 2 mol / L hydrochloric acid (1 mL) was added, and the mixture was extracted with ethyl acetate (1 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give a white solid compound (13).
MS (ESI) m / z: 503.25 (M + H ^< + ^> )

Second Step To a solution of compound (13) (135 mg, 0.269 mmol) in methanol (2 mL) was added 2 mol / L aqueous sodium hydroxide solution (0.403 mL, 0.806 mmol), and the mixture was stirred with heating under reflux. After 30 minutes, 2 mol / L hydrochloric acid (2 mL) was added, and the mixture was extracted with ethyl acetate (2 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated, and purified by column chromatography to give Compound 4 as a white solid (101 mg, yield 77.0% (14th to 15th steps)). )
MS (ESI) m / z: 489.20 (M + H ^< + ^> )
¹ H-NMR (400 MHz, CDCl ₃ ): δ7.35-6.87 (8H, m), 4.88-4.60 (2H, m), 2.92 (1.5H, s), 2.71 (1.5H, s), 2.30-2.15 (12H, m), 0.83 (4.5H, d), 0.80 (4.5H, d)

Example 4 Synthesis of compounds 66 and 67

First Step To a toluene (2 mL) solution of compound (8 ′) (200 mg, 0.39 mmol) obtained by the same synthesis method as compound (8) in Example 1, cesium carbonate (193 mg, 0.593 mmol), 3 -Aminoquinoline (68.4 mg, 0.475 mmol), xanthophos (10.3 mg, 0.018 mmol), Pd (dba) ₂ (6.9 mg, 0.012 mmol) were added, and the mixture was stirred with heating under reflux. After 40 minutes, water (2 mL) was added and extracted with ethyl acetate (2 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give yellow foamy compound (14) (167 mg, yield 84.5%). .
MS (ESI) m / z: 500.20 (M + H ⁺ )

Second Step To a solution of compound (14) (160 mg, 0.320 mmol) in ethanol (1.6 mL) was added 2 mol / L aqueous sodium hydroxide solution (1.6 mL, 3.20 mmol), and the mixture was stirred with heating under reflux. After 30 minutes, 2 mol / L hydrochloric acid (1.6 mL) was added, and the mixture was extracted with ethyl acetate (2 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated, and purified by column chromatography to give a mixture of compound 66 and compound 67 (74.0 mg, yield 47.6%) as a yellow solid. )
MS (ESI) m / z: 486.15 (M + H ⁺ )
¹ H-NMR (400 MHz, CDCl ₃ ): δ8.95 (1H, d, J = 2.4 Hz), 8.66 (1H, d, J = 2.4 Hz), 8.02 (1H, d, J = 8.5 Hz), 7.75 (1H, d, J = 8.5Hz), 7.57-7.45 (3H, m), 7.17 (1H, d, J = 8.5Hz), 6.99 (2H, m), 6.54 (1H, s), 5.17 (1H, s), 3.87 (3H, s), 2.32 (3H, s), 2.26 (3H, s), 1.04 (9H, s)

Compound 66 and compound 67 were obtained by optical resolution of the mixture obtained in the second step by a known method.

Example 5 Synthesis of Compound 74

First Step To a solution of compound (8 ″) (100 mg, 0.188 mmol) obtained in the same synthesis method as compound (8) in Example 1 in toluene (1 mL), cesium carbonate (123 mg, 0.376 mmol), Cyclohexylmethanol (43.0 mg, 0.376 mmol), xanthophos (4.9 mg, 0.008 mmol) and Pd (dba) ₂ (3.24 mg, 0.005 mmol) were added, and the mixture was stirred with heating under reflux. After 4 hours, 2 mol / L hydrochloric acid (1 mL) was added, and the mixture was extracted with ethyl acetate (2 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give white foamy compound (15) (90.0 mg, yield 96.5%). Obtained.
MS (ESI) m / z: 496.25 (M + H ⁺ )

Second Step To a solution of compound (15) (90 mg, 0.182 mmol) in ethanol (0.9 mL) was added 2 mol / L aqueous sodium hydroxide solution (0.91 mL, 1.82 mmol), and the mixture was stirred with heating under reflux. After 1 hour, 2 mol / L hydrochloric acid (1 mL) was added, and the mixture was extracted with ethyl acetate (2 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated, and purified by column chromatography to give white solid compound 74 (40.0 mg, yield 45.7%).
MS (ESI) m / z: 482.20 (M + H ⁺ )
¹ H-NMR (400 MHz, CDCl ₃ ): δ7.14 (1H, s), 6.92-6.79 (2H, m), 5.10 (1H, s), 4.26-4.20 (2H, m), 4.16-4.06 (2H , m), 2.86-2.69 (2H, m), 2.23-2.13 (6H, m), 2.08-1.98 (2H, m), 1.92-1.05 (11H, m), 1.01 (9H, s)

Example 6 Synthesis of Compound 35

First Step To a solution of compound (10) (50 mg, 0.135 mmol) in dioxane (1 mL) was added sodium carbonate (42.9 mg, 0.405 mmol), 2-bromo-1-phenylethanone (81.0 mg, 0.25 mmol). 405 mmol) was added, and the mixture was stirred with heating under reflux. After 13 hours, 2 mol / L hydrochloric acid (1 mL) was added, and the mixture was extracted with ethyl acetate (2 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give yellow oily compound (16) (52.0 mg, yield 81.9%). It was.
MS (ESI) m / z: 471.2 (M + H ⁺ )
¹ H-NMR (400 MHz, CDCl ₃ ): δ8.02 (1H, d, J = 7.3 Hz), 7.75 (1H, s), 7.47-7.39 (2H, m), 7.38-7.28 (2H, m), 7.23-7.17 (1H, m), 7.03-6.93 (1H, m), 5.14 (1H, s), 2.78 (3H, s), 2.34 (6H, s), 2.31 (3H, s), 1.03 (9H, s)

Second Step To a solution of compound (16) (50 mg, 0.106 mmol) in ethanol (1.0 mL) was added 2 mol / L aqueous sodium hydroxide solution (0.532 mL, 1.07 mmol), and the mixture was stirred with heating under reflux. After 1 hour, 2 mol / L hydrochloric acid (1 mL) was added, and the mixture was extracted with ethyl acetate (2 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give beige solid compound 35 (25.0 mg, yield 51.5%).
MS (ESI) m / z: 457.10 (M + H ⁺ )

Example 7 Synthesis of Compound 40

First Step To a solution of compound (17) (5.58 g, 31.2 mmol) in DMF (56 mL) under a nitrogen atmosphere, zinc fluoride (4.84 g, 46.9 mmol), Pd (dba) ₂ (1.79 g). 3.12 mmol), P (t-Bu) ₃ (1.49 mL, 6.25 mmol) and silyl enol ether (20.44 g, 93.6 mmol) were added and stirred at 100 degrees. After 30 minutes, water (100 mL) was added, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give compound (18) (6.41 g, yield 71.2%) as a yellow solid. It was.
MS (ESI) m / z: 289.35 (M + H ⁺ )

Second Step To a solution of compound (18) (6.41 g, 22.2 mmol) in methanol (64 mL) was added 50% water-containing 10% Pd / C (1.2 g), and the mixture was stirred at 60 ° C. in a hydrogen atmosphere. After 12 hours, the mixture was filtered through Celite, and the filtrate was concentrated, and hexane was added and filtered to obtain an ocherous solid compound (19) (6.0 g, yield 92.3%).
MS (ESI) m / z: 293.40 (M + H ⁺ )

Third Step To a solution of compound (19) (6.0 g, 20.5 mmol) in acetonitrile (60 mL), NBS (4.02 g, 22.6 mmol) was added and stirred under ice cooling. After 30 minutes, saturated aqueous sodium hydrogen carbonate (60 mL) was added, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give yellow oily compound (20) (6.5 g, yield 85.3%). It was.
MS (ESI) m / z: 372.30 (M + H ⁺ )

Fourth Step To a DMF (120 mL) solution of the compound (20) (6.5 g, 17.5 mmol) in a nitrogen atmosphere, a 2 mol / L Na ₂ CO ₃ aqueous solution (26.3 mL, 52.5 mmol), 3,4- Dimethylphenylboronic acid (3.94 g, 26.3 mmol) and Pd (PPh ₃ ) ₄ (2.02 g, 1.75 mmol) were added and stirred at 140 degrees. After 1 hour, water (240 mL) was added, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give yellow foamy compound (21) (4.64 g, yield 66.8%). Obtained.
MS (ESI) m / z: 397.15 (M + H ⁺ )

Step 5 To a solution of compound (21) (50 mg, 0.126 mmol) in dichloroethane (1 mL) was added triethylamine (0.052 mL, 0.378 mmol) and cyclohexyl isocyanate (0.032 mL, 0.252 mmol). Stir. After 2 hours, 2 mol / L hydrochloric acid (1 mL) was added, and the mixture was extracted with dichloromethane (2 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give yellow foamy compound (22) (64.8 mg, yield 98.5%). Obtained.
MS (ESI) m / z: 522.25 (M + H ⁺ )

Step 6 To a solution of compound (22) (60 mg, 0.115 mmol) in ethanol (1 mL) was added 2 mol / L aqueous sodium hydroxide solution (1.15 mL, 2.3 mmol), and the mixture was stirred with heating under reflux. After 3 hours, 2 mol / L hydrochloric acid (1.2 mL) was added, and the mixture was extracted with ethyl acetate (2 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give white solid compound 40 (55.0 mg, yield 94.2%).
MS (ESI) m / z: 508.25 (M + H ⁺ )
¹ H-NMR (400 MHz, CDCl ₃ ): δ10.8 (1H, d, J = 7.2 Hz), 7.25-6.90 (3H, m), 5.11 (1H, s), 4.31 (1H, m), 3.88- 3.77 (1H, m), 3.69-3.48 (1H, m), 3.12-3.00 (1H, m), 2.57-2.43 (1H, m), 2.32- (3H, s), 2.29 (3H, s), 2.12 (3H, s), 2.03-1.22 (11H, m), 1.01 (9H, s)

Example 8 Synthesis of Compound 48

First Step To a solution of compound (21) (1 g, 2.52 mmol) in t-BuOH (5 mL) and water (5 mL), acetic acid (0.433 mL, 7.57 mmol), potassium permanganate (996 mg, 6.30 mmol). ) Was added and stirred at room temperature. After 30 minutes, ethanol (5 mL was added), 2 mol / L NaOH aqueous solution (5 mL) was added, the mixture was filtered through Celite, and extracted with ethyl acetate (10 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated, and purified by column chromatography to give white solid compound (23) (768 mg, yield 74.2%).
MS (ESI) m / z: 411.1 (M + H ⁺ )

Second Step To a solution of compound (23) (50 mg, 0.122 mmol) in DMF (1 mL) was added potassium carbonate (50.5 mg, 0.365 mmol) and bromomethylcyclohexane (0.034 mL, 0.244 mmol). , And stirred at 80 degrees. After 30 hours, 2 mol / L hydrochloric acid aqueous solution (1 mL) was added, and the mixture was extracted with ethyl acetate (10 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give yellow oily compound (24) (36.3 mg, yield 57.2%). It was.
MS (ESI) m / z: 507.20 (M + H ⁺ )

Step 3 To a solution of compound (24) (28 mg, 0.055 mmol) in ethanol (1 mL) was added 2 mol / L aqueous sodium hydroxide solution (0.553 mL, 1.11 mmol), and the mixture was stirred with heating under reflux. After 1 hour, 2 mol / L hydrochloric acid (1.2 mL) was added, and the mixture was extracted with ethyl acetate (2 mL × 3). The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated and purified by column chromatography to give white solid compound 48 (19.8 mg, yield 72.7%).
MS (ESI) m / z: 493.3 (M + H ⁺ )
¹ H-NMR (400 MHz, CDCl ₃ ): δ7.25-7.17 (3H, m), 5.08 (1H, s), 4.16-4.00 (2H, m), 3.12-3.01 (1H, m), 2.74-2.58 (3H, m), 2.32 (3H, s), 2.30 (3H, s), 2.27 (3H, s), 1.87-1.12 (11H, m), 1.00 (9H, s)

Example 9 Synthesis of Compound 45

First Step Compound (10) (100 mg, 0.270 mmol) was dissolved in pyridine (1 ml), naphthalene-1-sulfonyl chloride (92 mg, 0.405 mmol) was added, and the mixture was stirred at 80 ° C. for 2.5 hours. Further, naphthalene-1-sulfonyl chloride (46 mg, 0.202 mmol) was added and stirred at 80 ° C. for 3 hours. The reaction solution was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography to obtain a colorless foamy compound (25) (95 mg, 63% yield).
MS (ESI) m / z: 561 (M + H ⁺ )

Second Step To a solution of compound (25) (95 mg, 0.17 mmol) in methanol (2 mL) and tetrahydrofuran (0.5 ml) was added 2 mol / L aqueous sodium hydroxide solution (0.85 mL, 1.7 mmol) and heated. Stirred under reflux. After 5 hours, a saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated, and purified by column chromatography to give white solid compound 45 (70 mg, yield 76%).
MS (ESI) m / z: 547 (M + H ⁺ )
¹ H-NMR (CDCl ₃ ) δ: 9.03 (d, J = 8.7 Hz, 1H), 8.28 (d, J = 7.3 Hz, 1H), 7.98 (d, J = 8.3 Hz, 1H), 7.88 (d, J = 8.2 Hz, 1H), 7.64 (t, J = 7.7 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.8 Hz, 1H), 7.15 (m, 2H) , 6.87 (m, 1H), 4.94 (s, 1H), 2.28-2.12 (m, 12H), 0.95 (d, J = 5.3 Hz, 9H).

Example 10 Synthesis of Compound 22

First Step Compound (10) (50 mg, 0.14 mmol) was dissolved in pyridine (1 ml), benzoyl chloride (92 mg, 0.15 mmol) was added, and the mixture was stirred at room temperature for 3 hours. The reaction solution was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography to obtain a colorless foamy compound (26) (33 mg, 52% yield).
MS (ESI) m / z: 475 (M + H ^< + ^> )

Second Step To a solution of compound (26) (33 mg, 0.070 mmol) in methanol (1.5 mL) and tetrahydrofuran (0.5 ml) was added 2 mol / L aqueous sodium hydroxide solution (0.35 mL, 0.70 mmol). The mixture was stirred under reflux with heating. After 2 hours, a saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over sodium sulfate, concentrated, and purified by column chromatography to give white solid compound 22 (13 mg, 41% yield).
MS (ESI) m / z: 461 (M + H ⁺ )
¹ H-NMR (CDCl ₃ ) δ: 8.53 (br s, 1H), 7.95 (d, J = 7.6 Hz, 2H), 7.57-7.45 (m, 3H), 7.28-7.18 (m, 2H), 6.92 ( m, 1H), 5.12 (s, 1H), 2.31 (s, 1H), 2.29 (s, 1H), 2.24 (s, 1H), 2.19 (s, 1H), 1.04 (s, 9H).

Example 11 The following compounds were synthesized according to the above examples.

(Wherein R ¹ is methyl, R ² is tert-butyloxy, n is 1, R ⁴ is a hydrogen atom, and R ⁶ is methyl.)

The following compounds were also synthesized according to the above examples.

Example 12 According to the above Example, the following compounds can be synthesized.

Here, R ³ is any of the following groups.

Hereinafter, biological test examples of the compound of the present invention will be described.
Test Example 1 HIV Replication Inhibition Test HIV (HTLV-IIIB strain) persistently infected human T cell line Molt-4 clone 8 was cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum, and the supernatant was filtered to obtain virus titer. Was measured and stored at −80 ° C. On the other hand, each anti-human immunodeficiency virus active substance was diluted with the above culture medium to a predetermined concentration, and 50 μL was dispensed into a 96-well microplate. Subsequently, 100 μL (2.5 × 10 ⁴ cells) of the MT-4 cell suspension was dispensed, and 50 μl (60 pfu (plaque forming unit)) of the above-described HIV-containing supernatant diluted with the above culture medium. added.

After culturing at 37 ° C. for 4 days in a carbon dioxide incubator, all wells were treated with 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) 5 mg / mL), PBS 30 μL each was added and further cultured for 1 hour. At this time, since surviving cells reduce MTT to precipitate formazan, 150 μL of cell supernatant is removed from all wells, and 150 μL of lysate (10% Triton X-100 and 0.4% (v / V) HCl-added isopropanol) was added and shaken with a plate mixer to elute formazan. Formazan was measured at OD 560 nm and 690 nm (reference wavelength) using a microreader, and the results were compared with the control. 50% inhibition concentration of compound cytotoxicity by the virus was _{EC 50.}

As a result of the test, the EC ₅₀ of each Example compound was as shown in the following table.

Test Example 2 CYP Inhibition Test O-deethylation of 7-ethoxyresorufin as a typical substrate metabolic reaction of major human CYP5 molecular species (CYP1A2, 2C9, 2C19, 2D6, 3A4) using commercially available pooled human liver microsomes CYP1A2), methyl-hydroxylation of tolbutamide (CYP2C9), 4′-hydroxylation of mephenytoin (CYP2C19), O-demethylation of dextromethorphan (CYP2D6), and hydroxylation of terfenadine (CYP3A4) The degree to which the amount of metabolite produced was inhibited by the compound of the present invention was evaluated.

The reaction conditions were as follows: substrate, 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 microsome 0.2 mg protein / mL; compound concentration of the present invention 1, 5, 10, 20 μmol / L (4 points) .

As a reaction solution in a 96-well plate, each of 5 types of substrate, human liver microsome, and the compound of the present invention are added in the above composition in a 50 mmol / L Hepes buffer solution, and NADPH, a coenzyme, is added as an indicator for metabolic reaction. Started. After reacting at 37 ° C. for 15 minutes, the reaction was stopped by adding a methanol / acetonitrile = 1/1 (V / V) solution. After centrifuging at 3000 rpm for 15 minutes, resorufin (CYP1A2 metabolite) in the centrifugation supernatant was quantified with a fluorescent multi-label counter, tolbutamide hydroxide (CYP2C9 metabolite), mephenytoin 4 ′ hydroxide (CYP2C19 metabolite) Dextrorphan (CYP2D6 metabolite) and terfenadine alcohol (CYP3A4 metabolite) were quantified by LC / MS / MS.

Only DMSO as a solvent to dissolve the drug as a control that was added to the reaction system (100%), calculating the residual activity (%), using a concentration and inhibition rate, an IC ₅₀ by inverse estimation with the logistic model Calculated.

As a result of the test, all of the compounds 4 to 9 had an IC ₅₀ for the activities of CYP1A2, CYP2C19, CYP2D6, and CYP3A4 of 20 μM or more. .

Test Example 3 CYP3A4 Fluorescence MBI Test The CYP3A4 fluorescence MBI test is a test for examining the enhancement of CYP3A4 inhibition of the compounds of the present invention by metabolic reaction. 7-Benzyloxytrifluoromethylcoumarin (7-BFC) is debenzylated by the CYP3A4 enzyme (E. coli expression enzyme) to produce a fluorescent metabolite 7-hydroxytrifluoromethylcoumarin (7-HFC). CYP3A4 inhibition was evaluated using 7-HFC production reaction as an index.

The reaction conditions are as follows: substrate, 5.6 μmol / L 7-BFC; pre-reaction time, 0 or 30 minutes; reaction time, 15 minutes; reaction temperature, 25 ° C. (room temperature); CYP3A4 content (E. coli expression enzyme), Pre-reaction 62.5 pmol / mL, reaction 6.25 pmol / mL (10-fold dilution); compound concentration of the present invention, 0.625, 1.25, 2.5, 5, 10, 20 μmol / L (6 points) ).

The enzyme and the compound solution of the present invention are added to the 96-well plate as a pre-reaction solution in K-Pi buffer (pH 7.4) in the above-mentioned pre-reaction composition, and the substrate and K-Pi buffer are added to another 96-well plate. A part of the solution was transferred so as to be diluted by 1/10, and a reaction using NADPH as a coenzyme was started as an indicator (no pre-reaction). After reaction for a predetermined time, acetonitrile / 0.5 mol / L The reaction was stopped by adding Tris (trishydroxyaminomethane) = 4/1 (V / V). In addition, NADPH is also added to the remaining pre-reaction solution to start the pre-reaction (pre-reaction is present), and after pre-reaction for a predetermined time, one plate is diluted to 1/10 with the substrate and K-Pi buffer. The reaction was started by shifting the part. After the reaction for a predetermined time, the reaction was stopped by adding acetonitrile / 0.5 mol / L Tris (trishydroxyaminomethane) = 4/1 (V / V). The fluorescence value of 7-HFC, which is a metabolite, was measured using a fluorescent plate reader on the plate on which each index reaction was performed. (Ex = 420nm, Em = 535nm)

A control (100%) was obtained by adding only DMSO, which is a solvent in which the compound of the present invention was dissolved, to the reaction system, and the residual activity (%) when each concentration of the compound of the present invention was added was calculated. Was used to calculate IC ₅₀ by inverse estimation using a logistic model. The case where the difference in IC ₅₀ values was 5 μmol / L or more was designated as (+), and the case where it was 3 μmol / L or less was designated as (−).

Test Example 4 Metabolic Stability Test A commercially available pooled human liver microsome and the compound of the present invention were reacted for a certain period of time, and the residual rate was calculated by comparing the reaction sample with the unreacted sample to evaluate the degree of metabolism of the compound of the present invention in the liver. .

In 0.2 mL buffer (50 mmol / L Tris-HCl pH 7.4, 150 mmol / L potassium chloride, 10 mmol / L magnesium chloride) containing 0.5 mg protein / mL human liver microsomes in the presence of 1 mmol / L NADPH The reaction was carried out at 37 ° C. for 0 or 30 minutes (oxidative reaction). After the reaction, 50 μL of the reaction solution was added to 100 μL of a methanol / acetonitrile = 1/1 (v / v) solution, mixed, and centrifuged at 3000 rpm for 15 minutes. The compound of the present invention in the centrifugal supernatant was quantified by LC / MS / MS, and the residual amount of the compound of the present invention after the reaction was calculated with the compound amount at 0 minute reaction as 100%. The hydrolysis reaction was carried out in the absence of NADPH, and the glucuronic acid conjugation reaction was carried out in the presence of 5 mmol / L UDP-glucuronic acid instead of NADPH, and thereafter the same operation was carried out.

Test Example 5 Solubility test The solubility of the compound of the present invention was determined under the condition of addition of 1% DMSO. Prepare a 10 mmol / L compound solution in DMSO, add 6 μL of the compound solution of the present invention to pH 6.8 artificial intestinal fluid (0.2 mol / L potassium dihydrogen phosphate test solution 250 mL, add 0.2 mol / L NaOH test solution 118 mL, water) Was added to 594 μL. After allowing to stand at 25 ° C. for 16 hours, the mixed solution was subjected to suction filtration. The filtrate was diluted 2-fold with methanol / water = 1/1 (V / V), and the concentration in the filtrate was measured by HPLC or LC / MS / MS using the absolute calibration curve method.

Test Example 6 Fluctuation Ames Test
The mutagenicity of the compounds of the present invention was evaluated.
20 μL of Salmonella typhimurium TA98 strain, TA100 strain, which has been cryopreserved, is inoculated into 10 mL liquid nutrient medium (2.5% Oxoid nutritive broth No. 2) and cultured at 37 ° C. for 10 hours before shaking. For the TA98 strain, 9 mL of the bacterial solution was centrifuged (2000 × g, 10 minutes) to remove the culture solution. 9 mL of Micro F buffer (K ₂ HPO ₄ : 3.5 g / L, KH ₂ PO ₄ : 1 g / L, (NH ₄ ) ₂ SO ₄ : 1 g / L, trisodium citrate dihydrate: 0. MicroF containing 110 mL Exposure medium (Biotin: 8 μg / mL, Histidine: 0.2 μg / mL, Glucose: 8 mg / mL) suspended in 25 g / L, MgSO ₄ · 7H ₂ 0: 0.1 g / L) Buffer). The TA100 strain was added to 120 mL of Exposure medium with respect to the 3.16 mL bacterial solution to prepare a test bacterial solution. Compound DMSO solution of the present invention (maximum dose of 50 mg / mL to several-fold dilution at 2-3 times common ratio), DMSO as a negative control, and non-metabolic activation conditions as a positive control, 50 μg / mL 4-TA Nitroquinoline-1-oxide DMSO solution, 0.25 μg / mL 2- (2-furyl) -3- (5-nitro-2-furyl) acrylamide DMSO solution for TA100 strain, TA98 under metabolic activation conditions 40 μg / mL 2-aminoanthracene DMSO solution for the strain and 20 μg / mL 2-aminoanthracene DMSO solution for the TA100 strain, respectively, and 588 μL of the test bacterial solution (498 μL of the test bacterial solution and S9 under metabolic activation conditions). mix 90 μL of the mixture) and incubate with shaking at 37 ° C. for 90 minutes. 460 μL of the bacterial solution exposed to the compound of the present invention was added 2300 μL of Indicator medium (MicroF buffer containing biotin: 8 μg / mL, histidine: 0.2 μg / mL, glucose: 8 mg / mL, bromocresol purple: 37.5 μg / mL). 50 μL each, and dispensed into 48 wells / dose of the microplate, and statically cultured at 37 ° C. for 3 days. Since wells containing bacteria that have acquired growth ability due to mutation of the amino acid (histidine) synthase gene change from purple to yellow due to pH change, the number of bacterial growth wells that changed to yellow in 48 wells per dose was counted. Evaluate compared to negative control group. The negative mutagenicity was indicated as (−) and the positive mutagenicity as (+).

Test Example 7 BA Test Oral Absorbability Examination Materials and Methods (1) Animals used: Mice or SD rats are used.
(2) Breeding conditions: Mice or SD rats are allowed to freely take solid feed and sterilized tap water.
(3) Setting of dose and grouping: oral administration and intravenous administration are administered at a predetermined dose. Set the group as follows. (Dose may vary for each compound)
Oral administration 1-30 mg / kg (n = 2-3)
Intravenous administration 0.5-10 mg / kg (n = 2-3)
(4) Preparation of administration liquid: Oral administration is administered as a solution or suspension. Intravenous administration is administered after solubilization.
(5) Administration method: Oral administration is forcibly administered into the stomach with an oral sonde. Intravenous administration is performed from the tail vein using a syringe with a needle.
(6) Evaluation item: Blood is collected over time, and the concentration of the compound of the present invention in plasma is measured using LC / MS / MS.
(7) Statistical analysis: The plasma concentration-time curve area (AUC) is calculated using the non-linear least squares program WinNonlin (registered trademark) for the plasma concentration of the compound of the present invention, and the oral administration group and intravenous administration The bioavailability (BA) of the compound of the present invention is calculated from the AUC of the group.

Test Example 8 hERG Test For the purpose of evaluating the risk of extending the electrocardiogram QT interval of the compound of the present invention, HEK293 cells expressing a human ether-a-go-go related gene (hERG) channel were used and important for the ventricular repolarization process. The effect of the compounds of the present invention on the delayed rectifier K ⁺ current (I _Kr ) playing a role was investigated.
Using a fully automatic patch clamp system (PatchXpress 7000A, Axon Instruments Inc.) and holding the cells at a membrane potential of −80 mV by whole cell patch clamp method, a +40 mV depolarization stimulus was applied for 2 seconds, followed by a −50 mV repolarization. The I _Kr elicited when the stimulus was applied for 2 seconds was recorded. After the generated current is stabilized, an extracellular fluid (NaCl: 135 mmol / L, KCl: 5.4 mmol / L, NaH ₂ PO ₄ : 0.3 mmol / L, in which the compound of the present invention is dissolved at a target concentration, CaCl ₂ · 2H ₂ O: 1.8 mmol / L, MgCl ₂ · 6H ₂ O: 1 mmol / L, glucose: 10 mmol / L, HEPES (4- (2-hydroxyethyl) -1-piperazine ethersulfonic acid, 4- (2- Hydroxyethyl) -1-piperazineethanesulfonic acid): 10 mmol / L, pH = 7.4) was applied to the cells for 10 minutes at room temperature. From the obtained I _Kr , the absolute value of the maximum tail current was measured using the analysis software (DataXpress ver. 1, Molecular Devices Corporation) based on the current value at the holding membrane potential. Furthermore, the inhibition rate with respect to the maximum tail current before application of the compound of the present invention was calculated, and compared with the vehicle application group (0.1% dimethyl sulfoxide solution), the effect of the compound of the present invention on I _Kr was evaluated.

Test Example 9 Powder Solubility Test An appropriate amount of the compound of the present invention is put in an appropriate container, and JP-1 solution (2.0 g of sodium chloride, water is added to 7.0 mL of hydrochloric acid to 1000 mL), JP-2 solution ( Add 500 mL of water to 500 mL of phosphate buffer solution at pH 6.8), add 20 mmol / L sodium taurocholate (TCA) / JP-2 solution (add JP-2 solution to 1.08 g of TCA to make 100 mL) 200 μL at a time. did. When the entire amount is dissolved after the addition of the test solution, the compound of the present invention is appropriately added. After sealing and shaking at 37 ° C. for 1 hour, the mixture was filtered, and 100 μL of methanol was added to 100 μL of each filtrate to perform 2-fold dilution. The dilution factor was changed as necessary. After confirming that there were no bubbles and precipitates, the mixture was sealed and shaken. The compound of the present invention was quantified using HPLC by an absolute calibration curve method.

The following formulation examples are merely illustrative and are not intended to limit the scope of the invention in any way.
Formulation Example 1 Tablet 15 mg of the present compound
Lactose 15mg
Calcium stearate 3mg
Ingredients other than calcium stearate are uniformly mixed, crushed and granulated, and dried to obtain granules of an appropriate size. Next, calcium stearate is added and compressed to form tablets.

Formulation Example 2 Capsule Compound of the present invention 10 mg
Magnesium stearate 10mg
Lactose 80mg
Are mixed uniformly to make a powder as a fine powder or powder. It is filled into a capsule container to form a capsule.

Formulation Example 3 Granules Compound of the present invention 30 g
Lactose 265g
Magnesium stearate 5g
After mixing well, compression molding, pulverizing, sizing, and sieving to make granules of appropriate size.

The compound according to the present invention can be a useful drug as a therapeutic agent for viral infections such as AIDS.

Claims

Formula (I):

(In the formula, a broken line indicates the presence or absence of a bond, provided that adjacent broken lines do not indicate the presence of a bond at the same time,
R 1 is a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted A non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
Each R 2 is independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted Alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, or substituted or unsubstituted alkynylsulfanyl,
n is 1 or 2,
R 3 represents a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic group. A heterocyclic group,
R 4 represents a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle A formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R 5 is absent, hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted unsubstituted An aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R 6 is halogen, cyano, nitro, or —Z 6 —R 61 ,
Here, Z 6 is a single bond, —O—, —S—, —NR 62 —, —CO—, —CS—, —SO 2 —, —O—CO—, —CO—O—, —NR. 62 —CO—, —CO—NR 62 —, —CH 2 —CO—NR 62 —, —NR 63 —CO—NR 62 —, —NR 62 —CS—, —CS—NR 62 —, —NR 63 — CS—NR 62 —, —NR 62 —SO 2 —, —SO 2 —NR 62 —, or —NR 63 —SO 2 —NR 62 —,
R 61 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle A formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R 62 and R 63 are each independently a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
Z 6 is -NR 62 -, - CO-NR 62 -, - CH 2 -CO-NR 62 -, - NR 63 -CO-NR 62 -, - CS-NR 62 -, - NR 63 -CS-NR 62 In the case of —, —SO 2 —NR 62 —, or —NR 63 —SO 2 —NR 62 —, R 61 and R 62 together with the adjacent nitrogen atom are substituted or unsubstituted aromatic heterocyclic A group or a substituted or unsubstituted non-aromatic heterocyclic group, and R 7 is halogen, cyano, nitro, or —Z 7 —R 71 ,
Here, Z 7 is a single bond, —O—, —S—, —NR 72 —, —CO—, —CS—, —SO 2 —, —O—CO—, —CO—O—, —NR. 72 —CO—, —CO—NR 72 —, —CH 2 —CO—NR 72 —, —NR 73 —CO—NR 72 —, —NR 72 —CS—, —CS—NR 72 —, —NR 73 — CS—NR 72 —, —NR 72 —SO 2 —, —SO 2 —NR 72 —, or —NR 73 —SO 2 —NR 72 —,
R 71 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle A formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R 72 and R 73 are each independently a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
Z 7 is -NR 72 -, - CO-NR 72 -, - CH 2 -CO-NR 72 -, - NR 73 -CO-NR 72 -, - CS-NR 72 -, - NR 73 -CS-NR 72 In the case of —, —SO 2 —NR 72 —, or —NR 73 —SO 2 —NR 72 —, R 71 and R 72 together with the adjacent nitrogen atom are substituted or unsubstituted aromatic heterocyclic May form a group or a substituted or unsubstituted non-aromatic heterocyclic group,
Here, R 1 and R 7 together with adjacent carbon atoms are substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted May form an aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R 5 and R 7 together with the adjacent nitrogen and carbon atoms may form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group ,
R 5 and R 6 may be combined with adjacent nitrogen and carbon atoms to form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group. . )
Or a pharmaceutically acceptable salt thereof (excluding the following compounds):
R 5 is absent, the compound or a pharmaceutically acceptable salt thereof according to claim 1.
The compound according to claim 2 represented by formula (II) or a pharmaceutically acceptable salt thereof.
The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, wherein R 4 is a hydrogen atom.
The compound according to any one of claims 1 to 4, wherein n is 1, or a pharmaceutically acceptable salt thereof.
The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R 2 is substituted or unsubstituted alkyloxy.
The compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, wherein R 6 is substituted or unsubstituted alkyl.
The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 7, wherein R 1 is substituted or unsubstituted alkyl.
R 7 is —Z 7 —R 71 , Z 7 is a single bond, —NR 72 —, —O—, —NR 72 —CO—, —CO—NR 72 —, —CH 2 —CO—NR 72 —. , -NR 73 -CO-NR 72 - , - NR 72 -CS -, - CS-NR 72 -, - NR 73 -CS-NR 72 -, - NR 72 -SO 2 -, - SO 2 -NR 72 - a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 8 - or -NR 73 -SO 2 -NR 72,.
R 7 is —Z 7 —R 71 , Z 7 is a single bond, —NR 72 —, —NR 72 —CO—, —CO—NR 72 —, —CH 2 —CO—NR 72 —, —NR 73 10. The compound according to claim 9 or a pharmaceutically acceptable salt thereof, which is —CO—NR 72 —, —NR 73 —CS—NR 72 —, —NR 72 —SO 2 —, or —NR 73 —SO 2 —NR 72 —. Salt.
R 71 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted nonaromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, Or the compound or its pharmaceutically acceptable salt of Claim 9 or 10 which is a substituted or unsubstituted non-aromatic heterocyclic group.
R 7 is -Z 7 -R 71, Z 7 is -NR 73 -CO-NR 72 - a and, R 71 is a substituted or unsubstituted non-aromatic carbocyclic group, claims 9-11 Or a pharmaceutically acceptable salt thereof.
R 1 and R 7 together with adjacent carbon atoms form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group. Or a pharmaceutically acceptable salt thereof.
Formula (III):

Indicated by
X is —C (R 10 ) 2 —, —NR 9 —, or —O—,
Y is —C (R 10 ) 2 —, —CO—, or —SO 2 —,
W is —C (R 10 ) 2 —, —NR 10 —, or —O—,
R 9 is halogen, cyano, nitro, or —Z 9 —R 91 ,
Here, Z 9 is a single bond, —O—, —S—, —NR 92 —, —CO—, —CS—, —SO 2 —, —O—CO—, —CO—O—, —NR. 92 —CO—, —CO—NR 92 —, —CH 2 —CO—NR 92 —, —NR 93 —CO—NR 92 —, —NR 92 —CS—, —CS—NR 92 —, —NR 93 — CS—NR 92 —, —NR 92 —SO 2 —, —SO 2 —NR 92 —, or —NR 93 —SO 2 —NR 92 —,
R 91 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle A formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R 92 and R 93 are each independently a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
Z 9 is -NR 92 -, - CO-NR 92 -, - CH 2 -CO-NR 92 -, - NR 93 -CO-NR 92 -, - CS-NR 92 -, - NR 93 -CS-NR 92 In the case of —, —SO 2 —NR 92 —, or —NR 93 —SO 2 —NR 92 —, R 91 and R 92 together with the adjacent nitrogen atom are substituted or unsubstituted aromatic heterocyclic May form a group or a substituted or unsubstituted non-aromatic heterocyclic group, and
R 10 each independently represents a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted A non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
14. A compound according to claim 13 or a pharmaceutically acceptable salt thereof.
X is —NR 9 —, R 9 is —Z 9 —R 91 , Z 9 is —CO—NR 92 —, and R 91 is a substituted or unsubstituted non-aromatic carbocyclic group. The compound according to claim 14, or a pharmaceutically acceptable salt thereof.
2. R 5 and R 7 together with the adjacent nitrogen and carbon atoms form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group. Or a pharmaceutically acceptable salt thereof.
Formulas (IV) to (VI):

Indicated by one of the
R 8 is halogen, cyano, nitro, or —Z 8 —R 81 ;
Here, Z 8 is a single bond, —O—, —S—, —NR 82 —, —CO—, —CS—, —SO 2 —, —O—CO—, —CO—O—, —NR. 82 —CO—, —CO—NR 82 —, —CH 2 —CO—NR 82 —, —NR 83 —CO—NR 82 —, —NR 82 —CS—, —CS—NR 82 —, —NR 83 — CS—NR 82 —, —NR 82 —SO 2 —, —SO 2 —NR 82 —, or —NR 83 —SO 2 —NR 82 —,
R 81 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle A formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
R 82 and R 83 are each independently a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
Z 8 is -NR 82 -, - CO-NR 82 -, - CH 2 -CO-NR 82 -, - NR 83 -CO-NR 82 -, - CS-NR 82 -, - NR 83 -CS-NR 82 In the case of —, —SO 2 —NR 82 —, or —NR 83 —SO 2 —NR 82 —, R 81 and R 82 together with the adjacent nitrogen atom are substituted or unsubstituted aromatic heterocyclic May form a group or a substituted or unsubstituted non-aromatic heterocyclic group,
The compound according to claim 16 or a pharmaceutically acceptable salt thereof.
The compound according to any of claims 1 to 17, wherein R 3 is substituted or unsubstituted phenyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted chromanyl, or substituted or unsubstituted benzomorpholinyl. Or a pharmaceutically acceptable salt thereof.
R 1 is substituted or unsubstituted alkyl, R 2 is substituted or unsubstituted alkyloxy, n is 1, and R 3 is substituted or unsubstituted phenyl, substituted or unsubstituted cycloalkenyl, substituted Or unsubstituted chromanyl, or substituted or unsubstituted benzomorpholinyl, R 4 is a hydrogen atom, R 5 is absent, and R 6 is substituted or unsubstituted alkyl. 12. The compound according to any one of 11 or a pharmaceutically acceptable salt thereof.
R 1 and R 7 together with the adjacent carbon atom form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group, and R 2 is substituted or unsubstituted And n is 1, R 3 is substituted or unsubstituted phenyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted chromanyl, or substituted or unsubstituted benzomorpholinyl, The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 7, wherein R 4 is a hydrogen atom, R 5 is not present, and R 6 is a substituted or unsubstituted alkyl.
R 1 is substituted or unsubstituted alkyl, R 2 is substituted or unsubstituted alkyloxy, n is 1, and R 3 is substituted or unsubstituted phenyl, substituted or unsubstituted cycloalkenyl, substituted Or unsubstituted chromanyl, or substituted or unsubstituted benzomorpholinyl, R 4 is a hydrogen atom, and R 5 and R 7 are substituted or unsubstituted together with the adjacent nitrogen and carbon atoms. The compound according to claim 1, which forms an aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group, and R 6 is substituted or unsubstituted alkyl, or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition comprising the compound according to any one of claims 1 to 21 or a pharmaceutically acceptable salt thereof.
The pharmaceutical composition according to claim 22, which has an anti-HIV action.