WO2013157622A1 - Hiv replication inhibitor - Google Patents

Hiv replication inhibitor Download PDF

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Publication number
WO2013157622A1
WO2013157622A1 PCT/JP2013/061575 JP2013061575W WO2013157622A1 WO 2013157622 A1 WO2013157622 A1 WO 2013157622A1 JP 2013061575 W JP2013061575 W JP 2013061575W WO 2013157622 A1 WO2013157622 A1 WO 2013157622A1
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substituted
unsubstituted
group
aromatic heterocyclic
compound
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PCT/JP2013/061575
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French (fr)
Japanese (ja)
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杉山　修一
俊行 秋山
善之 垰田
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塩野義製薬株式会社
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Publication of WO2013157622A1 publication Critical patent/WO2013157622A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Definitions

  • the present invention relates to a novel compound having an antiviral action, and more particularly to an anti-HIV drug.
  • HIV human immunodeficiency virus
  • AIDS acquired immunodeficiency syndrome
  • 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.
  • Patent Document 21 International Application PCT / JP2012 / 0775544, Japanese Patent Application No. 2013-016433, Japanese Patent Application No. 2013-071415.
  • 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.
  • 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
  • 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
  • antiviral drugs eg, antiretroviral drugs, anti-HIV
  • 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 or
  • 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-ar
  • 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 —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 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
  • R 72 and R 73 are each independently 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
  • R 72 and R 73 are each independently a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted
  • 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
  • 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 ,
  • Z 9 is a single bond, —O—, —S—, —NR 92 —, —CO—, —CS—, —SO 2 —, —O—CO—, —CO—O—, —NR.
  • 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
  • R 8 Indicated by one of the R 8 is 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.
  • 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
  • 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
  • R 4 is a hydrogen atom
  • R 5 is absent
  • R 6 is a substituted or unsubstituted alkyl, or a pharmaceutically acceptable salt thereof Salt
  • R 1 is substituted or unsubstituted alkyl
  • R 2 is substituted or unsubstituted alkyloxy
  • n 1, and R 3 is substituted or unsubstituted
  • 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).
  • viruses particularly HIV (eg, HIV-1) and its resistant viruses. Therefore, it is useful for prevention or treatment of viral infections (eg AIDS).
  • 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.
  • alkyl examples 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.
  • alkenyl include 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • bicyclic aromatic heterocyclic group examples 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.
  • aromatic heterocyclic group having 3 or more rings examples 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.
  • 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.
  • non-aromatic heterocyclic group having two or more rings examples 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.
  • 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.
  • alkenyl 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.
  • 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.
  • alkenyl 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.
  • 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.
  • 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.
  • alkynylimino 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.
  • 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.
  • alkenylcarbonylimino 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.
  • alkynylcarbonylimino 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.
  • alkenyloxyimino 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.
  • alkynyloxyimino ethynyloxyimino, propynyloxyimino and the like can be mentioned.
  • Alkylcarbonyloxy means a group in which the above “alkylcarbonyl” is bonded to an oxygen atom.
  • 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.
  • alkenylcarbonyl ethylenylcarbonyloxy, propenylcarbonyloxy and the like can be mentioned.
  • Alkynylcarbonyloxy means a group in which the above “alkynylcarbonyl” is bonded to an oxygen atom.
  • alkynylcarbonyloxy 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.
  • 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.
  • alkenyl 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.
  • alkynylsulfanyl 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.
  • alkenyl 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.
  • 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
  • “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
  • aromatic carbocyclic alkyl examples 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
  • “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”. .
  • pyridylmethyl furanylmethyl, imidazolylmethyl, indolylmethyl, benzothiophenylmethyl, oxazolylmethyl, isoxazolylmethyl, thiazolylmethyl, isothiazolylmethyl, pyrazolylmethyl, isopyrazolylmethyl, pyrrolidinylmethyl, benz Oxazolylmethyl, group shown below
  • Non-aromatic heterocyclic alkyl means alkyl substituted with one or more of the above “non-aromatic heterocyclic groups”.
  • the alkyl portion is substituted with the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group” and / or “aromatic heterocyclic group”.
  • non-aromatic heterocyclic alkyl For example, tetrahydropyranylmethyl, morpholinylethyl, piperidinylmethyl, piperazinylmethyl, groups shown below
  • “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
  • 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
  • “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.
  • Non-aromatic heterocyclic alkyloxy means alkyloxy substituted with one or more of the above “non-aromatic heterocyclic groups”.
  • 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
  • “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”.
  • “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.
  • 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”.
  • the alkyl moiety is substituted with the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group” and / or “aromatic heterocyclic group”.
  • 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
  • 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
  • “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.
  • pyridylmethyloxycarbonyl furanylmethyloxycarbonyl, imidazolylmethyloxycarbonyl, indolylmethyloxycarbonyl, benzothiophenylmethyloxycarbonyl, oxazolylmethyloxycarbonyl, isoxazolylmethyloxycarbonyl, thiazolylmethyl Oxycarbonyl, isothiazolylmethyloxycarbonyl, pyrazolylmethyloxycarbonyl, isopyrazolylmethyloxycarbonyl, pyrrolidinylmethyloxycarbonyl, benzoxazolylmethyloxycarbonyl, groups shown below
  • Non-aromatic heterocyclic alkyloxycarbonyl means alkyloxycarbonyl substituted with one or more of the above “non-aromatic heterocyclic groups”.
  • the alkyl moiety is substituted with the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group” and / or “aromatic heterocyclic group”.
  • non-aromatic heterocyclic alkyloxycarbonyl For example, tetrahydropyranylmethyloxy, morpholinylethyloxy, piperidinylmethyloxy, piperazinylmethyloxy, groups shown below
  • “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
  • Non-aromatic carbocyclic alkyloxyalkyl means alkyloxyalkyl substituted with one or more of the above “non-aromatic carbocyclic groups”.
  • 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
  • “Aromatic heterocyclic alkyloxyalkyl” means alkyloxyalkyl substituted with one or more of the above “aromatic heterocyclic groups”.
  • 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”.
  • pyridylmethyloxymethyl furanylmethyloxymethyl, imidazolylmethyloxymethyl, indolylmethyloxymethyl, benzothiophenylmethyloxymethyl, oxazolylmethyloxymethyl, isoxazolylmethyloxymethyl, thiazolylmethyl Oxymethyl, isothiazolylmethyloxymethyl, pyrazolylmethyloxymethyl, isopyrazolylmethyloxymethyl, pyrrolidinylmethyloxymethyl, benzoxazolylmethyloxymethyl, groups shown below
  • Non-aromatic heterocyclic alkyloxyalkyl means alkyloxyalkyl substituted with one or more of the above “non-aromatic heterocyclic groups”.
  • “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”.
  • non-aromatic heterocyclic alkyloxyalkyl substituted with “aromatic heterocyclic group”. For example, tetrahydropyranylmethyloxymethyl, morpholinylethyloxymethyl, piperidinylmethyloxymethyl, piperazinylmethyloxymethyl, groups shown below
  • “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.
  • 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.
  • aromatic heterocyclic alkyl 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.
  • tetrahydropyranylmethylamino, morpholinylethylamino, piperidinylmethylamino, piperazinylmethylamino and the like can be mentioned.
  • 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.
  • 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.
  • 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.
  • phenylsulfanyl and naphthylsulfanyl examples thereof include phenylsulfanyl and naphthylsulfanyl.
  • “Aromatic carbocyclic sulfonyl” means a group in which “aromatic carbocycle” is bonded to a sulfonyl group.
  • aromatic carbocycle a group in which “aromatic carbocycle” is bonded to a sulfonyl group.
  • phenylsulfonyl, naphthylsulfonyl and the like can be mentioned.
  • Non-aromatic carbocyclic oxy means a group in which “non-aromatic carbocycle” is bonded to an oxygen atom.
  • 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.
  • Non-aromatic carbocycle carbonyl means a group in which “non-aromatic carbocycle” is bonded to a carbonyl group.
  • non-aromatic carbocyclic oxycarbonyl means a group in which the above “non-aromatic carbocyclic oxy” is bonded to a carbonyl group.
  • cyclopropyloxycarbonyl, cyclohexyloxycarbonyl, cyclohexenyloxycarbonyl and the like can be mentioned.
  • 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.
  • 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.
  • 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.
  • “Aromatic heterocycle carbonyl” means a group in which “aromatic heterocycle” is bonded to a carbonyl group.
  • “Aromatic heterocyclic oxycarbonyl” means a group in which the above “aromatic heterocyclic oxy” is bonded to a carbonyl group.
  • 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.
  • 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.
  • pyridylsulfanyl, oxazolylsulfanyl and the like can be mentioned.
  • “Aromatic heterocycle sulfonyl” means a group in which “aromatic heterocycle” is bonded to a sulfonyl group.
  • pyridylsulfonyl, oxazolylsulfonyl and the like can be mentioned.
  • Non-aromatic heterocyclic oxy means a group in which “non-aromatic heterocyclic” is bonded to an oxygen atom.
  • 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.
  • Non-aromatic heterocyclic carbonyl means a group in which “non-aromatic heterocyclic” is bonded to a carbonyl group.
  • piperidinylcarbonyl, tetrahydrofurylcarbonyl and the like can be mentioned.
  • non-aromatic heterocyclic oxycarbonyl means a group in which the above “non-aromatic heterocyclic oxy” is bonded to a carbonyl group.
  • piperidinyloxycarbonyl, tetrahydrofuryloxycarbonyl and the like can be mentioned.
  • 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.
  • 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.
  • 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.
  • piperidinylsulfonyl, tetrahydrofurylsulfonyl and the like can be mentioned.
  • 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, alkeny
  • 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, alkyl
  • 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.
  • 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
  • a spiro ring may be formed together with cycloalkane, cycloalkene, cycloalkyne, oxirane, oxetane, thiirane and the like.
  • 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 Til
  • 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.
  • 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,
  • 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.
  • 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 unsub
  • 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.
  • 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.
  • 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.
  • 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 I 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 alky
  • Z 7 is more preferably a single bond, —O—, —NR 72 —, —NR 72 —CO—, —CO—NR 72 —, —CH 2 —CO—NR 72 —, —NR 73.
  • 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.
  • 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.
  • 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.
  • 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
  • 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
  • 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.
  • 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 .
  • 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 —).
  • 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 heteroaryl
  • 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 —.
  • X is —NR 9 —
  • Y is —CH 2 — or —CO—
  • 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 unsub
  • 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 .
  • Z 9 is more preferably a single bond, —CO—, —CS—, —SO 2 —, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —.
  • 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.
  • 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.
  • 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 I 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.
  • R 10 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.
  • 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).
  • the compound of formula (I) is preferably of formula (IV ) To (VI).
  • 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 alkeny
  • substituents are exemplified by halogen, alkyl, haloalkyl, alkoxy and the like.
  • 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.
  • 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 I 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.
  • 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).
  • 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
  • R 1 is substituted or unsubstituted alkyl
  • 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
  • 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 substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non
  • 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-
  • 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
  • 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
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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 8 is a substituted or unsubstituted aromatic carbocyclic group.
  • R 1 is substituted or unsubstituted alkyl
  • 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
  • R 6 is substituted or unsubstituted alkyl
  • R 8 is a substituted or unsubstituted aromatic carbocyclic group.
  • 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 8 is a substituted or unsubstituted aromatic carbocyclic group.
  • R 1 is substituted or unsubstituted alkyl
  • 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
  • R 6 is substituted or unsubstituted alkyl
  • R 8 is a substituted or unsubstituted aromatic carbocyclic group.
  • R 8 does not exist for the compound of the formula (VI).
  • R 1 is substituted or unsubstituted alkyl
  • R 2 is substituted or unsubstituted alkyloxy
  • n is 1
  • 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
  • R 6 is A compound that is substituted or unsubstituted alkyl
  • R 7 is —Z 7 —R 71 (Z 7 is —NH—CO—NH—; R 71 is a substituted or unsubstituted aromatic carbocyclic group) .
  • 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
  • R 6 is A substituted or unsubstituted alkyl
  • R 7 is —Z 7 —R 71 (Z 7 is —NH—CO—NH—; R 71 is a substituted or unsubstituted non-aromatic carbocyclic group).
  • 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).
  • 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).
  • R 4 is a hydrogen atom. It is a point to have.
  • 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.
  • 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.
  • 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.
  • 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.
  • a suitable catalyst such as Pd / C
  • 14 C-labeled compounds can be prepared by using raw materials having 14 C carbon.
  • 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, fum
  • 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.
  • a solvate for example, a hydrate etc.
  • 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).
  • solvent molecules for example, water molecules
  • the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof 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.
  • 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.
  • the compound represented by formula (I) or a pharmaceutically acceptable salt thereof has a hydroxyl group
  • prodrugs such as acyloxy derivatives and sulfonyloxy derivatives produced by reacting sulfonyl anhydride and mixed anhydride or by reacting with a condensing agent.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • a base such as potassium carbonate, sodium carbonate, potassium phosphate and boronic acid a7, or boronic ester
  • a catalyst such as dibenzylideneacetone palladium, palladium acetate, dichlorobistriphenylphosphin
  • 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.
  • a catalyst such as palladium carbon, palladium hydroxide, Raney nickel
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • a base such as potassium carbonate, calcium carbonate, potassium phosphate and the like and R 4 -I, R 4 -Br, R 4.
  • 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.
  • 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.
  • 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.
  • compound f9 can be obtained in the same manner as in the sixth step in 1) above.
  • compound f10 can be obtained in the same manner as in the seventh step in 1) above.
  • 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.
  • compound f14 can be obtained in the same manner as in the sixth step in 1) above.
  • 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.
  • 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.
  • 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.
  • 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.
  • compound n10 can be obtained in the same manner as in the fourth step in 1) above.
  • compound N-1 can be obtained in the same manner as in the fifth step in 1) above.
  • compound N-2 can be obtained in the same manner as in the eleventh step in 1) 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.
  • 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.
  • compound p4 can be obtained in the same manner as in the eighth step in 14) above.
  • compound p6 can be obtained in the same manner as in the fourth step in 1) above.
  • compound P-1 can be obtained in the same manner as in the fifth step in 1) above.
  • compound P-2 can be obtained in the same manner as in the eleventh step in 1) above.
  • Second 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.
  • compound Q-2 can be obtained in the same manner as in the eleventh step in 1) 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.
  • 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.
  • 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.
  • 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.
  • Second 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.
  • 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.
  • a base such as potassium carbonate, sodium carbonate, potassium phosphate, boronic acid or boronic acid ester
  • 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
  • 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.
  • 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.
  • the compound of the present invention 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.
  • CYP enzymes eg, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, etc.
  • CYP3A4 CYP3A4
  • CYP3A4 CYP3A4
  • e) Not mutagenic.
  • f) Low cardiovascular risk.
  • h) It shows a strong medicinal effect against resistant viruses.
  • i) It is difficult to express resistant viruses.
  • 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.
  • a commonly used dosage form such as tablets, granules, powders, capsules and the like according to conventional methods.
  • 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.
  • отное отное отное отное отное о ⁇ ное ком ⁇ онентs 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.
  • a concomitant drug for the purpose of enhancing the action of the compound or reducing the dose of the compound.
  • 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.
  • 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.
  • 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.
  • 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.
  • reverse transcriptase inhibitor examples include AZT, 3TC, didanosine, sarcitabine, sanylvudine, abacavir, tenofovir, emtricitabine, nevirabin, efavirenz, coupleravirin, etravirin, delavirdine and the like.
  • protease inhibitors examples include indinavir, ritonavir, saquinavir, nelfinavir, amprenavir, atanazavir, lopinavir, fosamprenavir, darunavir, atazanavir, branavir, tipranavir and the like.
  • integrase inhibitor examples include raltegravir, elvitegravir, JTK-656, dolutegravir, S-265744 and the like.
  • anti-HIV drugs include, for example, invasion inhibitors such as maraviroc and bicrivirok, and fusion inhibitors such as enfuvirtide, sifuvirtide, and albuvirtide.
  • Example 11 The following compounds were synthesized according to the above examples.
  • R 1 is methyl, R 2 is tert-butyloxy, n is 1, R 4 is a hydrogen atom, and R 6 is methyl.
  • Example 12 According to the above Example, the following compounds can be synthesized.
  • R 3 is any of the following groups.
  • 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.
  • each anti-human immunodeficiency virus active substance was diluted with the above culture medium to a predetermined concentration, and 50 ⁇ L was dispensed into a 96-well microplate.
  • 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.
  • reaction conditions were as follows: substrate, 0.5 ⁇ mol / L ethoxyresorufin (CYP1A2), 100 ⁇ mol / L tolbutamide (CYP2C9), 50 ⁇ mol / L S-mephenytoin (CYP2C19), 5 ⁇ mol / L dextromethorphan (CYP2D6), 1 ⁇ mol / 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 ⁇ mol / L (4 points) .
  • resorufin CYP1A2 metabolite
  • CYP1A2 metabolite resorufin in the centrifugation supernatant was quantified with a fluorescent multi-label counter
  • tolbutamide hydroxide CYP2C9 metabolite
  • mephenytoin 4 ′ hydroxide CYP2C19 metabolite
  • Dextrorphan CYP2D6 metabolite
  • terfenadine alcohol CYP3A4 metabolite
  • 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.
  • reaction conditions are as follows: substrate, 5.6 ⁇ mol / 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 ⁇ mol / 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).
  • 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.
  • 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.
  • DMSO a solvent in which the compound of the present invention was dissolved
  • 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. .
  • 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.
  • 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 ⁇ g / mL, Histidine: 0.2 ⁇ g / 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 ⁇ g / mL 4-TA Nitroquinoline-1-oxide DMSO solution, 0.25 ⁇ g / mL 2- (2-furyl) -3- (5-nitro-2-furyl) acrylamide DMSO solution for TA100 strain, TA98 under metabolic activation conditions 40 ⁇ g / mL 2-aminoanthracene DMSO solution for the strain and 20 ⁇ g / mL 2-aminoanthracene DMSO solution for the TA100 strain, respectively, and 588 ⁇ L of the test bacterial solution (498 ⁇ L of the test bacterial solution and S9 under metabolic activation conditions).
  • Intravenous administration is performed from the tail vein using a syringe with a needle.
  • 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.
  • 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.
  • 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.
  • a fully automatic patch clamp system PatchXpress 7000A, Axon Instruments Inc.
  • a +40 mV depolarization stimulus was applied for 2 seconds, followed by a ⁇ 50 mV repolarization.
  • 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.
  • the compound of the present invention was quantified using HPLC by an absolute calibration curve method.
  • 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.

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複製阻害剤HIV replication inhibitor
　本発明は、抗ウイルス作用を有する新規化合物、更に詳しくは、抗ＨＩＶ薬に関する。 The present invention relates to a novel compound having an antiviral action, and more particularly to an anti-HIV drug.
　ウイルスのなかでも、レトロウイルスの一種であるヒト免疫不全ウイルス（Ｈｕｍａｎ　Ｉｍｍｕｎｏｄｅｆｉｃｉｅｎｃｙ　Ｖｉｒｕｓ、以下ＨＩＶと略す）は、後天性免疫不全症候群（Ａｃｑｕｉｒｅｄ　ｉｍｍｕｎｏｄｅｆｉｃｉｅｎｃｙ　ｓｙｎｄｒｏｍｅ、以下エイズ（ＡＩＤＳ）と略す）の原因となることが知られている。そのエイズの治療薬としては、これまでのところ逆転写酵素阻害剤（ＡＺＴ、３ＴＣ等）、プロテアーゼ阻害剤（インディナビル等）、およびインテグラーゼ阻害剤（ラルテグラビル等）が主流であるが、腎臓障害等の副作用や耐性ウイルスの出現等の問題が判明しており、それらとは異なる作用メカニズムを有する抗ＨＩＶ薬の開発が期待されている。 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.
　また、エイズの治療においては、耐性ウイルスが容易に出現するという理由から、現在、多剤併用療法が効果的であると報告されている。抗ＨＩＶ薬としては、逆転写酵素阻害剤、プロテアーゼ阻害剤、インテグラーゼ阻害剤の３種が臨床で使用されているが、同じ作用メカニズムを有する薬剤はしばしば交叉耐性を示し、または付加的な効果を示すに過ぎず、異なった作用メカニズムの抗ＨＩＶ薬の開発が要望されている。 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.
　特許文献１には、ＨＩＶ逆転写酵素阻害剤としてカルボキシメチルベンゼン骨格を有する化合物が報告されている。また、本発明と構造が比較的類似したＨＩＶ複製阻害剤として、カルボキシメチルピリジン誘導体（特許文献２～８、１４、１９）、カルボキシメチルピリミジン誘導体（特許文献８～１１）、フェニル酢酸誘導体（特許文献１２～１３）、三環性カルボキシメチルピリジン誘導体（特許文献１５）、カルボキシメチルピリドン誘導体（特許文献１６）、置換五員環化合物（特許文献１７）および置換六員環化合物（特許文献１８）が報告されている。特許文献１８には六員環化合物が広く開示されており、特許文献２～８、１４、１９には、ピリジン誘導体が広く開示されているが、４位にカルボキシメチル構造を有するピリジン誘導体はいずれの文献にも記載されていない。 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.
　特許文献２０には、本発明と構造が比較的類似した化合物が記載されているが、抗癌薬に関する文献である。また、非特許文献１および２には、本発明と構造が比較的類似した化合物が記載されているが、合成技術に関する文献である。 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.
　さらに、本出願人らによって、ＨＩＶ複製阻害剤が特許出願されている（特許文献２１、国際出願ＰＣＴ／ＪＰ２０１２／０７７５４４号、日本国特許出願２０１３－０１６４３３号、日本国特許出願２０１３－０７１４１５号）。 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). .
国際公開２００８／０７１５８７号パンフレットInternational Publication No. 2008/071587 Pamphlet 国際公開２００７／１３１３５０号パンフレットInternational Publication No. 2007/131350 Pamphlet 国際公開２００９／０６２２８５号パンフレットInternational Publication No. 2009/062285 Pamphlet 国際公開２００９／０６２２８８号パンフレットInternational Publication No. 2009/062288 Pamphlet 国際公開２００９／０６２２８９号パンフレットInternational Publication No. 2009/062289 Pamphlet 国際公開２００９／０６２３０８号パンフレットInternational Publication No. 2009/062308 Pamphlet 国際公開２０１０／１３００３４号パンフレットInternational Publication 2010/130034 Pamphlet 国際公開２０１０／１３０８４２号パンフレットInternational Publication 2010/130842 Pamphlet 国際公開２０１１／０１５６４１号パンフレットInternational publication 2011/015641 pamphlet 国際公開２０１１／０７６７６５号パンフレットInternational Publication No. 2011-077665 Pamphlet
国際公開２０１２／０３３７３５号パンフレットInternational Publication 2012/033735 Pamphlet 国際公開２０１２／００３４９７号パンフレットInternational Publication 2012/003497 Pamphlet 国際公開２０１２／００３４９８号パンフレットInternational Publication 2012/003498 Pamphlet 国際公開２０１２／０６５９６３号パンフレットInternational Publication No. 2012/065963 Pamphlet 国際公開２０１２／０６６４４２号パンフレットInternational Publication 2012/066642 Pamphlet 国際公開２０１２／１０２９８５号パンフレットInternational Publication 2012/102985 Pamphlet 国際公開２０１２／１３７１８１号パンフレットInternational Publication 2012/137181 Pamphlet 国際公開２０１２／１４０２４３号パンフレットInternational Publication 2012/140243 Pamphlet 国際公開２０１３／０１２６４９号パンフレットInternational publication 2013/012649 pamphlet 日本国出願公開２００１－１５１７７６号Japanese Application Publication No. 2001-151777
国際公開２０１３／００２３５７号パンフレットInternational Publication 2013/002357 Pamphlet
　本発明の目的は、抗ウイルス活性を有する新規化合物を提供することにある。本発明は、より好ましくは、ＨＩＶ複製阻害作用を有する抗ＨＩＶ薬を提供する。 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.
　本発明者らは鋭意検討した結果、新規なＨＩＶ複製阻害剤を見出した。さらに、本発明化合物およびそれらを含有する医薬が、抗ウイルス薬（例：抗レトロウイルス薬、抗ＨＩＶ薬、抗ＨＴＬＶ－１（Ｈｕｍａｎ　Ｔ　ｃｅｌｌ　ｌｅｕｋｅｍｉａ　ｖｉｒｕｓ　ｔｙｐｅ　１：ヒトＴ細胞白血病ウイルス１型）薬、抗ＦＩＶ（Ｆｅｌｉｎｅ　ｉｍｍｕｎｏｄｅｆｉｃｉｅｎｃｙ　ｖｉｒｕｓ　：ネコエイズウイルス）薬、抗ＳＩＶ（Ｓｉｍｉａｎ　ｉｍｍｕｎｏｄｅｆｉｃｉｅｎｃｙ　ｖｉｒｕｓ　：サルエイズウイルス）薬）、特に抗ＨＩＶ薬、抗ＡＩＤＳ薬、またはその関連疾患の治療薬等として有用であることを見出し、以下に示す本発明を完成した。 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）式（Ｉ）： (1) Formula (I):
Figure JPOXMLDOC01-appb-C000006
（式中、破線は結合の存在または非存在を示し、ただし、隣接する破線が同時に結合の存在を示すことはなく、
Ｒ１は、水素原子、ハロゲン、シアノ、ニトロ、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
Ｒ２は、それぞれ独立して、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換のアルキルオキシ、置換若しくは非置換のアルケニルオキシ、置換若しくは非置換のアルキニルオキシ、置換若しくは非置換のアルキルスルファニル、置換若しくは非置換のアルケニルスルファニル、または置換若しくは非置換のアルキニルスルファニルであり、
ｎは、１または２であり、
Ｒ３は、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
Ｒ４は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
Ｒ５は、存在しないか、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
Ｒ６は、ハロゲン、シアノ、ニトロ、または－Ｚ６－Ｒ６１であり、
ここで、Ｚ６は、単結合、－Ｏ－、－Ｓ－、－ＮＲ６２－、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－Ｏ－ＣＯ－、－ＣＯ－Ｏ－、－ＮＲ６２－ＣＯ－、－ＣＯ－ＮＲ６２－、－ＣＨ２－ＣＯ－ＮＲ６２－、－ＮＲ６３－ＣＯ－ＮＲ６２－、－ＮＲ６２－ＣＳ－、－ＣＳ－ＮＲ６２－、－ＮＲ６３－ＣＳ－ＮＲ６２－、－ＮＲ６２－ＳＯ２－、－ＳＯ２－ＮＲ６２－、または－ＮＲ６３－ＳＯ２－ＮＲ６２－であり、
Ｒ６１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
Ｒ６２およびＲ６３は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニルであり、
Ｚ６が－ＮＲ６２－、－ＣＯ－ＮＲ６２－、－ＣＨ２－ＣＯ－ＮＲ６２－、－ＮＲ６３－ＣＯ－ＮＲ６２－、－ＣＳ－ＮＲ６２－、－ＮＲ６３－ＣＳ－ＮＲ６２－、－ＳＯ２－ＮＲ６２－、または－ＮＲ６３－ＳＯ２－ＮＲ６２－の場合は、Ｒ６１とＲ６２が隣接する窒素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良く、ならびに
Ｒ７は、ハロゲン、シアノ、ニトロ、または－Ｚ７－Ｒ７１であり、
ここで、Ｚ７は、単結合、－Ｏ－、－Ｓ－、－ＮＲ７２－、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－Ｏ－ＣＯ－、－ＣＯ－Ｏ－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７２－ＣＳ－、－ＣＳ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、－ＳＯ２－ＮＲ７２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－であり、
Ｒ７１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
Ｒ７２およびＲ７３は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニルであり、
Ｚ７が－ＮＲ７２－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＣＳ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＳＯ２－ＮＲ７２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－の場合は、Ｒ７１とＲ７２が隣接する窒素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良く、
ここで、Ｒ１とＲ７は、隣接する炭素原子と一緒になって、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基を形成しても良く、
Ｒ５とＲ７は、隣接する窒素原子および炭素原子と一緒になって、置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良く、
Ｒ５とＲ６は、隣接する窒素原子および炭素原子と一緒になって、置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良い。）
で示される化合物（以下の化合物を除く）、またはその製薬上許容される塩、
Figure JPOXMLDOC01-appb-C000006
(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):
Figure JPOXMLDOC01-appb-C000007
（２）Ｒ５が存在しない、上記（１）記載の化合物またはその製薬上許容される塩、
（３）式（ＩＩ）で示される、上記（２）記載の化合物またはその製薬上許容される塩、
Figure JPOXMLDOC01-appb-C000007
(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,
Figure JPOXMLDOC01-appb-C000008
（４）Ｒ４が水素原子である、上記（１）～（３）のいずれかに記載の化合物、またはその製薬上許容される塩、
（５）ｎが１である、上記（１）～（４）のいずれかに記載の化合物、またはその製薬上許容される塩、
（６）Ｒ２が置換若しくは非置換のアルキルオキシである、上記（１）～（５）のいずれかに記載の化合物、またはその製薬上許容される塩、
（７）Ｒ６が置換若しくは非置換のアルキルである、上記（１）～（６）のいずれかに記載の化合物、またはその製薬上許容される塩、
（８）Ｒ１が置換若しくは非置換のアルキルである、上記（１）～（７）のいずれかに記載の化合物またはその製薬上許容される塩、
（９）Ｒ７が－Ｚ７－Ｒ７１であり、Ｚ７が単結合、－Ｏ－、－ＮＲ７２－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７２－ＣＳ－、－ＣＳ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、－ＳＯ２－ＮＲ７２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－である、上記（１）～（８）のいずれかに記載の化合物またはその製薬上許容される塩、
（１０）Ｒ７が－Ｚ７－Ｒ７１であり、Ｚ７が単結合、－ＮＲ７２－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－である、上記（９）記載の化合物またはその製薬上許容される塩、
（１１）Ｒ７１が水素原子、置換若しくは非置換のアルキル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基である、上記（９）または（１０）記載の化合物またはその製薬上許容される塩、
（１２）Ｒ７が－Ｚ７－Ｒ７１であり、Ｚ７が－ＮＲ７３－ＣＯ－ＮＲ７２－であり、Ｒ７１が置換若しくは非置換の非芳香族炭素環式基である、上記（９）～（１１）のいずれかに記載の化合物またはその製薬上許容される塩、
（１３）Ｒ１とＲ７が隣接する炭素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成する、上記（１）～（７）のいずれかに記載の化合物またはその製薬上許容される塩、
（１４）式（ＩＩＩ）：
Figure JPOXMLDOC01-appb-C000008
(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):
Figure JPOXMLDOC01-appb-C000009
で示され、
Ｘは、－Ｃ（Ｒ１０）２－、－ＮＲ９－、または－Ｏ－であり、
Ｙは、－Ｃ（Ｒ１０）２－、－ＣＯ－、または－ＳＯ２－であり、
Ｗは、－Ｃ（Ｒ１０）２－、－ＮＲ１０－、または－Ｏ－であり、
Ｒ９は、ハロゲン、シアノ、ニトロ、または－Ｚ９－Ｒ９１であり、
ここで、Ｚ９は、単結合、－Ｏ－、－Ｓ－、－ＮＲ９２－、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－Ｏ－ＣＯ－、－ＣＯ－Ｏ－、－ＮＲ９２－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＨ２－ＣＯ－ＮＲ９２－、－ＮＲ９３－ＣＯ－ＮＲ９２－、－ＮＲ９２－ＣＳ－、－ＣＳ－ＮＲ９２－、－ＮＲ９３－ＣＳ－ＮＲ９２－、－ＮＲ９２－ＳＯ２－、－ＳＯ２－ＮＲ９２－、または－ＮＲ９３－ＳＯ２－ＮＲ９２－であり、
Ｒ９１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
Ｒ９２およびＲ９３は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニルであり、
Ｚ９が－ＮＲ９２－、－ＣＯ－ＮＲ９２－、－ＣＨ２－ＣＯ－ＮＲ９２－、－ＮＲ９３－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、－ＮＲ９３－ＣＳ－ＮＲ９２－、－ＳＯ２－ＮＲ９２－、または－ＮＲ９３－ＳＯ２－ＮＲ９２－の場合は、Ｒ９１とＲ９２が隣接する窒素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良く、ならびに、
Ｒ１０は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基である、
上記（１３）記載の化合物またはその製薬上許容される塩、
（１５）Ｘが－ＮＲ９－であり、Ｒ９が－Ｚ９－Ｒ９１であり、Ｚ９が－ＣＯ－ＮＲ９２－であり、Ｒ９１が置換若しくは非置換の非芳香族炭素環式基である、上記（１４）記載の化合物またはその製薬上許容される塩、
（１６）Ｒ５とＲ７が隣接する窒素原子および炭素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成する、上記（１）記載の化合物またはその製薬上許容される塩、
（１７）式（ＩＶ）～（ＶＩ）：
Figure JPOXMLDOC01-appb-C000009
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):
Figure JPOXMLDOC01-appb-C000010
のいずれかで示され、
Ｒ８は、ハロゲン、シアノ、ニトロ、または－Ｚ８－Ｒ８１であり、
ここで、Ｚ８は、単結合、－Ｏ－、－Ｓ－、－ＮＲ８２－、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－Ｏ－ＣＯ－、－ＣＯ－Ｏ－、－ＮＲ８２－ＣＯ－、－ＣＯ－ＮＲ８２－、－ＣＨ２－ＣＯ－ＮＲ８２－、－ＮＲ８３－ＣＯ－ＮＲ８２－、－ＮＲ８２－ＣＳ－、－ＣＳ－ＮＲ８２－、－ＮＲ８３－ＣＳ－ＮＲ８２－、－ＮＲ８２－ＳＯ２－、－ＳＯ２－ＮＲ８２－、または－ＮＲ８３－ＳＯ２－ＮＲ８２－であり、
Ｒ８１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
Ｒ８２およびＲ８３は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニルであり、
Ｚ８が－ＮＲ８２－、－ＣＯ－ＮＲ８２－、－ＣＨ２－ＣＯ－ＮＲ８２－、－ＮＲ８３－ＣＯ－ＮＲ８２－、－ＣＳ－ＮＲ８２－、－ＮＲ８３－ＣＳ－ＮＲ８２－、－ＳＯ２－ＮＲ８２－、または－ＮＲ８３－ＳＯ２－ＮＲ８２－の場合は、Ｒ８１とＲ８２が隣接する窒素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良い、
上記（１６）記載の化合物またはその製薬上許容される塩、
（１８）Ｒ３が置換若しくは非置換のフェニル、置換若しくは非置換のシクロアルケニル、置換若しくは非置換のクロマニル、または置換若しくは非置換のベンゾモルホリニルである、上記（１）～（１７）のいずれかに記載の化合物またはその製薬上許容される塩、
（１９）Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換のフェニル、置換若しくは非置換のシクロアルケニル、置換若しくは非置換のクロマニル、または置換若しくは非置換のベンゾモルホリニルであり、Ｒ４が水素原子であり、Ｒ５が存在せず、Ｒ６が置換若しくは非置換のアルキルである、上記（１）～（１１）のいずれかに記載の化合物またはその製薬上許容される塩、
（２０）Ｒ１とＲ７が隣接する炭素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成し、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換のフェニル、置換若しくは非置換のシクロアルケニル、置換若しくは非置換のクロマニル、または置換若しくは非置換のベンゾモルホリニルであり、Ｒ４が水素原子であり、Ｒ５が存在せず、Ｒ６が置換若しくは非置換のアルキルである、上記（１）～（７）のいずれかに記載の化合物またはその製薬上許容される塩、
（２１）Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換のフェニル、置換若しくは非置換のシクロアルケニル、置換若しくは非置換のクロマニル、または置換若しくは非置換のベンゾモルホリニルであり、Ｒ４が水素原子であり、Ｒ５とＲ７が隣接する窒素原子および炭素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成し、Ｒ６が置換若しくは非置換のアルキルである、上記（１）記載の化合物またはその製薬上許容される塩、
（２２）上記（１）～（２１）のいずれかに記載の化合物またはその製薬上許容される塩を含有する医薬組成物、
（２３）抗ＨＩＶ作用を有する、上記（２２）記載の医薬組成物、
（２４）抗ウイルス的に有効量の上記（１）～（２１）のいずれかに記載の化合物をヒトに投与することを特徴とする、ウイルス感染症の治療方法、
（２５）ＨＩＶ感染症に対する、上記（２４）記載の治療方法、
（２６）ウイルス感染症の治療のための、上記（１）～（２１）のいずれかに記載の化合物またはその製薬上許容される塩、
（２７）ＨＩＶ感染症の治療のための、上記（２６）記載の化合物またはその製薬上許容される塩、
（２８）ウイルス感染症治療剤の製造のための、上記（１）～（２１）のいずれかに記載の化合物またはその製薬上許容される塩の使用、
（２９）ＨＩＶ感染症治療剤の製造のための、上記（２８）記載の使用。
Figure JPOXMLDOC01-appb-C000010
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.
　本発明化合物は、ウイルス、特にＨＩＶ（例：ＨＩＶ－１）やその耐性ウイルスに対して複製阻害活性を有する。よって、ウイルス感染症（例：エイズ）等の予防または治療に有用である。 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).
　以下に本明細書において用いられる各用語の意味を説明する。各用語は特に断りのない限り、単独で用いられる場合も、または他の用語と組み合わせて用いられる場合も、同一の意味で用いられる。 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.
　「ハロゲン」とは、フッ素原子、塩素原子、臭素原子、およびヨウ素原子を包含する。特にフッ素原子、および塩素原子が好ましい。 “Halogen” includes fluorine atom, chlorine atom, bromine atom, and iodine atom. In particular, a fluorine atom and a chlorine atom are preferable.
　「アルキル」とは、炭素数１～１５、好ましくは炭素数１～１０、より好ましくは炭素数１～６、さらに好ましくは炭素数１～４の直鎖または分枝状の炭化水素基を包含する。例えば、メチル、エチル、ｎ－プロピル、イソプロピル、ｎ－ブチル、イソブチル、ｓｅｃ－ブチル、ｔｅｒｔ－ブチル、ｎ－ペンチル、イソペンチル、ネオペンチル、ｎ－ヘキシル、イソヘキシル、ｎ－へプチル、イソヘプチル、ｎ－オクチル、イソオクチル、ｎ－ノニル、ｎ－デシル等が挙げられる。
　「アルキル」の好ましい態様として、メチル、エチル、ｎ－プロピル、イソプロピル、ｎ－ブチル、イソブチル、ｓｅｃ－ブチル、ｔｅｒｔ－ブチル、ｎ－ペンチルが挙げられる。さらに好ましい態様として、メチル、エチル、ｎ－プロピル、イソプロピル、ｔｅｒｔ－ブチルが挙げられる。 “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.
　「アルケニル」とは、任意の位置に１以上の二重結合を有する、炭素数２～１５、好ましくは炭素数２～１０、より好ましくは炭素数２～６、さらに好ましくは炭素数２～４の直鎖または分枝状の炭化水素基を包含する。例えば、ビニル、アリル、プロペニル、イソプロペニル、ブテニル、イソブテニル、プレニル、ブタジエニル、ペンテニル、イソペンテニル、ペンタジエニル、ヘキセニル、イソヘキセニル、ヘキサジエニル、ヘプテニル、オクテニル、ノネニル、デセニル、ウンデセニル、ドデセニル、トリデセニル、テトラデセニル、ペンタデセニル等が挙げられる。
　「アルケニル」の好ましい態様として、ビニル、アリル、プロペニル、イソプロペニル、ブテニルが挙げられる。 “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.
　「アルキニル」とは、任意の位置に１以上の三重結合を有する、炭素数２～１０、好ましくは炭素数２～８、さらに好ましくは炭素数２～６、さらに好ましくは炭素数２～４の直鎖または分枝状の炭化水素基を包含する。例えば、エチニル、プロピニル、ブチニル、ペンチニル、ヘキシニル、ヘプチニル、オクチニル、ノニニル、デシニル等を包含する。これらはさらに任意の位置に二重結合を有していてもよい。
　「アルキニル」の好ましい態様として、エチニル、プロピニル、ブチニル、ペンチニルが挙げられる。 “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.
　「アルキレン」とは、炭素数１～１５、好ましくは炭素数１～１０、より好ましくは炭素数１～６、さらに好ましくは炭素数１～４の直鎖または分枝状の２価の炭化水素基を包含する。例えば、メチレン、エチレン、トリメチレン、プロピレン、テトラメチレン、ペンタメチレン、ヘキサメチレン等が挙げられる。 “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.
　「アルケニレン」とは、任意の位置に１以上の二重結合を有する、炭素数２～１５、好ましくは炭素数２～１０、より好ましくは炭素数２～６、さらに好ましくは炭素数２～４の直鎖または分枝状の２価の炭化水素基を包含する。例えば、ビニレン、プロペニレン、ブテニレン、ペンテニレン等が挙げられる。 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.
　「アルキニレン」とは、任意の位置に１以上の三重結合を有する、炭素数２～１５、好ましくは炭素数２～１０、より好ましくは炭素数２～６、さらに好ましくは炭素数２～４の直鎖または分枝状の２価の炭化水素基を包含する。これらはさらに任意の位置に二重結合を有していてもよい。例えば、エチニレン、プロピニレン、ブチニレン、ペンチニレン、ヘキシニレン等が挙げられる。 “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.
　「芳香族炭素環式基」とは、単環または２環以上の、芳香族炭化水素基を意味する。例えば、フェニル、ナフチル、アントリル、フェナントリル等が挙げられる。
　「芳香族炭素環式基」の好ましい態様として、フェニルが挙げられる。 “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.
　「非芳香族炭素環式基」とは、単環または２環以上の、非芳香族飽和炭化水素基または非芳香族不飽和炭化水素基を意味する。２環以上の非芳香族炭素環式基は、単環または２環以上の非芳香族炭素環式基に、上記「芳香族炭素環式基」における環が縮合したものも包含する。
　さらに、「非芳香族炭素環式基」は、以下のように架橋している基、またはスピロ環を形成する基も包含する。 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.
Figure JPOXMLDOC01-appb-C000011
　単環の非芳香族炭素環式基としては、炭素数３～１６が好ましく、より好ましくは炭素数３～１２、さらに好ましくは炭素数４～８である。例えば、シクロアルキル、シクロアルケニル等が挙げられる。
　「シクロアルキル」としては、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシル、シクロヘプチル、シクロオクチル、シクロノニル、シクロデシル等が挙げられる。
　「シクロアルケニル」としては、シクロプロペニル、シクロブテニル、シクロペンテニル、シクロヘキセニル、シクロヘプテニル、シクロヘキサジエニル等が挙げられる。
　２環以上の非芳香族炭素環式基としては、例えば、インダニル、インデニル、アセナフチル、テトラヒドロナフチル、フルオレニル、ジヒドロインデニル等が挙げられる。
Figure JPOXMLDOC01-appb-C000011
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.
　「芳香族複素環式基」とは、Ｏ、ＳおよびＮから任意に選択される同一または異なるヘテロ原子を環内に１以上有する、単環または２環以上の、芳香族環式基を意味する。
　２環以上の芳香族複素環式基は、単環または２環以上の芳香族複素環式基に、上記「芳香族炭素環式基」における環が縮合したものも包含する。
　単環の芳香族複素環式基としては、５～８員が好ましく、より好ましくは５員または６員である。例えば、ピロリル、イミダゾリル、ピラゾリル、ピリジル、ピリダジニル、ピリミジニル、ピラジニル、トリアゾリル、トリアジニル、テトラゾリル、フリル、チエニル、イソオキサゾリル、オキサゾリル、オキサジアゾリル、イソチアゾリル、チアゾリル、チアジアゾリル等が挙げられる。
　２環の芳香族複素環式基としては、例えば、インドリル、イソインドリル、インダゾリル、インドリジニル、キノリニル、イソキノリニル、シンノリニル、フタラジニル、キナゾリニル、ナフチリジニル、キノキサリニル、プリニル、プテリジニル、ベンズイミダゾリル、ベンズイソオキサゾリル、ベンズオキサゾリル、ベンズオキサジアゾリル、ベンズイソチアゾリル、ベンゾチアゾリル、ベンゾチアジアゾリル、ベンゾフリル、イソベンゾフリル、ベンゾチエニル、ベンゾトリアゾリル、イミダゾピリジル、トリアゾロピリジル、イミダゾチアゾリル、ピラジノピリダジニル、オキサゾロピリジル、チアゾロピリジル等が挙げられる。
　３環以上の芳香族複素環式基としては、例えば、カルバゾリル、アクリジニル、キサンテニル、フェノチアジニル、フェノキサチイニル、フェノキサジニル、ジベンゾフリル等が挙げられる。 “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.
　「非芳香族複素環式基」とは、Ｏ、ＳおよびＮから任意に選択される同一または異なるヘテロ原子を環内に１以上有する、単環または２環以上の、非芳香族環式基を意味する。
　２環以上の非芳香族複素環式基は、単環または２環以上の非芳香族複素環式基に、上記「芳香族炭素環式基」、「非芳香族炭素環式基」、および／または「芳香族複素環式基」におけるそれぞれの環が縮合したものも包含する。
　さらに、「非芳香族複素環式基」は、以下のように架橋している基、またはスピロ環を形成する基も包含する。 "Non-aromatic 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.
Figure JPOXMLDOC01-appb-C000012
　単環の非芳香族複素環式基としては、３～８員が好ましく、より好ましくは５員または６員である。例えば、ジオキサニル、チイラニル、オキシラニル、オキセタニル、オキサチオラニル、アゼチジニル、チアニル、チアゾリジニル、ピロリジニル、ピロリニル、イミダゾリジニル、イミダゾリニル、ピラゾリジニル、ピラゾリニル、ピペリジル、ピペラジニル、モルホリニル、モルホリノ、チオモルホリニル、チオモルホリノ、ジヒドロピリジル、テトラヒドロピリジル、テトラヒドロフリル、テトラヒドロピラニル、ジヒドロチアゾリル、テトラヒドロチアゾリル、テトラヒドロイソチアゾリル、ジヒドロオキサジニル、ヘキサヒドロアゼピニル、テトラヒドロジアゼピニル、テトラヒドロピリダジニル、ヘキサヒドロピリミジニル、ジオキソラニル、ジオキサジニル、アジリジニル、ジオキソリニル、オキセパニル、チオラニル、チイニル、チアジニル等が挙げられる。
　２環以上の非芳香族複素環式基としては、例えば、インドリニル、イソインドリニル、クロマニル、イソクロマニル、ジヒドロベンゾフリル、ベンゾジオキソリル、ベンゾジオキサニル、ベンゾモルホリニル等が挙げられる。
Figure JPOXMLDOC01-appb-C000012
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.
　「ヒドロキシアルキル」とは、１以上のヒドロキシ基が、上記「アルキル」の炭素原子に結合している水素原子と置き換わった基を意味する。例えば、ヒドロキシメチル、１－ヒドロキシエチル、２－ヒドロキシエチル、１－ヒドロキシプロピル、２－ヒドロキシプロピル、１，２－ヒドロキシエチル等が挙げられる。
　「ヒドロキシアルキル」の好ましい態様として、ヒドロキシメチルが挙げられる。 “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.
　「アルキルオキシ」とは、上記「アルキル」が酸素原子に結合した基を意味する。例えば、メトキシ、エトキシ、ｎ－プロピルオキシ、イソプロピルオキシ、ｎ－ブチルオキシ、ｔｅｒｔ－ブチルオキシ、イソブチルオキシ、ｓｅｃ－ブチルオキシ、ペンチルオキシ、イソペンチルオキシ、へキシルオキシ等が挙げられる。
　「アルキルオキシ」の好ましい態様として、メトキシ、エトキシ、ｎ－プロピルオキシ、イソプロピルオキシ、ｔｅｒｔ－ブチルオキシが挙げられる。 “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.
　「アルケニルオキシ」とは、上記「アルケニル」が酸素原子に結合した基を意味する。
例えば、ビニルオキシ、アリルオキシ、１－プロペニルオキシ、２－ブテニルオキシ、２－ペンテニルオキシ、２－ヘキセニルオキシ、２－ヘプテニルオキシ、２－オクテニルオキシ等が挙げられる。 “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.
　「アルキニルオキシ」とは、上記「アルキニル」が酸素原子に結合した基を意味する。
例えば、エチニルオキシ、１－プロピニルオキシ、２－プロピニルオキシ、２－ブチニルオキシ、２－ペンチニルオキシ、２－ヘキシニルオキシ、２－ヘプチニルオキシ、２－オクチニルオキシ等が挙げられる。 “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.
　「ハロアルキル」とは、１以上の上記「ハロゲン」が上記「アルキル」に結合した基を意味する。例えば、モノフルオロメチル、モノフルオロエチル、モノフルオロプロピル、２，２，３，３，３－ペンタフルオロプロピル、モノクロロメチル、トリフルオロメチル、トリクロロメチル、２，２，２－トリフルオロエチル、２，２，２－トリクロロエチル、１，２－ジブロモエチル、１，１，１－トリフルオロプロパン－２－イル等が挙げられる。
　「ハロアルキル」の好ましい態様として、トリフルオロメチル、トリクロロメチルが挙げられる。 “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.
　「ハロアルキルオキシ」とは、上記「ハロアルキル」が酸素原子に結合した基を意味する。例えば、モノフルオロメトキシ、モノフルオロエトキシ、トリフルオロメトキシ、トリクロロメトキシ、トリフルオロエトキシ、トリクロロエトキシ等が挙げられる。
　「ハロアルキルオキシ」の好ましい態様として、トリフルオロメトキシ、トリクロロメトキシが挙げられる。 “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.
　「アルキルオキシアルキル」とは、上記「アルキルオキシ」が上記「アルキル」に結合した基を意味する。例えば、メトキシメチル、メトキシエチル、エトキシメチル等が挙げられる。 “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.
　「アルキルオキシアルキルオキシ」とは、上記「アルキルオキシ」が上記「アルキルオキシ」に結合した基を意味する。例えば、メトキシメトキシ、メトキシエトキシ、エトキシメトキシ、エトキシエトキシ等が挙げられる。 “Alkyloxyalkyloxy” means a group in which the “alkyloxy” is bonded to the “alkyloxy”. Examples thereof include methoxymethoxy, methoxyethoxy, ethoxymethoxy, ethoxyethoxy and the like.
　「アルキルカルボニル」とは、上記「アルキル」がカルボニル基に結合した基を意味する。例えば、メチルカルボニル、エチルカルボニル、プロピルカルボニル、イソプロピルカルボニル、ｔｅｒｔ－ブチルカルボニル、イソブチルカルボニル、ｓｅｃ－ブチルカルボニル、ペンチルカルボニル、イソペンチルカルボニル、へキシルカルボニル等が挙げられる。
　「アルキルカルボニル」の好ましい態様として、メチルカルボニル、エチルカルボニル、ｎ－プロピルカルボニルが挙げられる。 “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.
　「アルケニルカルボニル」とは、上記「アルケニル」がカルボニル基に結合した基を意味する。例えば、エチレニルカルボニル、プロペニルカルボニル等が挙げられる。 “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.
　「アルキニルカルボニル」とは、上記「アルキニル」がカルボニル基に結合した基を意味する。例えば、エチニルカルボニル、プロピニルカルボニル等が挙げられる。 “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.
　「モノアルキルアミノ」とは、上記「アルキル」がアミノ基の窒素原子と結合している水素原子１個と置き換わった基を意味する。例えば、メチルアミノ、エチルアミノ、イソプロピルアミノ等が挙げられる。
　「モノアルキルアミノ」の好ましい態様として、メチルアミノ、エチルアミノが挙げられる。 “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.
　「ジアルキルアミノ」とは、上記「アルキル」がアミノ基の窒素原子と結合している水素原子２個と置き換わった基を意味する。２個のアルキル基は、同一でも異なっていてもよい。例えば、ジメチルアミノ、ジエチルアミノ、Ｎ，Ｎ－ジイソプロピルアミノ、Ｎ－メチル－Ｎ－エチルアミノ、Ｎ－イソプロピル－Ｎ－エチルアミノ等が挙げられる。
　「ジアルキルアミノ」の好ましい態様として、ジメチルアミノ、ジエチルアミノが挙げられる。 “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.
　「アルキルスルホニル」とは、上記「アルキル」がスルホニル基に結合した基を意味する。例えば、メチルスルホニル、エチルスルホニル、プロピルスルホニル、イソプロピルスルホニル、ｔｅｒｔ－ブチルスルホニル、イソブチルスルホニル、ｓｅｃ－ブチルスルホニル等が挙げられる。
　「アルキルスルホニル」の好ましい態様として、メチルスルホニル、エチルスルホニルが挙げられる。 “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.
　「アルケニルスルホニル」とは、上記「アルケニル」がスルホニル基に結合した基を意味する。例えば、エチレニルスルホニル、プロペニルスルホニル等が挙げられる。 “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.
　「アルキニルスルホニル」とは、上記「アルキニル」がスルホニル基に結合した基を意味する。例えば、エチニルスルホニル、プロピニルスルホニル等が挙げられる。 “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.
　「モノアルキルカルボニルアミノ」とは、上記「アルキルカルボニル」がアミノ基の窒素原子と結合している水素原子１個と置き換わった基を意味する。例えば、メチルカルボニルアミノ、エチルカルボニルアミノ、プロピルカルボニルアミノ、イソプロピルカルボニルアミノ、ｔｅｒｔ－ブチルカルボニルアミノ、イソブチルカルボニルアミノ、ｓｅｃ－ブチルカルボニルアミノ等が挙げられる。
　「モノアルキルカルボニルアミノ」の好ましい態様としては、メチルカルボニルアミノ、エチルカルボニルアミノが挙げられる。 “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.
　「ジアルキルカルボニルアミノ」とは、上記「アルキルカルボニル」がアミノ基の窒素原子と結合している水素原子２個と置き換わった基を意味する。２個のアルキルカルボニル基は、同一でも異なっていてもよい。例えば、ジメチルカルボニルアミノ、ジエチルカルボニルアミノ、Ｎ，Ｎ－ジイソプロピルカルボニルアミノ等が挙げられる。
　「ジアルキルカルボニルアミノ」の好ましい態様として、ジメチルカルボニルアミノ、ジエチルカルボニルアミノが挙げられる。 “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.
　「モノアルキルスルホニルアミノ」とは、上記「アルキルスルホニル」がアミノ基の窒素原子と結合している水素原子１個と置き換わった基を意味する。例えば、メチルスルホニルアミノ、エチルスルホニルアミノ、プロピルスルホニルアミノ、イソプロピルスルホニルアミノ、ｔｅｒｔ－ブチルスルホニルアミノ、イソブチルスルホニルアミノ、ｓｅｃ－ブチルスルホニルアミノ等が挙げられる。
　「モノアルキルスルホニルアミノ」の好ましい態様としては、メチルスルホニルアミノ、エチルスルホニルアミノが挙げられる。 “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.
　「ジアルキルスルホニルアミノ」とは、上記「アルキルスルホニル」がアミノ基の窒素原子と結合している水素原子２個と置き換わった基を意味する。２個のアルキルスルホニル基は、同一でも異なっていてもよい。例えば、ジメチルスルホニルアミノ、ジエチルスルホニルアミノ、Ｎ，Ｎ－ジイソプロピルスルホニルアミノ等が挙げられる。
　「ジアルキルカルボニルアミノ」の好ましい態様として、ジメチルスルホニルアミノ、ジエチルスルホニルアミノが挙げられる。 “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.
　「アルキルイミノ」とは、上記「アルキル」がイミノ基の窒素原子と結合している水素原子と置き換わった基を意味する。例えば、メチルイミノ、エチルイミノ、ｎ－プロピルイミノ、イソプロピルイミノ等が挙げられる。 “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.
　「アルケニルイミノ」とは、上記「アルケニル」がイミノ基の窒素原子と結合している水素原子と置き換わった基を意味する。例えば、エチレニルイミノ、プロペニルイミノ等が挙げられる。 “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.
　「アルキニルイミノ」とは、上記「アルキニル」がイミノ基の窒素原子と結合している水素原子と置き換わった基を意味する。例えば、エチニルイミノ、プロピニルイミノ等が挙げられる。 “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.
　「アルキルカルボニルイミノ」とは、上記「アルキルカルボニル」がイミノ基の窒素原子と結合している水素原子と置き換わった基を意味する。例えば、メチルカルボニルイミノ、エチルカルボニルイミノ、ｎ－プロピルカルボニルイミノ、イソプロピルカルボニルイミノ等が挙げられる。 “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.
　「アルケニルカルボニルイミノ」とは、上記「アルケニルカルボニル」がイミノ基の窒素原子と結合している水素原子と置き換わった基を意味する。例えば、エチレニルカルボニルイミノ、プロペニルカルボニルイミノ等が挙げられる。 “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.
　「アルキニルカルボニルイミノ」とは、上記「アルキニルカルボニル」がイミノ基の窒素原子と結合している水素原子と置き換わった基を意味する。例えば、エチニルカルボニルイミノ、プロピニルカルボニルイミノ等が挙げられる。 “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.
　「アルキルオキシイミノ」とは、上記「アルキルオキシ」がイミノ基の窒素原子と結合している水素原子と置き換わった基を意味する。例えば、メチルオキシイミノ、エチルオキシイミノ、ｎ－プロピルオキシイミノ、イソプロピルオキシイミノ等が挙げられる。 “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.
　「アルケニルオキシイミノ」とは、上記「アルケニルオキシ」がイミノ基の窒素原子と結合している水素原子と置き換わった基を意味する。例えば、エチレニルオキシイミノ、プロペニルオキシイミノ等が挙げられる。 “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.
　「アルキニルオキシイミノ」とは、上記「アルキニルオキシ」がイミノ基の窒素原子と結合している水素原子と置き換わった基を意味する。例えば、エチニルオキシイミノ、プロピニルオキシイミノ等が挙げられる。 “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.
　「アルキルカルボニルオキシ」とは、上記「アルキルカルボニル」が酸素原子に結合した基を意味する。例えば、メチルカルボニルオキシ、エチルカルボニルオキシ、プロピルカルボニルオキシ、イソプロピルカルボニルオキシ、ｔｅｒｔ－ブチルカルボニルオキシ、イソブチルカルボニルオキシ、ｓｅｃ－ブチルカルボニルオキシ等が挙げられる。
　「アルキルカルボニルオキシ」の好ましい態様としては、メチルカルボニルオキシ、エチルカルボニルオキシが挙げられる。 “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.
　「アルケニルカルボニルオキシ」とは、上記「アルケニルカルボニル」が酸素原子に結合した基を意味する。例えば、エチレニルカルボニルオキシ、プロペニルカルボニルオキシ等が挙げられる。 “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.
　「アルキニルカルボニルオキシ」とは、上記「アルキニルカルボニル」が酸素原子に結合した基を意味する。例えば、エチニルカルボニルオキシ、プロピニルカルボニルオキシ等が挙げられる。 “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.
　「アルキルオキシカルボニル」とは、上記「アルキルオキシ」がカルボニル基に結合した基を意味する。例えば、メチルオキシカルボニル、エチルオキシカルボニル、プロピルオキシカルボニル、イソプロピルオキシカルボニル、ｔｅｒｔ－ブチルオキシカルボニル、イソブチルオキシカルボニル、ｓｅｃ－ブチルオキシカルボニル、ペンチルオキシカルボニル、イソペンチルオキシカルボニル、へキシルオキシカルボニル等が挙げられる。
　「アルキルオキシカルボニル」の好ましい態様としては、メチルオキシカルボニル、エチルオキシカルボニル、プロピルオキシカルボニルが挙げられる。 “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.
　「アルケニルオキシカルボニル」とは、上記「アルケニルオキシ」がカルボニル基に結合した基を意味する。例えば、エチレニルオキシカルボニル、プロペニルオキシカルボニル等が挙げられる。 “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.
　「アルキニルオキシカルボニル」とは、上記「アルキニルオキシ」がカルボニル基に結合した基を意味する。例えば、エチニルオキシカルボニル、プロピニルオキシカルボニル等が挙げられる。 “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.
　「アルキルスルファニル」とは、上記「アルキル」がスルファニル基の硫黄原子と結合している水素原子と置き換わった基を意味する。例えば、メチルスルファニル、エチルスルファニル、ｎ－プロピルスルファニル、イソプロピルスルファニル等が挙げられる。 “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.
　「アルケニルスルファニル」とは、上記「アルケニル」がスルファニル基の硫黄原子と結合している水素原子と置き換わった基を意味する。例えば、エチレニルスルファニル、プロペニルスルファニル等が挙げられる。 “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.
　「アルキニルスルファニル」とは、上記「アルキニル」がスルファニル基の硫黄原子と結合している水素原子と置き換わった基を意味する。例えば、エチニルスルファニル、プロピニルスルファニル等が挙げられる。 “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.
　「アルキルスルフィニル」とは、上記「アルキル」がスルフィニル基に結合した基を意味する。例えば、メチルスルフィニル、エチルスルフィニル、ｎ－プロピルスルフィニル、イソプロピルスルフィニル等が挙げられる。 “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.
　「アルケニルスルフィニル」とは、上記「アルケニル」がスルフィニル基に結合した基を意味する。例えば、エチレニルスルフィニル、プロペニルスルフィニル等が挙げられる。 “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.
　「アルキニルスルフィニル」とは、上記「アルキニル」がスルフィニル基に結合した基を意味する。例えば、エチニルスルフィニル、プロピニルスルフィニル等が挙げられる。 “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.
　「モノアルキルカルバモイル」とは、上記「アルキル」がカルバモイル基の窒素原子と結合している水素原子１個と置き換わった基を意味する。例えば、メチルカルバモイル、エチルカルバモイル等が挙げられる。 “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.
　「ジアルキルカルバモイル」とは、上記「アルキル」がカルバモイル基の窒素原子と結合している水素原子２個と置き換わった基を意味する。２個のアルキル基は、同一でも異なっていてもよい。例えば、ジメチルカルバモイル、ジエチルカルバモイル等が挙げられる。 “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.
　「モノアルキルスルファモイル」とは、上記「アルキル」がスルファモイル基の窒素原子と結合している水素原子１個と置き換わった基を意味する。例えば、メチルスルファモイル、ジメチルスルファモイルモイル等が挙げられる。 “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.
　「ジアルキルスルファモイル」とは、上記「アルキル」がスルファモイル基の窒素原子と結合している水素原子２個と置き換わった基を意味する。２個のアルキル基は、同一でも異なっていてもよい。例えば、ジメチルカルバモイル、ジエチルカルバモイル等が挙げられる。 “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.
　「トリアルキルシリル」とは、上記「アルキル」３個がケイ素原子に結合している基を意味する。３個のアルキルは同一でも異なっていてもよい。例えば、トリメチルシリル、トリエチルシリル、ｔｅｒｔ－ブチルジメチルシリル等が挙げられる。 “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.
　「芳香族炭素環アルキル」、「非芳香族炭素環アルキル」、「芳香族複素環アルキル」、および「非芳香族複素環アルキル」、
「芳香族炭素環アルキルオキシ」、「非芳香族炭素環アルキルオキシ」、「芳香族複素環アルキルオキシ」、および「非芳香族複素環アルキルオキシ」、
「芳香族炭素環アルキルスルファニル」、「非芳香族炭素環アルキルスルファニル」、「芳香族複素環アルキルスルファニル」、および「非芳香族複素環アルキルスルファニル」、
「芳香族炭素環アルキルオキシカルボニル」、「非芳香族炭素環アルキルオキシカルボニル」、「芳香族複素環アルキルオキシカルボニル」、および「非芳香族複素環アルキルオキシカルボニル」、
「芳香族炭素環アルキルオキシアルキル」、「非芳香族炭素環アルキルオキシアルキル」、「芳香族複素環アルキルオキシアルキル」、および「非芳香族複素環アルキルオキシアルキル」、ならびに
「芳香族炭素環アルキルアミノ」、「非芳香族炭素環アルキルアミノ」、「芳香族複素環アルキルアミノ」、および「非芳香族複素環アルキルアミノ」のアルキル部分も、上記「アルキル」と同様である。 “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”.
　「芳香族炭素環アルキル」とは、１以上の上記「芳香族炭素環式基」で置換されているアルキルを意味する。例えば、ベンジル、フェネチル、フェニルプロピニル、ベンズヒドリル、トリチル、ナフチルメチル、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000013
等が挙げられる。
　「芳香族炭素環アルキル」の好ましい態様としては、ベンジル、フェネチル、ベンズヒドリルが挙げられる。
Figure JPOXMLDOC01-appb-C000013
Etc.
Preferable embodiments of “aromatic carbocyclic alkyl” include benzyl, phenethyl and benzhydryl.
　「非芳香族炭素環アルキル」とは、１以上の上記「非芳香族炭素環式基」で置換されているアルキルを意味する。また、「非芳香族炭素環アルキル」は、アルキル部分が上記「芳香族炭素環式基」で置換されている「非芳香族炭素環アルキル」も包含する。例えば、シクロプロピルメチル、シクロブチルメチル、シクロペンチルメチル、シクロへキシルメチル、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000014
等が挙げられる。
Figure JPOXMLDOC01-appb-C000014
Etc.
　「芳香族複素環アルキル」とは、１以上の上記「芳香族複素環式基」で置換されているアルキルを意味する。また、「芳香族複素環アルキル」は、アルキル部分が上記「芳香族炭素環式基」および／または「非芳香族炭素環式基」で置換されている「芳香族複素環アルキル」も包含する。例えば、ピリジルメチル、フラニルメチル、イミダゾリルメチル、インドリルメチル、ベンゾチオフェニルメチル、オキサゾリルメチル、イソキサゾリルメチル、チアゾリルメチル、イソチアゾリルメチル、ピラゾリルメチル、イソピラゾリルメチル、ピロリジニルメチル、ベンズオキサゾリルメチル、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000015
等が挙げられる。
Figure JPOXMLDOC01-appb-C000015
Etc.
　「非芳香族複素環アルキル」とは、１以上の上記「非芳香族複素環式基」で置換されているアルキルを意味する。また、「非芳香族複素環アルキル」は、アルキル部分が上記「芳香族炭素環式基」、「非芳香族炭素環式基」および／または「芳香族複素環式基」で置換されている「非芳香族複素環アルキル」も包含する。例えば、テトラヒドロピラニルメチル、モルホリニルエチル、ピペリジニルメチル、ピペラジニルメチル、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000016
等が挙げられる。
Figure JPOXMLDOC01-appb-C000016
Etc.
　「芳香族炭素環アルキルオキシ」とは、１以上の上記「芳香族炭素環式基」で置換されているアルキルオキシを意味する。例えば、ベンジルオキシ、フェネチルオキシ、フェニルプロピニルオキシ、ベンズヒドリルオキシ、トリチルオキシ、ナフチルメチルオキシ、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000017
等が挙げられる。
Figure JPOXMLDOC01-appb-C000017
Etc.
　「非芳香族炭素環アルキルオキシ」とは、１以上の上記「非芳香族炭素環式基」で置換されているアルキルオキシを意味する。また、「非芳香族炭素環アルキルオキシ」は、アルキル部分が上記「芳香族炭素環式基」で置換されている「非芳香族炭素環アルキルオキシ」も包含する。例えば、シクロプロピルメチルオキシ、シクロブチルメチルオキシ、シクロペンチルメチルオキシ、シクロへキシルメチルオキシ、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000018
等が挙げられる。
Figure JPOXMLDOC01-appb-C000018
Etc.
　「芳香族複素環アルキルオキシ」とは、１以上の上記「芳香族複素環式基」で置換されているアルキルオキシを意味する。また、「芳香族複素環アルキルオキシ」は、アルキル部分が上記「芳香族炭素環式基」および／または「非芳香族炭素環式基」で置換されている「芳香族複素環アルキルオキシ」も包含する。例えば、ピリジルメチルオキシ、フラニルメチルオキシ、イミダゾリルメチルオキシ、インドリルメチルオキシ、ベンゾチオフェニルメチルオキシ、オキサゾリルメチルオキシ、イソキサゾリルメチルオキシ、チアゾリルメチルオキシ、イソチアゾリルメチルオキシ、ピラゾリルメチルオキシ、イソピラゾリルメチルオキシ、ピロリジニルメチルオキシ、ベンズオキサゾリルメチルオキシ、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000019













等が挙げられる。
Figure JPOXMLDOC01-appb-C000019













Etc.
　「非芳香族複素環アルキルオキシ」とは、１以上の上記「非芳香族複素環式基」で置換されているアルキルオキシを意味する。また、「非芳香族複素環アルキルオキシ」は、アルキル部分が上記「芳香族炭素環式基」、「非芳香族炭素環式基」および／または「芳香族複素環式基」で置換されている「非芳香族複素環アルキルオキシ」も包含する。例えば、テトラヒドロピラニルメチルオキシ、モルホリニルエチルオキシ、ピペリジニルメチルオキシ、ピペラジニルメチルオキシ、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000020
等が挙げられる。
Figure JPOXMLDOC01-appb-C000020
Etc.
　「芳香族炭素環アルキルスルファニル」とは、１以上の上記「芳香族炭素環式基」で置換されているアルキルスルファニルを意味する。例えば、ベンジルスルファニル、フェネチルスルファニル、フェニルプロピニルスルファニル、ベンズヒドリルスルファニル、トリチルスルファニル、ナフチルメチルスルファニル等が挙げられる。 “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.
　「非芳香族炭素環アルキルスルファニル」とは、１以上の上記「非芳香族炭素環式基」で置換されているアルキルスルファニルを意味する。また、「非芳香族炭素環アルキルスルファニル」は、アルキル部分が上記「芳香族炭素環式基」で置換されている「非芳香族炭素環アルキルスルファニル」も包含する。例えば、シクロプロピルメチルスルファニル、シクロブチルメチルスルファニル、シクロペンチルメチルスルファニル、シクロへキシルメチルスルファニル等が挙げられる。 “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.
　「芳香族複素環アルキルスルファニル」とは、１以上の上記「芳香族複素環式基」で置換されているアルキルスルファニルを意味する。また、「芳香族複素環アルキルスルファニル」は、アルキル部分が上記「芳香族炭素環式基」および／または「非芳香族炭素環式基」で置換されている「芳香族複素環アルキルスルファニル」も包含する。例えば、ピリジルメチルスルファニル、フラニルメチルスルファニル、イミダゾリルメチルスルファニル、インドリルメチルスルファニル、ベンゾチオフェニルメチルスルファニル、オキサゾリルメチルスルファニル、イソキサゾリルメチルスルファニル、チアゾリルメチルスルファニル、イソチアゾリルメチルスルファニル、ピラゾリルメチルスルファニル、イソピラゾリルメチルスルファニル、ピロリジニルメチルスルファニル、ベンズオキサゾリルメチルスルファニル等が挙げられる。 “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.
　「非芳香族複素環アルキルスルファニル」とは、１以上の上記「非芳香族複素環式基」で置換されているアルキルスルファニルを意味する。また、「非芳香族複素環アルキルスルファニル」は、アルキル部分が上記「芳香族炭素環式基」、「非芳香族炭素環式基」および／または「芳香族複素環式基」で置換されている「非芳香族複素環アルキルスルファニル」も包含する。例えば、テトラヒドロピラニルメチルスルファニル、モルホリニルエチルスルファニル、ピペリジニルメチルスルファニル、ピペラジニルメチルスルファニル等が挙げられる。 “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.
　「芳香族炭素環アルキルオキシカルボニル」とは、１以上の上記「芳香族炭素環式基」で置換されているアルキルオキシカルボニルを意味する。例えば、ベンジルオキシカルボニル、フェネチルオキシカルボニル、フェニルプロピニルオキシカルボニル、ベンゾヒドリルオキシカルボニル、トリチルオキシカルボニル、ナフチルメチルオキシカルボニル、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000021
等が挙げられる。
Figure JPOXMLDOC01-appb-C000021
Etc.
　「非芳香族炭素環アルキルオキシカルボニル」とは、１以上の上記「非芳香族炭素環式基」で置換されているアルキルオキシカルボニルを意味する。また、「非芳香族炭素環アルキルオキシカルボニル」は、アルキル部分が上記「芳香族炭素環式基」で置換されている「非芳香族炭素環アルキルオキシカルボニル」も包含する。例えば、シクロプロピルメチルオキシカルボニル、シクロブチルメチルオキシカルボニル、シクロペンチルメチルオキシカルボニル、シクロへキシルメチルオキシカルボニル、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000022
等が挙げられる。
Figure JPOXMLDOC01-appb-C000022
Etc.
　「芳香族複素環アルキルオキシカルボニル」とは、１以上の上記「芳香族複素環式基」で置換されているアルキルオキシカルボニルを意味する。また、「芳香族複素環アルキルオキシカルボニル」は、アルキル部分が上記「芳香族炭素環式基」および／または「非芳香族炭素環式基」で置換されている「芳香族複素環アルキルオキシカルボニル」も包含する。例えば、ピリジルメチルオキシカルボニル、フラニルメチルオキシカルボニル、イミダゾリルメチルオキシカルボニル、インドリルメチルオキシカルボニル、ベンゾチオフェニルメチルオキシカルボニル、オキサゾリルメチルオキシカルボニル、イソキサゾリルメチルオキシカルボニル、チアゾリルメチルオキシカルボニル、イソチアゾリルメチルオキシカルボニル、ピラゾリルメチルオキシカルボニル、イソピラゾリルメチルオキシカルボニル、ピロリジニルメチルオキシカルボニル、ベンズオキサゾリルメチルオキシカルボニル、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000023





































等が挙げられる。
Figure JPOXMLDOC01-appb-C000023





































Etc.
　「非芳香族複素環アルキルオキシカルボニル」とは、１以上の上記「非芳香族複素環式基」で置換されているアルキルオキシカルボニルを意味する。また、「非芳香族複素環アルキルオキシカルボニル」は、アルキル部分が上記「芳香族炭素環式基」、「非芳香族炭素環式基」および／または「芳香族複素環式基」で置換されている「非芳香族複素環アルキルオキシカルボニル」も包含する。例えば、テトラヒドロピラニルメチルオキシ、モルホリニルエチルオキシ、ピペリジニルメチルオキシ、ピペラジニルメチルオキシ、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000024
等が挙げられる。
Figure JPOXMLDOC01-appb-C000024
Etc.
　「芳香族炭素環アルキルオキシアルキル」とは、１以上の上記「芳香族炭素環式基」で置換されているアルキルオキシアルキルを意味する。例えば、ベンジルオキシメチル、フェネチルオキシメチル、フェニルプロピニルオキシメチル、ベンゾヒドリルオキシメチル、トリチルオキシメチル、ナフチルメチルオキシメチル、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000025
等が挙げられる。
Figure JPOXMLDOC01-appb-C000025
Etc.
　「非芳香族炭素環アルキルオキシアルキル」とは、１以上の上記「非芳香族炭素環式基」で置換されているアルキルオキシアルキルを意味する。また、「非芳香族炭素環アルキルオキシアルキル」は、非芳香族炭素環が結合しているアルキル部分が上記「芳香族炭素環式基」で置換されている「非芳香族炭素環アルキルオキシアルキル」も包含する。例えば、シクロプロピルメチルオキシメチル、シクロブチルメチルオキシメチル、シクロペンチルメチルオキシメチル、シクロへキシルメチルオキシメチル、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000026
等が挙げられる。
Figure JPOXMLDOC01-appb-C000026
Etc.
　「芳香族複素環アルキルオキシアルキル」とは、１以上の上記「芳香族複素環式基」で置換されているアルキルオキシアルキルを意味する。また、「芳香族複素環アルキルオキシアルキル」は、芳香族複素環が結合しているアルキル部分が上記「芳香族炭素環式基」および／または「非芳香族炭素環式基」で置換されている「芳香族複素環アルキルオキシアルキル」も包含する。例えば、ピリジルメチルオキシメチル、フラニルメチルオキシメチル、イミダゾリルメチルオキシメチル、インドリルメチルオキシメチル、ベンゾチオフェニルメチルオキシメチル、オキサゾリルメチルオキシメチル、イソキサゾリルメチルオキシメチル、チアゾリルメチルオキシメチル、イソチアゾリルメチルオキシメチル、ピラゾリルメチルオキシメチル、イソピラゾリルメチルオキシメチル、ピロリジニルメチルオキシメチル、ベンズオキサゾリルメチルオキシメチル、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000027
等が挙げられる。
Figure JPOXMLDOC01-appb-C000027
Etc.
　「非芳香族複素環アルキルオキシアルキル」とは、１以上の上記「非芳香族複素環式基」で置換されているアルキルオキシアルキルを意味する。また、「非芳香族複素環アルキルオキシ」は、非芳香族複素環が結合しているアルキル部分が上記「芳香族炭素環式基」、「非芳香族炭素環式基」および／または「芳香族複素環式基」で置換されている「非芳香族複素環アルキルオキシアルキル」も包含する。例えば、テトラヒドロピラニルメチルオキシメチル、モルホリニルエチルオキシメチル、ピペリジニルメチルオキシメチル、ピペラジニルメチルオキシメチル、以下に示される基 “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
Figure JPOXMLDOC01-appb-C000028
等が挙げられる。
Figure JPOXMLDOC01-appb-C000028
Etc.
　「芳香族炭素環アルキルアミノ」とは、上記「芳香族炭素環アルキル」がアミノ基の窒素原子と結合している水素原子１個または２個と置き換わった基を意味する。例えば、ベンジルアミノ、フェネチルアミノ、フェニルプロピニルアミノ、ベンゾヒドリルアミノ、トリチルアミノ、ナフチルメチルアミノ、ジベンジルアミノ等が挙げられる。 “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.
　「非芳香族炭素環アルキルアミノ」とは、上記「非芳香族炭素環アルキル」がアミノ基の窒素原子と結合している水素原子１個または２個と置き換わった基を意味する。例えば、シクロプロピルメチルアミノ、シクロブチルメチルアミノ、シクロペンチルメチルアミノ、シクロへキシルメチルアミノ等が挙げられる。 “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.
　「芳香族複素環アルキルアミノ」とは、上記「芳香族複素環アルキル」がアミノ基の窒素原子と結合している水素原子１個または２個と置き換わった基を意味する。例えば、ピリジルメチルアミノ、フラニルメチルアミノ、イミダゾリルメチルアミノ、インドリルメチルアミノ、ベンゾチオフェニルメチルアミノ、オキサゾリルメチルアミノ、イソキサゾリルメチルアミノ、チアゾリルメチルアミノ、イソチアゾリルメチルアミノ、ピラゾリルメチルアミノ、イソピラゾリルメチルアミノ、ピロリジニルメチルアミノ、ベンズオキサゾリルメチルアミノ等が挙げられる。 “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.
　「非芳香族複素環アルキルアミノ」とは、上記「非芳香族複素環アルキル」がアミノ基の窒素原子と結合している水素原子１個または２個と置き換わった基を意味する。例えば、テトラヒドロピラニルメチルアミノ、モルホリニルエチルアミノ、ピペリジニルメチルアミノ、ピペラジニルメチルアミノ等が挙げられる。 “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.
　「芳香族炭素環オキシ」、「芳香族炭素環アミノ」、「芳香族炭素環カルボニル」、「芳香族炭素環オキシカルボニル」、「芳香族炭素環カルボニルアミノ」、「芳香族炭素環スルファニル」、および「芳香族炭素環スルホニル」の「芳香族炭素環」部分も、上記「芳香族炭素環式基」と同様である。
　「芳香族炭素環オキシ」とは、「芳香族炭素環」が酸素原子に結合した基を意味する。例えば、フェニルオキシ、ナフチルオキシ等が挙げられる。
　「芳香族炭素環アミノ」とは、「芳香族炭素環」がアミノ基の窒素原子と結合している水素原子１個または２個と置き換わった基を意味する。例えば、フェニルアミノ、ナフチルアミノ等が挙げられる。
　「芳香族炭素環カルボニル」とは、「芳香族炭素環」がカルボニル基に結合した基を意味する。例えば、フェニルカルボニル、ナフチルカルボニル等が挙げられる。
　「芳香族炭素環オキシカルボニル」とは、上記「芳香族炭素環オキシ」がカルボニル基に結合した基を意味する。例えば、フェニルオキシカルボニル、ナフチルオキシカルボニル等が挙げられる。
　「芳香族炭素環カルボニルアミノ」とは、上記「芳香族炭素環カルボニル」がアミノ基の窒素原子と結合している水素原子１個または２個と置き換わった基を意味する。例えば、フェニルカルボニルアミノ、ナフチルカルボニルアミノ等が挙げられる。
　「芳香族炭素環スルファニル」とは、「芳香族炭素環」がスルファニル基の硫黄原子と結合している水素原子と置き換わった基を意味する。例えば、フェニルスルファニル、ナフチルスルファニル等が挙げられる。
　「芳香族炭素環スルホニル」とは、「芳香族炭素環」がスルホニル基に結合した基を意味する。例えば、フェニルスルホニル、ナフチルスルホニル等が挙げられる。 "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.
　「非芳香族炭素環オキシ」、「非芳香族炭素環アミノ」、「非芳香族炭素環カルボニル」、「非芳香族炭素環オキシカルボニル」、「非芳香族炭素環カルボニルアミノ」、「非芳香族炭素環スルファニル」、および「非芳香族炭素環スルホニル」の「非芳香族炭素環」部分も、上記「非芳香族炭素環式基」と同様である。
　「非芳香族炭素環オキシ」とは、「非芳香族炭素環」が酸素原子に結合した基を意味する。例えば、シクロプロピルオキシ、シクロヘキシルオキシ、シクロへキセニルオキシ等が挙げられる。
　「非芳香族炭素環アミノ」とは、「非芳香族炭素環」がアミノ基の窒素原子と結合している水素原子１個または２個と置き換わった基を意味する。例えば、シクロプロピルアミノ、シクロヘキシルアミノ、シクロへキセニルアミノ等が挙げられる。
　「非芳香族炭素環カルボニル」とは、「非芳香族炭素環」がカルボニル基に結合した基を意味する。例えば、シクロプロピルカルボニル、シクロヘキシルカルボニル、シクロへキセニルカルボニル等が挙げられる。
　「非芳香族炭素環オキシカルボニル」とは、上記「非芳香族炭素環オキシ」がカルボニル基に結合した基を意味する。例えば、シクロプロピルオキシカルボニル、シクロヘキシルオキシカルボニル、シクロへキセニルオキシカルボニル等が挙げられる。
　「非芳香族炭素環カルボニルアミノ」とは、上記「非芳香族炭素環カルボニル」がアミノ基の窒素原子と結合している水素原子１個または２個と置き換わった基を意味する。例えば、シクロプロピルカルボニルアミノ、シクロヘキシルカルボニルアミノ、シクロへキセニルカルボニルアミノ等が挙げられる。
　「非芳香族炭素環スルファニル」とは、「非芳香族炭素環」がスルファニル基の硫黄原子と結合している水素原子と置き換わった基を意味する。例えば、シクロプロピルスルファニル、シクロヘキシルスルファニル、シクロヘキセニルスルファニル等が挙げられる。
　「非芳香族炭素環スルホニル」とは、「非芳香族炭素環」がスルホニル基に結合した基を意味する。例えば、シクロプロピルスルホニル、シクロヘキシルスルホニル、シクロヘキセニルスルホニル等が挙げられる。 "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.
　「芳香族複素環オキシ」、「芳香族複素環アミノ」、「芳香族複素環カルボニル」、「芳香族複素環オキシカルボニル」、「芳香族複素環カルボニルアミノ」、「芳香族複素環スルファニル」、および「芳香族複素環スルホニル」の「芳香族複素環」部分も、上記「芳香族複素環式基」と同様である。
　「芳香族複素環オキシ」とは、「芳香族複素環」が酸素原子に結合した基を意味する。例えば、ピリジルオキシ、オキサゾリルオキシ等が挙げられる。
　「芳香族複素環アミノ」とは、「芳香族複素環」がアミノ基の窒素原子と結合している水素原子１個または２個と置き換わった基を意味する。例えば、ピリジルアミノ、オキサゾリルアミノ等が挙げられる。
　「芳香族複素環カルボニル」とは、「芳香族複素環」がカルボニル基に結合した基を意味する。例えば、ピリジルカルボニル、オキサゾリルカルボニル等が挙げられる。
　「芳香族複素環オキシカルボニル」とは、上記「芳香族複素環オキシ」がカルボニル基に結合した基を意味する。例えば、ピリジルオキシカルボニル、オキサゾリルオキシカルボニル等が挙げられる。
　「芳香族複素環カルボニルアミノ」とは、上記「芳香族複素環カルボニル」がアミノ基の窒素原子と結合している水素原子１個または２個と置き換わった基を意味する。例えば、ピリジルカルボニルアミノ、オキサゾリルカルボニルアミノ等が挙げられる。
　「芳香族複素環スルファニル」とは、「芳香族複素環」がスルファニル基の硫黄原子と結合している水素原子と置き換わった基を意味する。例えば、ピリジルスルファニル、オキサゾリルスルファニル等が挙げられる。
　「芳香族複素環スルホニル」とは、「芳香族複素環」がスルホニル基に結合した基を意味する。例えば、ピリジルスルホニル、オキサゾリルスルホニル等が挙げられる。 “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.
　「非芳香族複素環オキシ」、「非芳香族複素環アミノ」、「非芳香族複素環カルボニル」、「非芳香族複素環オキシカルボニル」、「非芳香族複素環カルボニルアミノ」、「非芳香族複素環スルファニル」、および「非芳香族複素環スルホニル」の「非芳香族複素環」部分も、上記「非芳香族複素環式基」と同様である。
　「非芳香族複素環オキシ」とは、「非芳香族複素環」が酸素原子に結合した基を意味する。例えば、ピペリジニルオキシ、テトラヒドロフリルオキシ等が挙げられる。
　「非芳香族複素環アミノ」とは、「非芳香族複素環」がアミノ基の窒素原子と結合している水素原子１個と置き換わった基を意味する。例えば、ピペリジニルアミノ、テトラヒドロフリルアミノ等が挙げられる。
　「非芳香族複素環カルボニル」とは、「非芳香族複素環」がカルボニル基に結合した基を意味する。例えば、ピペリジニルカルボニル、テトラヒドロフリルカルボニル等が挙げられる。
　「非芳香族複素環オキシカルボニル」とは、上記「非芳香族複素環オキシ」がカルボニル基に結合した基を意味する。例えば、ピペリジニルオキシカルボニル、テトラヒドロフリルオキシカルボニル等が挙げられる。
　「非芳香族複素環カルボニルアミノ」とは、上記「非芳香族複素環カルボニル」がアミノ基の窒素原子と結合している水素原子１個または２個と置き換わった基を意味する。例えば、ピペリジニルカルボニルアミノ、テトラヒドロフリルカルボニルアミノ等が挙げられる。
　「非芳香族複素環スルファニル」とは、「非芳香族複素環」がスルファニル基の硫黄原子と結合している水素原子と置き換わった基を意味する。例えば、ピペリジニルスルファニル、テトラヒドロフリルスルファニル等が挙げられる。
　「非芳香族複素環スルホニル」とは、「非芳香族複素環」がスルホニル基に結合した基を意味する。例えば、ピペリジニルスルホニル、テトラヒドロフリルスルホニル等が挙げられる。 “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.
　「置換若しくは非置換のアルキル」、「置換若しくは非置換のアルケニル」、「置換若しくは非置換のアルキニル」、「置換若しくは非置換のハロアルキル」、「置換若しくは非置換のアルキルオキシ」、「置換若しくは非置換のアルケニルオキシ」、「置換若しくは非置換のアルキニルオキシ」、「置換若しくは非置換のハロアルキルオキシ」、「置換若しくは非置換のアルキルカルボニル」、「置換若しくは非置換のアルケニルカルボニル」、「置換若しくは非置換のアルキニルカルボニル」、「置換若しくは非置換のモノアルキルアミノ」、「置換若しくは非置換のジアルキルアミノ」、「置換若しくは非置換のアルキルスルホニル」、「置換若しくは非置換のアルケニルスルホニル」、「置換若しくは非置換のアルキニルスルホニル」、「置換若しくは非置換のモノアルキルカルボニルアミノ」、「置換若しくは非置換のジアルキルカルボニルアミノ」、「置換若しくは非置換のモノアルキルスルホニルアミノ」、「置換若しくは非置換のジアルキルスルホニルアミノ」、「置換若しくは非置換のアルキルイミノ」、「置換若しくは非置換のアルケニルイミノ」、「置換若しくは非置換のアルキニルイミノ」、「置換若しくは非置換のアルキルカルボニルイミノ」、「置換若しくは非置換のアルケニルカルボニルイミノ」、「置換若しくは非置換のアルキニルカルボニルイミノ」、「置換若しくは非置換のアルキルオキシイミノ」、「置換若しくは非置換のアルケニルオキシイミノ」、「置換若しくは非置換のアルキニルオキシイミノ」、「置換若しくは非置換のアルキルカルボニルオキシ」、「置換若しくは非置換のアルケニルカルボニルオキシ」、「置換若しくは非置換のアルキニルカルボニルオキシ」、「置換若しくは非置換のアルキルオキシカルボニル」、「置換若しくは非置換のアルケニルオキシカルボニル」、「置換若しくは非置換のアルキニルオキシカルボニル」、「置換若しくは非置換のアルキルスルファニル」、「置換若しくは非置換のアルケニルスルファニル」、「置換若しくは非置換のアルキニルスルファニル」、「置換若しくは非置換のアルキルスルフィニル」、「置換若しくは非置換のアルケニルスルフィニル」、「置換若しくは非置換のアルキニルスルフィニル」、「置換若しくは非置換のモノアルキルカルバモイル」、「置換若しくは非置換のジアルキルカルバモイル」、「置換若しくは非置換のモノアルキルスルファモイル」、および「置換若しくは非置換のジアルキルスルファモイル」の置換基としては、次の置換基が挙げられる。任意の位置の炭素原子が次の置換基から選択される１以上の基と結合していてもよい。
　置換基：ハロゲン、ヒドロキシ、カルボキシ、アミノ、イミノ、ヒドロキシアミノ、ヒドロキシイミノ、ホルミル、ホルミルオキシ、カルバモイル、スルファモイル、スルファニル、スルフィノ、スルホ、チオホルミル、チオカルボキシ、ジチオカルボキシ、チオカルバモイル、シアノ、ニトロ、ニトロソ、アジド、ヒドラジノ、ウレイド、アミジノ、グアニジノ、トリアルキルシリル、アルキルオキシ、アルケニルオキシ、アルキニルオキシ、ハロアルキルオキシ、アルキルカルボニル、アルケニルカルボニル、アルキニルカルボニル、モノアルキルアミノ、ジアルキルアミノ、アルキルスルホニル、アルケニルスルホニル、アルキニルスルホニル、モノアルキルカルボニルアミノ、ジアルキルカルボニルアミノ、モノアルキルスルホニルアミノ、ジアルキルスルホニルアミノ、アルキルイミノ、アルケニルイミノ、アルキニルイミノ、アルキルカルボニルイミノ、アルケニルカルボニルイミノ、アルキニルカルボニルイミノ、アルキルオキシイミノ、アルケニルオキシイミノ、アルキニルオキシイミノ、アルキルカルボニルオキシ、アルケニルカルボニルオキシ、アルキニルカルボニルオキシ、アルキルオキシカルボニル、アルケニルオキシカルボニル、アルキニルオキシカルボニル、アルキルスルファニル、アルケニルスルファニル、アルキニルスルファニル、アルキルスルフィニル、アルケニルスルフィニル、アルキニルスルフィニル、モノアルキルカルバモイル、ジアルキルカルバモイル、モノアルキルスルファモイル、ジアルキルスルファモイル、芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、非芳香族複素環式基、芳香族炭素環オキシ、非芳香族炭素環オキシ、芳香族複素環オキシ、非芳香族複素環オキシ、芳香族炭素環アミノ、非芳香族炭素環アミノ、芳香族複素環アミノ、非芳香族複素環アミノ、芳香族炭素環カルボニル、非芳香族炭素環カルボニル、芳香族複素環カルボニル、非芳香族複素環カルボニル、芳香族炭素環オキシカルボニル、非芳香族炭素環オキシカルボニル、芳香族複素環オキシカルボニル、非芳香族複素環オキシカルボニル、芳香族炭素環カルボニルアミノ、非芳香族炭素環カルボニルアミノ、芳香族複素環カルボニルアミノ、非芳香族複素環カルボニルアミノ、芳香族炭素環アルキルオキシ、非芳香族炭素環アルキルオキシ、芳香族複素環アルキルオキシ、非芳香族複素環アルキルオキシ、芳香族炭素環アルキルスルファニル、非芳香族炭素環アルキルスルファニル、芳香族複素環アルキルスルファニル、非芳香族複素環アルキルスルファニル、芳香族炭素環アルキルオキシカルボニル、非芳香族炭素環アルキルオキシカルボニル、芳香族複素環アルキルオキシカルボニル、非芳香族複素環アルキルオキシカルボニル、芳香族炭素環アルキルアミノ、非芳香族炭素環アルキルアミノ、芳香族複素環アルキルアミノ、非芳香族複素環アルキルアミノ、芳香族炭素環スルファニル、非芳香族炭素環スルファニル、芳香族複素環スルファニル、非芳香族複素環スルファニル、非芳香族炭素環スルホニル、芳香族炭素環スルホニル、芳香族複素環スルホニル、および非芳香族複素環スルホニル。 "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.
　「置換若しくは非置換の芳香族炭素環式基」、「置換若しくは非置換の非芳香族炭素環式基」、「置換若しくは非置換の芳香族複素環式基」、および「置換若しくは非置換の非芳香族複素環式基」、
「置換若しくは非置換の芳香族炭素環オキシ」、「置換若しくは非置換の非芳香族炭素環オキシ」、「置換若しくは非置換の芳香族複素環オキシ」、および「置換若しくは非置換の非芳香族複素環オキシ」、
「置換若しくは非置換の芳香族炭素環アミノ」、「置換若しくは非置換の非芳香族炭素環アミノ」、「置換若しくは非置換の芳香族複素環アミノ」、および「置換若しくは非置換の非芳香族複素環アミノ」、
「置換若しくは非置換の芳香族炭素環カルボニル」、「置換若しくは非置換の非芳香族炭素環カルボニル」、「置換若しくは非置換の芳香族複素環カルボニル」、および「置換若しくは非置換の非芳香族複素環カルボニル」、
「置換若しくは非置換の芳香族炭素環オキシカルボニル」、「置換若しくは非置換の非芳香族炭素環オキシカルボニル」、「置換若しくは非置換の芳香族複素環オキシカルボニル」、および「置換若しくは非置換の非芳香族複素環オキシカルボニル」、
「置換若しくは非置換の芳香族炭素環スルファニル」、「置換若しくは非置換の非芳香族炭素環スルファニル」、「置換若しくは非置換の芳香族複素環スルファニル」、および「置換若しくは非置換の非芳香族複素環スルファニル」、ならびに
「置換若しくは非置換の芳香族炭素環スルホニル」、「置換若しくは非置換の非芳香族炭素環スルホニル」、「置換若しくは非置換の芳香族複素環スルホニル」、および「置換若しくは非置換の非芳香族複素環スルホニル」の「芳香族炭素環」、「非芳香族炭素環」、「芳香族複素環」、および「非芳香族複素環」の環上の置換基としては、次の置換基が挙げられる。環上の任意の位置の原子が次の置換基から選択される１以上の基と結合していてもよい。
　置換基：ハロゲン、ヒドロキシ、カルボキシ、アミノ、イミノ、ヒドロキシアミノ、ヒドロキシイミノ、ホルミル、ホルミルオキシ、カルバモイル、スルファモイル、スルファニル、スルフィノ、スルホ、チオホルミル、チオカルボキシ、ジチオカルボキシ、チオカルバモイル、シアノ、ニトロ、ニトロソ、アジド、ヒドラジノ、ウレイド、アミジノ、グアニジノ、トリアルキルシリル、アルキル、アルケニル、アルキニル、ハロアルキル、ヒドロキシアルキル、アルキルオキシ、アルケニルオキシ、アルキニルオキシ、ハロアルキルオキシ、アルキルオキシアルキル、アルキルオキシアルキルオキシ、アルキルカルボニル、アルケニルカルボニル、アルキニルカルボニル、モノアルキルアミノ、ジアルキルアミノ、アルキルスルホニル、アルケニルスルホニル、アルキニルスルホニル、モノアルキルカルボニルアミノ、ジアルキルカルボニルアミノ、モノアルキルスルホニルアミノ、ジアルキルスルホニルアミノ、アルキルイミノ、アルケニルイミノ、アルキニルイミノ、アルキルカルボニルイミノ、アルケニルカルボニルイミノ、アルキニルカルボニルイミノ、アルキルオキシイミノ、アルケニルオキシイミノ、アルキニルオキシイミノ、アルキルカルボニルオキシ、アルケニルカルボニルオキシ、アルキニルカルボニルオキシ、アルキルオキシカルボニル、アルケニルオキシカルボニル、アルキニルオキシカルボニル、アルキルスルファニル、アルケニルスルファニル、アルキニルスルファニル、アルキルスルフィニル、アルケニルスルフィニル、アルキニルスルフィニル、モノアルキルカルバモイル、ジアルキルカルバモイル、モノアルキルスルファモイル、ジアルキルスルファモイル、芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、非芳香族複素環式基、芳香族炭素環オキシ、非芳香族炭素環オキシ、芳香族複素環オキシ、非芳香族複素環オキシ、芳香族炭素環アミノ、非芳香族炭素環アミノ、芳香族複素環アミノ、非芳香族複素環アミノ、芳香族炭素環カルボニル、非芳香族炭素環カルボニル、芳香族複素環カルボニル、非芳香族複素環カルボニル、芳香族炭素環オキシカルボニル、非芳香族炭素環オキシカルボニル、芳香族複素環オキシカルボニル、非芳香族複素環オキシカルボニル、非芳香族複素環オキシカルボニル、芳香族炭素環カルボニルアミノ、非芳香族炭素環カルボニルアミノ、芳香族複素環カルボニルアミノ、非芳香族複素環カルボニルアミノ、芳香族炭素環アルキル、非芳香族炭素環アルキル、芳香族複素環アルキル、非芳香族複素環アルキル、芳香族炭素環アルキルオキシ、非芳香族炭素環アルキルオキシ、芳香族複素環アルキルオキシ、非芳香族複素環アルキルオキシ、芳香族炭素環アルキルスルファニル、非芳香族炭素環アルキルスルファニル、芳香族複素環アルキルスルファニル、非芳香族複素環アルキルスルファニル、芳香族炭素環アルキルオキシカルボニル、非芳香族炭素環アルキルオキシカルボニル、芳香族複素環アルキルオキシカルボニル、非芳香族複素環アルキルオキシカルボニル、芳香族炭素環アルキルオキシアルキル、非芳香族炭素環アルキルオキシアルキル、芳香族複素環アルキルオキシアルキル、非芳香族複素環アルキルオキシアルキル、芳香族炭素環アルキルアミノ、非芳香族炭素環アルキルアミノ、芳香族複素環アルキルアミノ、非芳香族複素環アルキルアミノ、芳香族炭素環スルファニル、非芳香族炭素環スルファニル、芳香族複素環スルファニル、非芳香族複素環スルファニル、非芳香族炭素環スルホニル、芳香族炭素環スルホニル、芳香族複素環スルホニル、および非芳香族複素環スルホニル。 “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.
　また、「置換若しくは非置換の非芳香族炭素環式基」および「置換若しくは非置換の非芳香族複素環式基」は「オキソ」で置換されていてもよい。この場合、以下のように炭素原子上の２個の水素原子が置換されている基を意味する。 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.
Figure JPOXMLDOC01-appb-C000029
　さらに、「置換若しくは非置換の非芳香族炭素環式基」および「置換若しくは非置換の非芳香族複素環式基」は、以下のようにアルキレン、アルケニレン、若しくはアルキニレンにより架橋、または他の環、例えばシクロアルカン、シクロアルケン、シクロアルキン、オキシラン、オキセタン、チイラン等と共にスピロ環が形成されていても良い。
Figure JPOXMLDOC01-appb-C000029
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.
Figure JPOXMLDOC01-appb-C000030
Figure JPOXMLDOC01-appb-C000030
　上記、「置換若しくは非置換の非芳香族炭素環オキシ」、「置換若しくは非置換の非芳香族複素環オキシ」、「置換若しくは非置換の非芳香族炭素環アミノ」、「置換若しくは非置換の非芳香族複素環アミノ」、「置換若しくは非置換の非芳香族炭素環カルボニル」、「置換若しくは非置換の非芳香族複素環カルボニル」、「置換若しくは非置換の非芳香族炭素環オキシカルボニル」、「置換若しくは非置換の非芳香族複素環オキシカルボニル」、「置換若しくは非置換の非芳香族炭素環カルボニルアミノ」、「置換若しくは非置換の非芳香族複素環カルボニルアミノ」、「置換若しくは非置換の非芳香族炭素環スルファニル」、「置換若しくは非置換の非芳香族複素環スルファニル」、「置換若しくは非置換の非芳香族炭素環スルホニル」、および「置換若しくは非置換の非芳香族複素環スルホニル」の非芳香族炭素環、および非芳香族複素環部分も上記と同様に「オキソ」で置換されていてもよい。 "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".
　式（Ｉ）で示される化合物における好ましい態様を以下に示す。 Preferred embodiments of the compound represented by the formula (I) are shown below.
Figure JPOXMLDOC01-appb-C000031
　Ｒ１は、好ましくは、水素原子、ハロゲン、シアノ、ニトロ、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、より好ましくは、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニルであり、さらに好ましくは、置換若しくは非置換のアルキルであり、特に好ましくは、炭素数１～４のアルキルであり、最も好ましくは、メチルである。
Figure JPOXMLDOC01-appb-C000031
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.
　Ｒ２は、それぞれ独立して、好ましくは、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換のアルキルオキシ、置換若しくは非置換のアルケニルオキシ、置換若しくは非置換のアルキニルオキシ、置換若しくは非置換のアルキルスルファニル、置換若しくは非置換のアルケニルスルファニル、または置換若しくは非置換のアルキニルスルファニルであり、より好ましくは、置換若しくは非置換のアルキルオキシ、置換若しくは非置換のアルケニルオキシ、または置換若しくは非置換のアルキニルオキシであり、さらに好ましくは、置換若しくは非置換のアルキルオキシであり、特に好ましくは、炭素数１～４のアルキルオキシであり、最も好ましくは、ｔｅｒｔ－ブチルオキシである。 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は、好ましくは１または２であり、特に好ましくは１である。 N is preferably 1 or 2, particularly preferably 1.
　Ｒ３は、好ましくは、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、より好ましくは、置換若しくは非置換のフェニル、置換若しくは非置換のシクロアルケニル、置換若しくは非置換のクロマニル、または置換若しくは非置換のベンゾモルホリニルであり、さらに好ましくは置換若しくは非置換のフェニルまたは置換若しくは非置換のクロマニルである。 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.
　Ｒ３が置換基を有する場合、好ましい置換基は、ハロゲン、ヒドロキシ、アミノ、シアノ、オキソ、アルキル、ハロアルキル、アルケニル、アルキニル、ヒドロキシアルキル、アルキルオキシ、アルケニルオキシ、アルキニルオキシ、アルキルオキシアルキル、モノアルキルアミノ、ジアルキルアミノ、アルキルスルファニル、アルケニルスルファニル、またはアルキニルスルファニルであり、より好ましい置換基は、ハロゲン、アルキル、ハロアルキルまたはアルキルオキシであり、さらに好ましい置換基は、フルオロ、クロロ、ブロモ、ヨード、メチル、エチル、プロピル、イソプロピル、メチルオキシ、エチルオキシ、プロピルオキシ、イソプロピルオキシ、トリフルオロメチル、トリクロロメチル、トリブロモメチルまたはトリヨードメチルであり、特に好ましい置換基は、フルオロ、クロロ、メチル、メチルオキシ、イソプロピルオキシまたはトリフルオロメチルである。 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.
　Ｒ３は、さらに好ましくは、以下に示される基である。 R 3 is more preferably a group shown below.
Figure JPOXMLDOC01-appb-C000032
Figure JPOXMLDOC01-appb-C000032
Figure JPOXMLDOC01-appb-C000033
Figure JPOXMLDOC01-appb-C000033
　Ｒ４は、好ましくは、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、最も好ましくは、水素原子である。 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.
　Ｒ５は、好ましくは、存在しないか、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、特に好ましくは、存在しない。 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.
　Ｒ５が存在しない場合、式（Ｉ）で示される化合物は、 In the absence of R 5, the compound of formula (I) is
Figure JPOXMLDOC01-appb-C000034
のいずれかを示すが、好ましくは、式（ＩＩ）で示される構造を有する。
Figure JPOXMLDOC01-appb-C000034
Any one of the above, preferably has a structure represented by the formula (II).
Figure JPOXMLDOC01-appb-C000035
Figure JPOXMLDOC01-appb-C000035
　Ｒ６は、好ましくは、ハロゲン、シアノ、ニトロ、または－Ｚ６－Ｒ６１（Ｚ６は、単結合、－Ｏ－、－Ｓ－、－ＮＲ６２－、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－Ｏ－ＣＯ－、－ＣＯ－Ｏ－、－ＮＲ６２－ＣＯ－、－ＣＯ－ＮＲ６２－、－ＣＨ２－ＣＯ－ＮＲ６２－、－ＮＲ６３－ＣＯ－ＮＲ６２－、－ＮＲ６２－ＣＳ－、－ＣＳ－ＮＲ６２－、－ＮＲ６３－ＣＳ－ＮＲ６２－、－ＮＲ６２－ＳＯ２－、－ＳＯ２－ＮＲ６２－、または－ＮＲ６３－ＳＯ２－ＮＲ６２－；Ｒ６１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基；Ｒ６２およびＲ６３は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニル。ここで、Ｚ６が－ＮＲ６２－、－ＣＯ－ＮＲ６２－、－ＣＨ２－ＣＯ－ＮＲ６２－、－ＮＲ６３－ＣＯ－ＮＲ６２－、－ＣＳ－ＮＲ６２－、－ＮＲ６３－ＣＳ－ＮＲ６２－、－ＳＯ２－ＮＲ６２－、または－ＮＲ６３－ＳＯ２－ＮＲ６２－の場合は、Ｒ６１とＲ６２が隣接する窒素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良い）であり、より好ましくは、－Ｚ６－Ｒ６１である。
　ここで、Ｚ６は、より好ましくは、単結合、－ＮＲ６２－、－ＮＲ６２－ＣＯ－、－ＣＯ－ＮＲ６２－、－ＣＨ２－ＣＯ－ＮＲ６２－、－ＮＲ６３－ＣＯ－ＮＲ６２－、－ＮＲ６２－ＣＳ－、－ＣＳ－ＮＲ６２－、－ＮＲ６３－ＣＳ－ＮＲ６２－、－ＮＲ６２－ＳＯ２－、－ＳＯ２－ＮＲ６２－、または－ＮＲ６３－ＳＯ２－ＮＲ６２－であり、さらに好ましくは、単結合、－ＮＲ６２－、－ＮＲ６２－ＣＯ－、－ＣＯ－ＮＲ６２－、－ＣＨ２－ＣＯ－ＮＲ６２－、－ＮＲ６３－ＣＯ－ＮＲ６２－、－ＮＲ６３－ＣＳ－ＮＲ６２－、－ＮＲ６２－ＳＯ２－、または－ＮＲ６３－ＳＯ２－ＮＲ６２－であり、特に好ましくは、単結合である。Ｒ６１は、好ましくは、置換若しくは非置換のアルキル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、より好ましくは、アルキルであり、さらに好ましくはメチルである。Ｒ６２は、好ましくは、水素原子または置換若しくは非置換のアルキルであり、より好ましくは、水素原子またはアルキルであり、さらに好ましくは、水素原子である。Ｒ６３は、好ましくは、水素原子または置換若しくは非置換のアルキルであり、より好ましくは、水素原子またはアルキルであり、さらに好ましくは、水素原子である。
　Ｒ６１が置換されたアルキル、置換されたアルケニル、または置換されたアルキニルの場合、置換基は芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、または非芳香族複素環式基が好ましい。Ｒ６１が置換された芳香族炭素環式基、置換された非芳香族炭素環式基、置換された芳香族複素環式基、または置換された非芳香族複素環式基の場合、置換基はアルキル、アルケニル、アルキニル、芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、または非芳香族複素環式基が好ましい。
　Ｒ６は、さらに好ましくは、水素原子、ハロゲン、シアノ、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、または置換若しくは非置換の非芳香族炭素環式基であり、より好ましくは、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニルであり、さらに好ましくは、置換若しくは非置換のアルキルであり、特に好ましくは、炭素数１～４のアルキルであり、最も好ましくは、メチルである。 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.
　Ｒ７は、好ましくは、ハロゲン、シアノ、ニトロ、または－Ｚ７－Ｒ７１（Ｚ７は、単結合、－Ｏ－、－Ｓ－、－ＮＲ７２－、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－Ｏ－ＣＯ－、－ＣＯ－Ｏ－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７２－ＣＳ－、－ＣＳ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、－ＳＯ２－ＮＲ７２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－；Ｒ７１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基；Ｒ７２およびＲ７３は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニル。ここで、Ｚ７が－ＮＲ７２－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＣＳ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＳＯ２－ＮＲ７２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－の場合は、Ｒ７１とＲ７２が隣接する窒素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良い）であり、より好ましくは、－Ｚ７－Ｒ７１である。
　ここで、Ｚ７は、より好ましくは、単結合、－Ｏ－、－ＮＲ７２－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７２－ＣＳ－、－ＣＳ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、－ＳＯ２－ＮＲ７２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－であり、さらに好ましくは、単結合、－ＮＲ７２－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－であり、さらに好ましくは、－ＮＲ７２－または－ＮＲ７３－ＣＯ－ＮＲ７２－であり、特に好ましくは、－ＮＲ７３－ＣＯ－ＮＲ７２－であり、最も好ましくは、－ＮＨ－ＣＯ－ＮＨ－である。Ｒ７１は、好ましくは、置換若しくは非置換のアルキル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、より好ましくは、芳香族炭素環アルキル、非芳香族炭素環アルキル、芳香族複素環アルキル、非芳香族複素環アルキル、芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、または非芳香族複素環式基であり、さらに好ましくは、ベンジル、フェネチル、シクロヘキシル、ジヒドロインデニル、フェニル、ナフチル、ピリジル、ピリミジニルまたはシクロアルキルであり、特に好ましくは、４～８員のシクロアルキルである。Ｒ７２は、好ましくは、水素原子または置換若しくは非置換のアルキルであり、より好ましくは、水素原子またはアルキルであり、さらに好ましくは、水素原子またはメチルである。Ｒ７３は、好ましくは、水素原子または置換若しくは非置換のアルキルであり、より好ましくは、水素原子またはアルキルであり、さらに好ましくは、水素原子またはメチルであり、特に好ましくは水素原子である。Ｒ７１は、置換若しくは非置換の芳香族炭素環式基または置換若しくは非置換の非芳香族炭素環式基もより好ましく、置換若しくは非置換のシクロアルキルまたは置換若しくは非置換のフェニルもさらに好ましい。
　Ｒ７１が置換されたアルキル、置換されたアルケニル、または置換されたアルキニルの場合、置換基は芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、または非芳香族複素環式基が好ましく、芳香族炭素環式基がより好ましい。Ｒ７１が置換された芳香族炭素環式基、置換された非芳香族炭素環式基、置換された芳香族複素環式基、または置換された非芳香族複素環式基の場合、置換基はアルキル、アルケニル、アルキニル、芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、または非芳香族複素環式基が好ましい。
　Ｒ７は、さらに好ましくは、－Ｚ７－Ｒ７１（Ｚ７は、単結合、－Ｏ－、－ＮＲ７２－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－；Ｒ７１は、置換若しくは非置換のアルキル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基；Ｒ７２およびＲ７３は、それぞれ独立して、水素原子または置換若しくは非置換のアルキル）であり、特に好ましくは、－Ｚ７－Ｒ７１（Ｚ７は、単結合、－ＮＲ７２－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－；Ｒ７１は、芳香族炭素環アルキル、非芳香族炭素環アルキル、芳香族複素環アルキル、非芳香族複素環アルキル、芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、または非芳香族複素環式基；Ｒ７２は水素原子または置換若しくは非置換のアルキル；Ｒ７３は水素原子、あるいはＺ７は－ＮＲ７３－ＣＯ－ＮＲ７２－；Ｒ７１は、置換若しくは非置換の芳香族炭素環式基または置換若しくは非置換の非芳香族炭素環式基；Ｒ７２およびＲ７３は、それぞれ独立して、水素原子または置換若しくは非置換のアルキル）であり、最も好ましくは、－Ｚ７－Ｒ７１（Ｚ７は－ＮＨ－ＣＯ－ＮＨ－；Ｒ７１はシクロアルキル）である。 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).
　Ｒ７は、さらに好ましくは、以下に示される基である。 R 7 is more preferably a group shown below.
Figure JPOXMLDOC01-appb-C000036
Figure JPOXMLDOC01-appb-C000036
Figure JPOXMLDOC01-appb-C000037
Figure JPOXMLDOC01-appb-C000037
　Ｒ１とＲ７は、隣接する炭素原子と一緒になって、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基を形成しても良く、置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成するのがより好ましい
　Ｒ１とＲ７が隣接する炭素原子と一緒になって形成する環式基は、５～８員環の非芳香族複素環式基が好ましく、６員環がより好ましく、また、該環式基は、複数のＲＡで置換されていてもよい。ここで、ＲＡは、それぞれ独立して、好ましくは、ハロゲン、シアノ、ニトロ、オキソ、または－ＺＡ－ＲＡ１（ＺＡは、単結合、－Ｏ－、－Ｓ－、－ＮＲＡ２－、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－Ｏ－ＣＯ－、－ＣＯ－Ｏ－、－ＮＲＡ２－ＣＯ－、－ＣＯ－ＮＲＡ２－、－ＣＨ２－ＣＯ－ＮＲＡ２－、－ＮＲＡ３－ＣＯ－ＮＲＡ２－、－ＮＲＡ２－ＣＳ－、－ＣＳ－ＮＲＡ２－、－ＮＲＡ３－ＣＳ－ＮＲＡ２－、－ＮＲＡ２－ＳＯ２－、－ＳＯ２－ＮＲＡ２－、または－ＮＲＡ３－ＳＯ２－ＮＲＡ２－；ＲＡ１は、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基；ＲＡ２およびＲＡ３は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニル。ここで、ＺＡが－ＮＲＡ２－、－ＣＯ－ＮＲＡ２－、－ＣＨ２－ＣＯ－ＮＲＡ２－、－ＮＲＡ３－ＣＯ－ＮＲＡ２－、－ＣＳ－ＮＲＡ２－、－ＮＲＡ３－ＣＳ－ＮＲＡ２－、－ＳＯ２－ＮＲＡ２－、または－ＮＲＡ３－ＳＯ２－ＮＲＡ２－の場合は、ＲＡ１とＲＡ２が隣接する窒素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良い）であり、より好ましくは、オキソまたは－ＺＡ－ＲＡ１である。置換するＲＡの数は、５以下が好ましい。 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.
　Ｒ１とＲ７が隣接する炭素原子と一緒になって置換若しくは非置換の非芳香族複素環式基を形成する場合、式（Ｉ）で示される化合物は、好ましくは、式（ＩＩＩ）で示される構造を有する。 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.
Figure JPOXMLDOC01-appb-C000038
　ここで、Ｘは、－Ｃ（Ｒ１０）２－、－ＮＲ９－、または－Ｏ－が好ましく、－ＮＲ９－がより好ましい。Ｙは、－Ｃ（Ｒ１０）２－、－ＣＯ－、または－ＳＯ２－が好ましく、－ＣＨ２－または－ＣＯ－がより好ましい。Ｗは、－Ｃ（Ｒ１０）２－、－ＮＲ１０－、または－Ｏ－が好ましく、－ＣＨ２－がより好ましい。特に好ましくは、Ｘが－ＮＲ９－、Ｙが－ＣＨ２－または－ＣＯ－、Ｗが－ＣＨ２－である。
　Ｒ９は、好ましくは、ハロゲン、シアノ、ニトロ、または－Ｚ９－Ｒ９１（Ｚ９は、単結合、－Ｏ－、－Ｓ－、－ＮＲ９２－、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－Ｏ－ＣＯ－、－ＣＯ－Ｏ－、－ＮＲ９２－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＨ２－ＣＯ－ＮＲ９２－、－ＮＲ９３－ＣＯ－ＮＲ９２－、－ＮＲ９２－ＣＳ－、－ＣＳ－ＮＲ９２－、－ＮＲ９３－ＣＳ－ＮＲ９２－、－ＮＲ９２－ＳＯ２－、－ＳＯ２－ＮＲ９２－、または－ＮＲ９３－ＳＯ２－ＮＲ９２－；Ｒ９１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基；Ｒ９２およびＲ９３は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニル。ここで、Ｚ９が－ＮＲ９２－、－ＣＯ－ＮＲ９２－、－ＣＨ２－ＣＯ－ＮＲ９２－、－ＮＲ９３－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、－ＮＲ９３－ＣＳ－ＮＲ９２－、－ＳＯ２－ＮＲ９２－、または－ＮＲ９３－ＳＯ２－ＮＲ９２－の場合は、Ｒ９１とＲ９２が隣接する窒素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良い）であり、より好ましくは、－Ｚ９－Ｒ９１である。
　ここで、Ｚ９は、より好ましくは、単結合、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－であり、さらに好ましくは、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－であり、特に好ましくは、－ＣＯ－ＮＲ９２－であり、最も好ましくは、－ＣＯ－ＮＨ－である。
　Ｒ９１は、好ましくは、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換の芳香族炭素環式基、または置換若しくは非置換の非芳香族炭素環式基であり、より好ましくは、置換若しくは非置換のアルキル、置換若しくは非置換の芳香族炭素環式基または置換若しくは置換若しくは非置換の非芳香族炭素環式基であり、さらに好ましくは、メチル、ベンジル、フェニルまたはシクロアルキルであり、最も好ましくは、４～８員のシクロアルキルである。
　Ｒ９２は、好ましくは、水素原子または置換若しくは非置換のアルキルであり、より好ましくは、水素原子またはメチルであり、特に好ましくは水素原子である。Ｒ９３は、好ましくは、水素原子または置換若しくは非置換のアルキルであり、より好ましくは、水素原子またはメチルであり、特に好ましくは水素原子である。
　Ｒ９１が置換されたアルキル、置換されたアルケニル、または置換されたアルキニルの場合、置換基は芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、または非芳香族複素環式基が好ましく、芳香族炭素環式基がより好ましい。Ｒ９１が置換された芳香族炭素環式基、置換された非芳香族炭素環式基、置換された芳香族複素環式基、または置換された非芳香族複素環式基の場合、置換基はアルキル、アルケニル、アルキニル、芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、または非芳香族複素環式基が好ましい。
　Ｒ９は、さらに好ましくは、－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換の芳香族炭素環式基、または置換若しくは非置換の非芳香族炭素環式基；Ｒ９２は、水素原子または置換若しくは非置換のアルキル）であり、特に好ましくは、－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換の芳香族炭素環式基、または置換若しくは非置換の非芳香族複素環式基；Ｒ９２は水素原子）、最も好ましくは、－Ｚ９－Ｒ９１（Ｚ９は－ＣＯ－ＮＨ－；Ｒ９１はシクロアルキル）である。
Figure JPOXMLDOC01-appb-C000038
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).
　Ｒ９は、さらに好ましくは、以下に示される基である。 R 9 is more preferably a group shown below.
Figure JPOXMLDOC01-appb-C000039
Figure JPOXMLDOC01-appb-C000039
Figure JPOXMLDOC01-appb-C000040
　Ｒ９は、特に末端にシクロアルキル、フェニル等の環式基を有しているのが望ましい。該環式基はアダマンチル等のように架橋構造を有していてもよい。
　Ｒ１０は、それぞれ独立して、好ましくは、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルケニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、より好ましくは水素原子または置換若しくは非置換のアルキル、さらに好ましくは、水素原子である。
　Ｒ１０が置換されたアルキル、置換されたアルケニル、または置換されたアルキニルの場合、置換基は芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、または非芳香族複素環式基が好ましい。Ｒ１０が置換された芳香族炭素環式基、置換された非芳香族炭素環式基、置換された芳香族複素環式基、または置換された非芳香族複素環式基の場合、置換基はアルキル、アルケニル、アルキニル、芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、または非芳香族複素環式基が好ましい。
Figure JPOXMLDOC01-appb-C000040
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.
　Ｒ５とＲ７は、隣接する窒素原子および炭素原子と一緒になって、置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良い。
　Ｒ５とＲ７が隣接する窒素原子および炭素原子と一緒になって形成する環式基は、５～８員環が好ましく、５～６員環がより好ましく、５員環がさらに好ましく、また、それぞれ独立した複数のＲ８で置換されていてもよい。置換するＲ８の数は、２以下が好ましく、１以下がより好ましい。該環式基は、好ましくは窒素原子を１～４個含有し、より好ましくは、以下のいずれかの構造を示す（式中、破線は結合の存在または非存在を示し、ただし、隣接する破線が同時に結合の存在を示すことはない）。 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).
Figure JPOXMLDOC01-appb-C000041
Figure JPOXMLDOC01-appb-C000041
　Ｒ５とＲ７が隣接する窒素原子および炭素原子と一緒になって置換若しくは非置換の芳香族複素環式基を形成する場合、式（Ｉ）で示される化合物は、好ましくは、式（ＩＶ）～（ＶＩ）のいずれかで示される構造を有する。 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).
Figure JPOXMLDOC01-appb-C000042
　ここで、Ｒ８は、好ましくは、ハロゲン、シアノ、ニトロ、または－Ｚ８－Ｒ８１（Ｚ８は、単結合、－Ｏ－、－Ｓ－、－ＮＲ８２－、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－Ｏ－ＣＯ－、－ＣＯ－Ｏ－、－ＮＲ８２－ＣＯ－、－ＣＯ－ＮＲ８２－、－ＣＨ２－ＣＯ－ＮＲ８２－、－ＮＲ８３－ＣＯ－ＮＲ８２－、－ＮＲ８２－ＣＳ－、－ＣＳ－ＮＲ８２－、－ＮＲ８３－ＣＳ－ＮＲ８２－、－ＮＲ８２－ＳＯ２－、－ＳＯ２－ＮＲ８２－、または－ＮＲ８３－ＳＯ２－ＮＲ８２－；Ｒ８１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基；Ｒ８２およびＲ８３は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニル。ここで、Ｚ８が－ＮＲ８２－、－ＣＯ－ＮＲ８２－、－ＣＨ２－ＣＯ－ＮＲ８２－、－ＮＲ８３－ＣＯ－ＮＲ８２－、－ＣＳ－ＮＲ８２－、－ＮＲ８３－ＣＳ－ＮＲ８２－、－ＳＯ２－ＮＲ８２－、または－ＮＲ８３－ＳＯ２－ＮＲ８２－の場合は、Ｒ８１とＲ８２が隣接する窒素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良い）であり、より好ましくは、水素原子または置換若しくは非置換の芳香族炭素環式基であり、さらに好ましくは、置換若しくは非置換の芳香族炭素環式基であり、特に好ましくは、置換若しくは非置換のフェニルであり、最も好ましくは、フェニルである。該フェニルが置換されている場合、好ましい置換基はハロゲン、アルキル、ハロアルキル、アルコキシ等が例示される。
　Ｒ８１が置換されたアルキル、置換されたアルケニル、または置換されたアルキニルの場合、置換基は芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、または非芳香族複素環式基が好ましい。Ｒ８１が置換された芳香族炭素環式基、置換された非芳香族炭素環式基、置換された芳香族複素環式基、または置換された非芳香族複素環式基の場合、置換基はアルキル、アルケニル、アルキニル、芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、または非芳香族複素環式基が好ましい。
Figure JPOXMLDOC01-appb-C000042
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.
　Ｒ５とＲ６は、隣接する窒素原子および炭素原子と一緒になって、置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良い。
　例えば、式（Ｉ）は、以下に示される構造をとってもよい。 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.
Figure JPOXMLDOC01-appb-C000043
Figure JPOXMLDOC01-appb-C000043
　式（Ｉ）で示される化合物の好ましい態様として、式（ＩＩ）における、以下の１）～４）が挙げられる。 Preferred embodiments of the compound represented by the formula (I) include the following 1) to 4) in the formula (II).
Figure JPOXMLDOC01-appb-C000044
１）Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｒ７が－Ｚ７－Ｒ７１（Ｚ７は、単結合、－ＮＲ７２－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－；Ｒ７１は、置換若しくは非置換のアルキル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基；Ｒ７２は水素原子または置換若しくは非置換のアルキル；Ｒ７３は水素原子）である化合物。
２）Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｒ７が－Ｚ７－Ｒ７１（Ｚ７は、単結合、－ＮＲ７２－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－；Ｒ７１は、置換若しくは非置換のアルキル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基；Ｒ７２は水素原子または置換若しくは非置換のアルキル；Ｒ７３は水素原子）である化合物。
３）Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｒ７が－Ｚ７－Ｒ７１（Ｚ７は、単結合、－ＮＲ７２－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－；Ｒ７１は、置換若しくは非置換のアルキル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基；Ｒ７２は水素原子または置換若しくは非置換のアルキル；Ｒ７３は水素原子）である化合物。
４）Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｒ７が－Ｚ７－Ｒ７１（Ｚ７は、単結合、－ＮＲ７２－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－；Ｒ７１は、置換若しくは非置換のアルキル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基；Ｒ７２は水素原子または置換若しくは非置換のアルキル；Ｒ７３は水素原子）である化合物。
Figure JPOXMLDOC01-appb-C000044
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).
　式（Ｉ）で示される化合物の別の好ましい態様として、式（ＩＩＩ）における、以下の５）～２８）が挙げられる。 As another preferred embodiment of the compound represented by the formula (I), the following 5) to 28) in the formula (III) may be mentioned.
Figure JPOXMLDOC01-appb-C000045
５）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＯ－であり、Ｗが－ＣＨ２－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
６）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＯ－であり、Ｗが－ＣＨ２－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
７）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＯ－であり、Ｗが－ＣＨ２－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
８）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＯ－であり、Ｗが－ＣＨ２－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
９）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＨ２－であり、Ｗが－ＣＨ２－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
１０）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＨ２－であり、Ｗが－ＣＨ２－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
１１）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＨ２－であり、Ｗが－ＣＨ２－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
１２）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＨ２－であり、Ｗが－ＣＨ２－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
１３）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＯ－であり、Ｗが－ＮＨ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
１４）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＯ－であり、Ｗが－ＮＨ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
１５）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＯ－であり、Ｗが－ＮＨ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
１６）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＯ－であり、Ｗが－ＮＨ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
１７）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＳＯ２－であり、Ｗが－ＮＨ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
１８）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＳＯ２－であり、Ｗが－ＮＨ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
１９）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＳＯ２－であり、Ｗが－ＮＨ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
２０）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＳＯ２－であり、Ｗが－ＮＨ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
２１）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＯ－であり、Ｗが－Ｏ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
２２）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＯ－であり、Ｗが－Ｏ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
２３）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＯ－であり、Ｗが－Ｏ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
２４）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＣＯ－であり、Ｗが－Ｏ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
２５）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＳＯ２－であり、Ｗが－Ｏ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
２６）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＳＯ２－であり、Ｗが－Ｏ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
２７）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＳＯ２－であり、Ｗが－Ｏ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
２８）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、Ｙが－ＳＯ２－であり、Ｗが－Ｏ－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、単結合、－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、または－ＳＯ２－ＮＲ９２－；Ｒ９１は、置換若しくは非置換のアルキルまたは置換若しくは非置換の芳香族炭素環式基；Ｒ９２は水素原子）である化合物。
Figure JPOXMLDOC01-appb-C000045
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).
　式（Ｉ）で示される化合物の別の好ましい態様として、式（ＩＶ）～（ＶＩ）のいずれかにおける、以下の２９）～３２）が挙げられる。 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.
Figure JPOXMLDOC01-appb-C000046
２９）Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｒ８が置換若しくは非置換の芳香族炭素環式基である化合物。
３０）Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｒ８が置換若しくは非置換の芳香族炭素環式基である化合物。
３１）Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｒ８が置換若しくは非置換の芳香族炭素環式基である化合物。
３２）Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の非芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｒ８が置換若しくは非置換の芳香族炭素環式基である化合物。
　なお、２９）～３２）において、式（ＶＩ）の化合物については、Ｒ８は存在しない。
Figure JPOXMLDOC01-appb-C000046
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).
　式（Ｉ）で示される化合物の別の好ましい態様として、式（ＩＩ）における、以下の５１）～５２）、および式（ＩＩＩ）における、以下の５３）～５４）が挙げられる。 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).
Figure JPOXMLDOC01-appb-C000047
５１）Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｒ７が－Ｚ７－Ｒ７１（Ｚ７は、－ＮＨ－ＣＯ－ＮＨ－；Ｒ７１は、置換若しくは非置換の芳香族炭素環式基）である化合物。
５２）Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｒ７が－Ｚ７－Ｒ７１（Ｚ７は、－ＮＨ－ＣＯ－ＮＨ－；Ｒ７１は、置換若しくは非置換の非芳香族炭素環式基）である化合物。
Figure JPOXMLDOC01-appb-C000047
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.
Figure JPOXMLDOC01-appb-C000048
５３）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、ＹおよびＷが共に－ＣＨ２－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、－ＣＯ－ＮＨ－；Ｒ９１は、置換若しくは非置換の芳香族炭素環式基）である化合物。
５４）Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換の芳香族炭素環式基であり、Ｒ４が水素原子であり、Ｒ６が置換若しくは非置換のアルキルであり、Ｘが－ＮＲ９－であり、ＹおよびＷが共に－ＣＨ２－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は、－ＣＯ－ＮＨ－；Ｒ９１は、置換若しくは非置換の非芳香族炭素環式基）である化合物。
Figure JPOXMLDOC01-appb-C000048
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).
　本発明に係る化合物の特徴は、式（Ｉ）において、
（１）主骨格であるピリジン環に環式基（Ｒ３）が置換しており、
（２）同ピリジン環の４位において、－Ｃ（Ｒ２）ｎＣＯＯＲ４で（ｎ＝１、２）示される側鎖を有することにより、
ＨＩＶ複製阻害作用を有する点である。 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.
　本発明に係る化合物の別の特徴は、式（Ｉ）のＲ２として、好ましくは置換若しくは非置換のアルキルオキシ基が導入され、Ｒ４が水素原子であることにより、高いＨＩＶ複製阻害作用を有する点である。 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.
　本発明に係る化合物は耐性ウイルスに対して強いＨＩＶ複製阻害作用を示す。特に、Ｒ７が－Ｚ７－Ｒ７１（Ｚ７は－ＮＲ７３－ＣＯ－ＮＲ７２－；Ｒ７１は置換若しくは非置換の非芳香族炭素環式基）である式（ＩＩ）で示される化合物、およびＸが－ＮＲ９－であり、Ｒ９が－Ｚ９－Ｒ９１（Ｚ９は－ＣＯ－ＮＲ９２－；Ｒ９１は置換若しくは非置換の非芳香族炭素環式基）である式（ＩＩＩ）で示される化合物は、耐性ウイルスに対して強いＨＩＶ複製阻害作用を示す。即ち、本発明化合物の好ましい態様として、式（ＩＩ）におけるＲ７や式（ＩＩＩ）におけるＸにウレア構造が存在することは、強い薬効を示す上で重要である。 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.
　式（Ｉ）で示される化合物は、特定の異性体に限定するものではなく、全ての可能な異性体（例えば、ケト－エノール異性体、イミン－エナミン異性体、ジアステレオ異性体、アトロプ異性体、光学異性体、回転異性体等）、ラセミ体またはそれらの混合物を含む。 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.
　式（Ｉ）で示される化合物の一つ以上の水素、炭素および／または他の原子は、それぞれ水素、炭素および／または他の原子の同位体で置換され得る。そのような同位体の例としては、それぞれ２Ｈ、３Ｈ、１１Ｃ、１３Ｃ、１４Ｃ、１５Ｎ、１８Ｏ、１７Ｏ、３１Ｐ、３２Ｐ、３５Ｓ、１８Ｆ、１２３Ｉおよび３６Ｃｌのように、水素、炭素、窒素、酸素、リン、硫黄、フッ素、ヨウ素および塩素が包含される。式（Ｉ）で示される化合物は、そのような同位体で置換された化合物も包含する。該同位体で置換された化合物は、医薬品としても有用であり、式（Ｉ）で示される化合物のすべての放射性標識体を包含する。また該「放射性標識体」を製造するための「放射性標識化方法」も本発明に包含され、代謝薬物動態研究、結合アッセイにおける研究および／または診断のツールとして有用である。 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.
　式（Ｉ）で示される化合物の放射性標識体は、当該技術分野で周知の方法で調製できる。例えば、式（Ｉ）で示されるトリチウム標識化合物は、例えば、トリチウムを用いた触媒的脱ハロゲン化反応によって、式（Ｉ）で示される特定の化合物にトリチウムを導入することで調製できる。この方法は、適切な触媒、例えばＰｄ／Ｃの存在下、塩基の存在下または非存在下で、式（Ｉ）で示される化合物が適切にハロゲン置換された前駆体とトリチウムガスとを反応させることを包含する。他のトリチウム標識化合物を調製するための適切な方法としては、文書Ｉｓｏｔｏｐｅｓ　ｉｎ　ｔｈｅ　Ｐｈｙｓｉｃａｌ　ａｎｄ　Ｂｉｏｍｅｄｉｃａｌ　Ｓｃｉｅｎｃｅｓ，Ｖｏｌ．１，Ｌａｂｅｌｅｄ　Ｃｏｍｐｏｕｎｄｓ　（Ｐａｒｔ　Ａ），Ｃｈａｐｔｅｒ　６　（１９８７年）を参照にできる。１４Ｃ－標識化合物は、１４Ｃ炭素を有する原料を用いることによって調製できる。 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.
　式（Ｉ）で示される化合物の製薬上許容される塩としては、例えば、式（Ｉ）で示される化合物と、アルカリ金属（例えば、リチウム、ナトリウム、カリウム等）、アルカリ土類金属（例えば、カルシウム、バリウム等）、マグネシウム、遷移金属（例えば、亜鉛、鉄等）、アンモニア、有機塩基（例えば、トリメチルアミン、トリエチルアミン、ジシクロヘキシルアミン、エタノールアミン、ジエタノールアミン、トリエタノールアミン、メグルミン、ジエタノールアミン、エチレンジアミン、ピリジン、ピコリン、キノリン等）およびアミノ酸との塩、または無機酸（例えば、塩酸、硫酸、硝酸、炭酸、臭化水素酸、リン酸、ヨウ化水素酸等）、および有機酸（例えば、ギ酸、酢酸、プロピオン酸、トリフルオロ酢酸、クエン酸、乳酸、酒石酸、シュウ酸、マレイン酸、フマル酸、マンデル酸、グルタル酸、リンゴ酸、安息香酸、フタル酸、アスコルビン酸、ベンゼンスルホン酸、ｐ－トルエンスルホン酸、メタンスルホン酸、エタンスルホン酸等）との塩が挙げられる。特に塩酸、硫酸、リン酸、酒石酸、メタンスルホン酸との塩等が挙げられる。これらの塩は、通常行われる方法によって形成させることができる。 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.
　本発明の式（Ｉ）で示される化合物またはその製薬上許容される塩は、溶媒和物（例えば、水和物等）および／または結晶多形を形成する場合があり、本発明はそのような各種の溶媒和物および結晶多形も包含する。「溶媒和物」は、式（Ｉ）で示される化合物に対し、任意の数の溶媒分子（例えば、水分子等）と配位していてもよい。式（Ｉ）で示される化合物またはその製薬上許容される塩を、大気中に放置することにより、水分を吸収し、吸着水が付着する場合や、水和物を形成する場合がある。また、式（Ｉ）で示される化合物またはその製薬上許容される塩を、再結晶することでそれらの結晶多形を形成する場合がある。 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.
　本発明の式（Ｉ）で示される化合物またはその製薬上許容される塩は、プロドラッグを形成する場合があり、本発明はそのような各種のプロドラッグも包含する。プロドラッグは、化学的または代謝的に分解できる基を有する本発明化合物の誘導体であり、加溶媒分解によりまたは生理学的条件下でインビボにおいて薬学的に活性な本発明化合物となる化合物である。プロドラッグは、生体内における生理条件下で酵素的に酸化、還元、加水分解等を受けて式（Ｉ）で示される化合物に変換される化合物、胃酸等により加水分解されて式（Ｉ）で示される化合物に変換される化合物等を包含する。適当なプロドラッグ誘導体を選択する方法および製造する方法は、例えばＤｅｓｉｇｎ　ｏｆ　Ｐｒｏｄｒｕｇｓ，　Ｅｌｓｅｖｉｅｒ，　Ａｍｓｔｅｒｄａｍ　１９８５に記載されている。プロドラッグは、それ自身が活性を有する場合がある。 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.
　式（Ｉ）で示される化合物またはその製薬上許容される塩がヒドロキシル基を有する場合は、例えば、ヒドロキシル基を有する化合物と適当なアシルハライド、適当な酸無水物、適当なスルホニルクロライド、適当なスルホニルアンハイドライドおよびミックスドアンハイドライドとを反応させることにより或いは縮合剤を用いて反応させることにより製造されるアシルオキシ誘導体やスルホニルオキシ誘導体のようなプロドラッグが例示される。例えば、ＣＨ３ＣＯＯ－、Ｃ２Ｈ５ＣＯＯ－、ｔ－ＢｕＣＯＯ－、Ｃ１５Ｈ３１ＣＯＯ－、ＰｈＣＯＯ－、（ｍ－ＮａＯＯＣＰｈ）ＣＯＯ－、ＮａＯＯＣＣＨ２ＣＨ２ＣＯＯ－、ＣＨ３ＣＨ（ＮＨ２）ＣＯＯ－、ＣＨ２Ｎ（ＣＨ３）２ＣＯＯ－、ＣＨ３ＳＯ３－、ＣＨ３ＣＨ２ＳＯ３－、ＣＦ３ＳＯ３－、ＣＨ２ＦＳＯ３－、ＣＦ３ＣＨ２ＳＯ３－、ｐ－ＣＨ３－Ｏ－ＰｈＳＯ３－、ＰｈＳＯ３－、ｐ－ＣＨ３ＰｈＳＯ３－が挙げられる。 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.
（本発明の化合物の製造法）
　本発明に係る式（Ｉ）で示される化合物は、例えば、下記に示す一般的合成法によって製造することができる。また、抽出、精製等は、通常の有機化学の実験で行う処理を行えばよい。
　本発明の化合物の合成は、当該分野において公知の手法を参酌しながら実施することができる。 (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）化合物Ａ－１およびＡ－２の合成 1) Synthesis of compounds A-1 and A-2
Figure JPOXMLDOC01-appb-C000049
Figure JPOXMLDOC01-appb-C000049
Figure JPOXMLDOC01-appb-C000050
（式中、Ｒ３、Ｒ４、Ｒ７１は前記と同意義。Ｒ２’は置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニル等。）

第１工程
　水溶媒中、化合物ａ１にベンジルアミンを加え、５０℃～１５０℃、好ましくは７０℃～１３０℃で、０．１時間～８時間、好ましくは０．５時間～２時間反応させることにより、化合物ａ２を得ることができる。

第２工程
　ジクロロメタン、ＴＨＦ、ジクロロエタン等の溶媒中、またはそれらの混合溶媒中、化合物ａ２にピリジン、ルチジン、トリエチルアミンなどの塩基とトリフルオロメタンスルホン酸無水物、ｃｏｍｉｎ’ｓ試薬などのトリフラート化剤を加え、－５０℃～５０℃、好ましくは－３０℃～３０℃で、０．１時間～４時間、好ましくは０．５時間～１時間で反応させることにより、化合物ａ３を得ることができる。

第３工程
　ＤＭＦ、ＤＭＡ、ＴＨＦ、ジオキサン等の溶媒中、またはそれらの混合溶媒中、化合物ａ３にトリｔｅｒｔ－ブチルホスフィン、トリシクロヘキシルホスフィン、トリフェニルホスフィンなどのホスフィンとジベンジリデンアセトンパラジウム、酢酸パラジウム、ジクロロビストリフェニルホスフィンパラジウムなどの触媒とフッ化亜鉛と別途調整したシリルエノールエーテルａ４を加え、５０℃～１５０℃、好ましくは７０℃～１３０℃で、０．１時間～８時間、好ましくは０．５時間～２時間で反応させることにより、化合物ａ５を得ることができる。

第４工程
　ジクロロメタン、クロロホルム、ジクロロエタン等の溶媒中、またはそれらの混合溶媒中、化合物ａ５に臭素やＮＢＳなどの臭素化剤を加え、－５０℃～５０℃、好ましくは－３０℃～３０℃で、０．１時間～４時間、好ましくは０．５時間～１時間で反応させることにより、化合物ａ６を得ることができる。

第５工程
　ＤＭＦ、ＤＭＡ、ＴＨＦ、ジオキサン、水等の溶媒中、またはそれらの混合溶媒中、化合物ａ６に炭酸カリウム、炭酸ナトリウム、リン酸カリウムなどの塩基の水溶液とボロン酸ａ７、またはボロン酸エステルａ８とジベンジリデンアセトンパラジウム、酢酸パラジウム、ジクロロビストリフェニルホスフィンパラジウムなどの触媒を加え、５０℃～１５０℃、好ましくは７０℃～１３０℃で、０．１時間～８時間、好ましくは０．５～２時間で反応させることにより、化合物ａ９を得ることができる。

第６工程
　メタノール、酢酸エチル、酢酸等の溶媒中、またはそれらの混合溶媒中、化合物ａ９にパラジウム炭素、水酸化パラジウム、ラネーニッケルなどの触媒を加え、水素雰囲気下、３０℃～１３０℃、好ましくは５０℃～１１０℃で、０．１時間～８時間、好ましくは０．５～２時間で反応させることにより、化合物ａ１０を得ることができる。

第７工程
　化合物ａ１０より、第２工程と同様の方法で、化合物ａ１１を得ることができる。

第８工程　
　ＤＭＦ、ＤＭＡ、ＴＨＦ、ジオキサン等の溶媒中、またはそれらの混合溶媒中、化合物ａ１１にトリエチルアミン、ルチジン、ピリジンなどの塩基とベンジルアミンとジベンジリデンアセトンパラジウム、酢酸パラジウム、ジクロロビストリフェニルホスフィンパラジウムなどの触媒とキサントホス、トリ－ｔｅｒｔ－ブチルホスフィンなどの配位子を加え、５０℃～１５０℃、好ましくは７０℃～１３０℃で、０．１時間～８時間、好ましくは０．５～２時間で反応させることにより、化合物ａ１２を得ることができる。

第９工程
　化合物ａ１２より、第２工程と同様の方法で、化合物ａ１３を得ることができる。

第１０工程
　ジクロロエタン、ベンゼン、ジオキサン等の溶媒中、またはそれらの混合溶媒中、化合物ａ１３にトリエチルアミン、ルチジン、ピリジンなどの塩基とイソシアネートａ１４を加え、５０℃～１５０℃、好ましくは７０℃～１３０℃で、０．１時間～８時間、好ましくは０．５～２時間で反応させることにより、化合物Ａ－１を得ることができる。

第１１工程
　メタノール、ＴＨＦ、ジオキサンなどの溶媒中、またはそれらの混合溶媒中、化合物Ａ－１に水酸化ナトリウム水溶液、水酸化カリウム水溶液、水酸化リチウム水溶液などの塩基を加え、１０℃～１１０℃、好ましくは３０℃～９０℃で、０．１時間～８時間、好ましくは、０．５時間～１時間反応させることにより、化合物Ａ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000050
(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.
　ここで、ａ４は以下に示す方法により合成することができる。 Here, a4 can be synthesized by the following method.
Figure JPOXMLDOC01-appb-C000051
第１２工程
　ＴＨＦ、ジエチルエーテル、ジオキサン等の溶媒中、またはそれらの混合溶媒中、化合物ａ１５にｔｅｒｔ－ブタノール、イソプロパノール、メタノールなどのアルコールと、水素化ナトリウム、水素化リチウム、水素化カリウムなどの金属試薬を加え、２０℃～１２０℃、好ましくは４０℃から１００℃で、０．１時間～１２時間、好ましくは０．５時間～６時間反応させることにより、化合物ａ１６を得ることができる。

第１３工程
　ＤＭＦ、ＤＭＡ、ＴＨＦ、ジオキサン等の溶媒中、またはそれらの混合溶媒中、化合物ａ１６に炭酸カリウム、炭酸カルシウム、リン酸カリウムなどの塩基とＲ４－Ｉ、Ｒ４－Ｂｒ、Ｒ４－ＯＳＯ３Ｈなどを加え、－３０℃～７０℃、好ましくは－１０℃～５０℃で、０．１時間～５時間、好ましくは、０．５時間～１時間反応させることにより、化合物ａ１７を得ることができる。

第１４工程
　ＴＨＦ、ジエチルエーテル、ジオキサン等の溶媒中、またはそれらの混合溶媒中、化合物ａ１７にカリウムヘキサメチルジシラシド、リチウムヘキサメチルジシラシド、リチウムジイソプロピルアミドなどの塩基とＴＭＳＣｌ、ＴＭＳＯＴｆなどのシリル化剤を加え、－１３０℃～－２０℃、好ましくは－１１０℃から－５０℃で、０．１時間～５時間、好ましくは、０．５時間～１時間反応させることにより、化合物ａ４を得ることができる。
Figure JPOXMLDOC01-appb-C000051
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）化合物Ｂ－１およびＢ－２の合成 2) Synthesis of compounds B-1 and B-2
Figure JPOXMLDOC01-appb-C000052
（式中、各定義は前記と同意義。）

第１工程
　ＤＭＦ、ＤＭＡ、ＴＨＦ、ジオキサン等の溶媒中、またはそれらの混合溶媒中、化合物ａ１１にトリエチルアミン、ピリジンなどの塩基とアミンｂ１とジベンジリデンアセトンパラジウム、酢酸パラジウム、ジクロロビストリフェニルホスフィンパラジウムなどの触媒と臭化リチウム、臭化ナトリウム、臭化カリウムなどの無機塩を加え、一酸化炭素雰囲気下、５０℃～１５０℃、好ましくは７０℃～１３０℃で、０．１時間～８時間、好ましくは０．５～２時間で反応させることにより、化合物Ｂ－１を得ることができる。

第２工程
　化合物Ｂ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｂ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000052
(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）化合物Ｃ－１およびＣ－２の合成 3) Synthesis of compounds C-1 and C-2
Figure JPOXMLDOC01-appb-C000053
（式中、各定義は前記と同意義。）

第１工程
　化合物ａ１１より、前述の１）における第５工程と同様の方法で、化合物Ｃ－１を得ることができる。

第２工程
　化合物Ｃ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｃ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000053
(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）化合物Ｄ－１およびＤ－２の合成 4) Synthesis of compounds D-1 and D-2
Figure JPOXMLDOC01-appb-C000054
（式中、各定義は前記と同意義。）

第１工程
　ジクロロメタン、ＴＨＦ、ジクロロエタン等の溶媒中、またはそれらの混合溶媒中、化合物ａ１３にピリジン、ルチジン、トリエチルアミンなどの塩基と酸塩化物ｄ１を加え、－５０℃～５０℃、好ましくは－３０℃～３０℃で、０．１時間～４時間、好ましくは０．５時間～１時間で反応させることにより、化合物Ｄ－１を得ることができる。

第２工程
　化合物Ｄ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｄ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000054
(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）化合物Ｅ－１およびＥ－２の合成 5) Synthesis of compounds E-1 and E-2
Figure JPOXMLDOC01-appb-C000055
（式中、各定義は前記と同意義。）

第１工程
　ジクロロメタン、ＴＨＦ、ジクロロエタン等の溶媒中、またはそれらの混合溶媒中、化合物ａ１３にピリジン、ルチジン、トリエチルアミンなどの塩基とスルホン酸塩化物ｅ１を加え、－５０℃～５０℃、好ましくは－３０℃～３０℃で、０．１時間～４時間、好ましくは０．５時間～１時間で反応させることにより、化合物Ｅ－１を得ることができる。

第２工程
　化合物Ｅ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｅ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000055
(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）化合物Ｆ－１およびＦ－２の合成 6) Synthesis of compounds F-1 and F-2
Figure JPOXMLDOC01-appb-C000056
Figure JPOXMLDOC01-appb-C000056
Figure JPOXMLDOC01-appb-C000057
（式中、Ｒ２’、Ｒ３、Ｒ４、Ｒ９１は前記と同意義。Ｌ１は置換若しくは非置換のアルキル等。）

第１工程
　化合物ｆ１より、前述の１）における第１工程と同様の方法で、化合物ｆ２を得ることができる。

第２工程
　化合物ｆ２より、前述の１）における第２工程と同様の方法で、化合物ｆ３を得ることができる。

第３工程
　化合物ｆ３より、前述の１）における第３工程と同様の方法で、化合物ｆ４を得ることができる。

第４工程
　化合物ｆ４より、前述の１）における第４工程と同様の方法で、化合物ｆ５を得ることができる。

第５工程
　化合物ｆ５より、前述の１）における第５工程と同様の方法で、化合物ｆ８を得ることができる。

第６工程
　化合物ｆ８より、前述の１）における第６工程と同様の方法で、化合物ｆ９を得ることができる。

第７工程
　化合物ｆ９より、前述の１）における第７工程と同様の方法で、化合物ｆ１０を得ることができる。

第８工程
　化合物ｆ１０より、前述の１）における第８工程と同様の方法で、化合物ｆ１１を得ることができる。

第９工程　
　化合物ｆ１１より、前述の１）における第４工程と同様の方法で、化合物ｆ１２を得ることができる。

第１０工程
　化合物ｆ１２より、前述の１）における第５工程と同様の方法で、化合物ｆ１３を得ることができる。

第１１工程
　化合物ｆ１３より、前述の１）における第６工程と同様の方法で、化合物ｆ１４を得ることができる。

第１２工程
　化合物ｆ１４より、前述の４）における第１工程と同様の方法で、化合物Ｆ－１を得ることができる。

第１３工程
　化合物Ｆ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｆ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000057
(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）化合物Ｇ－１およびＧ－２の合成 7) Synthesis of compounds G-1 and G-2
Figure JPOXMLDOC01-appb-C000058
（式中、各定義は前記と同意義。）

第１工程
　ジオキサン、ＴＨＦ、ジエチルエーテル等の溶媒中、またはそれらの混合溶媒中、化合物ｆ１４に水素化ナトリウム、水素化カリウム、水素化リチウムなどの塩基とクロロギ酸フェニルｇ１を加え、－５０℃～５０℃、好ましくは－３０℃～３０℃で、０．１時間～４時間、好ましくは０．５時間～１時間で反応させることにより、化合物ｇ２を得ることができる。

第２工程
　ジクロロメタン、クロロホルム、ジクロロエタン等の溶媒中、またはそれらの混合溶媒中、化合物ｇ２にピリジン、ルチジン、トリエチルアミンなどの塩基とアミンｇ３を加え、－３０℃～７０℃、好ましくは－１０℃～５０℃で、０．１時間～８時間、好ましくは０．５時間～２時間で反応させることにより、化合物Ｇ－１を得ることができる。

第３工程
　化合物Ｇ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｇ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000058
(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）化合物Ｈ－１およびＨ－２の合成 8) Synthesis of compounds H-1 and H-2
Figure JPOXMLDOC01-appb-C000059
（式中、各定義は前記と同意義。）

第１工程
　化合物ｆ１０より、前述の１）における第８工程と同様の方法で、化合物ｈ１を得ることができる。

第２工程
　化合物ｈ１より、前述の１）における第４工程と同様の方法で、化合物ｈ２を得ることができる。

第３工程
　化合物ｈ２より、前述の１）における第５工程と同様の方法で、化合物Ｈ－１を得ることができる。

第４工程
　化合物Ｈ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｈ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000059
(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）化合物Ｉ－１およびＩ－２の合成 9) Synthesis of compounds I-1 and I-2
Figure JPOXMLDOC01-appb-C000060
（式中、各定義は前記と同意義。）

第１工程
　ジオキサン、ＴＨＦ、ジエチルエーテル等の溶媒中、またはそれらの混合溶媒中、化合物ｆ１４にボラン－ＴＨＦ、ボラン－ジエチルエーテル、ボラン－ジメチルスルファンなどの還元剤を加え、－３０℃～７０℃、好ましくは－１０℃～５０℃で、０．１時間～８時間、好ましくは０．５時間～２時間で反応させることにより、化合物ｉ１を得ることができる。

第２工程
　化合物ｉ１より、前述の４）における第１工程と同様の方法で、化合物Ｈ－１を得ることができる。

第三工程
　化合物Ｉ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｉ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000060
(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）化合物Ｊ－１およびＪ－２の合成 10) Synthesis of compounds J-1 and J-2
Figure JPOXMLDOC01-appb-C000061
（式中、各定義は前記と同意義。）

第１工程
　化合物ｉ１より、前述の７）における第１工程と同様の方法で、化合物ｊ１を得ることができる。

第２工程
　化合物ｊ１より、前述の７）における第２工程と同様の方法で、化合物Ｊ－１を得ることができる。

第３工程
　化合物Ｊ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｊ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000061
(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）化合物Ｋ－１およびＫ－２の合成 11) Synthesis of compounds K-1 and K-2
Figure JPOXMLDOC01-appb-C000062
（式中、各定義は前記と同意義。）

第１工程
　化合物Ｈ－１より、前述の９）における第１工程と同様の方法で、化合物Ｋ－１を得ることができる。

第２工程
　化合物Ｋ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｋ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000062
(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）化合物Ｌ－１およびＬ－２の合成 12) Synthesis of compounds L-1 and L-2
Figure JPOXMLDOC01-appb-C000063
（式中、各定義は前記と同意義。）

第１工程
　化合物ｆ１４より、前述の４）における第１工程と同様の方法で、化合物Ｌ－１を得ることができる。

第２工程
　化合物Ｌ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｌ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000063
(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）化合物Ｍ－１およびＭ－２の合成 13) Synthesis of compounds M-1 and M-2
Figure JPOXMLDOC01-appb-C000064
（式中、各定義は前記と同意義。）

第１工程
　化合物ｉ１より、前述の４）における第１工程と同様の方法で、化合物Ｍ－１を得ることができる。

第２工程
　化合物Ｍ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｍ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000064
(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）化合物Ｎ－１およびＮ－２の合成 14) Synthesis of compounds N-1 and N-2
Figure JPOXMLDOC01-appb-C000065
Figure JPOXMLDOC01-appb-C000065
Figure JPOXMLDOC01-appb-C000066
（式中、各定義は前記と同意義。）

第１工程
　化合物ｆ４より、前述の１）における第６工程と同様の方法で、化合物ｎ１を得ることができる。

第２工程
　化合物ｎ１より、前述の１）における第４工程と同様の方法で、化合物ｎ２を得ることができる。

第３工程
　化合物ｎ２より、前述の２）における第１工程と同様の方法で、化合物ｎ３を得ることができる。

第４工程
　化合物ｎ３より、前述の１）における第７工程と同様の方法で、化合物ｎ４を得ることができる。

第５工程
　化合物ｎ４より、前述の１）における第８工程と同様の方法で、化合物ｎ６を得ることができる。

第６工程
　化合物ｎ６より、前述の１）における第６工程と同様の方法で、化合物ｎ７を得ることができる。

第７工程
　化合物ｎ７より、前述の９）における第１工程と同様の方法で、化合物ｎ８を得ることができる。

第８工程
　ジクロロメタン、ＴＨＦ、ジクロロエタン等の溶媒中、またはそれらの混合溶媒中、化合物ｎ８にピリジン、ルチジン、トリエチルアミンなどの塩基とトリホスゲン、カルボニルジイミダゾール、炭酸ジエチル等の試薬を加え、－５０℃～５０℃、好ましくは－３０℃～３０℃で、０．１時間～４時間、好ましくは０．５時間～１時間で反応させることにより、化合物ｎ９を得ることができる。

第９工程
　化合物ｎ９より、前述の１）における第４工程と同様の方法で、化合物ｎ１０を得ることができる。

第１０工程
　化合物ｎ１０より、前述の１）における第５工程と同様の方法で、化合物Ｎ－１を得ることができる。

第１１工程
　化合物Ｎ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｎ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000066
(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）化合物Ｏ－１およびＯ－２の合成 15) Synthesis of compounds O-1 and O-2
Figure JPOXMLDOC01-appb-C000067
（式中、各定義は前記と同意義。）

第１工程
　ピリジン溶媒中、化合物ｎ８にアミド硫酸を加え、５０℃～１５０℃、好ましくは７０℃～１３０℃で、０．１時間～４時間、好ましくは０．５時間～１時間で反応させることにより、化合物ｏ１を得ることができる。

第２工程
　化合物ｏ１より、前述の１）における第４工程と同様の方法で、化合物ｏ２を得ることができる。

第３工程
　化合物ｏ２より、前述の１）における第５工程と同様の方法で、化合物Ｏ－２を得ることができる。

第４工程
　化合物Ｏ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｏ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000067
(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）化合物Ｐ－１およびＰ－２の合成 16) Synthesis of compounds P-1 and P-2
Figure JPOXMLDOC01-appb-C000068
（式中、各定義は前記と同意義。）

第１工程
　化合物ｆ５より、前述の１）における第５工程と同様の方法で、化合物ｐ１を得ることができる。

第２工程
　化合物ｐ１より、前述の１）における第７工程と同様の方法で、化合物ｐ２を得ることができる。

第３工程
　化合物ｐ２より、前述の１）における第８工程と同様の方法で、化合物ｐ３を得ることができる。

第４工程
　水とアセトンの混合溶媒中、化合物ｐ３に四酸化オスミウム、Ｎ－メチルモルホリンＮ－オキシドを加え、－５０℃～５０℃、好ましくは－３０℃～３０℃で、０．１時間～４時間、好ましくは０．５時間～１時間で反応させる。続いてＴＨＦと水の混合溶媒中、過ヨウ素酸ナトリウムを加え－５０℃～５０℃、好ましくは－３０℃～３０℃で、０．１時間～４時間、好ましくは０．５時間～１時間で反応させることにより、化合物ｐ４を得ることができる。

第５工程
　化合物ｐ４より、前述の１４）における第８工程と同様の方法で、化合物ｐ５を得ることができる。

第６工程
　化合物ｐ５より、前述の１）における第４工程と同様の方法で、化合物ｐ６を得ることができる。

第７工程
　化合物ｐ６より、前述の１）における第５工程と同様の方法で、化合物Ｐ－１を得ることができる。

第８工程
　化合物Ｐ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｐ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000068
(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）化合物Ｑ－１およびＱ－２の合成 17) Synthesis of compounds Q-1 and Q-2
Figure JPOXMLDOC01-appb-C000069
（式中、各定義は前記と同意義。）

第１工程
　ジクロロメタン、ＴＨＦ、ジクロロエタン等の溶媒中、またはそれらの混合溶媒中、化合物ｎ８にピリジン、ルチジン、トリエチルアミンなどの塩基と塩化チオニルを加え、－５０℃～５０℃、好ましくは－３０℃～３０℃で、０．１時間～４時間、好ましくは０．５時間～１時間で反応させることにより、化合物ｑ１を得ることができる。

第２工程
　アセトニトリル、水等の混合溶媒中、化合物ｑ１に四酸化ルテニウム、過ヨウ素酸ナトリウムを加え、－５０℃～５０℃、好ましくは－３０℃～３０℃で、０．１時間～４時間、好ましくは０．５時間～１時間で反応させることにより、化合物ｑ２を得ることができる。

第３工程
　化合物ｑ２より、前述の１）における第４工程と同様の方法で、化合物ｑ３を得ることができる。

第４工程
　化合物ｑ３より、前述の１）における第５工程と同様の方法で、化合物Ｑ－１を得ることができる。

第５工程
　化合物Ｑ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｑ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000069
(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）化合物Ｒ－１およびＲ－２の合成 18) Synthesis of compounds R-1 and R-2
Figure JPOXMLDOC01-appb-C000070
（式中、各定義は前記と同意義。）

第１工程
　ジオキサン、ＴＨＦ、エタノール等の溶媒中、またはそれらの混合溶媒中、化合物ａ１３に炭酸カリウム、炭酸ナトリウム、リン酸カリウムなどの塩基とブロモケトンｒ１を加え、５０℃～１５０℃、好ましくは７０℃～１２０℃で、１時間～２４時間、好ましくは０．５時間～６時間で反応させることにより、化合物Ｒ－１を得ることができる。

第２工程
　化合物Ｒ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｒ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000070
(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）化合物Ｓ－１およびＳ－２の合成 19) Synthesis of compounds S-1 and S-2
Figure JPOXMLDOC01-appb-C000071
（式中、各定義は前記と同意義。）

第１工程
　ジオキサン、ＴＨＦ、ＤＭＦ等の溶媒中、またはそれらの混合溶媒中、化合物ａ１３に炭酸カリウム、炭酸ナトリウム、炭酸水素ナトリウムなどの塩基とブロモアルキンｓ１を加え、５０℃～１５０℃、好ましくは７０℃～１２０℃で、１時間～２４時間、好ましくは０．５時間～６時間で反応させることにより、化合物Ｓ－１を得ることができる。

第２工程
　化合物Ｓ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｓ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000071
(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）化合物Ｔ－１およびＴ－２の合成 20) Synthesis of compounds T-1 and T-2
Figure JPOXMLDOC01-appb-C000072
（式中、各定義は前記と同意義。）

第１工程
　１，２－ジクロロベンゼン、トルエン、ＤＭＳＯ等の溶媒中、またはそれらの混合溶媒中、化合物ａ１３に１，１０－フェナントロリン、臭化銅、ヨウ化亜鉛、ニトリルｔ１を加え、８０℃～１８０℃、好ましくは１００℃から１６０℃で、０．１時間～４８時間、好ましくは１時間～２４時間反応させることにより、化合物Ｔ－１を得ることができる。

第２工程
　化合物Ｔ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｔ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000072
(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）化合物Ｕ－１およびＵ－２の合成 21) Synthesis of compounds U-1 and U-2
Figure JPOXMLDOC01-appb-C000073
（式中、各定義は前記と同意義。）

第１工程
　ＴＨＦ、ジエチルエーテル、トルエン等の溶媒中、またはそれらの混合溶媒中、化合物ａ１３にｎ－ブチルリチウム、水素化ナトリウム、リチウムジイソプロピルアミド等の塩基、アジドトリス（ジエチルアミノ）ホスホニウムブロマイドを加え、－１３０℃～－３０℃、好ましくは－１１０℃から－５０℃で、０．１時間～５時間、好ましくは、０．５時間～１時間反応させることにより、化合物Ｕ－１を得ることができる。

第２工程
　化合物Ｕ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｕ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000073
(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）化合物Ｖ－１およびＶ－２の合成 22) Synthesis of compounds V-1 and V-2
Figure JPOXMLDOC01-appb-C000074
（式中、各定義は前記と同意義。）

第１工程
　ＤＭＦ、ＤＭＡ、ＴＨＦ、ジオキサン等の溶媒中、またはそれらの混合溶媒中、化合物ａ１１に、トリエチルアミン、ルチジン、ピリジンなどの塩基、アルコール（Ｒ７１ＯＨ）、ジベンジリデンアセトンパラジウム、酢酸パラジウム、ジクロロビストリフェニルホスフィンパラジウムなどの触媒、およびキサントホス、Ｐ（ｔ－Ｂｕ）３などの配位子を加え、５０℃～１５０℃、好ましくは７０℃～１３０℃で、０．１時間～８時間、好ましくは０．５～２時間で反応させることにより、化合物Ｖ－１を得ることができる。

第２工程
　化合物Ｖ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｖ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000074
(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）化合物Ｗ－１、Ｗ－２、Ｗ－３およびＷ－４の合成 23) Synthesis of compounds W-1, W-2, W-3 and W-4
Figure JPOXMLDOC01-appb-C000075
（式中、各定義は前記と同意義。）

第１工程
　ＤＭＦ、ＤＭＡ、ＴＨＦ、ジオキサン等の溶媒中、またはそれらの混合溶媒中、化合物ｗ１に、トリｔｅｒｔ－ブチルホスフィン、トリシクロヘキシルホスフィン、トリフェニルホスフィンなどのホスフィン、ジベンジリデンアセトンパラジウム、酢酸パラジウム、ジクロロビストリフェニルホスフィンパラジウムなどの触媒、フッ化亜鉛、および化合物ａ４を加え、５０℃～１５０℃、好ましくは７０℃～１３０℃で、０．１時間～８時間、好ましくは０．５時間～２時間で反応させることにより、化合物ｗ２を得ることができる。

第２工程
　メタノール、酢酸エチル、酢酸等の溶媒中、またはそれらの混合溶媒中、化合物ｗ２にパラジウム炭素、水酸化パラジウム、ラネーニッケル触媒などの触媒を加え、水素雰囲気下、３０℃～１３０℃、好ましくは５０℃～１１０℃で、０．１時間～８時間、好ましくは０．５～２時間で反応させることにより、化合物ｗ３を得ることができる。

第３工程
　ジクロロメタン、クロロホルム、ジクロロエタン等の溶媒中、またはそれらの混合溶媒中、化合物ｗ３に、臭素、ＮＢＳなどの臭素化剤を加え、－５０℃～５０℃、好ましくは－３０℃～３０℃で、０．１時間～４時間、好ましくは０．５時間～１時間で反応させることにより、化合物ｗ４を得ることができる。

第４工程
　ＤＭＦ、ＤＭＡ、ＴＨＦ、ジオキサン、水等の溶媒中、またはそれらの混合溶媒中、化合物ｗ４に、炭酸カリウム、炭酸ナトリウム、リン酸カリウムなどの塩基の水溶液、ボロン酸またはボロン酸エステル、およびジベンジリデンアセトンパラジウム、酢酸パラジウム、ジクロロビストリフェニルホスフィンパラジウムなどの触媒を加え、５０℃～１５０℃、好ましくは７０℃～１３０℃で、０．１時間～８時間、好ましくは０．５～２時間で反応させることにより、化合物Ｗ－１を得ることができる。

第５工程
　ｔｅｒｔ－ブタノール水溶液中、化合物Ｗ－１に酢酸および過マンガン酸カリウムを加え、－５０℃～５０℃、好ましくは－３０℃～３０℃で、０．１時間～４時間、好ましくは０．５時間～１時間で反応させることにより、化合物Ｗ－３を得ることができる。

第６工程
　化合物Ｗ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｗ－２を得ることができる。また、化合物Ｗ－３より、同様の方法で化合物Ｗ－４を得ることができる。
Figure JPOXMLDOC01-appb-C000075
(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）化合物Ｘ－１およびＸ－２の合成 24) Synthesis of compounds X-1 and X-2
Figure JPOXMLDOC01-appb-C000076
（式中、各定義は前記と同意義。）

第１工程
　ＤＭＦ、ＤＭＡ、ＴＨＦ、ジオキサン、トルエン等の溶媒中、またはそれらの混合溶媒中、化合物ａ１１に、炭酸セシウム、炭酸カリウム、炭酸ナトリウム、トリエチルアミン、ルチジン、ピリジンなどの塩基、アミン（Ｒ７１ＮＨ２）、ジベンジリデンアセトンパラジウム、酢酸パラジウム、ジクロロビストリフェニルホスフィンパラジウムなどの触媒、およびキサントホス、Ｐ（ｔ－Ｂｕ）３などの配位子を加え、５０℃～１５０℃、好ましくは７０℃～１３０℃で、０．１時間～８時間、好ましくは０．５～２時間で反応させることにより、化合物Ｘ－１を得ることができる。

第２工程
　化合物Ｘ－１より、前述の１）における第１１工程と同様の方法で、化合物Ｘ－２を得ることができる。
Figure JPOXMLDOC01-appb-C000076
(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.
　本発明化合物は、ＨＩＶ複製阻害作用を有するため、エイズ等、ウイルス感染症の治療剤および／または予防剤として有用である。
　本発明化合物は、ＨＩＶ複製阻害作用のみならず、医薬としての有用性を備えており、好ましくは、下記いずれか、あるいは全ての優れた特徴を有している。
ａ）ＣＹＰ酵素（例えば、ＣＹＰ１Ａ２、ＣＹＰ２Ｃ９、ＣＹＰ２Ｃ１９、ＣＹＰ２Ｄ６、ＣＹＰ３Ａ４等）に対する阻害作用が弱い。
ｂ）高いバイオアベイラビリティー、適度なクリアランス等良好な薬物動態を示す。
ｃ）代謝安定性が高い。
ｄ）ＣＹＰ酵素（例えば、ＣＹＰ３Ａ４）に対し、本明細書に記載する測定条件の濃度範囲内で不可逆的阻害作用を示さない。
ｅ）変異原性を有さない。
ｆ）心血管系のリスクが低い。
ｇ）高い溶解性を示す。
ｈ）耐性ウイルスに対しても強い薬効を示す。
ｉ）耐性ウイルスを発現させにくい。 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.
　本発明の医薬組成物を投与する場合、経口的、非経口的のいずれの方法でも投与することができる。経口投与は常法に従って錠剤、顆粒剤、散剤、カプセル剤等の通常用いられる剤型に調製して投与すればよい。非経口投与は、注射剤等の通常用いられるいずれの剤型でも好適に投与することができる。本発明化合物は、好ましくは経口吸収性が高いため、経口剤として好適に使用できる。 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.
　本発明化合物の有効量にその剤型に適した賦形剤、結合剤、崩壊剤、滑沢剤等の各種医薬用添加剤を必要に応じて混合し、医薬組成物とすることができる。 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.
　本発明の医薬組成物の投与量は、患者の年齢、体重、疾病の種類や程度、投与経路等を考慮した上で設定することが望ましいが、成人に経口投与する場合、通常０．０５～１００ｍｇ／ｋｇ／日であり、好ましくは０．１～１０ｍｇ／ｋｇ／日の範囲内である。非経口投与の場合には投与経路により大きく異なるが、通常０．００５～１０ｍｇ／ｋｇ／日であり、好ましくは０．０１～１ｍｇ／ｋｇ／日の範囲内である。これを１日１回～数回に分けて投与すれば良い。 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.
　本発明化合物は、該化合物の作用の増強または該化合物の投与量の低減等を目的として、逆転写酵素阻害剤、プロテアーゼ阻害剤、インテグラーゼ阻害剤等（以下、併用薬剤と略記する）と組み合わせて用いることができる。この際、本発明化合物と併用薬剤の投与時期は限定されず、これらを投与対象に対し、同時に投与してもよいし、時間差をおいて投与してもよい。さらに、本発明化合物と併用薬剤とは、それぞれの活性成分を含む２種類の製剤として投与されてもよいし、両方の活性成分を含む単一の製剤として投与されてもよい。　 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. *
　併用薬剤の投与量は、臨床上用いられている用量を基準として適宜選択することができる。また、本発明化合物と併用薬剤の配合比は、投与対象、投与ルート、対象疾患、症状、組み合わせ等により適宜選択することができる。例えば、投与対象がヒトである場合、本発明化合物１重量部に対し、併用薬剤を０．０１～１００重量部用いればよい。 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.
　また、本発明化合物は、遺伝子治療の分野において、ＨＩＶやＭＬＶをもとにしたレトロウイルスベクターを用いる際に、目的の組織以外にレトロウイルスベクターの感染が広がるのを防止するために使用することができる。特に、試験管内で細胞等にベクターを感染しておいてから体内にもどすような場合に、本発明化合物を事前に投与しておくと、体内での余計な感染を防ぐことができる。 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.
　逆転写酵素阻害剤としては、例えば、ＡＺＴ、３ＴＣ、ジダノシン、ザルシタビン、サニルブジン、アバカビル、テノホビル、エムトリシタビン、ネビラビン、エファビレンツ、カプラビリン、エトラビリン、デラビルジン等が挙げられる。 Examples of the reverse transcriptase inhibitor include AZT, 3TC, didanosine, sarcitabine, sanylvudine, abacavir, tenofovir, emtricitabine, nevirabin, efavirenz, coupleravirin, etravirin, delavirdine and the like.
　プロテアーゼ阻害剤としては、例えば、インディナビル、リトナビル、サキナビル、ネルフィナビル、アンプレナビル、アタナザビル、ロピナビル、ホスアンプレナビル、ダルナビル、アタザナビル、ブレカナビル、ティプラナビル等が挙げられる。 Examples of protease inhibitors include indinavir, ritonavir, saquinavir, nelfinavir, amprenavir, atanazavir, lopinavir, fosamprenavir, darunavir, atazanavir, branavir, tipranavir and the like.
　インテグラーゼ阻害剤としては、例えば、ラルテグラビル、エルビテグラビル、ＪＴＫ－６５６、ドルテグラビル、Ｓ－２６５７４４等が挙げられる。 Examples of the integrase inhibitor include raltegravir, elvitegravir, JTK-656, dolutegravir, S-265744 and the like.
　その他の抗ＨＩＶ薬としては、例えば、マラビロク、ビクリビロク等の侵入阻害剤、エンフュビルタイド、シフュビルタイド、アルブビルタイド等の融合阻害剤等が挙げられる。 Other anti-HIV drugs include, for example, invasion inhibitors such as maraviroc and bicrivirok, and fusion inhibitors such as enfuvirtide, sifuvirtide, and albuvirtide.
　以下に本発明の実施例および参考例、ならびに試験例を挙げて本発明をさらに詳しく説明するが、本発明はこれらにより限定されるものではない。 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.
　また、本明細書中で用いる略語は以下の意味を表す。
Ａｃ：アセチル
ｎ－Ｂｕ：ｎ－ブチル
ｔ－Ｂｕ：ｔｅｒｔ－ブチル
Ｂｎ：ベンジル
Ｅｔ：エチル
ＤＭＥ：ジメトキシエタン
ＤＭＦ：Ｎ，Ｎ－ジメチルホルムアミド
ＤＣＭ：ジクロロメタン
ＤＭＳＯ：ジメチルスルホキシド
ｄｐｐｆ：１，１’－ビス（ジフェニルホスフィノ）フェロセン
Ｍｅ：メチル
ＭｓＯＨ：メタンスルホン酸
ＮＢＳ：Ｎ－ブロモスクシンイミド
ＮＣＳ：Ｎ－クロロスクシンイミド
ＮＩＳ：Ｎ－ヨードスクシンイミド
Ｐｈ：フェニル
ＴＢＳ：ｔｅｒｔ－ブチルジメチルシリル
ＴＨＦ：テトラヒドロフラン
Ｔｆ：トリフルオロメタンスルホニル
ＴＦＡ：トリフルオロ酢酸
ＴＭＳ：トリメチルシリル
Ｔｓ：ｐ－トルエンスルホニル 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
　各実施例で得られたＮＭＲ分析は３００ＭＨｚで行い、ＤＭＳＯ－ｄ６、ＣＤＣｌ３を用いて測定した。
　表中にＲＴとあるのは、ＬＣ／ＭＳ：液体クロマトグラフィー／質量分析でのリテンションタイムを表し以下の条件で測定した。なお、移動相中で２種の異性体として存在し得る化合物については、測定ピークが２本になり得る。
（測定条件）
カラム：Ｓｈｉｍ－ｐａｃｋ　ＸＲ－ＯＤＳ　（２．２μｍ、ｉ．ｄ．５０×３．０ｍｍ）　（島津製作所）
流速：１．６ｍＬ／分
ＵＶ検出波長：２５４ｎｍ
移動相：［Ａ］は０．１％ギ酸含有水溶液、［Ｂ］は０．１％ギ酸含有アセトニトリル溶液
グラジエント：３分間で１０％－１００％溶媒［Ｂ］のリニアグラジエントを行い、０．５分間、１００％溶媒［Ｂ］を維持した。 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.
実施例１　化合物５の合成 Example 1 Synthesis of Compound 5
Figure JPOXMLDOC01-appb-C000077
Figure JPOXMLDOC01-appb-C000077
Figure JPOXMLDOC01-appb-C000078
第１工程
　化合物（１）（２５ｇ、１７８ｍｍｏｌ）の水（２５０ｍＬ）溶液に、ベンジルアミン（１９．４９ｍｌ、１７８ｍｍｏｌ）を加え、加熱還流下５時間攪拌した。析出してきた固体をろ過し、メタノールで再結晶することにより、オレンジ色固体の化合物（２）（２１ｇ、収率５１．３％）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　２３０．０５（Ｍ＋Ｈ＋）

第２工程
　化合物（２）（２２ｇ、９６ｍｍｏｌ）のジクロロメタン（２００ｍＬ）溶液に、窒素雰囲気下、ピリジン（１０．０９ｍＬ、１２５ｍｍｏｌ）とトリフルオロメタンスルホン酸無水物（１７．８３ｍＬ、１０６ｍｍｏｌ）を氷冷下加え攪拌した。３０分後、２ｍｏｌ／Ｌ塩酸を加え、ジクロロメタン（１００ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、黄色油状の化合物（３）（３２ｇ、収率９２．３％）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　３６２．４０（Ｍ＋Ｈ＋）

第３工程
　化合物（３）のＤＭＦ（３００ｍＬ）溶液に、窒素雰囲気下、フッ化亜鉛（１３．７３ｇ、１３３ｍｍｏｌ）、ジベンジリデンアセトンパラジウム（５．０９ｇ、８．８６ｍｍｏｌ）　、トリｔｅｒｔ－ブチルホスフィン　（４．１６ｍＬ、１７．７１ｍｍｏｌ）、シリルエノールエーテル（５８．３ｇ、２６７ｍｍｏｌ）を加え、１００度で攪拌した。１時間後、水（３００ｍＬ）を加え、酢酸エチル（１００ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、黄色固体の化合物（４）（１６ｇ、収率５０．５％）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　３５８．６５（Ｍ＋Ｈ＋）

第４工程
　化合物（４）（９ｇ、２５．２ｍｍｏｌ）のアセトニトリル（１００ｍＬ）溶液に、ＮＢＳ（４．４８ｇ、２５．２ｍｍｏｌ）を加え氷冷下攪拌した。３０分後、飽和重曹水（１００ｍＬ）を加え、ジクロロメタン（１００ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物（５）（９．０２ｇ、収率８２．１％）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　４３６．０５（Ｍ＋Ｈ＋）

第５工程
　化合物（５）（１ｇ、２．２９２ｍｍｏｌ）のＤＭＦ（１０ｍＬ）溶液に、窒素雰囲気下、水（３．５ｍＬ）、ボロン酸（６８７ｍｇ、４．５８ｍｍｏｌ）、トリフェニルホスフィンパラジウム（２６５ｍｇ、０．２２９ｍｍｏｌ）、炭酸カリウム（９５１ｍｇ、６．８８ｍｍｏｌ）を加え、１４０度で攪拌した。１時間後、２ｍｏｌ／Ｌ塩酸（１００ｍＬ）を加え、酢酸エチル（１０ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、黄色液体の化合物（６）（８００ｍｇ、収率７５．６％）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　４６２．６０（Ｍ＋Ｈ＋）

第６工程
　化合物（６）（８００ｍｇ、１．７３３ｍｍｏｌ）の酢酸（１０ｍｌ）溶液に、パラジウム炭素（８０ｍｇ）を加え、水素雰囲気下、８０度で攪拌した。２時間後、セライトろ過し、ろ液を濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物（７）（２７０ｍｇ、収率４１．９％）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　３７２．１０（Ｍ＋Ｈ＋）

第７工程
　化合物（７）（２４０ｍｇ、０．６４６ｍｍｏｌ）のジクロロメタン（２ｍＬ）溶液に、窒素雰囲気下、ピリジン（０．０６８ｍＬ、０．８４ｍｍｏｌ）とトリフルオロメタンスルホン酸無水物（０．１２ｍＬ、０．７１１ｍｍｏｌ）を氷冷下加え攪拌した。３０分後、２ｍｏｌ／Ｌ塩酸を加え、ジクロロメタン（２ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、透明液体の化合物（８）（２８０ｍｇ、収率８６．１％）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　５０４．１５（Ｍ＋Ｈ＋）

第８工程
　化合物（８）（３００ｍｇ、０．５９６ｍｍｏｌ）の１、４－ジオキサン溶液（３ｍＬ）に窒素雰囲気下、炭酸セシウム（５８２ｍｇ、１．７８７ｍｍｏｌ）、ベンジルアミン（０．１３ｍＬ、１．１９２ｍｍｏｌ）、ジベンジリデンアセトンパラジウム（３４．３ｍｇ、０．０６ｍｍｏｌ）、キサントホス（６８．９ｍｇ、０．１１９ｍｍｏｌ），を加え加熱還流下攪拌した。２時間後、水を加え、酢酸エチル（３ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、黄色固体の化合物（９）（２７０ｍｇ、収率９８．４％）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　４６１．７０（Ｍ＋Ｈ＋）

第９工程
　化合物（９）（２６０ｍｇ、０．５６４ｍｍｏｌ）のメタノール（３ｍｌ）溶液に、パラジウム炭素（２６ｍｇ）を加え、水素雰囲気下、室温で攪拌した。５時間後、セライトろ過し、ろ液を濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物（１０）（１７０ｍｇ、収率８１．３％）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　３７１．５５（Ｍ＋Ｈ＋）

第１０工程
　化合物（１０）（３０ｍｇ、０．０８１ｍｍｏｌ）のジクロロエタン（１ｍＬ）溶液に、窒素雰囲気下、トリエチルアミン（０．０３４ｍＬ、０．２４３ｍｍｏｌ）、フェニルイソシアネート（０．０１８ｍＬ、０．１６２ｍｍｏｌ）を加え、６０度で攪拌した。３０分後、２ｍｏｌ／Ｌ塩酸（１ｍＬ）を加え、酢酸エチル（１ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、黄色液体の化合物（１１）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　４９０．２５（Ｍ＋Ｈ＋）

第１１工程
　化合物（１１）（３９．６ｍｇ、０．０８１ｍｍｏｌ）のメタノール（１ｍＬ）溶液に、２ｍｏｌ／Ｌ水酸化ナトリウム水溶液（０．１２１ｍＬ、０．２４３ｍｍｏｌ）を加え、加熱還流下攪拌した。１時間後、２ｍｏｌ／Ｌ塩酸（１ｍＬ）を加え、酢酸エチル（１ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物５（２５ｍｇ、収率６５．０％（第１０～１１工程））を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　４７６．２０（Ｍ＋Ｈ＋）
1H-NMR(400MHz, CDCl3): δ12.5(1H, s), 7.60-6.94(9H, m), 5.12(1H, s), 2.34-2.24(12H, m), 1.01(9H, s)
Figure JPOXMLDOC01-appb-C000078
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 )
実施例２　化合物１の合成 Example 2 Synthesis of Compound 1
Figure JPOXMLDOC01-appb-C000079
第１工程
　化合物（８）（２００ｍｇ、０．３９７ｍｍｏｌ）のＤＭＦ（２ｍＬ）溶液に、トリエチルアミン（０．１１ｍＬ、０．７９４ｍｍｏｌ）、ベンジルアミン（０．１３ｍＬ、１．１９２ｍｍｏｌ）、臭化リチウム（１０３ｍｇ、１．１９２ｍｍｏｌ）、トリフェニルホスフィンパラジウム（４５．９ｍｇ、０．０４ｍｍｏｌ）を加え、一酸化炭素雰囲気下で、加熱還流下攪拌した。３０分後、２ｍｏｌ／Ｌ塩酸（２ｍＬ）を加え、酢酸エチル（２ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物（１２）（１７８ｍｇ、収率９１．７％）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　４８９．２０（Ｍ＋Ｈ＋）

第２工程
　化合物（１２）（１７８ｍｇ、０．３６４ｍｍｏｌ）のメタノール（２ｍＬ）溶液に、２ｍｏｌ／Ｌ水酸化ナトリウム水溶液（０．５４６ｍＬ、１．０９３ｍｍｏｌ）を加え、加熱還流下攪拌した。３０分後、２ｍｏｌ／Ｌ塩酸（２ｍＬ）を加え、酢酸エチル（２ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物１（１４５ｍｇ、収率８３．９％）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　４７５．２０（Ｍ＋Ｈ＋）
1H-NMR(400MHz, CDCl3): 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)
Figure JPOXMLDOC01-appb-C000079
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)
実施例３　化合物４の合成 Example 3 Synthesis of Compound 4
Figure JPOXMLDOC01-appb-C000080
第１工程
　化合物（１２）（１００ｍｇ、０．２０５ｍｍｏｌ）のＴＨＦ（１ｍＬ）溶液に、窒素雰囲気下、水素化ナトリウム（９．８２ｍｇ、０．４０９ｍｍｏｌ）、ヨウ化メチル（０．０３２ｍＬ、０．５１２ｍｍｏｌ）を加え、氷冷下攪拌した。３時間後、２ｍｏｌ／Ｌ塩酸（１ｍＬ）を加え、酢酸エチル（１ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物（１３）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　５０３．２５（Ｍ＋Ｈ＋）

第２工程
　化合物（１３）（１３５ｍｇ、０．２６９ｍｍｏｌ）のメタノール（２ｍＬ）溶液に、２ｍｏｌ／Ｌ水酸化ナトリウム水溶液（０．４０３ｍＬ、０．８０６ｍｍｏｌ）を加え、加熱還流下攪拌した。３０分後、２ｍｏｌ／Ｌ塩酸（２ｍＬ）を加え、酢酸エチル（２ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物４（１０１ｍｇ、収率７７．０％（第１４～１５工程））を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　４８９．２０（Ｍ＋Ｈ＋）
1H-NMR(400MHz, CDCl3): 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)
Figure JPOXMLDOC01-appb-C000080
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)
実施例４　化合物６６、６７の合成 Example 4 Synthesis of compounds 66 and 67
Figure JPOXMLDOC01-appb-C000081
第１工程
　実施例１における化合物（８）と同様の合成法で得られる化合物（８’）（２００ｍｇ、０．３９ｍｍｏｌ）のトルエン（２ｍＬ）溶液に、炭酸セシウム（１９３ｍｇ、０．５９３ｍｍｏｌ）、３－アミノキノリン（６８．４ｍｇ、０．４７５ｍｍｏｌ）、キサントホス（１０．３ｍｇ、０．０１８ｍｍｏｌ）、Ｐｄ（ｄｂａ）２（６．９ｍｇ、０．０１２ｍｍｏｌ）を加え、加熱還流下攪拌した。４０分後、水（２ｍＬ）を加え、酢酸エチル（２ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、黄色泡状の化合物（１４）（１６７ｍｇ、収率８４．５％）を得た。
MS(ESI) m/z: 500.20(M+H+)

第２工程
　化合物（１４）（１６０ｍｇ、０．３２０ｍｍｏｌ）のエタノール（１．６ｍＬ）溶液に、２ｍｏｌ／Ｌ水酸化ナトリウム水溶液（１．６ｍＬ、３．２０ｍｍｏｌ）を加え、加熱還流下攪拌した。３０分後、２ｍｏｌ／Ｌ塩酸（１．６ｍＬ）を加え、酢酸エチル（２ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、黄色固体の化合物６６および化合物６７の混合物（７４．０ｍｇ、収率４７．６％）を得た。
MS(ESI) m/z: 486.15(M+H+)
1H-NMR(400MHz, CDCl3): δ8.95(1H, d, J=2.4Hz), 8.66(1H, d, J=2.4Hz), 8.02(1H, d,J= 8.5Hz), 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)

　なお、化合物６６および化合物６７は、第２工程で得られた混合物を公知の方法で光学分割することにより得た。
Figure JPOXMLDOC01-appb-C000081
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.
実施例５　化合物７４の合成 Example 5 Synthesis of Compound 74
Figure JPOXMLDOC01-appb-C000082
第１工程
　実施例１における化合物（８）と同様の合成法で得られる化合物（８’’）（１００ｍｇ、０．１８８ｍｍｏｌ）のトルエン（１ｍＬ）溶液に、炭酸セシウム（１２３ｍｇ、０．３７６ｍｍｏｌ）、シクロへキシルメタノール（４３．０ｍｇ、０．３７６ｍｍｏｌ）、キサントホス（４．９ｍｇ、０．００８ｍｍｏｌ）、Ｐｄ（ｄｂａ）２（３．２４ｍｇ、０．００５ｍｍｏｌ）を加え、加熱還流下攪拌した。４時間後、２ｍｏｌ／Ｌ塩酸（１ｍＬ）を加え、酢酸エチル（２ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、白色泡状の化合物（１５）（９０．０ｍｇ、収率９６．５％）を得た。
MS(ESI) m/z: 496.25(M+H+)

第２工程
　化合物（１５）（９０ｍｇ、０．１８２ｍｍｏｌ）のエタノール（０．９ｍＬ）溶液に、２ｍｏｌ／Ｌ水酸化ナトリウム水溶液（０．９１ｍＬ、１．８２ｍｍｏｌ）を加え、加熱還流下攪拌した。１時間後、２ｍｏｌ／Ｌ塩酸（１ｍＬ）を加え、酢酸エチル（２ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物７４（４０．０ｍｇ、収率４５．７％）を得た。
MS(ESI) m/z: 482.20(M+H+)
1H-NMR(400MHz, CDCl3): 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)
Figure JPOXMLDOC01-appb-C000082
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)
実施例６　化合物３５の合成 Example 6 Synthesis of Compound 35
Figure JPOXMLDOC01-appb-C000083
第１工程
　化合物（１０）（５０ｍｇ、０．１３５ｍｍｏｌ）のジオキサン（１ｍＬ）溶液に、炭酸ナトリウム（４２．９ｍｇ、０．４０５ｍｍｏｌ）、２－ブロモ－１－フェニルエタノン（８１．０ｍｇ、０．４０５ｍｍｏｌ）を加え、加熱還流下攪拌した。１３時間後、２ｍｏｌ／Ｌ塩酸（１ｍＬ）を加え、酢酸エチル（２ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、黄色油状の化合物（１６）（５２．０ｍｇ、収率８１．９％）を得た。
MS(ESI) m/z: 471.2(M+H+)
1H-NMR(400MHz, CDCl3): δ8.02(1H, d, J=7.3Hz), 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)

第２工程
　化合物（１６）（５０ｍｇ、０．１０６ｍｍｏｌ）のエタノール（１．０ｍＬ）溶液に、２ｍｏｌ／Ｌ水酸化ナトリウム水溶液（０．５３２ｍＬ、１．０７ｍｍｏｌ）を加え、加熱還流下攪拌した。１時間後、２ｍｏｌ／Ｌ塩酸（１ｍＬ）を加え、酢酸エチル（２ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、ベージュ固体の化合物３５（２５．０ｍｇ、収率５１．５％）を得た。
MS(ESI) m/z: 457.10(M+H+)
Figure JPOXMLDOC01-appb-C000083
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 + )
実施例７　化合物４０の合成 Example 7 Synthesis of Compound 40
Figure JPOXMLDOC01-appb-C000084
第１工程
　化合物（１７）（５．５８ｇ、３１．２ｍｍｏｌ）のＤＭＦ（５６ｍＬ）溶液に、窒素雰囲気下、フッ化亜鉛（４．８４ｇ、４６．９ｍｍｏｌ）、Ｐｄ（ｄｂａ）２（１．７９ｇ、３．１２ｍｍｏｌ）　、Ｐ（ｔ－Ｂｕ）３　（１．４９ｍＬ、６．２５ｍｍｏｌ）、シリルエノールエーテル（２０．４４ｇ、９３．６ｍｍｏｌ）を加え、１００度で攪拌した。３０分後、水（１００ｍＬ）を加え、酢酸エチル（１００ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、黄色固体の化合物（１８）（６．４１ｇ、収率７１．２％）を得た。
MS(ESI) m/z: 289.35(M+H+)

第２工程
　化合物（１８）（６．４１ｇ、２２．２ｍｍｏｌ）のメタノール（６４ｍＬ）溶液に、５０％含水１０％Ｐｄ／Ｃ（１．２ｇ）を加え、水素雰囲気下、６０度で攪拌した。１２時間後、セライトろ過し、ろ液を濃縮後、ヘキサンを加えろ過することにより、黄土色固体の化合物（１９）（６．０ｇ、収率９２．３％）を得た。
MS(ESI) m/z: 293.40(M+H+)

第３工程
　化合物（１９）（６．０ｇ、２０．５ｍｍｏｌ）のアセトニトリル（６０ｍＬ）溶液に、ＮＢＳ（４．０２ｇ、２２．６ｍｍｏｌ）を加え氷冷下攪拌した。３０分後、飽和重曹水（６０ｍＬ）を加え、酢酸エチル（１００ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、黄色油状の化合物（２０）（６．５ｇ、収率８５．３％）を得た。
MS(ESI) m/z: 372.30(M+H+)

第４工程
　化合物（２０）（６．５ｇ、１７．５ｍｍｏｌ）のＤＭＦ（１２０ｍＬ）溶液に、窒素雰囲気下、２ｍｏｌ／Ｌ　Ｎａ２ＣＯ３水溶液（２６．３ｍＬ、５２．５ｍｍｏｌ）、３，４－ジメチルフェニルボロン酸（３．９４ｇ、２６．３ｍｍｏｌ）、Ｐｄ（ＰＰｈ３）４（２．０２ｇ、１．７５ｍｍｏｌ）、を加え、１４０度で攪拌した。１時間後、水（２４０ｍＬ）を加え、酢酸エチル（１００ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、黄色泡状の化合物（２１）（４．６４ｇ、収率６６．８％）を得た。
MS(ESI) m/z: 397.15(M+H+)

第５工程
　化合物（２１）（５０ｍｇ、０．１２６ｍｍｏｌ）のジクロロエタン（１ｍＬ）溶液に、トリエチルアミン（０．０５２ｍＬ、０．３７８ｍｍｏｌ）、シクロヘキシルイソシアネート（０．０３２ｍＬ、０．２５２ｍｍｏｌ）を加え、加熱還流下攪拌した。２時間後、２ｍｏｌ／Ｌ塩酸（１ｍＬ）を加え、ジクロロメタン（２ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、黄色泡状の化合物（２２）（６４．８ｍｇ、収率９８．５％）を得た。
MS(ESI) m/z: 522.25(M+H+)

第６工程
　化合物（２２）（６０ｍｇ、０．１１５ｍｍｏｌ）のエタノール（１ｍＬ）溶液に、２ｍｏｌ／Ｌ水酸化ナトリウム水溶液（１．１５ｍＬ、２．３ｍｍｏｌ）を加え、加熱還流下攪拌した。３時間後、２ｍｏｌ／Ｌ塩酸（１．２ｍＬ）を加え、酢酸エチル（２ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物４０（５５．０ｍｇ、収率９４．２％）を得た。
MS(ESI) m/z: 508.25(M+H+)
1H-NMR(400MHz, CDCl3): δ10.8(1H, d, J=7.2Hz), 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)
Figure JPOXMLDOC01-appb-C000084
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)
実施例８　化合物４８の合成 Example 8 Synthesis of Compound 48
Figure JPOXMLDOC01-appb-C000085
第１工程
　化合物（２１）（１ｇ、２．５２ｍｍｏｌ）のｔ－ＢｕＯＨ（５ｍＬ）、水（５ｍＬ）溶液に、酢酸（０．４３３ｍＬ、７．５７ｍｍｏｌ）、過マンガン酸カリウム（９９６ｍｇ、６．３０ｍｍｏｌ）を加え、室温で攪拌した。３０分後、エタノール（５ｍＬを加え）、２ｍｏｌ／Ｌ　ＮａＯＨ水溶液（５ｍＬ）を加えセライトろ過し、酢酸エチル（１０ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物（２３）（７６８ｍｇ、収率７４．２％）を得た。
MS(ESI) m/z: 411.1(M+H+)

第２工程
　化合物（２３）（５０ｍｇ、０．１２２ｍｍｏｌ）のＤＭＦ（１ｍＬ）溶液に、炭酸カリウム（５０．５ｍｇ、０．３６５ｍｍｏｌ）、ブロモメチルシクロへキサン（０．０３４ｍＬ、０．２４４ｍｍｏｌ）を加え、８０度で攪拌した。３０時間後、２ｍｏｌ／Ｌ塩酸水溶液（１ｍＬ）を加え、酢酸エチル（１０ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、黄色油状の化合物（２４）（３６．３ｍｇ、収率５７．２％）を得た。
MS(ESI) m/z: 507.20(M+H+)

第３工程
　化合物（２４）（２８ｍｇ、０．０５５ｍｍｏｌ）のエタノール（１ｍＬ）溶液に、２ｍｏｌ／Ｌ水酸化ナトリウム水溶液（０．５５３ｍＬ、１．１１ｍｍｏｌ）を加え、加熱還流下攪拌した。１時間後、２ｍｏｌ／Ｌ塩酸（１．２ｍＬ）を加え、酢酸エチル（２ｍＬ×３）で抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物４８（１９．８ｍｇ、収率７２．７％）を得た。
MS(ESI) m/z: 493.3(M+H+)
1H-NMR(400MHz, CDCl3): 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)
Figure JPOXMLDOC01-appb-C000085
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)
実施例９　化合物４５の合成 Example 9 Synthesis of Compound 45
Figure JPOXMLDOC01-appb-C000086
第１工程
　化合物（１０）（１００ｍｇ，０．２７０ｍｍｏｌ）をピリジン（１ｍｌ）に溶解し、ナフタレン－１－スルホニルクロリド（９２ｍｇ，０．４０５ｍｍｏｌ）を加えて８０℃で２．５時間攪拌した。さらにナフタレン－１－スルホニルクロリド（４６ｍｇ，０．２０２ｍｍｏｌ）を加えて８０℃で３時間攪拌した。反応液を減圧濃縮し、得られた粗生成物をシリカゲルカラムクロマトグラフィーによって精製することにより、無色泡状物質の化合物（２５）（９５ｍｇ、収率６３％）を得た。
MS(ESI) m/z: 561(M+H+)

第２工程
　化合物（２５）（９５ｍｇ、０．１７ｍｍｏｌ）のメタノール（２ｍＬ）とテトラヒドロフラン（０．５ｍｌ）の溶液に、２ｍｏｌ／Ｌ水酸化ナトリウム水溶液（０．８５ｍＬ、１．７ｍｍｏｌ）を加え、加熱還流下攪拌した。５時間後、飽和塩化アンモニウム水溶液を加え、酢酸エチルで抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物４５（７０ｍｇ、収率７６％）を得た。
MS(ESI) m/z: 547(M+H+)
1H-NMR (CDCl3) 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).
Figure JPOXMLDOC01-appb-C000086
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).
実施例１０　化合物２２の合成 Example 10 Synthesis of Compound 22
Figure JPOXMLDOC01-appb-C000087
第１工程
　化合物（１０）（５０ｍｇ，０．１４ｍｍｏｌ）をピリジン（１ｍｌ）に溶解し、塩化ベンゾイル（９２ｍｇ，０．１５ｍｍｏｌ）を加えて室温で３時間攪拌した。反応液を減圧濃縮し、得られた粗生成物をシリカゲルカラムクロマトグラフィーによって精製することにより、無色泡状物質の化合物（２６）（３３ｍｇ、収率５２％）を得た。
ＭＳ（ＥＳＩ）　ｍ／ｚ：　４７５（Ｍ＋Ｈ＋）

第２工程
　化合物（２６）（３３ｍｇ、０．０７０ｍｍｏｌ）のメタノール（１．５ｍＬ）とテトラヒドロフラン（０．５ｍｌ）の溶液に、２ｍｏｌ／Ｌ水酸化ナトリウム水溶液（０．３５ｍＬ、０．７０ｍｍｏｌ）を加え、加熱還流下攪拌した。２時間後、飽和塩化アンモニウム水溶液を加え、酢酸エチルで抽出した。有機層を水、飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し濃縮後、カラムクロマトグラフィーによって精製することにより、白色固体の化合物２２（１３ｍｇ、収率４１％）を得た。
MS(ESI) m/z: 461(M+H+)
1H-NMR (CDCl3) 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).
Figure JPOXMLDOC01-appb-C000087
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).
実施例１１　上記実施例に従い、以下の化合物を合成した。 Example 11 The following compounds were synthesized according to the above examples.
Figure JPOXMLDOC01-appb-C000088
（式中、Ｒ１はメチル、Ｒ２はｔｅｒｔ－ブチルオキシ、ｎは１、Ｒ４は水素原子、Ｒ６はメチル。）
Figure JPOXMLDOC01-appb-C000088
(Wherein R 1 is methyl, R 2 is tert-butyloxy, n is 1, R 4 is a hydrogen atom, and R 6 is methyl.)
Figure JPOXMLDOC01-appb-T000089
Figure JPOXMLDOC01-appb-T000089
　上記実施例に従い、以下の化合物も合成した。 The following compounds were also synthesized according to the above examples.
Figure JPOXMLDOC01-appb-T000090
Figure JPOXMLDOC01-appb-T000090
Figure JPOXMLDOC01-appb-T000091
Figure JPOXMLDOC01-appb-T000091
Figure JPOXMLDOC01-appb-T000092
Figure JPOXMLDOC01-appb-T000092
Figure JPOXMLDOC01-appb-T000093
Figure JPOXMLDOC01-appb-T000093
Figure JPOXMLDOC01-appb-T000094
Figure JPOXMLDOC01-appb-T000094
Figure JPOXMLDOC01-appb-T000095
Figure JPOXMLDOC01-appb-T000095
Figure JPOXMLDOC01-appb-T000096
Figure JPOXMLDOC01-appb-T000096
Figure JPOXMLDOC01-appb-T000097
Figure JPOXMLDOC01-appb-T000097
Figure JPOXMLDOC01-appb-T000098
Figure JPOXMLDOC01-appb-T000098
Figure JPOXMLDOC01-appb-T000099
Figure JPOXMLDOC01-appb-T000099
Figure JPOXMLDOC01-appb-T000100
Figure JPOXMLDOC01-appb-T000100
Figure JPOXMLDOC01-appb-T000101
Figure JPOXMLDOC01-appb-T000101
Figure JPOXMLDOC01-appb-T000102
Figure JPOXMLDOC01-appb-T000102
Figure JPOXMLDOC01-appb-T000103
Figure JPOXMLDOC01-appb-T000103
Figure JPOXMLDOC01-appb-T000104
Figure JPOXMLDOC01-appb-T000104
Figure JPOXMLDOC01-appb-T000105
Figure JPOXMLDOC01-appb-T000105
実施例１２　上記実施例に従い、以下の化合物が合成可能である。 Example 12 According to the above Example, the following compounds can be synthesized.
Figure JPOXMLDOC01-appb-C000106
　ここで、Ｒ３は以下に示す基のいずれかである。
Figure JPOXMLDOC01-appb-C000106
Here, R 3 is any of the following groups.
Figure JPOXMLDOC01-appb-C000107
Figure JPOXMLDOC01-appb-C000107
　以下に、本発明化合物の生物試験例を記載する。
試験例１　ＨＩＶ複製阻害試験
　ＨＩＶ（ＨＴＬＶ－ＩＩＩＢ株）持続感染ヒトＴ細胞株Ｍｏｌｔ－４　ｃｌｏｎｅ８を、１０％牛胎児血清添加ＲＰＭＩ－１６４０培地で培養し、上清を濾過してウイルスの力価を測定し、－８０℃で保存した。一方、各抗ヒト免疫不全ウイルス活性物質を上記の培養培地で所定の濃度になるように希釈し、９６ウエルマイクロプレートに５０μＬずつ分注した。ついで、ＭＴ－４細胞浮遊液を１００μＬ（２．５×１０４細胞）ずつ分注し、更に上記ＨＩＶ含有上清を上記の培養培地で希釈したものを５０μｌ（６０ｐｆｕ（ｐｌａｑｕｅ　ｆｏｒｍｉｎｇ　ｕｎｉｔ））ずつ加えた。 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.
　炭酸ガス培養器内で３７℃、４日間培養した後、すべてのウエルに３－（４，５－ジメチルチアゾール－２－イル）－２，５－ジフェニルテトラゾリウムブロマイド（ＭＴＴ）５ｍｇ／ｍＬ）、ＰＢＳを３０μＬずつ加え、更に１時間培養した。このとき、生存する細胞はＭＴＴを還元してフォルマザンを析出するので、すべてのウエルから細胞上清を１５０μＬずつ取り除き、代わりに１５０μＬの溶解液（１０％トリトンＸ－１００および０．４％（ｖ／ｖ）ＨＣｌ添加イソプロパノール）を加え、プレートミキサーで振とうしてフォルマザンを溶出した。マイクロリーダーを用いてフォルマザンをＯＤ　５６０ｎｍと６９０ｎｍ（参照波長）で測定し、結果を被対照と比較した。ウイルスによる細胞障害を５０％抑制する化合物濃度をＥＣ５０とした。 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.
　試験の結果、各実施例化合物のＥＣ５０は、以下の表の通りであった。 As a result of the test, the EC 50 of each Example compound was as shown in the following table.
Figure JPOXMLDOC01-appb-T000108
Figure JPOXMLDOC01-appb-T000108
試験例２　ＣＹＰ阻害試験
　市販のプールドヒト肝ミクロソームを用いて、ヒト主要ＣＹＰ５分子種（ＣＹＰ１Ａ２、２Ｃ９、２Ｃ１９、２Ｄ６、３Ａ４）の典型的基質代謝反応として７－エトキシレゾルフィンのＯ－脱エチル化（ＣＹＰ１Ａ２）、トルブタミドのメチル－水酸化（ＣＹＰ２Ｃ９）、メフェニトインの４’－水酸化（ＣＹＰ２Ｃ１９）、デキストロメトルファンのＯ脱メチル化（ＣＹＰ２Ｄ６）、テルフェナジンの水酸化（ＣＹＰ３Ａ４）を指標とし、それぞれの代謝物生成量が本発明化合物によって阻害される程度を評価した。 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.
　反応条件は以下のとおり：基質、０．５μｍｏｌ／Ｌ　エトキシレゾルフィン（ＣＹＰ１Ａ２）、１００μｍｏｌ／Ｌ　トルブタミド（ＣＹＰ２Ｃ９）、５０μｍｏｌ／Ｌ　Ｓ－メフェニトイン（ＣＹＰ２Ｃ１９）、５μｍｏｌ／Ｌ　デキストロメトルファン（ＣＹＰ２Ｄ６）、１μｍｏｌ／Ｌ　テルフェナジン（ＣＹＰ３Ａ４）；反応時間、１５分；反応温度、３７℃；酵素、プールドヒト肝ミクロソーム０．２ｍｇ　タンパク質／ｍＬ；本発明化合物濃度、１、５、１０、２０μｍｏｌ／Ｌ（４点）。 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) .
　９６穴プレートに反応溶液として、５０ｍｍｏｌ／Ｌ　Ｈｅｐｅｓ緩衝液中に各５種の基質、ヒト肝ミクロソーム、本発明化合物を上記組成で加え、補酵素であるＮＡＤＰＨを添加して、指標とする代謝反応を開始した。３７℃、１５分間反応した後、メタノール／アセトニトリル＝１／１（Ｖ／Ｖ）溶液を添加することで反応を停止した。３０００ｒｐｍ、１５分間の遠心後、遠心上清中のレゾルフィン（ＣＹＰ１Ａ２代謝物）を蛍光マルチラベルカウンタで定量し、トルブタミド水酸化体（ＣＹＰ２Ｃ９代謝物）、メフェニトイン４’水酸化体（ＣＹＰ２Ｃ１９代謝物）、デキストロルファン（ＣＹＰ２Ｄ６代謝物）、テルフェナジンアルコール体（ＣＹＰ３Ａ４代謝物）をＬＣ／ＭＳ／ＭＳで定量した。 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.
　薬物を溶解した溶媒であるＤＭＳＯのみを反応系に添加したものをコントロール（１００％）とし、残存活性（％）を算出し、濃度と抑制率を用いて、ロジスティックモデルによる逆推定によりＩＣ５０を算出した。 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.
　試験の結果、化合物４～９のいずれも、ＣＹＰ１Ａ２、ＣＹＰ２Ｃ１９、ＣＹＰ２Ｄ６、およびＣＹＰ３Ａ４の活性に対するＩＣ５０が全て２０μＭ以上であった。。 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. .
試験例３　ＣＹＰ３Ａ４蛍光ＭＢＩ試験
　ＣＹＰ３Ａ４蛍光ＭＢＩ試験は、代謝反応による本発明化合物のＣＹＰ３Ａ４阻害の増強を調べる試験である。ＣＹＰ３Ａ４酵素（大腸菌発現酵素）により７－ベンジルオキシトリフルオロメチルクマリン（７－ＢＦＣ）が脱ベンジル化されて、蛍光を発する代謝物７－ハイドロキシトリフルオロメチルクマリン（７－ＨＦＣ）が生じる。７－ＨＦＣ生成反応を指標としてＣＹＰ３Ａ４阻害を評価した。 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.
　反応条件は以下のとおり：基質、５．６μｍｏｌ／Ｌ　７－ＢＦＣ；プレ反応時間、０または３０分；反応時間、１５分；反応温度、２５℃（室温）；ＣＹＰ３Ａ４含量（大腸菌発現酵素）、プレ反応時６２．５ｐｍｏｌ／ｍＬ、反応時６．２５ｐｍｏｌ／ｍＬ（１０倍希釈時）；本発明化合物濃度、０．６２５、１．２５、２．５、５、１０、２０μｍｏｌ／Ｌ（６点）。 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) ).
　９６穴プレートにプレ反応液としてＫ－Ｐｉ緩衝液（ｐＨ７．４）中に酵素、本発明化合物溶液を上記のプレ反応の組成で加え、別の９６穴プレートに基質とＫ－Ｐｉ緩衝液で１／１０希釈されるようにその一部を移行し、補酵素であるＮＡＤＰＨを添加して指標とする反応を開始し（プレ反応無）、所定の時間反応後、アセトニトリル／０．５ｍｏｌ／Ｌ　Ｔｒｉｓ（トリスヒドロキシアミノメタン）＝４／１（Ｖ／Ｖ）を加えることによって反応を停止した。また残りのプレ反応液にもＮＡＤＰＨを添加しプレ反応を開始し（プレ反応有）、所定時間プレ反応後、別のプレートに基質とＫ－Ｐｉ緩衝液で１／１０希釈されるように一部を移行し指標とする反応を開始した。所定の時間反応後、アセトニトリル／０．５ｍｏｌ／Ｌ　Ｔｒｉｓ（トリスヒドロキシアミノメタン）＝４／１（Ｖ／Ｖ）を加えることによって反応を停止した。それぞれの指標反応を行ったプレートを蛍光プレートリーダーで代謝物である７－ＨＦＣの蛍光値を測定した。（Ｅｘ＝４２０ｎｍ、Ｅｍ＝５３５ｎｍ） 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)
　本発明化合物を溶解した溶媒であるＤＭＳＯのみを反応系に添加したものをコントロール（１００％）とし、本発明化合物をそれぞれの濃度添加したときの残存活性（％）を算出し、濃度と抑制率を用いて、ロジスティックモデルによる逆推定によりＩＣ５０を算出した。ＩＣ５０値の差が５μｍｏｌ／Ｌ以上の場合を（＋）とし、３μｍｏｌ／Ｌ以下の場合を（－）とした。 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 (−).
試験例４　代謝安定性試験
　市販のプールドヒト肝ミクロソームと本発明化合物を一定時間反応させ、反応サンプルと未反応サンプルの比較により残存率を算出し、本発明化合物が肝で代謝される程度を評価した。 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. .
　ヒト肝ミクロソーム０．５ｍｇタンパク質／ｍＬを含む０．２ｍＬの緩衝液（５０ｍｍｏｌ／Ｌ　Ｔｒｉｓ－ＨＣｌ　ｐＨ７．４、１５０ｍｍｏｌ／Ｌ　塩化カリウム、１０ｍｍｏｌ／Ｌ　塩化マグネシウム）中で、１ｍｍｏｌ／Ｌ　ＮＡＤＰＨ存在下で３７℃、０分あるいは３０分間反応させた（酸化的反応）。反応後、メタノール／アセトニトリル＝１／１（ｖ／ｖ）溶液の１００μＬに反応液５０μＬを添加、混合し、３０００ｒｐｍで１５分間遠心した。その遠心上清中の本発明化合物をＬＣ／ＭＳ／ＭＳにて定量し、反応後の本発明化合物の残存量を０分反応時の化合物量を１００％として計算した。なお、加水分解反応はＮＡＤＰＨ非存在下で、グルクロン酸抱合反応はＮＡＤＰＨに換えて５ｍｍｏｌ／Ｌ　ＵＤＰ－グルクロン酸の存在下で反応を行い、以後同じ操作を実施した。 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.
試験例５　溶解性試験
　本発明化合物の溶解度は、１％ＤＭＳＯ添加条件下で決定した。ＤＭＳＯにて１０ｍｍｏｌ／Ｌ化合物溶液を調製し、本発明化合物溶液６　μＬをｐＨ６．８人工腸液（０．２ｍｏｌ／Ｌ　リン酸二水素カリウム試液　２５０ｍＬに０．２ｍｏｌ／Ｌ　ＮａＯＨ試液１１８ｍＬ、水を加えて１０００ｍＬとした）５９４μＬに添加した。２５℃で１６時間静置させた後、混液を吸引濾過した。濾液をメタノール／水＝１／１（Ｖ／Ｖ）にて２倍希釈し、絶対検量線法によりＨＰＬＣまたはＬＣ／ＭＳ／ＭＳを用いて濾液中濃度を測定した。 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.
試験例６　Ｆｌｕｃｔｕａｔｉｏｎ　Ａｍｅｓ　Ｔｅｓｔ
　本発明化合物の変異原性を評価した。
　凍結保存しているネズミチフス菌（Ｓａｌｍｏｎｅｌｌａ　ｔｙｐｈｉｍｕｒｉｕｍ　ＴＡ９８株、ＴＡ１００株）２０μＬを１０ｍＬ液体栄養培地（２．５％　Ｏｘｏｉｄ　ｎｕｔｒｉｅｎｔ　ｂｒｏｔｈ　Ｎｏ．２）に接種し３７℃にて１０時間、振盪前培養する。ＴＡ９８株は９ｍＬの菌液を遠心（２０００×ｇ、１０分間）して培養液を除去した。９ｍＬのＭｉｃｒｏ　Ｆ緩衝液（Ｋ２ＨＰＯ４：３．５ｇ／Ｌ、ＫＨ２ＰＯ４：１ｇ／Ｌ、（ＮＨ４）２ＳＯ４：１ｇ／Ｌ、クエン酸三ナトリウム二水和物：０．２５ｇ／Ｌ、ＭｇＳＯ４・７Ｈ２０：０．１ｇ／Ｌ）に菌を懸濁し、１１０ｍＬのＥｘｐｏｓｕｒｅ培地（ビオチン：８μｇ／ｍＬ、ヒスチジン：０．２μｇ／ｍＬ、グルコース：８ｍｇ／ｍＬを含むＭｉｃｒｏＦ緩衝液）に添加した。ＴＡ１００株は３．１６ｍＬ菌液に対しＥｘｐｏｓｕｒｅ培地１２０ｍＬに添加し試験菌液を調製した。本発明化合物ＤＭＳＯ溶液（最高用量５０ｍｇ／ｍＬから２～３倍公比で数段階希釈）、陰性対照としてＤＭＳＯ、陽性対照として非代謝活性化条件ではＴＡ９８株に対しては５０μｇ／ｍＬの４－ニトロキノリン－１－オキシドＤＭＳＯ溶液、ＴＡ１００株に対しては０．２５μｇ／ｍＬの２－（２－フリル）－３－（５－ニトロ－２－フリル）アクリルアミドＤＭＳＯ溶液、代謝活性化条件ではＴＡ９８株に対して４０μｇ／ｍＬの２－アミノアントラセンＤＭＳＯ溶液、ＴＡ１００株に対しては２０μｇ／ｍＬの２－アミノアントラセンＤＭＳＯ溶液それぞれ１２μＬと試験菌液５８８μＬ（代謝活性化条件では試験菌液４９８μＬとＳ９　ｍｉｘ　９０μＬの混合液）を混和し、３７℃にて９０分間、振盪培養する。本発明化合物を暴露した菌液４６０μＬを、Ｉｎｄｉｃａｔｏｒ培地（ビオチン：８μｇ／ｍＬ、ヒスチジン：０．２μｇ／ｍＬ、グルコース：８ｍｇ／ｍＬ、ブロモクレゾールパープル：３７．５μｇ／ｍＬを含むＭｉｃｒｏＦ緩衝液）２３００μＬに混和し５０μＬずつマイクロプレート４８ウェル／用量に分注し、３７℃にて３日間、静置培養した。アミノ酸（ヒスチジン）合成酵素遺伝子の突然変異によって増殖能を獲得した菌を含むウェルは、ｐＨ変化により紫色から黄色に変色するため、１用量あたり４８ウェル中の黄色に変色した菌増殖ウェルを計数し、陰性対照群と比較して評価する。変異原性が陰性のものを（－）、陽性のものを（＋）として示した。 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 (+).
試験例７　ＢＡ試験
経口吸収性の検討実験材料と方法
（１）使用動物：マウスあるいはＳＤラットを使用する。
（２）飼育条件：マウスあるいはＳＤラットは、固形飼料および滅菌水道水を自由摂取させる。
（３）投与量、群分けの設定：経口投与、静脈内投与を所定の投与量により投与する。以下のように群を設定する。（化合物ごとで投与量は変更有）
　経口投与　１～３０ｍｇ／ｋｇ（ｎ＝２～３）
　静脈内投与　０．５～１０ｍｇ／ｋｇ（ｎ＝２～３）
（４）投与液の調製：経口投与は溶液または懸濁液として投与する。静脈内投与は可溶化して投与する。
（５）投与方法：経口投与は、経口ゾンデにより強制的に胃内に投与する。静脈内投与は、注射針を付けたシリンジにより尾静脈から投与する。
（６）評価項目：経時的に採血し、血漿中本発明化合物濃度をＬＣ／ＭＳ／ＭＳを用いて測定する。
（７）統計解析：血漿中本発明化合物濃度推移について、非線形最小二乗法プログラムＷｉｎＮｏｎｌｉｎ（登録商標）を用いて血漿中濃度‐時間曲線下面積（ＡＵＣ）を算出し、経口投与群と静脈内投与群のＡＵＣから本発明化合物のバイオアベイラビリティ（ＢＡ）を算出する。 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.
試験例８　ｈＥＲＧ試験
　本発明化合物の心電図ＱＴ間隔延長リスク評価を目的として、ｈｕｍａｎ　ｅｔｈｅｒ－ａ－ｇｏ－ｇｏ　ｒｅｌａｔｅｄ　ｇｅｎｅ　（ｈＥＲＧ）チャンネルを発現させたＨＥＫ２９３細胞を用いて、心室再分極過程に重要な役割を果たす遅延整流Ｋ＋電流（ＩＫｒ）への本発明化合物の作用を検討した。
　全自動パッチクランプシステム（ＰａｔｃｈＸｐｒｅｓｓ　７０００Ａ、ＡｘｏｎＩｎｓｔｒｕｍｅｎｔｓ　Ｉｎｃ．）を用い、ホールセルパッチクランプ法により、細胞を－８０ｍＶの膜電位に保持した後、＋４０ｍＶの脱分極刺激を２秒間、さらに－５０ｍＶの再分極刺激を２秒間与えた際に誘発されるＩＫｒを記録した。発生する電流が安定した後、本発明化合物を目的の濃度で溶解させた細胞外液（ＮａＣｌ：１３５　ｍｍｏｌ／Ｌ、ＫＣｌ：５．４　ｍｍｏｌ／Ｌ、ＮａＨ２ＰＯ４：０．３ｍｍｏｌ／Ｌ、ＣａＣｌ２・２Ｈ２Ｏ：１．８ｍｍｏｌ／Ｌ、ＭｇＣｌ２・６Ｈ２Ｏ：１ｍｍｏｌ／Ｌ、グルコース：１０ｍｍｏｌ／Ｌ、ＨＥＰＥＳ（４－（２－ｈｙｄｒｏｘｙｅｔｈｙｌ）－１－ｐｉｐｅｒａｚｉｎｅｅｔｈａｎｅｓｕｌｆｏｎｉｃ　ａｃｉｄ、４－（２－ヒドロキシエチル）－１－ピペラジンエタンスルホン酸）：１０ｍｍｏｌ／Ｌ、ｐＨ＝７．４）を室温条件下で、１０分間細胞に適用させた。得られたＩＫｒから、解析ソフト（ＤａｔａＸｐｒｅｓｓ　ｖｅｒ．１、Ｍｏｌｅｃｕｌａｒ　Ｄｅｖｉｃｅｓ　Ｃｏｒｐｏｒａｔｉｏｎ）を使用して、保持膜電位における電流値を基準に最大テール電流の絶対値を計測した。さらに、本発明化合物適用前の最大テール電流に対する阻害率を算出し、媒体適用群（０．１％ジメチルスルホキシド溶液）と比較して、本発明化合物のＩＫｒへの影響を評価した。 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.
試験例９　粉末溶解度試験
　適当な容器に本発明化合物を適量入れ、各容器にＪＰ－１液（塩化ナトリウム２．０ｇ、塩酸７．０ｍＬに水を加えて１０００ｍＬとする）、ＪＰ－２液（ｐＨ６．８のリン酸塩緩衝液５００ｍＬに水５００ｍＬを加える）、２０ｍｍｏｌ／Ｌ　タウロコール酸ナトリウム（ＴＣＡ）／ＪＰ－２液（ＴＣＡ１．０８ｇにＪＰ－２液を加え１００ｍＬとする）を２００μＬずつ添加した。試験液添加後に全量溶解した場合には、適宜、本発明化合物を追加する。密閉して３７℃で１時間振とう後に濾過し、各濾液１００μＬにメタノール１００μＬを添加して２倍希釈を行った。希釈倍率は、必要に応じて変更した。気泡および析出物がないかを確認し、密閉して振とうした。絶対検量線法によりＨＰＬＣを用いて本発明化合物を定量した。 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.
　以下に示す製剤例は例示にすぎないものであり、発明の範囲を何ら限定することを意図するものではない。
製剤例１　錠剤
　　本発明化合物　　　　　　　　　１５ｍｇ
　　乳糖　　　　　　　　　　　　　１５ｍｇ
　　ステアリン酸カルシウム　　　　　３ｍｇ
　ステアリン酸カルシウム以外の成分を均一に混合し、破砕造粒して乾燥し、適当な大きさの顆粒剤とする。次にステアリン酸カルシウムを添加して圧縮成形して錠剤とする。 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.
製剤例２　カプセル剤
　　本発明化合物　　　　　　　　　１０ｍｇ
　　ステアリン酸マグネシウム　　　１０ｍｇ
　　乳糖　　　　　　　　　　　　　８０ｍｇ
を均一に混合して粉末または細粒状として散剤をつくる。それをカプセル容器に充填してカプセル剤とする。 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.
製剤例３　顆粒剤
　　本発明化合物　　　　　　　　　　　３０ｇ
　　乳糖　　　　　　　　　　　　　　２６５ｇ
　　ステアリン酸マグネシウム　　　　　　５ｇ
　よく混合し、圧縮成型した後、粉砕、整粒し、篩別して適当な大きさの顆粒剤とする。 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.
　本発明に係る化合物は、エイズ等、ウイルス感染症の治療剤として有用な医薬となり得る。 The compound according to the present invention can be a useful drug as a therapeutic agent for viral infections such as AIDS.

Claims (23)

  1. 式（Ｉ）：
    Figure JPOXMLDOC01-appb-C000001
    （式中、破線は結合の存在または非存在を示し、ただし、隣接する破線が同時に結合の存在を示すことはなく、
    Ｒ１は、水素原子、ハロゲン、シアノ、ニトロ、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
    Ｒ２は、それぞれ独立して、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換のアルキルオキシ、置換若しくは非置換のアルケニルオキシ、置換若しくは非置換のアルキニルオキシ、置換若しくは非置換のアルキルスルファニル、置換若しくは非置換のアルケニルスルファニル、または置換若しくは非置換のアルキニルスルファニルであり、
    ｎは、１または２であり、
    Ｒ３は、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
    Ｒ４は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
    Ｒ５は、存在しないか、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
    Ｒ６は、ハロゲン、シアノ、ニトロ、または－Ｚ６－Ｒ６１であり、
    ここで、Ｚ６は、単結合、－Ｏ－、－Ｓ－、－ＮＲ６２－、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－Ｏ－ＣＯ－、－ＣＯ－Ｏ－、－ＮＲ６２－ＣＯ－、－ＣＯ－ＮＲ６２－、－ＣＨ２－ＣＯ－ＮＲ６２－、－ＮＲ６３－ＣＯ－ＮＲ６２－、－ＮＲ６２－ＣＳ－、－ＣＳ－ＮＲ６２－、－ＮＲ６３－ＣＳ－ＮＲ６２－、－ＮＲ６２－ＳＯ２－、－ＳＯ２－ＮＲ６２－、または－ＮＲ６３－ＳＯ２－ＮＲ６２－であり、
    Ｒ６１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
    Ｒ６２およびＲ６３は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニルであり、
    Ｚ６が－ＮＲ６２－、－ＣＯ－ＮＲ６２－、－ＣＨ２－ＣＯ－ＮＲ６２－、－ＮＲ６３－ＣＯ－ＮＲ６２－、－ＣＳ－ＮＲ６２－、－ＮＲ６３－ＣＳ－ＮＲ６２－、－ＳＯ２－ＮＲ６２－、または－ＮＲ６３－ＳＯ２－ＮＲ６２－の場合は、Ｒ６１とＲ６２が隣接する窒素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良く、ならびに
    Ｒ７は、ハロゲン、シアノ、ニトロ、または－Ｚ７－Ｒ７１であり、
    ここで、Ｚ７は、単結合、－Ｏ－、－Ｓ－、－ＮＲ７２－、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－Ｏ－ＣＯ－、－ＣＯ－Ｏ－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７２－ＣＳ－、－ＣＳ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、－ＳＯ２－ＮＲ７２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－であり、
    Ｒ７１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
    Ｒ７２およびＲ７３は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニルであり、
    Ｚ７が－ＮＲ７２－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＣＳ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＳＯ２－ＮＲ７２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－の場合は、Ｒ７１とＲ７２が隣接する窒素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良く、
    ここで、Ｒ１とＲ７は、隣接する炭素原子と一緒になって、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基を形成しても良く、
    Ｒ５とＲ７は、隣接する窒素原子および炭素原子と一緒になって、置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良く、
    Ｒ５とＲ６は、隣接する窒素原子および炭素原子と一緒になって、置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良い。）
    で示される化合物（以下の化合物を除く）、またはその製薬上許容される塩。
    Figure JPOXMLDOC01-appb-C000002
         Formula (I):
    Figure JPOXMLDOC01-appb-C000001
    (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):
    Figure JPOXMLDOC01-appb-C000002
  2. Ｒ５が存在しない、請求項１記載の化合物またはその製薬上許容される塩。 R 5 is absent, the compound or a pharmaceutically acceptable salt thereof according to claim 1.
  3. 式（ＩＩ）で示される、請求項２記載の化合物またはその製薬上許容される塩。
    Figure JPOXMLDOC01-appb-C000003
         The compound according to claim 2 represented by formula (II) or a pharmaceutically acceptable salt thereof.
    Figure JPOXMLDOC01-appb-C000003
  4. Ｒ４が水素原子である、請求項１～３のいずれかに記載の化合物、またはその製薬上許容される塩。 The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, wherein R 4 is a hydrogen atom.
  5. ｎが１である、請求項１～４のいずれかに記載の化合物、またはその製薬上許容される塩。 The compound according to any one of claims 1 to 4, wherein n is 1, or a pharmaceutically acceptable salt thereof.
  6. Ｒ２が置換若しくは非置換のアルキルオキシである、請求項１～５のいずれかに記載の化合物、またはその製薬上許容される塩。 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.
  7. Ｒ６が置換若しくは非置換のアルキルである、請求項１～６のいずれかに記載の化合物、またはその製薬上許容される塩。 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.
  8. Ｒ１が置換若しくは非置換のアルキルである、請求項１～７のいずれかに記載の化合物またはその製薬上許容される塩。 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.
  9. Ｒ７が－Ｚ７－Ｒ７１であり、Ｚ７が単結合、－ＮＲ７２－、－Ｏ－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７２－ＣＳ－、－ＣＳ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、－ＳＯ２－ＮＲ７２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－である、請求項１～８のいずれかに記載の化合物またはその製薬上許容される塩。 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,.
  10. Ｒ７が－Ｚ７－Ｒ７１であり、Ｚ７が単結合、－ＮＲ７２－、－ＮＲ７２－ＣＯ－、－ＣＯ－ＮＲ７２－、－ＣＨ２－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＯ－ＮＲ７２－、－ＮＲ７３－ＣＳ－ＮＲ７２－、－ＮＲ７２－ＳＯ２－、または－ＮＲ７３－ＳＯ２－ＮＲ７２－である、請求項９記載の化合物またはその製薬上許容される塩。 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.
  11. Ｒ７１が水素原子、置換若しくは非置換のアルキル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基である、請求項９または１０記載の化合物またはその製薬上許容される塩。 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.
  12. Ｒ７が－Ｚ７－Ｒ７１であり、Ｚ７が－ＮＲ７３－ＣＯ－ＮＲ７２－であり、Ｒ７１が置換若しくは非置換の非芳香族炭素環式基である、請求項９～１１のいずれかに記載の化合物またはその製薬上許容される塩。 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.
  13. Ｒ１とＲ７が隣接する炭素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成する、請求項１～７のいずれかに記載の化合物またはその製薬上許容される塩。 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.
  14. 式（ＩＩＩ）：
    Figure JPOXMLDOC01-appb-C000004
    で示され、
    Ｘは、－Ｃ（Ｒ１０）２－、－ＮＲ９－、または－Ｏ－であり、
    Ｙは、－Ｃ（Ｒ１０）２－、－ＣＯ－、または－ＳＯ２－であり、
    Ｗは、－Ｃ（Ｒ１０）２－、－ＮＲ１０－、または－Ｏ－であり、
    Ｒ９は、ハロゲン、シアノ、ニトロ、または－Ｚ９－Ｒ９１であり、
    ここで、Ｚ９は、単結合、－Ｏ－、－Ｓ－、－ＮＲ９２－、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－Ｏ－ＣＯ－、－ＣＯ－Ｏ－、－ＮＲ９２－ＣＯ－、－ＣＯ－ＮＲ９２－、－ＣＨ２－ＣＯ－ＮＲ９２－、－ＮＲ９３－ＣＯ－ＮＲ９２－、－ＮＲ９２－ＣＳ－、－ＣＳ－ＮＲ９２－、－ＮＲ９３－ＣＳ－ＮＲ９２－、－ＮＲ９２－ＳＯ２－、－ＳＯ２－ＮＲ９２－、または－ＮＲ９３－ＳＯ２－ＮＲ９２－であり、
    Ｒ９１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
    Ｒ９２およびＲ９３は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニルであり、
    Ｚ９が－ＮＲ９２－、－ＣＯ－ＮＲ９２－、－ＣＨ２－ＣＯ－ＮＲ９２－、－ＮＲ９３－ＣＯ－ＮＲ９２－、－ＣＳ－ＮＲ９２－、－ＮＲ９３－ＣＳ－ＮＲ９２－、－ＳＯ２－ＮＲ９２－、または－ＮＲ９３－ＳＯ２－ＮＲ９２－の場合は、Ｒ９１とＲ９２が隣接する窒素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良く、ならびに、
    Ｒ１０は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基である、
    請求項１３記載の化合物またはその製薬上許容される塩。     Formula (III):
    Figure JPOXMLDOC01-appb-C000004
    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.
  15. Ｘが－ＮＲ９－であり、Ｒ９が－Ｚ９－Ｒ９１であり、Ｚ９が－ＣＯ－ＮＲ９２－であり、Ｒ９１が置換若しくは非置換の非芳香族炭素環式基である、請求項１４記載の化合物またはその製薬上許容される塩。 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.
  16. Ｒ５とＲ７が隣接する窒素原子および炭素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成する、請求項１記載の化合物またはその製薬上許容される塩。 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.
  17. 式（ＩＶ）～（ＶＩ）：
    Figure JPOXMLDOC01-appb-C000005
    のいずれかで示され、
    Ｒ８は、ハロゲン、シアノ、ニトロ、または－Ｚ８－Ｒ８１であり、
    ここで、Ｚ８は、単結合、－Ｏ－、－Ｓ－、－ＮＲ８２－、－ＣＯ－、－ＣＳ－、－ＳＯ２－、－Ｏ－ＣＯ－、－ＣＯ－Ｏ－、－ＮＲ８２－ＣＯ－、－ＣＯ－ＮＲ８２－、－ＣＨ２－ＣＯ－ＮＲ８２－、－ＮＲ８３－ＣＯ－ＮＲ８２－、－ＮＲ８２－ＣＳ－、－ＣＳ－ＮＲ８２－、－ＮＲ８３－ＣＳ－ＮＲ８２－、－ＮＲ８２－ＳＯ２－、－ＳＯ２－ＮＲ８２－、または－ＮＲ８３－ＳＯ２－ＮＲ８２－であり、
    Ｒ８１は、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、置換若しくは非置換のアルキニル、置換若しくは非置換の芳香族炭素環式基、置換若しくは非置換の非芳香族炭素環式基、置換若しくは非置換の芳香族複素環式基、または置換若しくは非置換の非芳香族複素環式基であり、
    Ｒ８２およびＲ８３は、それぞれ独立して、水素原子、置換若しくは非置換のアルキル、置換若しくは非置換のアルケニル、または置換若しくは非置換のアルキニルであり、
    Ｚ８が－ＮＲ８２－、－ＣＯ－ＮＲ８２－、－ＣＨ２－ＣＯ－ＮＲ８２－、－ＮＲ８３－ＣＯ－ＮＲ８２－、－ＣＳ－ＮＲ８２－、－ＮＲ８３－ＣＳ－ＮＲ８２－、－ＳＯ２－ＮＲ８２－、または－ＮＲ８３－ＳＯ２－ＮＲ８２－の場合は、Ｒ８１とＲ８２が隣接する窒素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成しても良い、
    請求項１６記載の化合物またはその製薬上許容される塩。     Formulas (IV) to (VI):
    Figure JPOXMLDOC01-appb-C000005
    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.
  18. Ｒ３が置換若しくは非置換のフェニル、置換若しくは非置換のシクロアルケニル、置換若しくは非置換のクロマニル、または置換若しくは非置換のベンゾモルホリニルである、請求項１～１７のいずれかに記載の化合物またはその製薬上許容される塩。 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.
  19. Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換のフェニル、置換若しくは非置換のシクロアルケニル、置換若しくは非置換のクロマニル、または置換若しくは非置換のベンゾモルホリニルであり、Ｒ４が水素原子であり、Ｒ５が存在せず、Ｒ６が置換若しくは非置換のアルキルである、請求項１～１１のいずれかに記載の化合物またはその製薬上許容される塩。 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.
  20. Ｒ１とＲ７が隣接する炭素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成し、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換のフェニル、置換若しくは非置換のシクロアルケニル、置換若しくは非置換のクロマニル、または置換若しくは非置換のベンゾモルホリニルであり、Ｒ４が水素原子であり、Ｒ５が存在せず、Ｒ６が置換若しくは非置換のアルキルである、請求項１～７のいずれかに記載の化合物またはその製薬上許容される塩。 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.
  21. Ｒ１が置換若しくは非置換のアルキルであり、Ｒ２が置換若しくは非置換のアルキルオキシであり、ｎが１であり、Ｒ３が置換若しくは非置換のフェニル、置換若しくは非置換のシクロアルケニル、置換若しくは非置換のクロマニル、または置換若しくは非置換のベンゾモルホリニルであり、Ｒ４が水素原子であり、Ｒ５とＲ７が隣接する窒素原子および炭素原子と一緒になって置換若しくは非置換の芳香族複素環式基または置換若しくは非置換の非芳香族複素環式基を形成し、Ｒ６が置換若しくは非置換のアルキルである、請求項１記載の化合物またはその製薬上許容される塩。 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.
  22. 請求項１～２１のいずれかに記載の化合物またはその製薬上許容される塩を含有する医薬組成物。 A pharmaceutical composition comprising the compound according to any one of claims 1 to 21 or a pharmaceutically acceptable salt thereof.
  23. 抗ＨＩＶ作用を有する、請求項２２記載の医薬組成物。 The pharmaceutical composition according to claim 22, which has an anti-HIV action.
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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014119636A1 (en) 2013-01-31 2014-08-07 塩野義製薬株式会社 Hiv replication inhibitor
US8987250B2 (en) 2012-04-20 2015-03-24 Gilead Sciences, Inc. Therapeutic compounds
US9006229B2 (en) 2011-04-21 2015-04-14 Gilead Sciences, Inc. Benzothiazole compounds and their pharmaceutical use
US9102614B2 (en) 2010-07-02 2015-08-11 Gilead Sciences, Inc. Naphth-2-ylacetic acid derivatives to treat AIDS
WO2015126765A1 (en) * 2014-02-19 2015-08-27 Bristol-Myers Squibb Company Inhibitors of human immunodeficiency virus replication
WO2015174511A1 (en) * 2014-05-16 2015-11-19 塩野義製薬株式会社 Tricyclic heterocyclic derivative having hiv replication-inhibiting effect
US9284323B2 (en) 2012-01-04 2016-03-15 Gilead Sciences, Inc. Naphthalene acetic acid derivatives against HIV infection
US9296758B2 (en) 2010-07-02 2016-03-29 Gilead Sciences, Inc. 2-quinolinyl-acetic acid derivatives as HIV antiviral compounds
US9376392B2 (en) 2012-01-04 2016-06-28 Gilead Sciences, Inc. 2-(tert-butoxy)-2-(7-methylquinolin-6-yl) acetic acid derivatives for treating AIDS
WO2017029631A1 (en) * 2015-08-20 2017-02-23 VIIV Healthcare UK (No.5) Limited Pyridin-3-yl acetic acid derivatives as inhibitors of human immunodeficiency virus replication
US10494380B2 (en) 2015-05-29 2019-12-03 Shionogi & Co., Ltd. Nitrogen-containing tricyclic derivatives having HIV replication inhibitory activity
US20210371388A1 (en) * 2020-05-12 2021-12-02 Baruch S. Blumberg Institute Bicyclic Carboxamide with Exocyclic Urea Derivatives as Antivirals for the Treatment of HBV Infection

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013002357A1 (en) * 2011-06-30 2013-01-03 塩野義製薬株式会社 Hiv replication inhibitor

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013002357A1 (en) * 2011-06-30 2013-01-03 塩野義製薬株式会社 Hiv replication inhibitor

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
AKSENOV,A.V. ET AL.: "Investigations in the region of 2,3'-biquinolyl 5. Investigation of the reaction of stabilized C-nucleophiles with 1-alkyl-3-(2-quinolyl)-quinolinium halides", CHEMISTRY OF HETEROCYCLIC COMPOUNDS, vol. 34, no. 9, 1999, pages 1045 - 1049 *
RUDLER,H. ET AL.: "Bis(trimethylsilyl)ketene acetals as C,O-dinucleophiles: One-pot formation of polycyclic y- and 5-lactones from pyridines and pyrazines", EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, no. 17, 2005, pages 3724 - 3744, XP055206759, DOI: doi:10.1002/ejoc.200500162 *

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* Cited by examiner, † Cited by third party
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US9296758B2 (en) 2010-07-02 2016-03-29 Gilead Sciences, Inc. 2-quinolinyl-acetic acid derivatives as HIV antiviral compounds
US9102614B2 (en) 2010-07-02 2015-08-11 Gilead Sciences, Inc. Naphth-2-ylacetic acid derivatives to treat AIDS
US9006229B2 (en) 2011-04-21 2015-04-14 Gilead Sciences, Inc. Benzothiazole compounds and their pharmaceutical use
US9376392B2 (en) 2012-01-04 2016-06-28 Gilead Sciences, Inc. 2-(tert-butoxy)-2-(7-methylquinolin-6-yl) acetic acid derivatives for treating AIDS
US9284323B2 (en) 2012-01-04 2016-03-15 Gilead Sciences, Inc. Naphthalene acetic acid derivatives against HIV infection
US9096586B2 (en) 2012-04-20 2015-08-04 Gilead Sciences, Inc. Therapeutic compounds
US8987250B2 (en) 2012-04-20 2015-03-24 Gilead Sciences, Inc. Therapeutic compounds
WO2014119636A1 (en) 2013-01-31 2014-08-07 塩野義製薬株式会社 Hiv replication inhibitor
US20180362543A1 (en) * 2013-01-31 2018-12-20 Shionogi & Co., Ltd. Hiv replication inhibitor
US9938271B2 (en) 2014-02-19 2018-04-10 VIIV Healthcare UK (No.5) Limited Inhibitors of human immunodeficiency virus replication
WO2015126765A1 (en) * 2014-02-19 2015-08-27 Bristol-Myers Squibb Company Inhibitors of human immunodeficiency virus replication
US9975906B2 (en) 2014-05-16 2018-05-22 Shionogi & Co., Ltd. Tricyclic heterocycle derivatives having HIV replication inhibitory effect
JPWO2015174511A1 (en) * 2014-05-16 2017-04-20 塩野義製薬株式会社 Tricyclic heterocyclic derivatives having HIV replication inhibitory action
WO2015174511A1 (en) * 2014-05-16 2015-11-19 塩野義製薬株式会社 Tricyclic heterocyclic derivative having hiv replication-inhibiting effect
US10494380B2 (en) 2015-05-29 2019-12-03 Shionogi & Co., Ltd. Nitrogen-containing tricyclic derivatives having HIV replication inhibitory activity
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WO2017029631A1 (en) * 2015-08-20 2017-02-23 VIIV Healthcare UK (No.5) Limited Pyridin-3-yl acetic acid derivatives as inhibitors of human immunodeficiency virus replication
US10106504B2 (en) 2015-08-20 2018-10-23 VIIV Healthcare UK (No.5) Limited Pyridin-3-yl acetic acid derivatives as inhibitors of human immunodeficiency virus replication
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