WO2005094805A1 - Imine derivative and amide derivative - Google Patents

Imine derivative and amide derivative Download PDF

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Publication number
WO2005094805A1
WO2005094805A1 PCT/JP2005/006464 JP2005006464W WO2005094805A1 WO 2005094805 A1 WO2005094805 A1 WO 2005094805A1 JP 2005006464 W JP2005006464 W JP 2005006464W WO 2005094805 A1 WO2005094805 A1 WO 2005094805A1
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Prior art keywords
group
substituent
hydroxy
hydroxypyrazole
compound
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PCT/JP2005/006464
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French (fr)
Japanese (ja)
Inventor
Rika Tanaka
Hirohisa Kitagawa
Masao Sasaki
Susumu Muto
Akiko Itai
Ryukou Tokuyama
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Institute Of Medicinal Molecular Design. Inc.
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Publication of WO2005094805A1 publication Critical patent/WO2005094805A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a production inhibitory effect of prostaglandin D2 (PGD2) and Z or hematopoietic type.
  • the present invention relates to a medicament having a PGD2 synthase inhibitory action and having an action such as an anti-allergy, anti-inflammatory, tissue damage-protecting action or anti-asthma.
  • Prostaglandin D2 is a type of arachidonic acid metabolite synthesized using prostaglandin H2 (PGH2) as an intermediate by the cyclooxygenase pathway in the arachidonic acid cascade. It is known that prostaglandin F2a (PGF2 ⁇ ), prostaglandin E2 (PGE2), prostaglandin I2 (PGI2) and thromboxane A2 (TXA2) are synthesized in addition to PGD2 from the synthetic pathway, You.
  • mast cells activated by binding of a complex of antigen and immunoglobulin E (IgE) that are thought to play a central role in allergic reactions Therefore, it is considered that the arachidonic acid metabolic cascade is activated and various inflammatory mediators derived from arachidonic acid are released, which plays an important role in causing allergic symptoms.
  • IgE immunoglobulin E
  • PGD2 is the most inflammatory mediator produced and released, and is detected at high concentrations in bronchoalveolar lavage fluid of asthmatic patients (The Journal of
  • H-PGDS hematopoietic enzymes
  • lipocalin enzymes Lipocalin-type enzymes are mainly distributed in the brain.Since PGD2 is a sleep inducer, it is implicated in inducing sleep, lowering body temperature, suppressing progestin secretion, and regulating pain and odor responses. It is known (Vitamins and hormones, Vol. 58, p. 89--120 (2000); The Journal of Biological Chemistry, Vol. 260, No. 23, p.
  • HQL-79 (4-benzhydryloxy-1- (3- (1H-tetrazol-5-yl)), a benzhydryloxy derivative having a tetrazole skeleton, has been used as an inhibitor of hematopoietic organ enzymes.
  • Propyl ⁇ pyridine is known, and it has been reported that HQL-79 suppresses eosinophil infiltration into the respiratory tract, delayed asthmatic reaction, and irritation of the respiratory tract as an asthma model.
  • Japanese Journal of Pharmacology, Vol. 78, No. l, p. 1-10 (1998); and Japanese Journal of Pharmacology, Vol. 78, No. l, p. 11-22 (1998)
  • its activity Is not enough.
  • a hydroxy-substituted aryl derivative having a pyrazolyl group, a naphthyl group, or the like bonded via a linking group for example, The Journal of Medicinal Chemistry, Vol. 44, No. 22, p. 3730-3745 ( And WO 01/89457 disclose compounds having an agonist effect on thrombopoietin receptors, which may be useful in the treatment of thrombocytopenia and other conditions associated with suppression of platelet production. It is described. However, according to The Journal of Medicinal Chemistry, Vol. 44, No. 22, p. 3730-3745 (2001), among the hydroxy-substituted aryl derivatives, the agonist action of the thrombopoietin receptor was observed.
  • -CH N-, -CONH- and -CHNH- are compounds of the thrombopoietin receptor No second strike activity is observed.
  • the above documents suggest and teach that the hydroxy-substituted aryl derivative has an inhibitory action on PGD2 production and an inhibitory action on Z or hematopoietic PGD2 synthase.
  • antiallergic agents such as ketotifen and terfenadine, antihistamines such as chlorphenamine-maleate, and antiinflammatory steroids are used for allergic diseases, but conventional antiallergic agents and antihistamines are not used. They may have sufficient medicinal properties, may not sufficiently suppress late allergic reactions, and may have central side effects such as drowsiness and sedation. Anti-inflammatory steroids are effective in suppressing late-onset allergic reactions. These drugs are not easy-to-use drugs due to the side effects such as immunosuppression. Therefore, selective and potent inhibitors of hematopoietic enzymes can be expected to be potent therapeutic agents for V, allergic inflammatory diseases, especially allergic asthma, which have fewer side effects than conventional drugs.
  • An object of the present invention is to develop a selective inhibitor of hematopoietic PGD2 synthase, and to provide an allergic inflammatory disease such as allergic rhinitis, which has little side effects and high safety, and particularly allergic asthma. It is to provide a medicament for treatment.
  • Hematopoietic PGD2 synthase is a subtype of Glutathione S-transferase (GST) and is an enzyme requiring Glutathione classified into ⁇ class GST.
  • GST Glutathione S-transferase
  • its three-dimensional structure has been elucidated by X-ray crystallography (see Cell, Vol. 90, ⁇ .6, ⁇ . 1085-1095 (1997)). It was reported that the ⁇ -helix has a short, wide and deep specific Cleft structure.
  • the present inventors used a computer-based molecular design method based on the analyzed three-dimensional structure to design a low-molecular-weight organic compound that could bind to the Cleft structure of hematopoietic PGD2 synthase. Synthesized.
  • the compound represented by the following general formula (I) can be converted into a hematopoietic PGD2 synthase.
  • the present invention provides
  • R 3 and R 4 are each independently a hydrogen atom, a halogen atom, and a C -C alkyl group which may have a substituent.
  • R 5 represents a C -C alkyl group which may have a substituent, or a C -C aryl group which may have a substituent Represents; R is substituted
  • a pharmacologically acceptable salt thereof and a substance selected from the group consisting of hydrates and solvates thereof, as a prostaglandin,
  • A may have a substituent C-C aryl group, may have a substituent 6 or more
  • B may have a substituent C-C aryl group, optionally having a substituent 5 to The medicament according to the above (1), which is a 13-membered heteroaryl group or a substituted or unsubstituted 5- or 10-membered partially saturated heterocyclic group;
  • A is a hydroxy-substituted C-C aryl group (the aryl group is further substituted in addition to the hydroxy group)
  • B has a substituent, and may be a 5- to 13-membered heteroaryl group
  • A is a hydroxy-substituted naphthyl group (the naphthyl group may have a substituent in addition to the hydroxy group);
  • B has a substituent and may be a virazolyl group
  • A is a 1-hydroxy-2-naphthyl group
  • B force is a hydrogen atom at position 1 and may have a substituent.
  • B is a C-C alkyl group optionally substituted at the 1-position,
  • Hydrogen atom optionally substituted C-C alkyl group, or optionally substituted
  • a good C-C aryl group which may have a hydrogen atom or a substituent at the 4-position.
  • B is a C-C atom which may have a hydrogen atom or a substituent at the 1-position.
  • 4-position is hydrogen atom
  • 5-position may have a substituent C-C aryl
  • a 6- to 10-membered heteroaryl group in which A is substituted with a hydroxy group (the heteroaryl The group may further have a substituent in addition to the hydroxy group, or);
  • B has a substituent and may be a 5-membered heteroaryl group
  • A is a hydroxy-substituted quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group);
  • B has a substituent and may be a virazolyl group
  • A is a 4-hydroxy-3-quinolyl group (the quinolyl group may have a substituent in addition to the hydroxy group);
  • B is a C-C alkyl group which may have a substituent at the 1-position, and may have a substituent
  • a C -C aryl group or a C -C aralkyl group which may have a substituent, wherein the 3-position is
  • a force A 9- or 10-membered partially saturated heterocyclic group containing one or two nitrogen atoms as a ring constituent atom (the partially saturated heterocyclic group may have a substituent and Y Is the position of the nitrogen atom which is a ring-constituting atom);
  • B has a substituent and may be a 5-membered heteroaryl group
  • A is a group selected from the following ring group ⁇ -3-1;
  • ⁇ ka N CH—;
  • B is a C-C alkyl group which may have a substituent at the 1-position, and may have a substituent
  • a C -C aryl group or a C -C aralkyl group which may have a substituent, wherein the 3-position is
  • the compound represented by the general formula (I) is a compound selected from the group consisting of the compounds represented by the compound Nos. 1 to 406 described in the present specification. The described medicament is provided.
  • the medicament according to any one of the above (1) to (13), which has one or more actions selected from the group consisting of an antiallergic action, an antiallergic inflammatory action, and an antiasthmatic action;
  • the medicament according to the above (1) which has an action of preventing exacerbation of brain damage and an action of improving the prognosis of brain damage or ⁇ or (13).
  • a compound represented by the above general formula (I), a pharmacologically acceptable salt thereof, and a hydrate thereof for the production of the above medicament are provided. And a solvate; use of the selected substance; a compound represented by the above general formula (I) and a pharmacologically A PGD2 production inhibitor comprising a substance selected from the group consisting of an acceptable salt thereof, and a hydrate and a solvate thereof as an active ingredient; a compound represented by the above general formula (I); A hematopoietic PGD2 synthase inhibitor comprising, as an active ingredient, a substance selected from the group consisting of acceptable salts thereof, and hydrates and solvates thereof; A method of inhibiting the compound selected from the group consisting of the compound represented by the general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate and a solvate thereof.
  • Acceptable salts, and it A method comprising administering to a mammal, including a human, an effective amount of a selected substance; selected from the group consisting of allergic diseases, allergic inflammatory diseases, and asthma
  • a method for preventing and / or treating one or more diseases comprising a compound represented by the above general formula (I), a pharmacologically acceptable salt thereof, and a hydrate and solvate thereof.
  • Group strength a method comprising the step of administering an effective amount of a selected substance to mammals including humans; a method for preventing exacerbation of brain damage, comprising the compound represented by the above general formula (I) and a pharmacologically active substance.
  • a method comprising administering to a mammal, including a human, an effective amount of a substance selected from the group consisting of hydrates and solvates thereof;
  • the general formula (I) A method comprising administering to a mammal, including a human, an effective amount of a selected substance, and a pharmacologically acceptable salt thereof, and a hydrate and solvate thereof.
  • a method for protecting the brain comprising the step of using a compound represented by the above general formula (I) and a pharmacologically acceptable salt thereof, and an effective substance selected from the group consisting of hydrates and solvates thereof.
  • a method comprising the step of administering an amount to a mammal, including a human; and a method for regulating a biological effect selected from the group consisting of estrous cycle, sleep, body temperature, pain sensation, and olfaction. And pharmacologically acceptable salts thereof, and hydrates and solvates thereof.
  • a method comprising the step of administering to a mammal, including a human, an effective amount of the selected substance. Is provided.
  • R 1M , R 2M , R 3M and R 4M are each independently A hydrogen atom, a halogen atom, and a C-C
  • R 5Q1 represents a C-C alkyl group which may have a substituent or a C- which may have a substituent
  • R 1001 represents an amino group which may have a substituent.
  • a 1Q1 is 2-hydroxy - be a 1-naphthyl group; ⁇ ⁇ 2-hydro carboxymethyl-4-sulfonyl -1 -Excluding compounds that are naphthyl groups]
  • a 1Q1 is a hydroxy-substituted naphthyl group (the naphthyl group may further have a substituent in addition to the hydroxy group;);
  • B 1Q1 is an optionally substituted pyrazolyl group, a salt thereof, or a hydrate or solvate thereof;
  • B 1Q1 is a C-C alkyl group optionally substituted at the 1-position,
  • the 4-position is a hydrogen atom, and the 5-position may have a substituent C-C
  • a 1M is a hydroxy-substituted quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group);
  • B 1Q1 is an optionally substituted pyrazolyl group, a salt thereof, or a hydrate or solvate thereof;
  • a 1M is a 4-hydroxy-3-quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group;).
  • B 1Q1 may have a C-C alkyl group optionally having a substituent at the 1-position, or a substituent
  • A1Q1 is a 9- or 10-membered partially saturated heterocyclic group containing 1 or 2 nitrogen atoms as a ring-constituting atom (the partially saturated heterocyclic group may have a substituent
  • the bond position to Y 1Q1 is the position of the nitrogen atom which is a ring-constituting atom);
  • B 1Q1 is an optionally substituted pyrazolyl group, a salt thereof, or a hydrate or solvate thereof;
  • a 1M is a group selected from the following ring group a ⁇ -3-1;
  • B 1Q1 may have a C-C alkyl group optionally having a substituent at the 1-position, or a substituent
  • the compound power represented by the general formula (II) The compound power represented by the compound Nos. 1 to 406 described in the present specification. Or a salt thereof, or a hydrate or solvate thereof, is provided as a novel substance.
  • Another aspect of the present invention is also selected from the group consisting of the compound represented by the above general formula (II), a pharmacologically acceptable salt thereof, and a hydrate and solvate thereof.
  • Containing active substance as an active ingredient; has a prostaglandin D2 (PGD2) production inhibitory action
  • PGD2 prostaglandin D2
  • the above-mentioned medicine having hematopoietic-type PGD2 synthase inhibitory action; the above-mentioned medicine having at least one action selected from the group consisting of antiallergic action, antiallergic inflammatory action and antiasthmatic action;
  • the above-mentioned medicines having a preventive action of exacerbation of brain damage and an improvement action of Z or brain prognosis; the above-mentioned medicines having a brain-protective action; and a sexual cycle controlling action, a sleep controlling action, a body temperature controlling action, an analgesic action, And a drug having at least one action selected from
  • Preventive action of exacerbation of brain injury A drug having an effect of improving the prognosis of Z or brain injury; selected from the group consisting of the compound represented by the above general formula (II) and pharmacologically acceptable salts thereof, and hydrates and solvates thereof.
  • a method for inhibiting the production of PGD2 in mammals including humans comprising a compound represented by the above general formula (II), a pharmaceutically acceptable salt thereof, and a hydrate thereof.
  • a method comprising administering an effective amount of a selected substance to mammals including humans; and a method for inhibiting hematopoietic PGD2 synthase in mammals including humans.
  • a method for improving the prognosis of brain injury comprising the compound represented by the above general formula (II), a pharmacologically acceptable salt thereof, and a hydrate and a solvent thereof.
  • Group strength consisting of Japanese comprising the step of administering to a mammal comprising: a method for protecting the brain, comprising the compound represented by the general formula (II) and a pharmacologically acceptable salt thereof, and a hydrate and a hydrate thereof.
  • a method comprising the step of administering an effective amount of a selected substance to a mammal, including a human; and a living body, wherein a group force consisting of estrous cycle, sleep, body temperature, pain, and smell is also selected.
  • a method of regulating the action comprising a group represented by the compound represented by the general formula (II) and a pharmacologically acceptable salt thereof, and a hydrate and a solvate thereof.
  • Administering an effective amount to a mammal, including a human, is provided.
  • -CH N-
  • -N CH-
  • -CONH- and -NHCO- are each represented by the following formula:
  • H, H O H, and H O are meant.
  • a and B each independently have a substituent, and may represent a hydrocarbon ring group or a substituent and represent a heterocyclic group.
  • the hydrocarbon ring group may be partially saturated, fully saturated, or deviated from an aromatic ring (aryl group). These groups can be bonded at any position on the ring.
  • aryl group examples include a phenyl group, a naphthyl group, an anthryl group, and a phananthryl group.
  • substituents including the aryl moiety (eg, an aralkyl group, an aryloxy group, an arylamino group, etc.).
  • Examples of the partially saturated hydrocarbon ring group include a cyclohexyl group, a cyclohexenyl group, an indenyl group and the like.
  • Examples of the completely saturated hydrocarbon ring group include cycloalkyl groups such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group; a bicyclo [3.2.1] octyl group; and an adamantyl group. .
  • heterocyclic group examples include a 3- to 14-membered monocyclic or condensed-ring group containing, as a ring-constituting atom, 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom, and a sulfur atom. I can do it. If they contain two or more heteroatoms, they may be the same or different.
  • the heterocyclic group may be partially saturated, fully saturated, or an aromatic ring (heteroaryl group). These groups can be attached at any position on the ring.
  • Heteroaryl groups include chel, furyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, benzothiopropyl, benzofurol, and isobenzothiophene.
  • 1.2.3-Triazolyl group 1,2,4-triazolyl group, tetrazolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazuryl group, quinolyl group, isoquinolyl group, phthalazyl group, naphthyridyl group, quinoxalinyl group, quinazolinyl Group, cinnolyl group, pteridinyl group,
  • 1.2.4-Triazyl group 1,3,5-triazyl group, carbazolyl group,
  • Partially saturated heterocyclic groups include a chromal group, an isochromanyl group, an imidazolyl group, a virazolyl group, an indole group, an isoindole group, a 1,2,3,4-tetrahydroquinolyl group, Examples thereof include a methylenedioxyphenyl group.
  • Examples of the fully saturated heterocyclic group include an azetidinyl group, a pyrrolidyl group, an imidazolidyl group, a bilazolidyl group, a piperidyl group, a piperazinyl group, a morpholinyl group, a thiomorpholinyl group, and a quinutalidinyl group.
  • the hydrocarbon ring group and heterocyclic group represented by A or B may have a substituent.
  • a certain functional group when a certain functional group has a “substituent, it may have a substituent” t, in such a case, the type, number, and substitution position of the substituent present in the functional group are as follows. There is no particular limitation. When two or more substituents are present, they may be the same or different.
  • Examples of such a substituent include a halogen atom (a fluorine atom, a chlorine atom, a bromine atom or an iodine atom may be used), an oxo group, a thioxo group, an oxoxide group, a nitro group, a nitroso group, a cyano group, an isocyano group.
  • a halogen atom a fluorine atom, a chlorine atom, a bromine atom or an iodine atom may be used
  • an oxo group a thioxo group
  • an oxoxide group a nitro group
  • a nitroso group a cyano group
  • an isocyano group an isocyano group.
  • hydrocarbon group examples include an alkyl group, an alkenyl group, an alkynyl group, an aryl group and an aralkyl group.
  • the alkyl group may be linear, branched, cyclic, or a combination thereof!
  • the cyclic alkyl group may be a monocyclic or condensed ring. More specifically, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, neopentyl, isopentyl, tert-butyl -Pentyl, n-hexyl, n-heptyl, n-octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, adamantyl and the like.
  • alkyl moiety of other substituents containing an alkyl moiety eg, an alkoxy group, an alkylamino group,
  • An alkenyl group may be linear, branched, cyclic, or a combination thereof, unless otherwise specified.
  • the cyclic alkyl group may be a monocyclic or condensed ring.
  • the number and position of double bonds present in the alkyl group are not particularly limited. More specifically, examples include a butyl group, an aryl group, an isopropyl group and an arenyl group.
  • the alkynyl group may be linear, branched or displaced unless otherwise specified.
  • the number and position of triple bonds present in the alkyl group are not particularly limited.
  • the alkenyl group may contain one or more double bonds. More specifically, examples include an ethur group and a propargyl group. The same applies to the alkyl moiety of other substituents containing an alkynyl moiety (for example, an alkyloxy group and the like).
  • the aralkyl group may be linear or branched unless otherwise specified. More specifically, examples thereof include a benzyl group, a 1-naphthylmethyl group, a 2-naphthylmethyl group, a 1-phenethyl group, and a 2-phenethyl group. The same applies to the aralkyl part of other substituents containing an aralkyl part (eg, an aralkyloxy group).
  • acryl group examples include a formyl group; an alkanol group such as an acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a valeryl group, an isovaleryl group, and a bivaloyl group; Alkyl group such as propioyl group; aroyl group such as benzoyl group, 1-naphthoyl group and 2-naphthoyl group; aralkyl carboxyl group such as benzylcarbon group; piperidinocarbon group; morpholino Heterocyclic carboyl groups such as carboyl group, furoyl group, tenoyl group, nicotinoyl group and isonicotinoyl group; carboxy groups; alkoxycarbonyl groups such as methoxycarbonyl groups; alkeoxy groups such as aryloxycarbonyl groups.
  • -Roxycarbol group propargylo Alkynyloxycarbyl groups such as xycarbonyl groups; aryloxycarbol groups such as phenoxycarbol groups; aralkyloxycarbonyl groups such as benzyloxycarbol groups; 4-piperidyloxycarboxy- A heterocyclic oxycarbyl group such as a benzyl group or a 3-pyridyloxycarbol group; an alkyl group such as a carbamoyl group or a methylcarbamoyl group; a dialkyl group such as a dimethylcarbamoyl group; a fluorcarbamoyl group; Arylalkyl groups such as benzylcarbamoyl group; sulfo groups; alkylsulfol groups such as mesyl group and propanesulfol group; alkenylsulfonyl groups such as arylsulfonyl group; propargylsul
  • substituents may be further substituted by the above-mentioned substituents.
  • substituents include halogenated alkyl groups such as trifluoromethyl group and pentafluoroethyl group; hydroxyalkyl groups such as hydroxymethyl group; carboxyalkyl groups such as carboxymethyl group; Halogenated alkanol groups such as trifluoroacetyl group; halogenated alkylsulfol groups such as trifluoromethanesulfol group; methoxycarbolamino group, tert-butoxycarbylamino group and the like.
  • alkoxysulfo-amino group such as a benzyloxycarbo-amino group; an alkylsulfo-amino group such as a mesylamino group; an arylsulfo-amino group such as a benzenesulfo-amino group.
  • a benzyloxycarbo-amino group an alkylsulfo-amino group such as a mesylamino group
  • an arylsulfo-amino group such as a benzenesulfo-amino group.
  • two or more of the above substituents may form a ring together with the atom to which they are bonded (carbon atom, nitrogen atom, etc.).
  • a ring may contain one or more heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom, and may have one or more substituents on the ring. May be.
  • the ring may be partially saturated, fully saturated, or a saturated ring, or an aromatic ring.
  • the hydrocarbon ring group which may have a substituent represented by A is preferably a C-C aryl group which may have a substituent, and more preferably a hydroxy-substituted C -C reel
  • the aryl group may further have a substituent in addition to the hydroxy group), particularly preferably a hydroxy-substituted naphthyl group (the naphthyl group is a hydroxy group and a further substituent group). And may be;)).
  • a hydrocarbon ring group having a substituent represented by A or an S-hydroxy-substituted naphthyl group (the naphthyl group may further have a substituent in addition to the hydroxy group;)
  • preferred examples include a group selected from the following ring group ex-1.
  • the hydrocarbon ring group which may have a substituent represented by A, is most preferably a 1-hydroxy-2-naphthyl group.
  • the heterocyclic group having a substituent represented by A may be a 6- or 13-membered heteroaryl group or a substituent. At least a 9- or 10-membered partially saturated heterocyclic group.
  • a heterocyclic group having a substituent represented by A or a heterocyclic group having a substituent is a 6- or 13-membered heteroaryl group, it is preferably hydroxy.
  • a 6- or 10-membered heteroaryl group (the heteroaryl group may further have a substituent in addition to the hydroxy group), more preferably a hydroxy-substituted quinolyl group (the quinolyl group is And further preferably a 4-hydroxy-3-quinolyl group (the quinolyl group further has a substituent in addition to the hydroxy group).
  • the heteroaryl group is preferably a group selected from the group consisting of a quinolyl group, an indolyl group, an indazolyl group, a benzothiazolyl group, a benzoxazolyl group, a carbazolyl group, a pyridyl group, a quinoxalinyl group and a dibenzofural group.
  • the 6- to 10-membered heteroaryl group is preferably a quinolyl group or a pyridyl group.
  • the heterocyclic group may have a substituent represented by A, and the heterocyclic group may be a hydroxy-substituted quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group, ;)), Preferred specific examples include groups selected from the following ring group oc-2-1.
  • the heterocyclic group may have a substituent represented by A, and the heterocyclic group may be a 4-hydroxy-3-quinolyl group (the quinolyl group may have a substituent in addition to the hydroxy group, In addition, when it is;), preferred V, specific examples include groups selected from the following ring group ex-2-2.
  • the heterocyclic group having a substituent represented by A or a heterocyclic group having a substituent is a 9- or 10-membered partially saturated heterocyclic group, More preferably, a 9- or 10-membered partially saturated heterocyclic group containing 1 or 2 nitrogen atoms as a ring-constituting atom (the partially saturated heterocyclic group may be substituted with Y Is the position of a nitrogen atom which is a ring-constituting atom), and is more preferably an isoindoline-2-yl group which may have a substituent, 1,2,3,4-tetrahydroisoquinoline-2-yl group and a substituent 1,2,3,4-tetrahydroquinazoline-3-yl having a 1,2-dihydroisoquinolin-2-yl group and a substituent! It is a group from which both basic power and group power are selected.
  • a substituent represented by A may have a heterocyclic group substituent, may have a substituent, may have an isoindolin-2-yl group, may have a substituent 1 , 2,3,4-tetrahydroisoquinolin-2-yl group, optionally having a substituent, 1,2-dihydroisoquinolin-2-yl group and optionally having a substituent 1,
  • substituent 1 2,3,4-tetrahydroisoquinolin-2-yl group
  • 1,2-dihydroisoquinolin-2-yl group optionally having a substituent 1
  • preferred examples thereof include groups selected from the following ring group ⁇ -3-1.
  • the hydrocarbon ring group which may have a substituent represented by ⁇ , is preferably a C-Caryl group which may have a substituent.
  • the hydrocarbon ring group When the hydrocarbon ring group has a substituent represented by ⁇ , the hydrocarbon ring group may have a substituent, or may be a C / C aryl group. Selected from group 13 -1-1
  • the heterocyclic group may preferably have a substituent, and may be a 5- or 13-membered heteroaryl group or a substituent.
  • a heterocyclic group having a substituent represented by B or a heterocyclic group having a substituent or a 5- or 13-membered heteroaryl group is preferred, it is preferably a 5-membered heteroaryl group.
  • (A) 1-position has a hydrogen atom, a C-C alkyl group which may have a substituent, and a substituent
  • a 9-membered heteroaryl group which may have a substituent; or a C-C alkyl group, which may have a substituent at the 3-position, or may have a substituent.
  • a 4-position is a hydrogen atom or a C-C alkoxycarboyl group which may have a substituent
  • (C) position 1 is a hydrogen atom or a C -C aryl group which may have a substituent; position 4 is water
  • a C-C alkyl group which may have a substituent at the 5-position, having a substituent
  • a heteroaryl group is preferably a pyrazolyl group, a carbazolyl group, an indolyl group, a benzimidazolyl group, a tetrazolyl group, a pyridyl group, a quinolyl group, a thiazolyl group, a benzothiazolyl group, an indazolyl group, a chelyl group, a benzothiopropyl group, or a furyl group. And a benzofural group.
  • the heterocyclic group may be
  • (A) 1-position has a hydrogen atom, a C-C alkyl group which may have a substituent, and a substituent
  • preferred specific examples include groups selected from the following ring group j8-2-1.
  • a 4-position is a hydrogen atom or a C-C alkoxycarboyl group which may have a substituent
  • preferred specific examples include groups selected from the following ring group j8-2-2.
  • (C) position 1 is a hydrogen atom or a C -C aryl group which may have a substituent; position 4 is water A C-C alkyl group which may have a substituent at the 5-position, having a substituent
  • Preferred specific examples include groups selected from the following ring group ⁇ -2-3.
  • heterocyclic group having a substituent represented by the formula (1) or (2) is a 5- or 10-membered partially saturated heterocyclic group having a substituent or a substituent
  • a preferred specific example is As an example, the following ring group j8-3-1 can be mentioned.
  • A may have a substituent C-C aryl group, may have a substituent 6 or more
  • B may have a substituent C-C aryl group, optionally having a substituent 5 to
  • A is hydroxy-substituted c-c aryl group (the aryl group is further substituted in addition to the hydroxy group)
  • a force A 6- to 10-membered heteroaryl group substituted with an S-hydroxy group (the heteroaryl The group may further have a substituent in addition to the hydroxy group, or);
  • A is a 9- or 10-membered partially saturated heterocyclic group containing 1 or 2 nitrogen atoms as ring-constituting atoms (the partially saturated heterocyclic group may have a substituent, and Is bonded to the nitrogen atom which is a ring-constituting atom);
  • A-hydroxy-substituted naphthyl group (the naphthyl group may have a substituent in addition to the hydroxy group);
  • a compound in which B has a substituent and may be a virazolyl group may be a virazolyl group.
  • A is a 1-hydroxy-2-naphthyl group
  • B force is a hydrogen atom at position 1 and may have a substituent.
  • B is a C-C alkyl group optionally substituted at the 1-position,
  • Hydrogen atom optionally substituted C-C alkyl group, or optionally substituted
  • a good C-C aryl group which may have a hydrogen atom or a substituent at the 4-position.
  • B is a C-C atom which may have a hydrogen atom or a substituent at the 1-position.
  • 4-position is hydrogen atom
  • 5-position may have a substituent C-C aryl
  • preferred specific examples of B include a group selected from the following ring group j8-2-1.
  • B include a group selected from the following ring group j8-2-2.
  • [Ring group ⁇ -2-2] 1- (4-methylphenyl) -3-methylvirazol-5-yl group, 1-phenylurazol-5-yl group, 1,3-diphenyl- Rubirazol-5-yl group, 1-phenyl-4- (ethoxycarbyl) pyrazole-5-yl group, 1-phenyl-3-methylpyrazole-5-yl group, 1-ethoxy Carboxyl-3-phenyl-4-azole group, 1-phenyl-3- (tert-butyl) pyrazol-5-yl group, 1- (4-chlorophenol)- 3-methylpyrazole-5-yl group, 1- (4-methoxyphenyl) -3-methylpyrazole-5-yl group, 1-benzyl-3-methylpyrazole-5-yl group, l- ( tert-butyl) -3-phenylpyrazole-5-yl group
  • preferred examples of B include, as specific examples, groups selected from the following ring group j8-2-4.
  • the compound corresponding to the above (0) is particularly preferably a compound selected from the group consisting of a compound represented by the following compound number described in the present specification.
  • A-hydroxy-substituted quinolyl group (the quinolyl group may have a substituent in addition to the hydroxy group);
  • a compound in which B has a substituent and may be a virazolyl group may be a virazolyl group.
  • A is a 4-hydroxy-3-quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group;).
  • B is a C-C alkyl group which may have a substituent at the 1-position, and may have a substituent
  • a C -C aryl group or a C -C aralkyl group which may have a substituent, wherein the 3-position is
  • a preferable example of B is, for example, a group selected from the following ring group j8-2-5.
  • the compound corresponding to the above GO is particularly preferably a compound selected from the group consisting of a compound represented by the following compound number described in the present specification.
  • a compound in which B has a substituent and may be a virazolyl group may be a virazolyl group.
  • a group is a group selected from the following ring group ⁇ -3-1;
  • B is a C-C alkyl group which may have a substituent at the 1-position, and may have a substituent
  • a C -C aryl group or a C -C aralkyl group which may have a substituent, wherein the 3-position is
  • ⁇ include groups selected from the following ring group j8-2-6 Can do.
  • the compound corresponding to the above (iii) is more preferably a compound selected from the group consisting of the following compound numbers described in the present specification.
  • the number of carbon atoms constituting an alkoxycarbonyl group is expressed as the total number of carbon atoms constituting an alkyl moiety and carbon atoms constituting a carbonyl moiety.
  • a C alkoxycarb group represents a methoxycarb group
  • a C alkoxycarb group represents a methoxycarb group
  • the 27 carboxy group represents an n- hexyloxycarbyl group, a (1-methylpentyl) oxycarbol group, a cyclohexyloxycarbol group, a cyclopentylmethoxycarboxy group or the like.
  • R 3 and R 4 are each independently a hydrogen atom, a halogen atom, and a C -C alkyl group which may have a substituent. Or a hydroxy group which may have a substituent;
  • R 5 represents a C -C alkyl group which may have a substituent, or a C -C aryl group which may have a substituent Represents;
  • R is substituted
  • R 3 and R 4 each independently represent a hydrogen atom or an optional substituent;
  • R 5 represents a hydrogen atom or an optional substituent;
  • R represents an amino group which may have a substituent]
  • the compounds represented by are excluded.
  • ⁇ and ⁇ each independently have a substituent, may have a hydrocarbon ring group or a substituent, and may represent a heterocyclic group.
  • the hydrocarbon ring group which may have a substituent represented by ⁇ , is preferably a C -C aryl group which may have a substituent, and is more preferably a hydroxy-substituted group.
  • the aryl group may further have a substituent in addition to the hydroxy group), particularly preferably a hydroxy-substituted naphthyl group (the naphthyl group is a hydroxy group and a further substituent group). And may be;)).
  • the optionally substituted hydrocarbon ring group represented by ⁇ is most preferably a 1-hydroxy-2-naphthyl group.
  • the heterocyclic group is preferably V having a substituent, or 6 or !!, or a 13-membered heteroaryl group, or! Is a 9- or 10-membered partially saturated heterocyclic group having a substituent.
  • heterocyclic group having a substituent represented by 1Q1 or a heterocyclic group having a substituent is a 6- to 13-membered heteroaryl group, it is preferably substituted with a hydroxy group.
  • a 6- or 10-membered heteroaryl group (the heteroaryl group may have a substituent in addition to the hydroxy group), and more preferably a hydroxy-substituted quinolyl group (the quinolyl group is a hydroxy group And further preferably a 4-hydroxy-3-quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group).
  • heterocyclic group has a substituent represented by ⁇ or may be a 6- or 13-membered heteroaryl group having a substituent or may be a 6- or 13-membered heteroaryl group
  • the heteroaryl group is preferably a group selected from the group consisting of quinolyl, indolyl, indazolyl, benzothiazolyl, benzoxazolyl, carbazolyl, pyridyl, quinoxalinyl and dibenzofuranyl groups.
  • a 6- to 10-membered heteroaryl group substituted with an S-hydroxy group having a substituent represented by ⁇ (the heteroaryl group may further have a substituent in addition to the hydroxy group)
  • the 6- to 10-membered heteroaryl group is preferably a quinolyl group or a pyridyl group.
  • preferred specific examples include groups selected from the following ring group ex 1 ex -2-1.
  • the heterocyclic group may have a substituent represented by ⁇ , and the heterocyclic group may be a 4-hydroxy-3-quinolyl group (the quinolyl group may have a substituent in addition to the hydroxy group, Or ;), a specific example is preferably a group selected from the following ring group ex 1 ⁇ - 2-2.
  • a heterocyclic group having a substituent represented by ⁇ or a heterocyclic group having a substituent is a 9- or 10-membered partially saturated heterocyclic group, More preferably, a 9- or 10-membered partially saturated heterocyclic group containing one or two nitrogen atoms as a ring-constituting atom (the partially saturated heterocyclic group may have a substituent Y 1M Is the position of the nitrogen atom which is a ring-constituting atom), and more preferably an isoindoline-2-yl group which may have a substituent, 1,2,3,4-tetrahydroisoquinolin-2-yl group having a substituent!
  • May have a substituent represented by ⁇ may have a heterocyclic group, may have a substituent, may have an isoindoline-2-yl group, may have a substituent 1,2,3,4-tetrahydroisoquinoline 2-yl group, may have a substituent! /, May be 1,2-dihydroisoquinolin-2-yl group and may have a substituent, 1,2,3,4-tetrahydro
  • preferred specific examples include a group selected from the following ring group a 1Q1-3 -l.
  • the hydrocarbon ring group which may have a substituent represented by B1Q1 is preferably a C-Caryl group which may have a substituent.
  • the heterocyclic group having a substituent represented by B 1Q1 or a heterocyclic group is preferably a 5- or 13-membered heteroaryl group, or a substituent.
  • a heterocyclic group having a substituent represented by B 1Q1 or a heterocyclic group having a substituent is a 5- or 13-membered heteroaryl group, preferably 5 Membered heteroaryl group, more preferably a pyrazolyl group optionally having a substituent, particularly preferably (A) hydrogen atom at the 1-position, optionally substituted C- C having an alkyl group and a substituent A C -C aryl group, an optionally substituted C -C aralkyl group, or
  • a 9-membered heteroaryl group which may have a substituent; or a C-C alkyl group, which may have a substituent at the 3-position, or may have a substituent.
  • a 4-position is a hydrogen atom or a C-C alkoxycarboyl group which may have a substituent
  • (C) position 1 is a hydrogen atom or a C -C aryl group which may have a substituent; position 4 is water
  • a C-C alkyl group which may have a substituent at the 5-position, having a substituent
  • a heteroaryl group is preferably a pyrazolyl group, a carbazolyl group, an indolyl group, a benzimidazolyl group, a tetrazolyl group, a pyridyl group, a quinolyl group, a thiazolyl group, a benzothiazolyl group, an indazolyl group, a thienyl group, a benzothiopropyl group, This group is selected from the group consisting of a furyl group and a benzofural group.
  • (A) 1-position has a hydrogen atom, a C-C alkyl group which may have a substituent, and a substituent
  • a 9-membered heteroaryl group which may have a substituent; or a C-C alkyl group, which may have a substituent at the 3-position, or may have a substituent.
  • preferred specific examples include a group selected from the following ring group ⁇ 81 () 1-2-1. [Ring group ⁇ -2-1] 1-phenyl-3-methyl-5-hydroxypyrazole-4-yl group, 1-phenyl
  • the heterocyclic group may be
  • An optionally substituted C-C alkyl group or an optionally substituted C-C aryl group A 4-position is a hydrogen atom or a C-C alkoxycarboyl group which may have a substituent;
  • preferred specific examples include a group selected from the following ring group ⁇ 81 () 1-2-2.
  • the heterocyclic group may be
  • (C) position 1 is a hydrogen atom or a C -C aryl group which may have a substituent; position 4 is water
  • a C-C alkyl group which may have a substituent at the 5-position, having a substituent
  • Preferred specific examples include groups selected from the following ring group ⁇ 1 ⁇ - 2-3.
  • heterocyclic group having a substituent represented by B 1Q1 or a heterocyclic group having a substituent and a 5- or 10-membered partially saturated heterocyclic group are preferred.
  • examples include groups selected from the following ring group j8 1Q1 -3-l.
  • ⁇ ⁇ may have a substituent C-C aryl group, may have a substituent 6 None
  • B 1Q1 may have a substituent, may be a C-C aryl group, may have a substituent, and may have 5 or more.
  • a 13-membered heteroaryl group or a compound having a substituent which may be a 5- or 10-membered partially saturated heterocyclic group.
  • a 1Q1 is a hydroxy-substituted c-c aryl group.
  • B 1Q1 is a compound having a substituent, and may be a 5- to 13-membered heteroaryl group.
  • a 1 () 1 is a 6- or 10-membered heteroaryl group substituted with a hydroxy group (the heteroaryl group may have a substituent in addition to the hydroxy group);
  • B 1Q1 is a 5-membered heteroaryl group having a substituent.
  • (iii) ⁇ is a 9- or 10-membered partially saturated atom containing one or two nitrogen atoms as ring-constituting atoms.
  • a sum heterocyclic group (the partially saturated heterocyclic group may have a substituent! ⁇ , And the bonding position with Y 1Q1 is the position of a ring-constituting nitrogen atom);
  • B 1 () 1 has a substituent and may be a 5-membered heteroaryl group.
  • a 1Q1 is a hydroxy-substituted naphthyl group (the naphthyl group may have a substituent in addition to the hydroxy group);
  • B 1Q1 is a compound having a substituent and possibly a virazolyl group.
  • A1M is a 1-hydroxy-2-naphthyl group
  • B 1 () 1 is a hydrogen atom at the 1-position, which may have a substituent.
  • B 1Q1 is a C 1 -C alkyl group optionally substituted at the 1-position,
  • B 1 (n is a C atom which may have a hydrogen atom or a substituent at the 1-position.
  • the 4-position is a hydrogen atom
  • the 5-position may have a substituent C -C
  • preferred examples of B 1Q1 include, as specific examples, groups selected from the following ring group ⁇ 1Q1-2 -l.
  • B 1Q1 include a group selected from the following ring group j8 ⁇ - 2-2.
  • Te you, the above (c), preferably of beta Omegaiota, as a specific example, can be a group selected from the following ring group j8 ⁇ -2-4.
  • the compound corresponding to the above (0) is particularly preferably a compound selected from the group consisting of a compound represented by the following compound number described in the present specification.
  • the compound corresponding to the above GO is preferably
  • ⁇ is a hydroxy-substituted quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group);
  • B 1Q1 is a compound having a substituent and possibly a virazolyl group.
  • a 1M is a 4-hydroxy-3-quinolyl group (the quinolyl group may have a substituent in addition to the hydroxy group;).
  • B 1Q1 may have a C-C alkyl group optionally having a substituent at the 1-position, or a substituent
  • beta Omegaiota leaves in the Rukoto mentioned a group selected from the following ring group ⁇ 1 ⁇ -2-5.
  • the compound corresponding to the above GO is particularly preferably the one described in the present specification.
  • the compound strength represented by the compound number is a compound to be selected.
  • a 1Q1 represents an optionally substituted isoindoline-2- yl group, an optionally substituted 1,2,3,4- tetrahydroisoquinolin-2-yl group, A 1,2-dihydroisoquinolin-2-yl group which may have a group and a 1,2,3,4-tetrahydroquinazoline-3-yl group which may have a substituent A group of choice;
  • B 1Q1 is a compound having a substituent and possibly a virazolyl group.
  • a 1M is a group selected from the following ring group a ⁇ - 3-1;
  • B 1Q1 may have a C-C alkyl group optionally having a substituent at the 1-position, or a substituent
  • beta Omegaiota following ring group
  • the compound corresponding to the above (m) is particularly preferably a compound selected from the group consisting of the following compound numbers described in the present specification.
  • the compound represented by the general formula (II) includes the following general formula (II-1):
  • R 1M , R 2M , R 3M and R 4M are each independently A hydrogen atom, a halogen atom, and a C-C
  • R 5Q1 represents a C-C alkyl group which may have a substituent or a C- which may have a substituent
  • R 1QQ1 represents an amino group which may have a substituent]
  • a 101 is a 2-hydroxy-1-naphthyl group ⁇ excluding compounds in which ⁇ is a 2-hydroxy-4-sulfo-1-naphthyl group.
  • R 1M , R 2M , R 3M and R 4M are each independently Represents a hydrogen atom or an optional substituent;
  • a 1Q1 is A 2-hydroxy-1-naphthyl group; excluding a compound in which ⁇ is a 2-hydroxy-4-sulfo-1-naphthyl group.
  • the compound represented by the above general formula (II) or a pharmacologically acceptable salt thereof, or a hydrate or solvate thereof, is a novel compound, and The use of the compound based on the substance invention is not particularly limited.
  • the compounds represented by the above general formulas (I) and (II) can form salts.
  • a metal salt such as a lithium salt, a sodium salt, a potassium salt, a magnesium salt, and a calcium salt, or an ammodimium salt or a methylammonium salt
  • Ammonium salts such as dimethylammonium salt, dimethylammonium salt, trimethylammonium salt, and dicyclohexylammonium salt.
  • a basic group for example, Hydrochloride, bromate, sulfate, nitrate, phosphate, etc., or methanesulfonate, benzenesulfonate, paratoluenesulfonate, acetate, propionate, tartrate
  • Organic salts such as fumarate, maleate, malate, oxalate, succinate, citrate, benzoate, mandelate, silicate, lac
  • the compounds represented by the above general formulas (I) and (II) or salts thereof may exist as hydrates or solvates. Any of the above substances may be used as the active ingredient of the medicament of the present invention. Further, the compounds represented by the general formulas (I) and (II) may have one or more asymmetric carbon atoms and may exist as stereoisomers such as optically active diastereomers. As the active ingredient of the medicament of the present invention, pure mixtures of stereoisomers, any mixture of enantiomers or diastereomers, racemates and the like may be used. Further, the compounds represented by the general formulas (I) and (II) may exist as tautomers depending on the type of the substituent. For example, in the case of the compound of Compound No. 1 described below, a tautomer represented by the following formula can be exemplified.
  • a tautomer in a pure form or a mixture thereof may be used.
  • the configuration may be either Z configuration or E configuration.
  • any configuration of geometric isomers or a mixture thereof may be used.
  • Me methyl group; Et: ethyl group; n- Pr: n-propyl group; n- Bu: n-butyl group; t- Bu: tert-butyl group; OMe: methoxy group; CO Me: methoxycarbol Group; CO Et: ethoxycarbol group;
  • the compound represented by the general formula (I) or (II) can be produced, for example, by the method shown below, but the production method of the compound is not limited to the following method.
  • the target compound (3) can be produced by reacting the aldehyde (1) and the amine (2) in a solvent.
  • the solvent used is not particularly limited as long as it does not adversely affect the reaction. Examples thereof include alcohols such as methanol, ethanol, and isopropanol; halogen solvents such as dichloromethane, dichloroethane, and chloroform; tetrahydrofuran.
  • Ethers such as 1,4-dioxane; aromatic solvents such as benzene, toluene, monochrome benzene, and 0-dichlorobenzene; amide solvents such as ⁇ , ⁇ -dimethylformamide and ⁇ -methylpyrrolidone; acetic acid; Organic acid solvents such as propionic acid; and mixed solvents of these solvents.
  • a catalyst may be used in this reaction. Examples of the catalyst used include salts such as sodium acetate, ammonium acetate, and potassium acetate; acids such as acetic acid and propionic acid; bases such as piperidine and pyrrolidine; and mixtures of these catalysts. be able to.
  • the reaction temperature is not particularly limited, but is usually from 0 ° C to the boiling point of the solvent used, preferably from room temperature to 150 ° C.
  • the reaction time depends on the reaction temperature and is usually 5 minutes to 3 days, preferably 5 minutes to 6 hours.
  • a compound represented by the formula (I), wherein Y is represented by -N CH-, is produced by replacing the combination of the aldehyde (1) and the amine (2) in the above reaction scheme 1. You can do it.
  • the compound in which Y is represented by -CONH- can be produced, for example, according to the method shown in the following reaction scheme 2.
  • the desired compound (5) can be produced by reacting the carboxylic acid (4) with the amine (2) in the presence of a condensing agent in a solvent.
  • a condensing agent examples include, for example, carbodiimides such as 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSCHC1); phosphorus trichloride, phosphorus oxychloride, salt chloride, etc. Acid nodogenizing agents.
  • the solvent used is not particularly limited as long as it does not adversely affect the reaction, and examples thereof include halogen solvents such as dichloromethane, dichloroethane, and chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; benzene And aromatic solvents such as toluene, monochrome benzene and 0-dichlorobenzene; amide solvents such as ⁇ , ⁇ -dimethylformamide and ⁇ -methylpyrrolidone; and mixed solvents of these solvents.
  • a reagent that promotes the reaction in this reaction may be used. Examples of the reagent used include bases such as triethylamine and pyridine.
  • the reaction temperature is not particularly limited, but is usually from 0 ° C to the boiling point of the solvent used, preferably from room temperature to 150 ° C.
  • the reaction time depends on the reaction temperature, but is usually 5 minutes to 3 days, preferably 5 minutes to 6 hours.
  • an acid nodroside, an acid anhydride or the like corresponding to the carboxylic acid (4) may be used.
  • the compound represented by the general formula (I) wherein Y is -NHCO- can be produced by replacing the combination of the carboxylic acid (4) and the amine (2) in the above reaction scheme 2. .
  • B is a 5-hydroxypyrazole-4-yl group (the group is further substituted in addition to the 5-position hydroxy group).
  • a compound having a group or a 2-hydroxyindole-3-yl group (the group may further have a substituent in addition to the 2-position hydroxy group) For example, it is manufactured by a method similar to “Procedure G” described in Journal of Medicinal Chemistry, Vol. 44, No. 25, p. 4339-4358 (2001).
  • B is a 5-hydroxypyrazol-4-yl group (the group is a 5-hydroxypyroxy group and a substituent other than the 5-position hydroxy group).
  • B is a 5-hydroxypyrazol-4-yl group (the group is a 5-hydroxypyroxy group and a substituent other than the 5-position hydroxy group).
  • the compound represented by the general formulas (I) and (II) may be produced using an optically active raw material.
  • a racemate may be produced and then subjected to optical resolution.
  • a method for optical resolution a method known to those skilled in the art can be used, and for example, high performance liquid chromatography using an optically active column can be used.
  • the compounds represented by the general formulas (I) and (II) produced by the above methods can be prepared by methods known to those skilled in the art, for example, extraction, precipitation, fractional chromatography, fractional crystallization, and suspension washing. It can be isolated and purified by, for example, recrystallization. Also, pharmacologically acceptable salts of the compound of the present invention, hydrates and solvates thereof can be produced by methods known to those skilled in the art.
  • the working examples of the present specification specifically describe methods for preparing representative compounds encompassed by the general formulas (I) and (II). Therefore, those skilled in the art can select appropriate reaction materials, reaction reagents, and reaction conditions while referring to the above description of the general production method and the description of the specific production method in Examples, and if necessary, By appropriately modifying or modifying these methods, any of the compounds included in the general formulas (I) and (II) can be produced. [0082]
  • the compounds represented by the general formulas (I) and (II) have an action of inhibiting PGD2 production and an action of inhibiting Z or hematopoietic PGD2 synthase, and are considered as allergic inflammation inhibitors. Can be suitably used.
  • the above medicament is useful as an active ingredient of a medicament for preventing and / or treating an inflammatory disease caused by an allergic reaction. More specifically, the medicament of the present invention is used for diseases considered to be involved in allergic inflammatory reactions such as contact dermatitis, atopic dermatitis, eczema, hay fever, asthma, and the like.
  • H-PGDS hematopoietic PGD2 synthase
  • DP receptor prostaglandin D receptor
  • H-PDGS inhibitor such as HQL-79 or an antagonist of DP receptor
  • HQL-79 or an antagonist of DP receptor an H-PDGS inhibitor
  • a brain injury model in transgenic mice that overexpresses H-PDGS
  • PGD2 is involved in the exacerbation of brain injury, as the damage is exacerbated. Therefore, a potent inhibitor of H-PDGS is useful as an agent useful for preventing exacerbation of brain injury and improving the prognosis of Z or brain injury, and the medicament of the present invention can also be used for this purpose.
  • the brain injury to which the medicament of the present invention is applied is not particularly limited.
  • traumatic injury due to a traffic accident cerebrovascular disorder such as cerebral infarction or cerebral hemorrhage, cerebral degenerative disease, demyelinating disease, etc. Forces that can exemplify things and the like are not limited to these.
  • PGD2 is known to be involved in the induction of sleep, hypothermia, suppression of luteinizing hormone secretion, and regulation of pain and odor responses (Vitamins and hormones, Vol. 58, p. 89 — 120 (2000); The Journal of Biological Chemistry, Vol. 260, No. 23, p. 12140— 12145 (1985); and Biochimica et Biophysica Acta, Vol. 1482, No. l— 2, p.259-271 (2000)), and the medicament of the present invention has at least one action selected from the group consisting of a sexual cycle control action, a sleep control action, a body temperature control action, an analgesic action, and an olfactory control action. Useful as a medicine.
  • the active ingredients of the medicament of the present invention include compounds represented by the general formulas (I) and (II), pharmacologically acceptable salts thereof, hydrates thereof, and solvates thereof.
  • One or more of the selected substances can be used.
  • the above-mentioned substance itself may be used as the medicament of the present invention, but preferably, the medicament of the present invention is used as an active ingredient and one or more pharmaceutically acceptable additives for pharmaceutical preparations.
  • a pharmaceutical composition comprising: In the above pharmaceutical composition, the ratio of the active ingredient to the pharmaceutical additive is about 1% to 90% by weight.
  • the medicament of the present invention can be administered, for example, as a pharmaceutical composition for oral administration such as granules, fine granules, powders, hard capsules, soft capsules, syrups, emulsions, suspensions, or liquids.
  • a pharmaceutical composition for oral administration such as granules, fine granules, powders, hard capsules, soft capsules, syrups, emulsions, suspensions, or liquids.
  • a preparation prepared as a pharmaceutical composition in the form of a powder may be dissolved at the time of use and used as an injection or infusion.
  • a solid or liquid pharmaceutical additive can be used.
  • the pharmaceutical additives may be either organic or inorganic. That is, when an oral solid preparation is produced, an excipient and, if necessary, a binder, a disintegrant, a lubricant, a coloring agent, a flavoring agent, etc. are added to the active substance, and then the tablet is prepared in a conventional manner. , Coated tablets, granules, powders, capsules and the like can be prepared.
  • the excipient to be used include lactose, sucrose, sucrose, glucose, corn starch, starch, talc, sorbitol, crystalline cellulose, dextrin, kaolin, calcium carbonate, and silicon dioxide.
  • binder examples include polyvinyl alcohol, polyvinyl ether, ethyl cellulose, methyl cellulose, gum arabic, tragacanth, gelatin, shellac, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, calcium citrate, dextrin, and pectin.
  • Lubricants include, for example, magnesium stearate, talc, polyethylene glycol, silica, hydrogenated spot oil and the like. I can make it. Any coloring agent can be used as long as it is normally permitted to be added to pharmaceutical products.
  • a flavoring agent cocoa powder, heart-shaped brain, aromatic acid, heart-shaped oil, dragon brain, cinnamon powder and the like can be used. These tablets and granules can be sugar-coated, gelatin-coated and optionally coated as needed. Further, if necessary, a preservative, an antioxidant and the like can be added.
  • liquid preparations for oral administration for example, emulsions, syrups, suspensions and liquid preparations
  • inert diluents such as water or vegetable oil
  • this preparation can contain adjuvants such as wetting agents, suspending agents, sweetening agents, flavoring agents, coloring agents and preservatives.
  • this preparation After preparing the liquid preparation, it may be filled into capsules of absorbable substance such as gelatin!
  • solvents or suspensions used for preparations for parenteral administration include, for example, water, propylene glycol, polyethylene glycol, benzyl alcohol, ethyl oleate, and lecithin. it can.
  • base used in the production of suppositories for example, cocoa butter, emulsified cocoa butter, laurin fat, and witetbsol can be mentioned.
  • the method for preparing the preparation is not particularly limited, and any method commonly used in the art can be used.
  • a carrier for example, dilution of water, ethyl alcohol, macrogol, propylene glycol, citric acid, acetic acid, phosphoric acid, lactic acid, sodium lactate, sulfuric acid and sodium hydroxide PH adjusters and buffers such as sodium citrate, sodium acetate and sodium phosphate; stabilizers such as sodium pyrosulfite, ethylenediaminetetraacetic acid, thioglycolic acid and thiolactic acid can be used.
  • a normal solubilizing agent, soothing agent, or local anesthetic which may contain sufficient amounts of salt, glucose, mannitol, or glycerin in the preparation to prepare an isotonic solution It is better to use agents.
  • an ointment for example, a paste, a cream or a gel, commonly used bases, stabilizers, wetting agents, preservatives and the like can be blended as required, and can be prepared by a conventional method.
  • Bases include, for example, white petrolatum, polyethylene, paraffin, glycerin, cellulose derivatives, polyethylene glycol, silicone Concrete and bentonite can be used.
  • preservative methyl noraoxybenzoate, ethyl ethyl paraoxybenzoate, propyl paraoxybenzoate and the like can be used.
  • the preparation When the preparation is in the form of a patch, the above-mentioned ointment, cream, gel, paste or the like can be applied to a usual support in a conventional manner.
  • a usual support woven or non-woven fabrics made of cotton, swoof and chemical fibers, and films or foam sheets of soft vinyl chloride, polyethylene and polyurethane can be suitably used.
  • the dose of the medicament of the present invention is not particularly limited.
  • the weight of the compound of the present invention per adult day is usually 0.01 to 5,000 mg. It is preferable to increase or decrease this dose appropriately according to the age, disease state and symptoms of the patient.
  • the daily dose may be administered once a day, divided into two or three times a day at appropriate intervals, or may be administered intermittently every few days.
  • the weight of the compound of the present invention is about 0.001 to 100 mg per adult per day.
  • Example 45 Compound number 45 (General synthesis method B)
  • WL 'WL [ ⁇ ) 8 ⁇ ' (s ⁇ ) ⁇ g :( i a a) WN °% os 3 ⁇ 4 ⁇
  • Example 76 Compound number 76
  • Example 77 Compound number 77
  • Example 87 Compound number 87
  • Example 93 Compound number 93
  • Example 94 Compound number 94

Abstract

A medicine having prostaglandin D2 (PGD2) production inhibitory activity and having as an active ingredient a substance selected from compounds represented by the general formula (I): A-Y-B {wherein A and B each independently represents an optionally substituted, cyclic hydrocarbon or heterocyclic group; and Y represents -CH=N-, -N=CH-, -CONH-, or -NHCO-, provided that the compounds represented by the following formula (I-1) [wherein X represents the formula -N=C(R5)- (wherein the left-side bond is bonded to the benzene ring and the right-side bond is bonded to the nitrogen atom) or the formula -NH-CH(R5)- (wherein the left-side bond is bonded to the benzene ring and the right-side bond is bonded to the nitrogen atom); R1, R2, R3, and R4 each independently represents hydrogen, halogeno, or optionally substituted C1-6 alkyl or hydroxy; R5 represents an optionally substituted C1-6 alkyl or C6-10 aryl group; and R represents optionally substituted amino] are excluded}, salts, hydrates, and solvates.

Description

明 細 書  Specification
ィミン誘導体及びアミド誘導体  Imine derivatives and amide derivatives
技術分野  Technical field
[0001] 本発明は、プロスタグランジン D2(PGD2)の産生抑制作用及び Z又は造血器型 [0001] The present invention relates to a production inhibitory effect of prostaglandin D2 (PGD2) and Z or hematopoietic type.
PGD2合成酵素阻害作用を有し、抗アレルギー、抗炎症、組織損傷保護作用又は抗 喘息等の作用を有する医薬に関するものである。 The present invention relates to a medicament having a PGD2 synthase inhibitory action and having an action such as an anti-allergy, anti-inflammatory, tissue damage-protecting action or anti-asthma.
背景技術  Background art
[0002] プロスタグランジン D2(PGD2)はァラキドン酸カスケード中のシクロォキシゲナーゼ経 路によりプロスタグランジン H2(PGH2)を中間体として合成されるァラキドン酸代謝物 の一種で、このような生合成経路からは PGD2の他にプロスタグランジン F2 a (PGF2 α )、プロスタグランジン E2(PGE2)、プロスタグランジン I2(PGI2)及びトロンボキサン A2(TXA2)が合成されることが知られて 、る。喘息やアレルギー性鼻炎などのアレル ギー性炎症疾患では、アレルギー反応の中心的役割を担っていると思われる抗原と 免疫グロブリン E(IgE)の複合体が結合して活性ィ匕されたマスト細胞にぉ 、て、ァラキ ドン酸代謝カスケードが活性化されてァラキドン酸に由来する種々の炎症性メデイエ 一ターが放出され、アレルギー症状の惹起に重要な役割をはたしているものと考えら れる。  [0002] Prostaglandin D2 (PGD2) is a type of arachidonic acid metabolite synthesized using prostaglandin H2 (PGH2) as an intermediate by the cyclooxygenase pathway in the arachidonic acid cascade. It is known that prostaglandin F2a (PGF2α), prostaglandin E2 (PGE2), prostaglandin I2 (PGI2) and thromboxane A2 (TXA2) are synthesized in addition to PGD2 from the synthetic pathway, You. In allergic inflammatory diseases such as asthma and allergic rhinitis, mast cells activated by binding of a complex of antigen and immunoglobulin E (IgE) that are thought to play a central role in allergic reactions Therefore, it is considered that the arachidonic acid metabolic cascade is activated and various inflammatory mediators derived from arachidonic acid are released, which plays an important role in causing allergic symptoms.
[0003] そのなかでも PGD2は最も多量に産生、放出される炎症性メディエーターであり、喘 息患者の気管支肺胞洗浄液中に高濃度で検出されている (The Journal of  [0003] Among them, PGD2 is the most inflammatory mediator produced and released, and is detected at high concentrations in bronchoalveolar lavage fluid of asthmatic patients (The Journal of
Immunology, Vol.129, No.4, p.1627— 1631(1982);及び The New England Journal of Medicine, Vol.315, No.13, p.800- 804(1986)参照)。実際に PGD2は強力な気道収縮 作用を示すだけではなぐ炎症に深く関与する好酸球を活性化する作用や気道過敏 性を誘発する作用を有することから、アレルギー性炎症疾患の中でもアレルギー性 喘息の病態に深く関わっているものと考えられる (The Journal of Immunology, Vol.129, No.4, p.1627— 1631(1982); The New England Journal of Medicine, Vol.315, No.13, p.800— 804(1986); The New England Journal of Medicine, Vol.311, No.4, p.209- 213(1984); The Journal of Immunology, Vol.148, No.l l, p.3536- 3542(1992); 及び Science, Vol.287, p.2013- 2017(2000)参照)。 Immunology, Vol. 129, No. 4, p. 1627-1631 (1982); and The New England Journal of Medicine, Vol. 315, No. 13, p. 800-804 (1986)). In fact, PGD2 not only exerts a powerful airway constriction effect, but also activates eosinophils that are deeply involved in inflammation and induces airway hyperreactivity. It is thought to be closely related to the disease state (The Journal of Immunology, Vol. 129, No. 4, p. 1627-1631 (1982); The New England Journal of Medicine, Vol. 315, No. 13, p. 800--804 (1986); The New England Journal of Medicine, Vol. 311, No. 4, p. 209-213 (1984); The Journal of Immunology, Vol. 148, No. ll, p. 3536-3542 ( 1992); And Science, Vol.287, p.2013-2017 (2000)).
[0004] PGH2より PGD2を合成する合成酵素には造血器型酵素 (H- PGDS)とリポカリン型酵 素の 2種類が知られている。リポカリン型酵素は主に脳内に分布し、 PGD2が睡眠誘 発物質であることから、睡眠の誘発、その他体温低下、黄体ホルモン分泌抑制、痛み や匂いの応答調節作用に関与していることが知られており (Vitamins and hormones, Vol.58, p.89— 120(2000); The Journal of Biological Chemistry, Vol.260, No.23, p.12140— 12145(1985);及び Biochimica et Biophysica Acta, Vol.1482, No.l— 2, p.259-271(2000)参照)、特に睡眠調節作用との関わりについては注目されている。 一方、造血器型酵素は主に胎盤、肺、マスト細胞、抗原提示細胞に分布していること から、アレルギー性炎症疾患には造血器型酵素が主に関与しているものと考えられ る (The Journal of Immunology, Vol.143, No.9, p.2982- 2989(1989); The Journal of Biological Chemistry, Vol.265, No.l, p.371- 375(1990);及び The Journal of Biological Chemistry, Vol.270, No.7, p.3239- 3246(1995)参照)。これまでに、造血器 型酵素の阻害剤として、テトラゾール骨格を有するベンズヒドリルォキシ誘導体である HQL- 79(4-ベンズヒドリルォキシ -1- {3- (1H-テトラゾール- 5-ィル)プロピル }ピリジン） が知られており、 HQL-79が喘息病態モデルにぉ 、て気道への好酸球浸潤および遅 発性喘息反応と 、つた気道炎症病態を抑制することが報告されて 、るが Japanese Journal of Pharmacology, Vol.78, No. l, p.1-10(1998);及び Japanese Journal of Pharmacology, Vol.78, No.l, p.11- 22(1998)参照)、その活性は十分とは言えない。  [0004] Two types of synthases that synthesize PGD2 from PGH2 are known: hematopoietic enzymes (H-PGDS) and lipocalin enzymes. Lipocalin-type enzymes are mainly distributed in the brain.Since PGD2 is a sleep inducer, it is implicated in inducing sleep, lowering body temperature, suppressing progestin secretion, and regulating pain and odor responses. It is known (Vitamins and hormones, Vol. 58, p. 89--120 (2000); The Journal of Biological Chemistry, Vol. 260, No. 23, p. 12140-- 12145 (1985); and Biochimica et Biophysica Acta , Vol.1482, No.l-2, p.259-271 (2000)), and particularly attention is paid to its relationship with the sleep regulating action. On the other hand, hematopoietic enzymes are mainly distributed in placenta, lung, mast cells, and antigen-presenting cells, suggesting that hematopoietic enzymes are mainly involved in allergic inflammatory diseases ( The Journal of Immunology, Vol.143, No.9, p.2982- 2989 (1989); The Journal of Biological Chemistry, Vol.265, No.l, p.371-375 (1990); and The Journal of Biological Chemistry, Vol.270, No.7, p.3239-3246 (1995)). To date, HQL-79 (4-benzhydryloxy-1- (3- (1H-tetrazol-5-yl)), a benzhydryloxy derivative having a tetrazole skeleton, has been used as an inhibitor of hematopoietic organ enzymes. Propyl} pyridine) is known, and it has been reported that HQL-79 suppresses eosinophil infiltration into the respiratory tract, delayed asthmatic reaction, and irritation of the respiratory tract as an asthma model. (See Japanese Journal of Pharmacology, Vol. 78, No. l, p. 1-10 (1998); and Japanese Journal of Pharmacology, Vol. 78, No. l, p. 11-22 (1998)), its activity. Is not enough.
[0005] 一方、ピラゾリル基やナフチル基などが連結基を介して結合したヒドロキシ置換ァリ ール誘導体として、例えば、 The Journal of Medicinal Chemistry, Vol.44, No.22, p.3730-3745(2001);及び国際公開第 01/89457号パンフレットにトロンボポェチン受 容体に対するァゴニスト作用を有する化合物が開示されており、血小板減少症及び 血小板産生の抑制を伴う他の症状の治療などに有用であることが記載されて 、る。し かしながら、 The Journal of Medicinal Chemistry, Vol.44, No.22, p.3730- 3745(2001) によれば、上記ヒドロキシ置換ァリール誘導体の中で、トロンボポェチン受容体のァゴ 二スト作用を有する化合物は連結基が- N=N-である化合物であり、連結基が  [0005] On the other hand, as a hydroxy-substituted aryl derivative having a pyrazolyl group, a naphthyl group, or the like bonded via a linking group, for example, The Journal of Medicinal Chemistry, Vol. 44, No. 22, p. 3730-3745 ( And WO 01/89457 disclose compounds having an agonist effect on thrombopoietin receptors, which may be useful in the treatment of thrombocytopenia and other conditions associated with suppression of platelet production. It is described. However, according to The Journal of Medicinal Chemistry, Vol. 44, No. 22, p. 3730-3745 (2001), among the hydroxy-substituted aryl derivatives, the agonist action of the thrombopoietin receptor was observed. The compound having is a compound wherein the linking group is -N = N-,
- CH=N -、 - CONH-及び- CH NH-である化合物にはトロンボポェチン受容体のァゴ 二スト活性が認められない。また、上記各文献には、上記ヒドロキシ置換ァリール誘導 体が PGD2産生抑制作用を有すること及び Z又は造血器型 PGD2合成酵素阻害作用 を有することは示唆も教示もされて 、な 、。 -CH = N-, -CONH- and -CHNH- are compounds of the thrombopoietin receptor No second strike activity is observed. In addition, the above documents suggest and teach that the hydroxy-substituted aryl derivative has an inhibitory action on PGD2 production and an inhibitory action on Z or hematopoietic PGD2 synthase.
[0006] 現在、アレルギー性の疾患にはケトチフェン、テルフエナジン等の抗アレルギー剤、 マレイン酸クロルフエ-ラミン等の抗ヒスタミン剤及び抗炎症性ステロイド剤が使用さ れているが、従来の抗アレルギー剤、抗ヒスタミン剤では薬効が十分でな力つたり、遅 発的アレルギー反応を十分に抑制しないことがあり、また、眠気、鎮静症状等の中枢 性副作用の問題がある。遅発的アレルギー反応の抑制には抗炎症性ステロイドが有 効である力 免疫抑制等の副作用の問題もあり、使いやすい薬剤とは言えない。従つ て、選択的で強力な造血器型酵素の阻害剤は、従来の薬剤と比べて副作用の少な V、アレルギー性炎症疾患、特にアレルギー性喘息の有力な治療薬となることが期待 できる。 [0006] At present, antiallergic agents such as ketotifen and terfenadine, antihistamines such as chlorphenamine-maleate, and antiinflammatory steroids are used for allergic diseases, but conventional antiallergic agents and antihistamines are not used. They may have sufficient medicinal properties, may not sufficiently suppress late allergic reactions, and may have central side effects such as drowsiness and sedation. Anti-inflammatory steroids are effective in suppressing late-onset allergic reactions. These drugs are not easy-to-use drugs due to the side effects such as immunosuppression. Therefore, selective and potent inhibitors of hematopoietic enzymes can be expected to be potent therapeutic agents for V, allergic inflammatory diseases, especially allergic asthma, which have fewer side effects than conventional drugs.
発明の開示  Disclosure of the invention
発明が解決しょうとする課題  Problems to be solved by the invention
[0007] 本発明の課題は、造血器型 PGD2合成酵素の選択的阻害剤を開発し、副作用が少 なく安全性の高 、優れたアレルギー性鼻炎等のアレルギー性炎症疾患、特にアレル ギー性喘息治療のための医薬を提供することにある。 [0007] An object of the present invention is to develop a selective inhibitor of hematopoietic PGD2 synthase, and to provide an allergic inflammatory disease such as allergic rhinitis, which has little side effects and high safety, and particularly allergic asthma. It is to provide a medicament for treatment.
課題を解決するための手段  Means for solving the problem
[0008] 造血器型 PGD2合成酵素は Glutathione S-transferase(GST)のサブタイプで σクラス GSTに分類される Glutathione要求性の酵素である。近年、 X線結晶構造解析により その 3次元構造が解明され (Cell, Vol.90, Νο.6, ρ.1085-1095(1997)参照)、この酵素 は他の GSTと比較し、 4番目の αヘリックスが短ぐ広く深い特異的な Cleft構造を持つ ことが報告された。本発明者らは、解析された 3次元構造に基づいて、コンピューター を用いた分子設計の手法を用い、造血器型 PGD2合成酵素の Cleft構造部分に結合 可能と思われる低分子有機化合物を設計、合成した。そして、所望の酵素阻害活性 が見出された化合物群についてさらに分子設計より導かれた方針に従って誘導化す ることにより、下記の一般式 (I)で表される化合物が造血器型 PGD2合成酵素 [0008] Hematopoietic PGD2 synthase is a subtype of Glutathione S-transferase (GST) and is an enzyme requiring Glutathione classified into σ class GST. In recent years, its three-dimensional structure has been elucidated by X-ray crystallography (see Cell, Vol. 90, Νο.6, ρ. 1085-1095 (1997)). It was reported that the α-helix has a short, wide and deep specific Cleft structure. The present inventors used a computer-based molecular design method based on the analyzed three-dimensional structure to design a low-molecular-weight organic compound that could bind to the Cleft structure of hematopoietic PGD2 synthase. Synthesized. Further, by derivatizing a group of compounds in which the desired enzyme inhibitory activity was found in accordance with a policy derived from molecular design, the compound represented by the following general formula (I) can be converted into a hematopoietic PGD2 synthase.
(H-PGDS)に対して極めて優れた阻害作用を有することを見出した。本発明を上記の 知見を基にして完成されたものである。 (H-PGDS) was found to have an extremely excellent inhibitory effect. The invention described above It was completed based on knowledge.
[0009] すなわち、本発明は、  That is, the present invention provides
(1)下記一般式 (I):  (1) The following general formula (I):
A-Y-B (I)  A-Y-B (I)
[式中、 A及び Bはそれぞれ独立して置換基を有していてもよい炭化水素環基又は置 換基を有していてもよいへテロ環基を表し； Yは- CH=N -、 - N=CH -、 - CONH-又は - NHCO-を表す。  [Wherein, A and B each independently represent a hydrocarbon ring group which may have a substituent or a heterocyclic group which may have a substituent; Y is -CH = N- , -N = CH-, -CONH- or -NHCO-.
但し、下記一般式 (1-1):  However, the following general formula (1-1):
[化 1]
Figure imgf000006_0001
[Chemical 1]
Figure imgf000006_0001
[式中、 Xは式- N=C(R5)- (式中、左側の結合手がベンゼン環に結合し、右側の結合 手が窒素原子に結合する)、又は式- NH-CH(R5)- (式中、左側の結合手がベンゼン 環に結合し、右側の結合手が窒素原子に結合する)を表し；
Figure imgf000006_0002
R3及び R4はそれ ぞれ独立して水素原子、ハロゲン原子、置換基を有していてもよい C - Cアルキル基 Wherein, X is the formula - N = C (R 5) - ( wherein the left bond is attached to the benzene ring, right bond is attached to the nitrogen atom), or the formula - NH-CH ( R 5 )-(where the left hand is bonded to the benzene ring and the right hand is bonded to the nitrogen atom);
Figure imgf000006_0002
R 3 and R 4 are each independently a hydrogen atom, a halogen atom, and a C -C alkyl group which may have a substituent.
1 6  1 6
、又は置換基を有していてもよいヒドロキシ基を表し； R5は置換基を有していてもよい C - Cアルキル基、又は置換基を有していてもよい C - C ァリール基を表し； Rは置換Or a hydroxy group which may have a substituent; R 5 represents a C -C alkyl group which may have a substituent, or a C -C aryl group which may have a substituent Represents; R is substituted
1 6 6 10 1 6 6 10
基を有して 、てもよ 、アミノ基を表す]で表される化合物は除く]  Excluding a compound having a group, which may represent an amino group]
で表される化合物及び薬理学的に許容されるその塩、並びにそれらの水和物及び 溶媒和物からなる群から選択される物質を有効成分として含み、プロスタグランジン And a pharmacologically acceptable salt thereof, and a substance selected from the group consisting of hydrates and solvates thereof, as a prostaglandin,
D2(PGD2)産生抑制作用を有する医薬を提供するものである。 It is intended to provide a medicament having a D2 (PGD2) production inhibitory action.
[0010] 本発明の好ましい態様によれば、 According to a preferred embodiment of the present invention,
(2) Yカ CH=N―、— N=CH―、— CONH—又は— NHCO—であり；  (2) Y = CH = N-, -N = CH-, -CONH- or -NHCO-;
Aが置換基を有していてもよい C - C ァリール基、置換基を有していてもよい 6ないし  A may have a substituent C-C aryl group, may have a substituent 6 or more
6 10  6 10
13員のへテロアリール基、或 、は置換基を有して 、てもよ 、9又は 10員の部分飽和 ヘテロ環基であり；  A 13-membered heteroaryl group or is a 9- or 10-membered partially saturated heterocyclic group having a substituent, and
Bが置換基を有していてもよい C - C ァリール基、置換基を有していてもよい 5ないし 13員のへテロアリール基、或 、は置換基を有して 、てもよ 、5な 、し 10員の部分飽和 ヘテロ環基である上記 (1)に記載の医薬； B may have a substituent C-C aryl group, optionally having a substituent 5 to The medicament according to the above (1), which is a 13-membered heteroaryl group or a substituted or unsubstituted 5- or 10-membered partially saturated heterocyclic group;
(3) Aがヒドロキシ置換 C - C ァリール基 (該ァリール基はヒドロキシ基のほかに更に置  (3) A is a hydroxy-substituted C-C aryl group (the aryl group is further substituted in addition to the hydroxy group)
6 10  6 10
換基を有して 、てもよ 、；)であり；  Having a substituent, may be;));
Yカ CH=N―、— N=CH―、— CONH—又は— NHCO—であり；  Y is CH = N-, -N = CH-, -CONH- or -NHCO-;
Bが置換基を有して 、てもよ 、5な 、し 13員のへテロアリール基である上記 (2)に記載 の医薬；  The pharmaceutical according to the above (2), wherein B has a substituent, and may be a 5- to 13-membered heteroaryl group;
(4) Aがヒドロキシ置換ナフチル基 (該ナフチル基はヒドロキシ基のほかに更に置換基 を有していてもよい)であり；  (4) A is a hydroxy-substituted naphthyl group (the naphthyl group may have a substituent in addition to the hydroxy group);
Yカ CH=N―、— N=CH―、— CONH—又は— NHCO—であり；  Y is CH = N-, -N = CH-, -CONH- or -NHCO-;
Bが置換基を有して 、てもよ 、ビラゾリル基である上記 (3)に記載の医薬；  The pharmaceutical according to the above (3), wherein B has a substituent and may be a virazolyl group;
[0011] (5) Aが 1-ヒドロキシ- 2-ナフチル基であり； (5) A is a 1-hydroxy-2-naphthyl group;
(a) Yカ N=CH-であり； B力 1位が水素原子、置換基を有していてもよい C - Cアル  (a) Y is N = CH-; B force is a hydrogen atom at position 1 and may have a substituent.
1 6 キル基、置換基を有していてもよい C - C ァリール基、置換基を有していてもよい C  16-C hyl group, C-C aryl group optionally having substituent (s) C-C aryl group, C group optionally having substituent (s)
6 10 7 6 10 7
- C ァラルキル基、又は置換基を有していてもよい 9員のへテロアリール基であり、 3-A C aralkyl group or a 9-membered heteroaryl group which may have a substituent,
12 12
位が置換基を有していてもよい C - Cアルキル基、又は置換基を有していてもよい C  C-C alkyl group which may have a substituent at the position, or C which may have a substituent
1 6 6 1 6 6
- C ァリール基であり、 5位力 Sヒドロキシ基であるピラゾール -4-ィル基； -A pyrazole-4-yl group which is a C aryl group and is a 5-position S hydroxy group;
10  Ten
(b) Yが- CH=N -であり； Bが、 1位が置換基を有していてもよい C - Cアルキル基、置  (b) Y is -CH = N-; B is a C-C alkyl group optionally substituted at the 1-position,
1 6  1 6
換基を有していてもよい C -C ァリール基、置換基を有していてもよい C -C ァラル  C -C aryl group which may have a substituent, C -C aryl which may have a substituent
6 10 7 12 キル基、又は置換基を有していてもよい C - Cアルコキシカルボニル基であり、 3位が  6 10 7 12 alkyl group or a C-C alkoxycarbonyl group which may have a substituent,
2 7  2 7
水素原子、置換基を有していてもよい C - Cアルキル基、又は置換基を有していても  Hydrogen atom, optionally substituted C-C alkyl group, or optionally substituted
1 6  1 6
よい C - C ァリール基であり、 4位が水素原子又は置換基を有していてもよい C - C了 A good C-C aryl group, which may have a hydrogen atom or a substituent at the 4-position.
6 10 2 7 ルコキシカルボ-ル基であるピラゾール -5-ィル基；或 、は 6 10 2 7 a pyrazole-5-yl group which is a alkoxycarbyl group;
(c) Yが- CH=N-であり； Bが、 1位が水素原子又は置換基を有していてもよい C - C 了  (c) Y is -CH = N-; B is a C-C atom which may have a hydrogen atom or a substituent at the 1-position.
6 10 リール基であり、 4位が水素原子であり、 5位が置換基を有していてもよい C - C ァリー  6 10 reel group, 4-position is hydrogen atom, 5-position may have a substituent C-C aryl
6 10 ル基、又はヒドロキシ基であるピラゾール -3-ィル基  6 10-pyrazole-3-yl group or hydroxy group
である上記 (4)に記載の医薬；  The medicament according to the above (4), which is
[0012] (6) Aがヒドロキシ基で置換された 6ないし 10員のへテロアリール基 (該ヘテロァリール 基はヒドロキシ基のほかに更に置換基を有して 、てもよ 、)であり； (6) A 6- to 10-membered heteroaryl group in which A is substituted with a hydroxy group (the heteroaryl The group may further have a substituent in addition to the hydroxy group, or);
Yカ N=CH-又は- CONH-であり； Y is N = CH- or -CONH-;
Bが置換基を有して 、てもよ 、5員のへテロアリール基である上記 (2)に記載の医薬； The pharmaceutical according to the above (2), wherein B has a substituent and may be a 5-membered heteroaryl group;
(7) Aがヒドロキシ置換キノリル基 (該キノリル基はヒドロキシ基のほかに更に置換基を 有していてもよい)であり； (7) A is a hydroxy-substituted quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group);
Yカ N=CH-又は- CONH-であり；  Y is N = CH- or -CONH-;
Bが置換基を有して 、てもよ 、ビラゾリル基である上記 (6)に記載の医薬；  The pharmaceutical according to the above (6), wherein B has a substituent and may be a virazolyl group;
(8) Aが 4-ヒドロキシ -3-キノリル基 (該キノリル基はヒドロキシ基のほかに更に置換基を 有していてもよい)であり；  (8) A is a 4-hydroxy-3-quinolyl group (the quinolyl group may have a substituent in addition to the hydroxy group);
Yカ N=CH—であり；  Y = N—CH—
Bが、 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよい  B is a C-C alkyl group which may have a substituent at the 1-position, and may have a substituent
1 6  1 6
C -C ァリール基、又は置換基を有していてもよい C -C ァラルキル基であり、 3位が A C -C aryl group or a C -C aralkyl group which may have a substituent, wherein the 3-position is
6 10 7 12 6 10 7 12
置換基を有していてもよい C - Cアルキル基であり、 5位がヒドロキシ基であるピラゾー A pyrazole having an optionally substituted C-C alkyl group, wherein the 5-position is a hydroxy group
1 6  1 6
ル -4-ィル基； Le-4-yl group;
である上記 (7)に記載の医薬； The medicament according to the above (7), which is
(9) A力 1又は 2個の窒素原子を環構成原子として含有する 9又は 10員の部分飽和 ヘテロ環基 (該部分飽和へテロ環基は置換基を有していてもよぐ Yとの結合位置は 環構成原子である窒素原子の位置である)であり； (9) A force A 9- or 10-membered partially saturated heterocyclic group containing one or two nitrogen atoms as a ring constituent atom (the partially saturated heterocyclic group may have a substituent and Y Is the position of the nitrogen atom which is a ring-constituting atom);
Yカ N=CH—であり； Y = N—CH—
Bが置換基を有して 、てもよ 、5員のへテロアリール基である上記 (2)に記載の医薬； The pharmaceutical according to the above (2), wherein B has a substituent and may be a 5-membered heteroaryl group;
(10) A力 置換基を有していてもよいイソインドリン- 2-ィル基、置換基を有していても よい 1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、置換基を有していてもよい 1,2-ジヒドロ イソキノリン- 2-ィル基及び置換基を有していてもよい 1,2,3,4-テトラヒドロキナゾリン -3-ィル基からなる群から選択される基であり； (10) A force Isoindoline-2-yl group which may have a substituent, 1,2,3,4-tetrahydroisoquinolin-2-yl group which may have a substituent, substitution From the group consisting of a 1,2-dihydroisoquinolin-2-yl group which may have a group and a 1,2,3,4-tetrahydroquinazoline-3-yl group which may have a substituent A group of choice;
Yカ N=CH—であり；  Y = N—CH—
Bが置換基を有して 、てもよ 、ビラゾリル基である上記 (9)に記載の医薬；  The pharmaceutical according to the above (9), wherein B has a substituent and may be a virazolyl group;
(11) Aが、下記環群 α -3-1から選択される基であり；  (11) A is a group selected from the following ring group α-3-1;
Υカ N=CH—であり； Bが、 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよい Υka N = CH—; B is a C-C alkyl group which may have a substituent at the 1-position, and may have a substituent
1 6  1 6
C -C ァリール基、又は置換基を有していてもよい C -C ァラルキル基であり、 3位が A C -C aryl group or a C -C aralkyl group which may have a substituent, wherein the 3-position is
6 10 7 12 6 10 7 12
置換基を有していてもよい C - Cアルキル基であり、 5位がヒドロキシ基であるピラゾー  A pyrazole having an optionally substituted C-C alkyl group, wherein the 5-position is a hydroxy group
1 6  1 6
ル -4-ィル基；  Le-4-yl group;
である上記 (10)に記載の医薬；並びに  The pharmaceutical according to the above (10), which is
[環群 α - 3-1] 1,3-ジォキソイソインドリン- 2-ィル基、 3-ヒドロキシ- 1-ォキソイソインド リン- 2-ィル基、 1-ォキソイソインドリン- 2-ィル基、 1,3-ジォキソ- 1,2,3,4-テトラヒドロイ ソキノリン- 2-ィル基、 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 3-ヒドロキ シ- 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 1-ォキソ -1,2-ジヒドロイソキノ リン- 2-ィル基、 4-ォキソ -1,2,3,4-テトラヒドロキナゾリン- 3-ィル基  [Ring group α-3-1] 1,3-Dioxoisoindoline-2-yl group, 3-hydroxy-1-oxoisoindoline-2-yl group, 1-oxoisoindoline-2-yl 1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 3- Hydroxy-1-oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2-dihydroisoquinolin-2-yl group, 4-oxo-1,2 , 3,4-tetrahydroquinazoline-3-yl group
(12)一般式 (I)で表される化合物が、本明細書に記載されたィ匕合物番号 1ないし 406 で表される化合物力 なる群力 選択される化合物である上記 (1)に記載の医薬が提 供される。  (12) The compound represented by the general formula (I) is a compound selected from the group consisting of the compounds represented by the compound Nos. 1 to 406 described in the present specification. The described medicament is provided.
[0014] さらに好ましい態様によれば、  According to a further preferred embodiment,
(13)造血器型 PGD2合成酵素阻害作用を有する上記 (1)ないし (12)のいずれ力 1項に 記載の医薬；  (13) the medicament according to any one of (1) to (12), which has a hematopoietic PGD2 synthase inhibitory action;
(14)抗アレルギー作用、抗アレルギー性炎症作用、及び抗喘息作用からなる群から 選択される 1以上の作用を有する上記 (1)ないし (13)のいずれか 1項に記載の医薬； (14) the medicament according to any one of the above (1) to (13), which has one or more actions selected from the group consisting of an antiallergic action, an antiallergic inflammatory action, and an antiasthmatic action;
(15)脳損傷の増悪の予防作用及び Ζ又は脳損傷の予後の改善作用を有する上記 (1)¾V、し (13)の!、ずれか 1項に記載の医薬； (15) The medicament according to the above (1), which has an action of preventing exacerbation of brain damage and an action of improving the prognosis of brain damage or Ζ or (13).
(16)脳保護作用を有する上記 (1)ないし (13)のいずれか 1項に記載の医薬；並びに、 (16) The medicament according to any one of the above (1) to (13), which has a brain-protective effect;
(17)性周期調節作用、睡眠調節作用、体温調節作用、鎮痛作用、及び嗅覚調節作 用力 なる群力 選択される 1以上の作用を有する上記 (1)ないし (13)のいずれ力 1項 に記載の医薬 (17) The sexual cycle regulating action, the sleep regulating action, the body temperature regulating action, the analgesic action, and the olfactory regulating action group force which is selected from the group consisting of one or more of the above (1) to (13) having at least one action to be selected The medicine described
が提供される。  Is provided.
[0015] 本発明の別の観点からは、上記の医薬の製造のための上記一般式 (I)で表される化 合物及び薬理学的に許容されるその塩、並びにそれらの水和物及び溶媒和物から なる群力 選択される物質の使用；上記一般式 (I)で表される化合物及び薬理学的に 許容されるその塩、並びにそれらの水和物及び溶媒和物からなる群力 選択される 物質を有効成分として含む PGD2産生抑制剤；上記一般式 (I)で表される化合物及び 薬理学的に許容されるその塩、並びにそれらの水和物及び溶媒和物からなる群から 選択される物質を有効成分として含む造血器型 PGD2合成酵素阻害剤；ヒトを含む哺 乳類動物において PGD2の産生を抑制する方法であって、上記一般式 (I)で表される 化合物及び薬理学的に許容されるその塩、並びにそれらの水和物及び溶媒和物か らなる群から選択される物質の有効量をヒトを含む哺乳類動物に投与する工程を含 む方法；ヒトを含む哺乳類動物において造血器型 PGD2合成酵素を阻害する方法で あって、上記一般式 (I)で表される化合物及び薬理学的に許容されるその塩、並びに それらの水和物及び溶媒和物からなる群力 選択される物質の有効量をヒトを含む 哺乳類動物に投与する工程を含む方法；アレルギー疾患、アレルギー性炎症疾患、 及び喘息からなる群から選択される 1以上の疾患を予防及び Z又は治療する方法で あって、上記一般式 (I)で表される化合物及び薬理学的に許容されるその塩、並びに それらの水和物及び溶媒和物からなる群力 選択される物質の有効量をヒトを含む 哺乳類動物に投与する工程を含む方法；脳損傷の増悪を予防する方法であって、 上記一般式 (I)で表される化合物及び薬理学的に許容されるその塩、並びにそれらの 水和物及び溶媒和物からなる群力 選択される物質の有効量をヒトを含む哺乳類動 物に投与する工程を含む方法；脳損傷の予後を改善する方法であって、上記一般 式 (I)で表される化合物及び薬理学的に許容されるその塩、並びにそれらの水和物及 び溶媒和物からなる群力 選択される物質の有効量をヒトを含む哺乳類動物に投与 する工程を含む方法；脳の保護方法であって、上記一般式 (I)で表される化合物及び 薬理学的に許容されるその塩、並びにそれらの水和物及び溶媒和物からなる群から 選択される物質の有効量をヒトを含む哺乳類動物に投与する工程を含む方法；並び に、性周期、睡眠、体温、痛覚、及び嗅覚からなる群から選択される生体作用の調節 方法であって、上記一般式 (I)で表される化合物及び薬理学的に許容されるその塩、 並びにそれらの水和物及び溶媒和物力 なる群力 選択される物質の有効量をヒト を含む哺乳類動物に投与する工程を含む方法が提供される。 [0015] From another viewpoint of the present invention, a compound represented by the above general formula (I), a pharmacologically acceptable salt thereof, and a hydrate thereof for the production of the above medicament are provided. And a solvate; use of the selected substance; a compound represented by the above general formula (I) and a pharmacologically A PGD2 production inhibitor comprising a substance selected from the group consisting of an acceptable salt thereof, and a hydrate and a solvate thereof as an active ingredient; a compound represented by the above general formula (I); A hematopoietic PGD2 synthase inhibitor comprising, as an active ingredient, a substance selected from the group consisting of acceptable salts thereof, and hydrates and solvates thereof; A method of inhibiting the compound selected from the group consisting of the compound represented by the general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate and a solvate thereof. Administering to a mammal, including a human, an amount of the compound; a method for inhibiting hematopoietic PGD2 synthase in a mammal, including a human, comprising the compound represented by the above general formula (I) and pharmacology. Acceptable salts, and it A method comprising administering to a mammal, including a human, an effective amount of a selected substance; selected from the group consisting of allergic diseases, allergic inflammatory diseases, and asthma A method for preventing and / or treating one or more diseases, comprising a compound represented by the above general formula (I), a pharmacologically acceptable salt thereof, and a hydrate and solvate thereof. Group strength: a method comprising the step of administering an effective amount of a selected substance to mammals including humans; a method for preventing exacerbation of brain damage, comprising the compound represented by the above general formula (I) and a pharmacologically active substance. A method comprising administering to a mammal, including a human, an effective amount of a substance selected from the group consisting of hydrates and solvates thereof; The general formula (I) A method comprising administering to a mammal, including a human, an effective amount of a selected substance, and a pharmacologically acceptable salt thereof, and a hydrate and solvate thereof. A method for protecting the brain, comprising the step of using a compound represented by the above general formula (I) and a pharmacologically acceptable salt thereof, and an effective substance selected from the group consisting of hydrates and solvates thereof. A method comprising the step of administering an amount to a mammal, including a human; and a method for regulating a biological effect selected from the group consisting of estrous cycle, sleep, body temperature, pain sensation, and olfaction. And pharmacologically acceptable salts thereof, and hydrates and solvates thereof. A method comprising the step of administering to a mammal, including a human, an effective amount of the selected substance. Is provided.
また、本発明により、 (18)下記一般式 (II): Also, according to the present invention, (18) The following general formula (II):
A101 - Y101 - B101 (II) A 101 -Y 101 -B 101 (II)
中、 A1Q1及び B1Mはそれぞれ独立して置換基を有していてもよい炭化水素環基又 は置換基を有していてもよいへテロ環基を表し； Υωΐは- CH=N -、 - N=CH -、 -CONH- 又は- NHCO-を表す。 Wherein A 1Q1 and B 1M each independently represent a hydrocarbon ring group which may have a substituent or a heterocyclic group which may have a substituent; and Υωΐ is -CH = N -, -N = CH-, -CONH- or -NHCO-.
但し、下記一般式 (II-1): However, the following general formula (II-1):
[化 2] [Formula 2]
Figure imgf000011_0001
Figure imgf000011_0001
[式中、 X1U1は式- N=C(RbU1)_ (式中、左側の結合手がベンゼン環に結合し、右側の結 合手が窒素原子に結合する)、又は式- NH-CH(R5Q1)- (式中、左側の結合手がベンゼ ン環に結合し、右側の結合手が窒素原子に結合する)を表し； R1M、 R2M、 R3M及び R4M はそれぞれ独立して水素原子、ハロゲン原子、置換基を有していてもよい C - Cアル Wherein X 1U1 is a compound of the formula -N = C (R bU1 ) _ (where the bond on the left is bonded to the benzene ring and the bond on the right is bonded to the nitrogen atom), or the formula -NH- CH (R 5Q1 )-(where the bond on the left is bonded to the benzene ring and the bond on the right is bonded to the nitrogen atom); R 1M , R 2M , R 3M and R 4M are each independently A hydrogen atom, a halogen atom, and a C-C
1 6 キル基、又は置換基を有していてもよいヒドロキシ基を表し； R5Q1は置換基を有してい てもよい C - Cアルキル基、又は置換基を有していてもよい C - C ァリール基を表し； Represents a 16- alkyl group or a hydroxy group which may have a substituent; R 5Q1 represents a C-C alkyl group which may have a substituent or a C- which may have a substituent; Represents a C aryl group;
1 6 6 10  1 6 6 10
R1001は置換基を有していてもよいアミノ基を表す。 ]で表される化合物、並びに Y101が - CH=N -又は- CONH-であり； A1Q1が 2-ヒドロキシ- 1-ナフチル基であり； Βωιが 2-ヒドロ キシ -4-スルホ -1-ナフチル基である化合物は除く] R 1001 represents an amino group which may have a substituent. Compounds represented by, and Y 101 is - CH = N - or - CONH-; A 1Q1 is 2-hydroxy - be a 1-naphthyl group; Β ωι 2-hydro carboxymethyl-4-sulfonyl -1 -Excluding compounds that are naphthyl groups]
で表される化合物若しくはその塩、又はそれらの水和物若しくはそれらの溶媒和物が 新規物質として提供される。 Or a salt thereof, or a hydrate or solvate thereof, as a novel substance.
本発明の好ましい態様によれば、  According to a preferred embodiment of the present invention,
(19) A1Q1がヒドロキシ置換ナフチル基 (該ナフチル基はヒドロキシ基のほかに更に置換 基を有して 、てもよ 、；)であり； (19) A 1Q1 is a hydroxy-substituted naphthyl group (the naphthyl group may further have a substituent in addition to the hydroxy group;);
Y101が— CH=N―、— N=CH―、— CONH—又は— NHCO—であり； Y 101 is —CH = N—, —N = CH—, —CONH— or —NHCO—;
B1Q1が置換基を有していてもよいピラゾリル基である上記 (18)に記載の化合物若しくは その塩、又はそれらの水和物若しくはそれらの溶媒和物； The compound according to the above (18), wherein B 1Q1 is an optionally substituted pyrazolyl group, a salt thereof, or a hydrate or solvate thereof;
(20) A1Mが 1-ヒドロキシ- 2-ナフチル基であり； (a) Y1Mが- N=CH-であり； B1Mが、 1位が水素原子、置換基を有していてもよい C - Cァ (20) A 1M is a 1-hydroxy-2-naphthyl group; (a) Y 1M is -N = CH-; B 1M is a hydrogen atom at the 1-position, which may have a substituent.
1 6 ルキル基、置換基を有していてもよい C - C ァリール基、置換基を有していてもよい C  16 alkyl group, optionally substituted C-C aryl group, optionally substituted C
6 10  6 10
- C ァラルキル基、又は置換基を有していてもよい 9員のへテロアリール基であり、 3 -A C aralkyl group or a 9-membered heteroaryl group which may have a substituent,
7 12 7 12
位が置換基を有していてもよい C - Cアルキル基、又は置換基を有していてもよい C C-C alkyl group which may have a substituent at the position, or C which may have a substituent
1 6 6 1 6 6
- C ァリール基であり、 5位力 Sヒドロキシ基であるピラゾール -4-ィル基； -A pyrazole-4-yl group which is a C aryl group and is a 5-position S hydroxy group;
10  Ten
(b) Y1Mが- CH=N -であり； B1Q1が、 1位が置換基を有していてもよい C - Cアルキル基、 (b) Y 1M is -CH = N-; B 1Q1 is a C-C alkyl group optionally substituted at the 1-position,
1 6  1 6
置換基を有していてもよい C -C ァリール基、置換基を有していてもよい C -C ァラ C -C aryl group which may have a substituent, C -C aryl group which may have a substituent
6 10 7 12 ルキル基、又は置換基を有していてもよい C - Cアルコキシカルボニル基であり、 3位  6 10 7 12 alkyl group, or an optionally substituted C-C alkoxycarbonyl group, 3-position
2 7  2 7
が水素原子、置換基を有していてもよい C - Cアルキル基、又は置換基を有していて Has a hydrogen atom, a C-C alkyl group which may have a substituent, or a substituent
1 6  1 6
もよい C - C ァリール基であり、 4位が水素原子又は置換基を有していてもよい C - CIs a C-C aryl group, and the C-C may have a hydrogen atom or a substituent at the 4-position.
6 10 2 7 アルコキシカルボ-ル基であるピラゾール -5-ィル基；或いは 6 10 2 7 a pyrazole-5-yl group which is an alkoxycarbol group; or
(c) Y1Q1が- CH=N-であり； Βωΐが、 1位が水素原子又は置換基を有していてもよい C (c) Y 1Q1 is -CH = N-; ΒωΒ is a hydrogen atom or a substituent which may have a substituent at the 1-position
6 6
- C ァリール基であり、 4位が水素原子であり、 5位が置換基を有していてもよい C - C-C aryl group, the 4-position is a hydrogen atom, and the 5-position may have a substituent C-C
10 6 ァリール基、又はヒドロキシ基であるピラゾール -3-ィル基 10 6 Aryl group or pyrazole-3-yl group which is hydroxy group
10  Ten
である上記 (19)に記載の化合物若しくはその塩、又はそれらの水和物若しくはそれら の溶媒和物； The compound according to the above (19) or a salt thereof, or a hydrate or solvate thereof;
(21) A1Mがヒドロキシ置換キノリル基 (該キノリル基はヒドロキシ基のほかに更に置換基 を有していてもよい)であり； (21) A 1M is a hydroxy-substituted quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group);
Y101が- N=CH-又は- CONH-であり； Y 101 is -N = CH- or -CONH-;
B1Q1が置換基を有していてもよいピラゾリル基である上記 (18)に記載の化合物若しくは その塩、又はそれらの水和物若しくはそれらの溶媒和物； The compound according to the above (18), wherein B 1Q1 is an optionally substituted pyrazolyl group, a salt thereof, or a hydrate or solvate thereof;
(22) A1Mが 4-ヒドロキシ -3-キノリル基 (該キノリル基はヒドロキシ基のほかに更に置換 基を有して 、てもよ 、；)であり； (22) A 1M is a 4-hydroxy-3-quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group;).
Y101が- N=CH-であり； Y 101 is -N = CH-;
B1Q1が、 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよ B 1Q1 may have a C-C alkyl group optionally having a substituent at the 1-position, or a substituent
1 6  1 6
い C - C ァリール基、又は置換基を有していてもよい C -C ァラルキル基であり、 3位A C-Caryl group or a C-Caralkyl group which may have a substituent,
6 10 7 12 6 10 7 12
が置換基を有していてもよい C - Cアルキル基であり、 5位力ヒドロキシ基であるピラゾ Is a C-C alkyl group which may have a substituent, and pyrazo is a 5-position hydroxy group.
1 6  1 6
ール -4-ィル基； である上記 (21)に記載の化合物若しくはその塩、又はそれらの水和物若しくはそれら の溶媒和物； -4-yl group; A compound according to the above (21) or a salt thereof, or a hydrate or solvate thereof;
(23) A1Q1が、 1又は 2個の窒素原子を環構成原子として含有する 9又は 10員の部分飽 和へテロ環基 (該部分飽和へテロ環基は置換基を有していてもよぐ Y1Q1との結合位 置は環構成原子である窒素原子の位置である)であり； (23) A1Q1 is a 9- or 10-membered partially saturated heterocyclic group containing 1 or 2 nitrogen atoms as a ring-constituting atom (the partially saturated heterocyclic group may have a substituent The bond position to Y 1Q1 is the position of the nitrogen atom which is a ring-constituting atom);
Y101が- N=CH-であり； Y 101 is -N = CH-;
B1Q1が置換基を有していてもよいピラゾリル基である上記 (18)に記載の化合物若しくは その塩、又はそれらの水和物若しくはそれらの溶媒和物； The compound according to the above (18), wherein B 1Q1 is an optionally substituted pyrazolyl group, a salt thereof, or a hydrate or solvate thereof;
[0019] (24) A1Mが、下記環群 a ωΐ-3-1から選択される基であり； (24) A 1M is a group selected from the following ring group a ωΐ -3-1;
Y101が— N=CH—であり； Y 101 is —N = CH—;
B1Q1が、 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよ B 1Q1 may have a C-C alkyl group optionally having a substituent at the 1-position, or a substituent
1 6  1 6
い C - C ァリール基、又は置換基を有していてもよい C -C ァラルキル基であり、 3位 A C-Caryl group or a C-Caralkyl group which may have a substituent,
6 10 7 12 6 10 7 12
が置換基を有していてもよい C - Cアルキル基であり、 5位力ヒドロキシ基であるピラゾ  Is a C-C alkyl group which may have a substituent, and pyrazo is a 5-position hydroxy group.
1 6  1 6
ール -4-ィル基；  -4-yl group;
である上記 (23)に記載の化合物若しくはその塩、又はそれらの水和物若しくはそれら の溶媒和物；並びに  Or a salt thereof, or a hydrate or solvate thereof, as described in (23) above, and
[環群ひ1。1- 3-1] 1,3-ジォキソイソインドリン- 2-ィル基、 3-ヒドロキシ- 1-ォキソイソイン ドリン- 2-ィル基、 1-ォキソイソインドリン- 2-ィル基、 1,3-ジォキソ- 1,2,3,4-テトラヒドロ イソキノリン- 2-ィル基、 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 3-ヒドロキ シ- 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 1-ォキソ -1,2-ジヒドロイソキノ リン- 2-ィル基、 4-ォキソ -1,2,3,4-テトラヒドロキナゾリン- 3-ィル基 [Ring group 1 . 1 - 3-1] 1,3-O Kiso isoindoline - 2 I group, 3-hydroxy - 1-Okisoisoin Dorin - 2 I group, 1-O Kiso isoindoline - 2 I group, 1,3-Dioxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 3-hydroxy-1 -Oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2-dihydroisoquinolin-2-yl group, 4-oxo-1,2,3,4 -Tetrahydroquinazoline-3-yl group
(25)一般式 (II)で表される化合物力 本明細書に記載されたィ匕合物番号 1ないし 406 で表される化合物力 なる群力 選択される化合物である上記 (18)に記載の化合物 若しくはその塩、又はそれらの水和物若しくはそれらの溶媒和物が新規物質として提 供される。  (25) The compound power represented by the general formula (II): The compound power represented by the compound Nos. 1 to 406 described in the present specification. Or a salt thereof, or a hydrate or solvate thereof, is provided as a novel substance.
[0020] 本発明の別の観点力もは、上記一般式 (II)で表される化合物及び薬理学的に許容 されるその塩、並びにそれらの水和物及び溶媒和物からなる群力 選択される物質 を有効成分として含む医薬；プロスタグランジン D2(PGD2)産生抑制作用を有する上 記の医薬；造血器型 PGD2合成酵素阻害作用を有する上記の医薬；抗アレルギー作 用、抗アレルギー性炎症作用、及び抗喘息作用力 なる群力 選択される 1以上の 作用を有する上記の医薬；脳損傷の増悪の予防作用及び Z又は脳損傷の予後の 改善作用を有する上記の医薬;脳保護作用を有する上記の医薬；並びに、性周期 調節作用、睡眠調節作用、体温調節作用、鎮痛作用、及び嗅覚調節作用からなる 群から選択される 1以上の作用を有する上記の医薬；上記の医薬の製造のための上 記一般式 (II)で表される化合物及び薬理学的に許容されるその塩、並びにそれらの 水和物及び溶媒和物からなる群力 選択される物質の使用；上記一般式 (II)で表さ れる化合物及び薬理学的に許容されるその塩、並びにそれらの水和物及び溶媒和 物からなる群から選択される物質を有効成分として含み、 PGD2産生抑制作用を有す る医薬；上記一般式 (II)で表される化合物及び薬理学的に許容されるその塩、並び にそれらの水和物及び溶媒和物からなる群から選択される物質を有効成分として含 み、造血器型 PGD2合成酵素阻害作用を有する医薬；上記一般式 (Π)で表される化 合物及び薬理学的に許容されるその塩、並びにそれらの水和物及び溶媒和物から なる群から選択される物質を有効成分として含み、抗アレルギー作用、抗アレルギー 性炎症作用、及び抗喘息作用力 なる群力 選択される 1以上の作用を有する医薬; 上記一般式 (II)で表される化合物及び薬理学的に許容されるその塩、並びにそれら の水和物及び溶媒和物力 なる群力 選択される物質を有効成分として含み、脳損 傷の増悪の予防作用及び Z又は脳損傷の予後の改善作用を有する医薬;上記一般 式 (Π)で表される化合物及び薬理学的に許容されるその塩、並びにそれらの水和物 及び溶媒和物からなる群から選択される物質を有効成分として含み、脳保護作用を 有する上記の医薬；上記一般式 (II)で表される化合物及び薬理学的に許容されるそ の塩、並びにそれらの水和物及び溶媒和物力 なる群力 選択される物質を有効成 分として含み、性周期調節作用、睡眠調節作用、体温調節作用、鎮痛作用、及び嗅 覚調節作用からなる群から選択される 1以上の作用を有する医薬；上記一般式 (II)で 表される化合物及び薬理学的に許容されるその塩、並びにそれらの水和物及び溶 媒和物からなる群から選択される物質を有効成分として含む、 PGD2産生抑制剤；上 記一般式 (II)で表される化合物及び薬理学的に許容されるその塩、並びにそれらの 水和物及び溶媒和物からなる群から選択される物質を有効成分として含む、造血器 型 PGD2合成酵素阻害剤；ヒトを含む哺乳類動物において PGD2の産生を抑制する 方法であって、上記一般式 (II)で表される化合物及び薬理学的に許容されるその塩、 並びにそれらの水和物及び溶媒和物力 なる群力 選択される物質の有効量をヒト を含む哺乳類動物に投与する工程を含む方法；ヒトを含む哺乳類動物において造 血器型 PGD2合成酵素を阻害する方法であって、上記一般式 (II)で表される化合物 及び薬理学的に許容されるその塩、並びにそれらの水和物及び溶媒和物からなる 群力 選択される物質の有効量をヒトを含む哺乳類動物に投与する工程を含む方法 アレルギー疾患、アレルギー性炎症疾患、及び喘息力 なる群力 選択される 1以上 の疾患を予防及び Z又は治療する方法であって、上記一般式 (II)で表される化合物 及び薬理学的に許容されるその塩、並びにそれらの水和物及び溶媒和物からなる 群力 選択される物質の有効量をヒトを含む哺乳類動物に投与する工程を含む方法 ；脳損傷の増悪を予防する方法であって、上記一般式 (II)で表される化合物及び薬 理学的に許容されるその塩、並びにそれらの水和物及び溶媒和物力 なる群力 選 択される物質の有効量をヒトを含む哺乳類動物に投与する工程を含む方法；脳損傷 の予後を改善する方法であって、上記一般式 (II)で表される化合物及び薬理学的に 許容されるその塩、並びにそれらの水和物及び溶媒和物からなる群力 選択される 物質の有効量をヒトを含む哺乳類動物に投与する工程を含む方法;脳の保護方法 であって、上記一般式 (II)で表される化合物及び薬理学的に許容されるその塩、並び にそれらの水和物及び溶媒和物力 なる群力 選択される物質の有効量をヒトを含 む哺乳類動物に投与する工程を含む方法；並びに、性周期、睡眠、体温、痛覚、及 び嗅覚からなる群力も選択される生体作用の調節方法であって、上記一般式 (II)で 表される化合物及び薬理学的に許容されるその塩、並びにそれらの水和物及び溶 媒和物からなる群力 選択される物質の有効量をヒトを含む哺乳類動物に投与する 工程を含む方法が提供される。 [0020] Another aspect of the present invention is also selected from the group consisting of the compound represented by the above general formula (II), a pharmacologically acceptable salt thereof, and a hydrate and solvate thereof. Containing active substance as an active ingredient; has a prostaglandin D2 (PGD2) production inhibitory action The above-mentioned medicine having hematopoietic-type PGD2 synthase inhibitory action; the above-mentioned medicine having at least one action selected from the group consisting of antiallergic action, antiallergic inflammatory action and antiasthmatic action; The above-mentioned medicines having a preventive action of exacerbation of brain damage and an improvement action of Z or brain prognosis; the above-mentioned medicines having a brain-protective action; and a sexual cycle controlling action, a sleep controlling action, a body temperature controlling action, an analgesic action, And a drug having at least one action selected from the group consisting of: and a olfactory controlling action; a compound represented by the above general formula (II) for the manufacture of the above drug; Group, consisting of salts and hydrates and solvates thereof Use of the selected substance; compounds represented by the above general formula (II), pharmacologically acceptable salts thereof, and hydration thereof And solvates from the group consisting of A medicament containing a selected substance as an active ingredient and having a PGD2 production inhibitory action; a compound represented by the above general formula (II) and a pharmacologically acceptable salt thereof, and a hydrate and a hydrate thereof. A medicament containing a substance selected from the group consisting of solvates as an active ingredient and having hematopoietic PGD2 synthase inhibitory activity; a compound represented by the above general formula (Π) and a pharmacologically acceptable drug Containing, as an active ingredient, a substance selected from the group consisting of a salt thereof, and a hydrate and solvate thereof, and an antiallergic action, an antiallergic inflammatory action, and an antiasthmatic action. A drug having the above action; a compound represented by the above general formula (II) and a pharmacologically acceptable salt thereof, and a hydrate and solvate thereof. Preventive action of exacerbation of brain injury A drug having an effect of improving the prognosis of Z or brain injury; selected from the group consisting of the compound represented by the above general formula (II) and pharmacologically acceptable salts thereof, and hydrates and solvates thereof The above-mentioned medicines having a cerebroprotective action containing the substance represented by the formula (I) as an active ingredient; the compound represented by the above general formula (II), and pharmacologically acceptable salts thereof, and hydrates and solvates thereof. A drug that contains the selected substance as an active ingredient and has at least one action selected from the group consisting of a sexual cycle control action, a sleep control action, a body temperature control action, an analgesic action, and an olfactory control action. Containing, as an active ingredient, a compound represented by the general formula (II) and a pharmacologically acceptable salt thereof, and a substance selected from the group consisting of hydrates and solvates thereof; Inhibitor; on A hematopoietic-type PGD2 containing, as an active ingredient, a compound represented by the general formula (II) and a pharmacologically acceptable salt thereof, and a substance selected from the group consisting of a hydrate and a solvate thereof. A method for inhibiting the production of PGD2 in mammals including humans, comprising a compound represented by the above general formula (II), a pharmaceutically acceptable salt thereof, and a hydrate thereof. A method comprising administering an effective amount of a selected substance to mammals including humans; and a method for inhibiting hematopoietic PGD2 synthase in mammals including humans. Group consisting of a compound represented by the general formula (II) and a pharmacologically acceptable salt thereof, and a hydrate and solvate thereof An effective amount of the selected substance is administered to mammals including humans Allergy A method for preventing and / or treating one or more diseases selected from the group consisting of a compound represented by the general formula (II) and a pharmacologically acceptable A method comprising administering to a mammal, including a human, an effective amount of a selected substance; a method for preventing exacerbation of brain damage; A compound represented by the above general formula (II) and a pharmacologically acceptable salt thereof, and a hydrate and solvate thereof. A method for improving the prognosis of brain injury, comprising the compound represented by the above general formula (II), a pharmacologically acceptable salt thereof, and a hydrate and a solvent thereof. Group strength consisting of Japanese A method comprising the step of administering to a mammal comprising: a method for protecting the brain, comprising the compound represented by the general formula (II) and a pharmacologically acceptable salt thereof, and a hydrate and a hydrate thereof. A method comprising the step of administering an effective amount of a selected substance to a mammal, including a human; and a living body, wherein a group force consisting of estrous cycle, sleep, body temperature, pain, and smell is also selected. A method of regulating the action, comprising a group represented by the compound represented by the general formula (II) and a pharmacologically acceptable salt thereof, and a hydrate and a solvate thereof. Administering an effective amount to a mammal, including a human, is provided.
発明を実施するための最良の形態 [0023] 本明細書にぉ 、て用いられる用語の意味は以下の通りである。 BEST MODE FOR CARRYING OUT THE INVENTION [0023] The meanings of the terms used in this specification are as follows.
本明細書において、 - CH=N -、 - N=CH -、 - CONH-及び- NHCO-は、それぞれ下記 式：  In the present specification, -CH = N-, -N = CH-, -CONH- and -NHCO- are each represented by the following formula:
[化 3]  [Formula 3]
— C = N— — N=C— — C -N— — N -C—  — C = N— — N = C— — C -N— — N -C—
H , H O H , H O を意味する。  H, H O H, and H O are meant.
以下、一般式 (I)及び (II)で表される化合物について具体的に説明する。 一般式 (I)において、 Yは- CH=N -、 - N=CH -、 - C0NH-又は- NHC0-を表す。好まし くは- CH=N -又は- N=CH-である。  Hereinafter, the compounds represented by formulas (I) and (II) will be specifically described. In the general formula (I), Y represents -CH = N-, -N = CH-, -C0NH- or -NHC0-. Preferably -CH = N- or -N = CH-.
A及び Bはそれぞれ独立して置換基を有して 、てもよ 、炭化水素環基又は置換基 を有して!/ヽてもよ ヽヘテロ環基を表す。  A and B each independently have a substituent, and may represent a hydrocarbon ring group or a substituent and represent a heterocyclic group.
炭化水素環基は単環又は縮合環のいずれでもよぐ部分飽和、完全飽和、又は芳 香環 (ァリール基)の 、ずれでもよ 、。これらの基は環上の任意の位置で結合すること ができる。  The hydrocarbon ring group may be partially saturated, fully saturated, or deviated from an aromatic ring (aryl group). These groups can be bonded at any position on the ring.
ァリール基としては、フ ニル基、ナフチル基、アントリル基、フ ナントリル基などを 挙げることができる。ァリール部分を含む他の置換基 (例えば、ァラルキル基、ァリー ルォキシ基、ァリールアミノ基など)のァリール部分についても同様である。  Examples of the aryl group include a phenyl group, a naphthyl group, an anthryl group, and a phananthryl group. The same applies to the aryl moiety of other substituents including the aryl moiety (eg, an aralkyl group, an aryloxy group, an arylamino group, etc.).
部分飽和の炭化水素環基としては、シクロへキセ-ル基、シクロへキサジェニル基 、インデニル基などを挙げることができる。  Examples of the partially saturated hydrocarbon ring group include a cyclohexyl group, a cyclohexenyl group, an indenyl group and the like.
完全飽和の炭化水素環基としては、シクロプロピル基、シクロブチル基、シクロペン チル基、シクロへキシル基などのシクロアルキル基；ビシクロ〔3.2.1〕ォクチル基；ァダ マンチル基などを挙げることができる。  Examples of the completely saturated hydrocarbon ring group include cycloalkyl groups such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group; a bicyclo [3.2.1] octyl group; and an adamantyl group. .
[0024] ヘテロ環基としては、窒素原子、酸素原子、及び硫黄原子から選ばれる 1ないし 4個 のへテロ原子を環構成原子として含有する 3ないし 14員の単環又は縮合環の基を挙 げることができる。 2個以上のへテロ原子を含む場合には、それらは同一でも異なって いてもよい。ヘテロ環基は部分飽和、完全飽和、又は芳香環 (ヘテロァリール基)のい ずれでもよ 、。これらの基は環上の任意の位置で結合することができる。 ヘテロァリール基としては、チェ-ル基、フリル基、ピロリル基、ォキサゾリル基、イソ キサゾリル基、チアゾリル基、イソチアゾリル基、イミダゾリル基、ピラゾリル基、ベンゾ チオフヱ-ル基、ベンゾフラ-ル基、イソべンゾチオフヱ-ル基、イソべンゾフラ-ル 基、インドリル基、イソインドリル基、インドリジニル基、インダゾリル基、プリ-ル基、ベ ンゾチアゾリル基、ベンズォキサゾリル基、ベンズイミダゾリル基、 1,2,3-チアジアゾリ ル基、 1,2,4-チアジアゾリル基、 1,3,4-チアジアゾリル基、 1,3,4-ォキサジァゾリル基、[0024] Examples of the heterocyclic group include a 3- to 14-membered monocyclic or condensed-ring group containing, as a ring-constituting atom, 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom, and a sulfur atom. I can do it. If they contain two or more heteroatoms, they may be the same or different. The heterocyclic group may be partially saturated, fully saturated, or an aromatic ring (heteroaryl group). These groups can be attached at any position on the ring. Heteroaryl groups include chel, furyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, benzothiopropyl, benzofurol, and isobenzothiophene. Group, isobenzofuroyl group, indolyl group, isoindolyl group, indolizinyl group, indazolyl group, prill group, benzothiazolyl group, benzoxazolyl group, benzimidazolyl group, 1,2,3-thiadiazolyl Group, 1,2,4-thiadiazolyl group, 1,3,4-thiadiazolyl group, 1,3,4-oxadiazolyl group,
1.2.3-トリァゾリル基、 1,2,4-トリァゾリル基、テトラゾリル基、ピリジル基、ピリダジニル 基、ピリミジニル基、ピラジュル基、キノリル基、イソキノリル基、フタラジュル基、ナフ チリジ-ル基、キノキサリニル基、キナゾリニル基、シンノリ-ル基、プテリジニル基、1.2.3-Triazolyl group, 1,2,4-triazolyl group, tetrazolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazuryl group, quinolyl group, isoquinolyl group, phthalazyl group, naphthyridyl group, quinoxalinyl group, quinazolinyl Group, cinnolyl group, pteridinyl group,
1.2.4-トリアジ-ル基、 1,3,5-トリアジ-ル基、カルバゾリル基、 |8 -カルボリニル基、ァ タリジ-ル基、フ ナントリジ-ル基、フ ナント口リニル基などを挙げることができる。 部分飽和のへテロ環基としては、クロマ-ル基、イソクロマニル基、イミダゾリ-ル基 、ビラゾリ-ル基、インドリ-ル基、イソインドリ-ル、 1,2,3,4-テトラヒドロキノリル基、メ チレンジォキシフヱニル基などを挙げることができる。 1.2.4-Triazyl group, 1,3,5-triazyl group, carbazolyl group, | 8-carbolinyl group, atalyzyl group, phenanthridyl group, funnant-linyl group, etc. Can be. Partially saturated heterocyclic groups include a chromal group, an isochromanyl group, an imidazolyl group, a virazolyl group, an indole group, an isoindole group, a 1,2,3,4-tetrahydroquinolyl group, Examples thereof include a methylenedioxyphenyl group.
完全飽和のへテロ環基としては、ァゼチジニル基、ピロリジ -ル基、イミダゾリジ-ル 基、ビラゾリジ-ル基、ピペリジル基、ピペラジニル基、モルホリニル基、チオモルホリ -ル基、キヌタリジニル基などを挙げることができる。  Examples of the fully saturated heterocyclic group include an azetidinyl group, a pyrrolidyl group, an imidazolidyl group, a bilazolidyl group, a piperidyl group, a piperazinyl group, a morpholinyl group, a thiomorpholinyl group, and a quinutalidinyl group. .
A又は Bで表される炭化水素環基及びへテロ環基は置換基を有して ヽてもよ ヽ。 本明細書にぉ 、て、ある官能基にっ 、て「置換基を有して 、てもよ 、」 t 、う場合に は、官能基に存在する置換基の種類、個数及び置換位置は特に限定されない。また 、 2個以上の置換基が存在する場合には、それらは同一であっても異なっていてもよ い。このような置換基としては、ハロゲン原子 (フッ素原子、塩素原子、臭素原子又は ヨウ素原子のいずれを用いてもよい)、ォキソ基、チォキソ基、ォキシド基、ニトロ基、 ニトロソ基、シァノ基、イソシァノ基、シアナト基、チオシアナト基、イソシアナト基、イソ チオシアナト基、ヒドロキシ基、スルファニル基、炭化水素基、ヘテロ環基、ァシル基、 アミノ基、ヒドラジノ基、ヒドラゾノ基、ジァゼ-ル基、ウレイド基、チォウレイド基、グァ -ジノ基、アミジノ基、アジド基、イミノ基、ヒドロキシァミノ基、ヒドロキシィミノ基、ァミノ ォキシ基、ジァゾ基、セミカルバジノ基、セミカルバゾノ基、ァロファニル基、ヒダントイ ル基、ボリル基、シリル基、スタニル基、セラ-ル基、ォキシド基などを挙げることがで きる。 The hydrocarbon ring group and heterocyclic group represented by A or B may have a substituent. In the present specification, when a certain functional group has a “substituent, it may have a substituent” t, in such a case, the type, number, and substitution position of the substituent present in the functional group are as follows. There is no particular limitation. When two or more substituents are present, they may be the same or different. Examples of such a substituent include a halogen atom (a fluorine atom, a chlorine atom, a bromine atom or an iodine atom may be used), an oxo group, a thioxo group, an oxoxide group, a nitro group, a nitroso group, a cyano group, an isocyano group. Group, cyanato group, thiocyanato group, isocyanato group, isothiocyanato group, hydroxy group, sulfanyl group, hydrocarbon group, heterocyclic group, acyl group, amino group, hydrazino group, hydrazono group, diazel group, ureide group, thioureide Group, gua-dino group, amidino group, azide group, imino group, hydroxyamino group, hydroxyimino group, aminooxy group, diazo group, semicarbazino group, semicarbazono group, arophanyl group, hydantoin And a benzyl group, a boryl group, a silyl group, a stannyl group, a ceryl group and an oxide group.
炭化水素基としては、アルキル基、ァルケ-ル基、アルキニル基、ァリール基、ァラ ルキル基などを挙げることができる。  Examples of the hydrocarbon group include an alkyl group, an alkenyl group, an alkynyl group, an aryl group and an aralkyl group.
[0026] アルキル基は、特に言及しな 、場合には、直鎖状、分岐鎖状、環状又はそれらの 組み合わせの!/、ずれでもよ!/、。環状のアルキル基は単環又は縮合環の 、ずれでもよ い。より具体的には、メチル基、ェチル基、 n-プロピル基、イソプロピル基、 n-ブチル 基、イソブチル基、 sec-ブチル基、 tert-ブチル基、 n-ペンチル基、ネオペンチル基、 イソペンチル基、 tert-ペンチル基、 n-へキシル基、 n-ヘプチル基、 n-ォクチル基、シ クロプロピル基、シクロブチル基、シクロペンチル基、シクロへキシル基、シクロプロピ ルメチル基、ァダマンチル基などを挙げることができる。アルキル部分を含む他の置 換基 (例えば、アルコキシ基、アルキルアミノ基、ジアルキルアミノ基など)のアルキル 部分についても同様である。  [0026] Unless otherwise specified, the alkyl group may be linear, branched, cyclic, or a combination thereof! The cyclic alkyl group may be a monocyclic or condensed ring. More specifically, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, neopentyl, isopentyl, tert-butyl -Pentyl, n-hexyl, n-heptyl, n-octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, adamantyl and the like. The same applies to the alkyl moiety of other substituents containing an alkyl moiety (eg, an alkoxy group, an alkylamino group, a dialkylamino group, etc.).
アルケニル基は、特に言及しない場合には、直鎖状、分岐鎖状、環状又はそれら の組み合わせの 、ずれでもよ 、。環状のァルケ-ル基は単環又は縮合環の 、ずれ でもよい。ァルケ-ル基に存在する二重結合の数及び位置は特に限定されない。よ り具体的には、ビュル基、ァリル基、イソプロべ-ル基、ァレニル基などを挙げること ができる。ァルケ-ル部分を含む他の置換基 (例えば、ァルケ-ルォキシ基など)のァ ルケ-ル部分にっ 、ても同様である。  An alkenyl group may be linear, branched, cyclic, or a combination thereof, unless otherwise specified. The cyclic alkyl group may be a monocyclic or condensed ring. The number and position of double bonds present in the alkyl group are not particularly limited. More specifically, examples include a butyl group, an aryl group, an isopropyl group and an arenyl group. The same applies to the alkali moiety of another substituent containing an alkali moiety (for example, an alkoxy group).
[0027] アルキニル基は、特に言及しな 、場合には、直鎖状、分岐鎖状の 、ずれでもよ 、。  [0027] The alkynyl group may be linear, branched or displaced unless otherwise specified.
アルキ-ル基に存在する三重結合の数及び位置は特に限定されな 、。該ァルケ- ル基は 1又は 2個以上の二重結合を含んでいてもよい。より具体的には、ェチュル基 、プロパルギル基などを挙げることができる。アルキニル部分を含む他の置換基 (例え ば、アルキ-ルォキシ基など)のアルキ-ル部分にっ ヽても同様である。  The number and position of triple bonds present in the alkyl group are not particularly limited. The alkenyl group may contain one or more double bonds. More specifically, examples include an ethur group and a propargyl group. The same applies to the alkyl moiety of other substituents containing an alkynyl moiety (for example, an alkyloxy group and the like).
ァラルキル基は、特に言及しない場合には、直鎖状、分岐鎖状のいずれでもよい。 より具体的には、ベンジル基、 1-ナフチルメチル基、 2-ナフチルメチル基、 1-フエネ チル基、 2-フエネチル基などを挙げることができる。ァラルキル部分を含む他の置換 基 (例えば、ァラルキルォキシ基など)のァラルキル部分にっ ヽても同様である。 ァシル基としては、ホルミル基；ァセチル基、プロピオニル基、ブチリル基、イソブチ リル基、バレリル基、イソバレリル基、ビバロイル基などのアルカノィル基；アタリロイル 基、メタクリロイル基、クロトノィル基、イソクロトノィル基などのァルケ-ルカルボ-ル 基；プロピオロイル基などのアルキ-ルカルボ-ル基；ベンゾィル基、 1-ナフトイル基 、 2-ナフトイル基などのァロイル基；ベンジルカルボ-ル基などのァラルキルカルボ- ル基；ピペリジノカルボ-ル基、モルホリノカルボ-ル基、フロイル基、テノィル基、二 コチノィル基、イソニコチノィル基などのへテロ環カルボ-ル基；カルボキシ基；メトキ シカルボニル基などのアルコキシカルボニル基；ァリルォキシカルボニル基などのァ ルケ-ルォキシカルボ-ル基；プロパルギルォキシカルボニル基などのアルキニル ォキシカルボ-ル基；フエノキシカルボ-ル基などのァリールォキシカルボ-ル基； ベンジルォキシカルボ-ル基などのァラルキルォキシカルボ-ル基； 4-ピペリジルォ キシカルボ-ル基、 3-ピリジルォキシカルボ-ル基などのへテロ環ォキシカルボ-ル 基；力ルバモイル基、メチルカルバモイル基などのアルキル力ルバモイル基；ジメチ ルカルバモイル基などのジアルキル力ルバモイル基；フ -ルカルバモイル基などの ァリール力ルバモイル基；ベンジルカルバモイル基などのァラルキル力ルバモイル基; スルホ基；メシル基、プロパンスルホ-ル基などのアルキルスルホ-ル基；ァリルスル ホニル基などのアルケニルスルホニル基；プロパルギルスルホニル基などのアルキニ ルスルホニル基；ベンゼンスルホ-ル基、 1-ナフチルスルホ-ル基、 2-ナフチルスル ホ-ル基などのァリ一ルスルホ -ル基；ベンジルスルホ-ル基などのァラルキルスル ホ-ル基；ピベリジノスルホ-ル基、モルホリノスルホ-ル基、 8-キノリルスルホ -ル基 などのへテロ環スルホ-ル基；スルファモイル基；メチルスルファモイル基などのアル キルスルファモイル基；ジメチルスルファモイル基などのジアルキルスルファモイル基; フエ-ルスルファモイル基などのァリールスルファモイル基；ベンジルスルファモイル 基などのァラルキルスルファモイル基；スルフエノ基；スルフヱナモイル基；ホスホノ基; ジメチルホスホノ基などのジアルキルホスホノ基；ジベンジルホスホノ基などのジァラ ルキルホスホノ基；ヒドロキシホスホ-ル基；チォホルミル基；ジチォカルボキシ基；ヒ ドロキシチォカルボ-ル基；スルファ-ルカルボ-ル基；チォカルバモイル基；グリオ キシロイル基；ォキサ口基などを挙げることができる。ァシル部分を含む他の置換基（ 例えば、ァシルォキシ基、ァシルァミノ基など)のァシル部分についても同様である。 The aralkyl group may be linear or branched unless otherwise specified. More specifically, examples thereof include a benzyl group, a 1-naphthylmethyl group, a 2-naphthylmethyl group, a 1-phenethyl group, and a 2-phenethyl group. The same applies to the aralkyl part of other substituents containing an aralkyl part (eg, an aralkyloxy group). Examples of the acryl group include a formyl group; an alkanol group such as an acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a valeryl group, an isovaleryl group, and a bivaloyl group; Alkyl group such as propioyl group; aroyl group such as benzoyl group, 1-naphthoyl group and 2-naphthoyl group; aralkyl carboxyl group such as benzylcarbon group; piperidinocarbon group; morpholino Heterocyclic carboyl groups such as carboyl group, furoyl group, tenoyl group, nicotinoyl group and isonicotinoyl group; carboxy groups; alkoxycarbonyl groups such as methoxycarbonyl groups; alkeoxy groups such as aryloxycarbonyl groups. -Roxycarbol group; propargylo Alkynyloxycarbyl groups such as xycarbonyl groups; aryloxycarbol groups such as phenoxycarbol groups; aralkyloxycarbonyl groups such as benzyloxycarbol groups; 4-piperidyloxycarboxy- A heterocyclic oxycarbyl group such as a benzyl group or a 3-pyridyloxycarbol group; an alkyl group such as a carbamoyl group or a methylcarbamoyl group; a dialkyl group such as a dimethylcarbamoyl group; a fluorcarbamoyl group; Arylalkyl groups such as benzylcarbamoyl group; sulfo groups; alkylsulfol groups such as mesyl group and propanesulfol group; alkenylsulfonyl groups such as arylsulfonyl group; propargylsulfonyl groups and the like. Alkynyl sulfonyl group; benzene sulfol Arylsulfol groups such as 1-naphthylsulfol group and 2-naphthylsulfol group; aralkylsulfol groups such as benzylsulfol group; piberidinosulfol group, morpholinosulfol group, Heterocyclic sulfol groups such as 8-quinolylsulfuryl group; sulfamoyl groups; alkylsulfamoyl groups such as methylsulfamoyl groups; dialkylsulfamoyl groups such as dimethylsulfamoyl groups; Aralkylsulfamoyl group such as benzylsulfamoyl group; sulfeno group; sulfenamoyl group; phosphono group; dialkylphosphono group such as dimethylphosphono group; diaralkylphosphono group such as dibenzylphosphono group Group; hydroxyphosphor group; thioformyl group; dithiocarboxy group; Xythiocarbyl group; sulfolcarbyl group; thiocarbamoyl group; glyoxyloyl group; Other substituents containing a For example, the same applies to an acyl moiety of an acyloxy group, an acylamino group and the like.
[0029] これらの置換基は、更に上記の置換基により置換されていてもよい。そのような例と して、トリフルォロメチル基、ペンタフルォロェチル基などのハロゲン化アルキル基；ヒ ドロキシメチル基などのヒドロキシアルキル基；カルボキシメチル基などのカルボキシ アルキル基；トリフルォロメトキシ基などのハロゲン化アルコキシ基；トリフルォロアセ チル基などのハロゲン化アルカノィル基；トリフルォロメタンスルホ-ル基などのハロ ゲン化アルキルスルホ-ル基；メトキシカルボ-ルァミノ基、 tert-ブトキシカルボ-ル アミノ基などのアルコキシカルボ-ルァミノ基；ベンジルォキシカルボ-ルァミノ基など のァラルキルォキシカルボ-ルァミノ基；メシルァミノ基などのアルキルスルホ-ルアミ ノ基；ベンゼンスルホ -ルァミノ基などのァリールスルホ -ルァミノ基などを挙げること ができる。  [0029] These substituents may be further substituted by the above-mentioned substituents. Examples thereof include halogenated alkyl groups such as trifluoromethyl group and pentafluoroethyl group; hydroxyalkyl groups such as hydroxymethyl group; carboxyalkyl groups such as carboxymethyl group; Halogenated alkanol groups such as trifluoroacetyl group; halogenated alkylsulfol groups such as trifluoromethanesulfol group; methoxycarbolamino group, tert-butoxycarbylamino group and the like. An alkoxysulfo-amino group such as a benzyloxycarbo-amino group; an alkylsulfo-amino group such as a mesylamino group; an arylsulfo-amino group such as a benzenesulfo-amino group. Can be mentioned.
また、上記の置換基のうち 2個以上の置換基がそれらが結合している原子 (炭素原 子、窒素原子など)と一緒になつて環を形成してもよい。このような環には、窒素原子 、酸素原子及び硫黄原子力 なる群力 選ばれる 1以上のへテロ原子が環構成原子 として含有されていてもよぐ環上には 1以上の置換基が存在していてもよい。環は単 環又は縮合環のいずれでもよぐ部分飽和、完全飽和、又は芳香環のいずれでもよ い。  In addition, two or more of the above substituents may form a ring together with the atom to which they are bonded (carbon atom, nitrogen atom, etc.). Such a ring may contain one or more heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom, and may have one or more substituents on the ring. May be. The ring may be partially saturated, fully saturated, or a saturated ring, or an aromatic ring.
[0030] Aで表される置換基を有して 、てもよ 、炭化水素環基は、好ましくは置換基を有し ていてもよい C - C ァリール基であり、更に好ましくはヒドロキシ置換 C -C ァリール  The hydrocarbon ring group which may have a substituent represented by A is preferably a C-C aryl group which may have a substituent, and more preferably a hydroxy-substituted C -C reel
6 10 6 10 基 (該ァリール基はヒドロキシ基のほかに更に置換基を有していてもよい)であり、特に 更に好ましくはヒドロキシ置換ナフチル基 (該ナフチル基はヒドロキシ基のほかに更に 置換基を有して 、てもよ 、；)である。  6 10 6 10 groups (the aryl group may further have a substituent in addition to the hydroxy group), particularly preferably a hydroxy-substituted naphthyl group (the naphthyl group is a hydroxy group and a further substituent group). And may be;)).
Aで表される置換基を有して 、てもよ 、炭化水素環基力 Sヒドロキシ置換ナフチル基（ 該ナフチル基はヒドロキシ基のほかに更に置換基を有して 、てもよ 、；)である場合、好 まし 、具体例として、下記環群 ex -ト 1から選択される基を挙げることができる。  A hydrocarbon ring group having a substituent represented by A or an S-hydroxy-substituted naphthyl group (the naphthyl group may further have a substituent in addition to the hydroxy group;) In the case of, preferred examples include a group selected from the following ring group ex-1.
[環群 α - 1-1] 5-ヒドロキシ- 2-ナフチル基、 3-ヒドロキシ- 2-ナフチル基、 1-ヒドロキシ -2-ナフチル基、 4-ヒドロキシ -3-メチル -1-ナフチル基、 5-ヒドロキシ -7-スルホ -2-ナ フチル基、 6-スルホ -8-ヒドロキシ- 2-ナフチル基、 5-ヒドロキシ- 1-ナフチル基、 7-ヒド 口キシ- 1-ナフチル基、 4-ヒドロキシ- 1-ナフチル基、 6-ヒドロキシ- 1-ナフチル基、 2-ヒ ドロキシ -1-ナフチル基 [Ring group α-1-1] 5-hydroxy-2-naphthyl group, 3-hydroxy-2-naphthyl group, 1-hydroxy-2-naphthyl group, 4-hydroxy-3-methyl-1-naphthyl group, 5 -Hydroxy-7-sulfo-2-naphthyl, 6-sulfo-8-hydroxy-2-naphthyl, 5-hydroxy-1-naphthyl, 7-hydr Oral xy-1-naphthyl, 4-hydroxy-1-naphthyl, 6-hydroxy-1-naphthyl, 2-hydroxy-1-naphthyl
Aで表される置換基を有して 、てもよ 、炭化水素環基は、最も好ましくは 1-ヒドロキ シ- 2-ナフチル基である。  The hydrocarbon ring group, which may have a substituent represented by A, is most preferably a 1-hydroxy-2-naphthyl group.
Aで表される置換基を有して 、てもよ 、ヘテロ環基は、好ましくは置換基を有して ヽ てもよ 、6な!、し 13員のへテロアリール基、或いは置換基を有して 、てもよ 、9又は 10 員の部分飽和へテロ環基である。  The heterocyclic group having a substituent represented by A may be a 6- or 13-membered heteroaryl group or a substituent. At least a 9- or 10-membered partially saturated heterocyclic group.
[0031] Aで表される置換基を有して 、てもよ 、ヘテロ環基が置換基を有して 、てもよ 、6な いし 13員のへテロアリール基である場合、好ましくはヒドロキシ基で置換された 6ない し 10員のへテロアリール基 (該ヘテロァリール基はヒドロキシ基のほかに更に置換基を 有していてもよい)であり、更に好ましくはヒドロキシ置換キノリル基 (該キノリル基はヒド ロキシ基のほかに更に置換基を有していてもよい)であり、特に更に好ましくは、 4-ヒド ロキシ -3-キノリル基 (該キノリル基はヒドロキシ基のほかに更に置換基を有していても よい)である。 When a heterocyclic group having a substituent represented by A or a heterocyclic group having a substituent is a 6- or 13-membered heteroaryl group, it is preferably hydroxy. A 6- or 10-membered heteroaryl group (the heteroaryl group may further have a substituent in addition to the hydroxy group), more preferably a hydroxy-substituted quinolyl group (the quinolyl group is And further preferably a 4-hydroxy-3-quinolyl group (the quinolyl group further has a substituent in addition to the hydroxy group). ).
Aで表される置換基を有して 、てもよ 、ヘテロ環基が置換基を有して 、てもよ 、6な いし 13員のへテロアリール基である場合、該 6ないし 13員のへテロアリール基は、好ま しくはキノリル基、インドリル基、インダゾリル基、ベンゾチアゾリル基、ベンズォキサゾ リル基、カルバゾリル基、ピリジル基、キノキサリニル基及びジベンゾフラ -ル基力 な る群から選択される基である。  A heterocyclic group having a substituent represented by A or a heterocyclic group having a substituent or a 6- or 13-membered heteroaryl group; The heteroaryl group is preferably a group selected from the group consisting of a quinolyl group, an indolyl group, an indazolyl group, a benzothiazolyl group, a benzoxazolyl group, a carbazolyl group, a pyridyl group, a quinoxalinyl group and a dibenzofural group.
Aで表される置換基を有して 、てもよ 、ヘテロ環基がヒドロキシ基で置換された 6な いし 10員のへテロアリール基 (該ヘテロァリール基はヒドロキシ基のほかに更に置換基 を有していてもよい)である場合、該 6ないし 10員のへテロアリール基は、好ましくはキ ノリル基又はピリジル基である。  A 6- or 10-membered heteroaryl group having a substituent represented by A and having a heterocyclic group substituted with a hydroxy group (the heteroaryl group further has a substituent in addition to the hydroxy group). The 6- to 10-membered heteroaryl group is preferably a quinolyl group or a pyridyl group.
[0032] Aで表される置換基を有して 、てもよ 、ヘテロ環基がヒドロキシ置換キノリル基 (該キ ノリル基はヒドロキシ基のほかに更に置換基を有して 、てもよ 、；)である場合、好ま ヽ 具体例として、下記環群 oc -2-1から選択される基を挙げることができる。 The heterocyclic group may have a substituent represented by A, and the heterocyclic group may be a hydroxy-substituted quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group, ;)), Preferred specific examples include groups selected from the following ring group oc-2-1.
[環群 α - 2-1] 8-ヒドロキシ- 2-キノリル基、 4-ヒドロキシ- 2-キノリル基、 7-クロ口- 4-ヒド 口キシキノリン- 3-ィル基、 4-ヒドロキシ -7- (トリフルォロメチル)キノリン- 3-ィル基、 2,4- ジヒドロキシ- 3-キノリル基、 4-ヒドロキシ -2- (トリフルォロメチル)キノリン- 3-ィル基、 4- ヒドロキシ- 3-キノリル基、 4-ヒドロキシ -2-メチルキノリン- 3-ィル基、 2-ェチル -4-ヒドロ キシキノリン- 3-ィル基、 4-ヒドロキシ -2- (ペンタフルォロェチル)キノリン- 3-ィル基、 7- フルォロ- 4-ヒドロキシキノリン- 3-ィル基、 6-フルォロ- 4-ヒドロキシキノリン- 3-ィル基、 4-ヒドロキシ -8-メチルキノリン- 3-ィル基、 6, 7-ジフルォロ- 4-ヒドロキシキノリン- 3-ィ ル基、 4-ヒドロキシ -7-メチルキノリン- 3-ィル基、 4-ヒドロキシ -6-メチルキノリン- 3-ィ ル基、 4-ヒドロキシ -8-メトキシキノリン- 3-ィル基、 4-ヒドロキシ -6-メトキシキノリン- 3-ィ ル基、 6-クロ口- 4-ヒドロキシキノリン- 3-ィル基、 6,7-ジメトキシ- 4-ヒドロキシキノリン -3-ィル基 [Ring group α-2-1] 8-hydroxy-2-quinolyl group, 4-hydroxy-2-quinolyl group, 7-chloro-4-hydroxy xyquinolin-3-yl group, 4-hydroxy-7- (Trifluoromethyl) quinoline-3-yl group, 2,4- Dihydroxy-3-quinolyl group, 4-hydroxy-2- (trifluoromethyl) quinolin-3-yl group, 4-hydroxy-3-quinolyl group, 4-hydroxy-2-methylquinolin-3-yl group , 2-ethyl-4-hydroxyquinolin-3-yl group, 4-hydroxy-2- (pentafluoroethyl) quinolin-3-yl group, 7-fluoro-4-hydroxyquinolin-3-yl Group, 6-fluoro-4-hydroxyquinolin-3-yl group, 4-hydroxy-8-methylquinolin-3-yl group, 6,7-difluoro-4-hydroxyquinolin-3-yl group, 4 -Hydroxy-7-methylquinolin-3-yl group, 4-hydroxy-6-methylquinolin-3-yl group, 4-hydroxy-8-methoxyquinolin-3-yl group, 4-hydroxy-6- Methoxyquinoline-3-yl group, 6-chloro-4-Hydroxyquinoline-3-yl group, 6,7-dimethoxy-4-hydroxyquinoline-3-yl group
[0033] Aで表される置換基を有して 、てもよ 、ヘテロ環基が 4-ヒドロキシ- 3-キノリル基 (該 キノリル基はヒドロキシ基のほかに更に置換基を有して 、てもよ 、；)である場合、好まし V、具体例として、下記環群 ex -2-2から選択される基を挙げることができる。  The heterocyclic group may have a substituent represented by A, and the heterocyclic group may be a 4-hydroxy-3-quinolyl group (the quinolyl group may have a substituent in addition to the hydroxy group, In addition, when it is;), preferred V, specific examples include groups selected from the following ring group ex-2-2.
[環群ひ- 2-2] 7-クロ口- 4-ヒドロキシキノリン- 3-ィル基、 4-ヒドロキシ -7- (トリフルォロメ チル)キノリン- 3-ィル基、 2,4-ジヒドロキシ- 3-キノリル基、 4-ヒドロキシ -2- (トリフルォロ メチル)キノリン- 3-ィル基、 4-ヒドロキシ- 3-キノリル基、 4-ヒドロキシ -2-メチルキノリン -3-ィル基、 2-ェチル -4-ヒドロキシキノリン- 3-ィル基、 4-ヒドロキシ -2- (ペンタフルォ ロェチル)キノリン- 3-ィル基、 7-フルォロ- 4-ヒドロキシキノリン- 3-ィル基、 6-フルォロ -4-ヒドロキシキノリン- 3-ィル基、 4-ヒドロキシ -8-メチルキノリン- 3-ィル基、 6,7-ジフ ルォ口- 4-ヒドロキシキノリン- 3-ィル基、 4-ヒドロキシ -7-メチルキノリン- 3-ィル基、 4-ヒ ドロキシ -6-メチルキノリン- 3-ィル基、 4-ヒドロキシ -8-メトキシキノリン- 3-ィル基、 4-ヒ ドロキシ -6-メトキシキノリン- 3-ィル基、 6-クロ口- 4-ヒドロキシキノリン- 3-ィル基、 6,7- ジメトキシ -4-ヒドロキシキノリン- 3-ィル基  [Ring group 2-2] 7-chloro-4-Hydroxyquinolin-3-yl group, 4-hydroxy-7- (trifluoromethyl) quinolin-3-yl group, 2,4-dihydroxy-3 -Quinolyl, 4-hydroxy-2- (trifluoromethyl) quinolin-3-yl, 4-hydroxy-3-quinolyl, 4-hydroxy-2-methylquinolin-3-yl, 2-ethyl- 4-hydroxyquinolin-3-yl group, 4-hydroxy-2- (pentafluoroethyl) quinolin-3-yl group, 7-fluoro-4-hydroxyquinolin-3-yl group, 6-fluoro-4- Hydroxyquinolin-3-yl group, 4-hydroxy-8-methylquinolin-3-yl group, 6,7-difluoro mouth-4-hydroxyquinolin-3-yl group, 4-hydroxy-7-methyl Quinoline-3-yl, 4-hydroxy-6-methylquinolin-3-yl, 4-hydroxy-8-methoxyquinolin-3-yl, 4-hydroxy-6-methoxyquinolyl 3-yl, 6-chloro-4-hydroxyquinolin-3-yl, 6,7-dimethoxy-4-hydroxyquinolin-3-yl
[0034] Aで表される置換基を有して 、てもよ 、ヘテロ環基が置換基を有して 、てもよ 、9又 は 10員の部分飽和へテロ環基である場合、更に好ましくは、 1又は 2個の窒素原子を 環構成原子として含有する 9又は 10員の部分飽和へテロ環基 (該部分飽和へテロ環 基は置換基を有していてもよぐ Yとの結合位置は環構成原子である窒素原子の位 置である)であり、特に更に好ましくは、置換基を有していてもよいイソインドリン- 2-ィ ル基、置換基を有していてもよい 1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、置換基を 有して 、てもよい 1 ,2-ジヒドロイソキノリン- 2-ィル基及び置換基を有して!/、てもよ!/ヽ 1,2,3,4-テトラヒドロキナゾリン- 3-ィル基力もなる群力も選択される基である。 [0034] When the heterocyclic group having a substituent represented by A or a heterocyclic group having a substituent is a 9- or 10-membered partially saturated heterocyclic group, More preferably, a 9- or 10-membered partially saturated heterocyclic group containing 1 or 2 nitrogen atoms as a ring-constituting atom (the partially saturated heterocyclic group may be substituted with Y Is the position of a nitrogen atom which is a ring-constituting atom), and is more preferably an isoindoline-2-yl group which may have a substituent, 1,2,3,4-tetrahydroisoquinoline-2-yl group and a substituent 1,2,3,4-tetrahydroquinazoline-3-yl having a 1,2-dihydroisoquinolin-2-yl group and a substituent! It is a group from which both basic power and group power are selected.
Aで表される置換基を有して 、てもよ 、ヘテロ環基力 置換基を有して 、てもよ 、ィ ソインドリン- 2-ィル基、置換基を有していてもよい 1,2,3,4-テトラヒドロイソキノリン- 2- ィル基、置換基を有して 、てもよい 1,2-ジヒドロイソキノリン- 2-ィル基及び置換基を有 していてもよい 1,2,3,4-テトラヒドロキナゾリン- 3-ィル基力もなる群力も選択される基で ある場合、好ましい具体例として、下記環群 α -3-1から選択される基を挙げることが できる。  May have a substituent represented by A, may have a heterocyclic group substituent, may have a substituent, may have an isoindolin-2-yl group, may have a substituent 1 , 2,3,4-tetrahydroisoquinolin-2-yl group, optionally having a substituent, 1,2-dihydroisoquinolin-2-yl group and optionally having a substituent 1, When the group is selected to have a group power of 2,3,4-tetrahydroquinazolin-3-yl group, preferred examples thereof include groups selected from the following ring group α-3-1.
[環群 α - 3-1] 1,3-ジォキソイソインドリン- 2-ィル基、 3-ヒドロキシ- 1-ォキソイソインド リン- 2-ィル基、 1-ォキソイソインドリン- 2-ィル基、 1,3-ジォキソ- 1,2,3,4-テトラヒドロイ ソキノリン- 2-ィル基、 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 3-ヒドロキ シ- 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 1-ォキソ -1,2-ジヒドロイソキノ リン- 2-ィル基、 4-ォキソ -1,2,3,4-テトラヒドロキナゾリン- 3-ィル基  [Ring group α-3-1] 1,3-Dioxoisoindoline-2-yl group, 3-hydroxy-1-oxoisoindoline-2-yl group, 1-oxoisoindoline-2-yl 1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 3- Hydroxy-1-oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2-dihydroisoquinolin-2-yl group, 4-oxo-1,2 , 3,4-tetrahydroquinazoline-3-yl group
Βで表される置換基を有して 、てもよ 、炭化水素環基は、好ましくは置換基を有し ていてもよい C - C ァリール基である。  The hydrocarbon ring group, which may have a substituent represented by Β, is preferably a C-Caryl group which may have a substituent.
6 10  6 10
Βで表される置換基を有して 、てもよ 、炭化水素環基が置換基を有して 、てもよ!/ヽ C -C ァリール基である場合、好ましい具体例として、下記環群 13 -1-1から選択され When the hydrocarbon ring group has a substituent represented by Β, the hydrocarbon ring group may have a substituent, or may be a C / C aryl group. Selected from group 13 -1-1
6 10 6 10
る基を挙げることがでさる。 Groups.
[環群 j8 - 1- 1] 3- [(4,6-ジクロロ- 1,3,5-トリァジン- 2-ィル)ァミノ]フエ-ル基、 3-ヒドロキ シ -4-メチルフエ-ル基、 3- (カルボキシメチル)フエ-ル基、 5-ヒドロキシ- 2-ナフチル 基、 2-フルォロ- 6-(1-イミダゾリル)フエ-ル基、 2-ピペリジノ -5- (トリフルォロメチル)フ ェ-ル基、 3-ヒドロキシフエ-ル基、 4-ヒドロキシ -3-メチルフエ-ル基、 4-メチルフエ- ル基、 4-ヒドロキシフヱ-ル基、 4-ヒドロキシビフエ-ル- 3-ィル基、 9-ォキソフルォレ ン -3-ィル基、 4-メトキシフエ-ル基、 4-フエノキシフエ-ル基、 4-スルファモイルフエ -ル基、 4-カルボキシフヱ-ル基、 2-ヒドロキシフヱ-ル基、 3--トロフヱ-ル基  [Ring group j8-1-1] 3-[(4,6-dichloro-1,3,5-triazin-2-yl) amino] phenyl, 3-hydroxy-4-methylphenyl , 3- (carboxymethyl) phenyl, 5-hydroxy-2-naphthyl, 2-fluoro-6- (1-imidazolyl) phenyl, 2-piperidino-5- (trifluoromethyl) phenyl Ball group, 3-hydroxyphenyl group, 4-hydroxy-3-methylphenyl group, 4-methylphenyl group, 4-hydroxyphenyl group, 4-hydroxybiphenyl-3-yl Group, 9-oxofluoren-3-yl group, 4-methoxyphenyl group, 4-phenoxyphenyl group, 4-sulfamoylphenyl group, 4-carboxyphenyl group, 2-hydroxyphenyl group , 3-Trofur-group
Bで表される置換基を有して 、てもよ 、ヘテロ環基は、好ましくは置換基を有して ヽ てもよ 、5な!、し 13員のへテロアリール基、或いは置換基を有して 、てもよ 、5な!、し 10員の部分飽和へテロ環基である。 Bで表される置換基を有して 、てもよ 、ヘテロ環基が置換基を有して 、てもよ 、5な ヽ し 13員のへテロアリール基である場合、好ましくは 5員のへテロアリール基であり、更 に好ましくは置換基を有して 、てもよ 、ビラゾリル基であり、特に更に好ましくは、Having a substituent represented by B, the heterocyclic group may preferably have a substituent, and may be a 5- or 13-membered heteroaryl group or a substituent. A 5- or 10-membered partially saturated heterocyclic group. When a heterocyclic group having a substituent represented by B or a heterocyclic group having a substituent or a 5- or 13-membered heteroaryl group is preferred, it is preferably a 5-membered heteroaryl group. A heteroaryl group, further preferably having a substituent, and may be a bilazolyl group, and particularly preferably,
(A) 1位が水素原子、置換基を有していてもよい C - Cアルキル基、置換基を有してい (A) 1-position has a hydrogen atom, a C-C alkyl group which may have a substituent, and a substituent
1 6  1 6
てもよい C - C ァリール基、置換基を有していてもよい C -C ァラルキル基、又は置 A C -C aryl group, an optionally substituted C -C aralkyl group, or
6 10 7 12  6 10 7 12
換基を有して 、てもよ 、9員のへテロアリール基であり； 3位が置換基を有して 、てもよ い C - Cアルキル基、又は置換基を有していてもよい C - C ァリール基であり； 5位がA 9-membered heteroaryl group, which may have a substituent; or a C-C alkyl group, which may have a substituent at the 3-position, or may have a substituent. C-C aryl group; 5th place
1 6 6 10 1 6 6 10
ヒドロキシ基であるピラゾール -4-ィル基； A pyrazole-4-yl group which is a hydroxy group;
(B) 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよい C  (B) C 1 -C alkyl group optionally having a substituent at position 1, C optionally having a substituent
1 6 6 1 6 6
- C ァリール基、置換基を有していてもよい C -C ァラルキル基、又は置換基を有し-A C aryl group, an optionally substituted C -C aralkyl group, or a substituted
10 7 12 10 7 12
ていてもよい C - Cアルコキシカルボ-ル基であり； 3位が水素原子、置換基を有して An optionally substituted C -C alkoxycarbonyl group; having a hydrogen atom at the 3-position and a substituent
2 7  2 7
いてもよい C - Cアルキル基、又は置換基を有していてもよい C - C ァリール基であり An optionally substituted C-C alkyl group or an optionally substituted C-C aryl group
1 6 6 10  1 6 6 10
； 4位が水素原子又は置換基を有していてもよい C - Cアルコキシカルボ-ル基であ  A 4-position is a hydrogen atom or a C-C alkoxycarboyl group which may have a substituent;
2 7  2 7
るピラゾール -5-ィル基；或いは Pyrazole-5-yl group; or
(C) 1位が水素原子又は置換基を有していてもよい C - C ァリール基であり； 4位が水  (C) position 1 is a hydrogen atom or a C -C aryl group which may have a substituent; position 4 is water
6 10  6 10
素原子であり； 5位が置換基を有していてもよい C - Cアルキル基、置換基を有してい A C-C alkyl group which may have a substituent at the 5-position, having a substituent
1 6  1 6
てもよい C - C ァリール基、又はヒドロキシ基であるピラゾール -3-ィル基 C-Caryl group or pyrazole-3-yl group which is a hydroxy group
6 10  6 10
である。 It is.
Bで表される置換基を有して 、てもよ 、ヘテロ環基が置換基を有して 、てもよ 、5な いし 13員のへテロアリール基である場合、該 5ないし 13員のへテロアリール基は、好ま しくはピラゾリル基、カルバゾリル基、インドリル基、ベンズイミダゾリル基、テトラゾリル 基、ピリジル基、キノリル基、チアゾリル基、ベンゾチアゾリル基、インダゾリル基、チェ -ル基、ベンゾチオフヱ-ル基、フリル基及びべンゾフラ-ル基からなる群から選択さ れる基である。  Having a substituent represented by B, or a heterocyclic group having a substituent or a 5- or 13-membered heteroaryl group, A heteroaryl group is preferably a pyrazolyl group, a carbazolyl group, an indolyl group, a benzimidazolyl group, a tetrazolyl group, a pyridyl group, a quinolyl group, a thiazolyl group, a benzothiazolyl group, an indazolyl group, a chelyl group, a benzothiopropyl group, or a furyl group. And a benzofural group.
Bで表される置換基を有して 、てもよ 、ヘテロ環基が、  Having a substituent represented by B, the heterocyclic group may be
(A) 1位が水素原子、置換基を有していてもよい C - Cアルキル基、置換基を有してい (A) 1-position has a hydrogen atom, a C-C alkyl group which may have a substituent, and a substituent
1 6  1 6
てもよい C - C ァリール基、置換基を有していてもよい C -C ァラルキル基、又は置 A C -C aryl group, an optionally substituted C -C aralkyl group, or
6 10 7 12  6 10 7 12
換基を有して 、てもよ 、9員のへテロアリール基であり； 3位が置換基を有して 、てもよ いじ - Cアルキル基、又は置換基を有していてもよい C - C ァリール基であり； 5位がA 9-membered heteroaryl group having a substituent; or a 3-membered heteroaryl group. A modified C-C alkyl group or a C-C aryl group which may have a substituent;
1 6 6 10 1 6 6 10
ヒドロキシ基であるピラゾール -4-ィル基 Pyrazol-4-yl group which is a hydroxy group
である場合、好ましい具体例として、下記環群 j8 -2-1から選択される基を挙げること ができる。 In the case of, preferred specific examples include groups selected from the following ring group j8-2-1.
[環群 13 -2-1] 1-フエ-ル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル - 3-(tert-ブチル )- 5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-フエ-ル- 5-ヒドロ キシピラゾール -4-ィル基、 1-(4-メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1- フエ-ル- 3-ェチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-クロ口フエ-ル) -3-メチ ル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-クロ口フエ-ル) -3-メチル -5-ヒドロキシピ ラゾール -4-ィル基、 1-(2-クロ口フエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル 基、 1-(4-メトキシフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-メチル フエ-ル)- 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-ぺ ンタフルォロェチル- 5-ヒドロキシピラゾール -4-ィル基、 1-ベンジル- 3-トリフルォロメ チル- 5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-トリフルォロメチル- 5-ヒドロキシ ピラゾール -4-ィル基、 1-ベンジル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-フルオロフェ-ル )-3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-[4- (トリフル ォロメチル)フエ-ル] -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3-フルオロフェ -ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3,5-ジクロロフエ-ル) -3-メチ ル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3,4-ジクロロフエ-ル) -3-メチル - 5-ヒドロキ シピラゾール -4-ィル基、 1-(2-メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4- ィル基、 1-(2,4-ジクロロフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3- メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-カルボキシフエ- ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-[3,5-ビス (トリフルォロメチル)フエ -ル] -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(2-フルオロフェ-ル )-3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-メトキシフエ-ル) -3-トリフルォロメチル -5- ヒドロキシピラゾール- 4-ィル基、 1- (4-フルオロフェ-ル )-3-トリフルォロメチル- 5-ヒド 口キシピラゾール -4-ィル基、 1-(3,5-ジクロロフヱ-ル)- 3-トリフルォロメチル- 5-ヒドロ キシピラゾール -4-ィル基、 1-(2,4-ジクロロフヱ-ル)- 3-トリフルォロメチル- 5-ヒドロキ シピラゾール -4-ィル基、 1-(2-ヒドロキシェチル) -3-トリフルォロメチル- 5-ヒドロキシピ ラゾール- 4-ィル基、 1- (4-クロ口フエ-ル)- 3-トリフルォロメチル- 5-ヒドロキシピラゾー ル _4_ィル基、卜ェチル—3_トリフルォロメチル— 5_ヒドロキシピラゾール _4_ィル基、 [Ring group 13-2-1] 1-phenyl-3-methyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3- (tert-butyl) -5-hydroxypyrazole-4 -Yl group, 1-methyl-3-phenyl-5-hydroxypyrazole-4-yl group, 1- (4-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl Group, 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-ethyl-5-hydroxypyrazol-4-yl group, 1- ( 4-methyl-3-hydroxy-5-hydroxypyrazole-4-yl group, 1- (3-chloropyrrole) -3-methyl-5-hydroxypyrazole-4-y Group, 1- (2-chlorophenol) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (4-methoxyphenyl) -3-methyl-5-hydroxypyrazole-4 -Yl group, 1- (4-methylphenyl) -3- 3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3 -Pentafluoroethyl-5-hydroxypyrazole-4-yl group, 1-benzyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-trifluoromethyl- 5-hydroxypyrazole-4-yl group, 1-benzyl-3-methyl-5-hydroxypyrazole-4-yl group, 1- (4-fluorophenyl) -3-methyl-5-hydroxypyrazole-4 -Yl group, 1- [4- (trifluoromethyl) phenyl] -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3-fluorophenyl) -3-methyl-5- Hydroxypyrazole-4-yl group, 1- (3,5-dichlorophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3,4-dichlorophenyl) -3 -Methyl-5-hydroxypyrazole-4-yl group, 1- (2-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2,4-dichlorophenyl) -3-methyl-5-hydroxypyrazo 4-yl group, 1- (3-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (4-carboxyphenyl) -3-methyl-5 -Hydroxypyrazole-4-yl group, 1- [3,5-bis (trifluoromethyl) phenyl] -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-fluorophenyl -Yl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (4-methoxyphenyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- ( 4-fluorophenyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3,5-dichlorophenyl) -3-trifluoromethyl-5-hydro Xypyrazole-4-yl group, 1- (2,4-dichlorophenyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (2-hydroxyethyl) -3 - triflate Ruo Russia methyl - 5 hydroxypivalic Razoru - 4-I group, 1- (4-black port Hue - Le) - 3-triflate Ruo Russia methyl - 5-hydroxypyrazole Eaux Le _ 4 _ I group, Bok Echiru - 3 _ triflate Ruo Russia methyl - 5 _ hydroxypyrazole _ 4 _ I group,
1-(2,2,2-トリフルォロェチル) -3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基 、 1-(3-フルオロフェ-ル )-3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 l-(tert-ブチル )-3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-シクロへ キシル -3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 l-(n-ブチル )-3-トリ フルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-ヒドロキシベンジル) -3-トリフ ルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(4-カルボキシフエ-ル)- 3-トリフ ルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-カルボキシフヱ-ル)- 3-トリフ ルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-スルファモイルフエ-ル) -3-メ チル- 5-ヒドロキシピラゾール -4-ィル基、 1- (ベンゾチアゾール -2-ィル) -3-メチル -5- ヒドロキシピラゾール -4-ィル基、 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル 基、 1-メチル -3-メトキシカルボ-ルメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(4- ニトロフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1 ,3-ジメチル- 5-ヒドロキ シピラゾール -4-ィル基、 1-メチル -3-ェチル -5-ヒドロキシピラゾール -4-ィル基、 1-メ チル -3-メトキシメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-メチル - 3-(n-プロピル )-5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-(n-ブチル )-5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-[3- (エトキシカルボ-ル)プロピル]- 5-ヒドロキシピラゾール -4-ィル基、 1-ェチル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1, 3-ジェチル -5- ヒドロキシピラゾール -4-ィル基、 1-(2-ヒドロキシェチル) -3-メチル -5-ヒドロキシピラゾ ール -4-ィル基、 1-(2-ヒドロキシェチル) -3-ェチル -5-ヒドロキシピラゾール -4-ィル基 、 1-フエ-ル -3-メトキシカルボ-ルメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ -ル- 3-カルボキシメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-[3- (エト キシカルボ-ル)プロピル]- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル -3-(3-カル ボキシプロピル)- 5-ヒドロキシピラゾール -4-ィル基 1- (2,2,2-trifluoroethyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-fluorophenyl) -3-trifluoromethyl- 5-hydroxypyrazole-4-yl group, l- (tert-butyl) -3-trifluoromethyl- 5-hydroxypyrazole-4-yl group, 1-cyclohexyl-3-trifluoromethyl- 5-hydroxypyrazole-4-yl group, l- (n-butyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-hydroxybenzyl) -3-trifluoromethyl-5 -Hydroxypyrazole-4-yl group, 1- (4-carboxyphenyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-carboxyphenyl) -3-trif Fluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-sulfamoylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (benzothia -2-yl) -3-methyl-5-hydroxypyrazole-4-yl group, 3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-methoxycarbo -Methyl-5-hydroxypyrazole-4-yl group, 1- (4-nitrophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1,3-dimethyl-5-hydroxypyrazole- 4-yl group, 1-methyl-3-ethyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-methoxymethyl-5-hydroxypyrazole-4-yl group, 1-methyl- 3- (n-propyl) -5-hydroxypyrazole-4-yl group, 1-methyl-3- (n-butyl) -5-hydroxypyrazol-4-yl group, 1-methyl-3- [3 -(Ethoxycarbol) propyl] -5-hydroxypyrazole-4-yl group, 1-ethyl-3-methyl-5-hydroxypyrazole-4-yl group, 1,3-getyl-5-hydroxypyrazole -4-yl group 1- (2-hydroxyethyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-hydroxyethyl) -3-ethyl-5-hydroxypyrazole-4-yl Group, 1-phenyl-3-methoxycarbolmethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-carboxymethyl-5-hydroxypyrazole-4-yl group, 1 -Phenyl-3- [3- (ethoxycarbol) propyl] -5-hydroxypyrazole-4-yl group, 1-phenyl-3- (3-carboxypropyl) -5-hydroxypyrazole- 4-yl group
Bで表される置換基を有して!/、てもよ!/、ヘテロ環基が、 (B) 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよい C Having a substituent represented by B! /, May be! /, A heterocyclic group, (B) C 1 -C alkyl group optionally having a substituent at position 1, C optionally having a substituent
1 6 6 1 6 6
- C ァリール基、置換基を有していてもよい C -C ァラルキル基、又は置換基を有し-A C aryl group, an optionally substituted C -C aralkyl group, or a substituted
10 7 12 10 7 12
ていてもよい C - Cアルコキシカルボ-ル基であり； 3位が水素原子、置換基を有して An optionally substituted C -C alkoxycarbonyl group; having a hydrogen atom at the 3-position and a substituent
2 7  2 7
いてもよい C - Cアルキル基、又は置換基を有していてもよい C - C ァリール基であり An optionally substituted C-C alkyl group or an optionally substituted C-C aryl group
1 6 6 10  1 6 6 10
； 4位が水素原子又は置換基を有していてもよい C - Cアルコキシカルボ-ル基であ  A 4-position is a hydrogen atom or a C-C alkoxycarboyl group which may have a substituent;
2 7  2 7
るピラゾール -5-ィル基 Pyrazole-5-yl group
である場合、好ましい具体例として、下記環群 j8 -2-2から選択される基を挙げること ができる。 In the case of, preferred specific examples include groups selected from the following ring group j8-2-2.
[環群 13 -2-2] 1-(4-メチルフエ-ル) -3-メチルビラゾール -5-ィル基、 1-フエ-ルビラ ゾール -5-ィル基、 1,3-ジフヱ-ルビラゾール -5-ィル基、 1-フエ-ル -4- (エトキシカル ボ -ル)ピラゾール -5-ィル基、 1-フエ-ル -3-メチルピラゾール -5-ィル基、 1-エトキシ カルボ-ル- 3-フエ-ルビラゾール -5-ィル基、 1-フエ-ル- 3-(tert-ブチル)ピラゾー ル -5-ィル基、 1-(4-クロ口フエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-メトキシフエ -ル) -3-メチルピラゾール -5-ィル基、 1-ベンジル -3-メチルピラゾール -5-ィル基、 l-(tert-ブチル )- 3-フエ-ルビラゾール -5-ィル基、 1-[4- (トリフルォロメチル)フエ-ル ]-3_メチルピラゾール _5_ィル基、 l-[4-(tert-ブチル)フエ-ル] -3-メチルピラゾール -5-ィル基、 1- (4-二トロフエ-ル)- 3-メチルピラゾール- 5-ィル基、 1- (3-クロ口- 4-メチ ルフエ-ル) -3-メチルピラゾール _5_ィル基、 1-(2-シァノエチル) -3-メチルピラゾール -5-ィル基、 1-(3,4-ジクロロフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(3-クロ口フエ -ル) -3-メチルピラゾール -5-ィル基、 1-(2,4-ジクロロフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-ブロモフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-フルオロフェ -ル) -3-メチルピラゾール -5-ィル基、 1-[4- (エトキシカルボ-ル)フエ-ル] -3-メチル ピラゾール -5-ィル基、 1-(4-ヒドロキシフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-カルボキシフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-スルファモイルフエ -ル) -3-メチルピラゾール -5-ィル基、 1-(4-クロ口フエ-ル)- 3-(tert-ブチル)ピラゾー ル -5-ィル基、 1-メチル -3-フエ-ルビラゾール -5-ィル基  [Ring group 13-2-2] 1- (4-methylphenyl) -3-methylvirazol-5-yl group, 1-phenylvinyl-5-yl group, 1,3-diphenyl- Rubirazol-5-yl group, 1-phenyl-4- (ethoxycarbyl) pyrazole-5-yl group, 1-phenyl-3-methylpyrazole-5-yl group, 1-ethoxy Carboxyl-3-phenyl-4-azole group, 1-phenyl-3- (tert-butyl) pyrazol-5-yl group, 1- (4-chlorophenol)- 3-methylpyrazole-5-yl group, 1- (4-methoxyphenyl) -3-methylpyrazole-5-yl group, 1-benzyl-3-methylpyrazole-5-yl group, l- ( tert-butyl) -3-phenylpyrazole-5-yl group, 1- [4- (trifluoromethyl) phenyl] -3_methylpyrazole_5_yl group, l- [4- (tert -Butyl) phenyl] -3-methylpyrazole-5-yl group, 1- (4-ditrophenyl) -3-methylpyrazole-5-yl group, 1- (3-chloro-4 -Methyl Ruffe- ) -3-Methylpyrazole_5_yl group, 1- (2-cyanoethyl) -3-methylpyrazole-5-yl group, 1- (3,4-dichlorophenyl) -3-methylpyrazole-5- Yl group, 1- (3-chlorophenol) -3-methylpyrazole-5-yl group, 1- (2,4-dichlorophenyl) -3-methylpyrazole-5-yl group, 1- (4-bromophenyl) -3-methylpyrazole-5-yl group, 1- (4-fluorophenyl) -3-methylpyrazole-5-yl group, 1- [4- (ethoxycarbo -Le) phenyl] -3-methylpyrazole-5-yl group, 1- (4-hydroxyphenyl) -3-methylpyrazole-5-yl group, 1- (4-carboxyphenyl) ) -3-Methylpyrazole-5-yl group, 1- (4-sulfamoylphenol) -3-methylpyrazole-5-yl group, 1- (4-chlorophenol) -3 -(tert-butyl) pyrazol-5-yl group, 1-methyl-3-phenolylazole-5-yl group
Bで表される置換基を有して!/、てもよ!/、ヘテロ環基が、  Having a substituent represented by B! /, May be! /, A heterocyclic group,
(C) 1位が水素原子又は置換基を有していてもよい C - C ァリール基であり； 4位が水 素原子であり； 5位が置換基を有していてもよい C - Cアルキル基、置換基を有してい (C) position 1 is a hydrogen atom or a C -C aryl group which may have a substituent; position 4 is water A C-C alkyl group which may have a substituent at the 5-position, having a substituent
1 6  1 6
てもよい C - C ァリール基、又はヒドロキシ基であるピラゾール -3-ィル基である場合、 When it is a C-C aryl group or a pyrazole-3-yl group which is a hydroxy group,
6 10  6 10
好ましい具体例として、下記環群 β -2-3から選択される基を挙げることができる。 Preferred specific examples include groups selected from the following ring group β-2-3.
[環群 13 -2-3] 1-フエ-ル- 5-ヒドロキシピラゾール -3-ィル基、 5-フエ-ルビラゾール -3-ィル基、 1-(3-クロ口- 4-メチルフエ-ル) -5-メチルピラゾール -3-ィル基、 1-フエ- ル -5-メチルピラゾール _3_ィル基、 1-(4-クロ口フエ-ル) -5-メチルピラゾール -3-ィル 基、 1-(4-ブロモフエ-ル) -5-メチルピラゾール -3-ィル基、 1-(4-メチルフエ-ル) -5-メ チルピラゾール -3-ィル基 [Ring group 13-2-3] 1-phenyl-5-hydroxypyrazole-3-yl group, 5-phenylpyrazole-3-yl group, 1- (3-chloro-4--4-methylphenyl- ) -5-methylpyrazole-3-yl group, 1-phenyl-5-methylpyrazole_3_yl group, 1- (4-chloropyrrole) -5-methylpyrazole-3-yl 1- (4-bromophenyl) -5-methylpyrazole-3-yl group, 1- (4-methylphenyl) -5-methylpyrazole-3-yl group
Βで表される置換基を有して 、てもよ 、ヘテロ環基が置換基を有して 、てもよ 、5な ヽ し 10員の部分飽和へテロ環基である場合、好ましい具体例として、下記環群 j8 -3-1 力 選択される基を挙げることができる。  In the case where the heterocyclic group having a substituent represented by the formula (1) or (2) is a 5- or 10-membered partially saturated heterocyclic group having a substituent or a substituent, a preferred specific example is As an example, the following ring group j8-3-1 can be mentioned.
[環群 13 -3-1] 1,5-ジメチル- 3-ォキソ -2-フヱ-ル- 2, 3-ジヒドロピラゾール -4-ィル基 、 1,3-ベンゾジォキソラン- 5-ィル基、 1,4-ベンゾジォキサン- 6-ィル基、 4,5, 6,7-テトラ ヒドロインダゾール -3-ィル基  [Ring group 13-3-1] 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydropyrazol-4-yl group, 1,3-benzodioxolan-5 -Yl group, 1,4-benzodioxane-6-yl group, 4,5,6,7-tetrahydroindazole-3-yl group
一般式 (I)で表される化合物としては、好ましくは、  As the compound represented by the general formula (I), preferably,
Yカ CH=N―、— N=CH―、— CONH—又は— NHCO—であり；  Y is CH = N-, -N = CH-, -CONH- or -NHCO-;
Aが置換基を有していてもよい C - C ァリール基、置換基を有していてもよい 6ないし  A may have a substituent C-C aryl group, may have a substituent 6 or more
6 10  6 10
13員のへテロアリール基、或 、は置換基を有して 、てもよ 、9又は 10員の部分飽和 ヘテロ環基であり；  A 13-membered heteroaryl group or is a 9- or 10-membered partially saturated heterocyclic group having a substituent, and
Bが置換基を有していてもよい C - C ァリール基、置換基を有していてもよい 5ないし  B may have a substituent C-C aryl group, optionally having a substituent 5 to
6 10  6 10
13員のへテロアリール基、或 、は置換基を有して 、てもよ 、5な 、し 10員の部分飽和 ヘテロ環基である化合物である。  A 13-membered heteroaryl group or a compound having a substituent and which may be a 5- or 10-membered partially saturated heterocyclic group.
更に好ましくは、下記 (0、 G0、（m)のいずれかに該当する化合物である。 More preferably, it is a compound corresponding to any of the following (0, G0, (m)).
(0 Aがヒドロキシ置換 c - c ァリール基 (該ァリール基はヒドロキシ基のほかに更に置  (0 A is hydroxy-substituted c-c aryl group (the aryl group is further substituted in addition to the hydroxy group)
6 10  6 10
換基を有して 、てもよ 、；)であり； Having a substituent, may be;));
Yカ CH=N―、— N=CH―、— CONH—又は— NHCO—であり；  Y is CH = N-, -N = CH-, -CONH- or -NHCO-;
Bが置換基を有して 、てもよ 、5な 、し 13員のへテロアリール基である化合物。  Compounds in which B has a substituent and may be a 5- to 13-membered heteroaryl group.
(ii) A力 Sヒドロキシ基で置換された 6な 、し 10員のへテロアリール基 (該ヘテロァリール 基はヒドロキシ基のほかに更に置換基を有して 、てもよ 、)であり； (ii) A force A 6- to 10-membered heteroaryl group substituted with an S-hydroxy group (the heteroaryl The group may further have a substituent in addition to the hydroxy group, or);
Yカ N=CH-又は- CONH-であり； Y is N = CH- or -CONH-;
Bが置換基を有して 、てもよ 、5員のへテロアリール基である化合物。  Compounds in which B has a substituent and may be a 5-membered heteroaryl group.
(iii) Aが、 1又は 2個の窒素原子を環構成原子として含有する 9又は 10員の部分飽和 ヘテロ環基 (該部分飽和へテロ環基は置換基を有していてもよぐ Yとの結合位置は 環構成原子である窒素原子の位置である)であり；  (iii) A is a 9- or 10-membered partially saturated heterocyclic group containing 1 or 2 nitrogen atoms as ring-constituting atoms (the partially saturated heterocyclic group may have a substituent, and Is bonded to the nitrogen atom which is a ring-constituting atom);
Yカ N=CH—であり；  Y = N—CH—
Bが置換基を有して 、てもよ 、5員のへテロアリール基である化合物。  Compounds in which B has a substituent and may be a 5-membered heteroaryl group.
上記 (0に該当する化合物としては、好ましくは、 As the compound corresponding to the above (0, preferably,
A力ヒドロキシ置換ナフチル基 (該ナフチル基はヒドロキシ基のほかに更に置換基を有 していてもよい)であり；  A-hydroxy-substituted naphthyl group (the naphthyl group may have a substituent in addition to the hydroxy group);
Yカ CH=N―、— N=CH―、— CONH—又は— NHCO—であり；  Y is CH = N-, -N = CH-, -CONH- or -NHCO-;
Bが置換基を有して 、てもよ 、ビラゾリル基である化合物である。 A compound in which B has a substituent and may be a virazolyl group.
更に好ましくは、 Aが 1-ヒドロキシ- 2-ナフチル基であり；  More preferably, A is a 1-hydroxy-2-naphthyl group;
(a) Yカ N=CH-であり； B力 1位が水素原子、置換基を有していてもよい C - Cアル  (a) Y is N = CH-; B force is a hydrogen atom at position 1 and may have a substituent.
1 6 キル基、置換基を有していてもよい C - C ァリール基、置換基を有していてもよい C  16-C hyl group, C-C aryl group optionally having substituent (s) C-C aryl group, C group optionally having substituent (s)
6 10 7 6 10 7
- C ァラルキル基、又は置換基を有していてもよい 9員のへテロアリール基であり、 3-A C aralkyl group or a 9-membered heteroaryl group which may have a substituent,
12 12
位が置換基を有していてもよい C - Cアルキル基、又は置換基を有していてもよい C C-C alkyl group which may have a substituent at the position, or C which may have a substituent
1 6 6 1 6 6
- C ァリール基であり、 5位力 Sヒドロキシ基であるピラゾール -4-ィル基； -A pyrazole-4-yl group which is a C aryl group and is a 5-position S hydroxy group;
10  Ten
(b) Yが- CH=N -であり； Bが、 1位が置換基を有していてもよい C - Cアルキル基、置  (b) Y is -CH = N-; B is a C-C alkyl group optionally substituted at the 1-position,
1 6  1 6
換基を有していてもよい C -C ァリール基、置換基を有していてもよい C -C ァラル C -C aryl group which may have a substituent, C -C aryl which may have a substituent
6 10 7 12 キル基、又は置換基を有していてもよい C - Cアルコキシカルボニル基であり、 3位が  6 10 7 12 alkyl group or a C-C alkoxycarbonyl group which may have a substituent,
2 7  2 7
水素原子、置換基を有していてもよい C - Cアルキル基、又は置換基を有していても Hydrogen atom, optionally substituted C-C alkyl group, or optionally substituted
1 6  1 6
よい C - C ァリール基であり、 4位が水素原子又は置換基を有していてもよい C - C了A good C-C aryl group, which may have a hydrogen atom or a substituent at the 4-position.
6 10 2 7 ルコキシカルボ-ル基であるピラゾール -5-ィル基；或 、は 6 10 2 7 a pyrazole-5-yl group which is a alkoxycarbyl group;
(c) Yが- CH=N-であり； Bが、 1位が水素原子又は置換基を有していてもよい C - C 了  (c) Y is -CH = N-; B is a C-C atom which may have a hydrogen atom or a substituent at the 1-position.
6 10 リール基であり、 4位が水素原子であり、 5位が置換基を有していてもよい C - C ァリー  6 10 reel group, 4-position is hydrogen atom, 5-position may have a substituent C-C aryl
6 10 ル基、又はヒドロキシ基であるピラゾール -3-ィル基 である化合物である。 6 10-pyrazole-3-yl group or hydroxy group Is a compound.
上記 (a)において、 Bの好ましい具体例として、下記環群 j8 -2-1から選択される基を 挙げることができる。  In the above (a), preferred specific examples of B include a group selected from the following ring group j8-2-1.
[環群 13 -2-1] 1-フエ-ル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル - 3-(tert-ブチル )- 5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-フエ-ル- 5-ヒドロ キシピラゾール -4-ィル基、 1-(4-メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1- フエ-ル- 3-ェチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-クロ口フエ-ル) -3-メチ ル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-クロ口フエ-ル) -3-メチル -5-ヒドロキシピ ラゾール -4-ィル基、 1-(2-クロ口フエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル 基、 1-(4-メトキシフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-メチル フエ-ル)- 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-ぺ ンタフルォロェチル- 5-ヒドロキシピラゾール -4-ィル基、 1-ベンジル- 3-トリフルォロメ チル- 5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-トリフルォロメチル- 5-ヒドロキシ ピラゾール -4-ィル基、 1-ベンジル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-フルオロフェ-ル )-3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-[4- (トリフル ォロメチル)フエ-ル] -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3-フルオロフェ -ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3,5-ジクロロフエ-ル) -3-メチ ル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3,4-ジクロロフエ-ル) -3-メチル - 5-ヒドロキ シピラゾール -4-ィル基、 1-(2-メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4- ィル基、 1-(2,4-ジクロロフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3- メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-カルボキシフエ- ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-[3,5-ビス (トリフルォロメチル)フエ -ル] -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(2-フルオロフェ-ル )-3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-メトキシフエ-ル) -3-トリフルォロメチル -5- ヒドロキシピラゾール- 4-ィル基、 1- (4-フルオロフェ-ル )-3-トリフルォロメチル- 5-ヒド 口キシピラゾール -4-ィル基、 1-(3,5-ジクロロフヱ-ル)- 3-トリフルォロメチル- 5-ヒドロ キシピラゾール -4-ィル基、 1-(2,4-ジクロロフヱ-ル)- 3-トリフルォロメチル- 5-ヒドロキ シピラゾール -4-ィル基、 1-(2-ヒドロキシェチル) -3-トリフルォロメチル- 5-ヒドロキシピ ラゾール- 4-ィル基、 1- (4-クロ口フエ-ル)- 3-トリフルォロメチル- 5-ヒドロキシピラゾー ル _4_ィル基、卜ェチル—3_トリフルォロメチル— 5_ヒドロキシピラゾール _4_ィル基、[Ring group 13-2-1] 1-phenyl-3-methyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3- (tert-butyl) -5-hydroxypyrazole-4 -Yl group, 1-methyl-3-phenyl-5-hydroxypyrazole-4-yl group, 1- (4-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl Group, 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-ethyl-5-hydroxypyrazol-4-yl group, 1- ( 4-methyl-3-hydroxy-5-hydroxypyrazole-4-yl group, 1- (3-chloropyrrole) -3-methyl-5-hydroxypyrazole-4-y Group, 1- (2-chlorophenol) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (4-methoxyphenyl) -3-methyl-5-hydroxypyrazole-4 -Yl group, 1- (4-methylphenyl) -3- 3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3 -Pentafluoroethyl-5-hydroxypyrazole-4-yl group, 1-benzyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-trifluoromethyl- 5-hydroxypyrazole-4-yl group, 1-benzyl-3-methyl-5-hydroxypyrazole-4-yl group, 1- (4-fluorophenyl) -3-methyl-5-hydroxypyrazole-4 -Yl group, 1- [4- (trifluoromethyl) phenyl] -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3-fluorophenyl) -3-methyl-5- Hydroxypyrazole-4-yl group, 1- (3,5-dichlorophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3,4-dichlorophenyl) -3 -Methyl-5-hydroxypyrazole-4-yl group, 1- (2-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2,4-dichlorophenyl) -3-methyl-5-hydroxypyrazo 4-yl group, 1- (3-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (4-carboxyphenyl) -3-methyl-5 -Hydroxypyrazole-4-yl group, 1- [3,5-bis (trifluoromethyl) phenyl] -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-fluorophenyl -Yl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (4-methoxyphenyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- ( 4-fluorophenyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3,5-dichloropropyl) -3-trifluoromethyl-5-hydroxy Pyrazole-4-yl group, 1- (2,4-dichloropropyl) -3-trifluoromethyl-5-hydroxy Cypyrazole-4-yl group, 1- (2-hydroxyethyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (4-chlorophenol) -3 - triflate Ruo Russia methyl - 5-hydroxypyrazole Eaux Le _ 4 _ I group, Bok Echiru - 3 _ triflate Ruo Russia methyl - 5 _ hydroxypyrazole _ 4 _ I group,
1-(2,2,2-トリフルォロェチル) -3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基 、 1-(3-フルオロフェ-ル )-3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 l-(tert-ブチル )-3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-シクロへ キシル -3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 l-(n-ブチル )-3-トリ フルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-ヒドロキシベンジル) -3-トリフ ルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(4-カルボキシフエ-ル)- 3-トリフ ルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-カルボキシフヱ-ル)- 3-トリフ ルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-スルファモイルフエ-ル) -3-メ チル- 5-ヒドロキシピラゾール -4-ィル基、 1- (ベンゾチアゾール -2-ィル) -3-メチル -5- ヒドロキシピラゾール -4-ィル基、 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル 基、 1-メチル -3-メトキシカルボ-ルメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(4- ニトロフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1 ,3-ジメチル- 5-ヒドロキ シピラゾール -4-ィル基、 1-メチル -3-ェチル -5-ヒドロキシピラゾール -4-ィル基、 1-メ チル -3-メトキシメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-メチル - 3-(n-プロピル )-5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-(n-ブチル )-5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-[3- (エトキシカルボ-ル)プロピル]- 5-ヒドロキシピラゾール -4-ィル基、 1-ェチル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1, 3-ジェチル -5- ヒドロキシピラゾール -4-ィル基、 1-(2-ヒドロキシェチル) -3-メチル -5-ヒドロキシピラゾ ール -4-ィル基、 1-(2-ヒドロキシェチル) -3-ェチル -5-ヒドロキシピラゾール -4-ィル基 、 1-フエ-ル -3-メトキシカルボ-ルメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ -ル- 3-カルボキシメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-[3- (エト キシカルボ-ル)プロピル]- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル -3-(3-カル ボキシプロピル)- 5-ヒドロキシピラゾール -4-ィル基 1- (2,2,2-trifluoroethyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-fluorophenyl) -3-trifluoromethyl- 5-hydroxypyrazole-4-yl group, l- (tert-butyl) -3-trifluoromethyl- 5-hydroxypyrazole-4-yl group, 1-cyclohexyl-3-trifluoromethyl- 5-hydroxypyrazole-4-yl group, l- (n-butyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-hydroxybenzyl) -3-trifluoromethyl-5 -Hydroxypyrazole-4-yl group, 1- (4-carboxyphenyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-carboxyphenyl) -3-trif Fluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-sulfamoylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (benzothia -2-yl) -3-methyl-5-hydroxypyrazole-4-yl group, 3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-methoxycarbo -Methyl-5-hydroxypyrazole-4-yl group, 1- (4-nitrophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1,3-dimethyl-5-hydroxypyrazole- 4-yl group, 1-methyl-3-ethyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-methoxymethyl-5-hydroxypyrazole-4-yl group, 1-methyl- 3- (n-propyl) -5-hydroxypyrazole-4-yl group, 1-methyl-3- (n-butyl) -5-hydroxypyrazol-4-yl group, 1-methyl-3- [3 -(Ethoxycarbol) propyl] -5-hydroxypyrazole-4-yl group, 1-ethyl-3-methyl-5-hydroxypyrazole-4-yl group, 1,3-getyl-5-hydroxypyrazole -4-yl group 1- (2-hydroxyethyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-hydroxyethyl) -3-ethyl-5-hydroxypyrazole-4-yl Group, 1-phenyl-3-methoxycarbolmethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-carboxymethyl-5-hydroxypyrazole-4-yl group, 1 -Phenyl-3- [3- (ethoxycarbol) propyl] -5-hydroxypyrazole-4-yl group, 1-phenyl-3- (3-carboxypropyl) -5-hydroxypyrazole- 4-yl group
上記 (b)にお 、て、 Bの好ま 、具体例として、下記環群 j8 -2-2から選択される基を 挙げることができる。 [環群 β -2-2] 1-(4-メチルフエ-ル) -3-メチルビラゾール -5-ィル基、 1-フエ-ルビラ ゾール -5-ィル基、 1,3-ジフヱ-ルビラゾール -5-ィル基、 1-フエ-ル -4- (エトキシカル ボ -ル)ピラゾール -5-ィル基、 1-フエ-ル -3-メチルピラゾール -5-ィル基、 1-エトキシ カルボ-ル- 3-フエ-ルビラゾール -5-ィル基、 1-フエ-ル- 3-(tert-ブチル)ピラゾー ル -5-ィル基、 1-(4-クロ口フエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-メトキシフエ -ル) -3-メチルピラゾール -5-ィル基、 1-ベンジル -3-メチルピラゾール -5-ィル基、 l-(tert-ブチル )- 3-フエ-ルビラゾール -5-ィル基、 1-[4- (トリフルォロメチル)フエ-ル ]-3_メチルピラゾール _5_ィル基、 l-[4-(tert-ブチル)フエ-ル] -3-メチルピラゾール -5-ィル基、 1- (4-二トロフエ-ル)- 3-メチルピラゾール- 5-ィル基、 1- (3-クロ口- 4-メチ ルフエ-ル) -3-メチルピラゾール _5_ィル基、 1-(2-シァノエチル) -3-メチルピラゾール -5-ィル基、 1-(3,4-ジクロロフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(3-クロ口フエ -ル) -3-メチルピラゾール -5-ィル基、 1-(2,4-ジクロロフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-ブロモフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-フルオロフェ -ル) -3-メチルピラゾール -5-ィル基、 1-[4- (エトキシカルボ-ル)フエ-ル] -3-メチル ピラゾール -5-ィル基、 1-(4-ヒドロキシフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-カルボキシフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-スルファモイルフエ -ル) -3-メチルピラゾール -5-ィル基、 1-(4-クロ口フエ-ル)- 3-(tert-ブチル)ピラゾー ル -5-ィル基、 1-メチル -3-フエ-ルビラゾール -5-ィル基 In the above (b), preferred examples of B include a group selected from the following ring group j8-2-2. [Ring group β-2-2] 1- (4-methylphenyl) -3-methylvirazol-5-yl group, 1-phenylurazol-5-yl group, 1,3-diphenyl- Rubirazol-5-yl group, 1-phenyl-4- (ethoxycarbyl) pyrazole-5-yl group, 1-phenyl-3-methylpyrazole-5-yl group, 1-ethoxy Carboxyl-3-phenyl-4-azole group, 1-phenyl-3- (tert-butyl) pyrazol-5-yl group, 1- (4-chlorophenol)- 3-methylpyrazole-5-yl group, 1- (4-methoxyphenyl) -3-methylpyrazole-5-yl group, 1-benzyl-3-methylpyrazole-5-yl group, l- ( tert-butyl) -3-phenylpyrazole-5-yl group, 1- [4- (trifluoromethyl) phenyl] -3_methylpyrazole_5_yl group, l- [4- (tert -Butyl) phenyl] -3-methylpyrazole-5-yl group, 1- (4-ditrophenyl) -3-methylpyrazole-5-yl group, 1- (3-chloro-4 -Methyl Ruffe- ) -3-Methylpyrazole_5_yl group, 1- (2-cyanoethyl) -3-methylpyrazole-5-yl group, 1- (3,4-dichlorophenyl) -3-methylpyrazole-5- Yl group, 1- (3-chlorophenol) -3-methylpyrazole-5-yl group, 1- (2,4-dichlorophenyl) -3-methylpyrazole-5-yl group, 1- (4-bromophenyl) -3-methylpyrazole-5-yl group, 1- (4-fluorophenyl) -3-methylpyrazole-5-yl group, 1- [4- (ethoxycarbo -Le) phenyl] -3-methylpyrazole-5-yl group, 1- (4-hydroxyphenyl) -3-methylpyrazole-5-yl group, 1- (4-carboxyphenyl) ) -3-Methylpyrazole-5-yl group, 1- (4-sulfamoylphenol) -3-methylpyrazole-5-yl group, 1- (4-chlorophenol) -3 -(tert-butyl) pyrazol-5-yl group, 1-methyl-3-phenolylazole-5-yl group
上記 (c)にお 、て、 Bの好ま U、具体例として、下記環群 j8 -2-4から選択される基を 挙げることができる。  In the above (c), preferred examples of B include, as specific examples, groups selected from the following ring group j8-2-4.
[環群 13 -2-4] 1-フエ-ル- 5-ヒドロキシピラゾール -3-ィル基、 5-フエ-ルビラゾール -3-ィル基  [Ring group 13 -2-4] 1-phenyl-5-hydroxypyrazole-3-yl group, 5-phenylpyrazole-3-yl group
上記 (0に該当する化合物としては、特に更に好ましくは、本明細書に記載された下 記化合物番号で表される化合物力 なる群力 選択される化合物である。  The compound corresponding to the above (0) is particularly preferably a compound selected from the group consisting of a compound represented by the following compound number described in the present specification.
•化合物番号: 3, 26, 27, 50, 54, 62ないし 67, 76ないし 78, 83, 84, 86, 87, 91, 92, 103, 112ないし 115, 120, 128, 133, 138ないし 140, 148, 158, 189ないし 191, 195, 196, 203, 208, 211, 212, 214, 216, 218, 221, 222, 228, 229, 236ないし 239, 243, 247, 253ないし 256, 258, 261, 262, 268ないし 271, 279, 284ないし 287, 294ないし 301, 317, 321ないし 324, 331, 337, 351,及び 353 Compound number: 3, 26, 27, 50, 54, 62 to 67, 76 to 78, 83, 84, 86, 87, 91, 92, 103, 112 to 115, 120, 128, 133, 138 to 140, 148, 158, 189 to 191, 195, 196, 203, 208, 211, 212, 214, 216, 218, 221, 222, 228, 229, 236 to 239, 243, 247, 253 to 256, 258, 261, 262, 268 or 271, 279, 284 or 287, 294 or 301, 317, 321 to 324, 331, 337, 351, and 353
上記 GOに該当する化合物としては、好ましくは、  As the compound corresponding to the above GO, preferably,
A力ヒドロキシ置換キノリル基 (該キノリル基はヒドロキシ基のほかに更に置換基を有し ていてもよい)であり；  A-hydroxy-substituted quinolyl group (the quinolyl group may have a substituent in addition to the hydroxy group);
Yカ N=CH-又は- CONH-であり；  Y is N = CH- or -CONH-;
Bが置換基を有して 、てもよ 、ビラゾリル基である化合物である。  A compound in which B has a substituent and may be a virazolyl group.
[0044] 更に好ましくは、 Aが 4-ヒドロキシ- 3-キノリル基 (該キノリル基はヒドロキシ基のほかに 更に置換基を有して 、てもよ 、；)であり； [0044] More preferably, A is a 4-hydroxy-3-quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group;).
Yカ N=CH—であり；  Y = N—CH—
Bが、 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよい  B is a C-C alkyl group which may have a substituent at the 1-position, and may have a substituent
1 6  1 6
C -C ァリール基、又は置換基を有していてもよい C -C ァラルキル基であり、 3位が A C -C aryl group or a C -C aralkyl group which may have a substituent, wherein the 3-position is
6 10 7 12 6 10 7 12
置換基を有していてもよい C - Cアルキル基であり、 5位がヒドロキシ基であるピラゾー  A pyrazole having an optionally substituted C-C alkyl group, wherein the 5-position is a hydroxy group
1 6  1 6
ル -4-ィル基；  Le-4-yl group;
である化合物である。  Is a compound.
[0045] このとき、 Bの好ま U、具体例として、下記環群 j8 -2-5から選択される基を挙げるこ とがでさる。  [0045] At this time, a preferable example of B is, for example, a group selected from the following ring group j8-2-5.
[環群 13 -2-5] 1-フエ-ル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3- トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(4-メチルフエ-ル) -3-メチ ル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-トリフルォロメチル- 5-ヒドロキシ ピラゾール -4-ィル基、 1-フ -ル- 3-ェチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-クロ口フエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3-クロ口フエ二 ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(2-クロ口フエ-ル) -3-メチル - 5-ヒ ドロキシピラゾール -4-ィル基、 1-(4-メトキシフエ-ル) -3-メチル -5-ヒドロキシピラゾー ル -4-ィル基、 1-ベンジル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-フルォ 口フエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3-フルオロフェ-ル )-3- メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(2-メチルフエ-ル) -3-メチル -5-ヒドロキ シピラゾール -4-ィル基、 1-(3-メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4- ィル基、 1-(2-フルオロフェ-ル )-3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-ェチ ル- 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-フルオロフヱ-ル )-3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル -3-(3-カルボ キシプロピル)- 5-ヒドロキシピラゾール -4-ィル基 [Ring group 13 -2-5] 1-phenyl-3-methyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl Group, 1- (4-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl Group, 1-fur-3-ethyl-5-hydroxypyrazole-4-yl group, 1- (4-chloropyrrole) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3-chlorophenol) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-chlorophenol) -3-methyl-5-hydroxypyrazole- 4-yl group, 1- (4-methoxyphenyl) -3-methyl-5-hydroxypyrazol-4-yl group, 1-benzyl-3-methyl-5-hydroxypyrazol-4-yl Group, 1- (4-fluoromethyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3-fluoro ) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3- Methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-fluorophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1-ethyl 3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-fluorophenyl) -3-trifluoromethyl-5-hydroxypyrazol-4-yl group, 1- Phenyl-3- (3-carboxypropyl) -5-hydroxypyrazole-4-yl group
[0046] 上記 GOに該当する化合物としては、特に更に好ましくは、本明細書に記載された下 記化合物番号で表される化合物力 なる群力 選択される化合物である。 The compound corresponding to the above GO is particularly preferably a compound selected from the group consisting of a compound represented by the following compound number described in the present specification.
•化合物番号: 267, 272, 273, 280, 281, 302ないし 306, 310, 312ないし 316, 318ない し 320, 325ないし 327, 329, 330, 332ないし 335, 338ないし 344, 352, 357, 367ないし 373, 378, 386, 390, 391,及び 401  Compound number: 267, 272, 273, 280, 281, 302 to 306, 310, 312 to 316, 318 or 320, 325 to 327, 329, 330, 332 to 335, 338 to 344, 352, 357, 367 Or 373, 378, 386, 390, 391, and 401
上記 Gii)に該当する化合物としては、好ましくは、  As the compound corresponding to the above Gii), preferably,
A力 置換基を有していてもよいイソインドリン- 2-ィル基、置換基を有していてもよい 1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、置換基を有していてもよい 1,2-ジヒドロイソ キノリン- 2-ィル基及び置換基を有していてもよい 1,2,3,4-テトラヒドロキナゾリン- 3-ィ ル基からなる群から選択される基であり；  A force Isoindoline-2-yl group which may have a substituent, 1,2,3,4-tetrahydroisoquinolin-2-yl group which may have a substituent, Selected from the group consisting of an optionally substituted 1,2-dihydroisoquinolin-2-yl group and an optionally substituted 1,2,3,4-tetrahydroquinazoline-3-yl group Group;
Yカ N=CH—であり；  Y = N—CH—
Bが置換基を有して 、てもよ 、ビラゾリル基である化合物である。  A compound in which B has a substituent and may be a virazolyl group.
[0047] 更に好ましくは、 A力 下記環群 α -3-1から選択される基であり； [0047] More preferably, A group is a group selected from the following ring group α-3-1;
Υカ N=CH—であり；  Υka N = CH—;
Bが、 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよい  B is a C-C alkyl group which may have a substituent at the 1-position, and may have a substituent
1 6  1 6
C -C ァリール基、又は置換基を有していてもよい C -C ァラルキル基であり、 3位が A C -C aryl group or a C -C aralkyl group which may have a substituent, wherein the 3-position is
6 10 7 12 6 10 7 12
置換基を有していてもよい C - Cアルキル基であり、 5位がヒドロキシ基であるピラゾー  A pyrazole having an optionally substituted C-C alkyl group, wherein the 5-position is a hydroxy group
1 6  1 6
ル -4-ィル基；  Le-4-yl group;
である化合物である。  Is a compound.
[環群 α - 3-1] 1,3-ジォキソイソインドリン- 2-ィル基、 3-ヒドロキシ- 1-ォキソイソインド リン- 2-ィル基、 1-ォキソイソインドリン- 2-ィル基、 1,3-ジォキソ- 1,2,3,4-テトラヒドロイ ソキノリン- 2-ィル基、 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 3-ヒドロキ シ- 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 1-ォキソ -1,2-ジヒドロイソキノ リン- 2-ィル基、 4-ォキソ -1,2,3,4-テトラヒドロキナゾリン- 3-ィル基  [Ring group α-3-1] 1,3-Dioxoisoindoline-2-yl group, 3-hydroxy-1-oxoisoindoline-2-yl group, 1-oxoisoindoline-2-yl 1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 3- Hydroxy-1-oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2-dihydroisoquinolin-2-yl group, 4-oxo-1,2 , 3,4-tetrahydroquinazoline-3-yl group
このとき、 Βの好ましい具体例として、下記環群 j8 -2-6から選択される基を挙げること ができる。 At this time, preferred specific examples of Β include groups selected from the following ring group j8-2-6 Can do.
[環群 β -2-6] 1-フエ-ル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3- トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-トリフルォロメチ ル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-ェチル -5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-ペンタフルォロェチル -5-ヒドロキシピラゾール -4-ィル基、 1-ベンジル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-フルオロフェ-ル )-3- メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(2-メチルフエ-ル) -3-メチル -5-ヒドロキ シピラゾール -4-ィル基、 1-フエ-ル -3-(3-カルボキシプロピル)- 5-ヒドロキシピラゾー ル -4-ィル基  [Ring group β-2-6] 1-phenyl-3-methyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl Group, 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-ethyl-5-hydroxypyrazol-4-yl group, 1-phenyl -3-pentafluoroethyl-5-hydroxypyrazole-4-yl group, 1-benzyl-3-methyl-5-hydroxypyrazole-4-yl group, 1- (4-fluorophenyl) -3 -Methyl-5-hydroxypyrazole-4-yl group, 1- (2-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3- (3- (Carboxypropyl) -5-hydroxypyrazole-4-yl group
上記 (iii)に該当する化合物としては、特に更に好ましくは、本明細書に記載された下 記化合物番号で表される化合物力 なる群力 選択される化合物である。 The compound corresponding to the above (iii) is more preferably a compound selected from the group consisting of the following compound numbers described in the present specification.
•化合物番号: 359, 360, 364ないし 366, 375ないし 377, 379ないし 385, 388, 389, 392 ないし 400, 405,及び 406 Compound number: 359, 360, 364 to 366, 375 to 377, 379 to 385, 388, 389, 392 to 400, 405, and 406
本明細書において、アルコキシカルボ二ル基を構成する炭素原子の個数は、アル キル部分を構成する炭素原子とカルボニル部分を構成する炭素原子の総数として表 す。例えば、 Cアルコキシカルボ-ル基はメトキシカルボ-ル基を表し、 Cアルコキシ  In the present specification, the number of carbon atoms constituting an alkoxycarbonyl group is expressed as the total number of carbon atoms constituting an alkyl moiety and carbon atoms constituting a carbonyl moiety. For example, a C alkoxycarb group represents a methoxycarb group, and a C alkoxy
2 7 カルボ-ル基は n-へキシルォキシカルボ-ル基、（1-メチルペンチル)ォキシカルボ- ル基、シクロへキシルォキシカルボ-ル基、シクロペンチルメトキシカルボ-ル基など を表す。 The 27 carboxy group represents an n- hexyloxycarbyl group, a (1-methylpentyl) oxycarbol group, a cyclohexyloxycarbol group, a cyclopentylmethoxycarboxy group or the like.
一般式 (I)で表される化合物としては、下記一般式 (1-1):  As the compound represented by the general formula (I), the following general formula (1-1):
[化 4]  [Formula 4]
Figure imgf000035_0001
Figure imgf000035_0001
[式中、 Xは式- N=C(R5)- (式中、左側の結合手がベンゼン環に結合し、右側の結合 手が窒素原子に結合する)、又は式- NH-CH(R5)- (式中、左側の結合手がベンゼン 環に結合し、右側の結合手が窒素原子に結合する)を表し；
Figure imgf000035_0002
R3及び R4はそれ ぞれ独立して水素原子、ハロゲン原子、置換基を有していてもよい C - Cアルキル基 、又は置換基を有していてもよいヒドロキシ基を表し； R5は置換基を有していてもよい C - Cアルキル基、又は置換基を有していてもよい C - C ァリール基を表し； Rは置換Wherein, X is the formula - N = C (R 5) - ( wherein the left bond is attached to the benzene ring, right bond is attached to the nitrogen atom), or the formula - NH-CH ( R 5 )-(where the left hand is bonded to the benzene ring and the right hand is bonded to the nitrogen atom);
Figure imgf000035_0002
R 3 and R 4 are each independently a hydrogen atom, a halogen atom, and a C -C alkyl group which may have a substituent. Or a hydroxy group which may have a substituent; R 5 represents a C -C alkyl group which may have a substituent, or a C -C aryl group which may have a substituent Represents; R is substituted
1 6 6 10 1 6 6 10
基を有して 、てもよ 、アミノ基を表す]で表される化合物は除く。  Having a group, and which represents an amino group].
[0049] 好ましくは、上記一般式 (1-1):  [0049] Preferably, the above general formula (1-1):
[式中、 Xは式- N=C(R5)- (式中、左側の結合手がベンゼン環に結合し、右側の結合手 が窒素原子に結合する)、又は式- NH-CH(R5)- (式中、左側の結合手がベンゼン環に 結合し、右側の結合手が窒素原子に結合する)を表し；
Figure imgf000036_0001
R3及び R4はそれぞれ 独立して水素原子又は任意の置換基を表し； R5は水素原子又は任意の置換基を表 し； Rは置換基を有していてもよいアミノ基を表す]で表される化合物は除く。 Wherein, X is the formula - N = C (R 5) - ( wherein the left bond is attached to the benzene ring, right bond is attached to the nitrogen atom), or the formula - NH-CH ( R 5 )-(where the bond on the left is bonded to the benzene ring and the bond on the right is bonded to the nitrogen atom);
Figure imgf000036_0001
R 3 and R 4 each independently represent a hydrogen atom or an optional substituent; R 5 represents a hydrogen atom or an optional substituent; R represents an amino group which may have a substituent] The compounds represented by are excluded.
一般式 (Π)において、 ΥΩΐは- CH=N -、 - N=CH -、 - CONH-又は- NHCO-を表す。好 ましくは- CH=N -又は- N=CH-である。 In the general formula (Π), ΥΩΐ represents —CH = N—, —N = CH—, —CONH—, or —NHCO—. Preferably, -CH = N- or -N = CH-.
ΑΩΐ及び ΒΩΐはそれぞれ独立して置換基を有して 、てもよ 、炭化水素環基又は置 換基を有して 、てもよ 、ヘテロ環基を表す。 {Ω} and {Ω} each independently have a substituent, may have a hydrocarbon ring group or a substituent, and may represent a heterocyclic group.
[0050] ΑΩΙで表される置換基を有して 、てもよ 、炭化水素環基は、好ましくは置換基を有 していてもよい C -C ァリール基であり、更に好ましくはヒドロキシ置換 C -C ァリール [0050] The hydrocarbon ring group, which may have a substituent represented by {Ω} , is preferably a C -C aryl group which may have a substituent, and is more preferably a hydroxy-substituted group. C-C reel
6 10 6 10 基 (該ァリール基はヒドロキシ基のほかに更に置換基を有していてもよい)であり、特に 更に好ましくはヒドロキシ置換ナフチル基 (該ナフチル基はヒドロキシ基のほかに更に 置換基を有して 、てもよ 、；)である。  6 10 6 10 groups (the aryl group may further have a substituent in addition to the hydroxy group), particularly preferably a hydroxy-substituted naphthyl group (the naphthyl group is a hydroxy group and a further substituent group). And may be;)).
ΑΩΙで表される置換基を有して 、てもよ 、炭化水素環基力 Sヒドロキシ置換ナフチル 基 (該ナフチル基はヒドロキシ基のほかに更に置換基を有して 、てもよ 、；)である場合 、好ましい具体例として、下記環群ひ 1Q1-i-iから選択される基を挙げることができる。 A hydrocarbon ring group having a substituent represented by {Ω} , or an S-hydroxy-substituted naphthyl group (the naphthyl group may further have a substituent in addition to the hydroxy group; )), Preferred specific examples include groups selected from the following ring group 1Q1- ii.
[環群 oc 101-1-1] 5-ヒドロキシ- 2-ナフチル基、 3-ヒドロキシ- 2-ナフチル基、 1-ヒドロキ シ- 2-ナフチル基、 4-ヒドロキシ -3-メチル -1-ナフチル基、 5-ヒドロキシ -7-スルホ -2- ナフチル基、 6-スルホ -8-ヒドロキシ- 2-ナフチル基、 5-ヒドロキシ- 1-ナフチル基、 7- ヒドロキシ- 1-ナフチル基、 4-ヒドロキシ- 1-ナフチル基、 6-ヒドロキシ- 1-ナフチル基、 2-ヒドロキシ- 1-ナフチル基 [Ring group oc 101 -1-1] 5-hydroxy-2-naphthyl group, 3-hydroxy-2-naphthyl group, 1-hydroxy-2-naphthyl group, 4-hydroxy-3-methyl-1-naphthyl group , 5-hydroxy-7-sulfo-2-naphthyl, 6-sulfo-8-hydroxy-2-naphthyl, 5-hydroxy-1-naphthyl, 7-hydroxy-1-naphthyl, 4-hydroxy-1 -Naphthyl, 6-hydroxy-1-naphthyl, 2-hydroxy-1-naphthyl
[0051] ΑΩΙで表される置換基を有していてもよい炭化水素環基は、最も好ましくは 1-ヒドロ キシ -2-ナフチル基である。 A で表される置換基を有して 、てもよ 、ヘテロ環基は、好ましくは置換基を有して V、てもよ 、6な!、し 13員のへテロアリール基、或!、は置換基を有して 、てもよ 、9又は 10員の部分飽和へテロ環基である。 [0051] The optionally substituted hydrocarbon ring group represented by {Ω} is most preferably a 1-hydroxy-2-naphthyl group. Having a substituent represented by A, the heterocyclic group is preferably V having a substituent, or 6 or !!, or a 13-membered heteroaryl group, or! Is a 9- or 10-membered partially saturated heterocyclic group having a substituent.
A1Q1で表される置換基を有して 、てもよ 、ヘテロ環基が置換基を有して 、てもよ 、6 ないし 13員のへテロアリール基である場合、好ましくはヒドロキシ基で置換された 6な いし 10員のへテロアリール基 (該ヘテロァリール基はヒドロキシ基のほかに更に置換基 を有していてもよい)であり、更に好ましくはヒドロキシ置換キノリル基 (該キノリル基はヒ ドロキシ基のほかに更に置換基を有していてもよい)であり、特に更に好ましくは、 4-ヒ ドロキシ- 3-キノリル基 (該キノリル基はヒドロキシ基のほかに更に置換基を有していて ちょい)である。 A When the heterocyclic group having a substituent represented by 1Q1 or a heterocyclic group having a substituent is a 6- to 13-membered heteroaryl group, it is preferably substituted with a hydroxy group. A 6- or 10-membered heteroaryl group (the heteroaryl group may have a substituent in addition to the hydroxy group), and more preferably a hydroxy-substituted quinolyl group (the quinolyl group is a hydroxy group And further preferably a 4-hydroxy-3-quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group). ).
Αωιで表される置換基を有して 、てもよ 、ヘテロ環基が置換基を有して 、てもよ 、6 ないし 13員のへテロアリール基である場合、該 6ないし 13員のへテロアリール基は、好 ましくはキノリル基、インドリル基、インダゾリル基、ベンゾチアゾリル基、ベンズォキサ ゾリル基、カルバゾリル基、ピリジル基、キノキサリニル基及びジベンゾフラニル基から なる群から選択される基である。 When the heterocyclic group has a substituent represented by ωωι or may be a 6- or 13-membered heteroaryl group having a substituent or may be a 6- or 13-membered heteroaryl group, The heteroaryl group is preferably a group selected from the group consisting of quinolyl, indolyl, indazolyl, benzothiazolyl, benzoxazolyl, carbazolyl, pyridyl, quinoxalinyl and dibenzofuranyl groups.
Αωιで表される置換基を有して 、てもよ 、ヘテロ環基力 Sヒドロキシ基で置換された 6 ないし 10員のへテロアリール基 (該ヘテロァリール基はヒドロキシ基のほかに更に置換 基を有していてもよい)である場合、該 6ないし 10員のへテロアリール基は、好ましくは キノリル基又はピリジル基である。 A 6- to 10-membered heteroaryl group substituted with an S-hydroxy group having a substituent represented by ωι (the heteroaryl group may further have a substituent in addition to the hydroxy group) The 6- to 10-membered heteroaryl group is preferably a quinolyl group or a pyridyl group.
Αωιで表される置換基を有して 、てもよ 、ヘテロ環基力 Sヒドロキシ置換キノリル基 (該 キノリル基はヒドロキシ基のほかに更に置換基を有して 、てもよ 、；)である場合、好まし い具体例として、下記環群 ex 1Μ-2-1から選択される基を挙げることができる。 A heterocyclic group having a substituent represented by ωωι , or an S-hydroxy-substituted quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group; In this case, preferred specific examples include groups selected from the following ring group ex 1 ex -2-1.
[環群 (X 101-2-1] 8-ヒドロキシ -2-キノリル基、 4-ヒドロキシ -2-キノリル基、 7-クロ口- 4-ヒ ドロキシキノリン- 3-ィル基、 4-ヒドロキシ -7- (トリフルォロメチル)キノリン- 3-ィル基、 2,4-ジヒドロキシ- 3-キノリル基、 4-ヒドロキシ -2- (トリフルォロメチル)キノリン- 3-ィル基 、 4-ヒドロキシ- 3-キノリル基、 4-ヒドロキシ -2-メチルキノリン- 3-ィル基、 2-ェチル -4- ヒドロキシキノリン- 3-ィル基、 4-ヒドロキシ -2- (ペンタフルォロェチル)キノリン- 3-ィル 基、 7-フルォロ- 4-ヒドロキシキノリン- 3-ィル基、 6-フルォロ- 4-ヒドロキシキノリン- 3-ィ ル基、 4-ヒドロキシ -8-メチルキノリン- 3-ィル基、 6,7-ジフルォロ- 4-ヒドロキシキノリン -3-ィル基、 4-ヒドロキシ -7-メチルキノリン- 3-ィル基、 4-ヒドロキシ -6-メチルキノリン -3-ィル基、 4-ヒドロキシ -8-メトキシキノリン- 3-ィル基、 4-ヒドロキシ -6-メトキシキノリン -3-ィル基、 6-クロ口- 4-ヒドロキシキノリン- 3-ィル基、 6,7-ジメトキシ- 4-ヒドロキシキノ リン- 3-ィル基 [Ring group (X 101 -2-1) 8-hydroxy-2-quinolyl group, 4-hydroxy-2-quinolyl group, 7-chloro-4--4-hydroxyquinolin-3-yl group, 4-hydroxy -7- (trifluoromethyl) quinolin-3-yl group, 2,4-dihydroxy-3-quinolyl group, 4-hydroxy-2- (trifluoromethyl) quinolin-3-yl group, 4- Hydroxy-3-quinolyl, 4-hydroxy-2-methylquinolin-3-yl, 2-ethyl-4-hydroxyquinolin-3-yl, 4-hydroxy-2- (pentafluoroethyl) Quinoline-3-yl group, 7-fluoro-4-hydroxyquinoline-3-yl group, 6-fluoro-4-hydroxyquinoline-3-y 4-hydroxy-8-methylquinolin-3-yl group, 6,7-difluoro-4-hydroxyquinolin-3-yl group, 4-hydroxy-7-methylquinolin-3-yl group, 4-hydroxy-6-methylquinolin-3-yl group, 4-hydroxy-8-methoxyquinolin-3-yl group, 4-hydroxy-6-methoxyquinolin-3-yl group, 6-chloro- 4-hydroxyquinoline-3-yl group, 6,7-dimethoxy-4-hydroxyquinoline-3-yl group
[0053] Αωιで表される置換基を有して 、てもよ 、ヘテロ環基が 4-ヒドロキシ -3-キノリル基（ 該キノリル基はヒドロキシ基のほかに更に置換基を有して 、てもよ 、；)である場合、好 まし 、具体例として、下記環群 ex 1Μ-2-2から選択される基を挙げることができる。 The heterocyclic group may have a substituent represented by ωωι , and the heterocyclic group may be a 4-hydroxy-3-quinolyl group (the quinolyl group may have a substituent in addition to the hydroxy group, Or ;), a specific example is preferably a group selected from the following ring group ex 1Μ- 2-2.
[環群 (X 101-2-2] 7-クロ口- 4-ヒドロキシキノリン- 3-ィル基、 4-ヒドロキシ- 7- (トリフルォ ロメチル)キノリン- 3-ィル基、 2,4-ジヒドロキシ- 3-キノリル基、 4-ヒドロキシ -2- (トリフル ォロメチル)キノリン- 3-ィル基、 4-ヒドロキシ- 3-キノリル基、 4-ヒドロキシ -2-メチルキノ リン- 3-ィル基、 2-ェチル -4-ヒドロキシキノリン- 3-ィル基、 4-ヒドロキシ -2- (ペンタフル ォロェチル)キノリン- 3-ィル基、 7-フルォロ- 4-ヒドロキシキノリン- 3-ィル基、 6-フルォ 口- 4-ヒドロキシキノリン- 3-ィル基、 4-ヒドロキシ -8-メチルキノリン- 3-ィル基、 6,7-ジフ ルォ口- 4-ヒドロキシキノリン- 3-ィル基、 4-ヒドロキシ -7-メチルキノリン- 3-ィル基、 4-ヒ ドロキシ -6-メチルキノリン- 3-ィル基、 4-ヒドロキシ -8-メトキシキノリン- 3-ィル基、 4-ヒ ドロキシ -6-メトキシキノリン- 3-ィル基、 6-クロ口- 4-ヒドロキシキノリン- 3-ィル基、 6,7- ジメトキシ -4-ヒドロキシキノリン- 3-ィル基 [Ring group (X 101 -2-2) 7-chloro-4-Hydroxyquinolin-3-yl group, 4-hydroxy-7- (trifluoromethyl) quinolin-3-yl group, 2,4-dihydroxy -3-quinolyl group, 4-hydroxy-2- (trifluoromethyl) quinolin-3-yl group, 4-hydroxy-3-quinolyl group, 4-hydroxy-2-methylquinolin-3-yl group, 2- Ethyl-4-hydroxyquinolin-3-yl group, 4-hydroxy-2- (pentafluoroethyl) quinolin-3-yl group, 7-fluoro-4-hydroxyquinolin-3-yl group, 6-fluoro mouth -4-hydroxyquinoline-3-yl group, 4-hydroxy-8-methylquinoline-3-yl group, 6,7-difluoro mouth-4-hydroxyquinoline-3-yl group, 4-hydroxy- 7-methylquinoline-3-yl group, 4-hydroxy-6-methylquinoline-3-yl group, 4-hydroxy-8-methoxyquinolin-3-yl group, 4-hydroxy-6-methoxyoxy group Norin-3-yl group, 6-chloro-4-Hydroxyquinolin-3-yl group, 6,7-dimethoxy-4-hydroxyquinolin-3-yl group
[0054] Αωιで表される置換基を有して 、てもよ 、ヘテロ環基が置換基を有して 、てもよ 、9 又は 10員の部分飽和へテロ環基である場合、更に好ましくは、 1又は 2個の窒素原子 を環構成原子として含有する 9又は 10員の部分飽和へテロ環基 (該部分飽和へテロ 環基は置換基を有していてもよぐ Y1Mとの結合位置は環構成原子である窒素原子の 位置である)であり、特に更に好ましくは、置換基を有していてもよいイソインドリン- 2- ィル基、置換基を有していてもよい 1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、置換基 を有して!/、てもよい 1,2-ジヒドロイソキノリン- 2-ィル基及び置換基を有して!/、てもよ!/ヽ 1,2,3,4-テトラヒドロキナゾリン- 3-ィル基力もなる群力も選択される基である。 When a heterocyclic group having a substituent represented by ωωι or a heterocyclic group having a substituent is a 9- or 10-membered partially saturated heterocyclic group, More preferably, a 9- or 10-membered partially saturated heterocyclic group containing one or two nitrogen atoms as a ring-constituting atom (the partially saturated heterocyclic group may have a substituent Y 1M Is the position of the nitrogen atom which is a ring-constituting atom), and more preferably an isoindoline-2-yl group which may have a substituent, 1,2,3,4-tetrahydroisoquinolin-2-yl group having a substituent! / Or 1,2-dihydroisoquinolin-2-yl group and having a substituent ! /, It may be! / ヽ 1,2,3,4-tetrahydroquinazoline-3-yl is a group from which the group power and the group power are also selected.
Αωιで表される置換基を有して 、てもよ 、ヘテロ環基力 置換基を有して 、てもよ ヽ イソインドリン- 2-ィル基、置換基を有していてもよい 1,2,3,4-テトラヒドロイソキノリン -2-ィル基、置換基を有して!/、てもよい 1,2-ジヒドロイソキノリン- 2-ィル基及び置換基 を有していてもよい 1,2,3,4-テトラヒドロキナゾリン- 3-ィル基力もなる群力も選択される 基である場合、好ましい具体例として、下記環群 a 1Q1-3-lから選択される基を挙げる ことができる。 May have a substituent represented by ωι , may have a heterocyclic group, may have a substituent, may have an isoindoline-2-yl group, may have a substituent 1,2,3,4-tetrahydroisoquinoline 2-yl group, may have a substituent! /, May be 1,2-dihydroisoquinolin-2-yl group and may have a substituent, 1,2,3,4-tetrahydro In the case where the quinazoline-3- yl group and the group strength are also selected, preferred specific examples include a group selected from the following ring group a 1Q1-3 -l.
[環群 。1- 3-1] 1,3-ジォキソイソインドリン- 2-ィル基、 3-ヒドロキシ- 1-ォキソイソイン ドリン- 2-ィル基、 1-ォキソイソインドリン- 2-ィル基、 1,3-ジォキソ- 1,2,3,4-テトラヒドロ イソキノリン- 2-ィル基、 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 3-ヒドロキ シ- 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 1-ォキソ -1,2-ジヒドロイソキノ リン- 2-ィル基、 4-ォキソ -1,2,3,4-テトラヒドロキナゾリン- 3-ィル基 [Ring group. 1 - 3-1] 1,3-O Kiso isoindoline - 2 I group, 3-hydroxy - 1-Okisoisoin Dorin - 2 I group, 1-O Kiso isoindoline - 2 I group, 1,3-Dioxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 3-hydroxy-1 -Oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2-dihydroisoquinolin-2-yl group, 4-oxo-1,2,3,4 -Tetrahydroquinazoline-3-yl group
B1Q1で表される置換基を有して 、てもよ 、炭化水素環基は、好ましくは置換基を有し ていてもよい C - C ァリール基である。 The hydrocarbon ring group which may have a substituent represented by B1Q1 is preferably a C-Caryl group which may have a substituent.
6 10  6 10
[0055] Βωΐで表される置換基を有して 、てもよ 、炭化水素環基が置換基を有して 、てもよ いじ -C ァリール基である場合、好ましい具体例として、下記環群 13 ωΐ-ト 1から選択[0055] When a hydrocarbon group having a substituent represented by {ω} or a hydrocarbon ring group having a substituent is a -C aryl group, preferred specific examples are as follows. Ring group 13 ωΐ- select from 1
6 10 6 10
される基を挙げることができる。  Groups that can be mentioned.
[環群 j8 1M- 1- 1] 3- [(4,6-ジクロロ- 1,3,5-トリァジン- 2-ィル)ァミノ]フエ-ル基、 3-ヒドロ キシ -4-メチルフエ-ル基、 3- (カルボキシメチル)フエ-ル基、 5-ヒドロキシ- 2-ナフチ ル基、 2-フルォロ- 6-(1-イミダゾリル)フエ-ル基、 2-ピペリジノ -5- (トリフルォロメチル） フエ-ル基、 3-ヒドロキシフエ-ル基、 4-ヒドロキシ -3-メチルフエ-ル基、 4-メチルフエ -ル基、 4-ヒドロキシフエ-ル基、 4-ヒドロキシビフエ-ル- 3-ィル基、 9-ォキソフルォ レン- 3-ィル基、 4-メトキシフエ-ル基、 4-フエノキシフエ-ル基、 4-スルファモイルフエ -ル基、 4-カルボキシフヱ-ル基、 2-ヒドロキシフヱ-ル基、 3--トロフヱ-ル基 [Ring group j8 1M -1-1] 3-[(4,6-dichloro-1,3,5-triazin-2-yl) amino] phenyl group, 3-hydroxy-4-methylphenyl Group, 3- (carboxymethyl) phenyl, 5-hydroxy-2-naphthyl, 2-fluoro-6- (1-imidazolyl) phenyl, 2-piperidino-5- (trifluoromethyl ) Phenol, 3-hydroxyphenyl, 4-hydroxy-3-methylphenyl, 4-methylphenyl, 4-hydroxyphenyl, 4-hydroxybiphenyl-3- , 9-oxofluorene-3-yl, 4-methoxyphenyl, 4-phenoxyphenyl, 4-sulfamoylphenyl, 4-carboxyphenyl, 2-hydroxyphenyl Group, 3--trophyl group
B1Q1で表される置換基を有して 、てもよ 、ヘテロ環基は、好ましくは置換基を有して ヽ てもよ 、5な!、し 13員のへテロアリール基、或いは置換基を有して 、てもよ 、5な!、し 10員の部分飽和へテロ環基である。 The heterocyclic group having a substituent represented by B 1Q1 or a heterocyclic group is preferably a 5- or 13-membered heteroaryl group, or a substituent. A 5- or 10-membered partially saturated heterocyclic group.
[0056] B1Q1で表される置換基を有して 、てもよ 、ヘテロ環基が置換基を有して 、てもよ 、5 ないし 13員のへテロアリール基である場合、好ましくは 5員のへテロアリール基であり 、更に好ましくは置換基を有していてもよいピラゾリル基であり、特に更に好ましくは、 (A) 1位が水素原子、置換基を有していてもよい C - Cアルキル基、置換基を有してい てもよい C - C ァリール基、置換基を有していてもよい C -C ァラルキル基、又は置When a heterocyclic group having a substituent represented by B 1Q1 or a heterocyclic group having a substituent is a 5- or 13-membered heteroaryl group, preferably 5 Membered heteroaryl group, more preferably a pyrazolyl group optionally having a substituent, particularly preferably (A) hydrogen atom at the 1-position, optionally substituted C- C having an alkyl group and a substituent A C -C aryl group, an optionally substituted C -C aralkyl group, or
6 10 7 12 6 10 7 12
換基を有して 、てもよ 、9員のへテロアリール基であり； 3位が置換基を有して 、てもよ い C - Cアルキル基、又は置換基を有していてもよい C - C ァリール基であり； 5位がA 9-membered heteroaryl group, which may have a substituent; or a C-C alkyl group, which may have a substituent at the 3-position, or may have a substituent. C-C aryl group; 5th place
1 6 6 10 1 6 6 10
ヒドロキシ基であるピラゾール -4-ィル基； A pyrazole-4-yl group which is a hydroxy group;
(B) 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよい C  (B) C 1 -C alkyl group optionally having a substituent at position 1, C optionally having a substituent
1 6 6 1 6 6
- C ァリール基、置換基を有していてもよい C -C ァラルキル基、又は置換基を有し-A C aryl group, an optionally substituted C -C aralkyl group, or a substituted
10 7 12 10 7 12
ていてもよい C - Cアルコキシカルボ-ル基であり； 3位が水素原子、置換基を有して An optionally substituted C -C alkoxycarbonyl group; having a hydrogen atom at the 3-position and a substituent
2 7  2 7
いてもよい C - Cアルキル基、又は置換基を有していてもよい C - C ァリール基であり An optionally substituted C-C alkyl group or an optionally substituted C-C aryl group
1 6 6 10  1 6 6 10
； 4位が水素原子又は置換基を有していてもよい C - Cアルコキシカルボ-ル基であ  A 4-position is a hydrogen atom or a C-C alkoxycarboyl group which may have a substituent;
2 7  2 7
るピラゾール -5-ィル基；或いは Pyrazole-5-yl group; or
(C) 1位が水素原子又は置換基を有していてもよい C - C ァリール基であり； 4位が水  (C) position 1 is a hydrogen atom or a C -C aryl group which may have a substituent; position 4 is water
6 10  6 10
素原子であり； 5位が置換基を有していてもよい C - Cアルキル基、置換基を有してい A C-C alkyl group which may have a substituent at the 5-position, having a substituent
1 6  1 6
てもよい C - C ァリール基、又はヒドロキシ基であるピラゾール -3-ィル基 C-Caryl group or pyrazole-3-yl group which is a hydroxy group
6 10  6 10
である。 It is.
Βωΐで表される置換基を有して 、てもよ 、ヘテロ環基が置換基を有して 、てもよ 、5 ないし 13員のへテロアリール基である場合、該 5ないし 13員のへテロアリール基は、好 ましくはピラゾリル基、カルバゾリル基、インドリル基、ベンズイミダゾリル基、テトラゾリ ル基、ピリジル基、キノリル基、チアゾリル基、ベンゾチアゾリル基、インダゾリル基、チ ェニル基、ベンゾチオフヱ-ル基、フリル基及びべンゾフラ-ル基からなる群から選 択される基である。 When the heterocyclic group has a substituent represented by Βωΐ or is a 5- or 13-membered heteroaryl group, and the heterocyclic group is a 5- or 13-membered heteroaryl group, A heteroaryl group is preferably a pyrazolyl group, a carbazolyl group, an indolyl group, a benzimidazolyl group, a tetrazolyl group, a pyridyl group, a quinolyl group, a thiazolyl group, a benzothiazolyl group, an indazolyl group, a thienyl group, a benzothiopropyl group, This group is selected from the group consisting of a furyl group and a benzofural group.
B1Q1で表される置換基を有して 、てもよ 、ヘテロ環基が、 Having a substituent represented by B 1Q1 , and optionally a heterocyclic group,
(A) 1位が水素原子、置換基を有していてもよい C - Cアルキル基、置換基を有してい (A) 1-position has a hydrogen atom, a C-C alkyl group which may have a substituent, and a substituent
1 6  1 6
てもよい C - C ァリール基、置換基を有していてもよい C -C ァラルキル基、又は置 A C -C aryl group, an optionally substituted C -C aralkyl group, or
6 10 7 12  6 10 7 12
換基を有して 、てもよ 、9員のへテロアリール基であり； 3位が置換基を有して 、てもよ い C - Cアルキル基、又は置換基を有していてもよい C - C ァリール基であり； 5位がA 9-membered heteroaryl group, which may have a substituent; or a C-C alkyl group, which may have a substituent at the 3-position, or may have a substituent. C-C aryl group; 5th place
1 6 6 10 1 6 6 10
ヒドロキシ基であるピラゾール -4-ィル基 Pyrazol-4-yl group which is a hydroxy group
である場合、好ましい具体例として、下記環群 ι8 1()1-2-1から選択される基を挙げるこ とがでさる。 [環群 β -2-1] 1-フエ-ル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ルIn the case of, preferred specific examples include a group selected from the following ring group ι81 () 1-2-1. [Ring group β-2-1] 1-phenyl-3-methyl-5-hydroxypyrazole-4-yl group, 1-phenyl
- 3-(tert-ブチル )- 5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-フエ-ル- 5-ヒドロ キシピラゾール -4-ィル基、 1-(4-メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール-3- (tert-butyl) -5-hydroxypyrazole-4-yl group, 1-methyl-3-phenyl-5-hydroxypyrazole-4-yl group, 1- (4-methylphenyl ) -3-Methyl-5-hydroxypyrazole
-4-ィル基、 1-フエ-ル- 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1- フエ-ル- 3-ェチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-クロ口フエ-ル) -3-メチ ル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-クロ口フエ-ル) -3-メチル -5-ヒドロキシピ ラゾール -4-ィル基、 1-(2-クロ口フエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル 基、 1-(4-メトキシフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-メチル フエ-ル)- 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-ぺ ンタフルォロェチル- 5-ヒドロキシピラゾール -4-ィル基、 1-ベンジル- 3-トリフルォロメ チル- 5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-トリフルォロメチル- 5-ヒドロキシ ピラゾール -4-ィル基、 1-ベンジル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、-4-yl group, 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-ethyl-5-hydroxypyrazole-4-yl Group, 1- (4-chlorophenol) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3-chlorophenol) -3-methyl-5-hydroxypyr Lazol-4-yl group, 1- (2-chlorophenol) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (4-methoxyphenyl) -3-methyl-5 -Hydroxypyrazole-4-yl group, 1- (4-methylphenyl) -3- 3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-pentafluoro Oloethyl-5-hydroxypyrazole-4-yl group, 1-benzyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-trifluoromethyl-5-hydroxypyrazole -4-yl group, 1-benzyl-3-methyl-5-hydroxypyra Lumpur-4-I group,
1-(4-フルオロフェ-ル )-3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-[4- (トリフル ォロメチル)フエ-ル] -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3-フルオロフェ1- (4-fluorophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- [4- (trifluoromethyl) phenyl] -3-methyl-5-hydroxypyrazole-4- Yl group, 1- (3-fluorophen
-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3,5-ジクロロフエ-ル) -3-メチ ル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3,4-ジクロロフエ-ル) -3-メチル - 5-ヒドロキ シピラゾール -4-ィル基、 1-(2-メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4- ィル基、 1-(2,4-ジクロロフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3- メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-カルボキシフエ- ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-[3,5-ビス (トリフルォロメチル)フエ-Yl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3,5-dichlorophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- ( 3,4-dichlorophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1 -(2,4-dichlorophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group , 1- (4-carboxyphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- [3,5-bis (trifluoromethyl) phenyl
-ル] -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(2-フルオロフェ-ル )-3-メチル-Le] -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-fluorophenyl) -3-methyl
-5-ヒドロキシピラゾール -4-ィル基、 1-(4-メトキシフエ-ル) -3-トリフルォロメチル -5- ヒドロキシピラゾール- 4-ィル基、 1- (4-フルオロフェ-ル )-3-トリフルォロメチル- 5-ヒド 口キシピラゾール -4-ィル基、 1-(3,5-ジクロロフヱ-ル)- 3-トリフルォロメチル- 5-ヒドロ キシピラゾール -4-ィル基、 1-(2,4-ジクロロフヱ-ル)- 3-トリフルォロメチル- 5-ヒドロキ シピラゾール -4-ィル基、 1-(2-ヒドロキシェチル) -3-トリフルォロメチル- 5-ヒドロキシピ ラゾール- 4-ィル基、 1- (4-クロ口フエ-ル)- 3-トリフルォロメチル- 5-ヒドロキシピラゾー ル _4_ィル基、卜ェチル—3_トリフルォロメチル— 5_ヒドロキシピラゾール _4_ィル基、 l-(2,2,2-トリフルォロェチル) -3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基 、 1-(3-フルオロフェ-ル )-3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 l-(tert-ブチル )-3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-シクロへ キシル -3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 l-(n-ブチル )-3-トリ フルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-ヒドロキシベンジル) -3-トリフ ルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(4-カルボキシフエ-ル)- 3-トリフ ルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-カルボキシフヱ-ル)- 3-トリフ ルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-スルファモイルフエ-ル) -3-メ チル- 5-ヒドロキシピラゾール -4-ィル基、 1- (ベンゾチアゾール -2-ィル) -3-メチル -5- ヒドロキシピラゾール -4-ィル基、 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル 基、 1-メチル -3-メトキシカルボ-ルメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(4- ニトロフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1 ,3-ジメチル- 5-ヒドロキ シピラゾール -4-ィル基、 1-メチル -3-ェチル -5-ヒドロキシピラゾール -4-ィル基、 1-メ チル -3-メトキシメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-メチル - 3-(n-プロピル )-5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-(n-ブチル )-5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-[3- (エトキシカルボ-ル)プロピル]- 5-ヒドロキシピラゾール -4-ィル基、 1-ェチル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1, 3-ジェチル -5- ヒドロキシピラゾール -4-ィル基、 1-(2-ヒドロキシェチル) -3-メチル -5-ヒドロキシピラゾ ール -4-ィル基、 1-(2-ヒドロキシェチル) -3-ェチル -5-ヒドロキシピラゾール -4-ィル基 、 1-フエ-ル -3-メトキシカルボ-ルメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ -ル- 3-カルボキシメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-[3- (エト キシカルボ-ル)プロピル]- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル -3-(3-カル ボキシプロピル)- 5-ヒドロキシピラゾール -4-ィル基 -5-Hydroxypyrazol-4-yl group, 1- (4-methoxyphenyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (4-fluorophenyl)- 3-Trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3,5-dichloropropyl) -3- 3-trifluoromethyl-5-hydroxypyrazole-4-yl group , 1- (2,4-dichloropropyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (2-hydroxyethyl) -3-trifluoromethyl-5- hydroxypivalic Razoru - 4-I group, 1- (4-black port Hue - Le) - 3-triflate Ruo Russia methyl - 5-hydroxypyrazole Eaux Le _ 4 _ I group, Bok Echiru - 3 _ Torifuruoro methyl - 5 _ hydroxypyrazole _ 4 _ I group, l- (2,2,2-trifluoroethyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-fluorophenyl) -3-trifluoromethyl- 5-hydroxypyrazole-4-yl group, l- (tert-butyl) -3-trifluoromethyl- 5-hydroxypyrazole-4-yl group, 1-cyclohexyl-3-trifluoromethyl- 5-hydroxypyrazole-4-yl group, l- (n-butyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-hydroxybenzyl) -3-trifluoromethyl-5 -Hydroxypyrazole-4-yl group, 1- (4-carboxyphenyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-carboxyphenyl) -3-trif Fluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-sulfamoylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (benzothia -2-yl) -3-methyl-5-hydroxypyrazole-4-yl group, 3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-methoxycarbo -Methyl-5-hydroxypyrazole-4-yl group, 1- (4-nitrophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1,3-dimethyl-5-hydroxypyrazole- 4-yl group, 1-methyl-3-ethyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-methoxymethyl-5-hydroxypyrazole-4-yl group, 1-methyl- 3- (n-propyl) -5-hydroxypyrazole-4-yl group, 1-methyl-3- (n-butyl) -5-hydroxypyrazol-4-yl group, 1-methyl-3- [3 -(Ethoxycarbol) propyl] -5-hydroxypyrazole-4-yl group, 1-ethyl-3-methyl-5-hydroxypyrazole-4-yl group, 1,3-getyl-5-hydroxypyrazole -4-yl group 1- (2-hydroxyethyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-hydroxyethyl) -3-ethyl-5-hydroxypyrazole-4-yl Group, 1-phenyl-3-methoxycarbolmethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-carboxymethyl-5-hydroxypyrazole-4-yl group, 1 -Phenyl-3- [3- (ethoxycarbol) propyl] -5-hydroxypyrazole-4-yl group, 1-phenyl-3- (3-carboxypropyl) -5-hydroxypyrazole- 4-yl group
Βωιで表される置換基を有して 、てもよ 、ヘテロ環基が、 Having a substituent represented by ω ωι , the heterocyclic group may be
(Β) 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよい C  (Β) C 1 -C alkyl group optionally substituted at 1-position, C optionally substituted
1 6 6 1 6 6
- C ァリール基、置換基を有していてもよい C -C ァラルキル基、又は置換基を有し-A C aryl group, an optionally substituted C -C aralkyl group, or a substituted
10 7 12 10 7 12
ていてもよい C - Cアルコキシカルボニル基であり； 3位が水素原子、置換基を有して An optionally substituted C -C alkoxycarbonyl group; having a hydrogen atom at the 3-position and a substituent
2 7  2 7
いてもよい C - Cアルキル基、又は置換基を有していてもよい C - C ァリール基であり ； 4位が水素原子又は置換基を有していてもよい C - Cアルコキシカルボ-ル基であ An optionally substituted C-C alkyl group or an optionally substituted C-C aryl group A 4-position is a hydrogen atom or a C-C alkoxycarboyl group which may have a substituent;
2 7  2 7
るピラゾール -5-ィル基 Pyrazole-5-yl group
である場合、好ましい具体例として、下記環群 ι8 1()1-2-2から選択される基を挙げるこ とがでさる。 In the case of, preferred specific examples include a group selected from the following ring group ι81 () 1-2-2.
[環群 13 101-2-2] 1-(4-メチルフエ-ル) -3-メチルビラゾール -5-ィル基、 1-フエ-ルビ ラゾール _5_ィル基、 ジフエ-ルビラゾール _5_ィル基、卜フエ-ルー 4_ (エトキシカ ルポ-ル)ピラゾール -5-ィル基、 1-フエ-ル -3-メチルピラゾール -5-ィル基、 1-ェトキ シカルボ-ル- 3-フエ-ルビラゾール -5-ィル基、 1-フエ-ル- 3-(tert-ブチル)ピラゾ ール -5-ィル基、 1-(4-クロ口フエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-メトキシ フエ-ル) -3-メチルピラゾール -5-ィル基、 1-ベンジル -3-メチルピラゾール -5-ィル基 、 l-(tert-ブチル )- 3-フエ-ルビラゾール -5-ィル基、 1-[4- (トリフルォロメチル)フエ- ル] _3_メチルピラゾール _5_ィル基、 l-[4-(tert-ブチル)フエ-ル] -3-メチルピラゾー ル -5-ィル基、 1-(4-二トロフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(3-クロ口- 4-メ チルフエ-ル) -3-メチルビラゾール -5-ィル基、 1-(2-シァノエチル) -3-メチルビラゾー ル -5-ィル基、 1-(3,4-ジクロロフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(3-クロ口 フエ-ル) -3-メチルピラゾール -5-ィル基、 1-(2,4-ジクロロフエ-ル) -3-メチルピラゾ ール -5-ィル基、 1-(4-ブロモフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-フルォ 口フエ-ル) -3-メチルピラゾール -5-ィル基、 1-[4- (エトキシカルボ-ル)フエ-ル] -3- メチルピラゾール -5-ィル基、 1-(4-ヒドロキシフエ-ル) -3-メチルピラゾール -5-ィル基 、 1-(4-カルボキシフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-スルファモイルフエ -ル) -3-メチルピラゾール -5-ィル基、 1-(4-クロ口フエ-ル)- 3-(tert-ブチル)ピラゾー ル -5-ィル基、 1-メチル -3-フエ-ルビラゾール -5-ィル基 [Ring group 13 101 2-2] 1- (4-Mechirufue - Le) -3-methyl Vila-5 I group, 1-Hue - ruby Razoru _ 5 _ I group, Jifue - Rubirazoru _ 5 _____________________________________ Group, triphenyl 4 _ (ethoxy alcohol) pyrazole-5-yl group, 1-phenyl-3-methylpyrazole-5-yl group, 1-ethoxycarbol-3 -Phenylpyrazole-5-yl group, 1-phenyl-3- (tert-butyl) pyrazole-5-yl group, 1- (4-chlorophenol) -3-methylpyrazole -5-yl group, 1- (4-methoxyphenyl) -3-methylpyrazole-5-yl group, 1-benzyl-3-methylpyrazole-5-yl group, l- (tert-butyl )-3-Phenylpyrazole-5-yl group, 1- [4- (trifluoromethyl) phenyl] _3_methylpyrazole_5_yl group, l- [4- (tert-butyl) phenyl -Yl] -3-methylpyrazole-5-yl group, 1- (4-ditrophenyl) -3-methylpyrazole-5-yl group, 1- (3-chloro-4--4-methyl (Ethyl) -3-methylbiazol-5-yl group, 1- (2-cyanoethyl) -3-methylbiazol-5-yl group, 1- (3,4-dichlorophenyl) -3- Methylpyrazole-5-yl group, 1- (3-chlorophenol) -3-methylpyrazole-5-yl group, 1- (2,4-dichlorophenyl) -3-methylpyrazole- 5-yl group, 1- (4-bromophenyl) -3-methylpyrazole-5-yl group, 1- (4-fluorophenol) -3-methylpyrazole-5-yl group, 1- [4- (ethoxycarbol) phenyl] -3-methylpyrazole-5-yl group, 1- (4-hydroxyphenyl) -3-methylpyrazole-5-yl group, 1 -(4-carboxyphenyl) -3-methylpyrazole-5-yl group, 1- (4-sulfamoylphenyl) -3-methylpyrazole-5-yl group, 1- (4- 3- (tert-butyl) pyrazole-5-yl group, 1-methyl-3-phenylvirazol-5-yl group
Βωιで表される置換基を有して 、てもよ 、ヘテロ環基が、 Having a substituent represented by ω ωι , the heterocyclic group may be
(C) 1位が水素原子又は置換基を有していてもよい C - C ァリール基であり； 4位が水  (C) position 1 is a hydrogen atom or a C -C aryl group which may have a substituent; position 4 is water
6 10  6 10
素原子であり； 5位が置換基を有していてもよい C - Cアルキル基、置換基を有してい A C-C alkyl group which may have a substituent at the 5-position, having a substituent
1 6  1 6
てもよい C - C ァリール基、又はヒドロキシ基であるピラゾール -3-ィル基である場合、 When it is a C-C aryl group or a pyrazole-3-yl group which is a hydroxy group,
6 10  6 10
好ましい具体例として、下記環群 β 1Μ-2-3から選択される基を挙げることができる。 Preferred specific examples include groups selected from the following ring group β 1Μ- 2-3.
[環群 β 101-2-3] 1-フエ-ル- 5-ヒドロキシピラゾール -3-ィル基、 5-フエ-ルビラゾー ル -3-ィル基、 1-(3-クロ口- 4-メチルフエ-ル) -5-メチルピラゾール -3-ィル基、 1-フエ -ル -5-メチルピラゾール -3-ィル基、 1-(4-クロ口フエ-ル) -5-メチルピラゾール -3-ィ ル基、 1-(4-ブロモフエ-ル) -5-メチルピラゾール -3-ィル基、 1-(4-メチルフエ-ル )-5_メチルピラゾール _3_ィル基 [Ring group β 101 -2-3] 1-phenyl-5-hydroxypyrazole-3-yl group, 5-phenylazole Le-3-yl group, 1- (3-chloro-4-Methylphenyl) -5-methylpyrazole-3-yl group, 1-phenyl-5-methylpyrazole-3-yl group , 1- (4-chlorophenol) -5-methylpyrazole-3-yl group, 1- (4-bromophenyl) -5-methylpyrazole-3-yl group, 1- (4- Methylphenyl) -5_methylpyrazole_3_yl group
B1Q1で表される置換基を有して 、てもよ 、ヘテロ環基が置換基を有して 、てもよ 、5 ないし 10員の部分飽和へテロ環基である場合、好ましい具体例として、下記環群 j8 1Q1-3-lから選択される基を挙げることができる。 Preferred specific examples when the heterocyclic group having a substituent represented by B 1Q1 or a heterocyclic group having a substituent and a 5- or 10-membered partially saturated heterocyclic group are preferred. Examples include groups selected from the following ring group j8 1Q1 -3-l.
[環群 13 101-3-1] 1,5-ジメチル- 3-ォキソ -2-フエ-ル- 2,3-ジヒドロピラゾール- 4-ィル 基、 1,3-ベンゾジォキソラン- 5_ィル基、 1,4-ベンゾジォキサン- 6-ィル基、 4,5, 6,7-テ トラヒドロインダゾール -3-ィル基 [Ring group 13 101 -3-1] 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydropyrazol-4-yl group, 1,3-benzodioxolan-5 _Yl group, 1,4-benzodioxan-6-yl group, 4,5,6,7-tetrahydroindazole-3-yl group
一般式 (II)で表される化合物としては、好ましくは、  As the compound represented by the general formula (II), preferably,
Y101が— CH=N―、— N=CH―、— CONH—又は— NHCO—であり； Y 101 is —CH = N—, —N = CH—, —CONH— or —NHCO—;
Αωιが置換基を有していてもよい C - C ァリール基、置換基を有していてもよい 6ない Α ωι may have a substituent C-C aryl group, may have a substituent 6 None
6 10  6 10
し 13員のへテロアリール基、或いは置換基を有して 、てもよ 、9又は 10員の部分飽和 ヘテロ環基であり； A 13-membered heteroaryl group or a 9- or 10-membered partially saturated heterocyclic group having a substituent;
B1Q1が置換基を有して 、てもよ 、C - C ァリール基、置換基を有して 、てもよ 、5な ヽ B 1Q1 may have a substituent, may be a C-C aryl group, may have a substituent, and may have 5 or more.
6 10  6 10
し 13員のへテロアリール基、或いは置換基を有して 、てもよ 、5な 、し 10員の部分飽 和へテロ環基である化合物である。 A 13-membered heteroaryl group or a compound having a substituent, which may be a 5- or 10-membered partially saturated heterocyclic group.
更に好ましくは、下記 (0、 G0、（m)のいずれかに該当する化合物である。 More preferably, it is a compound corresponding to any of the following (0, G0, (m)).
(0 A1Q1がヒドロキシ置換 c - c ァリール基 (該ァリール基はヒドロキシ基のほかに更に (0 A 1Q1 is a hydroxy-substituted c-c aryl group.
6 10  6 10
置換基を有して 、てもよ 、；)であり； Having a substituent, may be;));
Y101が— CH=N―、― N=CH―、― CONH—又は— NHCO—であり； Y 101 is —CH = N—, —N = CH—, —CONH— or —NHCO—;
B1Q1が置換基を有して 、てもよ 、5な 、し 13員のへテロアリール基である化合物。 B 1Q1 is a compound having a substituent, and may be a 5- to 13-membered heteroaryl group.
(ii) A1()1がヒドロキシ基で置換された 6な 、し 10員のへテロアリール基 (該ヘテロァリー ル基はヒドロキシ基のほかに更に置換基を有していてもよい)であり； (ii) A 1 () 1 is a 6- or 10-membered heteroaryl group substituted with a hydroxy group (the heteroaryl group may have a substituent in addition to the hydroxy group);
Y101が- N=CH-又は- CONH-であり； Y 101 is -N = CH- or -CONH-;
B1Q1が置換基を有して 、てもよ 、5員のへテロアリール基である化合物。 A compound wherein B 1Q1 is a 5-membered heteroaryl group having a substituent.
(iii) Αωιが、 1又は 2個の窒素原子を環構成原子として含有する 9又は 10員の部分飽 和へテロ環基 (該部分飽和へテロ環基は置換基を有して! ^、てもよく、 Y1Q1との結合位 置は環構成原子である窒素原子の位置である)であり； (iii) ωωι is a 9- or 10-membered partially saturated atom containing one or two nitrogen atoms as ring-constituting atoms. A sum heterocyclic group (the partially saturated heterocyclic group may have a substituent! ^, And the bonding position with Y 1Q1 is the position of a ring-constituting nitrogen atom);
Y101が- N=CH-であり； Y 101 is -N = CH-;
B1()1が置換基を有して 、てもよ 、5員のへテロアリール基である化合物。 A compound in which B 1 () 1 has a substituent and may be a 5-membered heteroaryl group.
上記 (0に該当する化合物としては、好ましくは、  As the compound corresponding to the above (0, preferably,
A1Q1がヒドロキシ置換ナフチル基 (該ナフチル基はヒドロキシ基のほかに更に置換基を 有していてもよい)であり； A 1Q1 is a hydroxy-substituted naphthyl group (the naphthyl group may have a substituent in addition to the hydroxy group);
Y101が— CH=N―、— N=CH―、— CONH—又は— NHCO—であり； Y 101 is —CH = N—, —N = CH—, —CONH— or —NHCO—;
B1Q1が置換基を有して 、てもよ 、ビラゾリル基である化合物である。 B 1Q1 is a compound having a substituent and possibly a virazolyl group.
[0061] 更に好ましくは、 A1Mが 1-ヒドロキシ -2-ナフチル基であり； [0061] More preferably, A1M is a 1-hydroxy-2-naphthyl group;
(a) Y1Mが- N=CH-であり； B1()1が、 1位が水素原子、置換基を有していてもよい C - Cァ (a) Y 1M is -N = CH-; B 1 () 1 is a hydrogen atom at the 1-position, which may have a substituent.
1 6 ルキル基、置換基を有していてもよい C -C ァリール基、置換基を有していてもよい C  16 alkyl group, optionally substituted C -C aryl group, optionally substituted C
6 10  6 10
- C ァラルキル基、又は置換基を有していてもよい 9員のへテロアリール基であり、 3 -A C aralkyl group or a 9-membered heteroaryl group which may have a substituent,
7 12 7 12
位が置換基を有していてもよい C - Cアルキル基、又は置換基を有していてもよい C  C-C alkyl group which may have a substituent at the position, or C which may have a substituent
1 6 6 1 6 6
- C ァリール基であり、 5位力 Sヒドロキシ基であるピラゾール -4-ィル基； -A pyrazole-4-yl group which is a C aryl group and is a 5-position S hydroxy group;
10  Ten
(b) Y1Mが- CH=N-であり； B1Q1が、 1位が置換基を有していてもよい C -Cアルキル基、 (b) Y 1M is -CH = N-; B 1Q1 is a C 1 -C alkyl group optionally substituted at the 1-position,
1 6  1 6
置換基を有していてもよい C -C ァリール基、置換基を有していてもよい C -C ァラ  C -C aryl group which may have a substituent, C -C aryl group which may have a substituent
6 10 7 12 ルキル基、又は置換基を有していてもよい C -Cアルコキシカルボニル基であり、 3位  6 10 7 12 alkyl group, or an optionally substituted C-C alkoxycarbonyl group, 3-position
2 7  2 7
が水素原子、置換基を有していてもよい C -Cアルキル基、又は置換基を有していて  Has a hydrogen atom, an optionally substituted C-C alkyl group, or an optionally substituted
1 6  1 6
もよい C - C ァリール基であり、 4位が水素原子又は置換基を有していてもよい C - C Is a C-C aryl group, and the C-C may have a hydrogen atom or a substituent at the 4-position.
6 10 2 7 アルコキシカルボ-ル基であるピラゾール -5-ィル基；或いは 6 10 2 7 a pyrazole-5-yl group which is an alkoxycarbol group; or
(c) Y1Q1が- CH=N-であり； B1(nが、 1位が水素原子又は置換基を有していてもよい C (c) Y 1Q1 is -CH = N-; B 1 (n is a C atom which may have a hydrogen atom or a substituent at the 1-position.
6 6
-C ァリール基であり、 4位が水素原子であり、 5位が置換基を有していてもよい C -C-C aryl group, the 4-position is a hydrogen atom, and the 5-position may have a substituent C -C
10 6 ァリール基、又はヒドロキシ基であるピラゾール -3 -ィル基 10 6 Pyrazole-3-yl group which is aryl group or hydroxy group
10  Ten
である化合物である。  Is a compound.
[0062] 上記 (a)にお 、て、 B1Q1の好ま U、具体例として、下記環群 β 1Q1-2-lから選択される 基を挙げることができる。 In the above (a), preferred examples of B 1Q1 include, as specific examples, groups selected from the following ring group β 1Q1-2 -l.
[環群 β 101-2-1] 1-フエ-ル- 3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-フエニル - 3-(tert-ブチル )- 5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-フエ-ル- 5-ヒドロ キシピラゾール -4-ィル基、 1-(4-メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール[Ring group β 101 -2-1] 1-phenyl-3-methyl-5-hydroxypyrazole-4-yl group, 1-phenyl -3- (tert-butyl) -5-hydroxypyrazole-4-yl group, 1-methyl-3-phenyl-5-hydroxypyrazole-4-yl group, 1- (4-methylphenyl ) -3-Methyl-5-hydroxypyrazole
-4-ィル基、 1-フエ-ル- 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1- フエ-ル- 3-ェチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-クロ口フエ-ル) -3-メチ ル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-クロ口フエ-ル) -3-メチル -5-ヒドロキシピ ラゾール -4-ィル基、 1-(2-クロ口フエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル 基、 1-(4-メトキシフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-メチル フエ-ル)- 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-ぺ ンタフルォロェチル- 5-ヒドロキシピラゾール -4-ィル基、 1-ベンジル- 3-トリフルォロメ チル- 5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-トリフルォロメチル- 5-ヒドロキシ ピラゾール -4-ィル基、 1-ベンジル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、-4-yl group, 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-ethyl-5-hydroxypyrazole-4-yl Group, 1- (4-chlorophenol) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3-chlorophenol) -3-methyl-5-hydroxypyr Lazol-4-yl group, 1- (2-chlorophenol) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (4-methoxyphenyl) -3-methyl-5 -Hydroxypyrazole-4-yl group, 1- (4-methylphenyl) -3- 3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-pentafluoro Oloethyl-5-hydroxypyrazole-4-yl group, 1-benzyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-trifluoromethyl-5-hydroxypyrazole -4-yl group, 1-benzyl-3-methyl-5-hydroxypyra Lumpur-4-I group,
1-(4-フルオロフェ-ル )-3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-[4- (トリフル ォロメチル)フエ-ル] -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3-フルオロフェ1- (4-fluorophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- [4- (trifluoromethyl) phenyl] -3-methyl-5-hydroxypyrazole-4- Yl group, 1- (3-fluorophen
-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3,5-ジクロロフエ-ル) -3-メチ ル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3,4-ジクロロフエ-ル) -3-メチル - 5-ヒドロキ シピラゾール -4-ィル基、 1-(2-メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4- ィル基、 1-(2,4-ジクロロフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3- メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-カルボキシフエ- ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-[3,5-ビス (トリフルォロメチル)フエ-Yl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3,5-dichlorophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- ( 3,4-dichlorophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1 -(2,4-dichlorophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group , 1- (4-carboxyphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- [3,5-bis (trifluoromethyl) phenyl
-ル] -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(2-フルオロフェ-ル )-3-メチル-Le] -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-fluorophenyl) -3-methyl
-5-ヒドロキシピラゾール -4-ィル基、 1-(4-メトキシフエ-ル) -3-トリフルォロメチル -5- ヒドロキシピラゾール- 4-ィル基、 1- (4-フルオロフェ-ル )-3-トリフルォロメチル- 5-ヒド 口キシピラゾール -4-ィル基、 1-(3,5-ジクロロフヱ-ル)- 3-トリフルォロメチル- 5-ヒドロ キシピラゾール -4-ィル基、 1-(2,4-ジクロロフヱ-ル)- 3-トリフルォロメチル- 5-ヒドロキ シピラゾール -4-ィル基、 1-(2-ヒドロキシェチル) -3-トリフルォロメチル- 5-ヒドロキシピ ラゾール- 4-ィル基、 1- (4-クロ口フエ-ル)- 3-トリフルォロメチル- 5-ヒドロキシピラゾー ル _4_ィル基、卜ェチル—3_トリフルォロメチル— 5_ヒドロキシピラゾール _4_ィル基、 -5-Hydroxypyrazol-4-yl group, 1- (4-methoxyphenyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (4-fluorophenyl)- 3-Trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3,5-dichloropropyl) -3- 3-trifluoromethyl-5-hydroxypyrazole-4-yl group , 1- (2,4-dichloropropyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (2-hydroxyethyl) -3-trifluoromethyl-5- hydroxypivalic Razoru - 4-I group, 1- (4-black port Hue - Le) - 3-triflate Ruo Russia methyl - 5-hydroxypyrazole Eaux Le _ 4 _ I group, Bok Echiru - 3 _ Torifuruoro methyl - 5 _ hydroxypyrazole _ 4 _ I group,
1-(2,2,2-トリフルォロェチル) -3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基 、 l-(3-フルオロフェ-ル )-3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 l-(tert-ブチル )-3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-シクロへ キシル -3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 l-(n-ブチル )-3-トリ フルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-ヒドロキシベンジル) -3-トリフ ルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(4-カルボキシフエ-ル)- 3-トリフ ルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-カルボキシフヱ-ル)- 3-トリフ ルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-スルファモイルフエ-ル) -3-メ チル- 5-ヒドロキシピラゾール -4-ィル基、 1- (ベンゾチアゾール -2-ィル) -3-メチル -5- ヒドロキシピラゾール -4-ィル基、 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル 基、 1-メチル -3-メトキシカルボ-ルメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(4- ニトロフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1 ,3-ジメチル- 5-ヒドロキ シピラゾール -4-ィル基、 1-メチル -3-ェチル -5-ヒドロキシピラゾール -4-ィル基、 1-メ チル -3-メトキシメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-メチル - 3-(n-プロピル )-5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-(n-ブチル )-5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-[3- (エトキシカルボ-ル)プロピル]- 5-ヒドロキシピラゾール -4-ィル基、 1-ェチル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1, 3-ジェチル -5- ヒドロキシピラゾール -4-ィル基、 1-(2-ヒドロキシェチル) -3-メチル -5-ヒドロキシピラゾ ール -4-ィル基、 1-(2-ヒドロキシェチル) -3-ェチル -5-ヒドロキシピラゾール -4-ィル基 、 1-フエ-ル -3-メトキシカルボ-ルメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ -ル- 3-カルボキシメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-[3- (エト キシカルボ-ル)プロピル]- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル -3-(3-カル ボキシプロピル)- 5-ヒドロキシピラゾール -4-ィル基 1- (2,2,2-trifluoroethyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group , L- (3-fluorophenyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, l- (tert-butyl) -3-trifluoromethyl-5-hydroxypyrazole-4 -Yl group, 1-cyclohexyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl group, l- (n-butyl) -3-trifluoromethyl-5-hydroxypyrazole-4-y Group, 1- (3-hydroxybenzyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (4-carboxyphenyl) -3-trifluoromethyl-5-hydroxypyrazole-4 -Yl group, 1- (3-carboxyphenyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-sulfamoylphenyl) -3-methyl-5 -Hydroxypyrazole-4-yl group, 1- (benzothiazol-2-yl) -3-methyl-5-hydroxypyrazole-4-yl group, 3-trifluoromethyl-5 -Hydroxypyrazole-4-yl group, 1-methyl-3-methoxycarbolmethyl-5-hydroxypyrazole-4-yl group, 1- (4-nitrophenyl) -3-methyl-5-hydroxypyrazole -4-yl group, 1,3-dimethyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-ethyl-5-hydroxypyrazole-4-yl group, 1-methyl-3- Methoxymethyl-5-hydroxypyrazole-4-yl group, 1-methyl-3- (n-propyl) -5-hydroxypyrazole-4-yl group, 1-methyl-3- (n-butyl) -5 -Hydroxypyrazole-4-yl group, 1-methyl-3- [3- (ethoxycarbol) propyl] -5-hydroxypyrazole-4-yl group, 1-ethyl-3-methyl-5-hydroxy Pyrazole-4-yl group, 1,3-getyl-5-hydroxypyrazole-4-yl group, 1- (2-hydroxyethyl) -3-methyl-5-hydroxypyrazol-4-y Group, 1- (2-hydroxy 3-ethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-methoxycarbolmethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-yl Carboxymethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3- [3- (ethoxycarbol) propyl] -5-hydroxypyrazole-4-yl group, 1-phenyl -3- (3-carboxypropyl) -5-hydroxypyrazole-4-yl group
上記 (b)にお 、て、 B1Q1の好ま 、具体例として、下記環群 j8 ωι-2-2から選択される 基を挙げることができる。 In the above (b), preferred examples of B 1Q1 include a group selected from the following ring group j8 ωι- 2-2.
[環群 13 101-2-2] 1-(4-メチルフエ-ル) -3-メチルビラゾール -5-ィル基、 1-フエ-ルビ ラゾール _5_ィル基、 ジフエ-ルビラゾール _5_ィル基、卜フエ-ルー 4_ (エトキシカ ルポ-ル)ピラゾール -5-ィル基、 1-フエ-ル -3-メチルピラゾール -5-ィル基、 1-ェトキ シカルボ-ル- 3-フエ-ルビラゾール -5-ィル基、 1-フエ-ル- 3-(tert-ブチル)ピラゾ ール -5-ィル基、 1-(4-クロ口フエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-メトキシ フエ-ル) -3-メチルピラゾール -5-ィル基、 1-ベンジル -3-メチルピラゾール -5-ィル基 、 l-(tert-ブチル )- 3-フエ-ルビラゾール -5-ィル基、 1-[4- (トリフルォロメチル)フエ- ル] _3_メチルピラゾール _5_ィル基、 l-[4-(tert-ブチル)フエ-ル] -3-メチルピラゾー ル -5-ィル基、 1-(4-二トロフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(3-クロ口- 4-メ チルフエ-ル) -3-メチルビラゾール -5-ィル基、 1-(2-シァノエチル) -3-メチルビラゾー ル -5-ィル基、 1-(3,4-ジクロロフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(3-クロ口 フエ-ル) -3-メチルピラゾール -5-ィル基、 1-(2,4-ジクロロフエ-ル) -3-メチルピラゾ ール -5-ィル基、 1-(4-ブロモフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-フルォ 口フエ-ル) -3-メチルピラゾール -5-ィル基、 1-[4- (エトキシカルボ-ル)フエ-ル] -3- メチルピラゾール -5-ィル基、 1-(4-ヒドロキシフエ-ル) -3-メチルピラゾール -5-ィル基 、 1-(4-カルボキシフエ-ル) -3-メチルピラゾール -5-ィル基、 1-(4-スルファモイルフエ -ル) -3-メチルピラゾール -5-ィル基、 1-(4-クロ口フエ-ル)- 3-(tert-ブチル)ピラゾー ル -5-ィル基、 1-メチル -3-フエ-ルビラゾール -5-ィル基 [Ring group 13 101 2-2] 1- (4-Mechirufue - Le) -3-methyl Vila-5 I group, 1-Hue - ruby Razoru _ 5 _ I group, Jifue - Rubirazoru _ 5 _____________________________________ Group, triphenyl 4 _ (ethoxy alcohol) pyrazole-5-yl group, 1-phenyl-3-methylpyrazole-5-yl group, 1-ethoxycarbol-3 -Fervirazole-5-yl group, 1-phenyl-3- (tert-butyl) pyrazo 5-yl group, 1- (4-chlorophenyl) -3-methylpyrazole-5-yl group, 1- (4-methoxyphenyl) -3-methylpyrazole-5 Yl group, 1-benzyl-3-methylpyrazole-5-yl group, l- (tert-butyl) -3-phenylpyrazol-5-yl group, 1- [4- (trifluoromethyl) Phenyl] _3_methylpyrazole _5_yl group, l- [4- (tert-butyl) phenyl] -3-methylpyrazol-5-yl group, 1- (4-ditrophenyl) -3-methylpyrazole-5-yl group, 1- (3-chloro-4-methylthiol) -3-methylvirazole-5-yl group, 1- (2-cyanoethyl) -3- Methylbiazol-5-yl group, 1- (3,4-dichlorophenyl) -3-methylpyrazole-5-yl group, 1- (3-chlorophenol) -3-methylpyrazole-5 -Yl group, 1- (2,4-dichlorophenyl) -3-methylpyrazole-5-yl group, 1- (4-bromophenyl) -3-methylpyrazole-5-yl group, 1- (4-fluo -Yl) -3-methylpyrazole-5-yl group, 1- [4- (ethoxycarbol) phenyl] -3-methylpyrazole-5-yl group, 1- (4-hydroxyphenyl- 3-methylpyrazole-5-yl group, 1- (4-carboxyphenyl) -3-methylpyrazole-5-yl group, 1- (4-sulfamoylphenyl) -3 -Methylpyrazole-5-yl group, 1- (4-chlorophenol) -3- (tert-butyl) pyrazole-5-yl group, 1-methyl-3-phenylvirazole-5- Yl group
[0064] 上記 (c)にお 、て、 Βωιの好まし 、具体例として、下記環群 j8 ωΐ-2-4から選択される 基を挙げることができる。 [0064] Te you, the above (c), preferably of beta Omegaiota, as a specific example, can be a group selected from the following ring group j8 ωΐ -2-4.
[環群 13 101-2-4] 1-フエ-ル- 5-ヒドロキシピラゾール -3-ィル基、 5-フエ-ルビラゾー ル -3-ィル基 [Ring group 13 101 -2-4] 1-phenyl-5-hydroxypyrazole-3-yl group, 5-phenylvinylazol-3-yl group
上記 (0に該当する化合物としては、特に更に好ましくは、本明細書に記載された下 記化合物番号で表される化合物力 なる群力 選択される化合物である。  The compound corresponding to the above (0) is particularly preferably a compound selected from the group consisting of a compound represented by the following compound number described in the present specification.
•化合物番号: 3, 26, 27, 50, 54, 62ないし 67, 76ないし 78, 83, 84, 86, 87, 91, 92, 103, 112ないし 115, 120, 128, 133, 138ないし 140, 148, 158, 189ないし 191, 195, 196, 203, 208, 211, 212, 214, 216, 218, 221, 222, 228, 229, 236ないし 239, 243, 247, 253ないし 256, 258, 261, 262, 268ないし 271, 279, 284ないし 287, 294ないし 301, 317, 321ないし 324, 331, 337, 351,及び 353  Compound number: 3, 26, 27, 50, 54, 62 to 67, 76 to 78, 83, 84, 86, 87, 91, 92, 103, 112 to 115, 120, 128, 133, 138 to 140, 148, 158, 189 to 191, 195, 196, 203, 208, 211, 212, 214, 216, 218, 221, 222, 228, 229, 236 to 239, 243, 247, 253 to 256, 258, 261, 262, 268 to 271, 279, 284 to 287, 294 to 301, 317, 321 to 324, 331, 337, 351 and 353
[0065] 上記 GOに該当する化合物としては、好ましくは、 [0065] The compound corresponding to the above GO is preferably
Αωιがヒドロキシ置換キノリル基 (該キノリル基はヒドロキシ基のほかに更に置換基を有 していてもよい)であり； Y が- N=CH-又は- CONH-であり； Αωι is a hydroxy-substituted quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group); Y is -N = CH- or -CONH-;
B1Q1が置換基を有して 、てもよ 、ビラゾリル基である化合物である。 B 1Q1 is a compound having a substituent and possibly a virazolyl group.
更に好ましくは、 A1Mが 4-ヒドロキシ -3-キノリル基 (該キノリル基はヒドロキシ基のほか に更に置換基を有して 、てもよ 、；)であり； More preferably, A 1M is a 4-hydroxy-3-quinolyl group (the quinolyl group may have a substituent in addition to the hydroxy group;).
Y101が- N=CH-であり； Y 101 is -N = CH-;
B1Q1が、 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよ B 1Q1 may have a C-C alkyl group optionally having a substituent at the 1-position, or a substituent
1 6  1 6
い C - C ァリール基、又は置換基を有していてもよい C -C ァラルキル基であり、 3位 A C-Caryl group or a C-Caralkyl group which may have a substituent,
6 10 7 12 6 10 7 12
が置換基を有していてもよい C - Cアルキル基であり、 5位力ヒドロキシ基であるピラゾ  Is a C-C alkyl group which may have a substituent, and pyrazo is a 5-position hydroxy group.
1 6  1 6
ール -4-ィル基；  -4-yl group;
である化合物である。  Is a compound.
[0066] このとき、 Βωιの好まし 、具体例として、下記環群 β 1Μ-2-5から選択される基を挙げ ることがでさる。 [0066] In this case, preferably the beta Omegaiota, as a specific example, leaves in the Rukoto mentioned a group selected from the following ring group β 1Μ -2-5.
[環群 13 101-2-5] 1-フエ-ル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(4-メチルフエ-ル) -3-メ チル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-トリフルォロメチル- 5-ヒドロキ シピラゾール -4-ィル基、 1-フ -ル- 3-ェチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-クロ口フエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3-クロ口フエ二 ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(2-クロ口フエ-ル) -3-メチル - 5-ヒ ドロキシピラゾール -4-ィル基、 1-(4-メトキシフエ-ル) -3-メチル -5-ヒドロキシピラゾー ル -4-ィル基、 1-ベンジル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-フルォ 口フエ-ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(3-フルオロフェ-ル )-3- メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(2-メチルフエ-ル) -3-メチル -5-ヒドロキ シピラゾール -4-ィル基、 1-(3-メチルフエ-ル) -3-メチル -5-ヒドロキシピラゾール -4- ィル基、 1-(2-フルオロフェ-ル )-3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-ェチ ル- 3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-(3-フルオロフヱ-ル )-3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル -3-(3-カルボ キシプロピル)- 5-ヒドロキシピラゾール -4-ィル基 [Ring group 13 101 -2-5] 1-phenyl-3-methyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-trifluoromethyl-5-hydroxypyrazole-4-y 1- (4-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl Group, 1-fur-3-ethyl-5-hydroxypyrazole-4-yl group, 1- (4-chlorophenol) -3-methyl-5-hydroxypyrazole-4-yl group , 1- (3-chlorophenol) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-chlorophenol) -3-methyl-5-hydroxypyrazole -4-yl group, 1- (4-methoxyphenyl) -3-methyl-5-hydroxypyrazol-4-yl group, 1-benzyl-3-methyl-5-hydroxypyrazole-4-y 1- (4-fluoromethyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3-fluoro Phenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (3- Methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-fluorophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1-ethyl -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1- (3-fluorophenyl) -3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-phenyl -L-3- (3-carboxypropyl) -5-hydroxypyrazole-4-yl group
[0067] 上記 GOに該当する化合物としては、特に更に好ましくは、本明細書に記載された下 記化合物番号で表される化合物力 なる群力 選択される化合物である。 [0067] The compound corresponding to the above GO is particularly preferably the one described in the present specification. The compound strength represented by the compound number is a compound to be selected.
•化合物番号: 267, 272, 273, 280, 281 , 302ないし 306, 310, 312ないし 316, 318ない し 320, 325ないし 327, 329, 330, 332ないし 335, 338ないし 344, 352, 357, 367ないし 373, 378, 386, 390, 391 ,及び 401  Compound number: 267, 272, 273, 280, 281, 302 to 306, 310, 312 to 316, 318 or 320, 325 to 327, 329, 330, 332 to 335, 338 to 344, 352, 357, 367 Or 373, 378, 386, 390, 391, and 401
上記 Gii)に該当する化合物としては、好ましくは、  As the compound corresponding to the above Gii), preferably,
A1Q1が、置換基を有していてもよいイソインドリン- 2-ィル基、置換基を有していてもよ い 1 ,2,3,4-テトラヒドロイソキノリン- 2-ィル基、置換基を有していてもよい 1 ,2-ジヒドロイ ソキノリン- 2-ィル基及び置換基を有していてもよい 1 ,2,3,4-テトラヒドロキナゾリン- 3- ィル基からなる群から選択される基であり； A 1Q1 represents an optionally substituted isoindoline-2- yl group, an optionally substituted 1,2,3,4- tetrahydroisoquinolin-2-yl group, A 1,2-dihydroisoquinolin-2-yl group which may have a group and a 1,2,3,4-tetrahydroquinazoline-3-yl group which may have a substituent A group of choice;
Υ101が— N=CH—であり； Υ 101 is —N = CH—;
B1Q1が置換基を有して 、てもよ 、ビラゾリル基である化合物である。 B 1Q1 is a compound having a substituent and possibly a virazolyl group.
更に好ましくは、 A1Mが、下記環群 a ωΐ-3-1から選択される基であり； More preferably, A 1M is a group selected from the following ring group aωΐ- 3-1;
Y101が— N=CH—であり； Y 101 is —N = CH—;
B1Q1が、 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよ B 1Q1 may have a C-C alkyl group optionally having a substituent at the 1-position, or a substituent
1 6  1 6
い C - C ァリール基、又は置換基を有していてもよい C -C ァラルキル基であり、 3位A C-Caryl group or a C-Caralkyl group which may have a substituent,
6 10 7 12 6 10 7 12
が置換基を有していてもよい C - Cアルキル基であり、 5位力ヒドロキシ基であるピラゾ Is a C-C alkyl group which may have a substituent, and pyrazo is a 5-position hydroxy group.
1 6  1 6
ール -4-ィル基； -4-yl group;
である化合物である。 Is a compound.
[環群ひ1。1- 3-1] 1 ,3-ジォキソイソインドリン- 2-ィル基、 3-ヒドロキシ- 1-ォキソイソイン ドリン- 2-ィル基、 1-ォキソイソインドリン- 2-ィル基、 1 ,3-ジォキソ- 1 ,2,3,4-テトラヒドロ イソキノリン- 2-ィル基、 1-ォキソ -1 ,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 3-ヒドロキ シ- 1-ォキソ -1 ,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 1-ォキソ -1 ,2-ジヒドロイソキノ リン- 2-ィル基、 4-ォキソ -1 ,2,3,4-テトラヒドロキナゾリン- 3-ィル基 [Ring group 1 . 1 - 3-1] 1, 3-di O Kiso isoindoline - 2 I group, 3-hydroxy - 1-Okisoisoin Dorin - 2 I group, 1-O Kiso isoindoline - 2 I group, 1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 3-hydroxy-1 -Oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2-dihydroisoquinolin-2-yl group, 4-oxo-1,2,3,4 -Tetrahydroquinazoline-3-yl group
このとき、 Βωιの好ましい具体例として、下記環群 |8 ωι-2-6から選択される基を挙げる ことができる。 In this case, preferred specific examples of beta Omegaiota, following ring group | can be a group selected from 8 ωι -2-6.
[環群 13 101-2-6] 1-フエ-ル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-メチル -3-トリフルォロメチル- 5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-トリフルォロ メチル -5-ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-ェチル -5-ヒドロキシピラゾ ール -4-ィル基、 1-フエ-ル- 3-ペンタフルォロェチル -5-ヒドロキシピラゾール -4-ィ ル基、 1-ベンジル -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(4-フルオロフェ- ル) -3-メチル -5-ヒドロキシピラゾール -4-ィル基、 1-(2-メチルフエ-ル) -3-メチル -5- ヒドロキシピラゾール -4-ィル基、 1-フエ-ル- 3-(3-カルボキシプロピル)- 5-ヒドロキシ ピラゾール -4-ィル基 [Ring group 13 101 -2-6] 1-phenyl-3-methyl-5-hydroxypyrazole-4-yl group, 1-methyl-3-trifluoromethyl-5-hydroxypyrazole-4-y Group, 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole-4-yl group, 1-phenyl-3-ethyl-5-hydroxypyrazo 4-yl group, 1-phenyl-3-pentafluoroethyl-5-hydroxypyrazole-4-yl group, 1-benzyl-3-methyl-5-hydroxypyrazole-4-yl Group, 1- (4-fluorophenyl) -3-methyl-5-hydroxypyrazole-4-yl group, 1- (2-methylphenyl) -3-methyl-5-hydroxypyrazole-4-yl 1-phenyl-3- (3-carboxypropyl) -5-hydroxypyrazole-4-yl group
上記 (m)に該当する化合物としては、特に更に好ましくは、本明細書に記載された 下記化合物番号で表される化合物力 なる群力 選択される化合物である。  The compound corresponding to the above (m) is particularly preferably a compound selected from the group consisting of the following compound numbers described in the present specification.
•化合物番号: 359, 360, 364ないし 366, 375ないし 377, 379ないし 385, 388, 389, 392 ないし 400, 405,及び 406  Compound number: 359, 360, 364 to 366, 375 to 377, 379 to 385, 388, 389, 392 to 400, 405, and 406
[0069] 一般式 (II)で表される化合物としては、下記一般式 (II-1): The compound represented by the general formula (II) includes the following general formula (II-1):
[化 5]  [Formula 5]
Figure imgf000051_0001
Figure imgf000051_0001
[式中、 X1U1は式- N=C(RbU1)_ (式中、左側の結合手がベンゼン環に結合し、右側の結 合手が窒素原子に結合する)、又は式- NH-CH(R5Q1)- (式中、左側の結合手がベンゼ ン環に結合し、右側の結合手が窒素原子に結合する)を表し； R1M、 R2M、 R3M及び R4M はそれぞれ独立して水素原子、ハロゲン原子、置換基を有していてもよい C - Cアル Wherein X 1U1 is a compound of the formula -N = C (R bU1 ) _ (where the bond on the left is bonded to a benzene ring and the bond on the right is bonded to a nitrogen atom), or the formula -NH- CH (R 5Q1 )-(where the bond on the left is bonded to the benzene ring and the bond on the right is bonded to the nitrogen atom); R 1M , R 2M , R 3M and R 4M are each independently A hydrogen atom, a halogen atom, and a C-C
1 6 キル基、又は置換基を有していてもよいヒドロキシ基を表し； R5Q1は置換基を有してい てもよい C - Cアルキル基、又は置換基を有していてもよい C - C ァリール基を表し； Represents a 16- alkyl group or a hydroxy group which may have a substituent; R 5Q1 represents a C-C alkyl group which may have a substituent or a C- which may have a substituent; Represents a C aryl group;
1 6 6 10 1 6 6 10
R1QQ1は置換基を有していてもよいアミノ基を表す]で表される化合物、並びに Y1Mが - CH=N -又は- CONH-であり； A101が 2-ヒドロキシ- 1-ナフチル基であり； Βωιが 2-ヒドロ キシ -4-スルホ -1-ナフチル基である化合物は除く。 R 1QQ1 represents an amino group which may have a substituent], and Y 1M is —CH = N— or —CONH—; and A 101 is a 2-hydroxy-1-naphthyl group 化合物 excluding compounds in which ωι is a 2-hydroxy-4-sulfo-1-naphthyl group.
[0070] 好ましくは、上記一般式 (II- 1): [0070] Preferably, the above general formula (II-1):
[式中、 Χ1Μは式- N=C(R5Q1)- (式中、左側の結合手がベンゼン環に結合し、右側の結 合手が窒素原子に結合する)、又は式- NH-CH(R5Q1)- (式中、左側の結合手がベンゼ ン環に結合し、右側の結合手が窒素原子に結合する)を表し； R1M、 R2M、 R3M及び R4M はそれぞれ独立して水素原子又は任意の置換基を表し； R5Mは水素原子又は任意 の置換基を表し； R1QQ1は置換基を有して 、てもよ 、アミノ基を表す]で表される化合物 、並びに Y1Q1が- CH=N -又は- CONH-であり； A1Q1が 2-ヒドロキシ- 1-ナフチル基であり ； Βωιが 2-ヒドロキシ -4-スルホ -1-ナフチル基である化合物は除く。 Wherein 式 1Μ is the formula -N = C (R 5Q1 )-(where the left hand is bonded to the benzene ring and the right hand is bonded to the nitrogen atom), or the formula -NH- CH (R 5Q1 )-(where the bond on the left is bonded to the benzene ring and the bond on the right is bonded to the nitrogen atom); R 1M , R 2M , R 3M and R 4M are each independently Represents a hydrogen atom or an optional substituent; R 5M represents a hydrogen atom or an optional substituent R 1QQ1 has a substituent, and may represent an amino group], and Y 1Q1 is —CH = N— or —CONH—; and A 1Q1 is A 2-hydroxy-1-naphthyl group; excluding a compound in which ωι is a 2-hydroxy-4-sulfo-1-naphthyl group.
[0071] 上記一般式 (II)で表される化合物若しくは薬理学的に許容されるその塩、又はそれ らの水和物若しくはそれらの溶媒和物はいずれも新規ィヒ合物であり、本物質発明に 基づく化合物の用途に関しては特に限定されない。  [0071] The compound represented by the above general formula (II) or a pharmacologically acceptable salt thereof, or a hydrate or solvate thereof, is a novel compound, and The use of the compound based on the substance invention is not particularly limited.
上記一般式 (I)及び (II)で表される化合物は塩を形成することができる。薬理学的に 許容される塩としては、酸性基が存在する場合には、例えば、リチウム塩、ナトリウム 塩、カリウム塩、マグネシウム塩、カルシウム塩等の金属塩、又はアンモ-ゥム塩、メ チルアンモ -ゥム塩、ジメチルアンモ -ゥム塩、トリメチルアンモ -ゥム塩、ジシクロへ キシルアンモ-ゥム塩等のアンモ-ゥム塩をあげることができ、塩基性基が存在する 場合には、例えば、塩酸塩、臭酸塩、硫酸塩、硝酸塩、リン酸塩等の鉱酸塩、あるい はメタンスルホン酸塩、ベンゼンスルホン酸塩、パラトルエンスルホン酸塩、酢酸塩、 プロピオン酸塩、酒石酸塩、フマール酸塩、マレイン酸塩、リンゴ酸塩、シユウ酸塩、 コハク酸塩、クェン酸塩、安息香酸塩、マンデル酸塩、ケィ皮酸塩、乳酸塩等の有機 酸塩をあげることができる。グリシンなどのアミノ酸と塩を形成する場合もある。本発明 の医薬の有効成分としては、薬学的に許容される塩も好適に用いることができる。  The compounds represented by the above general formulas (I) and (II) can form salts. As the pharmacologically acceptable salt, when an acidic group is present, for example, a metal salt such as a lithium salt, a sodium salt, a potassium salt, a magnesium salt, and a calcium salt, or an ammodimium salt or a methylammonium salt Ammonium salts such as dimethylammonium salt, dimethylammonium salt, trimethylammonium salt, and dicyclohexylammonium salt.In the case where a basic group is present, for example, , Hydrochloride, bromate, sulfate, nitrate, phosphate, etc., or methanesulfonate, benzenesulfonate, paratoluenesulfonate, acetate, propionate, tartrate Organic salts such as fumarate, maleate, malate, oxalate, succinate, citrate, benzoate, mandelate, silicate, lactate, etc. . It may form salts with amino acids such as glycine. As the active ingredient of the medicament of the present invention, pharmaceutically acceptable salts can also be suitably used.
[0072] 上記一般式 (I)及び (II)で表される化合物又はその塩は、水和物又は溶媒和物とし て存在する場合もある。本発明の医薬の有効成分としては、上記のいずれの物質を 用いてもよい。また、一般式 (I)及び (II)で表される化合物は 1以上の不斉炭素を有す る場合があり、光学活性体ゃジァステレオマーなどの立体異性体として存在する場 合がある。本発明の医薬の有効成分としては、純粋な形態の立体異性体、光学対掌 体又はジァステレオマーの任意の混合物、ラセミ体などを用いてもよい。更に、一般 式 (I)及び (II)で表される化合物は置換基の種類によって互変異性体として存在する 場合がある。例えば、後述する化合物番号 1の化合物の場合、下記式で表される互 変異性体を例示することができる。  The compounds represented by the above general formulas (I) and (II) or salts thereof may exist as hydrates or solvates. Any of the above substances may be used as the active ingredient of the medicament of the present invention. Further, the compounds represented by the general formulas (I) and (II) may have one or more asymmetric carbon atoms and may exist as stereoisomers such as optically active diastereomers. As the active ingredient of the medicament of the present invention, pure mixtures of stereoisomers, any mixture of enantiomers or diastereomers, racemates and the like may be used. Further, the compounds represented by the general formulas (I) and (II) may exist as tautomers depending on the type of the substituent. For example, in the case of the compound of Compound No. 1 described below, a tautomer represented by the following formula can be exemplified.
[化 6] [Formula 6]
Figure imgf000053_0001
Figure imgf000053_0001
本発明の医薬の有効成分としては、純粋な形態の互変異性体又はそれらの混合物 を用いてもよい。更に、一般式 (I)及び (II)で表される化合物がォレフィン、ィミン、ァゾ などの二重結合を有する場合には、その配置は Z配置又は E配置のいずれでもよぐ 本発明の医薬の有効成分としてはいずれかの配置の幾何異性体又はそれらの混合 物を用いてもよい。 As an active ingredient of the medicament of the present invention, a tautomer in a pure form or a mixture thereof may be used. Further, when the compounds represented by the general formulas (I) and (II) have a double bond such as olefin, imine, or azo, the configuration may be either Z configuration or E configuration. As the active ingredient of the medicament, any configuration of geometric isomers or a mixture thereof may be used.
[0073] 一般式 (I)又は (II)で表される本発明の化合物のうち、好ましい化合物として以下の 化合物を挙げることができるが、本発明の化合物はこれらの化合物に限定されること はない。また、一般式 (I)で表される化合物には一般式 (II)で表される化合物が包含さ れることは自明であり、下記表における A、 B及び Yには一般式 (II)における A1Q1、 B101 及び Y1Q1がそれぞれ包含されることは言うまでもない。 [0073] Among the compounds of the present invention represented by the general formula (I) or (II), the following compounds can be mentioned as preferred compounds, but the compounds of the present invention are not limited to these compounds. Absent. It is obvious that the compound represented by the general formula (I) includes the compound represented by the general formula (II), and A, B and Y in the following table represent It goes without saying that A 1Q1 , B 101 and Y 1Q1 are each included.
下記表において用いられる略語の意味は下記の通りである。  The meanings of the abbreviations used in the following table are as follows.
Me:メチル基； Et:ェチル基； n- Pr:n-プロピル基； n- Bu:n-ブチル基； t- Bu:tert-ブチ ル基； OMe:メトキシ基； CO Me:メトキシカルボ-ル基； CO Et:エトキシカルボ-ル基;  Me: methyl group; Et: ethyl group; n- Pr: n-propyl group; n- Bu: n-butyl group; t- Bu: tert-butyl group; OMe: methoxy group; CO Me: methoxycarbol Group; CO Et: ethoxycarbol group;
2 2  twenty two
Ac:ァセチル基； OMs:メシル基； OTs:トシル基  Ac: acetyl group; OMs: mesyl group; OTs: tosyl group
[0074] [表 1] [Table 1]
Figure imgf000054_0001
Figure imgf000054_0001
合番号物
Figure imgf000055_0001
Figure imgf000056_0001
/vu/ O oosooifcldS0sAV 99 Joint number
Figure imgf000055_0001
Figure imgf000056_0001
/ vu / O oosooifcldS0sAV 99
Figure imgf000057_0001
Figure imgf000057_0001
Figure imgf000058_0001
Figure imgf000059_0001
Figure imgf000060_0001
Figure imgf000058_0001
Figure imgf000059_0001
Figure imgf000060_0001
Figure imgf000061_0001
Figure imgf000062_0001
Figure imgf000063_0001
Figure imgf000064_0001
t-
Figure imgf000061_0001
Figure imgf000062_0001
Figure imgf000063_0001
Figure imgf000064_0001
t-
89 - N=CH - 89-N = CH-
t-t-
90 - N=CH -
Figure imgf000065_0001
90-N = CH-
Figure imgf000065_0001
t-Bu  t-Bu
OH  OH
91 -CH=N-  91 -CH = N-
02N 0 2 N
OH  OH
92 -CH=N- ヽ N - N、 92 -CH = N- ヽ N- N ,
OH OH
93 - CH=N -  93-CH = N-
OH OH
Me CI Me CI
94 -NHCO - 人 ,N -Me 94 -NHCO-People, N -Me
Me Me
OH  OH
95 -NHCO - ο,ΧΧ 、N - N N、 95 -NHCO-ο, ΧΧ, N- N N ,
Me Me
96 - CH=N -96-CH = N-
N 'N 97 - CH:N-N ' N 97-CH: N-
98 -CH=N-98 -CH = N-
99 - CH=N -
Figure imgf000066_0001
99-CH = N-
Figure imgf000066_0001
OH  OH
100 - CH=N -  100-CH = N-
OH OH OH OH
101 -CH=N-  101 -CH = N-
OH OH
102 - CH=N- 102-CH = N-
FF
OH NC OH NC
103 - CH=N - - N  103-CH = N--N
H H
, N - N _  , N-N _
104 - CH=N - ヽ
Figure imgf000067_0001
Figure imgf000068_0001
Figure imgf000069_0001
Figure imgf000070_0001
Figure imgf000071_0001
Figure imgf000072_0001
Figure imgf000073_0001
Figure imgf000074_0001
Figure imgf000075_0001
Figure imgf000076_0001
Figure imgf000077_0001
Figure imgf000078_0001
104-CH = N-ヽ
Figure imgf000067_0001
Figure imgf000068_0001
Figure imgf000069_0001
Figure imgf000070_0001
Figure imgf000071_0001
Figure imgf000072_0001
Figure imgf000073_0001
Figure imgf000074_0001
Figure imgf000075_0001
Figure imgf000076_0001
Figure imgf000077_0001
Figure imgf000078_0001
Figure imgf000079_0001
A-Y-B
Figure imgf000079_0001
AYB
Figure imgf000080_0001
Figure imgf000081_0001
Figure imgf000082_0001
C
Figure imgf000080_0001
Figure imgf000081_0001
Figure imgf000082_0001
C
o  o
Figure imgf000083_0001
Figure imgf000083_0001
1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1
2  2
II II II II il II II 11 o o  II II II II il II II 11 o o
lid  lid
1 ！ 1 1 ！ 1 1  1! 1 1! 1 1
\ f ェ z \ F E z
ェ X z
Figure imgf000083_0002
ό X X z
Figure imgf000083_0002
ό
Figure imgf000084_0001
Figure imgf000085_0001
Figure imgf000086_0001
Figure imgf000087_0001
Figure imgf000088_0001
/vu/ O oosoozfcldS0sAV
Figure imgf000084_0001
Figure imgf000085_0001
Figure imgf000086_0001
Figure imgf000087_0001
Figure imgf000088_0001
/ vu / O oosoozfcldS0sAV
Figure imgf000089_0001
Figure imgf000089_0001
Figure imgf000090_0001
Figure imgf000091_0001
Figure imgf000092_0001
Figure imgf000093_0001
Figure imgf000094_0001
Figure imgf000095_0001
Figure imgf000096_0001
Figure imgf000097_0001
Figure imgf000098_0001
Figure imgf000090_0001
Figure imgf000091_0001
Figure imgf000092_0001
Figure imgf000093_0001
Figure imgf000094_0001
Figure imgf000095_0001
Figure imgf000096_0001
Figure imgf000097_0001
Figure imgf000098_0001
Figure imgf000099_0001
Figure imgf000100_0001
Figure imgf000101_0001
Figure imgf000102_0001
Figure imgf000103_0001
Figure imgf000104_0001
一般式 (I)又は (II)で表される化合物は、例えば、以下に示した方法によって製造す ることができるが、上記化合物の製造方法は下記の方法に限定されることはない。 一般式 (I)で表される化合物において Yが- CH=N-で表される化合物は、例えば、下 記の反応工程式 1に示す方法に従って製造することができる。
Figure imgf000099_0001
Figure imgf000100_0001
Figure imgf000101_0001
Figure imgf000102_0001
Figure imgf000103_0001
Figure imgf000104_0001
The compound represented by the general formula (I) or (II) can be produced, for example, by the method shown below, but the production method of the compound is not limited to the following method. The compound represented by the general formula (I) wherein Y is represented by —CH = N— can be produced, for example, according to the method shown in the following reaction scheme 1.
[反応工程式 1] [Reaction process formula 1]
[化 7] (1 ) (3) [Formula 7] (1) (3)
(式中、 A及び Bは前記と同意義である） (Wherein A and B are as defined above)
[0077] アルデヒド (1)とァミン (2)を溶媒中反応させることにより、 目的化合物 (3)を製造するこ とができる。用いられる溶媒としては、反応に悪影響を与えないものであれば特に限 定されず、例えば、メタノール、エタノール、イソプロパノールなどのアルコール類；ジ クロロメタン、ジクロロエタン、クロ口ホルムなどのハロゲン系溶媒；テトラヒドロフラン、 1,4-ジォキサンなどのエーテル類；ベンゼン、トルエン、モノクロ口ベンゼン、 0-ジクロ 口ベンゼンなどの芳香族系溶媒； Ν,Ν-ジメチルホルムアミド、 Ν-メチルピロリドンなど のアミド系溶媒；酢酸、プロピオン酸などの有機酸系溶媒；又はこれらの溶媒の混合 溶媒を挙げることができる。また、本反応において触媒を用いてもよい。用いられる触 媒としては、例えば、酢酸ナトリウム、酢酸アンモ-ゥム、酢酸カリウムなどの塩；酢酸 、プロピオン酸などの酸；ピぺリジン、ピロリジンなどの塩基；又はこれらの触媒の混合 物を挙げることができる。反応温度は特に限定されないが、通常 0°Cないし使用する 溶媒の沸点、好適には室温ないし 150°Cである。反応時間は反応温度によって左右 される力 通常 5分ないし 3日間、好適には 5分ないし 6時間である。 [0077] The target compound (3) can be produced by reacting the aldehyde (1) and the amine (2) in a solvent. The solvent used is not particularly limited as long as it does not adversely affect the reaction. Examples thereof include alcohols such as methanol, ethanol, and isopropanol; halogen solvents such as dichloromethane, dichloroethane, and chloroform; tetrahydrofuran. Ethers such as 1,4-dioxane; aromatic solvents such as benzene, toluene, monochrome benzene, and 0-dichlorobenzene; amide solvents such as Ν, Ν-dimethylformamide and Ν-methylpyrrolidone; acetic acid; Organic acid solvents such as propionic acid; and mixed solvents of these solvents. Further, a catalyst may be used in this reaction. Examples of the catalyst used include salts such as sodium acetate, ammonium acetate, and potassium acetate; acids such as acetic acid and propionic acid; bases such as piperidine and pyrrolidine; and mixtures of these catalysts. be able to. The reaction temperature is not particularly limited, but is usually from 0 ° C to the boiling point of the solvent used, preferably from room temperature to 150 ° C. The reaction time depends on the reaction temperature and is usually 5 minutes to 3 days, preferably 5 minutes to 6 hours.
一般式 (I)で表される化合物にぉ 、て Yが- N=CH-で表される化合物は、上記反応 工程式 1におけるアルデヒド (1)とァミン (2)の組み合わせを入れ替えることにより製造す ることがでさる。  A compound represented by the formula (I), wherein Y is represented by -N = CH-, is produced by replacing the combination of the aldehyde (1) and the amine (2) in the above reaction scheme 1. You can do it.
[0078] 一般式 (I)で表される化合物において Yが- CONH-で表される化合物は、例えば、下 記の反応工程式 2に示す方法に従って製造することができる。  [0078] In the compound represented by the general formula (I), the compound in which Y is represented by -CONH- can be produced, for example, according to the method shown in the following reaction scheme 2.
[反応工程式 2]  [Reaction process formula 2]
[化 8]  [Formula 8]
H2N - B (2) A_c -N -B H 2 N-B (2) A _c -N -B
A-C00H ^ A- C00H ^
(4) (5) (4) (5)
(式中、 A及び Bは前記と同意義である) カルボン酸 (4)とァミン (2)を縮合剤の存在下、溶媒中反応させることにより、 目的化 合物 (5)を製造することができる。用いられる縮合剤としては、例えば、 1-ェチル -3-(3-ジメチルァミノプロピル)カルボジイミド塩酸塩 (WSC · HC1)などのカルボジイミド; 三塩化リン、ォキシ塩化リン、塩ィ匕チォ-ルなどの酸ノヽロゲン化剤を挙げることがで きる。用いられる溶媒としては、反応に悪影響を与えないものであれば特に限定され ず、例えば、ジクロロメタン、ジクロロエタン、クロ口ホルムなどのハロゲン系溶媒；テト ラヒドロフラン、 1,4-ジォキサンなどのエーテル類；ベンゼン、トルエン、モノクロ口ベン ゼン、 0-ジクロロベンゼンなどの芳香族系溶媒； Ν,Ν-ジメチルホルムアミド、 Ν-メチル ピロリドンなどのアミド系溶媒；又はこれらの溶媒の混合溶媒を挙げることができる。ま た、本反応において反応を促進させる試薬を用いてもよい。用いられる試薬としては 、例えば、トリェチルァミン、ピリジンなどの塩基を挙げることができる。反応温度は特 に限定されないが、通常 0°Cないし使用する溶媒の沸点、好適には室温ないし 150°C である。反応時間は反応温度によって左右されるが、通常 5分ないし 3日間、好適に は 5分ないし 6時間である。また、カルボン酸 (4)の替わりに対応する酸ノヽロゲンィ匕物、 酸無水物などを用いてもょ 、。 (Wherein, A and B are as defined above) The desired compound (5) can be produced by reacting the carboxylic acid (4) with the amine (2) in the presence of a condensing agent in a solvent. Examples of the condensing agent to be used include, for example, carbodiimides such as 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSCHC1); phosphorus trichloride, phosphorus oxychloride, salt chloride, etc. Acid nodogenizing agents. The solvent used is not particularly limited as long as it does not adversely affect the reaction, and examples thereof include halogen solvents such as dichloromethane, dichloroethane, and chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; benzene And aromatic solvents such as toluene, monochrome benzene and 0-dichlorobenzene; amide solvents such as の, Ν-dimethylformamide and Ν-methylpyrrolidone; and mixed solvents of these solvents. Further, a reagent that promotes the reaction in this reaction may be used. Examples of the reagent used include bases such as triethylamine and pyridine. The reaction temperature is not particularly limited, but is usually from 0 ° C to the boiling point of the solvent used, preferably from room temperature to 150 ° C. The reaction time depends on the reaction temperature, but is usually 5 minutes to 3 days, preferably 5 minutes to 6 hours. In addition, an acid nodroside, an acid anhydride or the like corresponding to the carboxylic acid (4) may be used.
一般式 (I)で表される化合物において Yが- NHCO-で表される化合物は、上記反応 工程式 2におけるカルボン酸 (4)とァミン (2)の組み合わせを入れ替えることにより製造 することができる。  The compound represented by the general formula (I) wherein Y is -NHCO- can be produced by replacing the combination of the carboxylic acid (4) and the amine (2) in the above reaction scheme 2. .
また、一般式 (I)で表される化合物において、 Yカ N=CH-であり、 Bが 5-ヒドロキシピ ラゾール -4-ィル基 (該基は 5位のヒドロキシ基の他に更に置換基を有して 、てもよ 、） 又は 2-ヒドロキシインドール- 3-ィル基 (該基は 2位のヒドロキシ基の他に更に置換基を 有していてもよい)である化合物は、例えば、 Journal of Medicinal Chemistry, Vol.44, No.25, p.4339-4358(2001)に記載された「Procedure G」と同様の方法によって製造 することちでさる。  Further, in the compound represented by the general formula (I), Y is N = CH-, and B is a 5-hydroxypyrazole-4-yl group (the group is further substituted in addition to the 5-position hydroxy group). A compound having a group or a 2-hydroxyindole-3-yl group (the group may further have a substituent in addition to the 2-position hydroxy group) For example, it is manufactured by a method similar to “Procedure G” described in Journal of Medicinal Chemistry, Vol. 44, No. 25, p. 4339-4358 (2001).
さらに、一般式 (I)で表される化合物において、 Yカ N=CH-であり、 Bが 5-ヒドロキシ ピラゾール -4-ィル基 (該基は 5位のヒドロキシ基の他に更に置換基を有していてもよ い)である化合物は、例えば、 Synthesis, p.543-544(1976)に記載された化合物 2aの 合成例と同様の方法によって製造することもできる。 [0080] 上記反応にぉ 、て、官能基の保護、脱保護；又は官能基の導入、修飾などが必要 な場合、例えば、当業者に広く知られている下記の公知文献に記載又は引用された 方法を用いることができる。 Further, in the compound represented by the general formula (I), Y is N = CH-, and B is a 5-hydroxypyrazol-4-yl group (the group is a 5-hydroxypyroxy group and a substituent other than the 5-position hydroxy group). May be produced, for example, by the same method as in the synthesis example of compound 2a described in Synthesis, p. 543-544 (1976). [0080] When the above reaction requires protection or deprotection of a functional group, or introduction or modification of a functional group, for example, it is described or cited in the following known documents widely known to those skilled in the art. Method can be used.
[公知文献]  [Publication]
• Protective Groups in Organic syntheses, Vol.3, John Wiley & Sons, Inc.  • Protective Groups in Organic syntheses, Vol. 3, John Wiley & Sons, Inc.
• Handbook of Reagents for Organic Synthesis, Vol.1— 4, John Wiley & Sons, Inc. •Fiesers' Reagents for Organic Synthesis, Vol.1— 20, John Wiley & Sons, Inc.  • Handbook of Reagents for Organic Synthesis, Vol.1— 4, John Wiley & Sons, Inc.Fiesers' Reagents for Organic Synthesis, Vol.1— 20, John Wiley & Sons, Inc.
• Comprehensive Organic Transformations： A Guide to Functional Group  • Comprehensive Organic Transformations: A Guide to Functional Group
Preparations, Vol.2, John Wiley & Sons, Inc.  Preparations, Vol. 2, John Wiley & Sons, Inc.
• Compendium of Organic Synthetic Methods, Vol.1— 10, John Wiley & Sons, Inc. • Compendium of Organic Synthetic Methods, Vol.1— 10, John Wiley & Sons, Inc.
• Encyclopedia of Reagents for Organic Synthesis, Vol.1— 8, John Wiley & Sons, Inc. また、一般式 (II)で表される化合物も上記一般式 (I)で表される化合物と同様の方法 に従って製造することができる。 • Encyclopedia of Reagents for Organic Synthesis, Vol. 1—8, John Wiley & Sons, Inc. Also, the compound represented by the general formula (II) can be prepared in the same manner as the compound represented by the general formula (I). Can be manufactured.
[0081] 一般式 (I)及び (II)で表される化合物力 S1以上の不斉炭素を有し、その光学活性体を 製造する場合には、光学活性な原料を用いて製造してもよいし、一旦ラセミ体を製造 した後に光学分割してもよい。光学分割の方法としては当業者に周知の方法を用い ることができ、例えば、光学活性カラムを用いた高速液体クロマトグラフィーを用いるこ とがでさる。 [0081] When the compound represented by the general formulas (I) and (II) has an asymmetric carbon of at least S1 and has an optically active form, it may be produced using an optically active raw material. Alternatively, a racemate may be produced and then subjected to optical resolution. As a method for optical resolution, a method known to those skilled in the art can be used, and for example, high performance liquid chromatography using an optically active column can be used.
以上のような方法で製造された一般式 (I)及び (II)で表される化合物は当業者に周 知の方法、例えば、抽出、沈殿、分画クロマトグラフィー、分別結晶化、懸濁洗浄、再 結晶などにより、単離、精製することができる。また、本発明化合物の薬理学的に許 容される塩、並びにそれらの水和物及びそれらの溶媒和物も、それぞれ当業者に周 知の方法で製造することができる。  The compounds represented by the general formulas (I) and (II) produced by the above methods can be prepared by methods known to those skilled in the art, for example, extraction, precipitation, fractional chromatography, fractional crystallization, and suspension washing. It can be isolated and purified by, for example, recrystallization. Also, pharmacologically acceptable salts of the compound of the present invention, hydrates and solvates thereof can be produced by methods known to those skilled in the art.
本明細書の実施例には、一般式 (I)及び (II)に包含される代表的化合物の製造方法 が具体的に説明されている。従って、当業者は、上記の一般的な製造方法の説明及 び実施例の具体的製造方法の説明を参照しつつ、適宜の反応原料、反応試薬、反 応条件を選択し、必要に応じてこれらの方法に適宜の修飾ないし改変を加えることに よって、一般式 (I)及び (II)に包含される化合物をいずれも製造可能である。 [0082] 一般式 (I)及び (II)で示される化合物は PGD2の産生を抑制する作用及び Z又は造 血器型 PGD2合成酵素に対する阻害作用を有しており、アレルギー性炎症抑制剤と して好適に用いることができる。上記の医薬は、アレルギー反応に起因する炎症疾患 の予防及び Z又は治療のための医薬の有効成分として有用である。より具体的には 、本発明の医薬は、次に示すようなアレルギー性炎症反応が関与していると考えられ る疾患、例えば接触性皮膚炎、アトピー性皮膚炎、湿疹、花粉症、喘息、気管支炎、 血管炎、鼻炎、鼻閉、間質性肺炎、関節炎、眼炎、結膜炎、神経炎、中耳炎、脳脊 髄炎、膀胱炎、喉頭炎、食物アレルギー、昆虫アレルギー、薬物アレルギー、ァナフ エラキシーショックなどのアレルギー性疾患、更には PGD2の過剰産生による血管拡 張や血管透過性昂進や炎症細胞の浸潤を伴う組織障害の拡大の予防及び Z又は 治療薬として有用である。 The working examples of the present specification specifically describe methods for preparing representative compounds encompassed by the general formulas (I) and (II). Therefore, those skilled in the art can select appropriate reaction materials, reaction reagents, and reaction conditions while referring to the above description of the general production method and the description of the specific production method in Examples, and if necessary, By appropriately modifying or modifying these methods, any of the compounds included in the general formulas (I) and (II) can be produced. [0082] The compounds represented by the general formulas (I) and (II) have an action of inhibiting PGD2 production and an action of inhibiting Z or hematopoietic PGD2 synthase, and are considered as allergic inflammation inhibitors. Can be suitably used. The above medicament is useful as an active ingredient of a medicament for preventing and / or treating an inflammatory disease caused by an allergic reaction. More specifically, the medicament of the present invention is used for diseases considered to be involved in allergic inflammatory reactions such as contact dermatitis, atopic dermatitis, eczema, hay fever, asthma, and the like. Bronchitis, vasculitis, rhinitis, nasal congestion, interstitial pneumonia, arthritis, ophthalmitis, conjunctivitis, neuritis, otitis media, encephalomyelitis, cystitis, laryngitis, food allergies, insect allergies, drug allergies, Xanajuela It is useful as a prophylactic and / or therapeutic agent for allergic diseases such as xie shock, as well as vasodilatation due to overproduction of PGD2, increased vascular permeability, and tissue damage associated with infiltration of inflammatory cells.
[0083] また、最近の研究から、脳血管障害、脳変性疾患、脱髄疾患等の疾患による脳損 傷部位では、ミクログリア細胞やマクロファージにお 、て造血器型 PGD2合成酵素 (H-PGDS)の発現が増加し、損傷部位で顕著な活性ィ匕が認められるァストログリア細 胞ではプロスタグランジン D受容体 (DP受容体)が誘導されることが確認された (特願 2002-204725号明細書参照)。脳損傷モデル動物に HQL-79の様な H- PDGS阻害剤 または DP受容体の拮抗剤を投与するとァストログリア細胞の活性ィ匕が抑制され、 H-PDGS大量発現トランスジエニックマウスでの脳損傷モデルでは損傷が増悪される ことから、 PGD2が脳損傷の増悪に関係していることは明らかである。従って、 H-PDGSの強力な阻害剤は、脳損傷の増悪の予防及び Z又は脳損傷の予後の改善 に有用な薬剤として有用であり、本発明の医薬もこの目的に使用できる。本発明の医 薬の適用対象となる脳損傷は特に限定されず、例えば、交通事故等による外傷性の もの、脳梗塞や脳出血等の脳血管障害によるもの、脳変性疾患、脱髄疾患等による ものなどを例示することができる力 これらに限定されることはない。  [0083] Recent studies have shown that hematopoietic PGD2 synthase (H-PGDS) can be found in microglial cells and macrophages at sites of brain injury caused by diseases such as cerebrovascular disease, cerebral degenerative disease, and demyelinating disease. It has been confirmed that prostaglandin D receptor (DP receptor) is induced in astroglial cells in which the expression of liposomes is increased and remarkable activity is observed at the injury site (Japanese Patent Application No. 2002-204725). reference). When an H-PDGS inhibitor such as HQL-79 or an antagonist of DP receptor is administered to a brain injury model animal, the activity of astroglial cells is suppressed, and a brain injury model in transgenic mice that overexpresses H-PDGS It is clear that PGD2 is involved in the exacerbation of brain injury, as the damage is exacerbated. Therefore, a potent inhibitor of H-PDGS is useful as an agent useful for preventing exacerbation of brain injury and improving the prognosis of Z or brain injury, and the medicament of the present invention can also be used for this purpose. The brain injury to which the medicament of the present invention is applied is not particularly limited.For example, traumatic injury due to a traffic accident, cerebrovascular disorder such as cerebral infarction or cerebral hemorrhage, cerebral degenerative disease, demyelinating disease, etc. Forces that can exemplify things and the like are not limited to these.
更に、 PGD2が、睡眠の誘発、体温低下、黄体ホルモン分泌抑制、痛みや匂いの応 答調節作用に関与していることが知られていることから (Vitamins and hormones, Vol.58, p.89— 120(2000); The Journal of Biological Chemistry, Vol.260, No.23, p.12140— 12145(1985);及び Biochimica et Biophysica Acta, Vol.1482, No.l— 2, p.259-271(2000)参照)、本発明の医薬は、性周期調節作用、睡眠調節作用、体温 調節作用、鎮痛作用、及び嗅覚調節作用からなる群力 選ばれる 1以上の作用を有 する医薬として有用である。 Furthermore, PGD2 is known to be involved in the induction of sleep, hypothermia, suppression of luteinizing hormone secretion, and regulation of pain and odor responses (Vitamins and hormones, Vol. 58, p. 89 — 120 (2000); The Journal of Biological Chemistry, Vol. 260, No. 23, p. 12140— 12145 (1985); and Biochimica et Biophysica Acta, Vol. 1482, No. l— 2, p.259-271 (2000)), and the medicament of the present invention has at least one action selected from the group consisting of a sexual cycle control action, a sleep control action, a body temperature control action, an analgesic action, and an olfactory control action. Useful as a medicine.
[0084] 本発明の医薬の有効成分としては、一般式 (I)及び (II)で表される化合物及び薬理 学的に許容されるそれらの塩、並びにそれらの水和物及びそれらの溶媒和物からな る群力 選ばれる物質の 1種又は 2種以上を用いることができる。本発明の医薬として は上記の物質自体を用いてもよいが、好適には、本発明の医薬は有効成分である上 記の物質と 1又は 2以上の薬学的に許容される製剤用添加物とを含む医薬組成物の 形態で提供される。上記医薬組成物において、製剤用添加物に対する有効成分の 割合は、 1重量％から 90重量％程度である。 [0084] The active ingredients of the medicament of the present invention include compounds represented by the general formulas (I) and (II), pharmacologically acceptable salts thereof, hydrates thereof, and solvates thereof. One or more of the selected substances can be used. The above-mentioned substance itself may be used as the medicament of the present invention, but preferably, the medicament of the present invention is used as an active ingredient and one or more pharmaceutically acceptable additives for pharmaceutical preparations. And in the form of a pharmaceutical composition comprising: In the above pharmaceutical composition, the ratio of the active ingredient to the pharmaceutical additive is about 1% to 90% by weight.
本発明の医薬は、例えば、顆粒剤、細粒剤、散剤、硬カプセル剤、軟カプセル剤、 シロップ剤、乳剤、懸濁剤、又は液剤などの経口投与用の医薬組成物として投与し てもよいし、静脈内投与、筋肉内投与、若しくは皮下投与用の注射剤、点滴剤、坐剤 、経皮吸収剤、経粘膜吸収剤、点鼻剤、点耳剤、点眼剤、吸入剤などの非経口投与 用の医薬組成物として投与することもできる。粉末の形態の医薬組成物として調製さ れた製剤を用時に溶解して注射剤又は点滴剤として使用してもよい。  The medicament of the present invention can be administered, for example, as a pharmaceutical composition for oral administration such as granules, fine granules, powders, hard capsules, soft capsules, syrups, emulsions, suspensions, or liquids. Good, intravenous, intramuscular or subcutaneous injections, drops, suppositories, transdermal absorbents, transmucosal absorbents, nasal drops, ear drops, eye drops, inhalants, etc. It can also be administered as a pharmaceutical composition for parenteral administration. A preparation prepared as a pharmaceutical composition in the form of a powder may be dissolved at the time of use and used as an injection or infusion.
[0085] 医薬用組成物の製造には、固体又は液体の製剤用添加物を用いることができる。 [0085] For the production of a pharmaceutical composition, a solid or liquid pharmaceutical additive can be used.
製剤用添加物は有機又は無機のいずれであってもよい。すなわち、経口用固形製 剤を製造する場合は、主薬に賦形剤、さらに必要に応じて結合剤、崩壊剤、滑沢剤 、着色剤、矯味矯臭剤などを加えた後、常法により錠剤、被覆錠剤、顆粒剤、散剤、 カプセル剤などの形態の製剤を調製することができる。用いられる賦形剤としては、 例えば、乳糖、蔗糖、白糖、ブドウ糖、コーンスターチ、デンプン、タルク、ソルビット、 結晶セルロース、デキストリン、カオリン、炭酸カルシウム、ニ酸ィ匕ケィ素などを挙げる ことができる。結合剤としては、例えば、ポリビュルアルコール、ポリビュルエーテル、 ェチルセルロース、メチルセルロース、アラビアゴム、トラガント、ゼラチン、シェラック、 ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、クェン酸カルシ ゥム、デキストリン、ぺクチンなどを挙げることができる。滑沢剤としては、例えば、ステ アリン酸マグネシウム、タルク、ポリエチレングリコール、シリカ、硬化直物油などを挙 げることができる。着色剤としては、通常医薬品に添加することが許可されているもの であればいずれも使用することができる。矯味矯臭剤としては、ココア末、ハツ力脳、 芳香酸、ハツ力油、龍脳、桂皮末などを使用することができる。これらの錠剤、顆粒剤 には、糖衣、ゼラチン衣、その他必要により適宜コーティングを付することができる。ま た、必要に応じて、防腐剤、抗酸化剤等を添加することができる。 The pharmaceutical additives may be either organic or inorganic. That is, when an oral solid preparation is produced, an excipient and, if necessary, a binder, a disintegrant, a lubricant, a coloring agent, a flavoring agent, etc. are added to the active substance, and then the tablet is prepared in a conventional manner. , Coated tablets, granules, powders, capsules and the like can be prepared. Examples of the excipient to be used include lactose, sucrose, sucrose, glucose, corn starch, starch, talc, sorbitol, crystalline cellulose, dextrin, kaolin, calcium carbonate, and silicon dioxide. Examples of the binder include polyvinyl alcohol, polyvinyl ether, ethyl cellulose, methyl cellulose, gum arabic, tragacanth, gelatin, shellac, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, calcium citrate, dextrin, and pectin. Can be mentioned. Lubricants include, for example, magnesium stearate, talc, polyethylene glycol, silica, hydrogenated spot oil and the like. I can make it. Any coloring agent can be used as long as it is normally permitted to be added to pharmaceutical products. As a flavoring agent, cocoa powder, heart-shaped brain, aromatic acid, heart-shaped oil, dragon brain, cinnamon powder and the like can be used. These tablets and granules can be sugar-coated, gelatin-coated and optionally coated as needed. Further, if necessary, a preservative, an antioxidant and the like can be added.
[0086] 経口投与のための液体製剤、例えば、乳剤、シロップ剤、懸濁剤、液剤の製造には 、一般的に用いられる不活性な希釈剤、例えば水又は植物油を用いることができる。 この製剤には、不活性な希釈剤以外に、補助剤、例えば湿潤剤、懸濁補助剤、甘味 剤、芳香剤、着色剤又は保存剤を配合することができる。液体製剤を調製した後、ゼ ラチンのような吸収されうる物質のカプセル中に充填してもよ!/、。非経口投与用の製 剤、例えば注射剤又は坐剤等の製造に用いられる溶剤又は懸濁剤としては、例えば 、水、プロピレングリコール、ポリエチレングリコール、ベンジルアルコール、ォレイン 酸ェチル、レシチンを挙げることができる。坐剤の製造に用いられる基剤としては、例 えば、カカオ脂、乳化カカオ脂、ラウリン脂、ウイテツブゾールを挙げることができる。 製剤の調製方法は特に限定されず、当業界で汎用されている方法はいずれも利用 可能である。  [0086] In the preparation of liquid preparations for oral administration, for example, emulsions, syrups, suspensions and liquid preparations, commonly used inert diluents such as water or vegetable oil can be used. In addition to the inert diluent, this preparation can contain adjuvants such as wetting agents, suspending agents, sweetening agents, flavoring agents, coloring agents and preservatives. After preparing the liquid preparation, it may be filled into capsules of absorbable substance such as gelatin! Examples of solvents or suspensions used for preparations for parenteral administration, such as injections or suppositories, include, for example, water, propylene glycol, polyethylene glycol, benzyl alcohol, ethyl oleate, and lecithin. it can. As the base used in the production of suppositories, for example, cocoa butter, emulsified cocoa butter, laurin fat, and witetbsol can be mentioned. The method for preparing the preparation is not particularly limited, and any method commonly used in the art can be used.
注射剤の形態にする場合には、担体として、例えば、水、エチルアルコール、マクロ ゴール、プロピレングリコール、クェン酸、酢酸、リン酸、乳酸、乳酸ナトリウム、硫酸及 び水酸ィ匕ナトリウム等の希釈剤；クェン酸ナトリウム、酢酸ナトリウム及びリン酸ナトリウ ム等の pH調整剤及び緩衝剤；ピロ亜硫酸ナトリウム、エチレンジァミン四酢酸、チォ グリコール酸及びチォ乳酸等の安定化剤等が使用できる。なお、この場合、等張性 の溶液を調製するために十分な量の食塩、ブドウ糖、マン-トール又はグリセリンを 製剤中に配合してもよぐ通常の溶解補助剤、無痛化剤又は局所麻酔剤等を使用す ることちでさる。  In the case of injectable form, as a carrier, for example, dilution of water, ethyl alcohol, macrogol, propylene glycol, citric acid, acetic acid, phosphoric acid, lactic acid, sodium lactate, sulfuric acid and sodium hydroxide PH adjusters and buffers such as sodium citrate, sodium acetate and sodium phosphate; stabilizers such as sodium pyrosulfite, ethylenediaminetetraacetic acid, thioglycolic acid and thiolactic acid can be used. In this case, a normal solubilizing agent, soothing agent, or local anesthetic, which may contain sufficient amounts of salt, glucose, mannitol, or glycerin in the preparation to prepare an isotonic solution It is better to use agents.
[0087] 軟膏剤、例えば、ペースト、クリーム及びゲルの形態にする場合には、通常使用さ れる基剤、安定剤、湿潤剤及び保存剤等を必要に応じて配合することができ、常法 により成分を混合して製剤化することができる。基剤としては、例えば、白色ワセリン、 ポリエチレン、パラフィン、グリセリン、セルロース誘導体、ポリエチレングリコール、シリ コン及びベントナイト等を使用することができる。保存剤としては、ノラオキシ安息香 酸メチル、パラォキシ安息香酸ェチル、パラォキシ安息香酸プロピル等を使用するこ とができる。貼付剤の形態にする場合には、通常の支持体に上記軟膏、クリーム、ゲ ル又はペースト等を常法により塗布することができる。支持体としては、綿、スフ及び 化学繊維カゝらなる織布又は不織布；軟質塩化ビニル、ポリエチレン及びポリウレタン 等のフィルム又は発泡体シートを好適に使用できる。 [0087] In the case of an ointment, for example, a paste, a cream or a gel, commonly used bases, stabilizers, wetting agents, preservatives and the like can be blended as required, and can be prepared by a conventional method. Can be formulated by mixing the components. Bases include, for example, white petrolatum, polyethylene, paraffin, glycerin, cellulose derivatives, polyethylene glycol, silicone Concrete and bentonite can be used. As the preservative, methyl noraoxybenzoate, ethyl ethyl paraoxybenzoate, propyl paraoxybenzoate and the like can be used. When the preparation is in the form of a patch, the above-mentioned ointment, cream, gel, paste or the like can be applied to a usual support in a conventional manner. As the support, woven or non-woven fabrics made of cotton, swoof and chemical fibers, and films or foam sheets of soft vinyl chloride, polyethylene and polyurethane can be suitably used.
本発明の医薬の投与量は特に限定されないが、経口投与の場合には、成人一日 あたり本発明化合物の重量として通常 0.01〜5,000mgである。この投与量を患者の 年令、病態、症状に応じて適宜増減することが好ましい。前記一日量は一日に一回、 又は適当な間隔をおいて一日に 2〜3回に分けて投与してもよいし、数日おきに間歇 投与してもよい。注射剤として用いる場合には、成人一日あたり本発明化合物重量と して 0.001〜100mg程度である。  The dose of the medicament of the present invention is not particularly limited. In the case of oral administration, the weight of the compound of the present invention per adult day is usually 0.01 to 5,000 mg. It is preferable to increase or decrease this dose appropriately according to the age, disease state and symptoms of the patient. The daily dose may be administered once a day, divided into two or three times a day at appropriate intervals, or may be administered intermittently every few days. When used as an injection, the weight of the compound of the present invention is about 0.001 to 100 mg per adult per day.
実施例  Example
[0088] 以下、実施例により本発明を更に具体的に説明するが、本発明の範囲は下記の実 施例の範囲に限定されることはない。実施例中の化合物番号は、上記の表において 示された化合物番号に対応して ヽる。  [0088] Hereinafter, the present invention will be described more specifically with reference to Examples, but the scope of the present invention is not limited to the following Examples. The compound numbers in the examples correspond to the compound numbers shown in the above table.
[0089] 例 1:化合物番号 1  Example 1: Compound No. 1
(1) 3-メチル -5-ォキソ -1-フエ-ル- 4,5-ジヒドロピラゾール- 4-カルバルデヒド (一般合 成法 α )  (1) 3-methyl-5-oxo-1-phenyl-4,5-dihydropyrazole-4-carbaldehyde (general synthesis method α)
3-メチル -1-フエ-ル- 4,5-ジヒドロピラゾール- 5-オン (2.90g, 16.6mmol)の Ν,Ν-ジメ チルホルムアミド (4ml)溶液に、氷冷下、ォキシ塩化リン (1.85ml, 193.8mmol)をカロえ、 80°Cで 1時間攪拌した。反応混合物を室温まで冷却後、氷水にあけ、室温で終夜攪 拌した。析出した固体を濾取、水洗、減圧乾燥した。この固体をイソプロピルエーテ ルで洗浄して、標題ィ匕合物の黄色固体 (1.70g, 50%)を得た。  To a solution of 3-methyl-1-phenyl-4,5-dihydropyrazol-5-one (2.90 g, 16.6 mmol) in Ν, Ν-dimethylformamide (4 ml) was added phosphorus oxychloride (1.85 g) under ice-cooling. ml, 193.8 mmol) and stirred at 80 ° C for 1 hour. After cooling the reaction mixture to room temperature, it was poured into ice water and stirred at room temperature overnight. The precipitated solid was collected by filtration, washed with water, and dried under reduced pressure. The solid was washed with isopropyl ether to obtain a yellow solid (1.70 g, 50%) of the title compound.
'H-NMRCCDCl ): δ 2.43(3H, s), 7.28— 7.33(1H, m), 7.42-7.48(2H, m),  'H-NMRCCDCl): δ 2.43 (3H, s), 7.28-7.33 (1H, m), 7.42-7.48 (2H, m),
3  Three
7.79-7.82(2H, m), 9.52(1H, s), 9.90(1H, s).  7.79-7.82 (2H, m), 9.52 (1H, s), 9.90 (1H, s).
(2)化合物番号 1(一般合成法 A)  (2) Compound No. 1 (General synthesis method A)
6-ァミノ- 1-ナフトール (159mg, lmmol)、 3-メチル -5-ォキソ -1-フエ-ル- 4,5-ジヒド •(ZH6 ΐ=ί" 'P 'HWn '(ζΗ ·ζ=Γ 'Ρ Ήΐ)8Γ6 WZl=i 'Ρ 'Ηΐ)ΐΖ·8 Z'Z=i 'Ρ 'Ηΐ) ·8 '(ω ' )W -WL '(ω 'H2)SZ"Z-S9"Z '(ω
Figure imgf000112_0001
'(ω Ήΐ) Γ -εΓ Ήε)εε 9 :( p-os a)H N-HT °% 6 ¾τ 6-amino-1-naphthol (159 mg, lmmol), 3-methyl-5-oxo-1-phenyl-4,5-dihydride • (ZH6 ΐ = ί "'P' HWn '( ζ Η · ζ = Γ' Ρ Ήΐ) 8Γ6 WZl = i 'Ρ' Ηΐ) ΐΖ8 Z'Z = i 'Ρ' Ηΐ) ') W -WL' (ω 'H2) SZ "Z-S9"Z' (ω
Figure imgf000112_0001
'(ω Ήΐ) Γ -εΓ Ήε) εε 9 :( p-os a) H NH T °% 6 ¾τ
s各粱呦^ ： Sfii s each siang 呦 ^: Sfii
•(s 'Ηΐ)86·6 '(zH2"8=f 'P 'Ηΐ)0 ·8 ^HVL=i 'P Ήΐ)96"Ζ '(ω Ή^)Ζ9"Ζ '(zHS"8=f 'P Ήΐ)63·Ζ '(ω Ή^)23· '(s Ήε) ·ε '(s Ήε) 3·ζ S :( P-OS a)H N-HT °%Z6 ? ill
Figure imgf000112_0002
'P 'Ηΐ) ·8 '(ζΗΓΐ '8·8=ί" 'PP 'H2)S0"8
Figure imgf000112_0003
'(ω • (s' Ηΐ) 86 · 6 '(zH2 "8 = f' P 'Ηΐ) 0 · 8 ^ HVL = i' P Ήΐ) 96" Ζ '(ω Ή ^) Ζ9 "Ζ'(zHS" 8 = f 'P Ήΐ) 63Ζ Ζ' (ω Ή ^) 23 · '(s Ήε) · ε' ( s Ήε) 3ζ ζ S :( P-OS a) H NH T °% Z6? ill
Figure imgf000112_0002
'P' Ηΐ) 8 '( ζ ΗΓΐ' 8 · 8 = ί "'PP' H2) S0" 8
Figure imgf000112_0003
'(ω
'HWL-e^L '(ω Ήΐ)ΖΓΖ-2Γ Ήε)εε 9 :( P-OS a)H N-HT °% ¾1 ε各粱呦^ m
Figure imgf000112_0004
'P 'Ηΐ)89·ΐΐ '(s Ήΐ)86 ΐ '(zHS"ST=f 'P 'HT)S8"8 '(s 'HT)S2"8 '(ω 'H2)20"8-66"Z '(ω 'H2)6Z"Z-TZ"Z '(ω 'HS)S Z— ΐε· '(ω Ήΐ)8ΓΖ-2ΓΖ '(s Ήε)3ε·ζ S :( P-OS a)H N-HT °%26*¾1
Figure imgf000112_0005
'HWL-e ^ L' (ω Ήΐ) ΖΓΖ-2Γ Ήε) εε 9 :( P-OS a) H NH T °% ¾1 εEach beam 呦 ^ m
Figure imgf000112_0004
'P' Ηΐ) 89 · ΐΐ '( s Ήΐ) 86 ΐ' (zHS "ST = f 'P' HT) S8" 8 '( s ' HT) S2 "8 '(ω' H2) 20" 8-66 "Z '(ω' H2) 6Z" Z-TZ "Z '(ω' HS) SZ— ΐε · ((ω Ήΐ) 8ΓΖ-2ΓΖ '(s Ήε) 3εζS :( P-OS a) H NH T °% 26 * ¾1
Figure imgf000112_0005
90 〜 9ε、 ¾ 09ε〜 ε (^ε〜8ΐε 9is〜sis οτε 9οε〜ζοε 96S〜S6S isz 90 to 9ε, ¾ 09ε to ε (^ ε to 8ΐε 9is to sis οτε 9οε to ζοε 96S to S6S isz
→SZ llZ、S 〜 I9S S2、SSS〜SSS、9 〜 、9SS〜SSS、IS IS、S 〜 、ΐ6ΐ〜 8ΐ Ί8ΐ〜εΖΐ、UI〜69I、 9ΐ〜 、( 〜8SI、SSI〜ISI 〜 SSI ZZ\ 〜6ΐΐ、9ΐΐ〜96、S6〜98 8〜SZ、U〜ZL、89〜09 8S、9S〜9 、„〜S各粱呦 → SZ llZ, S to I9S S2, SSS to SSS, 9 to, 9SS to SSS, IS IS, S to, {6 to 8} ΐ8 to εΖΐ, UI to 69I, 9 to, (to 8SI, SSI to ISI to SSI ZZ \ ~ 6ΐΐ, 9ΐΐ ~ 96, S6 ~ 98 8 ~ SZ, U ~ ZL, 89 ~ 09 8S, 9S ~ 9, „~ S
呦^ ¾止 2 呦 ^ ¾Stop 2
-
Figure imgf000112_0006
-
Figure imgf000112_0006
•(ZH6 i=f 'p Ήΐ)ε3·π • (ZH6 i = f 'p Ήΐ) ε3π
'(s Ήΐ)^ ΐ WZl=i 'P Ήΐ)9Ζ·8 '(ΖΗΓ6=Γ 'P Ήΐ)6Γ8 '(ζΗΐ·ΐ '8·8=ί" 'PP 'H2)20"8 '(ZHS =f 'P 'Ηΐ)Ζ6· '^ΗΖ 'Γ6=Γ 'PP 'Ηΐ)0ΓΖ '(ω 'Hf L-Z^L '( s Ήΐ) ^ ΐ WZl = i' P Ήΐ) 9Ζ8 '( Ζ ΗΓ6 = Γ' P Ήΐ) 6Γ8 '( ζ Ηΐ · ΐ' 888 = ί "'PP' H2) 20" 8 ' (ZHS = f 'P' Ηΐ) Ζ6 · '^ ΗΖ' Γ6 = Γ 'PP' Ηΐ) 0ΓΖ '(ω' Hf LZ ^ L
'(ω Ήΐ)8ΓΖ-2ΓΖ '(ΖΗ9 '6"S=f 'PP 'Ηΐ) 8·9 '(s Ήε)εε 9 :(9Ρ— OS ) Η顺— Ητ '(ω Ήΐ) 8ΓΖ-2ΓΖ' (ΖΗ9 '6 "S = f' PP 'Ηΐ) 8.9' ( s Ήε) εε 9 :( 9 Ρ— OS) Η 顺 — Η τ
。 %88 '^oz)^ U^^mn、ェっ 一 ^ m^ m-^n ^ ^^m^ ^ ^ ^ m w ^
Figure imgf000112_0007
0 S081760/S00Z OAV 'Ρ Ήΐ)33·Π '(s
Figure imgf000113_0001
'Ρ Ήΐ)0Γ8 '(ΖΗΖ·Ζ=ί" 'Ρ 'H2)S0"8 . % 88 '^ oz) ^ U ^^ mn, e ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^
Figure imgf000112_0007
0 S081760 / S00Z OAV 'Ρ Ήΐ) 33ΠΠ' (s
Figure imgf000113_0001
'Ρ Ήΐ) 0Γ8' (ΖΗΖ · Ζ = ί "'Ρ' H2) S0" 8
'(ΖΗΟ·8=1" 'Ρ 'HT)S8"Z '(ω 'HZ)Z9'L-WL '(ω 'HS)8^" -0^" '(ΖΗ6·ΐ=ί" 'Ρ Ήΐ)82"Ζ  '(ΖΗΟ · 8 = 1 "' Ρ 'HT) S8" Z' (ω 'HZ) Z9'L-WL' (ω 'HS) 8 ^ "-0 ^"' (ΖΗ6 · ΐ = ί "'Ρ Ήΐ) 82 "Ζ
'(ω Ήΐ)8Γζ-εΓζ '(s Ήε)ζο· '(s 'u vz 9 :( oswa) 顺— ΗΤ °%Ϊ6 ? Φ '(ω Ήΐ) 8Γζ-εΓζ' (s Ήε) ζο · '( s ' u vz 9 :( oswa) 顺 — Η Τ °% Ϊ6? Φ
π各粱呦^ --urn π each beam 呦 ^ --urn
•(ΖΗΓΠ=Γ 'Ρ 'Ηΐ)6ε ΐ '(ΖΗΓΠ=Γ 'Ρ 'Ηΐ)88·8 '^ΗΥ8=ί 'Ρ 'HT)28"8 • ( Ζ ΗΓΠ = Γ 'Ρ' Ηΐ) 6ε ΐ '( Ζ ΗΓΠ = Γ' Ρ 'Ηΐ) 88 · 8' ^ ΗΥ8 = ί 'Ρ' HT) 28 "8
(ω 'Η )60·8- WT8 '(ΖΗΖ·Ζ=ί" 'Ρ Ήΐ)06"Ζ '(ω 'H2)TZ"Z-T9"Z '(ω lWZ)LYL-WL '(saq (ω 'Η) 60 · 8- WT8' (ΖΗΖ · Ζ = ί "'Ρ Ήΐ) 06"Ζ' (ω 'H2) TZ "Z-T9"Z' (ω l WZ) LYL-WL '(saq
Ήΐ)6ΓΖ '(ΖΗ ·Ζ=1" Ήΐ)ΖΓΖ '(s Ήε) ε 9 :(9Ρ— OS^a) 顺— Ητ °%86 ¾ί Ήΐ) 6ΓΖ '(ΖΗ · Ζ = 1 "Ήΐ) ΖΓΖ' (s Ήε) ε 9 :( 9 Ρ— OS ^ a) 顺 — Η τ °% 86 ¾ί
οι各粱呦^  οι each siang 呦 ^
-(^ΗΖτΐ=ί 'Ρ Ήΐ)ε3·Π '(saq 'HT)89"6'(zH2-ST=f 'Ρ 'Ηΐ)ΖΖ·8 '(s Ήΐ)8Γ8 '(ω '蹄 ΐ·8- ΐ0·8 '(ω Ήε)88·Ζ— ΓΖ '(ω -(^ ΗΖτΐ = ί 'Ρ Ήΐ) ε3Π' (saq 'HT) 89 "6' ( z H2-ST = f 'Ρ' Ηΐ) ΖΖ8 '( s Ήΐ) 8Γ8' (ω ' · 8- ΐ0 · 8 '(ω Ήε) 88 · Ζ— ΓΖ' (ω
'H S 'Z— 6ε· '(ω Ήΐ)8ΓΖ-2Γ 'm)WZ 9 :(9Ρ— OSWa) Ν— Ητ °%96 ¾ί 'HS' Z— 6ε · '(ω Ήΐ) 8ΓΖ-2Γ' m) WZ 9 :( 9 Ρ— OSWa) Ν— Η τ °% 96 ¾ί
6各粱呦^ -em 6 each 呦
Figure imgf000113_0002
Figure imgf000113_0002
'P 'Ηΐ)¾·ΐΐ '(s Ήΐ)92·Π '(zHS-ST=f 'P 'HT)29"8 '(ω 'HS)WT8— ΐ0·8 '(ΖΗΓ2=Γ 'P' Ηΐ) ¾ · ΐΐ '(s Ήΐ) 92 · Π' (zHS-ST = f 'P' HT) 29 "8 '(ω' HS) WT8— ΐ0 · 8 '( Ζ ΗΓ2 = Γ
'P Ήΐ)9Ζ·Ζ '(ω 'Hf)SVL-SZ-L '(ΖΗΓ2 '8·8=ί" 'PP 'HT)62"Z '(ω Ήΐ)3ΓΖ-0ΓΖ 'P Ήΐ) 9Ζ · Ζ' (ω 'Hf) SVL-SZ-L' ( Ζ ΗΓ2 '8.88 = ί "' PP 'HT) 62"Z' (ω Ήΐ) 3ΓΖ-0ΓΖ
'(ΖΗΓ2=Γ '； 'Ηΐ)Ζ ·9 '(s 'HS)0S 9 :(9Ρ— Ν— Ητ °%S8 ? φ '( Ζ ΗΓ2 = Γ';'Ηΐ) Ζ · 9' ( s ' HS) 0S 9 :( 9 Ρ— Ν— Η τ °% S8? Φ
8各粱呦^ -s 8 each siang 呦 ^ -s
•(sjq 'Ηΐ)68·εΐ '( q 'HI)S8 ΐ '(s Ήΐ)ε ·8 '(s-i 'Ηΐ)89·8 '(s 'Ηΐ)ε ·8 '(ΖΗΓ8=Γ 'P Ήΐ)ΐΓ8 '(ΖΗΖ·Ζ=1" 'Ρ 'H2)00"8 (Sjq 'Ηΐ) 68 · ε' (q 'HI) S8 ΐ' ( s Ήΐ) ε8 '(si' Ηΐ) 898 '( s ' Ηΐ) ε8 '( Ζ ΗΓ8 = Γ' P Ήΐ) ΐΓ8 '(ΖΗΖ · Ζ = 1 "' Ρ 'H2) 00" 8
'(ΖΗ ·8=ί" 'Ρ Ήΐ)96"Ζ '(ω 'HT)SZ"Z-89"Z '(ω 'HI)9S'Z— SS'Z '(ω ΉΖ)ΖΥ L  '(ΖΗ · 8 = ί "' Ρ Ήΐ) 96" Ζ '(ω' HT) SZ "Z-89" Z '(ω' HI) 9S'Z— SS'Z '(ω ΉΖ) ΖΥ L
'； ' )fVL '(s Ήε)9ε 9 :(9ρ— oswa) 顺— ΗΤ °%S8 ? Φ ';') FVL '(s Ήε) 9ε 9 :( 9 ρ- oswa)顺- Η Τ °% S8 Φ?
\ [ΐ6οο] \ [ΐ6οο]
•(ZH6 I=f• (ZH6 I = f
'Ρ Ήΐ)Ζ3·Π '(ζΗε·6=ί" 'Ρ 'Ηΐ)68·8 '(ΖΗ6 ΐ=ί" 'Ρ 'Ηΐ)8Ζ·8 '(ω Ήε)80·8— ΐ0·8 'Ρ Ήΐ) Ζ3ΠΠ' (ζΗε6 = ί "'Ρ' Ηΐ) 68688 '(ΖΗ6 ΐ = ί"' Ρ 'Ηΐ) 8Ζ8' (ω Ήε) 80 · 88 ΐ0.8
'(ω 'H2)06"Z-98"Z '^ΗΖ'Ζ 'S"6=f 'PP Ήΐ)08"Ζ '(ω 'HS)TS"Z-0^"Z '(zW =f ' Ήΐ)3ΓΖ '(saq 'HI)8S'9 '(s 'HS)SS 9 :( OSW I) 顺— HT °% 8 ¾T '(ω' H2) 06 "Z-98" Z '^ ΗΖ'Ζ' S "6 = f 'PP Ήΐ) 08"Ζ' (ω 'HS) TS "Z-0 ^"Z' (zW = f 'Ήΐ) 3ΓΖ' (saq 'HI) 8S'9' ( s ' HS) SS 9 :( OSW I) 顺 — H T °% 8 ¾T
9各粱呦^ -9
Figure imgf000113_0003
S081760/S00Z OAV 6ΐ各粱呦 -6l K600] 9 each 呦 ^ -9
Figure imgf000113_0003
S081760 / S00Z OAV 6ΐEach 呦 6l K600]
•(ZH6 ΐ=ί" 'P 'Ηΐ)6 ·ΐΐ WZl=i 'P 'Ηΐ) Ζ·8 '(ΖΗΓ6=Γ 'P 'Ηΐ) ΐ·8 '(ω Ήε)90·8- ΐ0·8 '(ZHS 'Γ6=Γ 'ΡΡ 'Ηΐ)ΟΓΖ 'HT)29"Z '(ω • (ZH6 ΐ = ί "'P' Ηΐ) 6ΐΐWZl = i 'P' Ηΐ) 88 '( Ζ ΗΓ6 = Γ' P 'Ηΐ) 88' (ω Ήε) 90 · 8 ΐ0 · 8 '(ZHS' Γ6 = Γ 'ΡΡ' Ηΐ) ΟΓΖ 'HT) 29 "Z' (ω
'H S 'Z— 6ε· '(ω 'HZ)LVL-\VL 'ΗΖ^Ζ 9 :( OSW I) 顺— Ητ °% 6 ¾ί 'HS' Z— 6ε · '(ω' HZ) LVL- \ VL 'ΗΖ ^ Ζ 9 :( OSW I) 顺 — Η τ °% 6'
8ΐ各粱呦^ -si  8ΐEach 呦 ^ -si
"(ω '蹄 0·8- 86 '(ω 'Η ·Ζ- 08 '(ω 'H9)2Z"Z-0S"Z  "(ω 'Hoof 0 · 8-86' (ω 'Η · Ζ-08' (ω 'H9) 2Z" Z-0S "Z
'(ω
Figure imgf000114_0001
'(ω 'HW -er Ήε) ε 9 :(ει αつ) Η顺— ΗΤ °%S6 ? Φ '(ω
Figure imgf000114_0001
'(ω' HW -er Ήε) ε 9 :( ε ι α つ) Η 顺 — Η Τ °% S6? Φ
•(ω 'H2)20"8-86" 'Ηΐ)6Ζ· '(ω ·Ζ—Ζε· • (ω 'H2) 20 "8-86"' Ηΐ) 6Ζ · '(ω · Ζ—Ζε ·
'(ω Ήΐ)6ΓΖ-εΓΖ
Figure imgf000114_0002
'Ρ 'Ηΐ)06·9 '(ΖΗΖ =1" 'Ρ 'Ηΐ)9Γ9 '(ΖΗΖ'(ω Ήΐ) 6ΓΖ-εΓΖ
Figure imgf000114_0002
'Ρ' Ηΐ) 06 · 9 '(ΖΗΖ = 1 "' Ρ 'Ηΐ) 9Γ9' (ΖΗΖ
's'8=f 'ρ Ήΐ)οζ·9 '(ω 'HW -^ '(s Ήε)οε 9 -(OQOWn-^ °%96 ¾Τ 's'8 = f' ρ Ήΐ) οζ9 '(ω' HW-^ '( s Ήε) οε 9-(OQOWn- ^ °% 96 ¾Τ
9ΐ各粱呦^ -9i 9 呦 each 呦 ^ -9i
•(ZH6 ΐ=ί" 'P 'Ηΐ)½·ΐΐ '(ζΗ9·ΐ '2"8=Γ 'ΡΡ 'Ηΐ)98·8 '(ΖΗ6 ΐ=ί" 'Ρ 'Ηΐ) Ζ·8 • (ZH6 ΐ = ί "'P' Ηΐ) ½ · ΐΐ '(ζΗ9 · ΐ' 2" 8 = Γ 'ΡΡ' Ηΐ) 98 · 8 '(ΖΗ6 ΐ = ί "' Ρ 'Ηΐ) Ζ · 8
'(ζΗ9·ΐ '2"8=Γ 'ΡΡ Ήΐ)2ε·8 '(ω 'Η ·8- 00·8 '(ζΗΐ· ' ·8=ί" 'PP 'HI)ZS'Z '(ω '(ζΗ9 · ΐ' 2 "8 = Γ 'ΡΡ Ήΐ) 2ε · 8' (ω 'Η · 8- 00 · 8' ( ζ Ηΐ · '· 8 = ί"' PP 'HI) ZS'Z' ( ω
'm L-ez-L '(^ ΉΪ)8ΓΖ-2Γ Ήε)εε 9 :(9ρ— oswa) Ν— ΗΤ °% Ζ ¾Τ 'm L-ez-L' (^ ΉΪ) 8ΓΖ-2Γ Ήε) εε 9 :( 9 ρ— oswa) Ν— Η Τ °% Ζ ¾Τ
SI各粱呦^ - i SI each 呦 ^-i
•(ΖΗ6 ΐ=ί" 'P 'HWU WZl=i 'P Ήΐ)0Ζ·8 '(s 'Ηΐ)60·8 • (ΖΗ6 ΐ = ί "'P' HWU WZl = i 'P Ήΐ) 0Ζ8' ( s ' Ηΐ) 60 · 8
'(zH0"8=f 'P 'H2)20"8 '(zH8"8=f 'P 'HT)S8" 'Ηΐ) Z '(ω Ήε)^Ζ—εε· '( z H0 "8 = f' P 'H2) 20"8' ( z H8 "8 = f 'P' HT) S8"'Ηΐ)Z' (ω Ήε) ^ Ζ—εε
'(ΖΗ ·ζ=ί" ' )fVL '(s Ήε)2ε·ζ s :(9p— oswa) 顺— HT °%S8 ? Φ '(ΖΗ · ζ = ί "') fVL '( s Ήε) 2εζζ s :( 9 p— oswa) 顺 — H T °% S8? Φ
•(ZH9 i=f 'p ' )zviV(s Ήΐ)3ε·π • (ZH9 i = f 'p') zviV ( s Ήΐ) 3επ
'(ZH9 I=f 'P 'HT)SZ"8 '(s Ήΐ)3Γ8 '(ω 'H2)66"Z-96"Z '(ω 'H2)68"Z-6Z"Z '(ω  '(ZH9 I = f' P 'HT) SZ "8' (s Ήΐ) 3Γ8 '(ω' H2) 66" Z-96 "Z '(ω' H2) 68" Z-6Z "Z '(ω
'Η ε ·Ζ—8ε· '(ω 'H\)LVL-ZVL '(s Ήε)ΐε 9 :( OSWa) 顺— HT °%96 ¾T 'Η ε · Ζ-8ε ·' (ω 'H \) LVL-ZVL' (s Ήε) ΐε 9 :( OSWa) 顺 — H T °% 96 ¾T
ει各粱呦 K600] ει each sword K600]
"(ω 'Ηΐ)6ΐ·8- 9Γ8 '(ω "(ω 'Ηΐ) 6ΐ8-9Γ8' (ω
HS)90"8-Z6"Z '(s Ήΐ)ΐ6· '(ω 'HS)9S'Z- OS'Z '(ω 'H ·Ζ- ΐ · '(ω 'Ηΐ) - 9ΐ·  HS) 90 "8-Z6" Z '(s Ήΐ) ΐ6' (ω 'HS) 9S'Z- OS'Z' (ω 'H · Ζ- ΐ ·' (ω 'Ηΐ)-9ΐ
'(s Ήΐ)90·ζ (s
Figure imgf000114_0003
'(s Ήε) ε 9 :(ει α )Η顺- ΗΤ °%SZ ¾Τ '( s Ήΐ) 90
Figure imgf000114_0003
'(s Ήε) ε 9 :( ε ι α) Η 顺-Η Τ °% SZ ¾Τ
Figure imgf000114_0004
s S081760/S00Z OAV 'WL=[ Ήΐ)9ΓΖ '(s 'H6)S 'I 9 :( OSW I) 顺— HT °%S8 ? φ
Figure imgf000114_0004
s S081760 / S00Z OAV 'WL = [Ήΐ) 9ΓΖ' (s 'H6) S' I 9 :( OSW I) 顺 — H T °% S8? Φ
32- & Ζ\ •(ZHS I=f 'P 'HI)SS ΐ '(s 'Ηΐ) Οΐ 'WZl=i 'P 'Ηΐ)ΐ8·8 32- & Ζ \ (ZHS I = f 'P' HI) SS ΐ '( s ' Ηΐ) Οΐ' WZl = i 'P' Ηΐ) ΐ8
'P Ήΐ)6Γ8 '(ω 'HS)S0"8-66"Z '(ω 'HI)U'Z— 89· '(ω ' )WL-LZ'L '(ω  'P Ήΐ) 6Γ8' (ω 'HS) S0 "8-66" Z' (ω 'HI) U'Z— 89 ·' (ω ') WL-LZ'L' (ω
Ήΐ)6ΓΖ-ΖΓΖ '(ω 'HI)S8'9— 8·9 '(s Ήΐ) 6ΓΖ-ΖΓΖ '(ω' HI) S8'9— 8.9 '( s
Figure imgf000115_0001
Figure imgf000115_0001
•(s'HT)S -6 '(ra'H2)88"Z-^8"Z '{^'HZ)WL-ZVL '{^'H\)Z^ L-^ L '(s'H6)WI 9  • (s'HT) S -6 '(ra'H2) 88 "Z- ^ 8" Z' {^ 'HZ) WL-ZVL' {^ 'H \) Z ^ L- ^ L' (s'H6 ) WI 9
:( Iつ aつ) WN- Ht °%ooi ¾ί
Figure imgf000115_0002
一 :( I a a) WN- H t °% ooi ¾ί
Figure imgf000115_0002
one
、 ^ - 一 ^^c^ ^- s ' / ェ - ΐ- ^P - s- ( ^ : - ε )  , ^-One ^^ c ^ ^-s' /--ΐ- ^ P-s- (^:-ε)
'- z 600] '-z 600]
•(ΖΗΖ·Ζ=ί" 'Ρ Ή2)86"Ζ '(s Ήΐ)88"Ζ '(ω ' )ZVL-LZ'L '(ω 'HZ)SVL-fVL '(ΖΗΖ·Ζ=ί" 'Ρ 'Ηΐ)80· '(s 'HT)T8"S '(Jq Ήΐ)03·ζ 'HS)8^"2 9 :( !DaD)H N-HT °%98 ¾ί • (ΖΗΖ · Ζ = ί "'Ρ Ή2) 86"Ζ' (s Ήΐ) 88 "Ζ '(ω') ZVL-LZ'L '(ω' HZ) SVL-fVL '(ΖΗΖ · Ζ = ί"'Ρ' Ηΐ) 80 · '(s' HT) T8 "S '(Jq Ήΐ) 03ζζ' HS) 8 ^" 2 9 :(! DaD) H NH T °% 98 ¾ί
•(s 'Ηΐ)9 ·8 '(ω 'H2)00"8-96"Z '(ω 'Η 8·Ζ-9ΓΖ • ( s ' Ηΐ) 9 · 8 '(ω' H2) 00 "8-96" Z '(ω' Η 8
'(ω 'HWL-IZ-L '(ω Ήΐ)22· -9Γ 'HS)9S"2 9 :( !DaD)H N-HT °%88 ¾ί '(ω' HWL-IZ-L '(ω Ήΐ) 22 · -9Γ' HS) 9S "2 9 :(! DaD) H NH T °% 88 ¾ί
\ VZ\=[ 'P Ήΐ) 3·Π '(s 'HI)SZ'6 'W2T=f 'P 'HI) ·6 '(zH8"8=f 'P 'Ηΐ)8ε·8 '(ΖΗΖ·Ζ=1" 'P 'H2)T0"8 '(zH8"8=f 'P 'Ηΐ)0ΓΖ '(ω \ VZ \ = ['P Ήΐ) 3Π' (s 'HI) SZ'6' W2T = f 'P' HI) 6 '( z H8 "8 = f' P 'Ηΐ) 8ε8' ( Ζ · Ζ = 1 "'P' H2) T0" 8 '( z H8 "8 = f' P 'Ηΐ) 0ΓΖ' (ω
' )WL-LZ-L '(ω 'Η2)6ΓΖ-2ΓΖ '(s Ήε)0 9 :( OSWa) 顺— HT ¾ί ') WL-LZ-L' (ω 'Η2) 6ΓΖ-2ΓΖ' (s Ήε) 0 9 :( OSWa) 顺 — H T ¾ί
•(ω 'H2)00"8-98"Z '(s Ήΐ)98· • (ω 'H2) 00 "8-98" Z' (s Ήΐ) 98 ·
'(ω
Figure imgf000115_0003
'p 'Hi)erz '(ω 'HZ)LO'L-WL '(ω
Figure imgf000115_0003
'p' Hi) erz '(ω' HZ) LO'L-WL
'(ω 'HT)S6"9-26"9 '(^ 'H2)^8"9-28"9 '(s 'HS)0S"2 9 :( !DaD)H N-HT °%S6 ? φ '(ω' HT) S6 "9-26" 9 '(^' H2) ^ 8 "9-28" 9 '( s ' HS) 0S "2 9 :(! DaD) H NH T °% S6? φ
'P 'Ηΐ)ΐ9·ΐΐ
Figure imgf000115_0004
'Ρ Ήΐ)0Γ8 '(ω Ήε)Μ)·8— 86· 'P' Ηΐ) ΐ9
Figure imgf000115_0004
'Ρ Ήΐ) 0Γ8' (ω Ήε) Μ) 8—86
'8·8=ί" 'ΡΡ 'HT)SZ"Z '(s 'HT)^9" '(ω 'H2)S^" -6S" ^ΗΥΙ=ί 'Ρ 'HW '(ω Ήΐ)ΖΓΖ-2ΓΖ '(s Ήε) ε 9 :(9Ρ— OS^a) 顺— Ητ °%06 ¾ί
Figure imgf000115_0005
ε '(s Ήΐ)32·Π '(ζΗΐ·εΐ=ί" 'Ρ 'Ηΐ)89·8 '(zHO"T Ί'8=ί 'PP 'HZ)WS '^ΗΖ'Ζ=ί 'Ρ Ήΐ)8Ζ·Ζ '(ω 'Hf)SVL-6Z-L '^ΗΖ'Ζ '9·8=ί" 'PP 'HT)92"Z '(ω Ήΐ)8ΓΖ-2ΓΖ '8 · 8 = ί "' ΡΡ 'HT) SZ"Z' (s 'HT) ^ 9 "' (ω 'H2) S ^" -6S "^ ΗΥΙ = ί' Ρ 'HW' (ω Ήΐ) ΖΓΖ -2ΓΖ '(s Ήε) ε 9 :( 9 Ρ— OS ^ a) 顺 — Η τ °% 06 ¾ί
Figure imgf000115_0005
ε '( s Ήΐ) 32Π' (ζΗΐζΗΐεζΗΐ = ί "'Ρ' Ηΐ) 89 · 8 '( z HO" T Ί'8 = ί' PP 'HZ) WS' ^ ΗΖ'Ζ = ί 'Ρ Ήΐ) 8 Ζ Ζ '(ω' Hf) SVL-6Z-L '^ ΗΖ'Ζ' 9.88 ί "'PP' HT) 92" Z '(ω Ήΐ) 8ΓΖ-2ΓΖ
'； Ήΐ)6 ·9 '(s 'm)ZVl 9 :( OSW I) 顺— Ητ °% S ¾ί ΐε各粱呦 m '; Ήΐ) 6 · 9' ( s ' m) ZVl 9 :( OSW I) 顺 — Η τ °% S ΐ ΐε
•(ζΗε i=f 'ρ 'Ηΐ)80·ει • (ζΗε i = f 'ρ' Ηΐ) 80
'(s 'Ηΐ) Γ6 WZl=i 'P 'HT)28"8 '(ΖΗΖ·Ζ=1" 'P 'Ηΐ)0ε·8 '(ω 'HS)80'8— WT8
Figure imgf000116_0001
'( s ' Ηΐ) Γ6 WZl = i' P 'HT) 28 "8' (ΖΗΖΖΗΖ = 1"'P' Ηΐ) 0ε8 '(ω' HS) 80'8—WT8
Figure imgf000116_0001
'(ΖΗ ·Ζ=1" '； Ήΐ)8ΓΖ '(s 'HS)S '(s 'Η6) ·ΐ 9 :( OSWa) 顺— HT °%S9 ? φ '(ΖΗ · Ζ = 1 "'; Ήΐ) 8ΓΖ '(s' HS) S '(s' Η6) · ΐ 9 :( OSWa) 顺 — H T °% S9? Φ
•(ΖΗ6 I=f 'P 'Ηΐ)88·ΐΐ WZl=i 'P Ήΐ)2 ·8 '(s 'HI)W8 '(WT '9"8=f 'PP 'HZ)WS '(^ 'HS)S6 —( 'Z • (ΖΗ6 I = f 'P' Ηΐ) 88ΐΐWZl = i 'P Ήΐ) 2 · 8' ( s ' HI) W8 '(WT'9'8 = f 'PP' HZ) WS '(^' HS) S6 — ('Z
'(ω 'H2)8S"Z-Z^"Z '(ω 'H ·Ζ- 8S' '(zW =f Ήΐ)^ΓΖ ^HV =i 'HT)28"S '(ΖΗ · =1" 'Ρ 'HZ)6L-f '(s 'HS)SS 9 :( OSWd) N— HT °% ¾ί '(ω' H2) 8S "ZZ ^" Z '(ω' H · Ζ-8S '' (zW = f Ήΐ) ^ ΓΖ ^ HV = i 'HT) 28 "S' (ΖΗ · = 1"'Ρ'HZ)6L-f' ( s ' HS) SS 9 :( OSWd) N— H T °% ¾ί
•( q 'Ηΐ)ΐ6·ΐΐ '( q 'Ηΐ)8ε·ΐΐ '(S 'Ηΐ)88·8 '(ζΗΓ8=Γ 'P Ήΐ)60·8 '(ζΗΓ8=Γ 'P Ή2)00"8 '(saq Ήΐ)08"Ζ '(ω 'HT)SZ"Z-89"Z '(ω 'HZW L-QV L ^HVL=i ' Ήΐ)ΖΓΖ '(saq 'Ηΐ) 6·9 '(s 'm)WZ 9 :( OSWd) N— HT ¾T
Figure imgf000116_0002
• (q 'Ηΐ) ΐ6 · ΐΐ' (q 'Ηΐ) 8ε · ΐΐ' (S 'Ηΐ) 88 · 8' (ζ ΗΓ8 = Γ 'P Ήΐ) 60 · 8' (ζ ΗΓ8 = Γ 'P Ή2) 00 "8 '(saq Ήΐ) 08"Ζ' (ω 'HT) SZ "Z-89"Z' (ω 'HZW L-QV L ^ HVL = i' Ήΐ) ΖΓΖ '(saq' Ηΐ) 6.9 '( s ' m) WZ 9 :( OSWd) N— H T ¾T
Figure imgf000116_0002
'P 'HT)SZ"Z '(ZW
Figure imgf000116_0003
' 'HZ)WL '(ω'P' HT) SZ "Z '(ZW
Figure imgf000116_0003
'' HZ) WL '(ω
Ή ε· '(ω Ήΐ)εζ· '(ω 'ΗΪ)6ΓΖ '(s Ή ε· 9 :(ει αつ) Η顺— ΗΤ °%ΟΖ ¾Τ
Figure imgf000116_0004
Ή ε · '(ω Ήΐ) εζ ·' (ω 'ΗΪ) 6ΓΖ' (s Ή ε · 9 :( ε ι α つ) Η 顺 — Η Τ °% ΟΖ ¾Τ
Figure imgf000116_0004
'Ρ 'Ηΐ)εθ·8 '(ΖΗ0·8=ί" 'Ρ 'H2)S6"Z
Figure imgf000116_0005
Ι-ΖΖΊ '(ω
Figure imgf000116_0006
'HT)S6"9 '(s 'Η6)0 ·ΐ 9 :( <3つ) Η顺— Ητ ¾ί 'Ρ' Ηΐ) εθ · 8 '(ΖΗ0 · 8 = ί "' Ρ 'H2) S6" Z
Figure imgf000116_0005
Ι-ΖΖΊ '(ω
Figure imgf000116_0006
'HT) S6 "9' ( s ' Η6) 0 · ΐ 9 :( <3) Η 顺 — Η τ ¾ί
9S各粱呦 -9z 9S each 呦 -9z
•(ZH6 ΐ=ί" 'P Ήΐ)ΐ^2ΐ '(s Ήΐ)26 ΐ WZl=i 'P 'Ηΐ) 8·8 '(s 'Ηΐ) ·8 (ΖΗΓΐ 'S"8=f 'PP 'Η εθ·8 '(ω 'Ηΐ)98Ή8·Ζ '(ω 'Ηΐ)εΖ·Ζ—ΐΓΖ'(ω ' )W L-\Z' L
Figure imgf000116_0007
S081760/S00Z OAV 8S各粱呦^ -Sm 600] •(ω 'Ηΐ)Ζε·ΐΐ '(s Ήΐ)90 ΐ '(ω 'Ηΐ)Ζ8·8 '(ΖΗΖ·Ζ=1" 'Ρ 'HZ)WS '(ΖΗΓ6=Γ 'Ρ • (ZH6 ΐ = ί "'P Ήΐ) ΐ ^ 2ΐ' ( s Ήΐ) 26 ΐ WZl = i 'P' Ηΐ) 8.8 '( s ' Ηΐ) 8 (ΖΗΓΐ 'S" 8 = f' PP 'Η εθ8' (ω 'Ηΐ) 98Ή8Ή' (ω 'Ηΐ) εΖΗΐΖΐΓΖ ((ω') W L- \ Z 'L
Figure imgf000116_0007
S081760 / S00Z OAV 8S each beam 呦 ^ -Sm 600] • (ω 'Ηΐ) Ζε · ΐΐ' ( s Ήΐ) 90 ΐ '(ω' Ηΐ) Ζ8 · 8 '(ΖΗΖ · Ζ = 1 "' Ρ 'HZ) WS' ( Ζ ΗΓ6 = Γ 'Ρ
'HT)S6"Z '(ΖΗΐ·8=ί" ' 'H2)S9"Z '(ω ΉΖ)ίΥ L '(ΖΗΐ·6 'S =1" 'ΡΡ 'ΗΙ)Ζ£Ί ^ΗΖ'Ζ=ί 'HT) S6 "Z' (ΖΗΐ8 = ί" '' H2) S9 "Z '(ω ΉΖ) ίΥ L' (ΖΗΐ · 6 'S = 1"' ΡΡ 'ΗΙ) Ζ £ Ί ^ ΗΖ'Ζ = ί
'ρ Ήΐ)32· 'WL=[ '； ΉΪ)ΖΓΖ '(s Ήε)εε 9 :(9ρ— oswa) 顺— ΗΤ °%S6 ? Φ 'ρ Ήΐ) 32 ·' WL = ['; ΉΪ) ΖΓΖ' (s Ήε) εε 9 :( 9 ρ— oswa) 顺 — Η Τ °% S6? Φ
•(ZHO I=f• (ZHO I = f
'P 'Ηΐ) ΐ '( q Ήΐ)Ζ^ ΐ '(ΖΗ0 ΐ=ί" 'Ρ 'Ηΐ)ΐΖ·8 mVS=i 'Ρ Ήΐ)32·8 'P' Ηΐ) ΐ '(q Ήΐ) Ζ ^ ΐ' (ΖΗ0 ΐ = ί "'Ρ' Ηΐ) ΐΖ8 mVS = i 'Ρ Ήΐ) 32
'(zW8=f 'Ρ 'H2)S0"8 '(s Ήΐ)Μ)·8 ^HVS 'Ρ Ήΐ)06"Ζ VL=i 'Ρ 'HT)SZ"Z  '(zW8 = f' Ρ 'H2) S0 "8' (s Ήΐ) Μ) 8 ^ HVS 'Ρ Ήΐ) 06" Ζ VL = i' Ρ 'HT) SZ "Z
'(ΖΗΐ·8=ί" 'Ρ 'HT)OZ"Z
Figure imgf000117_0001
'(ΖΗΐ · 8 = ί "' Ρ 'HT) OZ" Z
Figure imgf000117_0001
' Ήΐ)9ΓΖ
Figure imgf000117_0002
'Ηΐ)Ζ6·9 '(s 'ΗΖ 'Ζ 9 :( Ν— Ητ °%89 ¾ί 'Ήΐ) 9ΓΖ
Figure imgf000117_0002
'Ηΐ) Ζ6 · 9' ( s 'ΗΖ' Ζ 9 :( Ν— Η τ °% 89 ¾ί
9ε各粱呦 -9  9ε each siang 呦 -9
\ VZ\=[ 'Ρ Ή\)ΖνΖ\ '(s Ήΐ)82 ΐ '{^HVZ\=[ 'Ρ 'Ηΐ)ε8·8 '(zHO"T '9·8=ί" \ VZ \ = ['Ρ Ή \) ΖνΖ \' ( s Ήΐ) 82 ΐ '{^ HVZ \ = [' Ρ 'Ηΐ) ε8 · 8' ( z HO "T '9 · 8 = ί"
PP 'H2)S0"8 '(ΖΗΐ ·8=ί" 'Ρ Ήΐ)06"Ζ
Figure imgf000117_0003
'Ρ 'HT)SZ"Z '(ω PP 'H2) S0 "8' (ΖΗΐ · 8 = ί"'Ρ Ήΐ) 06 "Ζ
Figure imgf000117_0003
'Ρ' HT) SZ "Z '(ω
'HZ)LVL- L '(ω 'm)ZZ-L- VL '(s Ήε)εε 9 :( OSWd) N— HT °%88 ¾ί 'HZ) LVL- L' (ω 'm) ZZ-L- VL' ( s Ήε) εε 9 :( OSWd) N— H T °% 88 ¾ί
es- & :esp }es- & : esp}
•(zW2T=f 'P Ήΐ ^ΐ '(s 'HWOT '(zW2T=f 'P 'Ηΐ)ΐ6·8 '(ω Ήε)60·8— S0'8• (zW2T = f 'P Ήΐ ^ ΐ' (s 'HWOT' (zW2T = f 'P' Ηΐ) ΐ6.8 · (ωΉε) 60) 8—S0'8
Figure imgf000117_0004
Figure imgf000117_0004
' Ήΐ)ΖΓΖ '(ΖΗ6·9=1" 'Ρ 'Ηΐ)ΐΟ· '(s Ήε ^ 9 :( OSWa) 顺— Ητ °%08 ¾ί 'Ήΐ) ΖΓΖ' (ΖΗ6 · 9 = 1 "'Ρ' Ηΐ) ΐΟ '' (s Ήε ^ 9 :( OSWa) 顺 — Η τ °% 08 ¾ί
•(ω 'Ηΐ)^·8— 6Γ8 '(ω 'Ηε)Ζ0·8- ΐ0·8 '(ω 'HT)26"Z-88"Z '(zHS'8=f 'Ρ 'HI)SZ'Z • (ω 'Ηΐ) ^ · 8— 6Γ8' (ω 'Ηε) Ζ0.8- ΐ0.8' (ω 'HT) 26 "Z-88" Z' (zHS'8 = f 'Ρ' HI) SZ 'Z
'(ω 'H9)Z9"Z-6S"Z '(ω Ήΐ)ΐ2·Ζ-9Γ 'm)WZ 9 :( <3つ) Η顺— Ητ °%Ζ8 ? φ '(ω' H9) Z9 "Z-6S" Z '(ω Ήΐ) ΐ2ΖΖ-9Γ' m) WZ 9 :( <3) Η 顺 — Η τ °% Ζ8? φ
εε各粱呦 -zm [9600] εε each 呦 -zm [9600]
•(zHS'SI=f 'P 'H\)WZ\ '(zHS'SI=f 'P 'HT)6S"8 • (zHS'SI = f 'P' H \) WZ \ '(zHS'SI = f' P 'HT) 6S "8
'(ΖΗΖ·Ζ=1" 'P 'H2)66"Z '(s Ήΐ)9^" '(ω ΉΖ)Ζνί-9£Ί ^HVL=i Ήΐ)2ΓΖ  '(ΖΗΖ · Ζ = 1 "' P 'H2) 66" Z' (s Ήΐ) 9 ^ "'(ω ΉΖ) Ζνί-9 £ Ί ^ HVL = i Ήΐ) 2ΓΖ
'(s 'HT)½"9'(zH8 =f 'Ρ 'Ηΐ)Ζ0·9 '(ΖΗ8 =Γ 'Ρ 'Ηΐ)90·9 q 'HT)28"S '(zHS'9=f 'b 'Ηΐ)88· '(s 'm)SZ'Z '(ζΗε·9=ί" 'P 'HS)6S"T 9 :( OSWa) 顺— HT °%S6 ? φ
Figure imgf000117_0005
'p Ήΐ)εε ΐ
Figure imgf000117_0006
s S081760/S00Z OAV 収率 65%。 H-NMR(DMSO-d ): δ 2.21(3H, s), 2.50(3H, s), 7.14(1H, t, J=7.4Hz),'( s ' HT) ½ "9 '( z H8 = f' Ρ 'Ηΐ) Ζ0.9' ( Ζ Η8 = Γ 'Ρ' Ηΐ) 909 q 'HT) 28"S'(zHS'9 = f ' b ' Ηΐ) 88 · '( s ' m) SZ'Z' (ζΗε9 = ί "'P' HS) 6S" T 9 :( OSWa) 顺 — H T °% S6? φ
Figure imgf000117_0005
'p Ήΐ) εε ΐ
Figure imgf000117_0006
s S081760 / S00Z OAV Yield 65%. H-NMR (DMSO-d): δ 2.21 (3H, s), 2.50 (3H, s), 7.14 (1H, t, J = 7.4Hz),
6 6
7.42(2H, t, J=8.0Hz), 7.55(2H, m), 7.63(1H, m), 7.89(1H, d, J=5.2Hz), 7.92(1H, d, J=5.5Hz), 8.00(1H, d, J=7.7Hz), 8.04(2H, m), 8.20(1H, d, J=11.8Hz), 11.28(1H, m). 例 39:化合物番号 39  7.42 (2H, t, J = 8.0Hz), 7.55 (2H, m), 7.63 (1H, m), 7.89 (1H, d, J = 5.2Hz), 7.92 (1H, d, J = 5.5Hz), 8.00 (1H, d, J = 7.7Hz), 8.04 (2H, m), 8.20 (1H, d, J = 11.8Hz), 11.28 (1H, m) .Example 39: Compound No. 39
収率 93%。 ^-NMRCCD OD): δ 2.32(3H, s), 7.18(1H, t, J=7.4Hz), 7.44(2H, t, Yield 93%. ^ -NMRCCD OD): δ 2.32 (3H, s), 7.18 (1H, t, J = 7.4Hz), 7.44 (2H, t,
3  Three
J=8.0Hz), 7.84(2H, m), 7.91(2H, m), 8.03(2H, dd, J=l.l, 8.5Hz), 8.14(1H, d, J=7.7Hz), 8.28(1H, dd, J=1.6, 8.0Hz), 8.87(1H, d, J=7.1Hz).  J = 8.0Hz), 7.84 (2H, m), 7.91 (2H, m), 8.03 (2H, dd, J = ll, 8.5Hz), 8.14 (1H, d, J = 7.7Hz), 8.28 (1H, dd, J = 1.6, 8.0Hz), 8.87 (1H, d, J = 7.1Hz).
例 40:化合物番号 40 Example 40: Compound number 40
収率 90%。 'H-NMRCDMSO-d ): δ 2.37(3Η, s), 7.19(1Η, m), 7.45(2Η, m), 90% yield. 'H-NMRCDMSO-d): δ 2.37 (3Η, s), 7.19 (1Η, m), 7.45 (2Η, m),
6  6
7.71(2Η, m), 7.88(2Η, m), 8.05(3Η, m), 8.17(1Η, m), 8.25(1Η, m), 8.82(1Η, m), 8.98(2Η, m), 12.35(1Η, brs).  7.71 (2Η, m), 7.88 (2Η, m), 8.05 (3Η, m), 8.17 (1Η, m), 8.25 (1Η, m), 8.82 (1Η, m), 8.98 (2Η, m), 12.35 (1Η, brs).
例 41:化合物番号 41 Example 41: Compound number 41
収率 93%。 'H-NMRCDMSO-d ): δ 2.34(3H, s), 7.14— 7.19(1H, m), 7.44(1H, t, Yield 93%. 'H-NMRCDMSO-d): δ 2.34 (3H, s), 7.14-7.19 (1H, m), 7.44 (1H, t,
6  6
J=8.0Hz), 7.93-8.04(6H, m), 8.18- 8.20(1H, m), 8.29- 8.32(1H, m), 8.44(1H, d, J=8.4Hz), 8.70(1H, d, J=13.0Hz), 13.70(1H, d, J=13.0Hz).  J = 8.0Hz), 7.93-8.04 (6H, m), 8.18- 8.20 (1H, m), 8.29-8.32 (1H, m), 8.44 (1H, d, J = 8.4Hz), 8.70 (1H, d , J = 13.0Hz), 13.70 (1H, d, J = 13.0Hz).
例 42:化合物番号 42 Example 42: Compound number 42
収率 76%。 'H-NMRCDMSO-d ): δ 2.33(3Η, s), 7.17(1Η, m), 7.43(2Η, m), Yield 76%. 'H-NMRCDMSO-d): δ 2.33 (3Η, s), 7.17 (1Η, m), 7.43 (2Η, m),
6  6
7.49(1Η, m), 7.82(1Η, dd, J=2.1, 8.7Hz), 7.97(2Η, d, J=8.5Hz), 8.18(1Η, m), 8.53(1Η, s).  7.49 (1Η, m), 7.82 (1Η, dd, J = 2.1, 8.7Hz), 7.97 (2Η, d, J = 8.5Hz), 8.18 (1Η, m), 8.53 (1Η, s).
例 43:化合物番号 43 Example 43: Compound number 43
収率 59%。 'H-NMRCDMSO-d ): δ 2.34(3H, s), 7.19(1H, t, J=7.4Hz), 7.36(1H, dd, Yield 59%. 'H-NMRCDMSO-d): δ 2.34 (3H, s), 7.19 (1H, t, J = 7.4Hz), 7.36 (1H, dd,
6  6
J=2.1, 8.7Hz), 7.44(2H, t, J=8.0Hz), 7.72(2H, m), 7.93(2H, m), 8.49(1H, s).  J = 2.1, 8.7Hz), 7.44 (2H, t, J = 8.0Hz), 7.72 (2H, m), 7.93 (2H, m), 8.49 (1H, s).
例 44:化合物番号 44 Example 44: Compound number 44
(1) l-(p-トルエンスルホ -ル)ォキシ -2-ナフチルァミン  (1) l- (p-toluenesulfol) oxy-2-naphthylamine
2-ァミノ- 1-ナフトール塩酸塩 (196mg, lmmol)、 p-トルエンスルホ-ルクロリド (210mg, l.lmmol)、トリェチルァミン (0.5ml)及びジクロロメタン (5ml)の混合物を室温で 終夜攪拌した。反応混合物をジクロロメタンで希釈、水洗し、無水硫酸ナトリウムで乾 燥した。溶媒を減圧留去して得られた残渣をシリカゲルカラムクロマトグラフィー (n-へ キサン Z酢酸ェチル =4Zl)で精製して、標題化合物の紫色粉末 (261mg, 83%)を得 た。 A mixture of 2-amino-1-naphthol hydrochloride (196 mg, lmmol), p-toluenesulfol-chloride (210 mg, l.lmmol), triethylamine (0.5 ml) and dichloromethane (5 ml) was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane, washed with water, and dried over anhydrous sodium sulfate. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (n-hexane). Purification with hexane Z (ethyl acetate = 4Zl) gave a purple powder (261 mg, 83%) of the title compound.
1H-NMR(DMSO-d ): δ 2.41(3H, s), 5.21(2H, s), 7.05(1H, dd, J=1.7, 8.8Hz),  1H-NMR (DMSO-d): δ 2.41 (3H, s), 5.21 (2H, s), 7.05 (1H, dd, J = 1.7, 8.8Hz),
6  6
7.15(1H, m), 7.30(1H, dt, J=1.4, 7.5Hz), 7.46(3H, m), 7.59(1H, d, J=8.8Hz), 7.68(1H, d, J=8.0Hz), 7.90(2H, dd, J=1.9, 8.5Hz).  7.15 (1H, m), 7.30 (1H, dt, J = 1.4, 7.5Hz), 7.46 (3H, m), 7.59 (1H, d, J = 8.8Hz), 7.68 (1H, d, J = 8.0Hz) ), 7.90 (2H, dd, J = 1.9, 8.5Hz).
(2)化合物番号 44  (2) Compound No. 44
収率 88%。 'H-NMRCDMSO-d ): δ 2.26(3H, s), 2.28(3H, s), 7.19(1H, t, J=7.4Hz),  Yield 88%. 'H-NMRCDMSO-d): δ 2.26 (3H, s), 2.28 (3H, s), 7.19 (1H, t, J = 7.4Hz),
6  6
7.36(2H, d, J=8.0Hz), 7.48(2H, t, J=8.0Hz), 7.58(1H, dt, J=l.l, 7.6Hz), 7.66(1H, dt, J=1.4, 8.2Hz), 7.95(2H, d, J=8.5Hz), 8.03(5H, m), 8.11(1H, d, J=8.8Hz), 8.50(1H, s), 11.48(1H, brs).  7.36 (2H, d, J = 8.0Hz), 7.48 (2H, t, J = 8.0Hz), 7.58 (1H, dt, J = ll, 7.6Hz), 7.66 (1H, dt, J = 1.4, 8.2Hz ), 7.95 (2H, d, J = 8.5Hz), 8.03 (5H, m), 8.11 (1H, d, J = 8.8Hz), 8.50 (1H, s), 11.48 (1H, brs).
[0099] 例 45:化合物番号 45(—般合成法 B) [0099] Example 45: Compound number 45 (General synthesis method B)
2-ァミノ- 1-ナフトール塩酸塩 (196mg, lmmol)、 2- (3-カルボキシァ-リノ)- 4,6-ジク ロロ— 1,3,5—トリァジン (314mg, l.lmmol), WSC -HCl(211mg, l.lmmol)及びジクロロメタ ン (5ml)の混合物を室温で終夜攪拌した。反応混合物をジクロロメタンで希釈、水洗し 、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去して得られた残渣をシリカゲルカラ ムクロマトグラフィー (n-へキサン Z酢酸ェチル =4Zl)で精製して、標題ィ匕合物の薄 茶色粉末 (120mg, 28%)を得た。 2-Amino-1-naphthol hydrochloride (196 mg, lmmol), 2- (3-carboxya-lino) -4,6-dichloro-1,3,5-triazine (314 mg, l.lmmol), WSC -HCl (211 mg, 1.1 mmol) and a mixture of dichloromethane (5 ml) were stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane, washed with water, and dried over anhydrous sodium sulfate. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography ( n- hexane Z ethyl acetate = 4Zl) to obtain a light brown powder (120 mg, 28%) of the title compound. Was.
^-NMRCDMSO-d ): δ 7.51(4H, m), 7.61(1H, t, J=8.0Hz), 7.87(2H, m), 7.93(1H,  ^ -NMRCDMSO-d): δ 7.51 (4H, m), 7.61 (1H, t, J = 8.0Hz), 7.87 (2H, m), 7.93 (1H,
6  6
d, J=8.2Hz), 8.23(2H, m), 9.75(1H, s), 10.37(1H, s), 11.33(1H, s).  d, J = 8.2Hz), 8.23 (2H, m), 9.75 (1H, s), 10.37 (1H, s), 11.33 (1H, s).
一般合成法 Bと同様の方法により、一般式 (I)において Yが- CONH-又は- NHCO-で ある下記化合物を得た。  By the same method as in the general synthesis method B, the following compound in which Y is —CONH— or —NHCO— in the general formula (I) was obtained.
化合物番号 57、 59、 69〜71、 74、 85、 94〜95、 117〜118、 124、 129〜130、 134〜137 、 141〜143、 168、 172、 182〜183、 192〜193、 213、 248〜252、 288〜293、 307〜309 、 311、及び 361〜363  Compound No. 57, 59, 69-71, 74, 85, 94-95, 117-118, 124, 129-130, 134-137, 141-143, 168, 172, 182-183, 192-193, 213, 248-252, 288-293, 307-309, 311, and 361-363
[0100] 例 46:化合物番号 46 [0100] Example 46: Compound number 46
収率 81%。 ^-NMRCDMSO-d ): δ 1.37(3H, t, J=7.1Hz), 4.52(2H, q, J=7.1Hz),  Yield 81%. ^ -NMRCDMSO-d): δ 1.37 (3H, t, J = 7.1Hz), 4.52 (2H, q, J = 7.1Hz),
6  6
7.30(1H, t, J=7.4Hz), 7.49(4H, m), 7.68(1H, d, J=8.2Hz), 7.76(2H, dd, J=6.3, 8.8Hz), 7.86(1H, m), 8.24(2H, m), 8.32(1H, dd, J=1.5, 8.7Hz), 9.02(1H, d, •(s Ήΐ)9Γ2ΐ '(ζΗΟ·ΐΐ=ί" 'Ρ Ήΐ)ε ·Π '(ζΗ8·π=ί" 'Ρ 'Ηΐ)66·6 '(ζΗ9·ΐ=ί" 'Ρ Ήΐ)23·8 '(ω Ή¾8Γ8
Figure imgf000120_0001
7.30 (1H, t, J = 7.4Hz), 7.49 (4H, m), 7.68 (1H, d, J = 8.2Hz), 7.76 (2H, dd, J = 6.3, 8.8Hz), 7.86 (1H, m ), 8.24 (2H, m), 8.32 (1H, dd, J = 1.5, 8.7Hz), 9.02 (1H, d, • ( s Ήΐ) 9Γ2ΐ '( ζ ΗΟ · ΐΐ = ί "' Ρ Ήΐ) ε · Π '(ζΗ8 · π = ί"' Ρ 'Ηΐ) 66 · 6' (ζΗ9 · ΐ = ί "'Ρ Ήΐ) 23 · 8 '(ω Ή¾8Γ8
Figure imgf000120_0001
' 'Η ΐ · '(ΖΗΖ·9=1" ' Ήΐ)3ΓΖ '(s Ήε)9ε 9 :( OSW I) 顺— Ητ
Figure imgf000120_0002
'' Η ΐ · '(ΖΗΖ · 9 = 1 "' Ήΐ) 3ΓΖ '(s Ήε) 9ε 9 :( OSW I) 顺 — Η τ
Figure imgf000120_0002
•(ω Ήε)ζε·8— οε·8 '(^ 'HS)80'8- so'8
Figure imgf000120_0003
'PP 'HT)OS"Z • (ω Ήε) ζε · 8— οε · 8 '(^' HS) 80'8- so'8
Figure imgf000120_0003
'PP' HT) OS "Z
' 'HZ)WL 'WL=[ Ήΐ)8ΓΖ '(s Ήε) ε·ζ g :( iつ aつ) WN °%os ¾τ
Figure imgf000120_0004
'' HZ) WL 'WL = [Ήΐ) 8ΓΖ' (s Ήε) εζζ g :( i a a) WN °% os ¾τ
Figure imgf000120_0004
' Ήΐ)9ΓΖ '(s 'HZ)W '( 'HDSST '(s 'Η6)ΐ ·ΐ 9 :( I a ) 顺- Ητ °%ΐ睡 ¾T
Figure imgf000120_0005
'Ήΐ) 9ΓΖ'(s' HZ) W '(' HDSST '(s' Η6) ΐΐ9: (I a) 顺-Η τ °% ΐSleep ¾T
Figure imgf000120_0005
•(s Ήΐ)8Ζ·8
Figure imgf000120_0006
• ( s Ήΐ) 8Ζ8
Figure imgf000120_0006
'(s Ήΐ) 2·9 '(s 'HZ)WZ '(s 'HS)8S 9 :( !DaD)H N-HT °%8S ? φ '( s Ήΐ) 2.9' ( s ' HZ) WZ '( s ' HS) 8S 9 :(! DaD) H NH T °% 8S? φ
OS各粱呦 :0Sfii
Figure imgf000120_0007
OS each 呦: 0Sfii
Figure imgf000120_0007
'Ρ Ήΐ)ΐ3·8 '(ω 'ΗΖ)Ζζ'8 '(ω 'H )S0'8 '(zH9"6=f 'Ρ 'HT)29"Z '(ΖΗ0·8=1" ' 'Ρ Ήΐ) ΐ3.8' (ω 'ΗΖ) Ζζ'8' (ω 'H) S0'8' ( z H9 "6 = f 'Ρ' HT) 29" Z '(ΖΗ0 · 8 = 1 "'
'HZ)WL '(ω Ήΐ)ΖΓΖ '(s Ήΐ)9 ·3 'HZ) Z 9 :( P-OS a)H N-HT °%8S ? φ 'HZ) WL' (ω Ήΐ) ΖΓΖ '(s Ήΐ) 9 3' HZ) Z 9 :( P-OS a) H NH T °% 8S? Φ
•(ω 'Η2)6Γ8 '(ΖΗΖ·Ζ=1" 'Ρ Ήΐ)0Γ8 '(ω 'HZ)WS '(ω ΉΫ)Ζ^ί '(ω Ήε) ·Ζ '(zW =f '； Ήΐ)9ΓΖ '(s Ήε)83·ζ '(s ΉΖ)ΖΖ 9 :( P-OS a)H N-HT °%SS ¾ί 粱呦 -sm
Figure imgf000120_0008
'P 'H2)S0"8 '(ω 'H2)T6"Z
Figure imgf000120_0009
'W 'Ηΐ)ΐ9· '(ω 'm)ZVL
Figure imgf000120_0010
• (ω 'Η2) 6Γ8' (ΖΗΖ · Ζ = 1 "'Ρ Ήΐ) 0Γ8' (ω 'HZ) WS' (ω ΉΫ) Ζ ^ ί '(ω Ήε) · Ζ' (zW = f '; Ήΐ ) 9ΓΖ '(s Ήε) 83ζ (' (s ΉΖ) ΖΖ 9 :( P-OS a) H NH T °% SS 呦 呦 -sm
Figure imgf000120_0008
'P' H2) S0 "8 '(ω' H2) T6" Z
Figure imgf000120_0009
'W' Ηΐ) ΐ9 · '(ω' m) ZVL
Figure imgf000120_0010
•(sjq 'Ηΐ)8ε·6 '(s Ήΐ)0Γ6 '(ζΗΓΐ=Γ
Figure imgf000120_0011
8 S081760/S00Z OAV ΐ9各粱呦 -i • (sjq 'Ηΐ) 8ε6' ( s Ήΐ) 0Γ6 '( ζ ΗΓΐ = Γ
Figure imgf000120_0011
8 S081760 / S00Z OAV ΐ9 sorghum 呦 -i
•(ζΗζ·8=Γ 'P 'HDLVS '(ZH6"T=f 'P 'Ηΐ) Γ8 '(s 'Ηΐ)εΐ·8 '(ΖΗΖ·Ζ=ί" 'P 'Ηΐ)ΐΐ·8 '(ΖΗΖ·Ζ=ί" 'P 'HT)6Z"Z '(ω 'ΗΖ)19Ί
Figure imgf000121_0001
'P 'H2)W • ( ζ Ηζ · 8 = Γ 'P' HDLVS '( Z H6 "T = f' P 'Ηΐ) Γ8' ( s 'Ηΐ) εΐ8' (ΖΗΖ · Ζ = ί"'P' Ηΐ) ΐΐ · 8 '(ΖΗΖ · Ζ = ί "' P 'HT) 6Z"Z' (ω 'ΗΖ) 19Ί
Figure imgf000121_0001
'P' H2) W
'(ΖΗ6·9 Τΐ=Γ 'PP 'HDSVL '(ω 'HZ)ZVL '(ZH8'8=f 'P 'H\)^L '(ω 'H\)WL '(ΖΗΓΖ=Γ 'b 'Η 8ε· '(ΖΗΓΖ=Γ 'HS)8S"T 9 :( <3つ) 顺— HT ¾ί
Figure imgf000121_0002
'P 'HT)TS"8 '(ω 'Η 0ΐ·8 '(ΖΗΟ·8=1" 'P Ήΐ)89"Ζ '(ω 'HT)6S"Z '(ω 'Hf)6VL '(ω 'Η£)9ΖΊ '(ΖΗΟ·=ί" 'Ρ Ήΐ)90"Ζ'(ΖΗ6 · Τΐ = Γ' PP 'HDSVL' (ω 'HZ) ZVL'(ZH8'8 = f 'P' H \) ^ L '(ω' H \) WL '( Ζ ΗΓΖ = Γ' b 'Η 8ε ·' ( Ζ ΗΓΖ = Γ 'HS) 8S "T 9 :( <3) 顺 — H T ¾ί
Figure imgf000121_0002
'P' HT) TS "8 '(ω' Η 0ΐ · 8 '(ΖΗΟ · 8 = 1"' P Ήΐ) 89 "Ζ '(ω' HT) 6S" Z '(ω' Hf) 6VL '(ω 'Η £) 9ΖΊ' (ΖΗΟ · = ί "'Ρ Ήΐ) 90" Ζ
'(ΖΗΓΖ=Γ Ή 6ε· '(ζΗΓΖ=Γ Ή νι 9 :(ει αつ) Η顺— Ητ °% Ζ ¾ί '( Ζ ΗΓΖ = Γ Ή 6ε ·' ( ζ ΗΓΖ = Γ Ή νι 9 :( ε ι α つ) Η 顺 — Η τ °% Ζ ¾ί
"(zH2"8=f"(zH2" 8 = f
'Ρ 'HDLVS '(ζΗ6·ΐ=ί" 'Ρ 'Ηΐ)ΐε·8 '(s 'Ηΐ) ΐ·8 '(zH0"8=f 'Ρ 'Ηΐ)60·8 '(zH0"8=f 'Ρ 'Ηΐ)8ΓΖ '(ω ' )WL-WL '(ω 'Η ·Ζ
Figure imgf000121_0003
'Ρ 'Ηΐ) Ζ '(ω 'Ηΐ) Ζ '(ΖΗΓΖ=Γ 'b 'HZ) '(ΖΗΓΖ=Γ Ήε)ε ·ΐ 9 :ODaD)H N-HT °%ιε ¾ί VL=[ 'P Ήΐ)2Γ6'Ρ' HDLVS '(ζΗ6 · ΐ = ί "' Ρ 'Ηΐ) ΐε · 8' ( s ' Ηΐ) ΐ · 8 '( z H0" 8 = f' Ρ 'Ηΐ) 60 · 8' ( z H0 " 8 = f 'Ρ' Ηΐ) 8ΓΖ '(ω') WL-WL '(ω' Η
Figure imgf000121_0003
'Ρ' Ηΐ) Ζ '(ω' Ηΐ) Ζ '( Ζ ΗΓΖ = Γ' b 'HZ)' ( Ζ ΗΓΖ = Γ Ήε) ε · ΐ 9 : ODaD) H NH T °% ιε VL VL = [' P Ήΐ) 2Γ6
(s
Figure imgf000121_0004
'(ω 'H2)S9"Z '(ω 'H2)TS"Z '(zH8"8=f 'P Ήΐ)ΐ^Ζ '(zHS" =f ^ Ήΐ)92"Ζ '(zH8"8=f 'P Ήΐ)90"Ζ(s
Figure imgf000121_0004
'(ω' H2) S9 "Z '(ω' H2) TS" Z '(zH8 "8 = f' P Ήΐ) ΐ ^ Ζ '(zHS" = f ^ Ήΐ) 92 "Ζ'(zH8" 8 = f 'P Ήΐ) 90 "Ζ
'(ΖΗΓΖ=Γ 'm)6Vf '(ΖΗΓΖ=Γ Ήε) ε·ΐ 9 :(ει αつ) Η顺— ΗΤ °%69 ¾Τ '( Ζ ΗΓΖ = Γ' m) 6Vf '( Ζ ΗΓΖ = Γ Ήε) εΐ9 :( ε ι α つ) Η 顺 — Η Τ °% 69 ¾Τ
•(ΖΗ8 1=1" 'Ρ Ήΐ)33·εΐ '(ZH8 I=f 'P 'Ηΐ)0Γ8 '(ΖΗ8· =1" ' 'Ηΐ)0 ·8 Wl 'VL=[ 'PP 'Ηΐ)ΐε·8 '(ω 'HS)S0"8-S8"Z '(ω 'HZ)LVL-WL '(ω ' )6VL-fVL '(s 'HS)SS 9 :( OSWa) 顺— HT °%S9 ? φ • (ΖΗ8 1 = 1 "'Ρ Ήΐ) 33 · εΐ' (ZH8 I = f 'P' Ηΐ) 0Γ8 '(ΖΗ8 · = 1"''Ηΐ) 0 · 8 Wl' VL = ['PP' Ηΐ) ΐε · 8 '(ω' HS ) S0 "8-S8" Z '(ω' HZ) LVL-WL '(ω') 6VL-fVL '(s' HS) SS 9 :( OSWa)顺- H T ° % S9? Φ
•(s 'HT)92"6 '(zHS'8=f 'P Ήΐ)ΐ2·8 '(ΖΗΟ·8=1" 'P Ήΐ)68"Ζ v\=[ 'P 'Ηΐ)ΖΖ· '(ω Ή^)99"Ζ '(ω Ή2)ΐ9"Ζ '(ω 'HT)8S"Z '(ω 'HS)TS"Z '(ζΗ6·ΐ=ί" 'Ρ 'Ηΐ)ε8·9 9 :( OSWa Η顺— HT °%ΖΖ ¾ί 各粱呦
Figure imgf000121_0005
6 S081760/S00Z OAV 'H S 'Z— 8ε· 'WL=[ 'ΗΪ)8ΓΖ '(s ' )Lvi 9 :(ει αつ) 顺— HT °%9 ¾ί • (s 'HT) 92 " 6'(zHS'8 = f 'P Ήΐ) ΐ2 · 8' (ΖΗΟ · 8 = 1"'P Ήΐ) 68 "Ζ v \ = [' P 'Ηΐ) ΖΖ ·' (ω Ή ^) 99 "Ζ '(ω Ή2) ΐ9"Ζ' (ω 'HT) 8S "Z' (ω 'HS) TS"Z' (ζΗ6ΐ = ί "'Ρ' Ηΐ) ε8 9 :( OSWa Η 顺 — H T °% ΖΖ ¾ί each beam
Figure imgf000121_0005
6 S081760 / S00Z OAV 'HS' Z— 8ε · 'WL = [' ΗΪ) 8ΓΖ '(s') Lvi 9 :( ε ι α つ) 顺 — H T °% 9 ¾ί
•(s 'Ηΐ)80·6 '(zH0"8=f• ( s 'Ηΐ) 80 · 6' ( z H0 "8 = f
'P 'Ηΐ)εε·8
Figure imgf000122_0001
'HI)S9"Z '(ω 'HS)9S"Z-8S"Z 'P' Ηΐ) εε8
Figure imgf000122_0001
'HI) S9 "Z' (ω 'HS) 9S" Z-8S "Z
'(ΖΗΓ6=Γ 'P Ήΐ)8ΓΖ '(s Ήΐ)εθ· 9 :( OSW I) 顺— HT °%96 ¾T '( Ζ ΗΓ6 = Γ' P Ήΐ) 8ΓΖ '(s Ήΐ) εθ9 :( OSW I) 顺 — H T °% 96 ¾T
Z9各粱呦 -19  Z9 each 呦 -19
•(s 'HI)S8'8
Figure imgf000122_0002
'P 'HT)SZ"Z '(ω 'H2)S9"Z '(ω 'HWL-WL • (s' HI) S8'8
Figure imgf000122_0002
'P' HT) SZ "Z '(ω' H2) S9" Z '(ω' HWL-WL
'(ω
Figure imgf000122_0003
'(s Ήΐ)ζε·9 '(s 'm)wi 9 :(ει αつ) 顺— HT °%S8 ? Φ '(ω
Figure imgf000122_0003
'(s Ήΐ) ζε · 9' ( s ' m) wi 9 :( ε ι α つ) 顺 — H T °% S8? Φ
•(zHO"S=f 'P • ( z HO "S = f 'P
'HT)S9"8 'P 'Ηΐ)98·8 '(ΖΗ8" '8·ΐ=ί" 'PP 'HZ)16'L '(ΖΗΖ·Ζ=ί" 'Ρ 'HI)U'Z  'HT) S9 "8' P 'Ηΐ) 98 · 8' (ΖΗ8" '8 · ΐ = ί "' PP 'HZ) 16'L' (ΖΗΖ · Ζ = ί" 'Ρ' HI) U'Z
'(w
Figure imgf000122_0004
'(s Ήΐ)ε ·9 '(w
Figure imgf000122_0004
'(s Ήΐ) ε9
'(ΖΗΓΖ=Γ 'b 'Η Ζ9· '(ΖΗΓΖ=Γ ^ 'HS)9S'I 9 -(OQDWH-^ °%8S ? φ '( Ζ ΗΓΖ = Γ' b 'Η Ζ9 ·' ( Ζ ΗΓΖ = Γ ^ 'HS) 9S'I 9-(OQDWH- ^ °% 8S? Φ
•(s 'Ηΐ)6Γ8 '(ΖΗΖ·Ζ=ί" 'P 'HT)SS"8
Figure imgf000122_0005
'P 'HT)SZ"Z '(ω 'H2)29"Z '(ω 'Η ) ·Ζ • (s 'Ηΐ) 6Γ8' (ΖΗΖ · Ζ = ί "'P' HT) SS" 8
Figure imgf000122_0005
'P' HT) SZ "Z '(ω' H2) 29" Z '(ω' Η) · Ζ
'(ω 'Ηΐ) ·Ζ '(s Ή2)3ε· '(s 'HT)62"9 '(s 'HS)6S"2 9： つ) WN— HT °%9 ¾ί'(ω' Ηΐ) · Ζ '(s Ή2) 3ε ·'(s' HT) 62 "9 '( s ' HS) 6S" 2 9: WN— H T °% 9 ¾ί
9各粱呦^ 9\ 9 each siang 呦 ^ 9 \
•(s 'Ηΐ)ΐε·εΐ '(s 'Ηΐ)ΐ ·6 '(ω 'Ηΐ)9ε·8- Γ8 '(s 'Ηΐ) ΐ·8 '(ΖΗΓ8=Γ 'Ρ 'Ηΐ)9 • ( s ' Ηΐ) ΐε · ε '' ( s ' Ηΐ) ΐ6 '(ω' Ηΐ) 9 ε8- Γ8 '( s ' Ηΐ) ΐ8' ( Ζ ΗΓ8 = Γ 'Ρ' Ηΐ) 9
'(ω 'HS)29"Z-ZS"Z '(ω 'HS)W -6^" '(ω 'Η ·Ζ- 0 ·Ζ '(ΖΗ ·8=ί" 'Ρ 'Ηΐ) Γ  '(ω' HS) 29 "Z-ZS" Z '(ω' HS) W -6 ^ "'(ω' Η · Ζ- 0 · Ζ '(ΖΗ · 8 = ί"' Ρ 'Ηΐ) Γ
'(ΖΗΓΖ=Γ Ήζ)ζζ^ '(ΖΗΓΖ=Γ Ήε)3ε·ΐ g :(ει αつ) Η顺— ΗΤ °%6 ¾Τ'( Ζ ΗΓΖ = Γ Ήζ) ζζ ^' ( Ζ ΗΓΖ = Γ Ήε) 3εΐΐ g :( ε ι α つ) Η 顺 — Η Τ °% 6 ¾Τ
Figure imgf000122_0006
： S9p} [εοιο]
Figure imgf000122_0006
: S9p} [εοιο]
•(s 'Ηΐ)88·8 '(ω 'Ηΐ)9ε·8 '(ω 'H2)S6"Z '(ω 'HS^ ^ '(ω • ( s 'Ηΐ) 88 · 8' (ω 'Ηΐ) 9ε · 8' (ω 'H2) S6 "Z' (ω 'HS ^ ^' (ω
'H )9S'Z '(ω 'H )S ' '(ω 'HS)9S"Z '(s Ήΐ)8Ζ·9 9 :( <3つ) Η顺— Ητ °%SS ¾ί 'H) 9S'Z' (ω 'H) S''(ω' HS) 9S "Z '(s Ήΐ) 8Ζ9 9 :( <3) Η 顺 — Η τ °% SS ¾ί
•(ΖΗ8 1=1"• (ΖΗ8 1 = 1 "
'Ρ 'Ηΐ)ε8·εΐ '(ΖΗ8 1=1" 'Ρ 'Ηΐ)69·8 '(ω 'Η ·8- '(ω 'H9)Z0"8-Z8"Z '(ω 'Ρ' Ηΐ) ε8 · εΐ '(ΖΗ8 1 = 1 "' Ρ 'Ηΐ) 69 · 8' (ω 'Η · 8-' (ω 'H9) Z0" 8-Z8 "Z' (ω
'm)6VL-fVL '(ω Ήΐ)22· - Γ 'H6)S 'I 9 :( OSWa) 顺— Ητ °%99 ¾ί t9t900 OZdr/lDd OZV S08^60/S00Z OAV 各粱呦^ ： szfii'm) 6VL-fVL' (ω Ήΐ) 22 ·-Γ 'H6) S' I 9 :( OSWa) 顺 ― Η τ °% 99 ¾ί t9t900 OZdr / lDd OZV S08 ^ 60 / S00Z OAV Each 呦
•(s 'Ηΐ)
Figure imgf000123_0001
• ( s ' Ηΐ)
Figure imgf000123_0001
'P Ήΐ)ΐ3·8 '(s 'Ηΐ)69· '(ΖΗ9·8=1" 'Ρ 'HT)S9"Z
Figure imgf000123_0002
'Ρ ΉΖ)Ζζ-∑ '(s 'Ηΐ)ΐΖ·9 '(s ΉΖ)\νΖ '(s Ήε)3ε·ζ 9 :( Ρ- OS Η顺- Ητ °%6 ¾ί
Figure imgf000123_0003
'P Ήΐ)ίΥ8 '(sjq Ήΐ)62"8 '(ω 'H2)S9"Z '(zHS" =f 'HI)8S'Z '(ω 'H ·Ζ '(ω ΉΖ)ίΖ' L '(zH8"8=f 'Ρ Ήΐ)8ΓΖ '(ΖΗ8·8=1" 'Ρ 'Ηΐ)ΐΟ· '(ω 'Ηΐ)ΐ9·9 9 :( <3つ) Η顺— Ητ °%S8 ? φ 'P Ήΐ) ΐ3 · 8' ( s 'Ηΐ) 69 ·' (ΖΗ9 · 8 = 1 "'Ρ' HT) S9" Z
Figure imgf000123_0002
'Ρ ΉΖ) Ζζ-∑' ( s ' Ηΐ) ΐΖ9 '( s ΉΖ) \ νΖ' ( s Ήε) 3εζ ζ 9 :( Ρ- OS Η 顺-τ τ °% 6 ¾ί
Figure imgf000123_0003
'P Ήΐ) ίΥ8' (sjq Ήΐ) 62 "8 '(ω' H2) S9" Z '(zHS) = f' HI) 8S'Z '(ω' H · Ζ '(ω ΉΖ) ίΖ' L ' (zH8 "8 = f 'Ρ Ήΐ) 8ΓΖ' (ΖΗ8 = 1 = 'Ρ' Ηΐ) ΐΟ '(ω' Ηΐ) ΐ9.99 :( <3) Η 顺 — Η τ °% S8 ? φ
•(ΖΗΓΖ '6·ΐ=ί" 'ΡΡ 'Ηΐ) ·8 '(ΖΗΓΖ '9·ΐ=ί" 'ΡΡ 'Ηΐ)εΐ·8
Figure imgf000123_0004
'； ΉΖ)ΖΥί '(zH9"Z=f Ήΐ)6ΓΖ '(s Ήΐ) 3·9 '(s 'm)fVl 9 :ODaD)H N-HT °%9ΐ ? φ • (ΖΗΓΖ '6 · ΐ = ί "' ΡΡ 'Ηΐ) · 8' ( Ζ ΗΓΖ '9 · ΐ = ί"' ΡΡ 'Ηΐ) εΐ8
Figure imgf000123_0004
'; ΉΖ) ΖΥί' ( z H9 "Z = f Ήΐ) 6ΓΖ '(s Ήΐ) 3.9' ( s ' m) fVl 9 : ODaD) H NH T °% 9ΐ? Φ
•(ZHS =f 'P Ήΐ)3Γ6 '(ZHS =f 'P 'Ηΐ) 9·8
Figure imgf000123_0005
(ZHS = f 'P' Ηΐ) 3Γ6 '(ZHS = f' P 'Ηΐ) 9
Figure imgf000123_0005
'PPP 'HT)S8"Z '(ΖΗΐ·8 Ό"Ζ '2"
Figure imgf000123_0006
'PPP' HT) S8 "Z '(ΖΗΐ · 8 Ό"Ζ' 2 "
Figure imgf000123_0006
'P 'HZ) L '(s Ήΐ)2 ·9 '(s 'HZ)ZVZ '(s 'HS)8S"2 9： つ) WN— HT ¾ί 'P' HZ) L '(s Ήΐ) 2 · 9' ( s ' HZ) ZVZ '( s ' HS) 8S "2 9: WN— H T ¾ί
ΪΖ各粱呦 -u ΪΖEach 呦 -u
•(zH0"9=f 'P 'Ηΐ)Ζ6 ΐ '(s 'Ηΐ)89 ΐ '(zH0"9=f 'P 'Ηΐ)ΐ6·8 '(ΖΗΖ·8=1" 'P Ήΐ)8Γ8 '(ZHO =1" 'P 'HT)8Z"Z '(ZHO 'Z"8=f 'PP 'HT)2S"Z '(ω 'Y^W L-ZY L '(zW8=f 'P• ( z H0 "9 = f 'P' Ηΐ) Ζ6 ΐ '( s ' Ηΐ) 89 ΐ '( z H0" 9 = f' P 'Ηΐ) ΐ6.8 · ((ΖΗΖ · 8 = 1 "' P Ήΐ ) 8Γ8 '(ZHO = 1 "' P 'HT) 8Z"Z' (ZHO 'Z "8 = f' PP 'HT) 2S"Z' (ω 'Y ^ W L-ZY L' (zW8 = f ' P
Η ζε· '(s 'ΗΪ)09·9 '(s
Figure imgf000123_0007
'(s Ήε) ττ'τ 9 :( oswa) 顺— Ht °%εε ¾TΗ ζε · '(s' ΗΪ) 09 · 9' ( s
Figure imgf000123_0007
'( s Ήε) ττ'τ 9 :( oswa) 顺 — H t °% εε ¾T
Figure imgf000123_0008
Figure imgf000123_0008
•(s Ήΐ)0Ζ ΐ '(ZHS'8 '6'6=f 'PP 'H2)9S"8 '(^ 'H2)½"Z-68"Z '(ω 'HT)T8"Z-9Z"Z '(ω 'HT)89"Z-S9"Z '(ω 'H ·Ζ- OS'Z '(zHS"8=f 'P 'HZ)0VL '(s 'Ηΐ)08·9 '(s 'HS)0S '(s 'HS)6S"2 9 つ) 顺— HT °%9S ? φ • ( s Ήΐ) 0Ζ ΐ '(ZHS'8'6'6 = f 'PP' H2) 9S "8 '(^' H2) ½" Z-68 "Z '(ω' HT) T8" Z-9Z "Z '(ω' HT) 89" Z-S9 "Z '(ω' H · Ζ- OS'Z '(zHS" 8 = f' P 'HZ) 0VL' ( s 'Ηΐ) 08 · 9' ( s ' HS) 0S '(s' HS) 6S "2 9) 顺 — H T °% 9S? φ
6½ ί¾?^ :69 "(s-i Ήΐ) ^2ΐ '(ΖΗΖ·6=1" 'Ρ 'Ηΐ)8ε·6 '(ζΗ8·ΐ '6·9=ί" '^Ρ 'Η 8ΐ·8 '^ΗΖΊ '6·8=ί" 'PP 'ΗΖ)Ζ0'8 '(ω 'H2)S8"Z-SZ"Z '(ω
Figure imgf000123_0009
1-31. 収率 44%。 H-NMR(CDC1 ): δ 2.15(3H, s), 2.37(3H, s), 6.04(1H, s), 7.24 (2H, d, 6½ ί¾? ^: 69 "(si Ήΐ) ^ 2ΐ '(ΖΗΖ6 = 1"' Ρ 'Ηΐ) 8ε6'(ζΗ8ΐ'6 · 9 = ί "'^ Ρ' Η 8ΐ8 ' ^ ΗΖΊ '6.8 · 8 = ί "' PP 'ΗΖ) Ζ0'8' (ω 'H2) S8" Z-SZ "Z' (ω
Figure imgf000123_0009
1-31. Yield 44%. H-NMR (CDC1): δ 2.15 (3H, s), 2.37 (3H, s), 6.04 (1H, s), 7.24 (2H, d,
3  Three
J=8.1Hz), 7.26(1H, s), 7.35— 7.38(2H, m), 7.53— 7.58(1H, m), 7.68-7.73(lH, m), 7.83(1H, dd, J=8.1, 1.3Hz), 8.10(1H, d, J=8.4Hz), 8.22— 8.23(1H, m), 8.94(1H, d, J=2.0Hz).  J = 8.1Hz), 7.26 (1H, s), 7.35- 7.38 (2H, m), 7.53-7.58 (1H, m), 7.68-7.73 (lH, m), 7.83 (1H, dd, J = 8.1, 1.3Hz), 8.10 (1H, d, J = 8.4Hz), 8.22-8.23 (1H, m), 8.94 (1H, d, J = 2.0Hz).
[0105] 例 76:化合物番号 76 [0105] Example 76: Compound number 76
(1) 5-ァミノ- 1- (4-クロ口フエ-ル)- 3-メチルビラゾール (一般合成法 β )  (1) 5-amino-1- (4-chlorophenol) -3-methylvirazole (general synthesis method β)
β -ァミノクロトノ-トリル (164mg, 2mmol)、 p-クロ口フエ-ルヒドラジン塩酸塩 (358mg, 2mmol)、酢酸 (2ml)及びエタノール (2ml)の混合物を 2.5時間加熱還流した。溶媒を減 圧留去した残渣に水を加え、酢酸ェチルで抽出した。酢酸ェチル層を飽和炭酸水 素ナトリウム水溶液で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去して得 られた残渣をシリカゲルカラムクロマトグラフィー (n-へキサン Zジクロロメタン = lZl) で精製して、標題化合物の淡黄色結晶 (350mg, 84%)を得た。  A mixture of β-aminocrotono-tolyl (164 mg, 2 mmol), p-chlorophenol hydrazine hydrochloride (358 mg, 2 mmol), acetic acid (2 ml) and ethanol (2 ml) was heated under reflux for 2.5 hours. Water was added to the residue obtained by evaporating the solvent under reduced pressure, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and dried over anhydrous sodium sulfate. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (n-hexane Z dichloromethane = lZl) to obtain pale yellow crystals of the title compound (350 mg, 84%).
'H-NMRCCDCl ): δ 2.22(3H, s), 3.73(2H, brs), 5.46(1H, s), 7.39-7.44(2H, m),  'H-NMRCCDCl): δ 2.22 (3H, s), 3.73 (2H, brs), 5.46 (1H, s), 7.39-7.44 (2H, m),
3  Three
7.49-7.54(2H, m).  7.49-7.54 (2H, m).
(2)化合物番号 76  (2) Compound No. 76
収率 36%。 'H-NMRCCDCl ): δ 2.38(3H, s), 6.29 (1H, s), 7.36 (2H, s), 7.48-7.62  Yield 36%. 'H-NMRCCDCl): δ 2.38 (3H, s), 6.29 (1H, s), 7.36 (2H, s), 7.48-7.62
3  Three
(6H, m), 7.76(1H, d, J=7.7Hz), 8.38(1H, d, J=8.7Hz), 8.80(1H, s), 13.42(1H, s).  (6H, m), 7.76 (1H, d, J = 7.7Hz), 8.38 (1H, d, J = 8.7Hz), 8.80 (1H, s), 13.42 (1H, s).
[0106] 例 77:化合物番号 77 [0106] Example 77: Compound number 77
(1) 1-メチル -3-フエ-ル- 4,5-ジヒドロピラゾール- 5-オン (一般合成法 γ )  (1) 1-methyl-3-phenyl-4,5-dihydropyrazol-5-one (general synthesis method γ)
ベンゾィル酢酸ェチル (1.92g, 10mmol)、メチルヒドラジン (0.58ml, l lmmol)及びエタ ノールの混合物を 1.5時間加熱還流した。反応混合物を室温まで冷却後、析出した 結晶を濾取し、エタノールで洗浄して、標題化合物の白色結晶 (1.32g, 76%)を得た。 1H-NMR(DMSO-d ): δ 3.56(3H, s), 5.79(1H, s), 7.24(1H, t, J=7.4Hz), 7.35(2H, t,  A mixture of ethyl benzoyl acetate (1.92 g, 10 mmol), methylhydrazine (0.58 ml, 11 mmol) and ethanol was heated at reflux for 1.5 hours. After the reaction mixture was cooled to room temperature, the precipitated crystals were collected by filtration and washed with ethanol to give white crystals of the title compound (1.32 g, 76%). 1H-NMR (DMSO-d): δ 3.56 (3H, s), 5.79 (1H, s), 7.24 (1H, t, J = 7.4Hz), 7.35 (2H, t,
6  6
J=7.4Hz), 7.68-7.71(2H, m), 11.01(1H, s).  J = 7.4Hz), 7.68-7.71 (2H, m), 11.01 (1H, s).
(2) 1-メチル -5-ォキソ -3-フエ-ル- 4,5-ジヒドロピラゾール- 4-カルバルデヒド 一般合成法 aと同様の方法により標題ィ匕合物を得た。収率 69%。 1H-NMR(CDC1 ):  (2) 1-methyl-5-oxo-3-phenyl-4,5-dihydropyrazole-4-carbaldehyde The title compound was obtained in the same manner as in General Synthesis Method a. Yield 69%. 1H-NMR (CDC1):
3 δ 3.72(3H, s), 7.40-7.50(4H, m), 7.65— 7.69(2H, m), 9.78(1H, s).  3 δ 3.72 (3H, s), 7.40-7.50 (4H, m), 7.65-7.69 (2H, m), 9.78 (1H, s).
(3)化合物番号 77 'V\=[ 'PP 'H¾08"Z '(s 'Ηΐ)9ΓΖ '(ΖΗ9" 'V\=[ 'W 'HT)S9"Z WL=i ' 'HI)8S'Z (3) Compound No. 77 'V \ = [' PP 'H¾08 "Z'(s' Ηΐ) 9ΓΖ '(ΖΗ9"' V \ = ['W' HT) S9 "Z WL = i '' HI) 8S'Z
'(ω 'HZ)Z^L-ZVL '(s Ήε)8 ·ε '(s 'HZ)WZ 9 :( P-OS a)H N-HT °%9 ¾T '(ω' HZ) Z ^ L-ZVL '(s Ήε) 8 ・ ε' ( s ' HZ) WZ 9 :( P-OS a) H NH T °% 9 ¾T
•(s 'Ηΐ)09·8 '(ΖΗΓΖ • ( s 'Ηΐ) 09 · 8' ( Ζ ΗΓΖ
:6·ΐ=ί" 'PP Ήΐ)2Γ8 VL=[ 'P 'Ηΐ)ΐΟ·8 '(ω 'H 96 - 98 '(ΖΗ0·8=1" ' 'HZ)ZVL  : 6ΐ = ί "'PP Ήΐ) 2Γ8 VL = [' P 'Ηΐ) ΐΟ8' (ω 'H 96-98' (ΖΗ0 · 8 = 1" '' HZ) ZVL
(s Ήΐ) 2· 'WL=[ 'Ηΐ)ΐ8· '(s Ήε)ΐε 9 :( P-OS a)H N-HT °%S8 ? ill ( s Ήΐ) 2 '' WL = ['Ηΐ) ΐ8''(s Ήε) ΐε 9 :( P-OS a) H NH T °% S8? ill
Ϊ8各粱呦^ -is [8010] •(zH0"8=f 'P 'HT)Z0"6
Figure imgf000125_0001
'P 'Ηΐ) Γ8 '(s Ήΐ)ΐΓ8 'P 'HI) Z Ϊ8 each beam 呦 ^ -is [8010] • ( z H0 "8 = f 'P' HT) Z0" 6
Figure imgf000125_0001
'P' Ηΐ) Γ8 '( s Ήΐ) ΐΓ8' P 'HI) Z
'(s 'HT)0Z"Z
Figure imgf000125_0002
'P 'HT)8S"Z '(s' HT) 0Z "Z
Figure imgf000125_0002
'P' HT) 8S "Z
'(zHZ"Z=f 'P 'HT " '(zH8"8=f 'P 'HT)S0"Z 9 :(9p— OSWd) N— HT °%8S ? φ '(zHZ "Z = f' P 'HT"' (zH8 "8 = f 'P' HT) S0" Z 9 :( 9 p— OSWd) N— H T °% 8S? φ
08各粱呦  08 each
•(s 'Ηΐ)9ε·6 '( q 'Ηΐ)Ζ0·6 '(s 'HI)S '8 '(ω 'Ηΐ)9ε·8 '(ZH0"9 '9"S=f 'PP 'Ηΐ)96· '(ΖΗ8·8=1" 'P 'HT)S8"Z '(ZH9'S
Figure imgf000125_0003
'P 'HT)S9"Z • (s' Ηΐ) 9ε · 6 '(q' Ηΐ) Ζ0 · 6 '(s' HI) S' 8 '(ω' Ηΐ) 9ε · 8 '(Z H0 "9'9" S = f 'PP 'Ηΐ) 96 ·' (ΖΗ8 · 8 = 1 "'P' HT) S8" Z '(ZH9'S
Figure imgf000125_0003
'P' HT) S9 "Z
'(ω 'HS)9"Z '(ZH6'S 'Ζτ=ί 'PP 'm)ZVL 9 :( P-OS a)H N-HT °%Z8 ? ill '(ω' HS) 9 "Z '(ZH6'S' Ζτ = ί 'PP' m) ZVL 9 :( P-OS a) H NH T °% Z8? ill
•(s 'HDOSTT '(s Ήΐ)8Ζ·8 '(ω 'Ηΐ)Ζε·8— Γ8 • ( s 'HDOSTT' (s Ήΐ) 8Ζ8 '(ω' Ηΐ) Ζε8— Γ8
'(ΖΗΖ·Ζ=ί" 'Ρ 'HT)SZ"Z '(ω 'H^)T9"Z-9^"Z '(ΖΗ0·ΐ=ί" 'Ρ 'H2)SS"Z '(ω 'Η2) eo" -so" '(s ΉΪ) LZ'9 '(s Ήε)68·ε '(s Ήε)8ε 9 :( iDaD)H N-HT °%6ε ? ί)ί '(ΖΗΖ · Ζ = ί "' Ρ 'HT) SZ"Z' (ω 'H ^) T9 "Z-9 ^"Z' (ΖΗ0 · ΐ = ί "'Ρ' H2) SS" Z '(ω 'Η2) eo "-so"' (s ΉΪ) LZ'9 '( s Ήε) 68 · ε' ( s Ήε) 8ε 9 :( iDaD) H NH T °% 6ε? Ί) ί
'(ω 'HS)66'9- 6·9 '(s ' )zv '(s Ήε) 8·ε '(sj Ήζ)89τ '(s Ήε) 9 :( iDaD)H N-HT °%sz ¾τ
Figure imgf000125_0004
'(ω' HS) 66'9-6.9 '( s ') zv '( s Ήε) 8 ·''(sj Ήζ) 89τ' ( s Ήε) 9 :( iDaD) H NH T °% sz ¾τ
Figure imgf000125_0004
/— ^ /^-ζ-( /-^Δ^^- )-1- ^^.- (ΐ) •(s Ήΐ)3ε ΐ
Figure imgf000125_0005
/ — ^ / ^-Ζ- (/-^ Δ ^^-) -1- ^^ .- (ΐ) • ( s Ήΐ) 3ε ΐ
Figure imgf000125_0005
'(ζΗε·6=ί" 'P Ήΐ)Ζ6"Ζ '(zH0"8=f 'P Ήΐ)68"Ζ '(ΖΗΓ8 'S"T=f 'PP 'H2)08"Z '(zH8"8=f '(ζΗε6 = ί "' P Ήΐ) Ζ6" Ζ '(zH0 "8 = f' P Ήΐ) 68" Ζ '(ΖΗΓ8' S "T = f 'PP' H2) 08" Z '(zH8 " 8 = f
'P 'HT)8S"Z '(ω 'HS)9S'Z— '(s 'HS)S 'S 9 :(9p— OSWa) 顺— HT °%9Z ¾T t9t900 OZdr/lDd ZZV S08^60/S00Z OAV ( /—、 ; M/-ェ - ε- ( ^ :- 卜 — s (τ) 'P' HT) 8S "Z '(ω' HS) 9S'Z— '(s' HS) S' S 9 :( 9 p— OSWa) 顺 — H T °% 9Z ¾T t9t900 OZdr / lDd ZZV S08 ^ 60 / S00Z OAV (/ —,; M / -e-ε- (^:-u — s (τ)
98各粱呦 -9S 98 each 呦 -9S
•(s 'Ηΐ) Ζτΐ '(ω 'Ηΐ)Ζ ·8— ε ·8 '(s 'Ηΐ)εΐ·8 '(ω 'Ηΐ)9ΓΖ— Ζ·Ζ '(ω 'H2)S9" -SS- '(ω 'HZ L-OVL
Figure imgf000126_0001
'Ρ 'HT)ZO"Z '(s 'Ηΐ)Ζ9·9 '(s 'HS)S '(s 'HS)ZS 9 :( P- OS 顺- Ητ °%ΐΐ ¾ί • ( s ' Ηΐ) Ζτΐ '(ω' Ηΐ) Ζ · 8— ε · 8 '( s ' Ηΐ) εΐ · 8' (ω 'Ηΐ) 9ΓΖ— Ζ · Ζ' (ω 'H2) S9 "-SS -'(ω' HZ L-OVL
Figure imgf000126_0001
'Ρ' HT) ZO "Z '(s' Ηΐ) Ζ9 9 '( s ' HS) S '( s ' HS) ZS 9 :( P- OS 顺-τ τ °% ΐΐ ¾ί
•(S'HT)69"ST '(s Ήΐ)2 ·8• ( S 'HT) 69 "ST' ( s Ήΐ) 2 · 8
'(ω 'Ηΐ)ε ·8— '(zW =f 'Ρ 'Ηΐ)ΖΖ· '(ω 'H2)29"Z-0S"Z '(ω 'ΗΖ) ΓΖ— 'Ζ'(ω' Ηΐ) ε · 8— '(zW = f' Ρ 'Ηΐ) ΖΖ' '(ω' H2) 29 "Z-0S" Z '(ω' ΗΖ) ΓΖ— 'Ζ
'(S 'ΗΪ) fV9 '(s Ή2) '(s Ήε)2ε·ζ s :( iつ αつ) WN— HT °% ¾T
Figure imgf000126_0002
'( S ' ΗΪ) fV9 '( s Ή2)' (s Ήε) 2εζ s :( i α) WN— H T °% ¾T
Figure imgf000126_0002
'(ω 'H2)zrz-er 'HI)6S'S 'H2)ere '(sjq Ή ιε'ε '(s 'HS)OS"S 9'(ω' H2) zrz-er 'HI) 6S'S' H2) ere '(sjq Ή ιε'ε' ( s ' HS) OS "S 9
■(
Figure imgf000126_0003
■ (
Figure imgf000126_0003
一 、 ; Μ/·^ — ε— べ:^— ΐ— — s (ΐ)
Figure imgf000126_0004
One,; Μ / · ^ — ε— all: ^ — ΐ— — s (ΐ)
Figure imgf000126_0004
•(zHS-ST=f 'P 'Ηΐ)εθ ΐ '^ΗΖτΐ=ί 'Ρ Ήΐ)6Ζ·8 '(ΖΗΓ8=Γ 'Ρ Ήΐ)^·8 '(zH0"6=f 'Ρ Ήΐ)20"8 '(zW8=f 'Ρ Ή2)06"Ζ '(zH0"6=f 'Ρ Ήΐ)ε9"Ζ '(ω lWZ)L^L-WL '(zW8=f 'Ρ 'Η2)ΐ2· '(s '\\Ζ)ΖΖ·Ζ '(s Ήε)ΐε 9 :( P-OS a)H N-HT °%ΐ6 ? φ • (zHS-ST = f 'P' Ηΐ) εθ ΐ '^ ΗΖτΐ = ί' Ρ Ήΐ) 6Ζ8 '( Ζ ΗΓ8 = Γ' Ρ Ήΐ) ^ · 8 '( z H0 "6 = f' Ρ Ήΐ ) 20 "8 '(zW8 = f' Ρ Ή2) 06" Ζ '(zH0 "6 = f' Ρ Ήΐ) ε9" Ζ '(ω l WZ) L ^ L-WL' (zW8 = f 'Ρ' Η2 ) ΐ2 '(s' \\ Ζ) ΖΖΖΖ Ζ' ( s Ήε) ΐε 9 :( P-OS a) H NH T °% ΐ6? φ
•(s'HT)Se-6 '(ZH9"8=f• (s'HT) Se-6 '(ZH9 "8 = f
'Ρ 'H2)99"Z '(ΖΗ9·8=ί" 'Ρ 'Η ·Ζ '(sjq 'Ηΐ)99·9 '(s 'HZ)ZVZ '(s 'HS)8S"2 9 :('Ρ' H2) 99 "Z '(ΖΗ9.8 = ί"' Ρ 'Η · Ζ' (sjq 'Ηΐ) 99 · 9' ( s ' HZ) ZVZ '( s ' HS) 8S "2 9 :(
DaD)H N-HT °%9 ¾ί
Figure imgf000126_0005
DaD) H NH T °% 9 ¾ί
Figure imgf000126_0005
、 ,
^ / - /— ^^c^ ^- s' ^P - s -( / ェ ^ - - ΐ- ^ - ε (ΐ) ε8各粱呦 -zsrn^ /-/ — ^^ c ^ ^-s' ^ P-s-(/ ^ ^--ΐ- ^-ε (ΐ) ε8 each beam -zsrn
•(s 'Ηΐ)0Γ8 '(zH0"8=f 'P 'Ηΐ)0ε·8 '(zH0"8=f 'P 'Ηΐ)ΐΟ·8 '(ZH9"Z
Figure imgf000126_0006
1731- S081760/S00Z OAV 物を室温まで冷却し、水を加え酢酸ェチルで抽出した。酢酸ェチル層を飽和炭酸水 素ナトリウム水溶液で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去して得 られた残渣をシリカゲルカラムクロマトグラフィー (n-へキサン Zジクロロメタン =2Zl) で精製して、標題化合物の白色結晶 (296mg, 69%)を得た。 • ( s 'Ηΐ) 0Γ8' ( z H0 "8 = f 'P' Ηΐ) 0ε8 '( z H0" 8 = f' P 'Ηΐ) ΐΟ8' ( Z H9 "Z
Figure imgf000126_0006
1731- S081760 / S00Z OAV The product was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and dried over anhydrous sodium sulfate. The residue obtained by evaporation of the solvent under reduced pressure was purified by silica gel column chromatography (n-hexane Z dichloromethane = 2Zl) to give the title compound as white crystals (296 mg, 69%).
1H-NMR(CDC1 ): δ 1.69(9H, s), 3.56(2H, brs), 5.90(1H, s), 7.21-7.37(3H, m),  1H-NMR (CDC1): δ 1.69 (9H, s), 3.56 (2H, brs), 5.90 (1H, s), 7.21-7.37 (3H, m),
3  Three
7.72-7.76(2H, m).  7.72-7.76 (2H, m).
(2)化合物番号 86 (2) Compound No. 86
収率 17%。 'H-NMRCCDCl ): δ 1.83(9H, s), 6.59(1H, s), 7.28-7.34(lH, m), Yield 17%. 'H-NMRCCDCl): δ 1.83 (9H, s), 6.59 (1H, s), 7.28-7.34 (lH, m),
3  Three
7.36-7.44(4H, m), 7.52-7.64(2H, m), 7.78-7.86(3H, m), 8.44- 8.48(1H, m), 8.76(1H, s), 13.83(1H, s).  7.36-7.44 (4H, m), 7.52-7.64 (2H, m), 7.78-7.86 (3H, m), 8.44- 8.48 (1H, m), 8.76 (1H, s), 13.83 (1H, s).
例 87:化合物番号 87 Example 87: Compound number 87
(1) 4- (トリフルォロメチル)フエ-ルヒドラジン (一般合成法 ε )  (1) 4- (trifluoromethyl) phenylhydrazine (general synthesis method ε)
4-ァミノべンゾトリフルオライド (483mg, 3mmol)に、氷冷下、濃塩酸 (3ml)をカ卩え、同 温で攪拌した。この混合物に、氷冷下、亜硝酸ナトリウム (214mg, 3.1mmol)の水溶液 (3ml)を 1時間かけてカ卩えた。この混合物に、氷冷下、塩化スズ (1.71g, 9mmol)の濃塩 酸溶液 (3ml)を 30分間かけて加え、次いで同温で 30分間攪拌した。不溶物を濾別し、 濾液に 5N水酸ィ匕ナトリウム水溶液をカ卩ぇアルカリ性とし、ジクロロメタンで抽出した。ジ クロロメタン層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留 去して、標題化合物の淡黄色結晶 (322mg, 61%)を得た。  Concentrated hydrochloric acid (3 ml) was added to 4-aminobenzotrifluoride (483 mg, 3 mmol) under ice cooling, and the mixture was stirred at the same temperature. An aqueous solution (3 ml) of sodium nitrite (214 mg, 3.1 mmol) was added to the mixture under ice cooling over 1 hour. To this mixture was added a concentrated hydrochloric acid solution (3 ml) of tin chloride (1.71 g, 9 mmol) over 30 minutes under ice-cooling, followed by stirring at the same temperature for 30 minutes. The insoluble material was filtered off, and the filtrate was made alkaline with a 5N sodium hydroxide aqueous solution and extracted with dichloromethane. The dichloromethane layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain pale yellow crystals of the title compound (322 mg, 61%).
1H-NMR(CDC1 ): δ 3.62(2H, brs), 5.45(1H, brs), 6.85(2H, d, J=8.7Hz), 7.46(2H,  1H-NMR (CDC1): δ 3.62 (2H, brs), 5.45 (1H, brs), 6.85 (2H, d, J = 8.7Hz), 7.46 (2H,
3  Three
d, J=8.7Hz). d, J = 8.7Hz).
(2) 5-ァミノ- 3-メチル -l-[4- (トリフルォロメチル)フエ-ル]ピラゾール  (2) 5-amino-3-methyl-l- [4- (trifluoromethyl) phenyl] pyrazole
一般合成法 βと同様の方法により標題ィ匕合物を得た。収率 71%。 1H-NMR(CDC1 ): The title compound was obtained in the same manner as in the general synthesis method β. Yield 71%. 1H-NMR (CDC1):
3 δ 2.23(3H, s), 3.79(2H, brs), 5.50(1H, s), 7.71(2H, d, J=9.1Hz), 7.76(2H, d, J=9.1Hz).  3 δ 2.23 (3H, s), 3.79 (2H, brs), 5.50 (1H, s), 7.71 (2H, d, J = 9.1Hz), 7.76 (2H, d, J = 9.1Hz).
(3)化合物番号 87  (3) Compound No. 87
収率 44%。 'H-NMRCCDCl ): δ 2.39(3H, s), 6.31(1H, s), 7.37(2H, s), Yield 44%. 'H-NMRCCDCl): δ 2.39 (3H, s), 6.31 (1H, s), 7.37 (2H, s),
3  Three
7.49-7.63(2H, m), 7.76-7.84(5H, m), 8.37- 8.40(1H, m), 8.83(1H, s), 13.39(lH,s). •(ω 'HS) T8— 6S'8 '(ω 'H2)06"Z-S8"Z '(s 'HI) S'S '(sjq 'H2)S8"S '(s 'HS) S 9 :(7.49-7.63 (2H, m), 7.76-7.84 (5H, m), 8.37- 8.40 (1H, m), 8.83 (1H, s), 13.39 (lH, s). • (ω 'HS) T8— 6S'8' (ω 'H2) 06 "Z-S8"Z'(s' HI) S'S '(sjq' H2) S8 "S '( s ' HS) S 9 :(
DaD)H N-HT °%6i ¾ί
Figure imgf000128_0001
DaD) H NH T °% 6i ¾ί
Figure imgf000128_0001
一 、 ; Μ/·^ - S- ( / ェ cH - - ΐ- - S (ΐ)  I,; Μ / · ^-S- (/ c cH--ΐ--S (ΐ)
•(s Ήΐ)03·εΐ '(s Ήΐ)6Ζ·8 '(ΖΗΐ·6=ί" 'Ρ 'Ηΐ)Ζε·8 '(ΖΗΐ·8=ί" 'Ρ 'Ηΐ)9ΓΖ '(ω 'H9)09"Z-Z^"Z '(ΖΗΟ·ΐ=ί" 'Ρ H2)SS- '(s Ήΐ) 2-9 '(s 'HS)8S"2 '(s 'Η6)6ε·ΐ 9 :( OSWa) 顺— Ητ °%ΐε ¾ί • ( s Ήΐ) 03 · εΐ '(s Ήΐ) 6Ζ · 8' (ΖΗΐ · 6 = ί "'Ρ' Ηΐ) Ζε · 8 '(ΖΗΐ · 8 = ί"' Ρ 'Ηΐ) 9ΓΖ' (ω ' H9) 09 "ZZ ^" Z '(ΖΗΟ · ΐ = ί "' Ρ H2) SS- '(s Ήΐ) 2-9' ( s ' HS) 8S" 2 '( s ' Η6) 6εΐ: 9: (OSWa) 顺 — Η τ °% ΐε ¾ί
16各粱呦^ (ε)  16 each 呦 ^ (ε)
'H )WL '(s 'HZ)WL '(s 'Ηΐ) '(sjq )εΓε '(s 'HS)SS '(s Ή6) SS"T 9 :(
Figure imgf000128_0002
'H) WL'(s' HZ) WL '(s'Ηΐ)' (sjq) εΓε '( s ' HS) SS' ( s Ή6) SS "T 9 :(
Figure imgf000128_0002
一 、 ; Μ/·^ - ε- [ / ェ ( ^ :- s - ] -卜,^ - s (z) I,; Μ / · ^-ε- [/ ェ (^:-s-]-u, ^-s (z)
•(zH0"6=f 'P 'H ·Ζ '(ΖΗ0·6=1" 'Ρ 'Η 8Γ9 '(s 'H6)62"T 9 :(• ( z H0 "6 = f 'P' H · Ζ '(ΖΗ0 · 6 = 1"' Ρ 'Η 8Γ9' ( s ' H6) 62 "T 9 :(
DaD)H N-HT °%os ¾τ
Figure imgf000128_0003
DaD) H NH T °% os ¾τ
Figure imgf000128_0003
•(ω 'H2)S2"8 '(ω Ήε)0Γ8 '(ω Ή2)09"Ζ '(zH0"8=f ' 'Η ε · '(ω 'HZ)LVL '(ω 'Ηΐ)98·9 '(s 'Η6)9 ·ΐ 9 :( <3つ) Η顺— Ητ °% 9 ¾ί (Ω 'H2) S2 "8' (ω Ήε) 0Γ8 '(ω Ή2) 09"Ζ' (zH0 "8 = f '' Η ε · '(ω' HZ) LVL '(ω' Ηΐ) 98 9 '( s ' Η6) 9 · ΐ 9 :( <3) Η 顺 — Η τ °% 9 ¾ί
06各粱呦  06 each
Xs 'Ηΐ)ΐ ·0ΐ
Figure imgf000128_0004
X s ' Ηΐ) ΐ 0ΐ
Figure imgf000128_0004
'Ρ Ή2)90"8
Figure imgf000128_0005
'(ZH ·Ζ=ί"'Ρ Ή2) 90 "8
Figure imgf000128_0005
'(ZH · Ζ = ί "
' 'HT)02"Z '(ζΗε·9=ί" 'Ρ 'Ηΐ)ΐΟ· '(s 'H6)S 'I 9 :( OSWa) 顺— Ητ °%8S ? φ '' HT) 02 "Z '(ζΗε9 = ί"' Ρ 'Ηΐ) ΐΟ' (s 'H6) S' I 9 :( OSWa) 顺 — Η τ °% 8S? Φ
68各粱呦 -6S  68 each 呦 -6S
'HWZl '(s Ήΐ)28 ΐ 'HWZl' ( s Ήΐ) 28 ΐ
' 'H2)½" '(ΖΗΐ·6=ί" '
Figure imgf000128_0006
'' H2) ½ "'(ΖΗΐ · 6 = ί"'
Figure imgf000128_0006
'Ρ Ήΐ)3ε· '(ΖΗ ·Ζ=1" '； Ήΐ)ΖΓΖ '(s 'Η6)0 ·ΐ 9 :( OSWa) 顺— Ητ °%9 ¾ί 'Ρ Ήΐ) 3ε ·' (ΖΗ · Ζ = 1 "'; Ήΐ) ΖΓΖ'(s' Η6) 0 · ΐ 9 :( OSWa) 顺 — Η τ °% 9 ¾ί
88各粱呦 -ss
Figure imgf000128_0007
931- S081760/S00Z OAV (2)化合物番号 92 88 each 呦
Figure imgf000128_0007
931- S081760 / S00Z OAV (2) Compound No. 92
収率 48%。 'H-NMRCCDCl ): δ 2.40(3H, s), 6.33(1Η, s), 7.38(2Η, s), Yield 48%. 'H-NMRCCDCl): δ 2.40 (3H, s), 6.33 (1Η, s), 7.38 (2Η, s),
3  Three
7.51-7.64(2Η, m), 7.78(1Η, d, J=8.4Hz), 7.91(2H, d, J=9.4Hz), 8.38- 8.41(3H, m), 8.84(1H, s), 13.35(1H, s).  7.51-7.64 (2Η, m), 7.78 (1Η, d, J = 8.4Hz), 7.91 (2H, d, J = 9.4Hz), 8.38-8.41 (3H, m), 8.84 (1H, s), 13.35 (1H, s).
例 93:化合物番号 93 Example 93: Compound number 93
収率 100%。 'H-NMRCDMSO-d ): δ 2.15 (3Η, s), 6.85(1Η, d, J=2.0Hz), Yield 100%. 'H-NMRCDMSO-d): δ 2.15 (3Η, s), 6.85 (1Η, d, J = 2.0Hz),
6  6
6.93— 6.98(2H, m), 7.17(1H, d, J=7.7Hz), 7.32(1H, d, J=9.1Hz), 7.71(1H, d, J=8.1Hz), 7.43-7.56(lH, m), 7.59- 7.64(1H, m), 7.71(1H, d, J=8.1Hz), 8.31(1H, d, J=7.7Hz), 8.83(1H, d, J=8.4Hz), 9.70(1H, s).  6.93-6.98 (2H, m), 7.17 (1H, d, J = 7.7Hz), 7.32 (1H, d, J = 9.1Hz), 7.71 (1H, d, J = 8.1Hz), 7.43-7.56 (lH , m), 7.59- 7.64 (1H, m), 7.71 (1H, d, J = 8.1Hz), 8.31 (1H, d, J = 7.7Hz), 8.83 (1H, d, J = 8.4Hz), 9.70 (1H, s).
例 94:化合物番号 94 Example 94: Compound number 94
(1) l-(3-クロ口- 4-メチルフエ-ル)- 3-エトキシカルボ-ル -5-メチルビラゾール (一般 合成法 ζ )  (1) l- (3-chloro-4-methylphenol) -3-ethoxycarbol-5-methylvirazole (general synthesis method ζ)
J ournal of Heterocylic Chemistry, Vol.30, p.307- 311(1993)に記載された 3-ブチル -5-エトキシカルボニル- 1-フエニルピラゾール及び 5-ブチル -3-エトキシカルボニル -1-フエ二ルビラゾールの合成法と同様の方法により標題ィ匕合物を得た。  3-butyl-5-ethoxycarbonyl-1-phenylpyrazole and 5-butyl-3-ethoxycarbonyl-1-phenyl described in J ournal of Heterocylic Chemistry, Vol. 30, p. 307-311 (1993). The title compound was obtained in the same manner as in the synthesis of ruvirazole.
(2) 1-(3-クロ口- 4-メチルフエ-ル)- 3-カルボキシ -5-メチルビラゾール (一般合成法 7? )  (2) 1- (3-chloro-4-methylphenyl) -3-carboxy-5-methylvirazole (General synthesis method 7?)
Chemical and Pharmaceutical Bulletin, Vol.47, No.6, p.857- 868(1999)に記載され た 4-クロ口- 1-(2,5-ジフルオロフェ-ル )- 5-(4-フルオロフェ -ル)ピラゾール- 3-カル ボン酸の合成法と同様の方法により標題ィ匕合物を得た。  Chemical and Pharmaceutical Bulletin, Vol. 47, No. 6, p. 857-868 (1999), 4-chloro-1- (2,5-difluorophenyl) -5- (4-fluorophene- G) The title compound was obtained in the same manner as in the synthesis of pyrazole-3-carbonic acid.
(3)化合物番号 94  (3) Compound No. 94
収率 50%。 'H-NMRCDMSO-d ): δ 2.41(3H, s), 2.43(3H, s), 6.86(1H, d, J=0.6Hz), Yield 50%. 'H-NMRCDMSO-d): δ 2.41 (3H, s), 2.43 (3H, s), 6.86 (1H, d, J = 0.6Hz),
6  6
7.42-7.52(3H, m), 7.58(2H, d, J=1.2Hz), 7.80— 7.86(2H, m), 8.00(1H, d, J=9.0Hz), 8.20(1H, d, J=8.7Hz), 9.87(1H, s), 10.06(1H, s).  7.42-7.52 (3H, m), 7.58 (2H, d, J = 1.2Hz), 7.80― 7.86 (2H, m), 8.00 (1H, d, J = 9.0Hz), 8.20 (1H, d, J = 8.7Hz), 9.87 (1H, s), 10.06 (1H, s).
例 95:化合物番号 95 Example 95: Compound number 95
(1) l-(3-クロ口- 4-メチルフエ-ル)- 5-エトキシカルボ-ル -3-メチルピラゾール 例 94(1)の副生成物として得た。  (1) l- (3-chloro-4-Methylphenyl) -5-ethoxycarbol-3-methylpyrazole Obtained as a by-product of Example 94 (1).
(2) 1-(3-クロ口- 4-メチルフエ-ル)- 5-カルボキシ -3-メチルピラゾール 'Ρ 'Ηΐ)ΐΟ· '(ZHS ' 0·9=ί" 'ΡΡ 'Ηΐ)98·9 9 :( OSW I) 顺— Ητ °% 6 ¾ί (2) 1- (3-chloro-4-methylphenyl) -5-carboxy-3-methylpyrazole 'Ρ' Ηΐ) ΐΟ '' (ZHS '0 · 9 = ί "' ΡΡ 'Ηΐ) 98 · 9 9 :( OSW I) 顺 — Η τ °% 6 ¾ί
ΐθΐ各粱呦 ： TOTpi} [WIO] •(s 'H\)ZVZ\ '(ΖΗΖ·Ζ=1" 'P 'Ηΐ)96·8 '(ΖΗΓ8=Γ 'Ρ Ή\)ΖΖ^ '(ΖΗΓ8=Γ 'Ρ 'HDZL'L ΐθΐeach beam: TOTpi} [WIO] • ( s ' H \) ZVZ \ '(ΖΗΖ · Ζ = 1 "' P 'Ηΐ) 96 · 8' ( Ζ ΗΓ8 = Γ 'Ρ Ή \) ΖΖ ^' ( Ζ ΗΓ8 = Γ 'Ρ'HDZL'L
'(ω 'HT)99"Z-09"Z '(ω ' )WL-ZYL
Figure imgf000130_0001
'Ρ 'ΗΙ)££Ί '(ω 'WWL-LVL '(ω' HT) 99 "Z-09" Z '(ω') WL-ZYL
Figure imgf000130_0001
'Ρ' ΗΙ) ££ Ί '(ω' WWL-LVL
'(zW8=f 'Ρ 'Ηΐ)00· '(s Ήε)99·ε 9 :( P-OS a)H N-HT °%ΐ6 ? φ οοι各粱呦^ '(zW8 = f' Ρ 'Ηΐ) 00''(s Ήε) 99 · ε 9 :( P-OS a) H NH T °% ΐ6? φ οοι each beam 呦 ^
'(ZHS'8=f 'P 'Ηΐ) 8 S6"Z '(ΖΗΐ·6=ί" 'P Ήΐ)Ζ8 '(ZHS'8 = f' P 'Ηΐ) 8 S6 "Z' (ΖΗΐ6 = ί" 'P Ήΐ) Ζ8
'P Ήΐ)08"Ζ 'H ' Ήΐ)ΐ9"Ζ ' 'H2)9S"Z '(ω 'P Ήΐ) 08 "Ζ' H 'Ήΐ) ΐ9" Ζ' 'H2) 9S "Z' (ω
'm¾VL-LZ
Figure imgf000130_0002
'P Ήΐ)3Γ 'Ηΐ)88·9 9 :( !DaD)H N-HT °%8S ? φ 'm¾VL-LZ
Figure imgf000130_0002
'P Ήΐ) 3Γ' Ηΐ) 88 9 9: (! DaD) H NH T °% 8S? Φ
66各粱呦 :66 66 each siang 呦: 66
•(s 'Ηΐ)99·6 '(zHS'8=f 'P Ήΐ)9Γ8 '(ΖΗΓ6=Γ 'P 'Ηΐ)98· '(ΖΗ0·8=1"• ( s ' Ηΐ) 99 · 6 '(zHS'8 = f' P Ήΐ) 9Γ8 '( Ζ ΗΓ6 = Γ' P 'Ηΐ) 98 ·' (ΖΗ0 · 8 = 1 "
'ρ Ήΐ)6 · z'z=[ 'ρ Ήΐ)εζ·ζ '(ω Ήε)ε9"ζ '(ω 'HS)W '(ω Ήζ)ζη 'ρ Ήΐ) 6 z'z = [' ρ Ήΐ) εζζ '(ω Ήε) ε9 "ζ' (ω 'HS) W' (ω Ήζ) ζη
'(ΖΗΓ6=Γ 'Ρ 'HDfVL '(ζΗ2·ζ=Γ 'Ρ 'Ηΐ)93·9 9 :( !DaD)H N-HT °%IS ¾ί '( Ζ ΗΓ6 = Γ' Γ 'HDfVL' ( ζ Η2ζ = Γ 'Ρ' Ηΐ) 930.99: (! DaD) H NH T °% IS ¾ί
86各粱呦 -se 86 each-呦 se
•(s 'HT)29"6 '(zH8"8=f 'P Ήΐ)8Γ8 '(ΖΗΓ6=Γ 'P 'HT)S8" 8=1" 'P 'Ηΐ)6ΓΖ '(ω Ήε)09"Ζ
Figure imgf000130_0003
'PP ΉΖ)0Υί • ( s ' HT) 29 "6 '( z H8" 8 = f' P Ήΐ) 8Γ8 '( Ζ ΗΓ6 = Γ' P 'HT) S8 "8 = 1"' P 'Ηΐ) 6ΓΖ' (ω Ήε) 09 "Ζ
Figure imgf000130_0003
'PP ΉΖ) 0Υί
'(ΖΗΓ6=Γ 'P Ήΐ)εΓΖ '(s Ήΐ)8ε·9 '(s 'HZ)WZ 9 :( !DaD)H N-HT °%6S ? φ '( Ζ ΗΓ6 = Γ' P Ήΐ) εΓΖ '(s Ήΐ) 8ε9' ( s ' HZ) WZ 9 :(! DaD) H NH T °% 6S? Φ
•(s 'Ηΐ)ε8·6 '(zHS'8=f 'P 'Ηΐ) 9·8 '(ΖΗΓ6=Γ 'P 'Ηΐ)εθ·8 '(zH6"Z=f 'P 'Ηΐ)06· • ( s 'Ηΐ) ε8 6'(zHS'8 = f 'P' Ηΐ) 9 8 '( Ζ ΗΓ6 = Γ' P 'Ηΐ) εθ8' ( z H6 "Z = f 'P' Ηΐ ) 06
'(ΖΗΓΖ
Figure imgf000130_0004
'Ρ '(ΖΗΓΖ
Figure imgf000130_0004
'Ρ
Ηΐ)9ΓΖ '(s 'Ηΐ)ΐ6·9 '(s 'HZ)WZ '(s 'HS)0S"2 9 :( P-OS a)H N-HT °%9 ¾ί Ηΐ) 9ΓΖ '(s' Ηΐ) ΐ6.9 '( s ' HZ) WZ '( s ' HS) 0S "2 9 :( P-OS a) H NH T °% 9 ¾ί
96各粱呦 -96 [επο] 96 each siang 呦 -96 [επο]
•(s Ήΐ)Ζ2 ΐ '(s 'HI)9S'6 • ( s Ήΐ) Ζ2 ΐ '( s ' HI) 9S'6
'(ω 'Ηΐ)^·8— 8Γ8 '(ω 'HT)S8"Z-28"Z ^ΗΓΖ=ί 'Ρ 'HT)ZS"Z '(ω 'H9)0S"Z-9S"Z  '(ω' Ηΐ) ^ · 8—8Γ8 '(ω' HT) S8 "Z-28" Z ^ ΗΓΖ = ί 'Ρ' HT) ZS "Z '(ω' H9) 0S" Z-9S "Z
'(s Ήΐ)εο· '(s Ήε)9ε '(s 'm)z^z 9 :( p-os a)H N-HT °% ¾τ '( s Ήΐ) εο ·' (s Ήε) 9ε '( s ' m) z ^ z 9 :( p-os a) H NH T °% ¾τ
S6各粱呦 (ε)
Figure imgf000130_0005
831- S081760/S00Z OAV J=9.1Hz), 7.31-7.38(3H, m), 7.46- 7.51(1H, m), 7.61-7.74(3H, m), 7.97(1H, d, J=2.0Hz), 8.22(1H, d, J=9.1Hz), 8.33- 8.36(1H, m), 9.12(1H, d, J=8.4Hz), 10.25(1H s). S6 each 呦 (ε)
Figure imgf000130_0005
831- S081760 / S00Z OAV J = 9.1Hz), 7.31-7.38 (3H, m), 7.46-7.51 (1H, m), 7.61-7.74 (3H, m), 7.97 (1H, d, J = 2.0Hz), 8.22 (1H, d , J = 9.1Hz), 8.33- 8.36 (1H, m), 9.12 (1H, d, J = 8.4Hz), 10.25 (1H s).
例 102:化合物番号 102 Example 102: Compound number 102
収率 50%。 ^-NMRCDMSO-d ): δ 7.05-7.16(3Η, m), 7.26— 7.30(3Η, m), 7.39(1Η, Yield 50%. ^ -NMRCDMSO-d): δ 7.05-7.16 (3Η, m), 7.26-7.30 (3Η, m), 7.39 (1Η,
6  6
dd, J=8.4,5.7Hz), 7.47-7.52(1Η, m), 7.57-7.61(1Η, m), 7.67(1Η, s), 7.73(1Η, d, J=8.4Hz), 8.38(1H, d, J=8.1Hz), 8.66(1H, s), 13.45(1H, s). dd, J = 8.4,5.7Hz), 7.47-7.52 (1Η, m), 7.57-7.61 (1Η, m), 7.67 (1Η, s), 7.73 (1Η, d, J = 8.4Hz), 8.38 (1H , d, J = 8.1Hz), 8.66 (1H, s), 13.45 (1H, s).
例 103:化合物番号 103 Example 103: Compound number 103
(1) 5-ァミノ- 1-(2-シァノエチル) -3-メチルビラゾール  (1) 5-amino-1- (2-cyanoethyl) -3-methylvirazole
一般合成法 βと同様の方法により標題ィ匕合物を得た。収率 36%。 'H-NMRCCDCl  The title compound was obtained in the same manner as in the general synthesis method β. Yield 36%. 'H-NMRCCDCl
3 Three
): δ 2.16(3H, s), 2.86(2H, t, J=6.4Hz), 3.49(2H, brs), 4.21(2H, t, J=6.4Hz), 5.42(1H, s). ): δ 2.16 (3H, s), 2.86 (2H, t, J = 6.4Hz), 3.49 (2H, brs), 4.21 (2H, t, J = 6.4Hz), 5.42 (1H, s).
(2)化合物番号 103  (2) Compound No. 103
収率 38%。 'H-NMRCCDCl ): δ 2.30(3H, s), 2.97(2H, t, J=6.9Hz), 4.51(2H, t, Yield 38%. 'H-NMRCCDCl): δ 2.30 (3H, s), 2.97 (2H, t, J = 6.9Hz), 4.51 (2H, t,
3  Three
J=6.9Hz), 6.12(1H, s), 7.37(2H, s), 7.53— 7.65(2H, m), 7.78(1H, d, J=8.7Hz), 8.44(1H, d, J=8.4Hz), 8.76(1H, s), 13.59(lH,s).  J = 6.9Hz), 6.12 (1H, s), 7.37 (2H, s), 7.53-7.65 (2H, m), 7.78 (1H, d, J = 8.7Hz), 8.44 (1H, d, J = 8.4 Hz), 8.76 (1H, s), 13.59 (lH, s).
例 104:化合物番号 104 Example 104: Compound number 104
収率 84%。 'H-NMRCDMSO-d ): δ 7.12(1Η, d, J=9.3Hz), 7.34(1Η, s), Yield 84%. 'H-NMRCDMSO-d): δ 7.12 (1Η, d, J = 9.3Hz), 7.34 (1Η, s),
6  6
7.38-7.44(2Η, m), 7.46-7.56(2Η, m), 7.61(1Η, t, J=7.7Hz), 7.81- 7.84(3H, m), 7.98(1H, d, J=9.3Hz), 8.50(1H, d, J=8.2Hz), 9.83(1H, s).  7.38-7.44 (2Η, m), 7.46-7.56 (2Η, m), 7.61 (1Η, t, J = 7.7Hz), 7.81- 7.84 (3H, m), 7.98 (1H, d, J = 9.3Hz) , 8.50 (1H, d, J = 8.2Hz), 9.83 (1H, s).
例 105:化合物番号 105 Example 105: Compound number 105
収率 75%。 'H-NMRCCDCl ): δ 1.62-1.68(2H,m), 1.86- 1.94(4Η, m), 2.97(4Η, t, Yield 75%. 'H-NMRCCDCl): δ 1.62-1.68 (2H, m), 1.86-1.94 (4Η, m), 2.97 (4Η, t,
3  Three
J=5.2Hz), 6.93(1H, d, J=9.1Hz), 7.10(1H, d, J=9.1Hz), 7.19(1H, d, J=8.7Hz), 7.41-7.50(3H, m), 7.55- 7.63(2H, m), 8.33(1H, d, J=8.7Hz), 8.52(1H, d, J=8.7Hz). 例 106:化合物番号 106  J = 5.2Hz), 6.93 (1H, d, J = 9.1Hz), 7.10 (1H, d, J = 9.1Hz), 7.19 (1H, d, J = 8.7Hz), 7.41-7.50 (3H, m) , 7.55- 7.63 (2H, m), 8.33 (1H, d, J = 8.7Hz), 8.52 (1H, d, J = 8.7Hz) .Example 106: Compound No. 106
収率 5%。 'H-NMRCCDCl ): δ 6.93(1H, d, J=9.1Hz), 7.07(1H, d, J=8.7Hz), Yield 5%. 'H-NMRCCDCl): δ 6.93 (1H, d, J = 9.1Hz), 7.07 (1H, d, J = 8.7Hz),
3  Three
7.51-7.72(12H, m), 8.11- 8.14(2H, m), 8.50- 8.53(1H, m), 12.58(1H, s).  7.51-7.72 (12H, m), 8.11- 8.14 (2H, m), 8.50- 8.53 (1H, m), 12.58 (1H, s).
例 107:化合物番号 107 収率 54%。 H-NMR(CDC1 ): δ 6.74-6.77(lH,m), 6.89- 6.92(2H, m), 6.99(1H, d,Example 107: Compound number 107 Yield 54%. H-NMR (CDC1): δ 6.74-6.77 (lH, m), 6.89-6.92 (2H, m), 6.99 (1H, d,
3 Three
J=8.7Hz), 7.11(1H, d, J=9.1Hz), 7.26— 7.32(1H, m), 7.45— 7.51(1H, m),  J = 8.7Hz), 7.11 (1H, d, J = 9.1Hz), 7.26― 7.32 (1H, m), 7.45― 7.51 (1H, m),
7.57-7.66(2H, m), 8.34(1H, s), 8.47(1H, d, J=8.1Hz). 7.57-7.66 (2H, m), 8.34 (1H, s), 8.47 (1H, d, J = 8.1Hz).
例 108:化合物番号 108 Example 108: Compound number 108
収率 79%。 'H-NMRCCDCl ): δ 2.31(3Η, s), 6.84(lH,d, J=8.4Hz), 7.01— 7.09(2H, 79% yield. 'H-NMRCCDCl): δ 2.31 (3Η, s), 6.84 (lH, d, J = 8.4Hz), 7.01-7.09 (2H,
3  Three
m), 7.15-7.17(2H, m), 7.45— 7.50(1H, m), 7.54— 7.60(1H, m), 7.66(1H, d, J=7.7Hz), 8.36(1H, s), 8.45-8.48(lH, m). m), 7.15-7.17 (2H, m), 7.45-7.50 (1H, m), 7.54-7.60 (1H, m), 7.66 (1H, d, J = 7.7Hz), 8.36 (1H, s), 8.45 -8.48 (lH, m).
例 109:化合物番号 109 Example 109: Compound number 109
収率 49%。 'H-NMRCCDCl ): δ 2.38(3Η, s), 7.00(1Η, d, J=8.7Hz), 7.14(1Η, d, Yield 49%. 'H-NMRCCDCl): δ 2.38 (3Η, s), 7.00 (1Η, d, J = 8.7Hz), 7.14 (1Η, d,
3  Three
J=8.7Hz), 7.24-7.25(4H, m), 7.44-7.50(lH, m), 7.55- 7.60(1H, m), 7.65(1H, d, J=7.1Hz), 8.39(1H, d, J=6.7Hz), 8.45- 8.48(1H, m).  J = 8.7Hz), 7.24-7.25 (4H, m), 7.44-7.50 (lH, m), 7.55- 7.60 (1H, m), 7.65 (1H, d, J = 7.1Hz), 8.39 (1H, d , J = 6.7Hz), 8.45- 8.48 (1H, m).
例 110:化合物番号 110 Example 110: Compound number 110
収率 36%。 'H-NMRCCDCl ): δ 1.44(9Η, s), 6.44(1Η, s), 7.14(1Η, d, J=9.1Hz), Yield 36%. 'H-NMRCCDCl): δ 1.44 (9Η, s), 6.44 (1Η, s), 7.14 (1Η, d, J = 9.1Hz),
3  Three
7.36-7.43(2Η, m), 7.48-7.52(2Η, m), 7.54— 7.66(3Η, m), 7.79(1Η, d, J=8.0Hz), 7.85(1H, d, J=9.1Hz), 8.22(1H, d, J=8.8Hz), 9.64(1H, s).  7.36-7.43 (2Η, m), 7.48-7.52 (2Η, m), 7.54― 7.66 (3Η, m), 7.79 (1Η, d, J = 8.0Hz), 7.85 (1H, d, J = 9.1Hz) , 8.22 (1H, d, J = 8.8Hz), 9.64 (1H, s).
例 111:化合物番号 111 Example 111: Compound number 111
収率 37%。 'H-NMRCCDCl ): δ 6.88(1H, d, J=9.1Hz), 7.03(1H, d, J=9.1Hz), Yield 37%. 'H-NMRCCDCl): δ 6.88 (1H, d, J = 9.1Hz), 7.03 (1H, d, J = 9.1Hz),
3  Three
7.43-7.49(lH, m), 7.54-7.65(2H, m), 7.99(1H, d, J=2.0Hz), 8.45- 8.49(1H, m), 8.55— 8.56(1H, m), 8.90(1H, d, J=9.1Hz).  7.43-7.49 (lH, m), 7.54-7.65 (2H, m), 7.99 (1H, d, J = 2.0Hz), 8.45- 8.49 (1H, m), 8.55-8.56 (1H, m), 8.90 ( (1H, d, J = 9.1Hz).
例 112:化合物番号 112 Example 112: Compound number 112
(1) 5-ァミノ- 1- (3,4-ジクロロフエ-ル)- 3-メチルビラゾール  (1) 5-Amino-1- (3,4-dichlorophenol) -3-methylvirazole
一般合成法 βと同様の方法により標題ィ匕合物を得た。収率 87%。 'H-NMRCCDCl ): δ 2.22(3H, s), 3.74(2H, brs), 5.47(1H, s), 7.45-7.53(2H, m), 7.76(1H, d, J=2.7Hz).  The title compound was obtained in the same manner as in the general synthesis method β. 87% yield. 'H-NMRCCDCl): δ 2.22 (3H, s), 3.74 (2H, brs), 5.47 (1H, s), 7.45-7.53 (2H, m), 7.76 (1H, d, J = 2.7Hz).
(2)化合物番号 112  (2) Compound No. 112
収率 56%。 'H-NMRCCDCl ): δ 2.38(3H, s), 6.29(1H, s), 7.36(2H, s), Yield 56%. 'H-NMRCCDCl): δ 2.38 (3H, s), 6.29 (1H, s), 7.36 (2H, s),
3  Three
7.50-7.55(2H, m), 7.58- 7.63(2H, m), 7.75-7.79(lH, m), 7.83(1H, d, J=2.0Hz), 8.38-8.4K1H, m), 8.81(1H, s), 13.40(1H, s). •(s 'Ηΐ)Ζ6·8 '(ω 'HZW^ '(ω 'Ηΐ)ΐε·8 '(s 'H\)W L 7.50-7.55 (2H, m), 7.58- 7.63 (2H, m), 7.75-7.79 (lH, m), 7.83 (1H, d, J = 2.0Hz), 8.38-8.4K1H, m), 8.81 (1H , s), 13.40 (1H, s). • (s' Ηΐ) Ζ6 · 8 '(ω' HZW ^ '(ω' Ηΐ) ΐε · 8 '( s ' H \) WL
'(ω 'Ηΐ)08· '(ω ' )L^L-WL '(s Ήε)3 ·ζ 9 つ) 顺— Ητ °%0ΐ ¾ί '(ω' Ηΐ) 08 · '(ω') L ^ L-WL '(s Ήε) 3 · ζ 9) 顺 — Η τ °% 0ΐ ¾ί
9ΐΐ各粱呦^ :9ΐΐ  9 呦 each 呦: 9 呦
.(S . (S
'Ηΐ)^·εΐ '(s 'Ηΐ)08·8 '(ΖΗΓ8=Γ 'Ρ 'Ηΐ)6ε·8 '(ω 'Ηΐ)8 - '(ω 'Η 9 - IS'Z 'Ηΐ) ^ · εΐ' ( s 'Ηΐ) 08 · 8' ( Ζ ΗΓ8 = Γ 'Ρ' Ηΐ) 6ε · 8 '(ω' Ηΐ) 8-'(ω' Η 9-IS'Z
'(s 'H2)9S"Z '(s 'HT)62"9 '(s 'HS)8S"2 9 つ) 顺— HT °% ¾ί '( s ' H2) 9S "Z '(s' HT) 62" 9 '( s ' HS) 8S "2 9) 顺 — H T °% ¾ί
en-^M^ ） en- ^ M ^)
•(ω 'Hi)09"z-ee-z '(ω 'HS)8^" -^- 'ΗΪ) S9"s '(sjq Ή2)ε ·ε '(s Ήε) 9 :(• (ω 'Hi) 09 "z-ee-z' (ω 'HS) 8 ^"-^-' ΗΪ) S9 "s '(sjq Ή2) ε · ε' (s Ήε) 9 :(
Iつ αつ) WN- ΗΤ 0%9ε*¾ί °^ ¾<¾?^®^ τ^)¾^ )#^^ d ^ ^- 一 、 ; Μ/·^ — ε—( / ェ rci i— — i— — s (ΐ) Iα) WN- Η Τ 0 % 9ε * ¾ί ° ^ ¾ <¾? ^ ® ^ τ ^) ¾ ^) # ^^ d ^ ^-one,; Μ / · ^ — ε— (/ ェ rci i— — i— — s (ΐ)
SII各粱呦 ： enp} [ζπο] SII each 呦: enp} [ζπο]
•(s 'Ηΐ) ΐ·εΐ '(s 'Ηΐ)ΖΖ·8 '(ω 'Ηΐ) Γ8— ΐε·8 '(ω 'Ηΐ)9ΓΖ— εΓΖ '(ω 'HS)29" -S^-• ( s ' Ηΐ) ΐ · εΐ '( s ' Ηΐ) ΖΖ · 8' (ω 'Ηΐ) Γ8— ΐε · 8' (ω 'Ηΐ) 9ΓΖ— εΓΖ' (ω 'HS) 29 "-S ^-
'(s Ή2)εε· '(s Ήΐ)62·9 '(s Ήε)6ε 9： ή α ) Ν- HT °% ¾Τ '( s Ή2) εε''(s Ήΐ) 62 · 9' ( s Ήε) 6ε 9: ή α) Ν- H T °% ¾Τ
m^ ^ (ζ) m ^ ^ (ζ)
•(ΖΗΟ =1" 'Ρ Ήΐ)½· '(zW8=f 'Ρ • (ΖΗΟ = 1 "'Ρ Ήΐ) ½' (zW8 = f 'Ρ
'Ηΐ) ·Ζ '(ΖΗ0 ' ·8=ί" 'ΡΡ 'Ηΐ)9ε· '(s 'HI)Z S '(sjq ' S'S '(s 'ΗΖ)ΖΖ 9 :('Ηΐ) · Ζ' (ΖΗ0 '· 8 = ί "' ΡΡ 'Ηΐ) 9ε ·'(s' HI) ZS '(sjq'S'S'( s ' ΗΖ) ΖΖ 9 :(
DaD)H N-HT °%S9*Xli ^Μ^^ΜΜ ^^^ Μ^ g ^ ^- DaD) H NH T °% S9 * Xli ^ Μ ^^ ΜΜ ^^^ Μ ^ g ^ ^-
•(s 'Ηΐ) ·εΐ '(s 'Ηΐ)ΐ8·8 '(ΖΗΖ·Ζ=ί" 'Ρ 'Ηΐ)8ε·8 • ( s 'Ηΐ) · εΐ' ( s 'Ηΐ) ΐ8 · 8' (ΖΗΖ · Ζ = ί "'Ρ' Ηΐ) 8ε · 8
'(ω 'H6)T9"Z-9S"Z '(s 'HT)62"9 '(s 'HS)8S"2 9 つ) Η顺— Ητ °% ¾ί '(ω' H6) T9 "Z-9S" Z '(s' HT) 62 "9 '( s ' HS) 8S" 2 9) Η 顺 — Η τ °% ¾ί
επ各粱呦^ (z) επ each beam 呦 ^ (z)
•(ZH0
Figure imgf000133_0001
• (ZH0
Figure imgf000133_0001
' 'Ηΐ)8ε· '(ω 'HT)0S"Z-92"Z '(s Ήΐ) ^·3 '(saq 'Η Γε '(s 'HS)SS 9 :(
Figure imgf000133_0002
'' Ηΐ) 8ε · '(ω' HT) 0S "Z-92" Z '(s Ήΐ) ^ · 3' (saq 'Η Γε' ( s ' HS) SS 9 :(
Figure imgf000133_0002
一 、 ; Μ/·^ — ε—( / ェ crn^— ε)— ΐ— — s a)  I,; Μ / · ^ — ε— (/ ェ crn ^ — ε) — ΐ— — s a)
επ各粱呦^ -zu
Figure imgf000133_0003
S081760/S00Z OAV (1) 3-エトキシカルボ-ル -5-メチル -1-フエ-ルビラゾール επ each beam 呦 ^ -zu
Figure imgf000133_0003
S081760 / S00Z OAV (1) 3-ethoxycarbol-5-methyl-1-phenylavirazole
一般合成法 ζと同様の方法により標題ィ匕合物を得た。  The title compound was obtained in the same manner as in General Synthesis Method II.
(2) 3-カルボキシ -5-メチル -1-フエ-ルビラゾール  (2) 3-carboxy-5-methyl-1-phenylavirazole
一般合成法 r?と同様の方法により標題ィ匕合物を得た。  The title compound was obtained in the same manner as in the general synthesis method r ?.
(3)化合物番号 117  (3) Compound No. 117
収率 57%。 'H-NMRCCDCl ): δ 2.39(3H, d, J=0.6Hz), 6.88(1H, d, J=0.6Hz), Yield 57%. 'H-NMRCCDCl): δ 2.39 (3H, d, J = 0.6Hz), 6.88 (1H, d, J = 0.6Hz),
3  Three
7.10(1H, d, J=8.7Hz), 7.37(1H, d, J=8.4Hz), 7.44- 7.59(6H, m), 7.74-7.77(lH, m), 8.44(1H, dd, J=8.1, 1.5Hz), 9.03(1H, brs), 10.15(1H, brs).  7.10 (1H, d, J = 8.7Hz), 7.37 (1H, d, J = 8.4Hz), 7.44- 7.59 (6H, m), 7.74-7.77 (lH, m), 8.44 (1H, dd, J = 8.1, 1.5Hz), 9.03 (1H, brs), 10.15 (1H, brs).
例 118:化合物番号 118 Example 118: Compound number 118
(1) 5-エトキシカルボ-ル -3-メチル -1-フエ-ルビラゾール  (1) 5-ethoxycarbol-3-methyl-1-phenylazole
例 117(1)の副生成物として得た。  Obtained as a by-product of Example 117 (1).
(2) 5-カルボキシ -3-メチル -1-フエ-ルビラゾール  (2) 5-carboxy-3-methyl-1-phenylavirazole
一般合成法 r?と同様の方法により標題ィ匕合物を得た。  The title compound was obtained in the same manner as in the general synthesis method r ?.
(3)化合物番号 118  (3) Compound No. 118
収率 49%。 'H-NMRCCDCl ): δ 2.41(3H, s), 6.68(1H, d, J=9.0Hz), 6.83(1H, s), Yield 49%. 'H-NMRCCDCl): δ 2.41 (3H, s), 6.68 (1H, d, J = 9.0Hz), 6.83 (1H, s),
3  Three
7.32(1H, d, J=8.7Hz), 7.44-7.56(7H, m), 7.71-7.75(2H, m), 8.34- 8.37(1H, m). 例 119:化合物番号 119  7.32 (1H, d, J = 8.7Hz), 7.44-7.56 (7H, m), 7.71-7.75 (2H, m), 8.34- 8.37 (1H, m) .Example 119: Compound No. 119
収率 68%。 'H-NMRCCDCl ): δ 6.94(1Η, d, J=9.1Hz), 7.08— 7.10(1Η, m), 7.13(1Η. Yield 68%. 'H-NMRCCDCl): δ 6.94 (1Η, d, J = 9.1Hz), 7.08-7.10 (1Η, m), 7.13 (1Η.
3  Three
d, J=8.7Hz), 7.31(1H, dd, J=7.7,0.7Hz), 7.44- 7.50(1H, m), 7.56- 7.62(3H, m), 8.43(1H, d, J=7.7Hz), 8.98(1H, d, J=7.7Hz). d, J = 8.7Hz), 7.31 (1H, dd, J = 7.7, 0.7Hz), 7.44- 7.50 (1H, m), 7.56- 7.62 (3H, m), 8.43 (1H, d, J = 7.7Hz) ), 8.98 (1H, d, J = 7.7Hz).
例 120:化合物番号 120 Example 120: Compound number 120
(1) 5-ァミノ- 1-(3-クロ口- 4-メチルフエ-ル) -3-メチルビラゾール  (1) 5-Amino-1- (3-chloro-4--4-methylphenol) -3-methylvirazole
一般合成法 βと同様の方法により標題ィ匕合物を得た。収率 78%。 'H-NMRCCDCl ): δ 2.22(3H, s), 2.40(3H, s), 3.74(2H, brs), 5.44(1H, s), 7.29(1H, d, J=8.0Hz), 7.36(1H, dd, J=8.0,2.0Hz), 7.58(1H, d, J=2.0Hz).  The title compound was obtained in the same manner as in the general synthesis method β. Yield 78%. 'H-NMRCCDCl): δ 2.22 (3H, s), 2.40 (3H, s), 3.74 (2H, brs), 5.44 (1H, s), 7.29 (1H, d, J = 8.0Hz), 7.36 (1H , dd, J = 8.0,2.0Hz), 7.58 (1H, d, J = 2.0Hz).
(2)化合物番号 120  (2) Compound No. 120
収率 36%。 'H-NMRCCDCl ): δ 2.39(3H, s), 2.47(3H, s), 6.29(1H, s), Yield 36%. 'H-NMRCCDCl): δ 2.39 (3H, s), 2.47 (3H, s), 6.29 (1H, s),
3  Three
7.36-7.39(3H, m), 7.44-7.62(3H, m), 7.69(1H, s), 7.76-7.78(lH, m), 8.39(1H, d, •(s 'Ηΐ)8ε·6 '(ω 'Ηΐ)6 ·8— 9 ·8 '(ω'Η 80·8— S0'8 '(ΖΗΖ·Ζ=ί" 'Ρ 'HT)8Z"Z '(zW8=f 'Ρ 'Ηΐ)ΐΖ· '(ω 'HS)Z9"Z-SS"Z '(s 'HT)OS"Z '(ΖΗΖ·8=ί" 'Ρ Ήΐ) η '(ΖΗΖ·8=ί" 'Ρ 'HT)SS"Z 9 :(¾αつ) Η顺— HT ¾ί 7.36-7.39 (3H, m), 7.44-7.62 (3H, m), 7.69 (1H, s), 7.76-7.78 (lH, m), 8.39 (1H, d, • ( s ' Ηΐ) 8ε · 6 '(ω' Ηΐ) 6 · 8—9 · 8 '(ω'Η 80 · 8—S0'8' (ΖΗΖ · Ζ = ί "'Ρ' HT) 8Z" Z '(zW8 = f' Ρ 'Ηΐ) ΐΖ''(ω' HS) Z9 "Z-SS" Z '(s' HT) OS "Z' (ΖΗΖ8 = ί"'Ρ Ήΐ) η' (ΖΗΖ · 8 = ί "'Ρ' HT) SS" Z 9: (¾α つ) Η 顺 — H T ¾ί
•(s 'Ηΐ)8ε·6 '(ΖΗΖ·Ζ=ί" 'P 'HDLVS '(ω 'HZ)L6' L-f6' L 'P 'Ηΐ)ΖΖ· '(ω 'H8)S9"Z-2S"Z 9 :(¾αつ) 顺— HT °%0S ¾ί • (s' Ηΐ) 8ε · 6 '(ΖΗΖ · Ζ = ί "' P 'HDLVS' (ω 'HZ) L6' L-f6 'L' P 'Ηΐ) ΖΖ''(ω' H8) S9" Z -2S "Z 9: (¾α つ) 顺 — H T °% 0S ¾ί
•(zH '8=f 'Ρ 'Ηΐ)εθ·6 '(ΖΗΓ8=Γ 'Ρ Ήΐ)εε·8 '(ΖΗΖ·ΐ=ί" 'Ρ 'Ηΐ)80·8 VL=[ 'Ρ Ήΐ)88"Ζ '(ω 'H )ZL' L-Z9' L '(ω 'HS)SS'Z- ΐ ·Ζ
Figure imgf000135_0001
'Ρ 'Ηΐ)ε。· 9 :(9Ρ— Ν— Ητ °%98 ¾ί 各粱呦 · Ζ • (zH '8 = f' Ρ 'Ηΐ) εθ6' ( Ζ ΗΓ8 = Γ 'Ρ Ήΐ) εε8' (ΖΗΖΖΗΖΐ = ί "'Ρ' Ηΐ) 808 VL = ['Ρ Ήΐ ) 88 "Ζ '(ω' H) ZL 'L-Z9' L '(ω' HS) SS'Z- ΐ
Figure imgf000135_0001
'Ρ' Ηΐ) ε. · 9 :( 9 Ρ— Ν— Η τ °% 98 ¾ί each beam · Ζ
•(s 'Ηΐ)εε·0ΐ '(wq 'HI)SZ'6 '(zH9"6=f 'P 'HI)SS'8 '(zHS'6=f 'P 'Ηΐ)98· '(ΖΗΟ·8=1" 'P 'HT)SZ"Z
Figure imgf000135_0002
( S 'Ηΐ) εε0ΐ' (wq 'HI) SZ'6' ( z H9 "6 = f 'P' HI) SS'8 '(zHS'6 = f' P 'Ηΐ) 98 ΖΗΟ · 8 = 1 "'P' HT) SZ" Z
Figure imgf000135_0002
' P 'H\) L '(ω Ήΐ)6ΓΖ-2ΓΖ '(s Ήε)90· 9 :( OSWd) N— HT °% 9 ¾T
Figure imgf000135_0003
'P' H \) L '(ω Ήΐ) 6ΓΖ-2ΓΖ' (s Ήε) 909 :( OSWd) N— H T °% 9 ¾T
Figure imgf000135_0003
•(s Ήΐ)ε9 ΐ '(ζΗ8·π=ί" 'p 'Hi)eo"6 'WL=[ 'p Ήΐ)εε·8 '(zH0"2=f 'p Ήΐ)εο·8• ( s Ήΐ) ε9 ΐ '( ζ Η8π = ί "' p 'Hi) eo"6' WL = ['p Ήΐ) εε8' ( z H0 "2 = f 'p Ήΐ) εο8
'(ω 'H2)SZ"Z-2Z"Z '(ω 'H2)99"Z-09"Z '(ω 'HS)0S"Z-2S"Z
Figure imgf000135_0004
'P 'ΗΙ)£ΖΊ '(ΖΗ ·8=1" 'P Ήΐ)0ΓΖ
Figure imgf000135_0005
'Ρ 'HT)28"9 9 :( OSWa) 顺— Ητ °%S8 ? φ
Figure imgf000135_0006
'(ω' H2) SZ "Z-2Z" Z '(ω' H2) 99 "Z-09" Z '(ω' HS) 0S "Z-2S" Z
Figure imgf000135_0004
'P' ΗΙ) £ ΖΊ '(ΖΗ · 8 = 1 "' P Ήΐ) 0ΓΖ
Figure imgf000135_0005
'Ρ' HT) 28 "9 9 :( OSWa) 顺 — Η τ °% S8? Φ
Figure imgf000135_0006
'P Ήΐ)89"Ζ '(ω 'HT)09"Z-eS"Z '(ω 'HT)Te" -9F '(ω
Figure imgf000135_0007
'P Ηΐ)6ΓΖ '(ΖΗΖ·8=1" 'P 'HT)Z0"Z '(ω 'H S6'9— 06·9 9 :( <3つ) 顺— HT °%86 ¾ί 'P Ήΐ) 89 "Ζ' (ω 'HT) 09" Z-eS "Z' (ω 'HT) Te"-9F' (ω
Figure imgf000135_0007
'P Ηΐ) 6ΓΖ' (ΖΗΖ8 = 1 "'P' HT) Z0" Z '(ω' H S6'9— 06 · 9 9 :( <3) 顺 — H T °% 86 ¾ί
•(ΖΗΓ6=Γ 'Ρ 'Ηΐ)66·8 mVS=i 'Ρ 'Ηΐ)9 ·8 '(ΖΗΖ·8=1" 'Ρ Ήΐ)02"8 '(s 'HT)^Z"Z '(ω 'H2)S9"Z-ZS"Z '(ω 'H^)0S" -22"
Figure imgf000135_0008
Figure imgf000135_0009
εεΐ· S081760/S00Z OAV οει各粱呦 (ε)• ( Ζ ΗΓ6 = Γ 'Ρ' Ηΐ) 66.8 mVS = i 'Ρ' Ηΐ) 9 · 8 '(ΖΗΖ8 = 1 "' Ρ Ήΐ) 02" 8 '( s ' HT) ^ Z "Z '(ω' H2) S9 "Z-ZS" Z '(ω' H ^) 0S "-22"
Figure imgf000135_0008
Figure imgf000135_0009
εεΐS081760 / S00Z OAV οει each 呦 (ε)
•(zH6=f 'P 'HZ)ZVL '(zH6=f 'P 'HZ ^L '(s 'Ηΐ)6Ζ·9 '(s 'HS)9S"2 9 :( • (z H6 = f 'P ' HZ) ZVL '(zH6 = f' P 'HZ ^ L'(s' Ηΐ) 6Ζ · 9 '(s' HS) 9S "2 9 :(
DaD)H N-HT °%i9 ¾ί
Figure imgf000136_0001
DaD) H NH T °% i9 ¾ί
Figure imgf000136_0001
"(ω
Figure imgf000136_0002
'b 'ΗΖ)ΖΥ '(s 'Η£)££'Ζ '(ZHZ
Figure imgf000136_0003
"(ω
Figure imgf000136_0002
'b' ΗΖ) ΖΥ '( s ' Η £) ££ 'Ζ' ( Z HZ
Figure imgf000136_0003
一 、 ; Μ/·^ - s - / ^ / ェ- ε- ( / ェ crn^- - ΐ (ΐ) οει各粱呦^ -oz •(S 'ΗΪ)88·8 '(^ Ήΐ)ζε·8— εε·81,; Μ / ^^-s-/ ^ /-ε- (/ cr crn ^--ΐ (ΐ) οει each beam 呦 ^ -oz • ( S 'ΗΪ) 88 · 8' (^ Ήΐ) ζε · 8— εε · 8
'(saq Ήΐ)88"Ζ '(ω 'HT)8Z"Z-SZ"Z '(ω
Figure imgf000136_0004
'Ρ 'HT)8S"Z '(ΖΗ6=Γ 'Ρ 'Ηΐ)ε6·9 '(s 'Ηΐ) 9 '(s 'HZ)WZ 9： N- HT °%0 ¾ί
Figure imgf000136_0005
'(saq Ήΐ) 88 "Ζ' (ω 'HT) 8Z" Z-SZ "Z' (ω
Figure imgf000136_0004
'Ρ' HT) 8S "Z '( Ζ Η6 = Γ' Ρ 'Ηΐ) ε6.9 · ( s ' Ηΐ) 9 '( s ' HZ) WZ 9: N-H T °% 0 ¾ί
Figure imgf000136_0005
•(zH6=f 'Ρ 'HZ)WL '(zH6=f 'P 'H2)8S"Z '(s Ήΐ)06·9 '(s 'HS)9S"2 9 :(
Figure imgf000136_0006
 • (z H6 = f 'Ρ ' HZ) WL '(z H6 = f' P 'H2) 8S "Z' (s Ήΐ) 06 · 9 '(s' HS) 9S" 2 9 :(
Figure imgf000136_0006
"(zH6=f 'P ΉΖ)ΙΥί '(zH6=f 'P 'H2)9S"Z '(s 'HT)28"9 '(zHZ=f 'b 'HZ)ZZ^ '(s 'HS)SS '(zHZ=f '； 'HS ·ΐ 9 :("(zH6 = f 'P ΉΖ) ΙΥί' (zH6 = f 'P' H2) 9S" Z '(s' HT) 28 "9' ( z HZ = f 'b' HZ) ZZ ^ '( s ' HS ) SS '( z HZ = f';'HS · ΐ 9 :(
DaD)H N-HT °%oi ¾ί
Figure imgf000136_0007
DaD) H NH T °% oi ¾ί
Figure imgf000136_0007
一 、 ; Μ/·^ - ε- / ^ / ェ- S -( / ェ crn^- - ΐ (ΐ)  I,; Μ / · ^-ε- / ^ /-S-(/ cr crn ^--ΐ (ΐ)
•(S 'HI) zra'(s • ( S 'HI) zra' ( s
'Ηΐ)08·8 '(ω 'Ηΐ)Ζε·8— Γ8 '(ω 'Ηΐ) · - Ζ '(ω 'UWLSVL '(s 'HS)SS 'Ηΐ) 08 · 8' (ω 'Ηΐ) Ζε · 8— Γ8' (ω 'Ηΐ) ·-Ζ' (ω 'UWLSVL' ( s ' HS) SS
'(ω 'm) Z-L-6VL '(s 'HT)62"9 '(s 'HS)8S"2 9 つ) 顺— HT °%ZS ¾ί '(ω' m) ZL-6VL '( s ' HT) 62 "9 '( s ' HS) 8S" 2 9) 顺 — H T °% ZS ¾ί
8SI各粱呦 (Z) 8SI each 呦 (Z)
•(ω 'H2)SS"Z-6^"Z '(ω 'Η2)8ΓΖ-0ΓΖ '(s 'HI)S 'S '(sjq 'H2)0Z"S '(s 'U£)ZZ'Z 9 :(• (ω 'H2) SS "Z-6 ^" Z' (ω 'Η2) 8ΓΖ-0ΓΖ' (s' HI) S 'S' (sjq 'H2) 0Z "S' (s' U £) ZZ ' Z 9 :(
DaD)H N-HT °%i8 ¾ί
Figure imgf000136_0008
DaD) H NH T °% i8 ¾ί
Figure imgf000136_0008
一 、 ; Μ/·^ - ε -( / -ェ ci / - - ΐ- - S (ΐ)  I,; Μ / · ^-ε-(/ -e ci /--ΐ--S (ΐ)
Figure imgf000136_0009
S081760/S00Z OAV 収率 31%。 H-NMR(DMSO-d ): δ 2.39(3H, s), 6.88(1H, s), 7.09(1H, d, J=8.5Hz)
Figure imgf000136_0009
S081760 / S00Z OAV Yield 31%. H-NMR (DMSO-d): δ 2.39 (3H, s), 6.88 (1H, s), 7.09 (1H, d, J = 8.5Hz)
6 6
7.37(1H, d, J=8.5Hz), 7.40- 7.55(6H, m), 7.73-7.78(lH, m), 8.40- 8.45(1H, m), 8.99(1H, brs), 10.1(1H, s).  7.37 (1H, d, J = 8.5Hz), 7.40- 7.55 (6H, m), 7.73-7.78 (lH, m), 8.40- 8.45 (1H, m), 8.99 (1H, brs), 10.1 (1H, s).
例 131:化合物番号 131 Example 131: Compound number 131
収率 40%。 ^-NMRCDMSO-d ): δ 7.20-7.48(2Η, m), 7.50— 7.65(2Η, m), Yield 40%. ^ -NMRCDMSO-d): δ 7.20-7.48 (2Η, m), 7.50― 7.65 (2Η, m),
6  6
7.65-7.80(2Η, m), 7.80— 7.90(1Η, m), 7.93(1Η, d, J=8.5Hz), 8.11(1Η, d, J=8Hz), 8.34(1H, d, J=8Hz), 9.40(1H, brs), 13.9(1H, brs).  7.65-7.80 (2Η, m), 7.80― 7.90 (1Η, m), 7.93 (1Η, d, J = 8.5Hz), 8.11 (1Η, d, J = 8Hz), 8.34 (1H, d, J = 8Hz) ), 9.40 (1H, brs), 13.9 (1H, brs).
例 132:化合物番号 132 Example 132: Compound number 132
収率 35%。 ^-NMRCDMSO-d ): δ 1.23(3Η, t, J=7Hz), 4.25(2Η, q, J=7Hz), Yield 35%. ^ -NMRCDMSO-d): δ 1.23 (3Η, t, J = 7Hz), 4.25 (2Η, q, J = 7Hz),
6  6
7.37(1H, d, J=8.5Hz), 7.40- 7.55(3H, m), 7.59(1H, t, J=7.5Hz), 7.65— 7.80(4H, m), 7.87(1H, d, J=8.5Hz), 8.35(1H, d, J=8.5Hz), 9.39(1H, brs), 13.7(1H, brs).  7.37 (1H, d, J = 8.5Hz), 7.40- 7.55 (3H, m), 7.59 (1H, t, J = 7.5Hz), 7.65― 7.80 (4H, m), 7.87 (1H, d, J = 8.5Hz), 8.35 (1H, d, J = 8.5Hz), 9.39 (1H, brs), 13.7 (1H, brs).
例 133:化合物番号 133 Example 133: Compound number 133
(1) 4- (エトキシカルボ-ル)フエ-ルヒドラジン  (1) 4- (ethoxycarbol) phenol hydrazine
一般合成法 εと同様の方法により標題ィ匕合物を得た。収率 74%。 'H-NMRCCDCl  The title compound was obtained in the same manner as in the general synthesis method ε. Yield 74%. 'H-NMRCCDCl
3 Three
): δ 1.37(3H, t, J=7.1Hz), 3.64(2H, brs), 4.33(2H, q, J=7.1Hz), 5.52(1H, brs), 6.79(2H, d, J=9.0Hz), 7.93 (2H, d, J=9.0Hz). ): δ 1.37 (3H, t, J = 7.1Hz), 3.64 (2H, brs), 4.33 (2H, q, J = 7.1Hz), 5.52 (1H, brs), 6.79 (2H, d, J = 9.0 Hz), 7.93 (2H, d, J = 9.0Hz).
(2) 5-ァミノ- 1-[4- (エトキシカルボ-ル)フエ-ル] -3-メチルビラゾール  (2) 5-amino-1- [4- (ethoxycarbol) phenyl] -3-methylvirazole
一般合成法 βと同様の方法により標題ィ匕合物を得た。収率 64%。 'H-NMRCCDCl  The title compound was obtained in the same manner as in the general synthesis method β. Yield 64%. 'H-NMRCCDCl
3 Three
): δ 1.41(3H, t, J=7.1Hz), 2.25(3H, s), 3.82(2H, brs), 4.40(2H, q, J=7.1Hz), 5.50(1H, s), 7.69(2H, d, J=8.8Hz), 8.14(2H, d, J=8.8Hz). ): δ 1.41 (3H, t, J = 7.1Hz), 2.25 (3H, s), 3.82 (2H, brs), 4.40 (2H, q, J = 7.1Hz), 5.50 (1H, s), 7.69 ( 2H, d, J = 8.8Hz), 8.14 (2H, d, J = 8.8Hz).
(3)化合物番号 133  (3) Compound No. 133
収率 22%。 'H-NMRCCDCl ): δ 1.43(3H, t, J=7.1Hz), 2.37(3H, s), 4.43(2H, q, Yield 22%. 'H-NMRCCDCl): δ 1.43 (3H, t, J = 7.1Hz), 2.37 (3H, s), 4.43 (2H, q,
3  Three
J=7.1Hz), 6.31(1H, s), 7.37(2H, s), 7.49— 7.63(6H, m), 7.75-7.78 (3H, m),  J = 7.1Hz), 6.31 (1H, s), 7.37 (2H, s), 7.49- 7.63 (6H, m), 7.75-7.78 (3H, m),
8.19-8.22(2H, m), 8.37- 8.39(1H, m), 8.82(1H, s), 13.41(1H, s). 8.19-8.22 (2H, m), 8.37- 8.39 (1H, m), 8.82 (1H, s), 13.41 (1H, s).
例 134:化合物番号 134 Example 134: Compound number 134
収率 12%。 'H-NMRCCDCl ): δ 5.40(2Η, s), 7.10(1Η, d, J=8.5Hz), 7.18-7.22(2Η, Yield 12%. 'H-NMRCCDCl): δ 5.40 (2Η, s), 7.10 (1Η, d, J = 8.5Hz), 7.18-7.22 (2Η,
3  Three
m), 7.30-7.55(9Η, m), 7.77(1Η, dd, J=7.5, 1.5Hz), 7.92(1H, s), 7.95(1H, s), 8.07(1H, dd, J=8, 1.5Hz), 8.45(1H, d, J=8Hz), 10.3(1H, s). '(s 'ΗΖ)ζΖ'8 '(zH0"8=f 'P Ήΐ)26"Ζ '^ΗΖ'Ζ '9 =f 'PP 'H2)S8"Z '(zH0"8=f ' m), 7.30-7.55 (9Η, m), 7.77 (1Η, dd, J = 7.5, 1.5Hz), 7.92 (1H, s), 7.95 (1H, s), 8.07 (1H, dd, J = 8, 1.5Hz), 8.45 (1H, d, J = 8Hz), 10.3 (1H, s). '(s' ΗΖ) ζΖ'8 '(zH0 "8 = f' P Ήΐ) 26" Ζ '^ ΗΖ'Ζ' 9 = f 'PP' H2) S8 "Z '(zH0" 8 = f'
Ήΐ)63· '(ω 'HZ)WL '(s Ήΐ)εε· '(s Ήε)8ε 9 :( oswa) 顺— Ητ °%π ¾Τ Ήΐ) 63 · '(ω' HZ) WL '(s Ήΐ) εε ·' (s Ήε) 8ε 9 :( oswa) 顺 — Η τ °% π ¾Τ
•(s Ήΐ)ΐ ΐ '(saq 'Ηΐ)66·8 '(ZHS'I 'S"Z=f 'PP Ή\)ΖΥ '(ZHS'I 'S"Z=f 'PP 'Ηΐ)ΖΖ·• (s Ήΐ) ΐ ΐ '(saq' Ηΐ) 66 · 8 '(ZHS'I' S "Z = f 'PP Ή \) ΖΥ' (ZHS'I 'S" Z = f' PP 'Ηΐ) ΖΖ ·
Figure imgf000138_0001
'P Ήΐ)ΟΓΖ '(zHS =f 'P 'Ηΐ)Ζ8·9 '(zHS =f 'P 'HS)6S"2 9 :( <3つ) 顺— HT °%0S ¾ί
Figure imgf000138_0001
'P Ήΐ) ΟΓΖ' ( z HS = f 'P' Ηΐ) Ζ8.9 '( z HS = f' P 'HS) 6S "2 9 :( <3) 顺 — H T °% 0S ¾ί
9ει各粱呦 (ε) 9ειEach 呦 (ε)
•(zHS'8=f 'Ρ ΉΖ)Ζ9Ί '(zHS"8=f 'Ρ 'H2)SS"Z '(s 'Ηΐ)08·9 '(s 'Η£)9£'Ζ 9 :(
Figure imgf000138_0002
• (zHS'8 = f 'Ρ ΉΖ) Ζ9Ί' (zHS "8 = f 'Ρ' H2) SS" Z '(s' Ηΐ) 089' ( s ' Η £) 9 £ 'Ζ 9 :(
Figure imgf000138_0002
'H2)SS"Z
Figure imgf000138_0003
'H2) SS "Z
Figure imgf000138_0003
' Ήε)ο ·ΐ 9： ή αつ) N- Ht °%ss ¾τ。 會 つ;呦^^ ii >(i)ssifi 'Ήε) ο · ΐ 9: ή α one) N- H t °% ss ¾τ .つ つ; 呦 ^^ ii> (i)
一 、 ; Μ/·^ - s - / ^ / 、^ ェ- ε -( / ェ rcl l- - ΐ (ΐ)  I,; Μ / · ^-s-/ ^ /, ^--ε-(/ r rcl l--ΐ (ΐ)
•(s 'Ηΐ)Ζ8·8 '(ω 'Ηΐ)Ζε·8— Ή 'Ηΐ)68·
Figure imgf000138_0004
• (s 'Ηΐ) Ζ8 · 8' (ω 'Ηΐ) Ζε · 8—Ή' Ηΐ) 68 ·
Figure imgf000138_0004
'(zHS'8=f 'Ρ 'Ηΐ) 6·9 '(s 'Ηΐ)8Ζ·9 '(s 'HZ)WZ 9 :( <3つ) Η顺— Ητ °%0S ¾ί '(zHS'8 = f' Ρ 'Ηΐ) 6.9' ( s ' Ηΐ) 8Ζ9 '( s ' HZ) WZ 9 :( <3) Η 顺 — Η τ °% 0S ¾ί
ssi各粱呦 (ε)  ssi each siang 呦 (ε)
•(zH6=f • (zH6 = f
'Ρ 'H2)S9"Z '(zH6=f 'P 'HZ)6£'L '(s 'Ηΐ) 8·9 '(s 'Η£) Ζ'Ζ 9 :( P- OSWa) 顺- H 'Ρ' H2) S9 "Z '(zH6 = f' P 'HZ) 6 £' L '( s ' Ηΐ) 8.9 '( s ' Η £) Ζ'Ζ 9 :( P- OSWa) 顺- H
T °%ooi ¾i ^m^ ^mn^ ^ u^ ^ ^-
Figure imgf000138_0005
 T °% ooi ¾i ^ m ^ ^ mn ^ ^ u ^ ^ ^-
Figure imgf000138_0005
'P 'H2)0S"Z '(s 'HT)28"9 '(zHZ=f 'b 'ΗΖ) Ζ' '(s 'HS)SS '(zHZ=f '； ΉΖ)ίΖ'\ 9 :(
Figure imgf000138_0006
'P' H2) 0S "Z '(s' HT) 28"9' ( z HZ = f 'b' ΗΖ) Ζ '' ( s ' HS) SS '( z HZ = f'; ΉΖ) ίΖ '\ 9 :(
Figure imgf000138_0006
一 、 ; Μ/·^ - ε - / ^ / 、^ ェ- s -( / ェ rci i- - ΐ )  I,; Μ / · ^-ε-/ ^ /, ^--s-(/ r rci i--ΐ)
SSI各粱呦 ： SSI p}
Figure imgf000138_0007
9ε ΐ· S081760/S00Z OAV 9.1 K1H, s), 10.23(1H, s), 11.30(1H, s). SSI each 呦: SSI p}
Figure imgf000138_0007
9ε SS081760 / S00Z OAV 9.1 K1H, s), 10.23 (1H, s), 11.30 (1H, s).
例 138:化合物番号 138 Example 138: Compound number 138
(1) 4- (ベンジルォキシ)フエ-ルヒドラジン  (1) 4- (benzyloxy) phenylhydrazine
一般合成法 εと同様の方法により標題化合物を得た。収率 23%。  The title compound was obtained in the same manner as in the general synthesis method ε. Yield 23%.
(2) 5-ァミノ- 1- [4- (ベンジルォキシ)フエ-ル]- 3-メチルビラゾール  (2) 5-Amino-1- [4- (benzyloxy) phenyl] -3-methylvirazole
一般合成法 βと同様の方法により標題ィ匕合物を得た。収率 13%。 'H-NMRCCDCl  The title compound was obtained in the same manner as in the general synthesis method β. Yield 13%. 'H-NMRCCDCl
3 Three
): δ 2.23(3H, s), 3.69(2H, brs), 5.10(2H, s), 5.44(1H, s), 7.01-7.07(2H, m), 7.33-7.46(7H, m). ): δ 2.23 (3H, s), 3.69 (2H, brs), 5.10 (2H, s), 5.44 (1H, s), 7.01-7.07 (2H, m), 7.33-7.46 (7H, m).
(3) 5-ァミノ- 1- (4-ヒドロキシフエ-ル)- 3-メチルビラゾール  (3) 5-amino-1- (4-hydroxyphenyl) -3-methylvirazole
5-ァミノ- 1- [4- (ベンジルォキシ)フエ-ル]- 3-メチルビラゾール (lOOmg, 0.36mmol) のエタノール溶液 (lml)に 5%パラジウム/炭素 (10mg)をカ卩え、水素雰囲気下、室温で 終夜攪拌した。不溶物をセライト濾過し、濾液を減圧濃縮して、標題化合物の淡黄色 結晶 (100%)を得た。  5-% palladium / carbon (10 mg) was added to an ethanol solution (1 ml) of 5-amino-1- [4- (benzyloxy) phenyl] -3-methylvirazole (100 mg, 0.36 mmol), and hydrogen atmosphere was added. The mixture was stirred at room temperature overnight. The insolubles were filtered through celite, and the filtrate was concentrated under reduced pressure to obtain pale yellow crystals (100%) of the title compound.
^-NMRCCDCl ): δ 2.23(3H, s), 3.71(2H, brs), 5.42(1H, s), 6.68(2H, d, J=8.7Hz),  ^ -NMRCCDCl): δ 2.23 (3H, s), 3.71 (2H, brs), 5.42 (1H, s), 6.68 (2H, d, J = 8.7Hz),
3  Three
7.16(2H, d, J=8.7Hz).  7.16 (2H, d, J = 8.7Hz).
(4)化合物番号 138  (4) Compound No. 138
収率 22%。 'H-NMRCDMSO-d ): δ 2.53(3H, s), 6.56(1H, s), 6.92(2H, d, J=8.7Hz), Yield 22%. 'H-NMRCDMSO-d): δ 2.53 (3H, s), 6.56 (1H, s), 6.92 (2H, d, J = 8.7Hz),
6  6
7.37(2H, d, J=8.7Hz), 7.44-7.66(4H, m), 7.88(1H, d, J=8.4Hz), 8.21(1H, d, J=8.1Hz), 9.15(1H, s), 9.80(1H, s), 13.62(1H, s).  7.37 (2H, d, J = 8.7Hz), 7.44-7.66 (4H, m), 7.88 (1H, d, J = 8.4Hz), 8.21 (1H, d, J = 8.1Hz), 9.15 (1H, s ), 9.80 (1H, s), 13.62 (1H, s).
例 139:化合物番号 139 Example 139: Compound number 139
(1) 5-ァミノ- 1-(4-カルボキシフエ-ル) -3-メチルビラゾール  (1) 5-amino-1- (4-carboxyphenyl) -3-methylvirazole
5-ァミノ- 1-[4- (エトキシカルボ-ル)フエ-ル] -3-メチルビラゾール (例 133(2)の化合 物： lOOmg, 0.41mmol)のエタノール溶液 (lml)に 5N水酸化ナトリウム水溶液 (82 /z g, 0.41mmol)をカ卩え、 4時間加熱還流した。反応混合物を室温まで冷却後、 2N塩酸をカロ えて酸性とした。溶媒を減圧留去して得られた残渣をシリカゲルカラムクロマトグラフィ 一 (ジクロロメタン Zメタノール =9Zl)で精製して、標題化合物の白色結晶 (79mg, 89%)を得た。  5-N-amino-1- [4- (ethoxycarbol) phenyl] -3-methylvirazole (Example 133 (2): 100 mg, 0.41 mmol) of ethanol solution (1 ml) in 5N hydroxide An aqueous sodium solution (82 / zg, 0.41 mmol) was added and heated under reflux for 4 hours. After the reaction mixture was cooled to room temperature, it was acidified by adding 2N hydrochloric acid. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (dichloromethane Z methanol = 9Zl) to obtain white crystals of the title compound (79 mg, 89%).
^-NMRCDMSO-d ): δ 2.07(3H, s), 5.36(1H, s), 5.44(2H, brs), 7.74(2H, d, •(s Ήΐ)8Γ6 '(ZHS'I 'Z=f 'PP 'Ηΐ)Ζε·8 '(ZHS'I ^ -NMRCDMSO-d): δ 2.07 (3H, s), 5.36 (1H, s), 5.44 (2H, brs), 7.74 (2H, d, • ( s Ήΐ) 8Γ6 '(ZHS'I' Z = f 'PP' Ηΐ) Ζε8 '(ZHS'I
Ηΐ)Ζ ·Ζ
Figure imgf000140_0001
Ηΐ) Ζ · Ζ
Figure imgf000140_0001
'(zH6=f 'P 'HT)99"9 '(s 'HZ)WZ '(s 'HZ)WZ 9 -(OQOWH-H^ °%ΐΐ ¾T'(zH6 = f' P 'HT) 99 "9' ( s ' HZ) WZ '( s ' HZ) WZ 9-(OQOWH-H ^ °% ΐΐ ¾T
Figure imgf000140_0002
Figure imgf000140_0002
Figure imgf000140_0003
'(s 'Ηΐ)98·9 '(s 'HZ)WZ '(s 'HS)SS 9
Figure imgf000140_0003
'( s ' Ηΐ) 989 '( s ' HZ) WZ '( s ' HS) SS 9
■(OQDWH-H, °%99 ¾ί ^Μ^^ΜΜ^ ^ Μ^ ^ ^-
Figure imgf000140_0004
'P lWZ)LZ'L 'P 'HT)2Z"9 '(zHZ=f 'b 'HZ)ZVf '(s 'HZ)\VZ '(zHS =f 'P 'HS)0S"2 '(zHZ=f '； 'HZ)ZV\ 9 :(
Figure imgf000140_0005
■ (OQDWH-H, °% 99 ¾ί ^ Μ ^^ ΜΜ ^ ^ Μ ^ ^ ^-
Figure imgf000140_0004
'P l WZ) LZ'L' P 'HT) 2Z "9' ( z HZ = f 'b' HZ) ZVf '( s ' HZ) \ VZ' ( z HS = f 'P' HS) 0S" 2 '( z HZ = f';'HZ) ZV \ 9 :(
Figure imgf000140_0005
一 ½ ( -ェ ^ - - ΐ- ^ - ε - / ^ / ェ- s a)  One ½ (-e ^--ΐ- ^-ε-/ ^ /-s a)
(s 'Ηΐ)8ε·εΐ '(s 'Ηΐ) 6
Figure imgf000140_0006
'P Ήΐ)ΐ6"Ζ '(ΖΗΖ·8=1" 'P Ή2)88"Ζ '(ω 'ΗΖ)69' L-f9' L '(ω 'HI)6S'Z— SS'Z '(s 'HS)SS'Z '(ΖΗ ·8=1" 'P ' )6VL '(s 'Ηΐ)99·9 '(s 'HZ 'Z 9 :( OSWd) N— HT °%SS ¾T( s ' Ηΐ) 8εεΐ '( s ' Ηΐ) 6
Figure imgf000140_0006
'P Ήΐ) ΐ6 "Ζ' (ΖΗΖ8 = 1"'P Ή2) 88 "Ζ' (ω 'ΗΖ) 69' L-f9 'L' (ω 'HI) 6S'Z—SS'Z' ( s' HS) SS'Z '(ΖΗ8 = 1 "' P ') 6VL' ( s ' Ηΐ) 99.9 '( s 'HZ' Z 9 :( OSWd) N— H T °% SS ¾T
Figure imgf000140_0007
Figure imgf000140_0007
"(zH6"8=f 'P 'H2)98"Z '(zH6"8=f 'P 'HT)8Z"Z '(s 'H2)8S"Z '(saq 'H 9 'S 'HT)9S"S '(s 'HS)Z0"2 9 :(9p— OSW I) 顺— H "(zH6" 8 = f'P'H2) 98 "Z '(zH6" 8 = f'P'HT) 8Z "Z'(s'H2)8S" Z '(saq'H9'S'HT) 9S "S '(s' HS) Z0" 2 9 :( 9 p— OSW I) 顺 — H
T °%i8 ¾i ^m^ ^mm^ ^ m & ^ ^- 一 、 ; Μ/·^ - ε -( / ェ / ¾ - - ΐ-,^ - s a) T °% i8 ¾i ^ m ^ ^ mm ^ ^ m & ^ ^-one,; Μ / ^^-ε-(/ / / ¾--ΐ-, ^-sa)
各粱呦 -o i zi  Each siang 呦 -o i zi
.(s . (s
'Ηΐ)ΐ ·εΐ '(s 'Ηΐ) ΐ·εΐ '(s Ήΐ)εζ·6 'WS=i 'P 'HI)SS'8 '(zH9"8=f 'P 'Η ΐΐ·8 '(ΖΗΐ·8=ί" 'P Ήΐ)06"Ζ
Figure imgf000140_0008
'P 'H2)08"Z '(ω 'HZ)S9' L-f9' L '(ω 'HI)ZS'Z— SS'Z '(ΖΗ ·8=1" 'P ' )6VL '(s 'Ηΐ)99·9 '(s 'HZ 'Z 9 :( OSWa) 顺— HT °% ¾T 'Ηΐ) ΐ εΐ' ( s 'Ηΐ) ΐεΐ' ( s Ήΐ) εζ6 'WS = i' P 'HI) SS'8' ( z H9 "8 = f 'P' Η 88 '(ΖΗΐ · 8 = ί "' P Ήΐ) 06" Ζ
Figure imgf000140_0008
'P' H2) 08 "Z '(ω' HZ) S9 'L-f9' L '(ω' HI) ZS'Z— SS'Z '(ΖΗ · 8 = 1"' P ') 6VL' ( s 'Ηΐ) 999' ( s 'HZ' Z 9 :( OSWa) 顺 — H T °% ¾T
6ει各粱呦 (z) 6ει each siang 呦 (z)
•(saq 'Ηΐ)06 ΐ 'P 'Η 66· '(ΖΗΖ·8=ί"
Figure imgf000140_0009
8ε ΐ· S081760/S00Z OAV
Figure imgf000141_0001
• (saq 'Ηΐ) 06 ΐ' P 'Η 66 ·' (ΖΗΖ · 8 = ί "
Figure imgf000140_0009
8ε SS081760 / S00Z OAV
Figure imgf000141_0001
•(ζΗ9"ΐ=Γ• ( ζ Η9 "ΐ = Γ
P 'Ηΐ) Οΐ '(s 'Ηΐ)89·8 '(ΖΗΓ6=Γ 'Ρ Ήΐ)ΖΓ8 '^ΗΖ'Ζ=ί 'Ρ 'HT)S6"Z '(ω 'Η ·ΖP 'Ηΐ) Οΐ' ( s 'Ηΐ) 89 · 8' ( Ζ ΗΓ6 = Γ 'Ρ Ήΐ) Ήΐ8' ^ ΗΖ'Ζ = ί 'Ρ' HT) S6 "Z '(ω' Η
'(ΖΗΓ6 ' τ=ί 'ρρ Ήΐ)ε9"ζ '(ω '蹄 s'z '(s Ήΐ)3ε· '(zH2"s=f 'ρ Ήΐ)εε·'(ΖΗΓ6' τ = ί 'ρρ Ήΐ) ε9 "ζ' (ω 'Hoof s'z' (s Ήΐ) 3ε '' (zH2" s = f 'ρ Ήΐ) εε
'(ZHS'S Ότ=ί 'ΡΡ 'Ηΐ)ε8·9 '(s 'm)fVZ 9 :( OS^a) 顺— Ητ °%89 ¾Τ '(ZHS'S Ότ = ί' ΡΡ 'Ηΐ) ε89' ( s ' m) fVZ 9 :( OS ^ a) 顺 — Η τ °% 89 ¾Τ
"(s-i Ήΐ)Ζ3·Π '(s Ήΐ)Ζ2 ΐ
Figure imgf000141_0002
'Ρ 'HI)SS'8 '(s 'Ηΐ)ΐΟ·8
Figure imgf000141_0003
I '(s 'HT)8S"Z "(si Ήΐ) Ζ3 · Π '(s Ήΐ) Ζ2 ΐ
Figure imgf000141_0002
'Ρ' HI) SS'8 '(s' Ηΐ) ΐΟ8
Figure imgf000141_0003
I '( s ' HT) 8S "Z
'Ρ 'm Z'L '(ΖΗ3·3=Γ 'P 'Ηΐ)88·9 '(s 'H9)9S 9 :( OSWa) 顺— HT °%89 ¾ί 'Ρ' m Z'L '( Ζ Η3 · 3 = Γ' P 'Ηΐ) 889' ( s ' H9) 9S 9 :( OSWa) H— H T °% 89 ¾ί
•(s 'Ηΐ)6·εΐ '(s 'Ηΐ)ε·Οΐ '(s-i 'HI)S6'6 '(zHS-8=f
Figure imgf000141_0004
'P 'HI)U'Z '(in
Figure imgf000141_0005
'； 'HT)SS"Z 9 :( OSW I) N— HT ¾T • ( s 'Ηΐ) 6εΐ' ( s 'Ηΐ) εΟΐ Οΐ' (si 'HI) S6'6' ( z HS-8 = f
Figure imgf000141_0004
'P' HI) U'Z '(in
Figure imgf000141_0005
';' HT) SS "Z 9 :( OSW I) N— H T ¾T
•(s Ήΐ)2 ΐ '(s-i 'Ηΐ) 0·6 '(ZHS'I 'Z=f 'PP 'HT)S^"8 '(ZHS'I 'Z=f 'PP 'HT)SZ"Z '(ZHS'I 'Z=f'P; 'HT)2S"Z '(ZHS'I
Figure imgf000141_0006
• ( s Ήΐ) 2 ΐ '(si' Ηΐ) 0 · 6 '(ZHS'I' Z = f 'PP' HT) S ^ "8 '(ZHS'I' Z = f 'PP' HT) SZ" Z '(ZHS'I' Z = f'P;'HT) 2S "Z'(ZHS'I
Figure imgf000141_0006
'ρ Ήΐ)ζ8·9 '(s Ή νζ '(ζΗ3 =Γ 'ρ Ήζ 'ζ 9 :(9ρ— oswa) 顺— Ητ °%εε ¾ί zw^ (ε)
Figure imgf000141_0007
'ρ Ήΐ) ζ8 · 9' ( s Ή νζ '( ζ Η3 = Γ' ρ Ήζ 'ζ 9 :( 9 ρ— oswa) 顺 — Η τ °% εε ¾ί zw ^ (ε)
Figure imgf000141_0007
'Ρ 'Η ·Ζ
Figure imgf000141_0008
'Ρ Ήε)εε 9 :(
Figure imgf000141_0009
'Ρ' Η · Ζ
Figure imgf000141_0008
'Ρ Ήε) εε 9 :(
Figure imgf000141_0009
'P 'Ηΐ)8Γ9 '(ΖΗ
Figure imgf000141_0010
'P' Ηΐ) 8Γ9 '( Ζ Η
Figure imgf000141_0010
' 'HZ)W\ 9 :(SI aつ) 顺- HT °%99 ¾ί つ 呦^ '' HZ) W \ 9: ( S I a) 顺-H T °% 99 ¾ί ^
一 ½ ( -ェ ^ - - ΐ- ^ - s - / ^ / ェ- ε (ΐ)
Figure imgf000141_0011
6εΐ· S081760/S00Z OAV 'P 'HT)8S"8 '(ζΗΐ 'S"Z=f '^Ρ 'H2)86"Z '(s 'Ul)SVL '(ζΗΐ 'S"Z=f 'P^ 'HZ)OV L '(ω 'ΗΖ)6Ζ' L- Z' L '(ζΗΐ
Figure imgf000142_0001
4 H 98 '(s 'U£)SZ'Z '(zHS"Z=f '^m 'H2)S0"2 9 :(9p— OSW I) 顺— HT °%09 ¾T One ½ (-e ^--ΐ- ^-s-/ ^ /-ε (ΐ)
Figure imgf000141_0011
6εΐS081760 / S00Z OAV 'P' HT) 8S "8 '( ζ Ηΐ'S" Z = f '^ Ρ' H2) 86 "Z '(s' Ul) SVL '( ζ Ηΐ'S" Z = f 'P ^' HZ) OV L '(ω' ΗΖ) 6Ζ 'L- Z' L '( ζ Ηΐ
Figure imgf000142_0001
4 H 98 '(s' U £) SZ'Z' (zHS "Z = f '^ m' H2) S0" 2 9 :( 9 p— OSW I) 顺 — H T °% 09 ¾T
ΐ3ΐ各粱呦^ -m ίΐζι ΐ3ΐEach 呦 呦 -m ίΐζι
•(zHST=f 'P Ήΐ)3·π• ( z HST = f 'P Ήΐ) 3π
'(s Ήΐ)3 ΐ
Figure imgf000142_0002
'P 'HT)SZ"Z '(s Ήΐ) 3 ΐ
Figure imgf000142_0002
'P' HT) SZ "Z
' 'HZ)OVL '(ω 'Η )Ο — 08·9 '(s 'm)6Z'z 9 :(9p— oswa) 顺— HT °% Z ¾T '' HZ) OVL '(ω' Η) Ο — 08 · 9 '( s ' m) 6Z'z 9 :( 9 p— oswa) 顺 — H T °% Z ¾T
OSI各粱呦 -0 i  OSI each-呦 i
•(ΖΗΓ8=Γ 'P 'HDLVS '(s 'Ηΐ)ε ·8 '(ΖΗΓ8=Γ 'P 'HT)Z9"Z '(ω 'HT)09"Z-WZ • ( Ζ ΗΓ8 = Γ 'P' HDLVS '( s ' Ηΐ) ε · 8' ( Ζ ΗΓ8 = Γ 'P' HT) Z9 "Z '(ω' HT) 09" Z-WZ
'(ui
Figure imgf000142_0003
'(ui
Figure imgf000142_0003
'P 'Ηΐ)90· '(ΖΗΖ·8=1" 'P 'Η Ζ6·9 '(s 'HS)S8"S 9 :( OSWd) N— HT ¾T 'P' Ηΐ) 90 · '(ΖΗΖ · 8 = 1 "' P 'Η Ζ6 · 9' ( s ' HS) S8" S 9 :( OSWd) N— H T ¾T
•(s 'Ηΐ)3 ·εΐ '(s 'Ηΐ)ε8·8 '(ω 'Ηΐ)0 ·8— Ζε·8 '(ω 'Ηΐ)6 - SrZ '(ω 'HW -6S" • ( s ' Ηΐ) 3 · εΐ '( s ' Ηΐ) ε8 · 8' (ω 'Ηΐ) 0 · 8— Ζε · 8' (ω 'Ηΐ) 6-SrZ' (ω 'HW -6S "
'(s 'H2)9S"Z '(s Ήΐ)9ε·9 '(s 'Η6)0 ·ΐ 9 :ODaD)H N-HT °% Z ¾ί'( s ' H2) 9S "Z' (s Ήΐ) 9ε9 '( s ' Η6) 0 ΐ9 : ODaD) H NH T °% Z ¾ί
Figure imgf000142_0004
Figure imgf000142_0004
•(ΖΗΓ6=Γ• ( Ζ ΗΓ6 = Γ
'P 'HZ)WL
Figure imgf000142_0005
'(s 'HI)SS'S '(sjq 'H2)69"S '(s 'Η6)0ε·ΐ 9 :('P' HZ) WL
Figure imgf000142_0005
'(s' HI) SS'S '(sjq' H2) 69 "S '( s ' Η6) 0εΐ9 :(
DaD)H N-HT °% z ¾ί
Figure imgf000142_0006
DaD) H NH T °% z ¾ί
Figure imgf000142_0006
一 ½ ( -ェ crn^— — I— ( ^ : W )— ε— — S (ΐ)  One ½ (-e crn ^ — — I— (^: W) — ε— — S (ΐ)
'P 'HT)6S"8
Figure imgf000142_0007
'P' HT) 6S "8
Figure imgf000142_0007
' Ήΐ)εζ· '(zH8=f ' 'HDfVL '(s 'HS)62"2 9 :( OSWa) 顺— HT °% Z ¾T 'Ήΐ) εζ' (zH8 = f '' HDfVL '( s ' HS) 62 "2 9 :( OSWa) 顺 — H T °% Z ¾T
•(zHS'8=f 'P Ήΐ)0Γ8• (zHS'8 = f 'P Ήΐ) 0Γ8
'(ω Ήε)80·8— ΐ0·8
Figure imgf000142_0008
'HT)SS"Z '(ω 'HW -9S" '(ω Ήε) 80 · 8— ΐ0 · 8
Figure imgf000142_0008
'HT) SS "Z' (ω 'HW -9S"
'(ZH2
Figure imgf000142_0009
'(ZH2
Figure imgf000142_0009
'B 'Η„· '(s Ήε) ε·ζ '(ZHS'Z=1" '； Ήε)8 ·ΐ 9 :(ει αつ) 顺— HT °%ΪΖ ¾T t9t900 OZdr/lDd O V S08^60/S00Z OAV J=13.5Hz), 11.3(1H, d, J=13.5Hz). 'B' Η "· '( s Ήε) ε · ζ'(ZHS'Z = 1"'; Ήε) 8 · ΐ 9 :( ε ι one alpha)顺- H T °% ΪΖ ¾T t9t900 OZdr / lDd OV S08 ^ 60 / S00Z OAV J = 13.5Hz), 11.3 (1H, d, J = 13.5Hz).
例 152:化合物番号 152 Example 152: Compound number 152
収率 88%。 'H-NMRCDMSO-d ): δ 2.32(3Η, s), 3.99(2Η, s), 7.14(1Η, tt, J=7.5, Yield 88%. 'H-NMRCDMSO-d): δ 2.32 (3Η, s), 3.99 (2Η, s), 7.14 (1Η, tt, J = 7.5,
6  6
1Hz), 7.33(1H, td J=7.5, 1Hz), 7.35- 7.45(3H, m), 7.55- 7.65(2H, m), 7.85— 7.99(3H m), 8.03(2H, dt, J=7.5, 1Hz), 8.70(1H, d, J=14Hz), 11.5(1H, d, J=14Hz).  1Hz), 7.33 (1H, td J = 7.5, 1Hz), 7.35- 7.45 (3H, m), 7.55- 7.65 (2H, m), 7.85- 7.99 (3H m), 8.03 (2H, dt, J = 7.5 , 1Hz), 8.70 (1H, d, J = 14Hz), 11.5 (1H, d, J = 14Hz).
例 153:化合物番号 153 Example 153: Compound number 153
収率 88%。 'H-NMRCDMSO-d ): δ 2.31(3Η, s), 7.14(1Η, t, J=7.5Hz), 7.37(1Η, t Yield 88%. 'H-NMRCDMSO-d): δ 2.31 (3Η, s), 7.14 (1Η, t, J = 7.5Hz), 7.37 (1Η, t
6  6
J=7.5Hz), 7.41(2H, t, J=8Hz), 7.50- 7.68(2H, m), 7.75(1H, dd, J=8, 2Hz), 7.80(1H, d, J=7.5Hz), 7.86(1H, d, J=7.5Hz), 7.88— 8.10(3H, m), 8.70(1H, d, J=13.5Hz), 11.4(1H, d, J=13.5Hz).  J = 7.5Hz), 7.41 (2H, t, J = 8Hz), 7.50- 7.68 (2H, m), 7.75 (1H, dd, J = 8, 2Hz), 7.80 (1H, d, J = 7.5Hz) , 7.86 (1H, d, J = 7.5Hz), 7.88-8.10 (3H, m), 8.70 (1H, d, J = 13.5Hz), 11.4 (1H, d, J = 13.5Hz).
例 154:化合物番号 154 Example 154: Compound number 154
収率 78%。 ^-NMRCDMSO-d ): δ 2.32(3Η, s), 5.51(1Η, d, J=7.5Hz), 5.93(1Η, d, Yield 78%. ^ -NMRCDMSO-d): δ 2.32 (3Η, s), 5.51 (1Η, d, J = 7.5Hz), 5.93 (1Η, d,
6  6
J=7.5Hz), 7.14(1H, t, J=7.5Hz), 7.29(1H, t, J=7.5Hz), 7.35— 7.45(3H, m), 7.55(1H, dd, J=8.5, 2Hz), 7.60(1H, d, J=7.5Hz), 7.79(1H, d, J=7.5Hz), 7.82— 7.90(2H, m), 8.02(2H, dd, J=8.5, 1Hz), 8.70(1H, d, J=12.5Hz), 11.5(1H, d, J=12.5Hz).  J = 7.5Hz), 7.14 (1H, t, J = 7.5Hz), 7.29 (1H, t, J = 7.5Hz), 7.35― 7.45 (3H, m), 7.55 (1H, dd, J = 8.5, 2Hz ), 7.60 (1H, d, J = 7.5Hz), 7.79 (1H, d, J = 7.5Hz), 7.82- 7.90 (2H, m), 8.02 (2H, dd, J = 8.5, 1Hz), 8.70 ( 1H, d, J = 12.5Hz), 11.5 (1H, d, J = 12.5Hz).
例 155:化合物番号 155 Example 155: Compound number 155
収率 85%。 'H-NMRCCDCl ): δ 7.06-7.22(7Η, m), 7.30- 7.40(4Η, m), Yield 85%. 'H-NMRCCDCl): δ 7.06-7.22 (7Η, m), 7.30- 7.40 (4Η, m),
3  Three
7.46-7.52(1Η, m), 7.55— 7.61(1Η, m), 7.68(1Η, d, J=7.7Hz), 8.46— 8.48(2Η, m). 例 156:化合物番号 156  7.46-7.52 (1Η, m), 7.55― 7.61 (1Η, m), 7.68 (1Η, d, J = 7.7Hz), 8.46― 8.48 (2Η, m) .Example 156: Compound No. 156
収率 9%。 'H-NMRCCDCl ): δ 6.02(2H, s), 6.83— 6.84(2H, m), 6.87— 6.88(1H, m), 9% yield. 'H-NMRCCDCl): δ 6.02 (2H, s), 6.83-6.84 (2H, m), 6.87-6.88 (1H, m),
3  Three
7.10(1H, d, J=8.7Hz), 7.19(1H, d, J=8.7Hz), 7.46- 51(1H, m), 7.54— 7.60(1H, m), 7.68(1H, d, J=7.7Hz), 8.41(1H, s), 8.45(1H, d, J=8.1Hz).  7.10 (1H, d, J = 8.7Hz), 7.19 (1H, d, J = 8.7Hz), 7.46-51 (1H, m), 7.54--7.60 (1H, m), 7.68 (1H, d, J = 7.7Hz), 8.41 (1H, s), 8.45 (1H, d, J = 8.1Hz).
例 157:化合物番号 157 Example 157: Compound number 157
収率 86%。 'H-NMRCCDCl ): δ 4.29(4Η, s), 6.83— 6.93(3Η, m), 7.05(1Η, d, 86% yield. 'H-NMRCCDCl): δ 4.29 (4Η, s), 6.83― 6.93 (3Η, m), 7.05 (1Η, d,
3  Three
J=8.7Hz), 7.16(1Η, d, J=8.7Hz), 7.45- 7.50(1H, m), 7.57(1H, td, J=7.4,1.3Hz), 7.67(1H, d, J=7.4Hz), 8.37(1H, s), 8.44- 8.47(1H, m).  J = 8.7Hz), 7.16 (1Η, d, J = 8.7Hz), 7.45- 7.50 (1H, m), 7.57 (1H, td, J = 7.4,1.3Hz), 7.67 (1H, d, J = 7.4 Hz), 8.37 (1H, s), 8.44- 8.47 (1H, m).
例 158:化合物番号 158 Example 158: Compound number 158
(1) 1 -フエ-ル- 3-トリフルォロメチル- 4,5-ジヒドロピラゾール- 5-オン ' Ήΐ)3ΓΖ '(ZH9'S '6'Ζ=ί 'PP 'Ηΐ) 8·9 9 :( P-OS a)H N-HT °%06 ¾ί (1) 1-phenyl-3-trifluoromethyl-4,5-dihydropyrazol-5-one 'Ήΐ) 3ΓΖ'(ZH9'S'6'Ζ = ί' PP 'Ηΐ) 8.9 9 :( P-OS a) H NH T °% 06 ¾ί
091各粱呦 (ε) 091 each siang 呦 (ε)
•(s 'HT)9S"6 '(zH9"Z=f 'P 'H2)28"Z '(ω ΉΖ) ν L-ZY L '(ω• (s 'HT) 9S "6' (zH9" Z = f 'P' H2) 28 "Z '(ω ΉΖ) ν L-ZY L' (ω
Ήΐ)εε· - ζ· '(jq 'ΗΪ)Ζ8· '(zH8" '9" =f 'nz)wz '(zH9-z=f ^ Ήε) ε·ΐ s :(Ήΐ) εε- ζ · '(jq' ΗΪ) Ζ8 · '(zH8 "'9" = f 'nz) wz' ( z H9-z = f ^ Ήε) εΐ s :(
DaD)H N-HT °%i8 ¾ί
Figure imgf000144_0001
DaD) H NH T °% i8 ¾ί
Figure imgf000144_0001
、 ^ - 一 ^^c^ ^- s ' / ェ - ΐ- ^P - s- ^エ- ε (ζ)  , ^-One ^^ c ^ ^-s' /--ΐ- ^ P-s- ^ e- ε (ζ)
"(ω 'H2)68"Z-98"Z '(ω ΉΖ)\Υ L-^Z' L '(ω 'HW -εΓ '(s Ήζ)ΖΥ£
Figure imgf000144_0002
'HS)S2"T 9 :( DaD)H N-HT °%96 ¾ί ^Μ^^ΜΜ^^^ Μ^ん ^^ 一 "(ω 'H2) 68" Z-98 "Z' (ω ΉΖ) \ Υ L- ^ Z 'L' (ω 'HW -εΓ' (s Ήζ) ΖΥ £
Figure imgf000144_0002
'HS) S2 "T 9 :( DaD) H NH T °% 96 ¾ί ^ Μ ^^ ΜΜ ^^^ Μ ^ n ^^ one
ベ - s - /— ½。 Ei、 ¾^- s ' / ェ - ΐ- ^エ- ε (ΐ)  Be-s-/ ——. Ei, ¾ ^-s' /--ΐ- ^ e- ε (ΐ)
09ΐ各粱呦^ :09ΐ "(s-i 'HWZl '(s Ήΐ)62 ΐ '(s 'Ηΐ)ΐ8·8 '(zH8"8=f 'P Ήΐ)ΐ2·8 '^ΗΖ'Ζ=ί 'P Ήΐ)0Γ8 '(ZH9"8 'S"T=f 'PP 'H2)Z6"Z '(ΖΗ0·6 'ΥΖ=ί 'PP 'HT)SZ"Z '(ΖΗΟ"Ζ '8·ΐ=ί" '^Ρ 'H2)0S"Z '(ω 'H2)6S"Z '(ZHS'Z
Figure imgf000144_0003
Figure imgf000144_0004
'P 'Ηΐ)88·8 '(zH '8=f 'P Ήΐ)92"8 '(zH8"8=f 'P 'Η2)0Γ8 '(ΖΗΖ·Ζ=1" 'P Ήΐ)66"Ζ '(ΖΗΖ·Ζ=1" P 'HT)S6"Z
Figure imgf000144_0005
'HT)SS"Z
Figure imgf000144_0006
Ήΐ)62"Ζ 9 :(9p— OSWa) 顺— HT °%89 ¾ί ssi各粱呦 (ε) 09 ΐ each beam ^: 09 ΐ "(si 'HWZl' ( s Ήΐ) 62 ΐ '( s ' Ηΐ) ΐ 8.8 '( z H8" 8 = f' P Ήΐ) ΐ 2 8 '^ ΗΖ' Ζ = 'P Ήΐ) 0Γ8' ( Z H9 "8 'S" T = f' PP 'H2) Z6 "Z' (ΖΗ0 · 6 'ΥΖ = ί' PP 'HT) SZ"Z' (ΖΗΟ "Ζ '8 ΐ = ί "'^ Ρ' H2) 0S" Z '(ω' H2) 6S "Z '(ZHS'Z
Figure imgf000144_0003
Figure imgf000144_0004
'P' Ηΐ) 88 · 8 '(zH' 8 = f 'P Ήΐ) 92 "8'(zH8" 8 = f 'P' Η2) 0Γ8 '(ΖΗΖ · Ζ = 1 "' P Ήΐ) 66" Ζ '(ΖΗΖ · Ζ = 1 "P' HT) S6" Z
Figure imgf000144_0005
'HT) SS "Z
Figure imgf000144_0006
Ήΐ) 62 "Ζ 9 :( 9 p— OSWa) 顺 — H T °% 89 ¾ί ssi each beam (ε)
9 :(
Figure imgf000144_0007
9 :(
Figure imgf000144_0007
、れ ,
- /—/^ c^ - s' ^ ci / fH- ε- / ェ - ΐ- ^ - s (z) -/ — / ^ C ^-s' ^ ci / fH- ε- /--ΐ- ^-s (z)
•(s ' )ZVZl '(ω 'H2)2Z-Z-89"Z '(ω lWZ)WL-LVL '(ω 'Ηΐ)ΐ ·Ζ— SS' '(s 'HT)^6"S 9 :( P-OS^a)H N-H • ( s ') ZVZl '(ω' H2) 2Z-Z-89 "Z '(ω l WZ) WL-LVL' (ω 'Ηΐ) ΐ · Ζ— SS''(s' HT) ^ 6" S 9 :( P-OS ^ a) H NH
Figure imgf000144_0008
S081760/S00Z OAV '(ζΗε·9 'Ζ'Ζ=ί 'ΡΡ 'Ηΐ) 8·9 '(s Ήε)εε 9 :( P-OS a)H N-HT °%S6 ? φ
Figure imgf000144_0008
S081760 / S00Z OAV '(ζΗε9'Ζ'Ζ = ί 'ΡΡ' Ηΐ) 8.9 '( s Ήε) εε 9 :( P-OS a) H NH T °% S6? φ
Figure imgf000145_0001
Figure imgf000145_0001
•(s 'Ηΐ)0 ·6• ( s ' Ηΐ) 0
'(zH0"2=f ' 'HT)68"Z '(ω 'Ηΐ)8ΓΖ— SZ'Z '(ω 'HZ)W L- Z' L 'HZ)WZ 9 :('( z H0 "2 = f''HT)68"Z' (ω 'Ηΐ) 8ΓΖ— SZ'Z' (ω 'HZ) W L- Z' L 'HZ) WZ 9 :(
DaD)H N-HT °% 8 ¾ί
Figure imgf000145_0002
- /— ^^c^ ^- s' - s- ^ - ε- ( / ェ crn^- ε)- ΐ (ζ) DaD) H NH T °% 8 ¾ί
Figure imgf000145_0002
-/-^^ c ^ ^-s'-s- ^-ε- (/ cr crn ^-ε)-ΐ (ζ)
'HT)S8"Z-T8"Z '(ω Ήΐ · -82· '(ω Ήΐ)9ΓΖ-2Γ 'HZ)WZ '(s 'HS)02"2 9 :('HT) S8 "Z-T8"Z' (ω Ήΐ · -82 · '(ω Ήΐ) 9ΓΖ-2Γ' HZ) WZ '( s ' HS) 02 "2 9 :(
DaD)H N-HT 0%9ε*¾ί °^ ¾<¾?^®^ τ^)¾^ )#^^ん ^^ 一 DaD) H NH T 0 % 9ε * ¾ί ° ^ ¾ <¾? ^ ® ^ τ ^) ¾ ^) # ^^ n ^^ one
ベ - s - /— ½。 Ei、 ¾^- s' ^ - ε -( / ェ crn^- ε)- ΐ (ΐ) ·εΐ=Γ 'Ρ 'Ηΐ ·ΐΐ '(s Ήΐ)^ ΐ '^ΗΖτΐ=ί 'Ρ Ήΐ)9Ζ·8 '(ΖΗΓ6=Γ 'Ρ Ήΐ)6Γ8 '(zH8"8=f 'Ρ 'H2)S0"8 '(zH6"T=f 'Ρ 'HT)Z6"Z '(ΖΗΓ6
Figure imgf000145_0003
'Ρ 'HZ)SVL '(ω 'HS)8S — ΐε·ΖBe-s-/ ——. Ei, ¾ ^-s '^-ε-(/ cr crn ^-ε)-ΐ (ΐ) εΐ = Γ' Ρ 'Ηΐ · Ηΐ' ( s Ήΐ) ^ ΐ '^ ΗΖτΐ = ί' Ρ Ήΐ) 9Ζ8 '( Ζ ΗΓ6 = Γ' Ρ Ήΐ) 6Γ8 '( z H8 "8 = f' Ρ 'H2) S0"8' ( z H6 "T = f 'Ρ' HT) Z6" Z '(ΖΗΓ6
Figure imgf000145_0003
'Ρ' HZ) SVL '(ω' HS) 8S — ΐε
'9 'ε =1" ' ) 8·9 '(s Ήε)εε 9 :(9ρ— oswa) τ °%S8 ? Φ '9' ε = 1 "') 8.9' ( s Ήε) εε 9 :( 9 ρ— oswa) τ °% S8? Φ
ΐ9ΐ各粱呦 (ε)  ΐ9ΐEach 呦 (ε)
DaD)H N-HT °%iz ¾ί
Figure imgf000145_0004
DaD) H NH T °% iz ¾ί
Figure imgf000145_0004
Λ Λ
- /— ^^c^ ^- S' - s- ^ - ε- ( / ェ crn^- - ΐ (Ζ) •(ω 'H2)98"Z-28"Z'(ra 'HS)ZS — εε· 'HZ)WZ '(s 'HS)02"2 9 :(-/ — ^^ c ^ ^-S '-s- ^-ε- (/ cr crn ^--ΐ (Ζ) • (ω' H2) 98 "Z-28" Z '(ra' HS) ZS — εε '' HZ) WZ '( s ' HS) 02 "2 9 :(
DaD)H N-HT DaD) H NH T
Figure imgf000145_0005
)
Figure imgf000145_0006
'Ρ 'Ηΐ)09·ΐΐ '(s Ήΐ)ε2 ΐ '(ΖΗ9·εΐ=ί" 'Ρ 'Ηΐ)ΖΖ·8 '(ΖΗΐ·6=ί" 'Ρ Ήΐ)8Γ8 '(ΖΗΖ·Ζ=ί" 'Ρ 'H2)S0"8 ^ΗΖ'Ζ=ΐ 'Ρ Ήΐ)Ζ6"Ζ '(ΖΗΐ·6
Figure imgf000145_0007
'(ω 'H2)8S"Z-SS"Z '(ΖΗ ·Ζ=ί"
Figure imgf000145_0008
S081760/S00Z OAV S9I各粱呦 - 9i
Figure imgf000146_0001
Figure imgf000145_0005
)
Figure imgf000145_0006
'Ρ' Ηΐ) 09ΐΐ ΐΐ '( s Ήΐ) ε2 ΐ' (ΖΗ9 ί "'Ρ' H2) S0" 8 ^ ΗΖ'Ζ = ΐ 'Ρ Ήΐ) Ζ6 "Ζ' (ΖΗΐ6
Figure imgf000145_0007
'(ω' H2) 8S "Z-SS" Z '(ΖΗ · Ζ = ί "
Figure imgf000145_0008
S081760 / S00Z OAV S9I Sangyo-9i
Figure imgf000146_0001
Figure imgf000146_0002
'Ρ Ήΐ)6Γ8 '(s 'HT)S6"Z 'Ρ 'Η 68·
Figure imgf000146_0002
'Ρ Ήΐ) 6Γ8' ( s ' HT) S6 "Z 'Ρ' Η 68
'(ΖΗΓ6 '6·ΐ=ί" 'ΡΡ 'Ηΐ)69· '(ω 'HS)8S — εε· '(zHS'8=f 'Ρ 'H2)66"9 '(ZH0"9 '( Ζ ΗΓ6' 6 · ΐ = ί "'ΡΡ' Ηΐ) 69 · '(ω' HS) 8S — εε ''(zHS'8 = f 'Ρ' H2) 66" 9 '( Z H0 "9
Ό'ζ=ί 'ρρ 'ΗΪ) 8·9 '(s Ήε)8 ·ε '(s Ήε)2ε·ζ g :(9ρ— oswa) 顺— ΗΤ °%ΟΟΪ ¾ΤΌ'ζ = ί 'ρρ' ΗΪ) 8 · 9 '(s Ήε) 8 · ε' (s Ήε) 2ε · ζ g :( 9 ρ- oswa)顺- Η Τ °% ΟΟΪ ¾Τ
9Ϊ各粱呦 (ε)  9 呦 each 呦 (ε)
Xs Ήΐ)93·6 X s Ήΐ) 93
'(s Ήΐ)3ε·6 '(ω 'H2)69"Z-^9"Z'(ra 'HS)66'9- 6·9 '(s Ήε) 8·ε '(s 'HZ)ZVZ 9 :('( s Ήΐ) 3ε6' (ω 'H2) 69 "Z- ^ 9"Z' (ra 'HS) 66'9-6.9' ( s Ήε) 8 · '( s ' HZ) ZVZ 9 :(
Iつ αつ) WN- Ητ °%ss ¾τ
Figure imgf000146_0003
I α) WN- Η τ °% ss ¾τ
Figure imgf000146_0003
、  ,
^ / - /— ^^c^ ^- s' ^P - s- ^ - ε -( / ェ - - ΐ (ζ)  ^ /-/ — ^^ c ^ ^-s' ^ P-s- ^-ε-(/---ΐ (ζ)
•(ω 'Η2)9 · -0 · '(ω 'HS) 6'9- 68·9 '(s '蹄 8·ε '(s 'HZ)OVZ '(s Ήε)6Γ2 9 :(・ (Ω 'Η2) 9 · -0 ·' (ω 'HS) 6'9-689' ( s 'hoof 8 · ε' ( s 'HZ) OVZ' ( s Ήε) 6Γ2 9 :(
Iつ aつ) WN- HT I one a) WN- H T
Figure imgf000146_0004
(ΐ)
Figure imgf000146_0004
(ΐ)
9ΐ各粱呦^ -f9i [τετο] •(zHs'n=f 'ρ Ήΐ)9ε·π  9ΐEach 呦 呦 -f9i [τετο] • (zHs'n = f 'ρ Ήΐ) 9ε
'(s Ήΐ)22 ΐ
Figure imgf000146_0005
'Ρ 'HT)S6"Z '( s Ήΐ) 22 ΐ
Figure imgf000146_0005
'Ρ' HT) S6 "Z
'(ZHS'8 ΎΖ=ί 'ΡΡ Ήΐ)99"Ζ '(ω Ήΐ)29"Ζ '(ω 'HS)6^" -2^" '(ω 'H2)ZS"Z-0S"Z  '(ZHS'8 ΎΖ = ί' ΡΡ Ήΐ) 99 "Ζ '(ω Ήΐ) 29" Ζ' (ω 'HS) 6 ^ "-2 ^"' (ω 'H2) ZS "Z-0S" Z
'(ΖΗ0·9 'S =1" 'ΡΡ 'Ηΐ)ε8·9 '(s Ήζ)6Ζ'Ζ 9 :( P-OS a)H N-HT °%66 ¾ί '(ΖΗ0 · 9' S = 1 "'ΡΡ' Ηΐ) ε8 · 9 '( s Ήζ) 6Ζ'Ζ 9 :( P-OS a) H NH T °% 66 ¾ί
ε9ΐ各粱呦 (ζ) ε9ΐEach 呦 (ζ)
Xs Ήΐ) 3·6 '( q Ήΐ)9ε·8 '(ω Ήΐ) 3· -ε3· '(ω
Figure imgf000146_0006
Ήε)„ 9 :( ιつ αつ) WN- ΗΤ °% ¾τ
Figure imgf000146_0007
X s Ήΐ) 3.6 '(q Ήΐ) 9ε8' (ω Ήΐ) 3 -ε3
Figure imgf000146_0006
Ήε) „9 :( ια α) WN- Η Τ °% ¾τ
Figure imgf000146_0007
、  ,
^ / - /— ^^c^ ^- s' ^P - s- ^ - ε -( / ェ crn^- s)- ΐ (ΐ)  ^ /-/ — ^^ c ^ ^-s' ^ P-s- ^-ε-(/ cr crn ^-s)-ΐ (ΐ)
•(zHS'SI=f 'Ρ 'Ηΐ)8 ·ΐΐ '(s 'Ηΐ) 0ΐ '^ΗΖτΐ=ί 'Ρ Ήΐ)9Ζ·8 W6=i 'Ρ Ήΐ)6Γ8 '(ΖΗΓ2=Γ Ήΐ)3Γ8 '(ω 'H2)86"Z '(ω 'Ηΐ)96· 'd6 'ε =1" 'ΡΡ (ZHS'SI = f 'Ρ' Ηΐ) 8ΐΐ '( s ' Ηΐ) 0ΐ '^ ΗΖτΐ = ί' Ρ Ήΐ) 9Ζ8 W6 = i 'Ρ Ήΐ) 6Γ8' ( Ζ Ζ2 = Γ Ήΐ) 3Γ8 '(ω' H2) 86 "Z '(ω' Ηΐ) 96 · 'd6' ε = 1"'ΡΡ
Ήΐ)ΐΖ·Ζ ' ' ) VL '(ω 'HS)8S — ΐε· '(ΖΗ0·8 'Γ2 '0·ΐ=ί" 'ΡΡΡ Ήΐ)6ΓΖ
Figure imgf000146_0008
S081760/S00Z OAV
Figure imgf000147_0001
Ήΐ) ΐΖ · Ζ '') VL '(ω' HS) 8S — ΐε · '(ΖΗ0 · 8' Γ2 '0 · ΐ = ί "' ΡΡΡ Ήΐ) 6ΓΖ
Figure imgf000146_0008
S081760 / S00Z OAV
Figure imgf000147_0001
'pp Ήΐ)3ε· '(ω 'H2)os" -eo" '(s Ήε)ιε 9 :(9p— oswa) 顺— HT °%88 ¾T
Figure imgf000147_0002
'pp Ήΐ) 3ε ·' (ω 'H2) os "-eo"' (s Ήε) ιε 9 :( 9 p— oswa) 顺 — H T °% 88 ¾T
Figure imgf000147_0002
'P 'HT)^8"8 '(s Ήΐ)£Ζ'8 '(ω 'H2)08"Z-89"Z '(ω 'HT)e9"Z-8S"Z '(ω 'HS)OS"Z-0^"Z  'P' HT) ^ 8 "8 '(s Ήΐ) £ Ζ'8' (ω 'H2) 08" Z-89 "Z' (ω 'HT) e9" Z-8S "Z' (ω 'HS) OS "Z-0 ^" Z
'(ω 'mWL-OZ-L '(s 'HT)82"Z '(s Ήε)ΐε 9 :( OSWa) 顺— HT °%06 ¾T '(ω' mWL-OZ-L '( s ' HT) 82 "Z' (s Ήε) ΐε 9 :( OSWa) 顺 — H T °% 06 ¾T
•(zHS'SI=f 'P 'Ηΐ)9·ΐΐ '(s • (zHS'SI = f 'P' Ηΐ) 9ΐΐ '' ( s
Ηΐ)0·ΐΐ '(zHS-ST=f 'P 'Ηΐ)06·8 '(s 'HT)92"8 '(zH2=f '； Ήΐ)2Γ8 '(ζΗΐ '2 '8=Γ 'ΡΡΡ Ηΐ) 0ΐΐΐΐ '(zHS-ST = f' P 'Ηΐ) 06 · 8' ( s 'HT) 92 "8' ( z H2 = f '; Ήΐ) 2Γ8' ( ζ Ηΐ '2' 8 = Γ 'ΡΡΡ
Ήΐ)66"Ζ '(ω 'H2)T8"Z-0Z"Z
Figure imgf000147_0003
'(s 'Ηΐ) · Ήΐ) 66 "Ζ '(ω' H2) T8" Z-0Z "Z
Figure imgf000147_0003
'(s' Ηΐ) ·
'(ζΗΐ '2 '8=Γ 'ΡΡΡ 'HWL '(s 'HS)SS 9 :( OSWd) Ν— Ητ °% 8 ¾ί '( ζ Ηΐ' 2 '8 = Γ' ΡΡΡ 'HWL'(s' HS) SS 9 :( OSWd) Ν— Η τ °% 8 ¾ί
69ΐ各粱呦 :69ΐ •(s_iq Ήΐ)ΐ ΐ '(s 'HT)28"8 '(s 69ΐEach beam: 69ΐ • (s_iq Ήΐ) ΐ ΐ '( s ' HT) 28 "8' ( s
'HT)2Z"8
Figure imgf000147_0004
'Ρ 'Ηΐ ·8 '(ω 'H2)S0"8 '(s Ήΐ)86"Ζ 'Ρ Ήΐ)28"Ζ '(ω 'HT) 2Z "8
Figure imgf000147_0004
'Ρ' Ηΐ · 8 '(ω' H2) S0 "8 '( s Ήΐ) 86"Ζ' Ρ Ήΐ) 28 "Ζ '(ω
'HS)SZ"Z-OS"Z '(ω 'H2)e^" -es" 'H9)os 9 :(9p— oswa) N— Ht °%ε ¾T 'HS) SZ "Z-OS"Z' (ω 'H2) e ^ "-es"' H9) os 9 :( 9 p— oswa) N— H t °% ε ¾T
891各粱呦 -S9i •(zHS'SI=f 'P 'Ηΐ)9·ΐΐ '(s 'Ηΐ)0·ΐΐ '(zHS'SI=f 'P 'Ηΐ)98·8 891 each beam -S9i (zHS'SI = f 'P' Ηΐ) 9ΐΐ '( s ' Ηΐ) 0ΐΐ'(zHS'SI = f 'P' Ηΐ) 98
'(s 'HT)S2"8
Figure imgf000147_0005
'(s' HT) S2 "8
Figure imgf000147_0005
'(ω 'HZ)ZVL- L '(s 'Ηΐ)ΐε· '(s 'HS)SS 9 :( OSWa) 顺— HT °%89 ¾T '(ω' HZ) ZVL- L '(s' Ηΐ) ΐε''(s' HS) SS 9 :( OSWa) 顺 — H T °% 89 ¾T
91各粱呦 -L9i βειο] 91 each siang 呦 -L9i βειο]
•(zHST=f 'P 'Ηΐ)Ζ·ΐΐ '(s Ήΐ)0·ΐΐ '(zHSI=f 'P 'Ηΐ) 8·8 ( Z HST = f 'P' Ηΐ) Ζ '(s Ήΐ) 0ΐΐ' ( z HSI = f 'P' Ηΐ) 8
'(s Ήΐ)^·8 '(zHZ=f 'P 'H2)88"Z '(ω 'HS)06 — ΟΓΖ '(ω 'HS)I — ' '(s 'Ηΐ)ΐε·'( s Ήΐ) ^ · 8' ( z HZ = f 'P' H2) 88 "Z '(ω' HS) 06 — ΟΓΖ '(ω' HS) I — ''(s' Ηΐ) ΐε ·
Figure imgf000147_0006
'(s Ήε)εε '(s Ήε)ιε 9 :(9p— oswa) 顺— HT °% 9 ¾T
Figure imgf000147_0006
'( s Ήε) εε' ( s Ήε) ιε 9 :( 9 p— oswa) 顺 — H T °% 9 ¾T
991各粱呦 :99ΐ •(zHST=f 'P 'Ηΐ)Ζ·ΐΐ '(s Ήΐ)6 ΐ 991 Each beam: 99 ΐ • ( z HST = f 'P' Ηΐ) Ζ ΐΐ '(s Ήΐ) 6 ΐ
'(zHST=f 'P 'Ηΐ)88·8 '(s Ήΐ)92"8 '(zHS" =f 'P 'Η εθ·8 '(ω 'H2)28"Z-0Z"Z
Figure imgf000147_0007
Ήΐ)3ΓΖ
Figure imgf000147_0008
'HS)TS"T 9 :(9p— OSW I) 顺— HT °%SS ¾T
Figure imgf000147_0009
S081760/S00Z OAV '(ω 'Ηΐ)Ζ6·9— '(ΖΗΖ·8=1" 'Ρ 'Ηΐ)08·9 9 :( OSW I) 顺— Ητ °%S8 ? φ '(zHST = f' P 'Ηΐ) 88 · 8' ( s Ήΐ) 92 "8 '(zHS" = f' P 'Η εθ · 8' (ω 'H2) 28 "Z-0Z" Z
Figure imgf000147_0007
Ήΐ) 3ΓΖ
Figure imgf000147_0008
'HS) TS "T 9 :( 9 p— OSW I) 顺 — H T °% SS ¾T
Figure imgf000147_0009
S081760 / S00Z OAV '(ω' Ηΐ) Ζ6 · 9— '(ΖΗΖ · 8 = 1 "' Ρ 'Ηΐ) 08 · 9 9 :( OSW I) 顺 — Η τ °% S8? φ
•(zH '8=f 'p 'ΗΪ)ΟΟ·6 mvs=i 'P 'Ηΐ)ΐε·8• (zH '8 = f' p 'ΗΪ) ΟΟ6 mvs = i' P 'Ηΐ) ΐε8
'(ZH 9"8=f 'P 'H2)S0"8 '(zH9"8=f 'P 'H2)99"Z '(ω 'ΗΖ)£ί' L-Z9' L '(ω 'HDW L-W L
Figure imgf000148_0001
'P 'Ηΐ)00· 9 :( P-OS a)H N-HT °%96 ¾ί
Figure imgf000148_0002
'P 'Ηΐ)00·6 '(ΖΗΖ·Ζ=ί" 'P 'Ηΐ) 8 '(ΖΗ ·8=ί" 'P Ή2)06"Ζ '(ω Ήε) - U'Z '(ω 'HT)89"Z-S9"Z '(ω 'HD^L-LVL '(s Ήζ)ΟΥί '(ΖΗΖ·8=1" 'Ρ Ήΐ)2ε· '(ΖΗΖ·8=1" 'Ρ 'Ηΐ)Μ)·Ζ 9 :( P-OS a)H N-HT °%ΐ6 ? φ '(ZH 9 "8 = f' P 'H2) S0"8' (zH9 "8 = f 'P' H2) 99" Z '(ω' ΗΖ) £ ί 'L-Z9' L '(ω' HDW LW L
Figure imgf000148_0001
'P' Ηΐ) 009 :( P-OS a) H NH T °% 96 ¾ί
Figure imgf000148_0002
'P' Ηΐ) 00 · 6 '(ΖΗΖ · Ζ = ί "' P 'Ηΐ) 8' (ΖΗ · 8 = ί"'P Ή2) 06 "Ζ' (ω Ήε)-U'Z '(ω' HT) 89 "Z-S9" Z '(ω' HD ^ L-LVL '(s Ήζ) ΟΥί' (ΖΗΖ8 = 1 "'Ρ Ήΐ) 2ε ·' (ΖΗΖ8 = 1"'Ρ' Ηΐ ) Μ) Ζ 9 :( P-OS a) H NH T °% ΐ6? Φ
•(ζΗεΐ=Γ 'ρ Ήΐ)^π '(ζΗετ=Γ• ( ζ Ηεΐ = Γ 'ρ Ήΐ) ^ π' ( ζ Ηετ = Γ
'Ρ 'Ηΐ)0Γ8 '(zHS"8=f 'Ρ 'H2)66"Z '(zHS"T=f 'Ρ Ήΐ)ΐ8"Ζ '(zH8=f 'Ρ Ήΐ)89"Ζ (ZHS'I
Figure imgf000148_0003
' 'HZ)ZVL 'Ρ' Ηΐ) 0Γ8 '(zHS "8 = f' Ρ 'H2) 66"Z' (zHS "T = f 'Ρ Ήΐ) ΐ8"Ζ' (zH8 = f 'Ρ Ήΐ) 89 "Ζ (ZHS' I
Figure imgf000148_0003
'' HZ) ZVL
' ΉΖ)Ζΐτ '(zH9=f ' 'H2)99"2 '(s Ήζ)Ζζ'Ζ 9 :( P-OS a)H N-HT °%08 ¾ί 'ΉΖ) Ζΐτ' ( z H9 = f '' H2) 99 "2 '( s Ήζ) Ζζ'Ζ 9 :( P-OS a) H NH T °% 08 ¾ί
SZI各粱呦 - Li •(zHST=f 'P 'Ηΐ)9·ΐΐ '(s 'Ηΐ)0·ΐΐ '(zHST=f 'P 'Ηΐ)ε8·8 (s 'HT)S2"8 '(zH6=f 'P 'H2)Z8"Z '(ω 'H2)08"Z-0Z"Z '(ω ΉΖ)θνί-Ζ£Ί '(s 'HT)OS"Z '(zH6=f 'P 'H2)86"9 '(s 'HS)ZZT '(s Ήε)εε 9 :( P-OS a)H N-HT °%06 ¾ί SZI each beam-Li • ( z HST = f 'P' Ηΐ) 9ΐΐ '( s ' Ηΐ) 0 · ΐΐ '( z HST = f' P 'Ηΐ) ε8 · 8 (s' HT) S2 " 8 '(zH6 = f' P 'H2) Z8 "Z' (ω 'H2) 08" Z-0Z "Z' (ω ΉΖ) θνί-Ζ £ Ί '( s ' HT) OS"Z' ( z H6 = f 'P' H2) 86 "9 '( s ' HS) ZZT' (s Ήε) εε 9 :( P-OS a) H NH T °% 06 ¾ί
•(zHST=f 'P 'Ηΐ)ε ΐ '(s Ήΐ)6 ΐ '(zHST=f 'Ρ 'HT)SZ"8 '(s 'Ηΐ) ·8 '(ω 'HS)S8"Z-SZ"Z
Figure imgf000148_0004
• ( z HST = f 'P' Ηΐ) ε ΐ '( s Ήΐ) 6 ΐ' ( z HST = f 'Ρ' HT) SZ "8 '(s' Ηΐ) · 8 '(ω' HS) S8" Z-SZ "Z
Figure imgf000148_0004
'(ω 'H2)8S"Z-0S"Z '(s 'HT)62"Z '(s Ήε)ε ·ε 9 :( P-OS a)H N-HT °%89 ¾ί '(ω' H2) 8S "Z-0S" Z '(s' HT) 62 "Z' (s Ήε) ε · ε 9 :( P-OS a) H NH T °% 89 ¾ί
•(s Ήΐ)6 ΐ• ( s Ήΐ) 6 ΐ
'(s 'Ηΐ)ε8·6 '(s 'Ηΐ)06·8
Figure imgf000148_0005
' HZ)OL'L '； 'HT)OS"Z '(ω 'HW -S2" 9 :( OSW I) 顺— HT °%S ¾T
Figure imgf000148_0006
'(s' Ηΐ) ε8 6 '(s' Ηΐ) 068
Figure imgf000148_0005
'HZ) OL'L';'HT) OS "Z' (ω 'HW -S2" 9 :( OSW I) 顺 — H T °% S ¾T
Figure imgf000148_0006
Figure imgf000148_0007
'P Ήΐ)6Ζ·8 '(ZHS'I
Figure imgf000148_0008
9 S081760/S00Z OAV '(s Ήΐ)68"Ζ
Figure imgf000149_0001
'ΗΖ)Ζ Ί
Figure imgf000148_0007
'P Ήΐ) 6Ζ8'(ZHS'I
Figure imgf000148_0008
9 S081760 / S00Z OAV '(s Ήΐ) 68 "Ζ
Figure imgf000149_0001
'ΗΖ) Ζ Ί
'(ΖΗΖ·Ζ Τΐ=Γ '； ρ Ήΐ)οε· '(s Ήε) 9 :( oswa) 顺— ΗΤ ¾Τ '( Ζ ΗΖ · Ζ Τΐ = Γ'; ρ Ήΐ) οε · '(s Ήε) 9 :( oswa) 顺 — Η Τ ¾Τ
•(s 'Ηΐ)ΐε·Οΐ '(s Ήΐ)92 ΐ '(zH8"8=f 'P 'HT)S8"Z '(ΖΗ6·9=1" 'P 'Ηΐ)08· '(zHO=f • ( s ' Ηΐ) ΐε · Οΐ '( s Ήΐ) 92 ΐ' ( z H8 "8 = f 'P' HT) S8" Z '(ΖΗ6 · 9 = 1 "' P 'Ηΐ) 08 ·' (zHO = f
'p 'HZ)WL '(ω
Figure imgf000149_0002
'W Ήΐ)οε· 'p' HZ) WL '(ω
Figure imgf000149_0002
'W Ήΐ) οε
'(ΖΗΓ6=Γ 'P 'HWL '(s 'Ηΐ)0 ·9 '(s 'HZ)LZ'Z 9 :( P-OS a)H N-HT °%0S ¾T '( Ζ ΗΓ6 = Γ' P 'HWL'(s' Ηΐ) 0 ・ 9 '( s ' HZ) LZ'Z 9 :( P-OS a) H NH T °% 0S ¾T
ε8ΐ各粱呦^ - [esTO] ε8ΐEach 呦 呦-[esTO]
•(s 'HDeSTT '(s 'Ηΐ) Οΐ '(ΖΗ ·8=1" 'P 'HI)SS'8 '(zH8"8=f 'P 'HT)26"Z • (s' HDeSTT '(s' Ηΐ) Οΐ' (ΖΗ · 8 = 1 "'P' HI) SS'8 '( z H8" 8 = f' P 'HT) 26 "Z
'(ΖΗΖ·Ζ=ί" 'P Ήΐ)68"Ζ
Figure imgf000149_0003
'(ΖΗΖ · Ζ = ί "' P Ήΐ) 68" Ζ
Figure imgf000149_0003
'(zH0"Z=f '； 'Ηΐ)ΐε· '(s 'Ηΐ)8ε·9 '(s Ήε) 2·ζ 9 :( P-OS a)H N-HT °%S ¾ί
Figure imgf000149_0004
'( z H0 "Z = f';'Ηΐ) ΐε ·' (s 'Ηΐ) 8ε · 9' ( s Ήε) 2ζζ 9 :( P-OS a) H NH T °% S ¾ί
Figure imgf000149_0004
'PP 'H2)66"Z
Figure imgf000149_0005
'P Ήΐ)ΐ6"Ζ '(s 'HT)9S"Z 'P 'HT)SS"Z '(ZHS'I
Figure imgf000149_0006
' lwz)m~z '(s Ήε)ιε '(zHS"9=f 'w* iwz)mz 9 :(9p— oswa) N— HT °% 8 ¾T
Figure imgf000149_0007
'P 'Η 00·8 '(ω 'HS)0S"Z-0S"Z
Figure imgf000149_0008
'PP' H2) 66 "Z
Figure imgf000149_0005
'P Ήΐ) ΐ6 "Ζ' (s 'HT) 9S"Z' P 'HT) SS "Z'(ZHS'I
Figure imgf000149_0006
' l wz) m ~ z' (s Ήε) ιε '(zHS "9 = f' w * i wz) mz 9 :( 9 p— oswa) N— H T °% 8 ¾T
Figure imgf000149_0007
'P' Η 00 · 8 '(ω' HS) 0S "Z-0S" Z
Figure imgf000149_0008
'(s Ήε)οε '(zHs-9=f 'p Ήε)9ε·ΐ 9 :( p-os a)H N-HT °%zz ¾τ '( s Ήε) οε' ( z Hs-9 = f 'p Ήε) 9εΐ 9 :( p-os a) H NH T °% zz ¾τ
08ΐ各粱呦^  08 呦 each 呦
•(zHST=f• ( z HST = f
'P 'Ηΐ) ·ΐΐ
Figure imgf000149_0009
'P' Ηΐ)
Figure imgf000149_0009
'P
Figure imgf000149_0010
'H ·Ζ '(ΖΗΐ 'P
Figure imgf000149_0010
'H · Ζ' (ΖΗΐ
's'z=f 'p^ ' )fVL '(s Ήε) 9 '(s Ήε)ιε 9 :( p-os a)H N-HT °%S8 ? Φ 's'z = f' p ^ ') fVL' ( s Ήε) 9 '( s Ήε) ιε 9 :( p-os a) H NH T °% S8? Φ
•(s 'HWOT '(ζΗ8·ΐΐ=ί"• ( s 'HWOT' ( ζ Η8 · ΐΐ = ί "
' 'Ηΐ)ΐε·8 '(ΖΗΖ·Ζ=ί" 'P 'HT)0Z"Z '(ω 'H2)S9"Z-ZS"Z '' Ηΐ) ΐε · 8 '(ΖΗΖ · Ζ = ί "' P 'HT) 0Z" Z' (ω 'H2) S9 "Z-ZS" Z
'(ω
Figure imgf000149_0011
'P Ήΐ)02"Ζ '(ω 'HT)2rZ-Z0"Z '(ω 'HT)S0"Z-00"Z
Figure imgf000149_0012
S081760/S00Z OAV 7.98(1H, d, J=7.3Hz), 8.01(2H, dd, J=l.l, 7.7Hz), 8.31(1H, d, J=8.1Hz), 8.84(1H, brs), 9.55(1H, s), 12.97(1H, brs). '(ω
Figure imgf000149_0011
'P Ήΐ) 02 "Ζ' (ω 'HT) 2rZ-Z0"Z' (ω 'HT) S0 "Z-00" Z
Figure imgf000149_0012
S081760 / S00Z OAV 7.98 (1H, d, J = 7.3Hz), 8.01 (2H, dd, J = ll, 7.7Hz), 8.31 (1H, d, J = 8.1Hz), 8.84 (1H, brs), 9.55 (1H, s ), 12.97 (1H, brs).
例 185:化合物番号 185 Example 185: Compound number 185
収率 23%。 'H-NMRCDMSO-d ): δ 6.97(1Η, d, J=8.1Hz), 7.3(1Η, dt, J=l.l, Yield 23%. 'H-NMRCDMSO-d): δ 6.97 (1Η, d, J = 8.1Hz), 7.3 (1Η, dt, J = l.l,
6  6
7.4Hz), 7.51(2H, t, J=7.7Hz), 7.61(1H, t, J=7.5Hz), 7.75(1H, t, J=7.5Hz), 7.82(1H, d, J=8.1Hz), 8.01(3H, d, J=7.7Hz), 8.26(1H, d, J=8.4Hz), 8.74(1H, s), 10.26(1H, s), 12.89(1H, brs).  7.4Hz), 7.51 (2H, t, J = 7.7Hz), 7.61 (1H, t, J = 7.5Hz), 7.75 (1H, t, J = 7.5Hz), 7.82 (1H, d, J = 8.1Hz) ), 8.01 (3H, d, J = 7.7Hz), 8.26 (1H, d, J = 8.4Hz), 8.74 (1H, s), 10.26 (1H, s), 12.89 (1H, brs).
例 186:化合物番号 186 Example 186: Compound number 186
(1) 3-ァミノ- 1-メチルインダゾール  (1) 3-amino-1-methylindazole
2-フルォ口べンゾ-トリル (0.50g, 4.128mmol)、メチルヒドラジン (0.64ml, 12.4mmol)、 及びエタノールの混合物を 8時間加熱還流した。反応混合物を減圧濃縮して得られ た残渣に 2N塩酸をカ卩ぇ酸性とし、酢酸ェチルで抽出した。酢酸ェチル層を飽和食塩 水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去して、標題化合物の淡 黄褐色結晶 (0.30g, 49%)を得た。  A mixture of 2-fluorobenzo-tolyl (0.50 g, 4.128 mmol), methylhydrazine (0.64 ml, 12.4 mmol), and ethanol was heated to reflux for 8 hours. The reaction mixture was concentrated under reduced pressure, 2N hydrochloric acid was added to the residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain pale yellow-brown crystals (0.30 g, 49%) of the title compound.
'H-NMRCCDCl ): δ 3.84(3H, s), 4.03( 2H, brs), 7.01(1H, t, J=7Hz), 7.20(1H, d,  'H-NMRCCDCl): δ 3.84 (3H, s), 4.03 (2H, brs), 7.01 (1H, t, J = 7Hz), 7.20 (1H, d,
3  Three
J=7Hz), 7.34(1H, t, J=7Hz), 7.54(1H, d, J=7Hz).  J = 7Hz), 7.34 (1H, t, J = 7Hz), 7.54 (1H, d, J = 7Hz).
(2)化合物番号 186  (2) Compound No. 186
収率 67%。 'H-NMRCDMSO-d ): δ 4.10(3H, s), 7.29(1H, t, J=7.5Hz), 7.36(1H, d, Yield 67%. 'H-NMRCDMSO-d): δ 4.10 (3H, s), 7.29 (1H, t, J = 7.5Hz), 7.36 (1H, d,
6  6
J=7.5Hz), 7.51(1H, t, J=7.5Hz), 7.58(1H, t, J=7.5Hz), 7.68(1H, t, J=7.5Hz), 7.71(2H, m), 7.86(1H, d, J=7.5Hz), 8.03(1H, d, J=7.5Hz), 8.36(1H, d, J=7.5Hz), 9.43(1H, s), 15.K1H, s).  J = 7.5Hz), 7.51 (1H, t, J = 7.5Hz), 7.58 (1H, t, J = 7.5Hz), 7.68 (1H, t, J = 7.5Hz), 7.71 (2H, m), 7.86 (1H, d, J = 7.5Hz), 8.03 (1H, d, J = 7.5Hz), 8.36 (1H, d, J = 7.5Hz), 9.43 (1H, s), 15.K1H, s).
例 187:化合物番号 187 Example 187: Compound number 187
収率 80%。 ^-NMRCDMSO-d ): δ 7.25-7.45(4Η, m), 7.51(2Η, t, J=7.5Hz), Yield 80%. ^ -NMRCDMSO-d): δ 7.25-7.45 (4Η, m), 7.51 (2Η, t, J = 7.5Hz),
6  6
7.75(1Η, d, J=7.5Hz), 7.84(1H, d, J=7.5Hz), 7.97(2H, d, J=7.5Hz), 8.45(1H, s), 8.97(1H, d, J=13.5Hz), 11.1(1H, s), 12.5(1H, d, J=13.5Hz).  7.75 (1Η, d, J = 7.5Hz), 7.84 (1H, d, J = 7.5Hz), 7.97 (2H, d, J = 7.5Hz), 8.45 (1H, s), 8.97 (1H, d, J = 13.5Hz), 11.1 (1H, s), 12.5 (1H, d, J = 13.5Hz).
例 188:化合物番号 188 Example 188: Compound number 188
収率 91%。 ^-NMRCDMSO-d ): δ 5.54(1Η, d, J=7.5Hz), 5.97(1Η, d, J=7.5Hz), Yield 91%. ^ -NMRCDMSO-d): δ 5.54 (1Η, d, J = 7.5Hz), 5.97 (1Η, d, J = 7.5Hz),
6  6
7.24-7.44(3H, m), 7.51(2H, t, J=8.5Hz), 7.61(1H, d, J=7Hz), 7.68(1H, dd, J=8, •(ZHS'8=f 'P Ήΐ)εζ·8 '(ζΗΐ 'S' =f 'PP 'H ·Ζ '(ω 'HT)0^"Z-02"Z '(zHZ=f 'b 'HZ)Wf '(s '1~^)81 '(zH =f '； Ήε)6^"ΐ 9 :( !DaD)H N-HT
Figure imgf000151_0001
、ェっ^ ^ ^ ^^m ^m^^ ^n ^m-^ ^ ° つ 7.24-7.44 (3H, m), 7.51 (2H, t, J = 8.5Hz), 7.61 (1H, d, J = 7Hz), 7.68 (1H, dd, J = 8, • (ZHS'8 = f 'P Ήΐ) εζ8' ( ζ Ηΐ 'S' = f 'PP' H · Ζ '(ω' HT) 0 ^ "Z-02" Z '(zHZ = f' b 'HZ) Wf'(s' 1 ~ ^) 81 '(zH = f'; Ήε) 6 ^ "ΐ 9 :(! DaD) H NH T
Figure imgf000151_0001
^^^^^ m ^ m ^^^ n ^ m-^^ °
° ^^、 i
Figure imgf000151_0002
^ Hェ- ε ° ^^, i
Figure imgf000151_0002
^ H-e
一 、^ベ ^ - ΐ - / ^ / ェ- ε (ΐ)
Figure imgf000151_0003
'(ΖΗΖ·εΐ=ί" 'Ρ 'Ηΐ)ε8·8 I, ^ be ^-ΐ-/ ^ / --ε (ΐ)
Figure imgf000151_0003
'(ΖΗΖεΐ = ί "' Ρ 'Ηΐ) ε8
'Ρ 'Ηΐ) 8 XS Ήΐ)3Γ8 '(ΖΗ2·8=Γ 'Ρ 'Ηΐ)εθ·8 '(zH0"8=f 'Ρ 'Ηΐ)00·8 '(ΖΗΖ·Ζ=1" 'Ρ Ήΐ)ΐ6"Ζ '(ΖΗε·6=ί" 'Ρ 'HDWL ^HVL=i 'HT)9S"Z '(ω ΉΖ)\^ L-W L '(ΖΗΖ·Ζ=1" 'Ρ Ήΐ)ζ· '(s 'HZ) Z 9 :( OSWa) Ν— Ητ °%08 ¾ί ΐ6ΐ各粱呦 :ΐ6ΐ '(ΖΗΖ·εΐ=ί" 'Ρ 'Ηΐ)ΐΟ ΐ '(s 'Ηΐ)8ε·0ΐ
Figure imgf000151_0004
'Ρ' Ηΐ) 8 X S Ήΐ) 3Γ8 '( Ζ Η2.8 = Γ' Ρ 'Ηΐ) εθ8' ( z H0 "8 = f 'Ρ' Ηΐ) 008 '(ΖΗΖΖΗΖ = 1 "'Ρ Ήΐ) ΐ6"Ζ' (ΖΗε · 6 = ί "'Ρ' HDWL ^ HVL = i 'HT) 9S"Z' (ω ΉΖ) \ ^ LW L '(ΖΗΖ · Ζ = 1 "' Ρ Ήΐ ) ζ '(s' HZ) Z 9 :( OSWa) Ν— Η τ °% 08 ¾ί ΐ6ΐEach beam: ΐ6ΐ' (ΖΗΖεΐ = ί "'Ρ' Ηΐ) ΐΟ ΐ '( s ' Ηΐ) 8ε0ΐ
Figure imgf000151_0004
'Ρ 'HT)28"8 '(ΖΗ2·8=Γ 'Ρ 'ΗΙ)ΖΖ'8 '(zH8"8=f 'Ρ 'H2)Z0"8 '(zH0"6=f 'Ρ 'Ηΐ)εθ·8
Figure imgf000151_0005
'Ρ' HT) 28 "8 '( Ζ Η2.8 = Γ' Ρ 'ΗΙ) ΖΖ'8' ( z H8" 8 = f 'Ρ' H2) Z0 "8 '( z H0" 6 = f' Ρ 'Ηΐ) εθ8
Figure imgf000151_0005
' 'HDSVL '(ΖΗ2·8=Γ 'P 'HZ)WL '(s 'HS)SS 9 :( OSWa) 顺— HT ¾T '' HDSVL '( Ζ Η2.8 = 8' P 'HZ) WL'(s' HS) SS 9 :( OSWa) 顺 — H T ¾T
061各粱呦^  061 each siang 呦 ^
•(zH9'SI=f 'P Ήΐ)0Γ2ΐ • (zH9'SI = f 'P Ήΐ) 0Γ2ΐ
'(ΖΗ9·εΐ=ί" 'P ' '(ΖΗ9 · εΐ = ί "' P '
'P 'HZ)WS  'P' HZ) WS
'HT)eS"Z '(ΖΗΐ·8
Figure imgf000151_0006
'HT) eS "Z' (ΖΗΐ8
Figure imgf000151_0006
'WL=[ 'b 'HZ)WZ 'WL=[ 'HS)62"T 9 :( OSWa) 顺— HT °% ¾T 'WL = [' b 'HZ) WZ' WL = ['HS) 62 "T 9 :( OSWa) 顺 — H T °% ¾T
681各粱呦 -6Si  681 each 呦 -6Si
'(saq 'HT)SZ"8 '(ω 'HS)66"Z-26"Z
Figure imgf000151_0007
Figure imgf000151_0008
6 S081760/S00Z OAV 3-エトキシカルボ-ルインダゾール： Heterocycles, Vol.43, No.12, '(saq' HT) SZ "8 '(ω' HS) 66" Z-26 "Z
Figure imgf000151_0007
Figure imgf000151_0008
6 S081760 / S00Z OAV 3-ethoxycarbo-luindazole: Heterocycles, Vol.43, No.12,
p.2701- 2712(1996)参照。 See p.2701-2712 (1996).
(2) 3-カルボキシ -1-メチルインダゾール  (2) 3-carboxy-1-methylindazole
3-エトキシカルボ-ル -1-メチルインダゾール (0.30g, 1.47mmol)、 2N水酸化ナトリウ ム水溶液及びメタノールの混合物を室温で 18時間攪拌した。反応混合物を減圧濃縮 して得られた残渣に水及び 2N塩酸を加え酸性とした。析出した固体を濾取して、標 題化合物の淡褐色結晶 (0.23g, 89%)を得た。  A mixture of 3-ethoxycarbol-1-methylindazole (0.30 g, 1.47 mmol), a 2N aqueous sodium hydroxide solution and methanol was stirred at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure, and water and 2N hydrochloric acid were added to the residue to make it acidic. The precipitated solid was collected by filtration to give the title compound as pale-brown crystals (0.23 g, 89%).
^-NMRCDMSO-d ): δ 4.15(3H, s), 7.32(1H, t, J=8Hz), 7.50(1H, t, J=8Hz),  ^ -NMRCDMSO-d): δ 4.15 (3H, s), 7.32 (1H, t, J = 8Hz), 7.50 (1H, t, J = 8Hz),
6  6
7.76(1H, d, J=8Hz), 8.10(1H, d, J=8Hz).  7.76 (1H, d, J = 8Hz), 8.10 (1H, d, J = 8Hz).
(3)化合物番号 192  (3) Compound No. 192
収率 46%。 ^-NMRCDMSO-d ): δ 4.24(3H, s), 7.37(1H, t, J=7.5Hz), Yield 46%. ^ -NMRCDMSO-d): δ 4.24 (3H, s), 7.37 (1H, t, J = 7.5Hz),
6  6
7.42-7.58(4H, m), 7.80— 7.90(2H, m), 8.13(1H, d, J=9Hz), 8.20- 8.30(2H, m), 9.94(1H, s), 10.2(1H, s).  7.42-7.58 (4H, m), 7.80- 7.90 (2H, m), 8.13 (1H, d, J = 9Hz), 8.20- 8.30 (2H, m), 9.94 (1H, s), 10.2 (1H, s ).
例 193:化合物番号 193 Example 193: Compound number 193
収率 13%。 ^-NMRCDMSO-d ): δ 4.23(3Η, s), 7.25-7.45(4Η, m), 7.55(1Η, t, Yield 13%. ^ -NMRCDMSO-d): δ 4.23 (3Η, s), 7.25-7.45 (4Η, m), 7.55 (1Η, t,
6  6
J=8Hz), 7.70(1Η, d, J=8Hz), 7.75-7.85(2H, m), 8.30(1H, d, J=8Hz), 8.90(1H, s), 9.72(1H, s), 10.9(1H, s).  J = 8Hz), 7.70 (1Η, d, J = 8Hz), 7.75-7.85 (2H, m), 8.30 (1H, d, J = 8Hz), 8.90 (1H, s), 9.72 (1H, s), 10.9 (1H, s).
例 194:化合物番号 194 Example 194: Compound number 194
(1) 1- (4-メチルフエ-ル)- 3-トリフルォロメチル- 4,5-ジヒドロピラゾール- 5-オン 一般合成法 γと同様の方法により標題ィ匕合物を得た。収率 71%。 1 (1) 1- (4-Methylphenyl) -3-trifluoromethyl-4,5-dihydropyrazol-5-one The title conjugate was obtained in the same manner as in the general synthesis method γ. Yield 71%. 1
H-NMR(DMSO-d ): δ 2.35(3H, s), 3.32(1H, brs), 5.88(1H, s), 7.30(2H, d, J=8Hz),  H-NMR (DMSO-d): δ 2.35 (3H, s), 3.32 (1H, brs), 5.88 (1H, s), 7.30 (2H, d, J = 8Hz),
6  6
7.58(2H, d, J=8Hz).  7.58 (2H, d, J = 8Hz).
(2) 1- (4-メチルフエ-ル)- 5-ォキソ -3-トリフルォロメチル- 4,5-ジヒドロピラゾール- 4- カルバルデヒド  (2) 1- (4-methylphenyl) -5-oxo-3-trifluoromethyl-4,5-dihydropyrazole-4-carbaldehyde
一般合成法 aと同様の方法により標題化合物を得た。収率 39%。 1 The title compound was obtained in the same manner as in General Synthesis Method a. Yield 39%. 1
H-NMR(DMSO-d ): δ 2.32(3H, s), 4.30(1H, brs), 7.23(2H, d, J=8Hz), 7.75(2H, d, H-NMR (DMSO-d): δ 2.32 (3H, s), 4.30 (1H, brs), 7.23 (2H, d, J = 8 Hz), 7.75 (2H, d,
6  6
J=8Hz), 9.49(1H, s).  J = 8Hz), 9.49 (1H, s).
(3)化合物番号 194 'C=f '； 'HT)68"S '(ΖΗ0· =1" 'P 'HZ)Wf 9 :( OSW I) 顺— HT °%ZZ ¾T (3) Compound No. 194 'C = f';'HT) 68 "S' (ΖΗ0 · = 1"'P' HZ) Wf 9 :( OSW I) 顺 — H T °% ZZ ¾T
861各粱呦 -S6i  861 sorghum -S6i
'P 'Ηΐ)9 ΐ '(s Ήΐ)ΓΠ 'Ρ 'Ηΐ) 6·8 'P' Ηΐ) 9 ΐ '( s Ήΐ) ΓΠ' Ρ 'Ηΐ) 6.8
'(s
Figure imgf000153_0001
6"Ζ 'Ρ Ήΐ)98" 'Ρ 'HT)SZ"Z '(s
Figure imgf000153_0001
6 "Ζ 'Ρ Ήΐ) 98"' Ρ 'HT) SZ "Z
'(zH8=f 'Ρ 'H2)TS"Z '(ω 'HW -92" 9 :( OSWa) 顺— Ητ °%0S ¾ί '(zH8 = f' Ρ 'H2) TS "Z' (ω 'HW -92" 9 :( OSWa) 顺 — Η τ °% 0S ¾ί
6ΐ各粱呦 -L6i [6S TO] =[ 'ρ Ήΐ)ο·εΐ '(s Ήΐ)8 ΐ 6ΐEach 呦 -L6i [6S TO] = ['ρ Ήΐ) ο · εΐ' ( s Ήΐ) 8 ΐ
'(ζΗ^ΐ=Γ 'Ρ 'Ηΐ)98·8 '(ΖΗ3·8=Γ 'Ρ 'ΗΙ) Ζ'8 '(ΖΗ6=Γ 'Ρ Ήΐ)0Γ8 '(ω 'HS)20"8-06"Z '( ζ Η ^ ΐ = Γ' Ρ 'Ηΐ) 98 · 8' ( Ζ Η3.8 = Γ 'Ρ' ΗΙ) Ζ'8 '( Ζ Η6 = Γ' Ρ Ήΐ) 0Γ8 '(ω' HS) 20 "8-06" Z
'(ω 'HS)89"Z-9^"Z '(zHS"Z=f '； 'HT)OS"Z 9 :( OSWa) 顺— HT °%8 ¾T '(ω' HS) 89 "Z-9 ^" Z '(zHS "Z = f';'HT)OS" Z 9 :( OSWa) 顺 — H T °% 8 ¾T
961各粱呦 (ε)  961 each siang 呦 (ε)
•(s Ήΐ)8Ζ·6 • ( s Ήΐ) 8Ζ6
'(ω 'H2)s8" -e " '(ω
Figure imgf000153_0002
9 :(9ρ— oswa) Ν— Η '(ω' H2) s8 "-e"'(ω
Figure imgf000153_0002
9 :( 9 ρ— oswa) Ν— Η
、 3^, 3 ^
Figure imgf000153_0003
(2)
Figure imgf000153_0003
(2)
•(ZHS'I 'S"Z=f 'PP 'H2)0Z"Z '(ZHS'I 'S"Z=f 'P^ 'H2)2S"Z  • (ZHS'I 'S "Z = f' PP 'H2) 0Z" Z' (ZHS'I 'S "Z = f' P ^ 'H2) 2S" Z
'(ZHS'I 'S"Z=f 'W 'HT)6S"Z '(s 'HT)S6"S '(sjq 'HI)SS'S 9 :( OSW I) N— H  '(ZHS'I' S "Z = f 'W' HT) 6S" Z '(s' HT) S6 "S '(sjq' HI) SS'S 9 :( OSW I) N— H
T °%ss ¾i ^ ^ ^mm^m^ mん ¾ 一 T °% ss ¾i ^ ^ ^ mm ^ m ^ m ¾ 一
ベ - S- /— : ΰ、 ¾^- S' / ェ - ΐ- ^エ ci / ^ベ - ε (ΐ)  Be-S-/ —: ΰ, ¾ ^ -S '/ e-ΐ- ^ e ci / ^ be-ε (ΐ)
961各粱呦 :96ΐ  961 each siang 呦: 96ΐ
•(zHST=f 'P 'Ηΐ)8 ΐ • ( z HST = f 'P' Ηΐ) 8 ΐ
'(s Ήΐ)Ζ ΐ
Figure imgf000153_0004
'Ρ Ήΐ)0Γ8
Figure imgf000153_0005
'(s Ήΐ) Ζ ΐ
Figure imgf000153_0004
'Ρ Ήΐ) 0Γ8
Figure imgf000153_0005
'(zHS"8=f 'ρ Ή οε· '(s Ήε)3ε·ζ s :(9ρ— oswa) 顺— HT °%ΟΖ ¾Τ '(zHS "8 = f' ρ Ήοε · '(s Ήε) 3εζζ s :( 9 ρ— oswa) 顺 — H T °% ΟΖ ¾Τ
S6I各粱呦 ： S6I  S6I each sword: S6I
'Ηΐ) ΐ '( q Ήΐ)3·Π '(saq 'Ηΐ)ε6·8 Ή ' )ZVS '(ω 'HS)06"Z-08"Z
Figure imgf000153_0006
'Ηΐ) ΐ' (q Ήΐ) 3Π Π '(saq' Ηΐ) ε6.8 Ή ') ZVS' (ω 'HS) 06 "Z-08" Z
Figure imgf000153_0006
'ρ 'ΗΪ) '(ω 'm)WL- -L '(s Ήε)3ε·ζ 9 :(9ρ— oswa) 顺— ΗΤ °%Ζ ¾Τ t9t900 OZdr/lDd V9V S081760/S00Z OAV •( q Ήΐ)ζ8τι '(s Ήΐ)εζ·6 mvs=i 'p Ήΐ)9ε·8 'ρ' ΗΪ) '(ω ' m) WL- -L '(s Ήε) 3ε · ζ 9 :( 9 ρ- oswa)顺- Η Τ °% Ζ ¾Τ t9t900 OZdr / lDd V9V S081760 / S00Z OAV • (q Ήΐ) ζ8τι '( s Ήΐ) εζ6 mvs = i' p Ήΐ) 9ε8
'(ΖΗΐ·8=ί" 'P 'HT)S6"Z '(ΖΗΖ·Ζ=ί" 'P 'H2)28"Z
Figure imgf000154_0001
Ήΐ)69"Ζ '(ΖΗΐ·8=ί" '(ΖΗΐ · 8 = ί "' P 'HT) S6"Z' (ΖΗΖ · Ζ = ί "'P' H2) 28" Z
Figure imgf000154_0001
Ήΐ) 69 "Ζ '(ΖΗΐ · 8 = ί"
'P Ήΐ)Ζ9"Ζ
Figure imgf000154_0002
ΉΖ) Υί 'P Ήΐ) Ζ9 "Ζ
Figure imgf000154_0002
ΉΖ) Υί
'(zH8"9=f ' 'Ηΐ)εε· '(s Ήΐ)ΖΟ· '(s 'HS)Z6"S 9 :( OS^a) 顺— Ητ °%88 ¾Τ '( z H8 "9 = f''Ηΐ)εε' (s Ήΐ) ΖΟ '(s' HS) Z6" S 9 :( OS ^ a) 顺 — Η τ °% 88 ¾Τ
sos各粱呦 -zoz sos each siang 呦 -zoz
•(ZH8 ΐ=ί" 'P 'Ηΐ)Ζ8·ΐΐ 'WZl=i 'P 'Ηΐ)0Γ8 '(s 'HI)SS'8
Figure imgf000154_0003
' Ήΐ)9Γ8 '(ω 'HW -06" '(ZHS'Z 'S"T=f '^Ρ 'HT)9S"Z '(ΖΗΐ·8=ί" 'P 'HT)TS"Z '(ΖΗΐ·8=ί" ' 'HD VL '(ZH " 'S"T=f 'PP • (ZH8 ΐ = ί "'P' Ηΐ) Ζ8ΐΐ ΐΐ 'WZl = i' P 'Ηΐ) 0Γ8'(s' HI) SS'8
Figure imgf000154_0003
'Ήΐ) 9Γ8' (ω 'HW -06 "'(ZHS'Z'S" T = f' ^ Ρ 'HT) 9S "Z' (ΖΗΐ · 8 = ί"'P' HT) TS "Z '( 8 · 8 = ί "'' HD VL '(ZH"' S "T = f 'PP
Ήΐ)8ΓΖ '(s 'HT)98"S '(s 'Η 08· '(s 'HS)SS 9 :( OSWd) N— HT
Figure imgf000154_0004
Ήΐ) 8ΓΖ '(s' HT) 98 "S '(s' Η08 · '( s ' HS) SS 9 :( OSWd) N— H T
Figure imgf000154_0004
SOS各粱呦^ :202p } [0W0] •(zH9'SI=f 'P  SOS each beam ^: 202p} [0W0] • (zH9'SI = f 'P
'Ηΐ)98·ΐΐ '(ZH8 I=f 'P Ήΐ)Ζ9"8 '(s 'ΗΙ)£Ζ'8 '(ω 'HS)26"Z-98"Z '(ZHS'Z 'S"T=f P 'Ηΐ) 98 · ΐΐ' (ZH8 I = f 'P Ήΐ) Ζ9 "8' ( s 'ΗΙ) £ Ζ'8' (ω 'HS) 26" Z-98 "Z'(ZHS'Z'S' T = f P
'HT)9S"Z '(ZHS'Z
Figure imgf000154_0005
'； 'HT)08"S 'HT) 9S "Z'(ZHS'Z
Figure imgf000154_0005
';' HT) 08 "S
'(ΖΗ8· =1" 'p 'm)SL-f '(s Ήε)εε '(s Ήε)οε 9 :(9p— oswa) N— Ht °%S9 ? Φ '(ΖΗ8 · = 1 "' p 'm) SL-f' ( s Ήε) εε '( s Ήε) οε 9 :( 9 p— oswa) N— H t °% S9? Φ
'P 'HT)0Z"8 '(s Ήΐ)3ζ·8
Figure imgf000154_0006
'P' HT) 0Z "8 '(s Ήΐ) 3ζ8
Figure imgf000154_0006
'(s 'HI) 8'S '(s Ή 08· '(s 'HS)SS 9 :( OSWa) 顺— HT °%06 ¾T '( s ' HI) 8'S' (s Ή 08 · '( s ' HS) SS 9 :( OSWa) 顺 — H T °% 06 ¾T
•(ZH8 I=f• (ZH8 I = f
'P 'Ηΐ)ΐ6·ΐΐ '^ΗΖτΐ=ί 'P ΉΪ)0Γ8 '(s 'Ηΐ) 8 '(ΖΗ ·8 Τΐ=Γ 'PP 'H2)20"8 '(ω 'P' Ηΐ) ΐ6ΐΐ '^ ΗΖτΐ = ί' P ΉΪ) 0Γ8 '( s ' Ηΐ) 8 '(ΖΗ · 8 Τΐ = Γ' PP 'H2) 20''8' (ω
'HS)S2"Z-06"Z '(ZHS" 'S"T=f '^P 'HT)9S"Z '(ZHS" 'S"T=f '^P Ήΐ)8^"Ζ '(ΖΗΐ·8=ί"  'HS) S2 "Z-06" Z' (ZHS "'S" T = f' ^ P 'HT) 9S "Z' (ZHS" 'S "T = f' ^ P Ήΐ) 8 ^" Ζ '( ΖΗΐ · 8 = ί "
' 'HZ)IVL
Figure imgf000154_0007
'P 'HZ ' '' HZ) IVL
Figure imgf000154_0007
'P' HZ '
'(zHS"Z=f 'b lWZ) VZ '(zHS" =f 'HS)0S"T 9 :(9p— OSWa) 顺— HT °%ZW^ '(zHS "Z = f' b l WZ) VZ '(zHS" = f' HS) 0S "T 9 :( 9 p— OSWa) 顺 — H T °% ZW ^
661各粱呦 :66ΐ •(ZH8 I=f 'P 'HI)ZS ΐ '(ZH8 I=f  661 Each beam: 66ΐ (ZH8 I = f 'P' HI) ZS ΐ '(ZH8 I = f
P 'HI)W8 '(s 'HI)SS'8 '(ω 'HS)00"8-26"Z '(ω 'H^)09"Z-9^"Z '(zHS" =f Ήΐ)62"Ζ
Figure imgf000154_0008
391- S081760/S00Z OAV •(s 'Ηΐ) 6 '(^ 'HS)8S" -2S- '(s Ή 'S 9 :(
Figure imgf000155_0001
P 'HI) W8' (s 'HI) SS'8' (ω 'HS) 00 "8-26"Z' (ω 'H ^) 09 "Z-9 ^"Z' (zHS "= f Ήΐ) 62 "Ζ
Figure imgf000154_0008
391- S081760 / S00Z OAV • ( s ' Ηΐ) 6 '(^' HS) 8S "-2S- '(s Ή' S 9 :(
Figure imgf000155_0001
、れ
Figure imgf000155_0002
(ζ),
Figure imgf000155_0002
(ζ)
•(ω 'Η3 · -6Γ '(s Ήΐ)00·9 '(s 'Η2)6Γ3 9 :(
Figure imgf000155_0003
• (ω 'Η3 · -6Γ' (s Ήΐ) 00 · 9 '( s ' Η2) 6Γ3 9 :(
Figure imgf000155_0003
ベ - s - /— ½。;m、 ¾^- s' ^ ci / fH- ε- べ:^- ΐ (ΐ)  Be-s-/ ——. ; m, ¾ ^-s' ^ ci / fH- ε- base: ^-ΐ (ΐ)
80S各粱呦 -SOZ 80S each siang 呦 -SOZ
•(sjq 'Ηΐ)Ζ6 ΐ '(s Ήΐ)2ΐ ΐ '(s 'Ηΐ)06·8 '(ω 'HS)Z0"8-S6"Z '(ω 'HZ^L-Z L '(ω 'm)WL-6VL '(ω 'm L-LZ-L 9 :( P-OS a)H N-HT °%ζε ¾ί
Figure imgf000155_0004
• (sjq 'Ηΐ) Ζ6 ΐ' ( s Ήΐ) 2ΐ ΐ '( s ' Ηΐ) 06 · 8 '(ω' HS) Z0 "8-S6" Z '(ω' HZ ^ LZ L '(ω' m ) WL-6VL '(ω' m L-LZ-L 9 :( P-OS a) H NH T °% ζε ¾ί
Figure imgf000155_0004
'Ρ Ήΐ)03·Π '(ΖΗ8 ΐ=ί" 'Ρ Ήΐ)0Ζ·8 '^ΗΥ8=ί 'Ρ 'H2)88"Z '(ω 'H2)98"Z-28"Z
Figure imgf000155_0005
'ΡΡ 'Ηΐ) ·Ζ '(ZHS" Τΐ=Γ ' Ρ 'Ηΐ)6ε· '(ZHS- Τΐ=Γ '； Ρ 'Ηΐ)ΐε· '(zW8=f 'Ρ 'HZ)IZ-L '(ΖΗΓ8=Γ 'Ρ 'HT)S6"S '(ΖΗΖ·Ζ=1" 'Ρ Ήΐ)ΐ3·3 'Η9)ΐε 9 :( P-OS a)H N-HT °%86 ¾ί 'Ρ Ήΐ) 03ΠΠ' (ΖΗ8 ΐ = ί "'Ρ Ήΐ) 0Ζ8' ^ ΗΥ8 = ί 'Ρ' H2) 88" Z '(ω' H2) 98 "Z-28" Z
Figure imgf000155_0005
'ΡΡ' Ηΐ) · Ζ '(ZHS) Τΐ = Γ' Ρ 'Ηΐ) 6ε ·' (ZHS- Τΐ = Γ ';Ρ' Ηΐ) ΐε '' (zW8 = f 'Ρ' HZ) IZ-L ' ( Ζ ΗΓ8 = Γ 'Ρ' HT) S6 "S '(ΖΗΖΖΗΖ = 1"' Ρ Ρ) ΐ3.3 'Η9) ΐε 9 :( P-OS a) H NH T °% 86 ¾ί
90S各粱呦 -90Z  90S each 呦 -90Z
'P Ήΐ)93·Π '^ΗΖτΐ=ί 'Ρ 'ΗΙ) 8 '(ΖΗ8·8 '0·ΐ=ί" 'ΡΡ 'ΗΖ)Ζ0'8 '(s 'Ηΐ)98·
Figure imgf000155_0006
'Ρ Ήΐ)09"Ζ '(ΖΗε·8
Figure imgf000155_0007
'P Ήΐ) 93Π' ^ ΗΖτΐ = ί 'Ρ' ΗΙ) 8 '(ΖΗ8 · 8' 0ΐ0 = ί "'ΡΡ' ΗΖ) Ζ0'8 '( s ' Ηΐ) 98
Figure imgf000155_0006
'Ρ Ήΐ) 09 "Ζ' (ΖΗε · 8
Figure imgf000155_0007
ΓΖ '(ΖΗΐ·8=ί" 'Ρ 'HT)S6"S '(ΖΗΖ·Ζ=ί" 'Ρ 'HI)SS'S
Figure imgf000155_0008
'； 'HS)82"T 9 :( P-OS a)H N-HT °%8Z ¾ί ΓΖ '(ΖΗΐ · 8 = ί "' Ρ 'HT) S6"S' (ΖΗΖ · Ζ = ί "'Ρ' HI) SS'S
Figure imgf000155_0008
';' HS) 82 "T 9 :( P-OS a) H NH T °% 8Z ¾ί
SOS各粱呦 - oz  SOS each 呦-oz
'Ηΐ)εε·ΐΐ '(ΖΗ8
Figure imgf000155_0009
'Ηΐ) εεΐΐ ΐΐ' (ΖΗ8
Figure imgf000155_0009
Figure imgf000155_0010
'P 'HT)8Z"Z '(ΖΗΐ·8=ί" 'P 'ΗΙ)ΖίΊ '(ω 'H2)S9"Z-8S"Z
Figure imgf000155_0010
'P' HT) 8Z "Z '(ΖΗΐ · 8 = ί"' P 'ΗΙ) ΖίΊ' (ω 'H2) S9 "Z-8S" Z
'P 'HZ)WL '(zHS'Z=f '； 'Ηΐ)9ε· 'HS)0S"2 9 :( P-OS a)H N-HT °%ΐ6 ? φ
Figure imgf000155_0011
891- S081760/S00Z OAV '9·ΐ=ί" 'ΡΡ 'H\)WL '(ΖΗΟ"Ζ Τΐ=Γ '^Ρ 'HT)OS"Z '(s 'HZ)WZ 9 '■( P-OS a)H N-HT 'P' HZ) WL '(zHS'Z = f';'Ηΐ) 9ε ·' HS) 0S "2 9 :( P-OS a) H NH T °% ΐ6? Φ
Figure imgf000155_0011
891- S081760 / S00Z OAV '9 · ΐ = ί "' ΡΡ 'H \) WL'(ΖΗΟ" Ζ Τΐ = Γ '^ Ρ' HT) OS "Z '(s' HZ) WZ 9' ■ (P-OS a) H NH T
、 ¾ louiu¾W)6'0 'S0S'0)ベ - S - /— ^^c^ ^- S' ^ ci / fH- S- ^
Figure imgf000156_0001
^ 一4 -1-,^, ¾ louiu¾W) 6'0 ' S 0S'0) B-S-/-^^ c ^ ^-S' ^ ci / fH- S- ^
Figure imgf000156_0001
^ 1-4-1, ^
^ ^wz^ m ) ^ ^ wz ^ m)
•(s Ήΐ)εε· '(s Ήε) 8·ε '(s 'm)fvz '(s Ήε)6ε·ε 9 :(9p— oswa) 顺— HT • ( s Ήΐ) εε · '(s Ήε) 8 · ε' ( s 'm) fvz' ( s Ήε) 6ε · ε 9 :( 9 p— oswa) 顺 — H T
Figure imgf000156_0002
Figure imgf000156_0002
Figure imgf000156_0003
、 ;^、- S' ^ ci / fH- S- ^ - ΐ
Figure imgf000156_0003
,; ^, -S '^ ci / fH-S-^-ΐ
( θ聊^!—)ベ - 一 ^^c^ ^- s' ^ ci / fH- ε- ^ - ΐ-ベ ^ ,^ ^ d (ΐ)
Figure imgf000156_0004
(θlia ^! —) ve-one ^^ c ^ ^-s' ^ ci / fH- ε- ^-ΐ-be ^, ^ ^ d (ΐ)
Figure imgf000156_0004
•(sjq 'Ηΐ)66 ΐ '(s 'Ηΐ)ε6·8 '(ω 'Η9)εΐ·8- '(ZW8 Ό"Ζ
Figure imgf000156_0005
'HT)S9"Z '(ΖΗΟ·8=1" ' 'H2)2S"Z '(zHS" =f 'HT)TS"Z 9 :(9ρ—〇SWa) 顺— HT °%89 ¾ί • (sjq 'Ηΐ) 66 ΐ' ( s 'Ηΐ) ε6 · 8' (ω 'Η9) εΐ8-' (ZW8 Ό "Ζ
Figure imgf000156_0005
'HT) S9 "Z' (ΖΗΟ8 = 1"'' H2) 2S "Z '(zHS" = f' HT) TS "Z 9 :( 9 ρ—〇SWa) 顺 — H T °% 89 ¾ί
•(ZH6 ΐ=ί" 'Ρ Ήΐ)3ε·2ΐ '(ζΗ6·ΐΐ=ί" 'Ρ 'Ηΐ)9Ζ·8 'WL=[ 'Ρ 'H2)20"8 '(s 'Ηΐ)98· • (ZH6 ΐ = ί "'Ρ Ήΐ) 3ε2ΐ' (ζΗ6ΐΐ = ί"'Ρ' Ηΐ) 9Ζ8 'WL = [' Ρ 'H2) 20 "8' ( s ' Ηΐ) 98
'(ΖΗ6·9=ί" 'Ρ 'HT)S8"Z
Figure imgf000156_0006
'Ρ 'HT)9S"Z '(ω
Figure imgf000156_0007
ΉΙ)Ζ£Ί '(ΖΗ6·9=ί" ' Ήΐ)ΖΓΖ '(ΖΗ6 · 9 = ί "' Ρ 'HT) S8" Z
Figure imgf000156_0006
'Ρ' HT) 9S "Z '(ω
Figure imgf000156_0007
ΉΙ) Ζ £ Ί '(ΖΗ6 · 9 = ί "' Ήΐ) ΖΓΖ
'ρ Ήΐ)ε6·3 '(zH0" =f 'ρ Ήΐ)ε3·3 '(s ' )fvi 9 :(9ρ— oswa) 顺— Ητ °%ζε ¾τ 'ρ Ήΐ) ε6 3' (zH0) = f 'ρ Ήΐ) ε3 3'(s') fvi 9 :( 9 ρ— oswa) 顺 — Η τ °% ζε ¾τ
60S各粱呦 -60Z •(s 'HT)28"8 '(ΖΗΓ8=Γ 'Ρ Ήΐ)32·8 '^ΗΖ'6=ί 'Ρ 'Ηΐ)90·8
Figure imgf000156_0008
'(ω
Figure imgf000156_0009
顺— Ητ °%6 ¾ί 60S each beam -60Z • ( s 'HT) 28 "8' ( Ζ ΗΓ8 = Γ 'Ρ Ήΐ) 32 · 8' ^ ΗΖ'6 = ί 'Ρ' Ηΐ) 90 · 8
Figure imgf000156_0008
'(ω
Figure imgf000156_0009
顺 — Η τ °% 6 ¾ί
80S各粱呦 (ε)
Figure imgf000156_0010
9V S081760/S00Z OAV
Figure imgf000157_0001
) 80S each 呦 (ε)
Figure imgf000156_0010
9V S081760 / S00Z OAV
Figure imgf000157_0001
)
•(s 'Ηΐ)8·εΐ '(s Ήΐ)3 ΐ • ( s 'Ηΐ) 8 · εΐ' ( s Ήΐ) 3 ΐ
'HT)S8"Z '(ω 'HS)SZ"Z-09"Z
Figure imgf000157_0002
'HT)ZS"Z '(ω 'ΗΖ)Ζ£' L-OZ' L 'HT) S8 "Z' (ω 'HS) SZ" Z-09 "Z
Figure imgf000157_0002
'HT) ZS "Z' (ω 'ΗΖ) Ζ £' L-OZ 'L
'(zHS"Z=f 'P 'HT)98"S '(zHS" =f 'P 'HI)8 'S 9 :( OSW I) 顺— HT °%S6 ？ φ '(zHS "Z = f' P 'HT) 98"S' (zHS "= f 'P' HI) 8 'S 9 :( OSW I) 顺 — H T °% S6?
•(ZH6 i=f 'p Ήΐ)ε6·π mvzi=i 'p ' ·8• (ZH6 i = f 'p Ήΐ) ε6π mvzi = i' p '8
'(ZHS'8=f 'P 'HWS '(ΖΗΐ·6=ί" 'P Ήΐ)66"Ζ
Figure imgf000157_0003
'P Ήΐ)68"Ζ '(ΖΗΐ·6=ί" 'P '(ZHS'8 = f' P 'HWS' (ΖΗΐ · 6 = ί "'P Ήΐ) 66" Ζ
Figure imgf000157_0003
'P Ήΐ) 68 "Ζ' (ΖΗΐ · 6 = ί"'P
'Ηΐ)ΐ9· '( 'ε·ΐ=ί" ' ρ Ήΐ)ε3· '(ΖΗΓΖ Τΐ=Γ '^Ρ Ήΐ)9 '(ω 'H2)9S" -TS- '(ω 'HS)82" -S2- '(s 'Η 88· '(s Ή Ζ'Ζ 9 :(9ρ— oswa) Ν— Ητ °%S6 ? ί)ί 'Ηΐ) ΐ9'('εΐ = ί "' ρ Ήΐ) ε3 '(ΖΗΓΖ Τΐ = Γ' ^ Ρ Ήΐ) 9 '(ω' H2) 9S" -TS- '(ω' HS) 82 "-S2- '(s' Η 88 ·' ( s Ή Ζ '' 9 :( 9 ρ— oswa) Ν— Η τ °% S6? Ί)
uz^ ^ (e)uz ^ ^ (e)
•(s Ήΐ)3 ·6 '( q Ήΐ)ζε·8 '(s Ήε) ε 9 :(• (s Ήΐ) 3 · 6 '(q Ήΐ) ζε · 8' ( s Ήε) ε 9 :(
DaD)H N-HT °%os ¾τ
Figure imgf000157_0004
DaD) H NH T °% os ¾τ
Figure imgf000157_0004
Λ Λ
- /— ^^c^ ^- S' ^ ci / fH- ε- - S- ^ - ΐ (f)  -/ — ^^ c ^ ^-S '^ ci / fH- ε--S- ^-ΐ (f)
。 ½ ェ T^V ¾ ^^ 一《呦^ ^本  .ェ T T ^ V ¾ ^^ One << 呦 ^ ^ book
。 %
Figure imgf000157_0005
、 /—, ェ、灞 n (. %
Figure imgf000157_0005
, / —, 灞, 灞 n (
。 つ
Figure imgf000157_0006
'§υι99ΐ)ベ - S - /— ½ . One
Figure imgf000157_0006
' §Υι 99ΐ) BE-S-/ — ½
ci、 ¾^- s' ^ ci / (H- ε- ^ - ΐ、 ¾ΐου™ΐ
Figure imgf000157_0007
Figure imgf000157_0008
ci, ¾ ^-s' ^ ci / (H- ε- ^-ΐ, ¾ΐ ου ™ ΐ
Figure imgf000157_0007
Figure imgf000157_0008
。 ί^= ェ Τコ Κα¾¾ ^^ 一) ¾^ ¾止《呦^： ^本 Kwo] . ί ^ = Τ Τ Κα¾¾ ^^ one) ¾ ^ ¾stop << 呦 ^: ^ this Kwo]
"(s-i 'HDZ Zl '(s Ήΐ)29 ΐ '(s 'Ηΐ)ΖΖ·8 '(ΖΗ ·8=1" 'Ρ 'Ηΐ) 8
Figure imgf000157_0009
'Ρ 'HT)S0"8 '(ΖΗΖ·Ζ=ί" 'Ρ Ήΐ)ΐ6"Ζ 'Ρ Ήΐ)09"Ζ '(ΖΗΐ·8 "(si 'HDZ Zl' ( s Ήΐ) 29 ΐ '( s ' Ηΐ) ΖΖ8' (ΖΗ · 8 = 1"'Ρ' Ηΐ) 8
Figure imgf000157_0009
'Ρ' HT) S0 "8 '(ΖΗΖ · Ζ = ί"' Ρ Ήΐ) ΐ6 "Ζ 'Ρ Ήΐ) 09"Ζ' (ΖΗΐ8
^9l7900/S00Zdf/X3d 9ΐ½Μ^ (ε)^ 9l7900 / S00Zdf / X3d 9ΐ½Μ ^ (ε)
•(s 'ΗΙ)£Ζ'6 '(zHS"8=f 'Ρ• (s' ΗΙ) £ Ζ'6 '(zHS "8 = f' Ρ
'Η ·8 'Ρ ΉΖ)£9Ί '(sjq 'Ηΐ)ΐ ·ε '(s 'HS)02"2 9 :(9ρ—〇SW I) 顺— Η 'Η · 8' Ρ ΉΖ) £ 9Ί '(sjq' Ηΐ) ΐ · ε '( s ' HS) 02 "2 9 :( 9 ρ—〇SW I) 顺 — Η
、 ^ -
Figure imgf000158_0001
, ^-
Figure imgf000158_0001
'Ρ 'Η 00·8 '(zH6=f 'Ρ 'Ηζ)8ΓΖ 'Ηΐ) 'S '(s '\ Ζ) 'Ζ 9 :(9ρ— OSWa) 顺— Η
Figure imgf000158_0002
(ΐ)
Figure imgf000158_0003
'Ρ' Η 00 · 8 '(zH6 = f' Ρ 'Ηζ) 8ΓΖ' Ηΐ) 'S' (s '\ Ζ)' Ζ 9 :( 9 ρ— OSWa) 顺 — Η
Figure imgf000158_0002
(ΐ)
Figure imgf000158_0003
'Ρ 'Ηΐ)98·8 '(s Ήΐ)32·8 '(ω 'HS)I0'8 '(ω 'Η Ο8· - ΟΓΖ '(ω 'Η ·Ζ- εε·Ζ '(s 'Ηΐ)ΐε·
Figure imgf000158_0004
' 'Η2)32· 'HS)SS 9 :( OSWd) Ν— Ητ °% 8 ¾ί 'Ρ 'Ηΐ)0 ΐ'Ρ' Ηΐ) 98 · 8 '( s Ήΐ) 32 · 8' (ω 'HS) I0'8' (ω 'Η Ο8 ·-ΟΓΖ' (ω 'Η · Ζ- εεΖΖ' ( s ' Ηΐ ) ΐε
Figure imgf000158_0004
'' Η2) 32 '' HS) SS 9 :( OSWd) Ν— Η τ °% 8 ¾ί 'Ρ' Ηΐ) 0 ΐ
'(s 'Ρ 'HT)S0"8 '(ω 'H2)S
Figure imgf000158_0005
S'Z '( s 'Ρ' HT) S0 "8 '(ω' H2) S
Figure imgf000158_0005
S'Z
' 'HDSVL '(zH6=f ' 'H2)92"Z '(s Ήε)εε 9 :(9P— OS^a) 顺— HT °%S8 ? ill
Figure imgf000158_0006
'' HDSVL '( z H6 = f''H2) 92 "Z' (s Ήε) εε 9 :( 9 P— OS ^ a) 顺 — H T °% S8? Ill
Figure imgf000158_0006
•(s • ( s
:Hi)es"6 '(ω 'H2)o8" -o " '(zH6=f ' 'H2)ss" '(s Ήε)εε 9 :(9p— oswa) 顺— H : Hi) es "6 '(ω' H2) o8" -o "'(zH6 = f''H2)ss"' (s Ήε) εε 9 :( 9 p— oswa) 顺 — H
、れ
Figure imgf000158_0007
(ζ) ,
Figure imgf000158_0007
(ζ)
.(III . (III
'H2)08"Z-09"Z '(ω 'H2)02"Z-S0" 'HI)WS '(s Ήε)^Γ2 9：( P-OS^a)H N-H 'H2) 08 "Z-09" Z' (ω 'H2) 02 "Z-S0"' HI) WS '(s Ήε) ^ Γ29: (P-OS ^ a) H N-H
T °%06 ¾τ ^m^ ^mm^ ^ mん ^^ 一
Figure imgf000158_0008
991- S081760/S00Z OAV
Figure imgf000159_0001
 T °% 06 ¾τ ^ m ^ ^ mm ^ ^ m ^^ one
Figure imgf000158_0008
991- S081760 / S00Z OAV
Figure imgf000159_0001
'Ρ 'Ηΐ)88·8 '(s 'HT)92"8 '(ω 'H¾06"Z-28"Z '(ω 'H2)08"Z-0Z"Z '(ω 'HS)OS"Z-SS"Z '(s Ήΐ)2ε· '(ω Ήΐ)0ΓΖ-06·9 '(s 'HS)9S 9 :(9Ρ— OSW I) 顺— Ητ °%09 ¾Τ 'Ρ 'Ηΐ)0 ΐ'Ρ' Ηΐ) 88 · 8 '(s' HT) 92 "8 '(ω'H¾06" Z-28 "Z '(ω' H2) 08" Z-0Z "Z '(ω' HS) OS" Z -SS "Z '( s Ήΐ) 2ε ·' (ω Ήΐ) 0ΓΖ-06 · 9 '( s ' HS) 9S 9 :( 9 Ρ— OSW I) 顺 — Η τ °% 09 ¾Τ 'Ρ' Ηΐ) 0 ΐ
'(sjq
Figure imgf000159_0002
'Ρ 'Ηΐ)εθ·8 '(ω 'HS)S6"Z-S8"Z
Figure imgf000159_0003
L-QV L '(ζΗε 'g-8=f 'ρ 'Ηΐ)96·9 '(s 'HZ) Z 9 :( OSWa) 顺— Ητ °%SI ¾ί
Figure imgf000159_0004
'(sjq
Figure imgf000159_0002
'Ρ' Ηΐ) εθ · 8 '(ω' HS) S6 "Z-S8" Z
Figure imgf000159_0003
L-QV L '(ζ Ηε ' g-8 = f 'ρ' Ηΐ) 969 '( s ' HZ) Z 9 :( OSWa) 顺 — Η τ °% SI ¾ί
Figure imgf000159_0004
•(s 'HT)SS"6 '(ω 'H2)0Z"Z-09"Z '(ui 'HI)SS'Z— 0 · '(ZHS 'S"8=f 'P Ήΐ)90"Ζ '(s 'HS)SS 9 :(9p—〇SWa) N— H
Figure imgf000159_0005
(ζ) • (s 'HT) SS "6' (ω 'H2) 0Z" Z-09 "Z' (ui 'HI) SS'Z— 0 ·' (ZHS 'S" 8 = f' P Ήΐ) 90 "Ζ '(s' HS) SS 9 :( 9 p—〇SWa) N— H
Figure imgf000159_0005
(ζ)
.(UI . (UI
'HZM-L-OVL '(ω 'HS)0rZ-00"Z '(s Ήΐ)^·3 '(s 'HZ) Z 9 :( P-OS a)H N-H 'HZM-L-OVL' (ω 'HS) 0rZ-00 "Z' (s Ήΐ) ^ 3 '(s' HZ) Z 9 : (P-OS a) H NH
τ °%86 ¾ί °^ ¾^^ ®^C)T^)¾^ )#^^ん ^^ 一
Figure imgf000159_0006
a) τ °% 86 ¾ί ° ^ ¾ ^^ ® ^ C) T ^) ¾ ^) # ^^
Figure imgf000159_0006
a)
•(zHST=f 'P 'Ηΐ) ·ΐΐ '(zHST=f 'P Ήΐ)2 ·8 '(ω 'H2)20"8 '(ω • ( z HST = f 'P' Ηΐ) · ΐΐ '(zHST = f' P Ήΐ) 2 · 8 '(ω' H2) 20 "8 '(ω
'HT)0S"
Figure imgf000159_0007
'HT) 0S "
Figure imgf000159_0007
'P 'HT)26"S '(zH =f 'P 'HI)IS'S '(s Ήε)ΐε 9 :( OSWa) 顺— HT °%S ¾T
Figure imgf000159_0008
'P' HT) 26 "S '(zH = f' P 'HI) IS'S' (s Ήε) ΐε 9 :( OSWa) 顺 — H T °% S ¾T
Figure imgf000159_0008
Figure imgf000159_0009
'P 'Ηΐ)0 ΐ '(s
Figure imgf000159_0009
'P' Ηΐ) 0 ΐ '( s
Ηΐ)^ ΐ '(zHS"ST=f 'P 'HT)S8"8 '(zHS"8=f 'P 'H2)Z2"8 '(zH8=f 'P 'HT)S2"8 '(zH6=f 'P 'Ηΐ)εθ·8
Figure imgf000159_0010
Ηΐ) ^ ΐ '(zHS "ST = f' P 'HT) S8"8' (zHS "8 = f 'P' H2) Z2" 8 '(zH8 = f' P 'HT) S2 "8' (zH6 = f 'P' Ηΐ) εθ8
Figure imgf000159_0010
'HT)ZS"Z '(zH8=f ' 'Ηΐ)6 · '(s 'HS)SS 9 :(9p— OSWa) 顺— HT °%8S ? φ t9t900 OZdr/lDd 19V S081760/S00Z OAV
Figure imgf000160_0001
'HS)9S"2 9'HT) ZS "Z' (zH8 = f '' Ηΐ) 6 ''s' HS) SS 9 :( 9 p— OSWa) 顺 — H T °% 8S?
Figure imgf000160_0001
'HS) 9S "2 9
:(ειつ αつ) WN- ΗΤ °%6 ¾τ
Figure imgf000160_0002
/ / - /—/^ c^ - s' ^ - s- ^ - ε- ( / ェ cm^ - ε)- ΐ (ζ):( ε ι つ α) WN- Η Τ °% 6 ¾τ
Figure imgf000160_0002
/ /-/ — / ^ C ^-s' ^-s- ^-ε- (/ cm cm ^-ε)-ΐ (ζ)
•(ZHS '6=f 'PP Ήΐ)Ζ0"8 'WZ '6=f 'PP 'HT)28"Z '(zH6=f 'P ' )ZVL '(s 'HZ) VZ '(s 'HZ)WZ 9 :( DaD)H N-HT °%98 ¾ί ^Μ^^ΜΜ^^^ Μ^ん ^^ 一 • (ZHS '6 = f' PP Ήΐ) Ζ0 "8 'WZ' 6 = f 'PP' HT) 28" Z '(zH6 = f' P ') ZVL' ( s ' HZ) VZ '( s ' HZ ) WZ 9 :( DaD) H NH T °% 98 ¾ί ^ Μ ^^ ΜΜ ^^^ Μ ^ ん ^^
ベ - s - /— ½。;m、 ¾^- s' ^ - ε -( / -ェ crn^d's)- ΐ (ΐ) zzz^ ^ '-zzz  Be-s-/ ——. ; m, ¾ ^-s '^-ε-(/ -e crn ^ d's)-ΐ (ΐ) zzz ^ ^' -zzz
•(z服 =f• ( z clothes = f
'P 'Ηΐ)96·ΐΐ '(s 'HDLVOl '{ =[ 'P 'Ηΐ)98·8 '(zH8=f 'P Ήΐ)εζ·8 '(s Ήΐ)0Γ8 '(s 'Ηΐ)60·8 '(zH6=f 'P 'Ηΐ)εθ·8 '(zHS'8=f 'P 'HT)T6"Z '(zH6=f 'P 'H\)WL '(ω 'HZ)^L-WL '(s Ήΐ)3ε· '(s 'HZ) Z 9 :( P-OS a)H N-HT °% 8 ¾T
Figure imgf000160_0003
'P' Ηΐ) 96ΐΐ '( s ' HDLVOl '{= [' P 'Ηΐ) 988' ( z H8 = f 'P Ήΐ) εζ8' ( s Ήΐ) 0Γ8 '( s ' Ηΐ) 60 · 8 '(z H6 = f' P 'Ηΐ) εθ · 8'(zHS'8 = f 'P' HT) T6 "Z '(zH6 = f' P 'H \) WL' (ω 'HZ) ^ L-WL '(s Ήΐ) 3ε''(s' HZ) Z 9 :( P-OS a) H NH T °% 8 ¾T
Figure imgf000160_0003
•(s Ήΐ)9Γ6 '(s 'WDWl '(s 'HT)S8"Z '(s 'uDZZ'L '(^ 'Ηΐ)06· '(s 'HS)9S"2 9 :(
Figure imgf000160_0004
• ( s Ήΐ) 9Γ6 '( s ' WDWl '( s ' HT) S8 "Z '(s'uDZZ'L'(^' Ηΐ) 06 · '( s ' HS) 9S" 2 9 :(
Figure imgf000160_0004
、れ ,
/ / - /—/^ c^ - S' ^ - S- ^ - ε- ( / ェ cm^ - S'S)- ΐ (ζ) / /-/ — / ^ C ^-S '^-S- ^-ε- (/ cm cm ^-S'S)-ΐ (ζ)
•(ω 'H2)06"Z-S8"Z '(s Ήΐ)3Γ 'HZ)9VZ '(s 'HZ)WZ 9 :(• (ω 'H2) 06 "Z-S8"Z' (s Ήΐ) 3Γ 'HZ) 9VZ' ( s ' HZ) WZ 9 :(
DaD)H N-HT °%08 ¾ί
Figure imgf000160_0005
一 DaD) H NH T °% 08 ¾ί
Figure imgf000160_0005
one
ベ - s - /— ½。;m、 ¾^- s' ^ - ε -( / -ェ cm^^- s's)- ΐ (ΐ)
Figure imgf000160_0006
Be-s-/ ——. ; m, ¾ ^-s' ^-ε-(/ -e cm ^^-s's)-ΐ (ΐ)
Figure imgf000160_0006
•(zHsi=f 'p Ήΐ)^π '(ζΗετ=Γ 'p 'ΗΪ) ·8• ( z Hsi = f 'p Ήΐ) ^ π' ( ζ Ηετ = Γ 'p' ΗΪ) 8
'(ω ΓΖ '(ω 'HZ)Z9'L-WL '(ω 'HI)OS'Z— ε ·'(ω ΓΖ' (ω 'HZ) Z9'L-WL' (ω 'HI) OS'Z— ε ·
Figure imgf000160_0007
'Ηΐ)ΐε· '(ω 'Ηΐ)Οΐ· - 06·9
Figure imgf000160_0007
'Ηΐ) ΐε' (ω 'Ηΐ) Οΐ-069
'Ρ Ήϊ)Ζ6' '(zHS" =f 'Ρ 'HT)2S"e '(s 'HS)SS"2 9 :(9ρ— OSWa) 顺— Ητ °%SS ¾ί
Figure imgf000160_0008
891- S081760/S00Z OAV (3)化合物番号 222 'Ρ Ήϊ) Ζ6''(zHS"=f' Ρ 'HT) 2S"e'(s' HS) SS "2 9 :( 9 ρ— OSWa) 顺 — Η τ °% SS ¾ί
Figure imgf000160_0008
891- S081760 / S00Z OAV (3) Compound No. 222
収率 10%。 'H-NMRCDMSO-d ): δ 2.34(3H, s), 7.46-7.59(2Η, m), 7.64(1Η, d,  Yield 10%. 'H-NMRCDMSO-d): δ 2.34 (3H, s), 7.46-7.59 (2Η, m), 7.64 (1Η, d,
6  6
J=8.5Hz), 7.69(1H, s), 7.91(1H, d, J=8Hz), 8.03(2H, dd, J=8.5, 2.5Hz), 8.23(1H, d, J=8Hz), 8.33(1H, d, J=2.5Hz), 8.95(1H, d, J=14Hz), 10.44(1H, s), 11.99(1H, s).  J = 8.5Hz), 7.69 (1H, s), 7.91 (1H, d, J = 8Hz), 8.03 (2H, dd, J = 8.5, 2.5Hz), 8.23 (1H, d, J = 8Hz), 8.33 (1H, d, J = 2.5Hz), 8.95 (1H, d, J = 14Hz), 10.44 (1H, s), 11.99 (1H, s).
[0147] 例 223:化合物番号 223 [0147] Example 223: Compound number 223
収率 93%。 'H-NMRCDMSO-d ): δ 2.34(3Η, s), 5.52(1Η, d, J=8.2Hz), 6.00(1Η, d,  Yield 93%. 'H-NMRCDMSO-d): δ 2.34 (3Η, s), 5.52 (1Η, d, J = 8.2Hz), 6.00 (1Η, d,
6  6
J=8.2Hz), 7.16(1H, t, J=7.4Hz), 7.35(1H, dt, J=1.4, 7.3Hz), 7.38— 7.45(3H, m), 7.62(1H, d, J=7.1Hz), 7.85(1H, d, J=6.6Hz), 7.99(2H, dd, J=1.2, 8.6Hz), 8.21(1H, s), 8.23(1H, s), 8.88(1H, d, J=12.4Hz), 11.83(1H, d, J=12.6Hz).  J = 8.2Hz), 7.16 (1H, t, J = 7.4Hz), 7.35 (1H, dt, J = 1.4, 7.3Hz), 7.38― 7.45 (3H, m), 7.62 (1H, d, J = 7.1 Hz), 7.85 (1H, d, J = 6.6Hz), 7.99 (2H, dd, J = 1.2, 8.6Hz), 8.21 (1H, s), 8.23 (1H, s), 8.88 (1H, d, J = 12.4Hz), 11.83 (1H, d, J = 12.6Hz).
例 224:化合物番号 224  Example 224: Compound number 224
収率 52%。 'H-NMRCDMSO-d ): δ 2.30(3Η, s), 2.70(2Η, t, J=6Hz), 3.10(2Η, t,  Yield 52%. 'H-NMRCDMSO-d): δ 2.30 (3Η, s), 2.70 (2Η, t, J = 6Hz), 3.10 (2Η, t,
6  6
J=6Hz), 7.14(1H, t, J=7.5Hz), 7.41(2H, t, J=7.5Hz), 7.63(1H, d, J=8.5Hz), 7.82(1H, dd, J=8.5, 2.5Hz), 7.93(1H, d, J=2.5Hz), 8.00(2H, d, J=7.5Hz), 8.68(1H, d, J=13Hz), 11.3(1H, d, J=13Hz).  J = 6Hz), 7.14 (1H, t, J = 7.5Hz), 7.41 (2H, t, J = 7.5Hz), 7.63 (1H, d, J = 8.5Hz), 7.82 (1H, dd, J = 8.5 , 2.5Hz), 7.93 (1H, d, J = 2.5Hz), 8.00 (2H, d, J = 7.5Hz), 8.68 (1H, d, J = 13Hz), 11.3 (1H, d, J = 13Hz) .
6-ァミノ- 1-インダノン：欧州特許出願公開第 0275131号明細書参照。  6-Amino-1-indanone: see EP-A-0275131.
例 225:化合物番号 225  Example 225: Compound number 225
収率 62%。 ^-NMRCDMSO-d ): δ 2.71(2H, t, J=6Hz), 3.12(2H, t, J=6Hz),  Yield 62%. ^ -NMRCDMSO-d): δ 2.71 (2H, t, J = 6Hz), 3.12 (2H, t, J = 6Hz),
6  6
7.28(1H, t, J=7.5Hz), 7.49(2H, t, J=7.5Hz), 7.67(1H, d, J=8.5Hz), 7.91(1H, dd, J=8.5, 1.5Hz), 7.94(1H, d, J=1.5Hz), 7.98(2H, d, J=7.5Hz), 8.75(1H, brs), 12.1(1H, brs).  7.28 (1H, t, J = 7.5Hz), 7.49 (2H, t, J = 7.5Hz), 7.67 (1H, d, J = 8.5Hz), 7.91 (1H, dd, J = 8.5, 1.5Hz), 7.94 (1H, d, J = 1.5Hz), 7.98 (2H, d, J = 7.5Hz), 8.75 (1H, brs), 12.1 (1H, brs).
[0148] 例 226:化合物番号 226  [0148] Example 226: Compound number 226
(1) 1-ヒドロキシ- 6-二トロインダン (一般合成法 ξ )  (1) 1-hydroxy-6-ditroindane (general synthesis method ξ)
6-ニトロ- 1-インダノン (0.33g, 1.863mmol)のメタノール (3ml)溶液に、水素化ホウ素ナ トリウム (0.07g, 1.863mmol)を加え、室温で 30分間攪拌した。溶媒を減圧留去して得ら れた残渣に水を加え、酢酸ェチルで抽出した。酢酸ェチル層を飽和食塩水で洗浄し 、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去して、標題化合物の淡褐色結晶 (0.30g, 90%)を得た。  To a solution of 6-nitro-1-indanone (0.33 g, 1.863 mmol) in methanol (3 ml) was added sodium borohydride (0.07 g, 1.863 mmol), and the mixture was stirred at room temperature for 30 minutes. Water was added to the residue obtained by evaporating the solvent under reduced pressure, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain pale brown crystals of the title compound (0.30 g, 90%).
^-NMRCCDCl ): δ 2.00-2.12(1H, m), 2.17(1H, brs), 2.55-2.70(1H, m), •(sjq 'Ηΐ)00·6 '(ω 'H^)S2- -00" '(sjq 'HT)S9"S '(s 'HWZ '(s 'HS)60 9 :(
Figure imgf000162_0001
^ -NMRCCDCl): δ 2.00-2.12 (1H, m), 2.17 (1H, brs), 2.55-2.70 (1H, m), • (sjq 'Ηΐ) 00 · 6' (ω 'H ^) S2- -00 "' (sjq 'HT) S9"S' ( s ' HWZ '( s ' HS) 60 9 :(
Figure imgf000162_0001
、 ,
^ / - /— ^^c^ ^- s' ^P - s -( / ェ ^ - - ΐ- ^ - ε (ζ)^ /-/ — ^^ c ^ ^-s' ^ P-s-(/ ^ ^--ΐ- ^-ε (ζ)
"(ω 'H^)OS"Z-OS"Z '(s 'HT)99"S '(s Ήε)8Γ2 '(s Ήε)2Γ2 9：( P-OS^a)H N-H "(ω 'H ^) OS" Z-OS "Z'(s' HT) 99" S '(s Ήε) 8Γ2' ( s Ήε) 2Γ2 9 :( P-OS ^ a) H NH
T °%ooi ¾ί °^ ¾<¾?^®^ τ^)¾^ )#^^ん ^^ 一 T °% ooi ¾ί ° ^ ¾ <¾? ^ ® ^ τ ^) ¾ ^) # ^^ n ^^
Figure imgf000162_0002
(ΐ)
Figure imgf000162_0002
(ΐ)
'Ρ 'Ηΐ) 9·8
Figure imgf000162_0003
'Ρ' Ηΐ) 9
Figure imgf000162_0003
'(ω 'Ηΐ 'S- OO'S '(ω 'Ηΐ)0Γε— OS'S '(ω 'Ηΐ)00·ε- 8 '(ω 'Ηΐ)08 - 9  '(ω' Ηΐ 'S- OO'S' (ω 'Ηΐ) 0Γε— OS'S' (ω 'Ηΐ) 00 · ε-8' (ω 'Ηΐ) 08-9
'(ω Ήΐ)ε - οε '(^ Ήΐ)06·ΐ- οζ·ΐ 9 :(9ρ- oswa) Ν- Ητ °% 8 ¾ί
Figure imgf000162_0004
'(ω Ήΐ) ε-οε' (^ Ήΐ) 06ΐ ΐ- οζΐ 9 :( 9 ρ- oswa) Ν- Η τ °% 8 ¾ί
Figure imgf000162_0004
Figure imgf000162_0005
'Ρ 'HT)SS"Z '(ω 'HZWL-WL Ήΐ)εΓΖ '(ΖΗ9=1" 'Ρ 'HI) TS '(zH9=f 'b 'HT)90"S '(ω 'Ηΐ)00·ε— S8 '(ω 'Ηΐ)08 — S9 '(ω 'HI)S — '(s 'm)6Z'Z '(ω 'Ηΐ)06·ΐ— 0Ζ·ΐ 9 :( OSWd) Ν— Ητ °%ΐΖ ¾ί
Figure imgf000162_0005
'Ρ' HT) SS "Z '(ω' HZWL-WL Ήΐ) εΓΖ '(ΖΗ9 = 1"' Ρ 'HI) TS' (zH9 = f ' b ' HT) 90 "S '(ω' Ηΐ) 00 · Ε— S8 '(ω' Ηΐ) 08 — S9 '(ω' HI) S — '( s ' m) 6Z'Z '(ω' Ηΐ) 06 · ΐ— 0Ζ · ΐ 9 :( OSWd) Ν— Τ τ °% ΐΖ ¾ί
^zz^ ^ (ε)
Figure imgf000162_0006
'ΡΡ 'Ηΐ)ΐ9·9 '(ΖΗ9=Γ ' ' )fV '(s-i ΉΖ)Ζ9τ '(ω 'Ηΐ)00·ε- 98 '(ω 'Ηΐ)8 - 9 ^ zz ^ ^ (ε)
Figure imgf000162_0006
'ΡΡ' Ηΐ) ΐ9 ・ 9 '( Ζ Η9 = Γ'')fV' (si ΉΖ) Ζ9τ '(ω' Ηΐ) 00 · ε- 98 '(ω' Ηΐ) 8-9
'(ω Ήΐ)½·ζ-0^·2 '(ω 'Ηΐ)86·ΐ— 8·ΐ Ή 'Ηΐ)ΐΖ·ΐ 9 つ) Η顺- Ητ '(ω Ήΐ) ½½ζ-0 ^ · 2' (ω 'Ηΐ) 86ΐ 8—8Ή Ή' Ηΐ)) ΐΖ9) Η 顺-Η τ
。 %08 ^z-^ ^^ ^mn ^m ^i ^mm、
Figure imgf000162_0007
. % 08 ^ z- ^ ^^ ^ mn ^ m ^ i ^ mm,
Figure imgf000162_0007
ベ^べ 、^ c^ — ΐ— — 9 (Ζ) 。^拳暈咪 ½各 ISISZSO绻 蘭 ΠΗ |、|、ί'^Ι：べ, べ ΐ- cW-- 9
Figure imgf000162_0008
Bebe, ^ c ^ — ΐ— — 9 (Ζ). ^ Fisted 咪 ½ each ISISZSO 蘭 orchid ΠΗ |, |, ί '^ Ι: Be, Be ΐ- cW-- 9
Figure imgf000162_0008
'Ηΐ)εΐ·8 '(ZHS'8=f 'P 'HT)8S"Z '(sjq 'HI)SS'S '(ω 'HI)0S'S— SO'S '(ω 'Ηΐ)00·ε— 08
Figure imgf000162_0009
091· S081760/S00Z OAV "(s-i 'H\)WZ\ '(zHS-6=f 'P 'Ηΐ)ε6·8 '(s 'Ηΐ)0ε·8 '(s Ήΐ) ζ·8 '(ΖΗ8·8 Τΐ=Γ 'Ηΐ) εΐ8'(ZHS'8 = f 'P' HT) 8S "Z '(sjq' HI) SS'S '(ω' HI) 0S'S— SO'S '(ω' Ηΐ) 00
Figure imgf000162_0009
091S081760 / S00Z OAV "(si 'H \) WZ \' ( z HS-6 = f 'P' Ηΐ) ε6.8 '( s ' Ηΐ) 0ε8 '( s Ήΐ) ζ8' (ΖΗ8 · 88 = Γ
'PP 'H¾S6"Z 'H2)TS"Z  'PP' H¾S6 "Z 'H2) TS" Z
'(ΖΗ8"Ζ Τ
Figure imgf000163_0001
'HT)OS"Z'(ΖΗ8 "Ζ Τ
Figure imgf000163_0001
'HT) OS "Z
Figure imgf000163_0002
'P 'HT)WS 9 :(9p— OSW I) 顺— HT °%08 ¾T
Figure imgf000163_0003
Figure imgf000163_0002
'P' HT) WS 9 :( 9 p— OSW I) 顺 — H T °% 08 ¾T
Figure imgf000163_0003
'HWU '^ΗΖτΐ=ί 'P Ήΐ)2 ·8 '(ΖΗΓ6=Γ 'P 'H2)S0"8 '(s 'Ηΐ)98· '(ΖΗ0·9=1" 'P 'HWU' ^ ΗΖτΐ = ί 'P Ήΐ) 2 · 8' ( Ζ ΗΓ6 = Γ 'P' H2) S0 "8 '( s ' Ηΐ) 98 · '(ΖΗ0 · 9 = 1"' P
'HT)^8"Z '(ΖΗΐ·8=ί" 'P 'Ηΐ)6ΓΖ ^HVL=i 'P Ήΐ)09"Ζ '(ZH2" Ό'Ζ=ί 'PP 'HI)SS'Z 'HT) ^ 8 "Z' (ΖΗΐ · 8 = ί" 'P' Ηΐ) 6ΓΖ ^ HVL = i 'P Ήΐ) 09 "Ζ' (ZH2" Ό'Ζ = ί 'PP' HI) SS'Z
'(ΖΗΐ·6=ί" 'P lWZ)LYL
Figure imgf000163_0004
'； Ρ 'HT)TS"Z '(ΖΗΖ·Ζ=ί" '(ΖΗΐ · 6 = ί "' P l WZ) LYL
Figure imgf000163_0004
';Ρ' HT) TS "Z '(ΖΗΖ · Ζ = ί"
'Ρ 'HT)S6"S '(ΖΗΖ·Ζ=1" 'Ρ 'ΗΙ)Ζ ' '(s Ήζ)Ζζ'Ζ 9 :( P-OS a)H N-HT °%S6 ? φ 'Ρ' HT) S6 "S '(ΖΗΖ · Ζ = 1"' Ρ 'ΗΙ) Ζ''( s Ήζ) Ζζ'Ζ 9 :( P-OS a) H NH T °% S6? Φ
OSS各粱呦 -OZZ [OSTO] OSS each 呦 -OZZ [OSTO]
\ =[ 'p Ήΐ)28·π '(s Ήΐ)εε·οΐ '(m =i 'p Ήΐ)6 ·8 '(zH8=f 'p \ = ['p Ήΐ) 28π' ( s Ήΐ) εεοΐ '(m = i' p Ήΐ) 6 · 8 '( z H8 = f' p
Ήΐ)02"8 '(zH6=f 'P Ήΐ)20"8 '(zHS" =f 'P Ήΐ)06"Ζ '(zHS"2=f 'P Ήΐ)ΐ8"Ζ '(zH6=f  Ήΐ) 02 "8 '(zH6 = f'P Ήΐ) 20" 8' (zHS "= f'P Ήΐ) 06" Ζ '(zHS "2 = f'P Ήΐ) ΐ8" Ζ' (zH6 = f
'P 'HT)S9"Z '(ω Ή^)93· -3ε· 'HS)86 9 :( P-OS a)H N-HT °%Z9 ? φ 'P' HT) S9 "Z '(ω Ή ^) 93 · -3ε ·' HS) 86 9 :( P-OS a) H NH T °% Z9? Φ
&zz^ ^ (ε) & zz ^ ^ (ε)
•(s Ήΐ)9Γ6 '(ZHS =f 'P Ήΐ)69"Ζ '(ZHS • (s Ήΐ) 9Γ6 '(ZHS = f' P Ήΐ) 69 "Ζ '(ZHS
'S"8=f 'PP Ήΐ) Υί '(zHS"8=f 'P 'HT)6S"Z '(s Ήε) Γ2 9 :(9p— OSWd) N— H
Figure imgf000163_0005
(Ζ) 'S "8 = f' PP Ήΐ) Υί '(zHS" 8 = f' P 'HT) 6S "Z' (s Ήε) Γ2 9 :( 9 p— OSWd) N— H
Figure imgf000163_0005
(Ζ)
。 呦^ 遨 コ ½^翁 ； ん¾ 一  .遨 ^ 遨
ベ - S - /— ½。;m、 ¾^- S'M/^ - ε -{Λ^^^ ^-ΫΖ)-\ (ΐ)  Ba-S-/ — ½. ; m, ¾ ^-S'M / ^-ε-{Λ ^^^ ^ -ΫΖ)-\ (ΐ)
•(zHST=f 'P 'Ηΐ)6·ΐΐ • ( z HST = f 'P' Ηΐ) 6
'( q 'Ηΐ)ε·0ΐ '(zHST=f 'P Ήΐ)8Ζ·8 '(zH6=f 'Ρ Ήΐ) ·8 '(ζΗ8=Γ 'Ρ Ήΐ)20·8
Figure imgf000163_0006
'(q' Ηΐ) ε0ΐ '( z HST = f' P Ήΐ) 8Ζ8 '( z H6 = f' Ρ Ήΐ) 8 '( ζ Η8 = Γ' Ρ Ήΐ) 20
Figure imgf000163_0006
'(ω 'H^)es- -os" '(s Ήε)οε '(s 'm)fz'z 9 :( p-os a)H N-HT °% ε ¾i '(ω' H ^) es- -os "'(s Ήε) οε' ( s ' m) fz'z 9 :( p-os a) H NH T °% ε ¾i
szz^(^^ (ε)
Figure imgf000163_0007
1-91. S081760/S00Z OAV
Figure imgf000164_0001
szz ^ (^^ (ε)
Figure imgf000163_0007
1-91. S081760 / S00Z OAV
Figure imgf000164_0001
•(s 'HT)6S"6 '(ω 'H2)SS"Z-9^"Z '(ω 'HT)0^"Z-OS"Z  • (s' HT) 6S "6 '(ω' H2) SS" Z-9 ^ "Z '(ω' HT) 0 ^" Z-OS "Z
'(in 'Hi)erz-80"z Ή 'HI)II'S Ήε)9ε '(s 'm)wz 9 :(9p— oswa) 顺— H '(in' Hi) erz-80 "z Ή 'HI) II'S Ήε) 9ε' ( s ' m) wz 9 :( 9 p— oswa) 顺 — H
^ / - /— ^^c^ ^- s' ^P - s -( / ェ ^ - ε)- ΐ- ^ - ε (ζ) ^ /-/ — ^^ c ^ ^-s' ^ P-s-(/ ^ ^-ε)-ΐ- ^-ε (ζ)
。 呦^ 遨 コ ½^翁 ； ん¾ 一 .遨 ^ 遨
Figure imgf000164_0002
(ΐ)
Figure imgf000164_0002
(ΐ)
9ss各粱呦^ -9zz [Ϊ3ΐ0]
Figure imgf000164_0003
9ss each 呦 ^ -9zz [Ϊ3ΐ0]
Figure imgf000164_0003
'Ρ 'Ηΐ)9·ΐΐ '(s Ήΐ)6 ΐ '(zHS'SI=f 'P 'HT)28"8 '(s 'Ηΐ) ·8 '(ω 'H2)08"Z-09"Z 'Ρ' Ηΐ) 9ΐΐ '( s Ήΐ) 6 ΐ'(zHS'SI = f 'P' HT) 28 "8 '( s ' Ηΐ) 8 '(ω' H2) 08" Z-09 " Z
'(ω 'm)ovL-fz-L '(s 'm)sz'z '(s 'u z'z 9 :(9p— oswa) N— HT °%9Ϊ ? Φ '(ω' m) ovL-fz-L '( s ' m) sz'z '( s ' u z'z 9 :( 9 p— oswa) N— H T °% 9Ϊ? Φ
SSS各粱呦 - zz SSS each 呦-zz
Figure imgf000164_0004
Figure imgf000164_0004
'Ρ 'HT)6Z"Z '(ω 'H2)29" -W  'Ρ' HT) 6Z "Z '(ω' H2) 29" -W
'
Figure imgf000164_0005
)WL 'PP Ήΐ)0 '
Figure imgf000164_0005
) WL 'PP Ήΐ) 0
'P 'HT)S6"S '(zH8=f 'P 'ΗΙ)Ζ ' '(s 'HS)SS 9 :( OSWd) N— HT °%Z ¾T
Figure imgf000164_0006
'P' HT) S6 "S '(zH8 = f' P 'ΗΙ) Ζ''( s ' HS) SS 9 :( OSWd) N— H T °% Z ¾T
Figure imgf000164_0006
'(ζΗΖ·ΐΐ=ί" 'P 'Ηΐ) 6·8 '(s 'HT)62"8 '(s 'HI)ZS'8 '(ΖΗΓ8=Γ 'P 'H2)86"Z '(zHZ'Z=f '(ζΗΖ · ΐΐ = ί "' P 'Ηΐ) 6 · 8' ( s ' HT) 62" 8 '( s ' HI) ZS'8' ( Ζ ΗΓ8 = Γ 'P' H2) 86 "Z '( zHZ'Z = f
'P Ήΐ)Ζ8"Ζ
Figure imgf000164_0007
'P Ήΐ) Ζ8 "Ζ
Figure imgf000164_0007
'； Ήΐ)9ΓΖ '(s Ήε) ε 9 :( oswa) 顺— HT °%86 ¾T '; Ήΐ) 9ΓΖ' (s Ήε) ε 9 :( oswa) 顺 — H T °% 86 ¾T
•( q 'H\)ZVZ\ '(s 'Ηΐ)ΖΖ·8 '(s 'HT)S0"8 '(ΖΗ8·8 • (q 'H \) ZVZ \' ( s 'Ηΐ) ΖΖ8' ( s 'HT) S0 "8' (ΖΗ8
Τ
Figure imgf000164_0008
'P 'HT)S8"Z '(ω 'H2)99"Z-T9"ZΤ
Figure imgf000164_0008
'P' HT) S8 "Z '(ω' H2) 99" Z-T9 "Z
Figure imgf000164_0009
Ήΐ)82"Ζ 9 :(
Figure imgf000164_0009
Ήΐ) 82 "Ζ 9 :(
P-OS a)H N-HT °% 8 ¾T。 呦^ 遨 翁^； a¾¾ ^^ 一
Figure imgf000164_0010
391- S081760/S00Z OAV 'P 'P 'Ηΐ)ΐ6·8 '(s 'Η 69·8 P-OS a) H NH T °% 8 ¾T. A 遨 ^^ one
Figure imgf000164_0010
391- S081760 / S00Z OAV 'P' P 'Ηΐ) ΐ6 · 8' ( s ' Η69 · 8
'P 'ΗΙ)£
Figure imgf000165_0001
'P 'HT)½"Z '(s 'HT)S8"Z 'P' ΗΙ) £
Figure imgf000165_0001
'P' HT) ½ "Z '(s' HT) S8" Z
'P 'HT)S9"Z '(ω 'H 6S'Z— Ζ · '(s 'HS)8S 9 :(9p— OSW I) 顺— HT °%SS ¾T 'P' HT) S9 "Z '(ω' H 6S'Z— Ζ · '(s' HS) 8S 9 :( 9 p— OSW I) 顺 — H T °% SS ¾T
&zz^ ^ (ε) & zz ^ ^ (ε)
•(s Ήΐ) 2·6 '(s 'Ηΐ)9Γ8 '(s 'HT)S -8 '(s 'HT)S6"Z '(s 'HI)8S'Z '(S 'HS)IS'S 9 :(• ( s 2) 2 6 '( s ' Ηΐ) 9 Γ 8 '( s ' HT) S -8 '( s ' HT) S6 "Z '(s' HI) 8S'Z '(S' HS) IS'S 9 :(
Iつ aつ) WN- Ht °%ιε ¾i
Figure imgf000165_0002
一 I one a) WN- H t °% ιε ¾i
Figure imgf000165_0002
one
、 ^ - 一
Figure imgf000165_0003
(ζ) •(s Ήΐ) Υί '(ω 'H2)SS"Z-0S"Z '(s 'H2)S "S '(s Ήε)00 9 :(, ^-One
Figure imgf000165_0003
(ζ) • (s Ήΐ) Υί '(ω' H2) SS "Z-0S" Z '(s' H2) S "S' (s Ήε) 00 9 :(
Iつ aつ) WN- HT 0%6ε*¾ί °^ ¾<¾?^®^ τ^)¾^ )#^^ん ^^ 一 - s - /— ^^c^ ^- s' ^ - ε- [ ェ ( ^ ci / fH) - s's]- ΐ (ΐ) I one a) WN- H T 0 % 6ε * ¾ί ° ^ ¾ <¾? ^ ® ^ τ ^) ¾ ^) # ^^ n ^^ one-s-/-^^ c ^ ^-s' ^ -ε- [((^ ci / fH)-s's]-ΐ (ΐ)
"(s-i 'Ηΐ)ΖΖ ΐ '(ΖΗ6·εΐ=ί" 'Ρ 'HWST '(s 'Ηΐ)ε ·0ΐ
Figure imgf000165_0004
'Ρ 'Ηΐ) 8·8 '(zW8=f 'Ρ Ήΐ)εζ·8 '(ΖΗ2· '0 =1" 'ΡΡ 'Η 6ΐ·8 '^ΗΖ'6=ί 'Ρ 'Ηΐ)Μ)·8 '(zH0"Z '8·ΐ=ί" 'ΡΡ 'H2)66"Z '(ΖΗΖ·Ζ=ί" 'Ρ 'Ηΐ)ΐ6· 6=1" 'Ρ 'H\)WL '(ΖΗΐ·8 Ό"Ζ 'S"T=f 'PPP 'HI)9S'Z '(ΖΗ0"Ζ Τΐ=Γ '； Ρ 'Ηΐ)8 · '(s 'HS)SS 9 :( OSW I) N— H
Figure imgf000165_0005
'P 'Ηΐ)ε8·ΐΐ '(s ΉΪ)82 Ϊ "(si 'Ηΐ) ΖΖ ΐ' (ΖΗ6 · εΐ = ί"'Ρ' HWST '( s ' Ηΐ) ε · 0ΐ
Figure imgf000165_0004
'Ρ' Ηΐ) 8 · 8 '(zW8 = f' Ρ Ήΐ) εζ8 '( Ζ Η2 ·' 0 = 1 "'ΡΡ' Η 6ΐ8 '^ ΗΖ'6 = ί' Ρ 'Ηΐ) Μ ) 8 '( z H0 "Z' 8 · ΐ = ί"'ΡΡ' H2) 66 "Z '(ΖΗΖ · Ζ = ί"' Ρ 'Ηΐ) ΐ6 6 = 1 "' Ρ 'H \) WL '(ΖΗΐ8 Ό "Ζ'S" T = f 'PPP' HI) 9S'Z '(ΖΗ0 "Ζ Τΐ = Γ'; Ρ 'Ηΐ) 8 ·'(s' HS) SS 9 :( OSW I ) N— H
Figure imgf000165_0005
'P' Ηΐ) ε8ΐΐ ΐΐ '( s ΉΪ) 82 Ϊ
'P 'Ηΐ)ΖΖ·8 '(zHS'8=f 'P 'HI ·8 '(ΖΗΓ6=Γ 'P 'HT)20"8 '^HVL=[ 'P 'Ηΐ)06· '(ω 'H2)S9"Z '(ZH9" Vl=f P 'HI)SS'Z '(ω 'Η )6 · ΐ · 'HS)62"2 9 ( v-osnaWH-H, °%ε ¾τ。 呦^ 遨 翁^； α¾¾ ^^ 一 'P' Ηΐ) ΖΖ8 '(zHS'8 = f' P 'HI · 8' ( Ζ ΗΓ6 = Γ 'P' HT) 20 "8 '^ HVL = [' P 'Ηΐ) 06 ·' (ω 'H2) S9 "Z'(ZH9" Vl = f P 'HI) SS'Z'(ω'Η) 6 · ΐ · 'HS) 62 "2 9 (v-osnaWH-H, °% εετ. 呦^^^^^^
•(zHS'SI=f 'P 'H\)VZ\• (zHS'SI = f 'P' H \) VZ \
'( q 'Ηΐ)ε·0ΐ '(zHS'SI=f 'P Ήΐ)08·8 '(zHS'8=f 'P 'Ηΐ) 8 '(zH6=f 'P 'Ηΐ)εθ·8 '(ω 'HS)½"Z-08"Z '(ZH6=f 'P 'Ηΐ)ε9·Ζ '(ω 'HZ L-ZVL '(ω 'HD L-ZZ'L'(q' Ηΐ) ε0ΐ '(zHS'SI = f' P Ήΐ) 08 · 8 '(zHS'8 = f' P 'Ηΐ) 8' ( z H6 = f 'P' Ηΐ) εθ8 '(ω' HS) ½ "Z-08" Z '(ZH6 = f' P 'Ηΐ) ε9Ζ Ζ' (ω 'HZ L-ZVL' (ω 'HD L-ZZ'L
'(ω 'HT)OO"Z-S8"9 '(s Ήε)9ε '(s Ήζ)ζζ-ζ 9 :(9p— oswa) 顺— HT °%Z ¾ί
Figure imgf000165_0006
891- S081760/S00Z OAV '(zHS" =f 'p Ήΐ)ΐ3·3 '(s Ήε) ·ε '(s Ήε)οε 9 :(9p— oswa) 顺— Ht °%96 ¾T 'Ηΐ)0 ΐ'(ω' HT) OO "Z-S8" 9 '( s Ήε) 9ε' ( s Ήζ) ζζ-ζ 9 :( 9 p— oswa) 顺 — H T °% Z ¾ί
Figure imgf000165_0006
891- S081760 / S00Z OAV '(zHS "= f' p Ήΐ) ΐ3.3 '(s Ήε) · ε' (s Ήε) οε 9 :( 9 p—oswa) 顺 — H t °% 96 ¾T 'Ηΐ) 0 ΐ
'(saq 'Ηΐ)ε·Οΐ 'Ηΐ)εθ·8 '(ω 'HS)S6"Z-S8"
Figure imgf000166_0001
'HDLVL '(zH6=f 'P 'Η 86·9 '(s 'HS)ZZT '(s Ήε)ΐε 9 :( P-OS a)H N-HT ¾ί '(saq' Ηΐ) ε · Οΐ 'Ηΐ) εθ · 8' (ω 'HS) S6 "Z-S8"
Figure imgf000166_0001
'HDLVL' (z H6 = f 'P' Η 86 · 9 '(s' HS) ZZT' (s Ήε) ΐε 9 :( P-OS a) H NH T ¾ί
•(ω Ήΐ) ·π- ε·π '(^• (ω Ήΐ) · π- ε · π '(^
'Ηΐ) 8- 9·8 '(ω Ήε)06· - 3ΓΖ '(ω 'H2)S9"Z-eS"Z '(ω 'H9)Se"Z-S2"Z
Figure imgf000166_0002
'Ηΐ) 8-9.8' (ω Ήε) 06 ·-3ΓΖ '(ω' H2) S9 "Z-eS" Z '(ω' H9) Se "Z-S2" Z
Figure imgf000166_0002
'P 'HT)26"S '(zHS"Z=f 'P 'HI)OS'S '(s 'HS)82"2 9 :( P-OS a)H N-HT °%99 ¾T 'P' HT) 26 "S '(zHS" Z = f' P 'HI) OS'S'(s' HS) 82 "2 9 :( P-OS a) H NH T °% 99 ¾T
•(ZHS'SI=【 'p Ήΐ)8·π '( q Ήΐ)ε·οΐ 'Wzi=i• (ZHS'SI = ['p Ήΐ) 8π' (q Ήΐ) ε · οΐ 'Wzi = i
'P 'Ηΐ)6Γ8 '(zH8=f 'P 'Ηΐ) ·8 '(zH6=f 'P 'HT)20"8 '(zH8=f 'P 'HT)06"Z '(zH6=f 'P 'HT)29"Z '(ω 'Η9)83· -32· '(s 'HS)0S"2 9 :( P-OS a)H N-HT °%6 ¾T
Figure imgf000166_0003
'P' Ηΐ) 6Γ8 '( z H8 = f' P 'Ηΐ) 8' ( z H6 = f 'P' HT) 20 "8 '( z H8 = f' P 'HT) 06"Z' (zH6 = f 'P' HT) 29 "Z '(ω' Η9) 83 -32 ''(s' HS) 0S" 2 9 :( P-OS a) H NH T °% 6 ¾T
Figure imgf000166_0003
•(s 'Ηΐ)99·6• ( s ' Ηΐ) 99.6
'(ω
Figure imgf000166_0004
'ΗΪ)8 · 6ε· '(ω Ήΐ)8ε·ζ- ΐε- 'HS)SS 9 ( p-os a)H N-HT °%6 ¾τ
Figure imgf000166_0005
Figure imgf000166_0006
(ζ)'(ω
Figure imgf000166_0004
'ΗΪ) 8 6 6' (ω Ήΐ) 8εε- ΐε- 'HS) SS 9 (p-os a) H NH T °% 6 ¾τ
Figure imgf000166_0005
Figure imgf000166_0006
(ζ)
。 呦^ 遨 コ 5¾^«翁 ; ん¾ 一 . 5 遨 ^ «Okin;
•(saq 'Ηΐ) VII '(saq Ήΐ) 0Z"8 '(ω Ήε) S8"Z-0Z"Z
Figure imgf000166_0007
• (saq 'Ηΐ) VII' (saq Ήΐ) 0Z "8 '(ω Ήε) S8" Z-0Z "Z
Figure imgf000166_0007
'P 'Ηΐ) 6S"Z
Figure imgf000166_0008
'P 'HT)26"S '(zHS'Z=f 'P 'HI)IS'S '(s 'HS)82"2 '(s 'HS) S 9 :( P- OS 顺- HT °%6S ? φ 'P' Ηΐ) 6S "Z
Figure imgf000166_0008
'P' HT) 26 "S '(zHS'Z = f' P 'HI) IS'S'(s' HS) 82" 2 '( s ' HS) S 9 :( P- OS 顺-H T °% 6S ? φ
•(zHS"ST=f
Figure imgf000166_0009
S081760/S00Z OAV 邈氺 ΐοιιιιιι ε-ζ 、^ベ 、 4 - Ζ'9'S' / - ^ / ェ- S• (zHS "ST = f
Figure imgf000166_0009
S081760 / S00Z OAV 邈 氺 ΐοιιιιιι ε-ζ, ^ be, 4-Ζ'9'S '/-^ /
Figure imgf000167_0001
Figure imgf000167_0001
OSS各粱呦^ -0 Z  OSS each 呦 ^ -0 Z
Xs Ήΐ)ε ΐ '(s 'HT)S8"6 '(ω Ήΐ)03·8-3^·8 '(ω 'HT)82"8-02"8 '(ω 'HT)06"Z-08"Z X s Ήΐ) ε ΐ '( s ' HT) S8 "6' (ω Ήΐ) 03 · 8-3 ^ · 8 '(ω' HT) 82" 8-02 "8 '(ω' HT) 06" Z -08 "Z
'(ω 'H2)e " -S9" '(ω 'H )SS'Z- ο · 9 :(9p- OSW I) 顺- ΗΤ °% ΐ ¾ί '(ω' H2) e "-S9"'(ω' H) SS'Z- ο · 9 :( 9 p- OSW I) 顺-Η Τ °% ΐ ¾ί
•(s 'Ηΐ)ε·0ΐ '(s Ήΐ)ε ·6 '(ω Ήΐ) 2·8-02·8 '(ω Ήΐ)3Γ8-30·8 '(ω 'H2)S6"Z-08"Z • ( s 'Ηΐ) ε0ΐ' ( s Ήΐ) ε · 6 '(ω Ήΐ) 2.8-02 · 8' (ω Ήΐ) 3Γ8-30 · 8 '(ω' H2) S6 "Z-08 "Z
'(in 'H )SS'Z s 'z '(ω
Figure imgf000167_0002
9 :(9ρ— oswa) 顺— ΗΤ °% ΐ ¾ί
Figure imgf000167_0003
'(in' H) SS'Z s 'z' (ω
Figure imgf000167_0002
9 :( 9 ρ— oswa) 顺 — Η Τ °% ΐ ¾ί
Figure imgf000167_0003
'Ηΐ)Ζ8 ΐ '(s Ήΐ)2Ζ ΐ '^ΗΖτΐ=ί 'Ρ 'Ηΐ)88·8 '(zH8"Z=f 'Ρ 'HI)SS'8 '(zHS'6=f 'Ρ 'Ηΐ)ΐΐ·8 '(zH9"Z=f 'Ρ 'H\)WL '(ΖΗ8 'Γ0ΐ=Γ ' Ρ 'H2)98"Z '(ΖΗ0·6=1" 'Ρ 'HT)S9"Z '(ω 'H2)T9"Z-6^"Z '(ΖΗ8 '6·6=ί" '^Ρ 'H2)90"Z '(s 'HS)08"S 9 :( Ρ- OSWa) 顺- Η 'Ηΐ) Ζ8 ΐ' ( s Ήΐ) 2Ζ ΐ '^ ΗΖτΐ = ί' Ρ 'Ηΐ) 88 · 8' ( z H8 "Z = f 'Ρ' HI) SS'8 '(zHS'6 = f' Ρ 'Ηΐ) ΐΐ8' ( z H9 "Z = f 'Ρ' H \) WL '(ΖΗ8' Γ0ΐ = Γ 'Ρ' H2) 98" Z '(ΖΗ0 · 6 = 1 "' Ρ 'HT) S9 "Z '(ω' H2) T9" Z-6 ^ "Z '(ΖΗ8' 6.6 · ί = '"' ^ Ρ 'H2) 90 "Z'(s' HS) 08" S 9 :( Ρ- OSWa ) 顺-Η
"(ω Ήΐ)^2ΐ-2·2ΐ '( q 'Ηΐ) ·0ΐ '(ω 'Ηΐ)08·8- S9'8
Figure imgf000167_0004
'HT)Z2"Z '(s 'Ηΐ)Ζ9·9 '(ω 'H ) SZ — 09 '(ω 'Η )08·ΐ— S9'I 9 :( OSWa) 顺— Ητ ¾ί "(ω Ήΐ) ^ 2ΐ-2 · 2ΐ '(q' Ηΐ) 0ΐ '(ω' Ηΐ) 08 · 8-S9'8
Figure imgf000167_0004
'HT) Z2 "Z'(s' Ηΐ) Ζ9 · 9 '(ω' H) SZ — 09 '(ω' Η) 08 · ΐ— S9'I 9 :( OSWa) 顺 — Η τ ¾ί
° (I66I)S06S— 698S'd 'ΐΐ·。Ν '6S"l°A 'URSIPH ρομηθθΏΐιιαΏ¾ pus γao] ^^ ：^:邈峯氺 /— 4 - 、 4 - 8'Z'9'S- - S
Figure imgf000167_0005
'P 'HT)S"n '(s 'Ηΐ)ΐ·0ΐ 'P 'H2)66"Z '(s Ήΐ)£γΐ '(zHS'Z=f ^ 'H2)6S"Z '(zHS" =f ^ Ήΐ)2ΓΖ '(s 'Ηΐ) 9·9 '(ω 'H ) SZ — 09 '(s 'm)6Z'Z '(ω 'Η )08·ΐ— 09·ΐ 9 :( OSWa) 顺— Ητ °%09 ¾ί ° (I66I) S06S—698S'd'ΐΐ. Ν '6S "l ° A' URSIPH ρομηθθΏΐιιαΏ¾ pus γao] ^^ ： ^: 邈 峰 氺 / — 4-, 4-8'Z'9'S--S
Figure imgf000167_0005
'P' HT) S "n '(s' Ηΐ) ΐ0ΐ 'P' H2) 66" Z '(s Ήΐ) £ γΐ'(zHS'Z = f ^ 'H2) 6S "Z'(zHS" = f ^ Ήΐ) 2ΓΖ '(s' Ηΐ) 9 · 9 '(ω' H) SZ — 09 '( s ' m) 6Z'Z '(ω' Η) 08 · ΐ— 09 · ΐ 9 :( OSWa ) 顺 — Η τ °% 09 ¾ί
"(ω 'Ηΐ)9·ΐΐ― ·ΐΐ '(ω 'HI)SZ'8— S9'8 '(ΖΗ6=Γ 'Ρ 'Η 88· '(ω 'H2)98"Z-08"Z
Figure imgf000167_0006
'PP 'HT)SS"Z "(ω 'Ηΐ) 9 · ΐΐ- · ΐΐ' (ω 'HI) SZ'8— S9'8' ( Ζ Η6 = Γ 'Ρ' Η 88 · '(ω' H2) 98" Z-08 "Z
Figure imgf000167_0006
'PP' HT) SS "Z
' 'HT)6S"Z
Figure imgf000167_0007
'Ηΐ)ΐε· '(ZH6=f 'Ρ Ή2)66"9 'P 'HT)26"S
Figure imgf000167_0008
991- S081760/S00Z OAV 化ナトリウム水溶液 (2.3ml, 4.6mmol)及びエタノールの混合物を、室温で 17時間攪拌 した。反応混合物を減圧濃縮し、得られた残渣に 2N塩酸を加え pHを 6とした。析出し た結晶を濾取して、標題化合物の淡褐色結晶 (0.33g, 84%)を得た。 '' HT) 6S "Z
Figure imgf000167_0007
'Ηΐ) ΐε ·' (ZH6 = f 'Ρ Ή2) 66 "9' P 'HT) 26" S
Figure imgf000167_0008
991- S081760 / S00Z OAV A mixture of aqueous sodium chloride solution (2.3 ml, 4.6 mmol) and ethanol was stirred at room temperature for 17 hours. The reaction mixture was concentrated under reduced pressure, and 2N hydrochloric acid was added to the obtained residue to adjust the pH to 6. The precipitated crystals were collected by filtration to give pale brown crystals of the title compound (0.33 g, 84%).
1H-NMR(CDC1 ): δ 1.60— 1.95(4H, m), 2.50— 2.85(4H, m), 3.89(2H, brs). 1H-NMR (CDC1): δ 1.60-1.95 (4H, m), 2.50-2.85 (4H, m), 3.89 (2H, brs).
3  Three
3-エトキシカルボ-ル- 4,5, 6,7-テトラヒドロインダゾール： Journal of Medicinal Chemistry, Vo.46, No.8, p.3945- 3951(2003)参照。  3-ethoxycarbol-4,5,6,7-tetrahydroindazole: See Journal of Medicinal Chemistry, Vo. 46, No. 8, p. 3945-3951 (2003).
(2)化合物番号 250 (2) Compound No. 250
収率 12%。 'H-NMRCDMSO-d ): δ 1.60- 1.80(4Η, m), 2.60- 2.80(4Η, m), Yield 12%. 'H-NMRCDMSO-d): δ 1.60-1.80 (4Η, m), 2.60-2.80 (4Η, m),
6  6
7.40-7.55(3Η, m), 7.82(1Η, d, J=8Hz), 8.07(1Η, d, J=9Hz), 8.19(1H, d, J=8Hz), 9.95(1H, s), 9.99(1H, brs), 13.0(1H, brs).  7.40-7.55 (3Η, m), 7.82 (1Η, d, J = 8Hz), 8.07 (1Η, d, J = 9Hz), 8.19 (1H, d, J = 8Hz), 9.95 (1H, s), 9.99 (1H, brs), 13.0 (1H, brs).
例 251:化合物番号 251 Example 251: Compound number 251
収率 36%。 'H-NMRCDMSO-d ): δ 7.40- 7.60(6Η, m), 7.82- 7.90(1Η, m), Yield 36%. 'H-NMRCDMSO-d): δ 7.40- 7.60 (6Η, m), 7.82- 7.90 (1Η, m),
6  6
8.00— 8.15(2Η, m), 8.20— 8.30(1Η, m), 8.44(1Η, s), 9.72(1Η, s), 10.5(1Η, s).  8.00- 8.15 (2Η, m), 8.20- 8.30 (1Η, m), 8.44 (1Η, s), 9.72 (1Η, s), 10.5 (1Η, s).
例 252:化合物番号 252 Example 252: Compound number 252
収率 34%。 'H-NMRCDMSO-d ): δ 6.70— 6.80(1H, m), 7.35— 7.55(4H, m), 7.61(1H, Yield 34%. 'H-NMRCDMSO-d): δ 6.70-6.80 (1H, m), 7.35-7.55 (4H, m), 7.61 (1H,
6  6
d, J=9Hz), 7.80-7.90(lH, m), 7.95— 8.05(1H, m), 8.15- 8.25(1H, m), 9.75(1H, s), 10.K1H, s). d, J = 9Hz), 7.80-7.90 (lH, m), 7.95-8.05 (1H, m), 8.15- 8.25 (1H, m), 9.75 (1H, s), 10.K1H, s).
例 253:化合物番号 253 Example 253: Compound number 253
(1) 1- (4-フルオロフェ-ル )-3-トリフルォロメチル- 4,5-ジヒドロピラゾール- 5-オン 一般合成法 γと同様の方法により標題ィ匕合物を得た。収率 67%。 1 (1) 1- (4-Fluorophenyl) -3-trifluoromethyl-4,5-dihydropyrazol-5-one The title conjugate was obtained in the same manner as in the general synthesis method γ. Yield 67%. 1
H-NMR(DMSO-d ): δ 5.96(1H, s), 7.36(2H, t, J=9Hz), 7.70-7.80(2H, m), 12.5(1H,  H-NMR (DMSO-d): δ 5.96 (1H, s), 7.36 (2H, t, J = 9Hz), 7.70-7.80 (2H, m), 12.5 (1H,
6  6
brs).  brs).
(2) 1- (4-フルオロフェ-ル )-5-ォキソ -3-トリフルォロメチル- 4,5-ジヒドロピラゾール -4-カルバルデヒド  (2) 1- (4-fluorophenyl) -5-oxo-3-trifluoromethyl-4,5-dihydropyrazole-4-carbaldehyde
一般合成法 aと同様の方法により標題化合物を得た。収率 73%。 1 The title compound was obtained in the same manner as in General Synthesis Method a. 73% yield. 1
H-NMR(DMSO-d ): δ 7.20(2H, t, J=9Hz), 7.95- 8.05(2H, m), 9.31(1H, s). H-NMR (DMSO-d): δ 7.20 (2H, t, J = 9Hz), 7.95-8.05 (2H, m), 9.31 (1H, s).
6  6
(3)化合物番号 253  (3) Compound No. 253
収率 46%。 ^-NMRCDMSO-d ): δ 7.34(2H, t, J=9Hz), 7.52(1H, t, J=9Hz), 'P 'HT)29"2T '(s Ήΐ)69 ΐ '(ζ服 =f 'P 'Ηΐ)68·8 '(zHS'8=f 'P 'Ηΐ) 8 '(zH6=f 'P Ήΐ)0Γ8 '(ω 'HZ)WL-WL '(ω 'HS)Z9"Z-6^"Z 9 :( OSW I) 顺— HT °%Z ¾T ee½ ^^ (ε)Yield 46%. ^ -NMRCDMSO-d): δ 7.34 (2H, t, J = 9Hz), 7.52 (1H, t, J = 9Hz), 'P' HT) 29 "2T '(s Ήΐ) 69 ΐ' (ζ clothes = f 'P' Ηΐ) 68 · 8 '(zHS'8 = f' P 'Ηΐ) 8' (z H6 = f 'P Ήΐ) 0Γ8 '(ω' HZ) WL-WL '(ω' HS) Z9 "Z-6 ^" Z 9 :( OSW I) 顺 — H T °% Z ¾T ee½ ^^ (ε)
•(saq 'HT)S0"6 '(s Ήΐ)3ε· '(ω 'H2)02" -Sr 9 :( oswa) 顺— H • (saq 'HT) S0 "6' (s Ήΐ) 3ε · '(ω' H2) 02" -Sr 9 :( oswa) 顺 — H
、 ^ - 一 ½。 ci、 ¾^- S' ^ ci / fH- S- ^ - S -( / -ェ eed's)- ΐ (Ζ) •(saq 'HI ΐ '(s Ήΐ)ΐ6"Ζ '(ω 'H2)S9"Z-eS"Z '(s 'HI)I6'S 9 :( P- OSW I) 顺- H
Figure imgf000169_0001
(ΐ) 各粱呦 - Z
Figure imgf000169_0002
'P 'Ηΐ)ΖΖ ΐ, ^-One ½. ci, ¾ ^-S '^ ci / fH- S- ^-S-(/ -e eed's)-ΐ (Ζ) • (saq' HI ΐ '(s Ήΐ) ΐ6 "Ζ' (ω 'H2) S9 "Z-eS" Z '(s' HI) I6'S 9 :( P- OSW I) 顺-H
Figure imgf000169_0001
(ΐ) Each Siang 呦-Z
Figure imgf000169_0002
'P' Ηΐ) ΖΖ ΐ
'(S "Ηΐ)ε8·0ΐ '(zHS-ST=f 'Ρ 'HT)26"8 '(zHS'Z=f 'Ρ 'HT)92"8 '(ω 'HS)SI'8— 80·8 '(zH8=f 'Ρ 'Ηΐ)ε · '(ω ' )WL-WL 9 :( Ν— Ητ ¾ί
Figure imgf000169_0003
'(S "Ηΐ) ε8 · 0ΐ' (zHS-ST = f 'Ρ' HT) 26" 8 '(zHS'Z = f' Ρ 'HT) 92 "8' (ω 'HS) SI'8—80 · 8 '(zH8 = f' Ρ 'Ηΐ) ε ·' (ω ') WL-WL 9 :( Ν— Η τ ¾ί
Figure imgf000169_0003
•(s Ήΐ)εε·6
Figure imgf000169_0004
'Ρ 'ΗΙ)Ζ£Ί 9 :(9ρ— Ν— Η • ( s Ήΐ) εε6
Figure imgf000169_0004
'Ρ' ΗΙ) Ζ £ Ί 9 :( 9 ρ— Ν— Η
τ °%6 ¾τ ^m^ ^mm^ ^ m η τ °% 6 ¾τ ^ m ^ ^ mm ^ ^ m η
、 ^ - 一 ½。 ci、 ¾^- S' ^ ci / fH- ε- ^P - S -( / -ェ cm^^- S'S)- ΐ (Ζ) , ^-One ½. ci, ¾ ^-S '^ ci / fH- ε- ^ P-S-(/ -e cm ^^-S'S)-ΐ (Ζ)
Figure imgf000169_0005
Figure imgf000169_0005
'Ρ
Figure imgf000169_0006
'Ρ Ήΐ)ΖΓΖ 'Ηΐ) Γ 'HT)S6"S Ήε) ε 9 :( lDaD)H N-HT 0%6 *¾ί ^Μ^^ΜΜ ^^^ Μ^ん ^^ 一
Figure imgf000169_0007
(ΐ) 'Ρ
Figure imgf000169_0006
'Ρ Ήΐ) ΖΓΖ' Ηΐ) Γ 'HT) S6 "S Ήε) ε 9 :( lDaD) H NH T 0 % 6 * ¾ί ^ Μ ^^ ΜΜ ^^^ Μ ^ ん ^^
Figure imgf000169_0007
(ΐ)
•(zHS'SI=f 'P 'Ηΐ)8 ΐ• (zHS'SI = f 'P' Ηΐ) 8 ΐ
'(s Ήΐ)8 ΐ '(zHS'SI=f 'P 'Ηΐ)68·8 '(zH8=f 'P 'HI)SS'8 '(zH6=f 'P Ήΐ)ΐΓ8 '(ω 'H2)80"8-96"Z '(zH8=f 'P 'HT)½"Z '(zH6=f 'P Ήΐ)29"Ζ '(zH6=f ' 'HT)eS"Z
Figure imgf000169_0008
19 V S081760/S00Z OAV 'H¾26"Z-S8"Z
Figure imgf000170_0001
'( s Ήΐ) 8 ΐ'(zHS'SI = f 'P' Ηΐ) 68 · 8 '( z H8 = f' P 'HI) SS'8' ( z H6 = f 'P Ήΐ) ΐΓ8' (ω 'H2) 80 "8-96"Z' (zH8 = f 'P' HT) ½ "Z '(zH6 = f' P Ήΐ) 29" Ζ '(zH6 = f''HT) eS "Z
Figure imgf000169_0008
19 V S081760 / S00Z OAV 'H¾26 "Z-S8" Z
Figure imgf000170_0001
'Ηΐ)εε· '(s 'HI)S6'S '(s 'HI)SS'S '(s 'HS) 'S 9 :(9p— OSW I) 顺— H 'Ηΐ) εε''(s' HI) S6'S'(s' HI) SS'S '(s'HS)' S 9 :( 9 p— OSW I) 顺 — H
T °%ss ¾i。 呦^ 遨 C)Tコ 翁^; a¾¾ ^^ 一 T °% ss ¾i. ) ^ Groud C) T KO ^^; a¾¾ ^^ one
09S各粱呦^ -09Z  09S each 呦 ^ -09Z
'ρ Ήΐ)ζε ΐ  'ρ Ήΐ) ζε ΐ
'(s 'Ηΐ)ΖΟ·ΐΐ
Figure imgf000170_0002
'Ρ 'HT)S8"8 '(s 'HT)8S"8 "Ζ '(s' Ηΐ) ΖΟ
Figure imgf000170_0002
'Ρ' HT) S8 "8 '( s ' HT) 8S" 8 "Ζ
'p Ήΐ)εζ·ζ '(ω
Figure imgf000170_0003
Ήΐ)οε" Ήε)3 ·ε 9 :(9p— oswa) 顺— Η 'p Ήΐ) εζ
Figure imgf000170_0003
Ήΐ) οε "Ήε) 3 · ε 9 :( 9 p— oswa) 顺 — Η
6SS各粱呦 :6SS 6SS each sword: 6SS
-(mZ'fl=i 'P 'HI)S8 ΐ '(s Ήΐ)9Ζ ΐ '(W I=f 'P 'Ηΐ)06·8
Figure imgf000170_0004
-(mZ'fl = i 'P' HI) S8 ΐ '( s Ήΐ) 9Ζ ΐ' (WI = f 'P' Ηΐ) 06
Figure imgf000170_0004
'P 'Ηΐ) 6· '(ζΗε·6=ί" 'P 'HT)S9"Z '(ω 'HWL-WL 9 :(9ρ— OSWa) Ν— Η 'P' Ηΐ) 6 · '(ζΗε · 6 = ί "' P 'HT) S9"Z' (ω 'HWL-WL 9 :( 9 ρ— OSWa) Ν— Η
τ °%οι ¾τ ^m^ ^mm^ ^ m m^m- 各粱呦^ :8S2p} [ STO] •(s 'Ηΐ)Ζ8·6 '(s 'Ηΐ)εΐ·6 '(s 'Ηΐ)60·6 '(zH8"Z=f 'P 'Ηΐ)ε9·8
Figure imgf000170_0005
'H2)88"Z-08"Z τ °% οι ¾τ ^ m ^ ^ mm ^ ^ mm ^ m- each beam ^^: 8S2p} [STO] • ( s ' Ηΐ) Ζ8 · 6 '( s ' Ηΐ) εΐ · 6' ( s ' Ηΐ) 606 '( z H8 "Z = f' P 'Ηΐ) ε9
Figure imgf000170_0005
'H2) 88 "Z-08" Z
'(zH8"8=f 'P 'HT)SZ"Z '(ω 'm^L-WL 9 :( OSWa) N— Ητ °%9ΐ ¾T '(zH8 "8 = f' P 'HT) SZ"Z' (ω 'm ^ L-WL 9 :( OSWa) N— Η τ °% 9ΐ ¾T
•(zH2T=f 'P Ήΐ)ε ·2ΐ '(s Ήΐ)09 ΐ '(ζΗ2ΐ=Γ 'P 'Ηΐ)ΖΖ·8
Figure imgf000170_0006
• ( z H2T = f 'P Ήΐ) ε 2ΐ' (s Ήΐ) 09 ΐ '( ζ Η2ΐ = Γ' P 'Ηΐ) ΖΖ8
Figure imgf000170_0006
'(saq 'HI)S8' '(ZH9=f ' 'H2)68"S
Figure imgf000170_0007
' 'H2)89"S 9 :( OSW I) 顺— H '(saq' HI) S8 '' (ZH9 = f '' H2) 68 "S
Figure imgf000170_0007
'' H2) 89 "S 9 :( OSW I) 顺 — H
τ °%9·ΐ ¾i。 呦^ 遨 C)Tコ 翁^; a¾¾ ^^ 一  τ °% 9 · ΐ ¾i. ) ^ Groud C) T KO ^^; a¾¾ ^^ one
932-^ ί¾?^ ） 932- ^ ί¾? ^)
•(s 'HT)6Z"S '(saq 'HI)SS'S
Figure imgf000170_0008
'HS)S0' 9 :( iDaD)H N-HT °%ooi ¾ί
Figure imgf000170_0009
一 • (s' HT) 6Z "S '(saq' HI) SS'S
Figure imgf000170_0008
'HS) S0' 9 :( iDaD) H NH T °% ooi ¾ί
Figure imgf000170_0009
one
ベ — s— /— ½。 Ei、 ¾^— s' ^ ci / fH— ε— ( ^エ 、^ 、 — s)— ΐ a)  Be — s — / — ½. Ei, ¾ ^ — s' ^ ci / fH— ε— (^ e, ^, — s) — ΐ a)
9SS各粱呦 -9 Z  9SS each 呦 -9 Z
•(z服 =f t9t900 OZdr/lDd 89 V S081760/S00Z OAV ζΙ.Λ(^^-Ζ- ^{Λ(—^Λ( . ^-\ (ΐ) 各粱呦 ： S92p} ·εΐ=Γ 'Ρ 'Ηΐ)09 ΐ '(s Ήΐ)ΐΖ ΐ
Figure imgf000171_0001
'Ρ HT)S6"Z '(ω 'HS)^9"Z-0S"Z '(zH6=f 'b 'HS)8Z' 9 :( OSW I) 顺— HT °%0S ¾T • ( z clothes = f t9t900 OZdr / lDd 89 V S081760 / S00Z OAV ζΙ.Λ (^^-Ζ- ^ {Λ (— ^ Λ (. ^-\ (ΐ) Each beam: S92p} · εΐ = Γ 'Ρ' Ηΐ) 09 ΐ '( s Ήΐ) ΐΖ ΐ
Figure imgf000171_0001
'Ρ HT) S6 "Z' (ω 'HS) ^ 9" Z-0S "Z' (zH6 = f ' b ' HS) 8Z '9 :( OSW I) 顺 — H T °% 0S ¾T
Z9Z^(^^ (ε) •(s 'HT)S -6 q 'HI)S6'9 '(zH8=f 'b 'H 9 :(
Figure imgf000171_0002
Z9Z ^ (^^ (ε) • ( s ' HT) S -6 q 'HI) S6'9' ( z H8 = f ' b ' H 9 :(
Figure imgf000171_0002
、 ^ - 一 , ^-One
½。 ci、 ¾^- S' ^ ci / fH- S- ( ^エ ci / fH- ΐ- - S (Z) ½. ci, ¾ ^-S '^ ci / fH- S- (^ e ci / fH- ΐ--S (Z)
•(s 'HT)T8"S '(zH6=f 'b 'HZ)Wf 9 :(• ( s 'HT) T8 "S' (zH6 = f ' b ' HZ) Wf 9 :(
DaD)H N-HT
Figure imgf000171_0003
一 - S - /— ½。 ci、 ¾^- S' ^ ci / fH- ε- ( ^エ ci / fH- ΐ (ΐ) DaD) H NH T
Figure imgf000171_0003
One-S-/ — ½. ci, ¾ ^-S '^ ci / fH- ε- (^ e ci / fH- ΐ (ΐ)
"(ζΗ2ΐ=Γ 'Ρ Ήΐ)9 ·2ΐ '(s Ήΐ)29 ΐ '(ζΗ2ΐ=Γ 'Ρ 'Ηΐ)8 8 '(zH8=f 'Ρ 'HT)S2"8 '(zH6=f 'Ρ 'Ηΐ)90·8 '(zH8=f 'Ρ Ήΐ)26"Ζ '(ω Ή£)Ζ9Ί-8νί '(zHS"Z=f 'b 'H2)Z8"S '(zHS"Z=f 'HS)92"T 9 :(9ρ—〇SWa) 顺— HT ¾ί "( ζ Η2ΐ = Γ 'Ρ Ήΐ) 9 · 2ΐ' (s Ήΐ) 29 ΐ '( ζ Η2ΐ = Γ' Ρ 'Ηΐ) 8 8' (zH8 = f 'Ρ' HT) S2" 8 '(zH6 = f 'Ρ' Ηΐ) 90 · 8 '(zH8 = f' Ρ Ήΐ) 26 "Ζ '(ω Ή £) Ζ9Ί-8νί'(zHS" Z = f 'b' H2) Z8 "S '(zHS" Z = f 'HS) 92 "T 9 :( 9 ρ—〇SWa) 顺 — H T ¾ί
•(s 'HT)SZ"6 '(saq Ήΐ)06"Ζ
Figure imgf000171_0004
• (s 'HT) SZ "6' (saq Ήΐ) 06" Ζ
Figure imgf000171_0004
Figure imgf000171_0005
Figure imgf000171_0005
、 ,
^ / - /— ^^c^ ^- S' ^ ci / fH- ε- - S- ^エ- ΐ (ζ)^ /-/ — ^^ c ^ ^-S '^ ci / fH- ε--S- ^ e- ΐ (ζ)
•(s Ήΐ)ΐ ·3
Figure imgf000171_0006
'； 'HS)62"T 9 :(• (s Ήΐ) ΐ · 3
Figure imgf000171_0006
';' HS) 62 "T 9 :(
DaD)H N-HT ¾ί
Figure imgf000171_0007
一 DaD) H NH T ¾ί
Figure imgf000171_0007
one
ベ - s - /— ½^ΰ、 ¾^- s' ^ ci / fH- ε- ^エ- ΐ (ΐ)  Be-s-/ — ½ ^ ΰ, ¾ ^-s' ^ ci / fH- ε- ^ d-ΐ (ΐ)
•(s 'Ηΐ)69·8 '(ω
Figure imgf000171_0008
S081760/S00Z OAV '(zHs- =f '； Ήΐ)εΓ '(sjq Ήΐ)8ε·ε '(s 'm)fz'z 9 :(9p— oswa) 顺— HT °%OI ¾T 拳 (S 6T)92 -d TON '8Γ°Λ •(saq Ήΐ)3·Π '(ω 'HT)eZ"Z-S9"Z • ( s 'Ηΐ) 69 · 8' (ω
Figure imgf000171_0008
S081760 / S00Z OAV '( z Hs- = f'; Ήΐ) εΓ '(sjq Ήΐ) 8ε · ε' ( s ' m) fz'z 9 :( 9 p— oswa) 顺 — H T °% OI ¾T Fist (S 6T) 92 -d TON '8Γ ° Λ • (saq Ήΐ) 3 · Π' (ω 'HT) eZ "Z-S9" Z
'(ω 'HZ)SZ'L-SVL '(ω 'HT)erz-eo"z Ή Ήε) ε·ε 9 :(9ρ— oswa) 顺— ΗΤ
Figure imgf000172_0001
'(ω' HZ) SZ'L-SVL '(ω' HT) erz-eo "z Ή Ήε) ε · 9 :( 9 ρ— oswa) 顺 — Η Τ
Figure imgf000172_0001
缀 一 ^ )(Ι。ωΐ¾6·0 <§ωοθ2 -^ -^'2-^ίί ^:ΰ^¾4^'ε'2'ΐ-ΰ --ε 缀 一 ^) (Ι.ωΐ¾6 · 0 <§ ωοθ2-^-^ '2- ^ ίί ^: ΰ ^ ¾4 ^'ε'2'ΐ-ΰ --ε
(つ ^^ 一)べ^^— ベ ίί/ ΰ、 4 ― ε ΐ— , — ε (ΐ)  (One ^ ^ I) base ^^ - base ίί / ΰ, 4 - ε ΐ-, - ε (ΐ)
-(mz'zi=i 'p Ήΐ)8ε ΐ -(mz'zi = i 'p Ήΐ) 8ε ΐ
'(s 'Ηΐ)60·ΐΐ '(ZHZ 1=1" 'P 'Ηΐ)88·8 '(s 'Ηΐ)0 ·8 '(zH9"Z=f 'P 'HT)28"Z '(zH8"Z=f '( s ' Ηΐ) 60ΐΐ' (ZHZ 1 = 1 "'P' Ηΐ) 88 · 8 '( s ' Ηΐ) 0 · 8' ( z H9" Z = f 'P' HT) 28 "Z ' (zH8 "Z = f
'p Ήΐ)εζ·ζ '(ω 'm)zvL-LZ'L 'HS)SO'S 9 :(9p— oswa) N— HT °% 8 ¾T 'p Ήΐ) εζζ' (ω 'm) zvL-LZ'L' HS) SO'S 9 :( 9 p—oswa) N— H T °% 8 ¾T
S9S各粱呦 - 9Z  S9S each 呦-9Z
•(s ' ) VZl '(s 'HT)Z8"8 '(ζΗ ·ε=ί" 'P • ( s ') VZl '( s ' HT) Z8 "8' (ζΗ · ε = ί"'P
'H2)Z2"8
Figure imgf000172_0002
'H2) Z2 "8
Figure imgf000172_0002
'P 'Ηΐ) 0·9 '(zH9"9=f 'P 'HI)SS'S '(s 'H2)Z0"S 9 :( OSWa) 顺— Ητ °%ΐΖ ¾T'P' Ηΐ) 0 · 9 '( z H9 "9 = f' P 'HI) SS'S'(s' H2) Z0" S 9 :( OSWa) 顺 — Η τ °% ΐΖ ¾T
9S各粱呦 -f9Z [63 TO] 9S each beam -f9Z [63 TO]
•(zwsi=f 'p Ήΐ)ε6·π • (zwsi = f 'p Ήΐ) ε6π
'^ΗΖ'ΖΙ=ί 'P 'Ηΐ)68·8 '(ω Ήε)^·8— '(zH9"Z=f 'P 'Ηΐ)εθ·8 '(zH0"T '8·8=ί" 'PP Ή2)00"8 '(ΖΗΖ·Ζ=ί" Ήΐ)69"Ζ
Figure imgf000172_0003
' 'HZ)fVL '^ ΗΖ'ΖΙ = ί' P 'Ηΐ) 68 · 8' (ω Ήε) ^ · 8— '( z H9 "Z = f' P 'Ηΐ) εθ · 8' ( z H0" T '8 · 8 = ί "'PP Ή2) 00"8' (ΖΗΖ · Ζ = ί "Ήΐ) 69" Ζ
Figure imgf000172_0003
'' HZ) fVL
'； ΉΪ)ΖΓΖ '(s Ήε)26·ε '(s Ήε) ε 9 :(9p— oswa) 顺— HT °%S9 ? Φ '; ΉΪ) ΖΓΖ' (s Ήε) 26 · ε '( s Ήε) ε 9 :( 9 p— oswa) 顺 — H T °% S9? Φ
S92-^ i¾J^ ）
Figure imgf000172_0004
'P 'HT)6Z"Z '(ΖΗΖ·Ζ=ί" 'P 'HT)2Z"Z S92- ^ i¾J ^)
Figure imgf000172_0004
'P' HT) 6Z "Z '(ΖΗΖ · Ζ = ί"' P 'HT) 2Z "Z
' 'ΗΙ)£νί '(zHS"Z=f Ήΐ)ΐ2· '(zH2"6=f 'P Ήΐ)2ΓΖ '(s 'H2)S9"S '(S 'HS)8S"S  '' ΗΙ) £ νί '(zHS "Z = f Ήΐ) ΐ2' (zH2" 6 = f 'P Ήΐ) 2ΓΖ' (s' H2) S9 "S '(S' HS) 8S" S
9 :(9p- OS^a) 顺- HT °%09 ¾T。 呦^^ 翁^； (ΐ)„ίϋ
Figure imgf000172_0005
Oil S081760/S00Z OAV 7.28(1H, t, J=7.5Hz), 7.35— 7.45(3H, m), 7.54(1H, t, J=7.5Hz), 7.95— 8.10(3H, m), 9.21(1H, d, J=13Hz), 11.6(1H, d, J=13Hz), 12.1(1H, s). 9 :( 9 p-OS ^ a) 顺-H T °% 09 ¾T.呦 ^^ Okina ^; (ΐ) „ίϋ
Figure imgf000172_0005
Oil S081760 / S00Z OAV 7.28 (1H, t, J = 7.5Hz), 7.35-7.45 (3H, m), 7.54 (1H, t, J = 7.5Hz), 7.95-8.10 (3H, m), 9.21 (1H, d, J = 13Hz), 11.6 (1H, d, J = 13Hz), 12.1 (1H, s).
例 268:化合物番号 268 Example 268: Compound number 268
(1) 1- (3-フルオロフェ-ル )-3-トリフルォロメチル- 4,5-ジヒドロピラゾール- 5-オン 一般合成法 γと同様の方法により標題化合物を得た。収率 79%。 1 (1) 1- (3-Fluorophenyl) -3-trifluoromethyl-4,5-dihydropyrazol-5-one The title compound was obtained by the same method as in the general synthesis method γ. 79% yield. 1
H-NMR(DMSO-d ): δ 5.96(1H, s), 7.20- 7.30(1H, m), 7.50- 7.65(3H, m), 12.8(1H,  H-NMR (DMSO-d): δ 5.96 (1H, s), 7.20-7.30 (1H, m), 7.50-7.65 (3H, m), 12.8 (1H,
6  6
brs). brs).
(2) 1- (3-フルオロフェ-ル )-5-ォキソ -3-トリフルォロメチル- 4,5-ジヒドロピラゾール -4-カルバルデヒド  (2) 1- (3-fluorophenyl) -5-oxo-3-trifluoromethyl-4,5-dihydropyrazole-4-carbaldehyde
一般合成法 ocと同様の方法により標題化合物を得た。収率 49%。 1 The title compound was obtained in the same manner as in the general synthesis method oc. Yield 49%. 1
H-NMR(DMSO-d ): δ 6.85— 6.96(1H, m), 7.35- 7.45(1H, m), 7.80— 7.90(1H, m), H-NMR (DMSO-d): δ 6.85-6.96 (1H, m), 7.35-7.45 (1H, m), 7.80-7.90 (1H, m),
6  6
7.94-7.95(lH, m), 9.32(1H, s).  7.94-7.95 (lH, m), 9.32 (1H, s).
(3)化合物番号 268  (3) Compound No. 268
収率 69%。 ^-NMRCDMSO-d ): δ 7.05- 7.20(1H, m), 7.45-7.70(4H, m), Yield 69%. ^ -NMRCDMSO-d): δ 7.05- 7.20 (1H, m), 7.45-7.70 (4H, m),
6  6
7.80-7.95(3H, m), 8.10(1H, d, J=9Hz), 8.26(1H, d, J=8Hz), 8.90(1H, s),  7.80-7.95 (3H, m), 8.10 (1H, d, J = 9Hz), 8.26 (1H, d, J = 8Hz), 8.90 (1H, s),
10.5— 11.0(1H, br), 12.5— 13.0(1H, br). 10.5—11.0 (1H, br), 12.5—13.0 (1H, br).
例 269:化合物番号 269 Example 269: Compound number 269
(1) l-(tert-ブチル )-3-トリフルォロメチル- 4,5-ジヒドロピラゾール- 5-オン  (1) l- (tert-butyl) -3-trifluoromethyl-4,5-dihydropyrazol-5-one
一般合成法 γと同様の方法により標題化合物を得た。収率 34%。 1 The title compound was obtained in the same manner as in General Synthesis Method γ. Yield 34%. 1
H-NMR(DMSO-d ): δ 1.53(9H, s), 5.72(1H, s), 11.5(1H, s).  H-NMR (DMSO-d): δ 1.53 (9H, s), 5.72 (1H, s), 11.5 (1H, s).
6  6
(2) l-(tert-ブチル )-5-ォキソ -3-トリフルォロメチル- 4,5-ジヒドロピラゾール- 4-カル バルデヒド  (2) l- (tert-butyl) -5-oxo-3-trifluoromethyl-4,5-dihydropyrazole-4-carbaldehyde
一般合成法 aと同様の方法により標題ィ匕合物を得た。収率 41%。 1H-NMR(CDC1 ): The title compound was obtained in the same manner as in General Synthesis Method a. Yield 41%. 1H-NMR (CDC1):
3 δ 1.64(9H, s), 9.41(1H, brs), 9.73(1H, s).  3 δ 1.64 (9H, s), 9.41 (1H, brs), 9.73 (1H, s).
(3)化合物番号 269  (3) Compound No. 269
収率 63%。 ^-NMRCDMSO-d ): δ 1.57(9H, s), 7.50(1H, t, J=7.5Hz), 7.56(1H, t, 63% yield. ^ -NMRCDMSO-d): δ 1.57 (9H, s), 7.50 (1H, t, J = 7.5Hz), 7.56 (1H, t,
6  6
J=7.5Hz), 7.60(1H, d, J=9Hz), 7.91(1H, d, J=7.5Hz), 8.04(1H, d, J=9Hz), 8.21(1H, d, J=7.5Hz), 8.74(1H, brs), 10.6(1H, brs), 12.9(1H, brs). '(zH8=f 'P 'ΗΙ)£Ζ'8 '(zH6=f 'P 'HT)S0"8 '(zH8=f 'P Ήΐ)26"Ζ '(zH6=f 'P Ήΐ)ΐ9"Ζ '(ω 'HS)SS'Z— S 'Z
Figure imgf000174_0001
'H 9·ΐ '(zHS"Z=f 'm^s Ήζ 'Ι '(zHS" =f '； Ήε)ΐ6 9 :( oswa) 顺— HT °%8S ¾T
Figure imgf000174_0002
J = 7.5Hz), 7.60 (1H, d, J = 9Hz), 7.91 (1H, d, J = 7.5Hz), 8.04 (1H, d, J = 9Hz), 8.21 (1H, d, J = 7.5Hz) ), 8.74 (1H, brs), 10.6 (1H, brs), 12.9 (1H, brs). '(zH8 = f' P 'ΗΙ) £ Ζ'8' (zH6 = f 'P' HT) S0 "8 '(zH8 = f' P Ήΐ) 26" Ζ '(zH6 = f' P Ήΐ) ΐ9 " Ζ '(ω' HS) SS'Z— S 'Z
Figure imgf000174_0001
'H 9 · ΐ' (zHS "Z = f 'm ^ s Ήζ' Ι '(zHS" = f'; Ήε) ΐ6 9 :( oswa) 顺 — H T °% 8S ¾T
Figure imgf000174_0002
•(s 'HT)SZ"6 '(zHS" =f ^ 'H2)Z6"S '(zHS" =f '^urn 'Η 69·ΐ '(zHS" =f '； s 'H2) 2"T '(zHS" =f '； Ήε)68 9 :( OSWa) 顺— H  • (s' HT) SZ "6 '(zHS" = f ^' H2) Z6 "S '(zHS" = f' ^ urn 'Η 69 · ΐ' (zHS "= f '; s' H2) 2" T '(zHS "= f'; Ήε) 68 9 :( OSWa) 顺 — H
T °%89 ¾i ^m^ ^mm^ ^ m n ^- -
Figure imgf000174_0003
 T °% 89 ¾i ^ m ^ ^ mm ^ ^ mn ^--
Figure imgf000174_0003
'Η Ζ9·ΐ '(zHS" =f 'm^s Ήζ) ΖΊ '(zHS" =f Ήε)Ζ8 9 :(9p—〇SWa) N— H 'Η Ζ9 · ΐ' (zHS "= f 'm ^ s Ήζ) ΖΊ'(zHS" = f Ήε) Ζ8 9 :( 9 p—〇SWa) N— H
T °%SS ¾i °^ ¾^^ ®^C)T^)¾^ )#^^ん ¾ 一 ベ - s - /— ^^c^ - s' ^ ci / fH- ε- ( ^ : - u)- ΐ (ΐ)
Figure imgf000174_0004
T °% SS ¾i ° ^ ¾ ^^ ® ^ C) T ^) ¾ ^) # ^^ んu)-ΐ (ΐ)
Figure imgf000174_0004
"(s-i 'Ηΐ)Ζ ΐ '(s Ήΐ)9 ΐ '(s-i Ήΐ)3Ζ·8 '(zH8=f 'P 'HI)SS'8 '(zH6=f 'P 'Ηΐ)εθ·8 '(zH8=f 'P Ήΐ)ΐ6"Ζ '(zH6=f 'P Ήΐ)09"Ζ '(ω 'ΗΖ)^ L-W L '(ω 'HD^Z' -QV "(si 'Ηΐ) Ζ ΐ' ( s Ήΐ) 9 ΐ '(si Ήΐ) 3Ζ8' ( z H8 = f 'P' HI) SS'8 '( z H6 = f' P 'Ηΐ) εθ 8 '(zH8 = f' P Ήΐ) ΐ6 "Ζ '(zH6 = f' P Ήΐ) 09" Ζ '(ω' ΗΖ) ^ LW L '(ω' HD ^ Z '-QV
'(ω 'Η8)06·ΐ- 09·ΐ '(ω 'H OS'I- ΟΓΐ 9 :(9ρ- Ν- Ητ °%ΖΖ ¾ί '(ω' Η8) 06ΐ-09ΐΐ '(ω' H OS'I- ΟΓΐ 9 :( 9 ρ- Ν- Η τ °% ΖΖ ¾ί
0 2-^ ί¾?^ (ε) Xs 'Ηΐ) 60 2- ^ ί¾? ^ (Ε) X s ' Ηΐ) 6
'(ω 'HI)S -ΟΓ '(ω 'Η9)00 — 08·ΐ '(ω 'Ηΐ)08'ΐ- S9'I '(ω 'HS)0S'I- SI'I 9 :(
Figure imgf000174_0005
Figure imgf000174_0006
(ζ)'(ω' HI) S -ΟΓ '(ω' Η9) 00 — 08 · ΐ '(ω' Ηΐ) 08'ΐ- S9'I '(ω' HS) 0S'I- SI'I 9 :(
Figure imgf000174_0005
Figure imgf000174_0006
(ζ)
•(s 'Ηΐ)Γΐΐ '(s Ήΐ)0 ·3• ( s 'Ηΐ) Γΐΐ' (s Ήΐ) 0
'(ω 'Ηΐ)0 — 00·， '(ω 'ΗΖ)06·ΐ- SS'I '(ω 'HS)0S'I- ΟΓΐ 9 :(9ρ— OSWa) 顺— Η '(ω' Ηΐ) 0 — 00 ·, '(ω' ΗΖ) 06 · ΐ- SS'I '(ω' HS) 0S'I- ΟΓΐ 9 :( 9 ρ— OSWa) 顺 — Η
τ °%6ε ¾τ ^m^ ^mm^ ^ mん ^^ 一
Figure imgf000174_0007
(ΐ)
Figure imgf000174_0008
ZLY S081760/S00Z OAV τ °%ΐ6 ¾τ
Figure imgf000175_0001
τ °% 6ε ¾τ ^ m ^ ^ mm ^ ^ m ^^ one
Figure imgf000174_0007
(ΐ)
Figure imgf000174_0008
ZLY S081760 / S00Z OAV τ °% ΐ6 ¾τ
Figure imgf000175_0001
"(s-i 'HI)SS ΐ '(s-i 'Ηΐ)88·8 '(s 'Ηΐ) ·8 Ήΐ)3Γ8 '(s Ήΐ)66"Ζ "(si 'HI) SS ΐ' (si 'Ηΐ) 88 · 8' (s 'Ηΐ) · 8 Ήΐ) 3Γ8' ( s Ήΐ) 66" Ζ
'P 'Ηΐ)ΐΓ
Figure imgf000175_0002
Ήΐ)ΙΥί 'P 'HT)SS"Z '(ΖΗΖ·Ζ=1" '； 'HS)62"Z '(s 'H 90'S '(s Ήε)80· 9 :( OSW I) 顺— HT °%Z9 ? φ'P' Ηΐ) ΐΓ
Figure imgf000175_0002
Ήΐ) ΙΥί 'P' HT) SS "Z '(ΖΗΖ · Ζ = 1"';'HS) 62 "Z' (s 'H 90'S' (s Ήε) 80 · 9 :( OSW I) 顺 — H T °% Z9? Φ
Figure imgf000175_0003
Figure imgf000175_0003
-(^ΗΖτΐ=ί 'P 'Ηΐ)8Γΐΐ '(ζΗΟ·εΐ=ί" 'P 'Ηΐ) 8·8 '(ΖΗ6 =Γ 'P Ήΐ)2ε·8 '(s 'Ηΐ) 8 '(zHO"Z=f 'P 'Ηΐ) ΐ·8 '(zHS'Z=f 'P 'H2)00"8 '(s Ήΐ)Ζ6"Ζ '(ΖΗΐ·8=ί" 'P 'HT)OZ"Z
Figure imgf000175_0004
'HT)OS"Z '(ω ΉΖ) νί-8£Ί -(^ ΗΖτΐ = ί 'P' Ηΐ) 8Γΐΐ '(ζΗΟεΐ = ί "' P 'Ηΐ) 8.8' ( Ζ Η6 = Γ 'P Ήΐ) 2ε8' ( s 'Ηΐ) 8' ( z HO "Z = f 'P' Ηΐ) ΐ8 '(zHS'Z = f' P 'H2) 00"8' (s Ήΐ) Ζ6 "Ζ '(ΖΗΐ8 = ί"' P 'HT) OZ "Z
Figure imgf000175_0004
'HT) OS "Z' (ω ΉΖ) νί-8 £ Ί
'； ΉΪ)3ΓΖ '(s Ήε)60· '(S 'm)wz 9 :(9p— oswa) N Ht °% ε ¾T '; ΉΪ) 3ΓΖ' (s Ήε) 60 · '( S ' m) wz 9 :( 9 p— oswa) NH t °% ε ¾T
•( • (
'P 'HT)S2"8 '(ω Ήε)0ΐ·8— 06·
Figure imgf000175_0005
'P' HT) S2 "8 '(ω Ήε) 0ΐ8—06
Figure imgf000175_0005
' 'Η ΐ ·
Figure imgf000175_0006
'； Ήΐ)3ΓΖ '(s Ήε)22·ζ 9 :( OSWd) Ν— Ητ °%99 ¾ί '' Η ΐ ·
Figure imgf000175_0006
'; Ήΐ) 3ΓΖ' (s Ήε) 22 · ζ 9 :( OSWd) Ν— Η τ °% 99 ¾ί
•(jq Ήΐ)ο·εΐ— s ΐ '( 'HI)S'II ε·π '(s 'ΗΪ)ΖΖ·8• (jq Ήΐ) ο · εΐ— s ΐ '(' HI) S'II ε · π '( s ' ΗΪ) ΖΖ8
'(zH8=f 'P 'HT)S2"8 '(ω 'HS)00"8-06"Z '(zH8=f ' 'HT)S8"Z '(zH8=f ' 'HT)eS"Z
Figure imgf000175_0007
Ήΐ)62"Ζ 9 :(9p—〇SW I) 顺— HT °% ¾T '(zH8 = f' P 'HT) S2 "8' (ω 'HS) 00" 8-06 "Z' (zH8 = f '' HT) S8" Z '(zH8 = f''HT) eS "Z
Figure imgf000175_0007
Ήΐ) 62 "Ζ 9 :( 9 p—〇SW I) 顺 — H T °% ¾T
° 餱 各 S60I9I- ベ - べ ίί,^ΰ、 ;^、- ΐ- ^ ci / fH- cH-- ε° 餱 Each S60I9I-be-be-ίί, ^ ΰ,; ^, -ΐ- ^ ci / fH- cH-- ε
•(saq 'Ηΐ)8·ΐΐ
Figure imgf000175_0008
'P 'HT)SZ"Z
Figure imgf000175_0009
'HT)S2"Z '(sjq 'HS) S 9 :(9p—〇SW I) 顺— H • (saq 'Ηΐ) 8 · ΐΐ
Figure imgf000175_0008
'P' HT) SZ "Z
Figure imgf000175_0009
'HT) S2 "Z' (sjq 'HS) S 9 :( 9 p—〇SW I) 顺 — H
T °%98 ¾ί °^ ¾^^®^ τ^)¾^ )#^^ 1 ^ -
Figure imgf000175_0010
 T °% 98 ¾ί ° ^ ¾ ^^ ® ^ τ ^) ¾ ^) # ^^ 1 ^-
Figure imgf000175_0010
•(jq 'Ηΐ)9 ΐ- S ΐ '(s Ήΐ)9 ΐ q 'HI)S8'8- SZ'8
Figure imgf000175_0011
S081760/S00Z OAV H-NMR(DMSO-d ): δ 4.11(3H, s), 7.30(1H, dt, J=8.0, 1.1Hz), 7.41(1H, t, • (jq 'Ηΐ) 9 ΐ- S ΐ' ( s Ήΐ) 9 ΐ q 'HI) S8'8- SZ'8
Figure imgf000175_0011
S081760 / S00Z OAV H-NMR (DMSO-d): δ 4.11 (3H, s), 7.30 (1H, dt, J = 8.0, 1.1Hz), 7.41 (1H, t,
6  6
J=7.4Hz), 7.51(3H, dt, J=12.0, 3.3Hz), 7.71(1H, d, J=8.2Hz), 7.96(2H, d, J=8.8Hz), 8.01(1H, s), 8.16(1H, d, J=7.7Hz), 8.48(1H, s), 8.95(1H, d, J=13.4Hz), 12.57(1H, d, J=13.4Hz).  J = 7.4Hz), 7.51 (3H, dt, J = 12.0, 3.3Hz), 7.71 (1H, d, J = 8.2Hz), 7.96 (2H, d, J = 8.8Hz), 8.01 (1H, s) , 8.16 (1H, d, J = 7.7Hz), 8.48 (1H, s), 8.95 (1H, d, J = 13.4Hz), 12.57 (1H, d, J = 13.4Hz).
例 277:化合物番号 277 Example 277: Compound number 277
収率 94%。 'H-NMRCDMSO-d ): δ 3.46(3Η, s), 4.08(3Η, s), 7.41(1Η, t, J=7.4Hz), 94% yield. 'H-NMRCDMSO-d): δ 3.46 (3Η, s), 4.08 (3Η, s), 7.41 (1Η, t, J = 7.4Hz),
6  6
7.51(1Η, t, J=7.7Hz), 7.71(1H, d, J=8.4Hz), 7.99(1H, s), 8.15(1H, d, J=8.1Hz), 8.43(1H, s), 8.85(1H, brs), 12.58(1H, brs).  7.51 (1Η, t, J = 7.7Hz), 7.71 (1H, d, J = 8.4Hz), 7.99 (1H, s), 8.15 (1H, d, J = 8.1Hz), 8.43 (1H, s), 8.85 (1H, brs), 12.58 (1H, brs).
例 278:化合物番号 278(—般合成法 E) Example 278: Compound number 278 (General synthesis method E)
Journal of Medicinal Chemistry, Vol.44, No.25, p.4339- 4358(2001)に記載された「 Procedure Gjと同様の方法により標題ィ匕合物を得た。  The title compound was obtained by the same method as in "Procedure Gj" described in Journal of Medicinal Chemistry, Vol. 44, No. 25, p. 4339-4358 (2001).
収率 55%。 ^-NMRCDMSO-d ): δ 6.85(1H, d, J=7.5Hz), 6.93(1H, t, J=7.5Hz), Yield 55%. ^ -NMRCDMSO-d): δ 6.85 (1H, d, J = 7.5Hz), 6.93 (1H, t, J = 7.5Hz),
6  6
7.00(1H, t, J=7.5Hz), 7.38(1H, t, J=8Hz), 7.49(1H, t, J=8Hz), 7.59(1H, d, J=8Hz), 7.62(1H, d, J=7.5Hz), 7.85(1H, d, J=8.5Hz), 7.95(1H, d, J=8Hz), 8.15(1H, d, J=8.5Hz), 8.75(1H, d, J=13.5Hz), 9.95(1H, s), 10.5(1H, s), 11.3(1H, d, J=13.5Hz). 例 279:化合物番号 279  7.00 (1H, t, J = 7.5Hz), 7.38 (1H, t, J = 8Hz), 7.49 (1H, t, J = 8Hz), 7.59 (1H, d, J = 8Hz), 7.62 (1H, d , J = 7.5Hz), 7.85 (1H, d, J = 8.5Hz), 7.95 (1H, d, J = 8Hz), 8.15 (1H, d, J = 8.5Hz), 8.75 (1H, d, J = 13.5Hz), 9.95 (1H, s), 10.5 (1H, s), 11.3 (1H, d, J = 13.5Hz) .Example 279: Compound number 279
(1) 1- (3-ヒドロキシベンジル) -3-トリフルォロメチル- 4,5-ジヒドロピラゾール- 5-オン 一般合成法 γと同様の方法により標題ィ匕合物を得た。収率 51%。 1 (1) 1- (3-Hydroxybenzyl) -3-trifluoromethyl-4,5-dihydropyrazol-5-one The title compound was obtained by the same method as in the general synthesis method γ. Yield 51%. 1
H-NMR(DMSO-d ): δ 5.06(2H, s), 5.77(1H, s), 6.50— 6.70(3H, m), 7.12(1H, t,  H-NMR (DMSO-d): δ 5.06 (2H, s), 5.77 (1H, s), 6.50-6.70 (3H, m), 7.12 (1H, t,
6  6
J=7.5Hz), 9.46(1H, brs), 11.9(1H, s).  J = 7.5Hz), 9.46 (1H, brs), 11.9 (1H, s).
(2) 4-ジメチルアミノメチレン- 1-(3-ヒドロキシベンジル) -3-トリフルォロメチル- 4,5-ジ ヒドロピラゾール- 5-オン  (2) 4-dimethylaminomethylene-1- (3-hydroxybenzyl) -3-trifluoromethyl-4,5-dihydropyrazol-5-one
一般合成法 Θと同様の方法により標題ィ匕合物を得た。  The title compound was obtained in the same manner as in General Synthesis Method II.
(3)化合物番号 279  (3) Compound No. 279
一般合成法 Cと同様の方法により標題化合物を得た。収率 49%。 1 The title compound was obtained in the same manner as in General Synthesis Method C. Yield 49%. 1
H-NMR(DMSO-d ): δ 4.96(2H, s), 6.65— 6.75(3H, m), 7.10- 7.20(1H, m), H-NMR (DMSO-d): δ 4.96 (2H, s), 6.65-6.75 (3H, m), 7.10-7.20 (1H, m),
6  6
7.45-7.55(2H, m), 7.59(1H, d, J=9Hz), 7.91(1H, d, J=8Hz), 8.05(1H, d, J=9Hz), 8.24(1H, d, J=8Hz), 8.81(1H, brs), 9.44(1H, brs), 10.6(1H, brs), 12.8(1H, brs). •(zHST=f 'P Ήΐ)^Π '(s Ήΐ)9 ΐ '(s Ήΐ)Ο ΐ
Figure imgf000177_0001
7.45-7.55 (2H, m), 7.59 (1H, d, J = 9Hz), 7.91 (1H, d, J = 8Hz), 8.05 (1H, d, J = 9Hz), 8.24 (1H, d, J = 8Hz), 8.81 (1H, brs), 9.44 (1H, brs), 10.6 (1H, brs), 12.8 (1H, brs). • ( z HST = f 'P Ήΐ) ^ Π' ( s Ήΐ) 9 ΐ '( s Ήΐ) Ο ΐ
Figure imgf000177_0001
P 'HDZVL '(ZHS 'ε·8=ί" 'PP Ήΐ)ΐΟ"Ζ '(zHS"8=f 'P 'HT)^8"9 9 :( P-OS^a)H N-H P 'HDZVL' ( Z HS 'ε8 = ί "' PP Ήΐ) ΐΟ" Ζ '(zHS "8 = f' P 'HT) ^ 8" 9 9 :( P-OS ^ a) H NH
•(zHST=f 'P 'Ηΐ)ε·ΐΐ '(s Ήΐ)9 ΐ '(s Ήΐ)Ο ΐ• ( z HST = f 'P' Ηΐ) εΐΐΐΐ '( s Ήΐ) 9 ΐ' ( s Ήΐ) Ο ΐ
·
Figure imgf000177_0002
' 'HT)6S"Z '(ZHS'I 'S"8=f 'PP 'Ηΐ)66·9 '(zHS"T=f 'P 'HT)S8"9 9 '·( P-OS^a)H N-H ·
Figure imgf000177_0002
'' HT) 6S "Z '(ZHS'I'S" 8 = f 'PP' Ηΐ) 66 · 9 '(zHS "T = f' P 'HT) S8" 9 9' · (P-OS ^ a ) H NH
•(ZHS'9=f 'P 'HI)S ΐ 'Wfl= 'P Ήΐ)ζ·2ΐ '(zHS^T=f 'P 'HT)S6"8 '(zHS"9=f 'P 'Ηΐ)06·8 '(zH2"8=f 'P 'ΗΙ)£Ζ'8 '(zHS"8=f 'P 'H2)66"Z
Figure imgf000177_0003
' 'HZ)6VL '(zH2-8=f ' 'HDZVL '(zH2-8=f ' 'HT)82"Z 9 :( OSWd) N— HT °%SS ¾T • (ZHS'9 = f 'P' HI) S ΐ 'Wfl =' P Ήΐ) ζ2ΐ '(zHS ^ T = f' P 'HT) S6 "8'(zHS" 9 = f 'P' Ηΐ ) 06 · 8 '(zH2 "8 = f' P 'ΗΙ) £ Ζ'8'(zHS" 8 = f 'P' H2) 66 "Z
Figure imgf000177_0003
'' HZ) 6VL '( z H2-8 = f''HDZVL' ( z H2-8 = f '' HT) 82 "Z 9 :( OSWd) N— H T °% SS ¾T
•(zHS'9=f 'P Ήΐ)^2ΐ '(zHW=f 'P 'Ηΐ) ·ΐΐ '(zHS'9=f 'P 'Ηΐ)0Γ8 '(ζ服 =f 'P 'HI)S9'8 '(zH8=f 'P 'HI)SS'8
Figure imgf000177_0004
' 'Ηΐ)ΐΖ· ' Ήΐ)99"Ζ '(ω 'HS)0S"Z-SS"Z • (zHS'9 = f 'P Ήΐ) ^ 2ΐ' ( z HW = f 'P' Ηΐ) ΐΐΐΐ '(zHS'9 = f' P 'Ηΐ) 0Γ8' ( ζ服 = f 'P' HI) S9'8 '( z H8 = f' P 'HI) SS'8
Figure imgf000177_0004
'' Ηΐ) ΐΖ '' Ήΐ) 99 "Ζ '(ω' HS) 0S" Z-SS "Z
'(ΖΗΪ '8=Γ 'ρ Ήΐ)εΓζ '(s 'u z'z 9 :(9ρ— oswa) 顺— ΗΤ °%S ¾ί '(Ζ ΗΪ' 8 = Γ 'ρ Ήΐ) εΓζ'(s' u z'z 9 :( 9 ρ- oswa)顺- Η Τ °% S ¾ί
082-^ ί¾?^ (Ζ) 082- ^ ί¾? ^ (Ζ)
。^拳 4 べ 各 S6090/S6绻 ^国:ベ - べ ίί,^ΰ、 ¾ ^- ΐ- cH - ε. ^ Fist 4 Be S6090 / S6 绻 ^ Country: Be-be ίί, ^ ΰ, ¾ ^-ΐ- cH-ε
•(sjq 'Ηΐ) ·ΐΐ '(ω Ήΐ)3Γ8-30·8 '(ω 'HWL-OVL '(ω 'ΗΙ) ΖΊ-0νί '(saq 'HS)S9' 9 :( Ρ- OSW I) 顺- Η (Sjq 'Ηΐ) ΐΐΐΐ (ω Ήΐ) 3Ήΐ8-30顺-Η
τ °%68 ¾τ τ °% 68 ¾τ
Figure imgf000177_0005
Figure imgf000177_0006
91V S081760/S00Z OAV
Figure imgf000178_0001
Figure imgf000177_0005
Figure imgf000177_0006
91V S081760 / S00Z OAV
Figure imgf000178_0001
'(zHS" =f Ήΐ)62" '(s Ήε) ·ε '(s '蹄 ·ε '(s Ή£)ζζτ 9 :(9p— oswa) 顺— H ベ - s- /— ½
Figure imgf000178_0002
(ζ) '(zHS "= f Ήΐ) 62"' (s Ήε) · ε '(s' hoof · ε' ( s Ή £) ζζτ 9 :( 9 p— oswa) 顺 — H be-s- / — ½
Figure imgf000178_0002
(ζ)
•(saq 'Ηΐ)8 ΐ
Figure imgf000178_0003
• (saq 'Ηΐ) 8 ΐ
Figure imgf000178_0003
' 'Ηΐ)6 · '(zHS" =f 'HT)9S"Z '(s 'Ηΐ 'S '(s 'HS) S 9 :(9p— OSWa) 顺— H '' Ηΐ) 6 · '(zHS "= f' HT) 9S" Z '(s'Ηΐ' S '(s' HS) S 9 :( 9 p— OSWa) 顺 — H
T °%98 ¾i。 呦^ 遨 C)Tコ 翁^; ん ^^ 一 T °% 98 ¾i.呦 ^ groud C) T KO ^^
Figure imgf000178_0004
(I)
Figure imgf000178_0004
(I)
•(ζΗΓ ΐ=ί" 'Ρ 'Ηΐ)80 ΐ '(s 'Ηΐ)ε ·Οΐ '(ΖΗΖ·εΐ=ί" 'Ρ 'Ηΐ)98·8 '(s Ήΐ)93·8 '(ΖΗΓ2 'Z'L=i 'W 'HT)62"8 WL=i 'Ρ 'ΗΙ)ΖΖ'8 '(zH0"6=f 'Ρ 'Ηΐ) 0·8• ( ζ ΗΓ ΐ = ί "'Ρ' Ηΐ) 80 ΐ '( s ' Ηΐ) ε · Οΐ' (ΖΗΖ · εΐ = ί"'Ρ' Ηΐ) 98 · 8 '( s Ήΐ) 93 · 8' ( Ζ ΗΓ2 'Z'L = i' W 'HT) 62 "8 WL = i' Ρ 'ΗΙ) ΖΖ'8' ( z H0" 6 = f 'Ρ' Ηΐ) 0
Figure imgf000178_0005
'Ρ Ήΐ)09"Ζ '(ΖΗΖ·ΐ=ί"
Figure imgf000178_0005
'Ρ Ήΐ) 09 "Ζ' (ΖΗΖ · ΐ = ί"
'HT)6S"Z '(zHS" =f 'Ρ 'HT)eS"Z '(zHS" =f Ήΐ)6Υί '(s 'HZ)£VL '(s 'Η£)9£'Ζ 9 '·( 'HT) 6S "Z'(zHS" = f 'Ρ' HT) eS "Z '(zHS" = f Ήΐ) 6Υί' ( s ' HZ) £ VL '( s ' Η £) 9 £' Ζ 9 ' · (
P-OS a)H N-HT 0% *¾ί。 呦^ 遨 翁^； α¾¾ ^^ 一 P-OS a) H NH T 0 % * ¾ί. Α¾¾ ^^ one
98S各粱呦^ [9910] Xs 'HWST
Figure imgf000178_0006
'P 'HWZl '(s Ήΐ)6Ζ ΐ 98S each 呦 ^ [9910] X s ' HWST
Figure imgf000178_0006
'P' HWZl '( s Ήΐ) 6Ζ ΐ
'(ζΗΐ^ΐ=Γ 'P 'Ηΐ)ε6·8 '(s 'Ηΐ)99·8 '(ΖΗΓ8=Γ 'Ρ 'H2)92"8 '^ΗΖ'6=ί 'Ρ Ήΐ)2Γ8 '( ζ Ηΐ ^ ΐ = Γ' P 'Ηΐ) ε6 · 8' ( s '99) 99 · 8 '( Ζ ΗΓ8 = Γ' Ρ 'H2) 92 "8' ^ ΗΖ'6 = ί 'Ρ Ήΐ) 2Γ8
'(ΖΗΖ·Ζ=ί" 'Ρ 'HT)½" '(ΖΗΖ·Ζ=ί" 'Ρ 'HT)S8"Z
Figure imgf000178_0007
'(ΖΗΖ · Ζ = ί "' Ρ 'HT) ½"' (ΖΗΖ · Ζ = ί "'Ρ' HT) S8" Z
Figure imgf000178_0007
'Ρ 'HT)S9"Z
Figure imgf000178_0008
'； 'HT)SS"Z 9 :( OSWa) 顺— H 'Ρ' HT) S9 "Z
Figure imgf000178_0008
';' HT) SS "Z 9 :( OSWa) 顺 — H
T °%9i ¾i ^m^ ^mm^ ^ m m^m- 各粱呦 :S82p} T °% 9i ¾i ^ m ^ ^ mm ^ ^ mm ^ m- each beam: S82p}
•(ZH9
Figure imgf000178_0009
• (ZH9
Figure imgf000178_0009
'P 'HT)92"8 '(ΖΗΓ2 '6·9=ί" 'PP 'Η2)6Γ8 6=1" 'P Ήΐ)2Γ8 '(ZH8"T O"Z=f 'PP ' 0·8 '(ZHS- =f 'P 'H\)WL '(ΖΗ0·6=1" 'P 'H\)W L '(ω 'HZ)W L-W L 9■( v-osnaWn-H, °% ¾τ。 呦^ 遨 翁^； a¾¾ ^^ 一
Figure imgf000178_0010
9 I- S081760/S00Z OAV '(ω 'HT)0S"8-02"8 '(ω Ήΐ)02·8-3Γ8 '(ω 'H2)S0"8-S6"Z '(ω 'HT)06"Z-S8"Z 'P' HT) 92 "8 '( Ζ ΗΓ2' 6.99 = ί"'PP' Η2) 6Γ8 6 = 1 "'P Ήΐ) 2Γ8' ( Z H8" TO "Z = f 'PP' 0.8 '( Z HS- = f' P 'H \) WL' (ΖΗ0.6 = 1 '''P' H \) WL '(ω' HZ) W LW L 9 ■ (v-osnaWn-H, °% ¾τ A¾¾ ^^ one
Figure imgf000178_0010
9 I- S081760 / S00Z OAV '(ω' HT) 0S "8-02" 8 '(ω Ήΐ) 02 · 8-3Γ8' (ω 'H2) S0 "8-S6"Z' (ω 'HT) 06 "Z-S8" Z
'(ω 'H2)0Z"Z-09"Z '(ω 'HS)SS'Z— S 'Z 9 :(9ρ— OSW I) 顺— Ητ °%0S ¾ί '(ω' H2) 0Z "Z-09" Z '(ω' HS) SS'Z— S 'Z 9 :( 9 ρ— OSW I) 顺 — Η τ °% 0S ¾ί
•(s 'Ηΐ) ·Οΐ • ( s ' Ηΐ) · Οΐ
'(s 'Ηΐ)9Γ6 '(ω 'Ηΐ)0ε·8— '(ω 'H2)06"Z-^8"Z '(s 'HT)28"Z '(zHS'8=f 'P '( s ' Ηΐ) 9Γ6 '(ω' Ηΐ) 0ε · 8— '(ω' H2) 06 "Z- ^ 8" Z '(s' HT) 28 "Z '(zHS'8 = f' P
Ήΐ)9Ζ"Ζ '(zH6=f 'P Ήΐ)99"Ζ '(ω 'HS)SS'Z— SS' 9 :( OSWa) 顺— HT °%SS ¾T Ήΐ) 9Ζ "Ζ '(zH6 = f' P Ήΐ) 99" Ζ '(ω' HS) SS'Z— SS '9 :( OSWa) 顺 — H T °% SS ¾T
•(s 'Ηΐ)0·ΐΐ '(s Ήΐ)ΐ ΐ
Figure imgf000179_0001
'P 'Ηΐ)ΐ ·8 '(ZHS'8=f • ( s 'Ηΐ) 0 · ΐΐ' ( s Ήΐ) ΐ ΐ
Figure imgf000179_0001
'P' Ηΐ) ΐ8 '(ZHS'8 = f
'P 'Ηΐ) Γ8 '(zHS'8=f ' 'HI)SS'8 '(zH6=f 'P 'ΗΙ)ΖΖ'8 '(zHS'8=f 'P Ήΐ)ΖΓ8
Figure imgf000179_0002
'P 'HT)W 'P' Ηΐ) Γ8 '(zHS'8 = f''HI)SS'8' ( z H6 = f 'P' ΗΙ) ΖΖ'8 '(zHS'8 = f' P Ήΐ) ΖΓ8
Figure imgf000179_0002
'P' HT) W
'(zHZ=f 'P 'HT)2S"Z '(zHZ=f '； Ήΐ)9Υί 9 :( OSWd) N— HT °%0S ¾T '(zHZ = f' P 'HT) 2S "Z' (zHZ = f '; Ήΐ) 9Υί 9 :( OSWd) N— H T °% 0S ¾T
•(s ΉΙ)Υ01 '(s Ήΐ)Ζ9"6 '(zHS"S=f 'P 'H2)28"8 '(ω 'Ηΐ)0ε·8— '(zHS"S=f 'P • (sΉΙ) Υ01 '(s () Ζ9 "6' (zHS" S = f'P 'H2) 28 "8' (ω'Ηΐ) 0ε8 — '(zHS" S = f'P
'Η Ζ6· '(ω 'HT)06"Z-08"Z '(ω 'H )SS'Z— 0，· 9 :( OSWd) N— Ητ °%8ΐ ¾T 'Η Ζ6 ·' (ω 'HT) 06 "Z-08"Z' (ω 'H) SS'Z— 0, 9 :( OSWd) N— τ τ °% 8ΐ ¾T
06S各粱呦^ z 06S each 呦 ^ z
•(sjq 'Ηΐ) ·0ΐ '(s 'Ηΐ)0Γ6 '(^ 'HI)SS'6- SI'6 • (sjq 'Ηΐ) 0ΐ' ( s ' Ηΐ) 0Γ6 '(^' HI) SS'6- SI'6
'(ω 'HT)S8"8-eZ"8 '(ω 'HT)e^"8-SS"8 '(ω 'Ηΐ)0ε·8— '(ω 'HT)06"Z-08"Z  '(ω' HT) S8 "8-eZ" 8 '(ω' HT) e ^ "8-SS" 8 '(ω' Ηΐ) 0ε · 8— '(ω' HT) 06 "Z-08" Z
'(ω 'HT)e9"z-ee"z '(ω 'H )SS'Z ο · 9 :(9p— oswa) 顺— HT °%8Ϊ ¾T '(ω' HT) e9 "z-ee" z '(ω' H) SS'Z ο · 9 :( 9 p—oswa) 顺 — H T °% 8Ϊ ¾T
68S各粱呦 [Ζ9Ϊ0] •(s Ήΐ)8 ΐ '(s 'Ηΐ)86·6 '(ω 'HI)S8'8— SZ'8 '(zH6=f 'P 'HT)9S"8 '(^ 'HS)SS'8— SI'8 68S each beam [Ζ9Ϊ0] • ( s Ήΐ) 8 ΐ '( s ' Ηΐ) 86 · 6' (ω 'HI) S8'8— SZ'8' ( z H6 = f 'P' HT) 9S "8 '(^' HS) SS'8— SI'8
'(in 'HT)er8-S0"8
Figure imgf000179_0003
'P Ήΐ)Ζ8"Ζ '(ω 'HT)eZ"Z-S9"Z 'P 'HT)SS"Z '(in' HT) er8-S0 "8
Figure imgf000179_0003
'P Ήΐ) Ζ8 "Ζ' (ω 'HT) eZ" Z-S9 "Z' P 'HT) SS" Z
'P 'HT)2S"Z '(ω 'HI)SS'Z— 0，· 9 :( OSW I) 顺— HT °%Z ¾T 'P' HT) 2S "Z '(ω' HI) SS'Z— 0, 9 :( OSW I) 顺 — H T °% Z ¾T
\ =[ 'P 'Ηΐ)8·ΐΐ '(s Ήΐ)9 ΐ '{ =[ 'P 'HI)S6'8 \ = ['P' Ηΐ) 8ΐΐ ΐΐ '( s Ήΐ) 9 ΐ' {= ['P' HI) S6'8
'(zH8=f 'P 'HT)S2"8 '(zH6=f 'P 'Ηΐ)90·8 '(zH8=f 'P Ήΐ)20"8 '(zH8=f 'P Ήΐ)26"Ζ  '(zH8 = f' P 'HT) S2 "8' (zH6 = f 'P' Ηΐ) 90 · 8 '(zH8 = f' P Ήΐ) 20" 8 '(zH8 = f' P Ήΐ) 26 "Ζ
'(ZH8=f 'P 'HDWL '(ZH6=f 'P 'HT)S9"Z
Figure imgf000179_0004
' 'HI)0S'Z '(ZH8 = f' P 'HDWL' (ZH6 = f 'P' HT) S9 "Z
Figure imgf000179_0004
'' HI) 0S'Z
'(zH8=f 'Ηΐ)8 · '(zH8=f 'HT)SS"Z '(s 9 :(9p— OSWa) 顺— H
Figure imgf000179_0005
II I S081760/S00Z OAV •(s 'HZ)SZ'Z '(s 'HZ)SVZ '(zHS" =f 'b 'HZ)ZVZ '(zHS" =f Ήε)8Γΐ 9 :(
Figure imgf000180_0001
(ΐ) '(zH8 = f' Ηΐ) 8 · '(zH8 = f' HT) SS "Z '(s 9 :( 9 p— OSWa) 顺 — H
Figure imgf000179_0005
II I S081760 / S00Z OAV • (s' HZ) SZ'Z '(s' HZ) SVZ' (zHS "= f 'b' HZ) ZVZ '(zHS" = f Ήε) 8Γΐ 9 :(
Figure imgf000180_0001
(ΐ)
•(z服 =f 'P 'Ηΐ)6·ΐΐ '(s 'Ηΐ)ε·Οΐ '(ζ服 =f 'P 'HI)S9'8 '(zH8=f 'P Ήΐ)02"8 '(zH6=f 'P Ήΐ)Ζ6"Ζ '(zH8=f 'P Ήΐ)88"Ζ '(zH6=f 'P Ήΐ)09"Ζ '(zH8=f • (z clothes = f 'P' Ηΐ) 6 · ΐΐ '(s' Ηΐ) ε · Οΐ' (ζ clothes = f 'P' HI) S9'8 '(z H8 = f' P Ήΐ) 02 "8 '(zH6 = f' P Ήΐ) Ζ6 "Ζ '(zH8 = f' P Ήΐ) 88" Ζ '(zH6 = f' P Ήΐ) 09 "Ζ '(zH8 = f
^ 'HT)SS"Z '(zH8=f ' Ήΐ) Υί 'HS)Z2"S '(s Ήε)6Γ2 9 :(9p— OSWa) 顺— H ^ 'HT) SS "Z' (zH8 = f 'Ήΐ) Υί' HS) Z2" S '(s Ήε) 6Γ2 9 :( 9 p— OSWa) 顺 — H
T °%i9 ¾i
Figure imgf000180_0002
 T °% i9 ¾i
Figure imgf000180_0002
•(S 'ΗΪ) 6·9 '(S Ήε)68·ε '(s Ήε)3ε·ε Ήε)62·ε '(s Ήε)0Γ2 9 :( • (S 'ΗΪ) 6 · 9' (S Ήε) 68 · ε '(s Ήε) 3ε · ε Ήε) 62 · ε' (s Ήε) 0Γ2 9 :(
Iつ aつ) WN- Ht °%06 ¾ί
Figure imgf000180_0003
I a a) WN- H t °% 06 ¾ί
Figure imgf000180_0003
Figure imgf000180_0004
(ΐ)
Figure imgf000180_0005
Figure imgf000180_0004
(ΐ)
Figure imgf000180_0005
'Ηΐ)00 ΐ '(s Ήΐ)8^ ΐ '(ζΗΖ·εΐ=ί" 'Ρ 'Ηΐ)88·8 '(s 'Hf)Z^S '(zH8"8=f 'Ρ 'HI)SS'8 'Ηΐ) 00 ΐ' ( s Ήΐ) 8 ^ ΐ '(ζΗΖ · εΐ = ί "' Ρ 'Ηΐ) 88 · 8' ( s 'Hf) Z ^ S' ( z H8" 8 = f 'Ρ' HI ) SS'8
'(ΖΗΟ·6=1" 'Ρ 'Ηΐ)Μ)·8
Figure imgf000180_0006
'(ΖΗΟ · 6 = 1 "' Ρ 'Ηΐ) Μ) · 8
Figure imgf000180_0006
Ήΐ)93·Ζ 'WL=[ '； ' )6VL '(s 'HS)9S 9 :( P-OS a)H N-HT °%06 ¾ί Ήΐ) 93Ζ 'WL = [';')6VL' ( s ' HS) 9S 9 :( P-OS a) H NH T °% 06 ¾ί
96S各粱呦 -96Z  96S each 呦 -96Z
•(ζΗΖ·εΐ=ί" 'Ρ 'Ηΐ)Ζ6·ΐΐ '(s 'Ηΐ)εε·Οΐ 'WZl=i 'Ρ Ήΐ)9Ζ·8 '(ΖΗΓ8=Γ 'Ρ 'Ηΐ) ·8 • (ζΗΖ · εΐ = ί "'Ρ' Ηΐ) Ζ6 · ΐΐ '(s' Ηΐ) εε · Οΐ' WZl = i 'Ρ Ήΐ) 9Ζ · 8' (Ζ ΗΓ8 = Γ 'Ρ' Ηΐ) · 8
'(ΖΗ8·8=ί" 'Ρ Ή2)68"Ζ
Figure imgf000180_0007
'(ΖΗ8 · 8 = ί "' Ρ Ή2) 68" Ζ
Figure imgf000180_0007
' )9VL '(s Ήζ) ∑τ '(s Ήε)39·ε '(s Ήε)οε·ε 9 :( p-os a)H N-HT °%Ζ9 ? Φ ') 9VL' ( s Ήζ) ∑τ '( s Ήε) 39 · ε' ( s Ήε) οε · 9 :( p-os a) H NH T °% Ζ9? Φ
S6S各粱呦 [8910] •(s Ήΐ)^Γ2ΐ '(s Ήΐ)ΐ9 ΐ S6S each beam [8910] • ( s Ήΐ) ^ Γ2ΐ '(s Ήΐ) ΐ9 ΐ
'(s 'HT)SZ"8 VS=i 'P 'HI)SS'8 ^ΗΖ'6=ί 'P 'HT)eO"8 '(zHZ'Z=f 'P Ήΐ)ΐ6"Ζ  '(s' HT) SZ "8 VS = i 'P' HI) SS'8 ^ ΗΖ'6 = ί 'P' HT) eO" 8 '(zHZ'Z = f' P Ήΐ) ΐ6 "Ζ
'(zH2"6=f 'P Ήΐ)09"Ζ '(ΖΗΓ8 '£Ί=ί ' P 'HI)SS'Z '(zH0"Z=f '； Ήΐ)6Υί 9 '·( v-osnaWH-H, °%ΐ ¾τ。 呦^ 遨 翁^； α¾¾ ^^ 一  '(zH2 "6 = f' P Ήΐ) 09" Ζ '(ΖΗΓ8' £ Ί = ί 'P' HI) SS'Z '(zH0 "Z = f'; Ήΐ) 6Υί 9 '· (v-osnaWH- H, °% ΐ ¾τ.
•(s Ήΐ)ΐ ΐ '(s Ήΐ)0 ΐ
Figure imgf000180_0008
S081760/S00Z OAV '(zHS"Z=f '； 'HZ)OVZ '(zHS"Z=f '； s Ήζ)Ζ9Ί '(zHS" =f '； Ήε)86 9 :(• ( s Ήΐ) ΐ ΐ '( s Ήΐ) 0 ΐ
Figure imgf000180_0008
S081760 / S00Z OAV '(zHS "Z = f';'HZ)OVZ'(zHS" Z = f '; s Ήζ) Ζ9Ί' (zHS "= f '; Ήε) 86 9 :(
Iつ αつ) WN- ΗΤ ο%ε6*¾ί
Figure imgf000181_0001
- S - /— ^^c^ ^- S' ( u)— ε- ^ - ΐ-ベ ^ ,^ ^ - (ΐ) οοε各粱呦^ :οοε I one α one) WN- Η Τ ο% ε6 * ¾ί
Figure imgf000181_0001
-S-/ — ^^ c ^ ^-S '(u) — ε- ^-ΐ-B ^, ^ ^-(ΐ) οοεEvery 呦 ^: οοε
'Ρ 'Ηΐ) ·8
Figure imgf000181_0002
' 'HT)W 'Ρ' Ηΐ) 8
Figure imgf000181_0002
'' HT) W
'(zH8=f ' ' )9VL '(s Ή 8ε· '(s Ήε)εε·ε '(s Ήε)ιε·ε 9 :(9p— oswa) 顺— H '( z H8 = f'')9VL' ( s Ή 8ε · '( s Ήε) εε · ε' ( s Ήε) ιε · ε 9 :( 9 p—oswa) 顺 —
662-^ i¾J^ (ε)662- ^ i¾J ^ (ε)
•(s ' )ovL '(s Ή εε· '(s Ήε)68·ε '(s Ήε)8ε·ε '(s Ήζ)ζζτ '(s Ήε)οε·ε 9 :(• ( s ') ovL '( s Ή εε''( s Ήε) 68 · ε' ( s Ήε) 8εε '( s Ήζ) ζζτ' ( s Ήε) οεε9 :(
DaD)H N-HT °%S6 ? Φ
Figure imgf000181_0003
DaD) H NH T °% S6? Φ
Figure imgf000181_0003
•(s 'm)svf '(s Ήε)6ε·ε '(s Ήε)6ε·ε '(s '蹄 ε·ε '(s Ήζ)βζτ 9 :( • (s 'm) svf' (s Ήε) 6ε · ε '(s Ήε) 6ε · ε' (s ' hoof ε · ε' (s Ήζ) βζτ 9 :(
DaD)H N-HT °%06 ¾ί
Figure imgf000181_0004
一 DaD) H NH T °% 06 ¾ί
Figure imgf000181_0004
one
ベ - s - /— ^^c^ - s' ^ - ΐ- ^ ^^ H - ε (ΐ)  Be-s-/ — ^^ c ^-s' ^-ΐ- ^ ^^ H-ε (ΐ)
•(zHST=f 'P• ( z HST = f 'P
Ηΐ)6·ΐΐ '(s Ήΐ)2 ΐ '(zHST=f 'P 'Ηΐ)Ζ9·8 '(zH8=f 'P Ήΐ)6Γ8 '(zH6=f 'P 'Ηΐ)66· Ηΐ) 6 ΐΐ '( s Ήΐ) 2 ΐ' ( z HST = f 'P' Ηΐ) Ζ9.8 '( z H8 = f' P Ήΐ) 6Γ8 '( z H6 = f' P 'Ηΐ) 66
'(ZH8=f 'P Ήΐ)88"Ζ '(ZH6=f 'P Ήΐ)09"Ζ
Figure imgf000181_0005
' 'HT)SS"Z ' 'H ΐ) ·Ζ '(s 'HS)62"S '(zHS"Z=f 'b 'H2)29"2 '(zHS" =f ^ 'HS)02"T 9 :( P-OS^a)H N-H '(ZH8 = f' P Ήΐ) 88 "Ζ '(ZH6 = f' P Ήΐ) 09" Ζ
Figure imgf000181_0005
'' HT) SS "Z '' H ΐ) · Ζ '(s' HS) 62"S' (zHS "Z = f 'b' H2) 29" 2 '(zHS "= f ^' HS) 02" T 9 :( P-OS ^ a) H NH
862-^ i¾J^ (ε) •(s 'HT)Z6"9 '(s 862- ^ i¾J ^ (ε) • ( s 'HT) Z6 "9' ( s
Ήε)88·ε '(s Ήε)9ε·ε '(s Ή£)βζ '(ZHS'Z=1" 'HZ)LVZ '(ZHS'Z=1" ^ Ήζ)ζζ'\ 9Ήε) 88 · ε '(s Ήε) 9ε · ε' ( s Ή £) βζ '(ZHS'Z = 1 "' HZ) LVZ '(ZHS'Z = 1" ^ Ήζ) ζζ' \ 9
■(OQDWH-H, °%96 ¾ί ^Μ^^ΜΜ ^^^ Μ^ Θ ^^ 一 ■ (OQDWH-H, °% 96 ¾ί ^ Μ ^^ ΜΜ ^^^ Μ ^ Θ ^^
ベ - s - /— ^^c^ - s' ^ - ΐ- ^エ- ε-ベ ^ ,^ ^ - (ζ)
Figure imgf000181_0006
61 S081760/S00Z OAV ( ¾ ^^ 一)ベ, cH-— , — (ΐ)Be-s-/ — ^^ c ^-s' ^-ΐ- ^ d-ε-be ^, ^ ^-(ζ)
Figure imgf000181_0006
61 S081760 / S00Z OAV ( ¾ ^^ 一) ve, cH-—, — (ΐ)
οε各粱呦^ -fom [ TO] οε each siang 呦 ^ -fom [TO]
"(sjq 'HS)8 ΐ '(s Ήΐ)Ζ9"8
Figure imgf000182_0001
"(sjq 'HS) 8 ΐ' (s Ήΐ) Ζ9" 8
Figure imgf000182_0001
'Ρ 'Ηΐ) 8
Figure imgf000182_0002
'Ηΐ) ·Ζ'Ρ' Ηΐ) 8
Figure imgf000182_0002
'Ηΐ)
Figure imgf000182_0003
'； 'HS)S2"T 9 :( OSW I) 顺— HT °%99 ¾T
Figure imgf000182_0003
'HS' S2 "T 9 :( OSW I) 顺 — H T °% 99 ¾T
εοε各粱呦 ： εοείϋ εοε each beam: εοείϋ
•(saq 'HS)8 ΐ '(s 'Ηΐ)89·8
Figure imgf000182_0004
• (saq 'HS) 8 ΐ'(s' Ηΐ) 89
Figure imgf000182_0004
' 'Ηΐ) 8· '(zHS"Z=f 'HT)SS"Z '(s Ήε)ε ·ε 9 :(9p— OSWa) 顺— HT °%S8 ¾T '' Ηΐ) 8 · '(zHS "Z = f' HT) SS" Z '(s Ήε) ε · ε 9 :( 9 p— OSWa) 顺 — H T °% S8 ¾T
sos各粱呦 -zom
Figure imgf000182_0005
sos each 呦
Figure imgf000182_0005
'P Ήΐ)02"8 '(zH6=f 'P Ήΐ)66"Ζ '(zH8=f 'P Ήΐ)88"Ζ '(zH6=f 'P 'HI)6S'Z '(zH8=f
Figure imgf000182_0006
'P Ήΐ) 02 "8' (zH6 = f 'P Ήΐ) 66"Ζ' (zH8 = f 'P Ήΐ) 88 "Ζ' (zH6 = f 'P' HI) 6S'Z '(zH8 = f
Figure imgf000182_0006
'Η ΐ9·ΐ '(zHS"Z=f '； s 'Η 8ε·ΐ '(zHS" =f '； 'HS)S6 9 :( OSWd) N— H ιοε各粱呦 (z)  'Η ΐ9 · ΐ' (zHS "Z = f '; s' Η 8ε · ΐ' (zHS" = f ';' HS) S6 9 :( OSWd) N— H ιοε each beam (z)
•(s 'HT)Z6"9 • (s' HT) Z6 " 9
'(s Ήε)88·ε '(s Ήε)3ε·ε '(s Ήε)6ζ·ε '(ZHS'Z=1" ^ Ήζ)ζνζ '(ZHS'Z=1" '^m  '(s Ήε) 88 ·' '(s Ήε) 3ε ·' '(s Ήε) 6ζζ ε' (ZHS'Z = 1 "^ Ήζ) ζνζ '(ZHS'Z = 1"' ^ m
'H2)8S"T '(zHS"Z=f 'Η 0 ·ΐ '(zHS" =f Ήε) 6·0 9 :(¾aつ) 顺— H  'H2) 8S "T' (zHS" Z = f 'Η 0 · ΐ' (zHS "= f Ήε) 6.09: (¾a)) — H
T :*¾i °^ ¾^^®^ τ^)¾^ )#^^ Θ ¾¾t ^ 一
Figure imgf000182_0007
(ΐ) T : * ¾i ° ^ ¾ ^^ ® ^ τ ^) ¾ ^) # ^^ Θ ¾¾t ^ one
Figure imgf000182_0007
(ΐ)
ΐοε各粱呦 ： losp} [ΟΖΪΟ]
Figure imgf000182_0008
'Ρ 'Ηΐ)0 ΐ Xs Ήΐ)2 ΐ ΐοε each siang 呦: losp} [ΟΖΪΟ]
Figure imgf000182_0008
'Ρ' Ηΐ) 0 ΐ X s Ήΐ) 2 ΐ
'Ρ 'HT)S9"8
Figure imgf000182_0009
'Ρ 'Ηΐ)88·
Figure imgf000182_0010
' 'HT)SS"Z ' 'Hl)ffl 'Η£)8Ζ'£ 'Ρ' HT) S9 "8
Figure imgf000182_0009
'Ρ' Ηΐ) 88
Figure imgf000182_0010
'' HT) SS "Z '' Hl) ffl 'Η £) 8Ζ' £
'ΗΖ)15τ '(zHS'Z=f '； s ΉΖ)59Ί '(zHS" =f '； Ήε)96 9 :( OSWa) 顺— Η
Figure imgf000182_0011
'ΗΖ) 15τ'(zHS'Z = f '; s ΉΖ) 59Ί' (zHS "= f '; Ήε) 96 9 :( OSWa) 顺 — Η
Figure imgf000182_0011
•(s 'Ηΐ)Ζ6·9 '(s Ήε)88·ε '(s 'HS)9S"S '(s 'HS)62"S
Figure imgf000182_0012
081· S081760/S00Z OAV 特開 2002-161095号公報に記載された参考例 1と同様の方法により標題化合物を 得た。収率 62%。 1H-NMR(CDC1 ): δ 5.88(2H, s), 6.65(2H, brs), 6.65- 6.75(2H, m), • (s 'Ηΐ) Ζ6 · 9' (s Ήε) 88 · ε '(s' HS) 9S "S '(s' HS) 62" S
Figure imgf000182_0012
081S081760 / S00Z OAV The title compound was obtained in the same manner as in Reference Example 1 described in JP-A-2002-161095. Yield 62%. 1H-NMR (CDC1): δ 5.88 (2H, s), 6.65 (2H, brs), 6.65-6.75 (2H, m),
3  Three
7.25-7.40(2H, m).  7.25-7.40 (2H, m).
(2) 2しァセチルァミノ- 2-二トロアセトフエノン (一般合成法 λ )  (2) 2-Diacetylamino-2-nitroacetophenone (general synthesis method λ)
特開 2002-161095号公報に記載された参考例 5と同様の方法により標題化合物を 得た。収率 95%。 1H-NMR(DMSO-d ): δ 2.11(3H, s), 6.40(2H, s), 7.27(1H, t,  The title compound was obtained in the same manner as in Reference Example 5 described in JP-A-2002-161095. 95% yield. 1H-NMR (DMSO-d): δ 2.11 (3H, s), 6.40 (2H, s), 7.27 (1H, t,
6  6
J=7.5Hz), 7.64(1H, t, J=7.5Hz), 7.76(1H, d, J=7.5Hz), 8.00(1H, d, J=7.5Hz), 10.64(1H, s).  J = 7.5Hz), 7.64 (1H, t, J = 7.5Hz), 7.76 (1H, d, J = 7.5Hz), 8.00 (1H, d, J = 7.5Hz), 10.64 (1H, s).
(3) 2-メチル -3-二トロ- 1,4-ジヒドロキノリン- 4-オン (一般合成法 ）  (3) 2-methyl-3-nitro-1,4-dihydroquinolin-4-one (general synthesis method)
特開 2002-161095号公報に記載された参考例 15と同様の方法により標題化合物を 得た。収率 87%。 'H-NMRCDMSO-d ): δ 2.52(3H, s), 7.46(1H, t, J=8Hz), 7.62(1H,  The title compound was obtained in the same manner as in Reference Example 15 described in JP-A-2002-161095. 87% yield. 'H-NMRCDMSO-d): δ 2.52 (3H, s), 7.46 (1H, t, J = 8Hz), 7.62 (1H,
6  6
d, J=8Hz), 7.78(1H, t, J=8Hz), 8.16(1H, d, J=8Hz), 12.4(1H, brs). d, J = 8Hz), 7.78 (1H, t, J = 8Hz), 8.16 (1H, d, J = 8Hz), 12.4 (1H, brs).
(4) 3-ァミノ- 2-メチル -1,4-ジヒドロキノリン- 4-オン  (4) 3-Amino-2-methyl-1,4-dihydroquinolin-4-one
一般合成法 tと同様の方法により標題化合物を得た。収率 96%。 1 The title compound was obtained in the same manner as in General Synthesis Method t. 96% yield. 1
H-NMR(DMSO-d ): δ 2.35(3H, s), 4.19(2H, brs), 7.10- 7.20(1H, m), 7.40-7.50(2H, H-NMR (DMSO-d): δ 2.35 (3H, s), 4.19 (2H, brs), 7.10-7.20 (1H, m), 7.40-7.50 (2H,
6  6
m), 8.00-8.07(lH, m), 11.4(1H, brs).  m), 8.00-8.07 (lH, m), 11.4 (1H, brs).
(5)化合物番号 304  (5) Compound No. 304
収率 87%。 'H-NMRCDMSO-d ): δ 2.23(3H, s), 2.57(3H, s), 7.12(1H, t, J=8Hz), 87% yield. 'H-NMRCDMSO-d): δ 2.23 (3H, s), 2.57 (3H, s), 7.12 (1H, t, J = 8Hz),
6  6
7.37(1H, t, J=7.5Hz), 7.40(2H, t, J=8Hz), 7.60(1H, d, J=7.5Hz), 7.70(1H, t, J=7.5Hz), 8.02(2H, d, J=8Hz), 8.17(1H, d, J=7.5Hz), 8.83(1H, d, J=13Hz), 11.1(1H, d, J=13Hz), 12.4(1H, s).  7.37 (1H, t, J = 7.5Hz), 7.40 (2H, t, J = 8Hz), 7.60 (1H, d, J = 7.5Hz), 7.70 (1H, t, J = 7.5Hz), 8.02 (2H , d, J = 8Hz), 8.17 (1H, d, J = 7.5Hz), 8.83 (1H, d, J = 13Hz), 11.1 (1H, d, J = 13Hz), 12.4 (1H, s).
例 305:化合物番号 305 Example 305: Compound number 305
収率 80%。 'H-NMRCDMSO-d ): δ 2.57(3Η, s), 3.44(3Η, s), 7.41(1Η, t, J=8Hz), Yield 80%. 'H-NMRCDMSO-d): δ 2.57 (3Η, s), 3.44 (3Η, s), 7.41 (1Η, t, J = 8Hz),
6  6
7.60(1Η, d, J=8Hz), 7.71(1H, t, J=8Hz), 8.17(1H, d, J=8Hz), 9.36(1H, brs), 11.8(1H, brs), 12.3(1H, s).  7.60 (1Η, d, J = 8Hz), 7.71 (1H, t, J = 8Hz), 8.17 (1H, d, J = 8Hz), 9.36 (1H, brs), 11.8 (1H, brs), 12.3 (1H , s).
例 306:化合物番号 306 Example 306: Compound number 306
収率 59%。 'H-NMRCDMSO-d ): δ 2.61(3Η, s), 7.30(1Η, t, J=7.5Hz), 7.42(1Η, t, Yield 59%. 'H-NMRCDMSO-d): δ 2.61 (3Η, s), 7.30 (1Η, t, J = 7.5Hz), 7.42 (1Η, t,
6  6
J=8Hz), 7.49(2H, t, J=7.5Hz), 7.62(1H, d, J=8Hz), 7.73(1H, t, J=8Hz), 7.98(2H, d, 'b 'Η Ζ8·ε '(s Ήε)83·ζ
Figure imgf000184_0001
'； Ή Ζ'Ι 9 :( OSW I) 顺— Ητ 。。晨 ¾ί J = 8Hz), 7.49 (2H, t, J = 7.5Hz), 7.62 (1H, d, J = 8Hz), 7.73 (1H, t, J = 8Hz), 7.98 (2H, d, 'b' Η Ζ8 · ε '( s Ήε) 83
Figure imgf000184_0001
'; Ή Ζ'Ι 9: (OSW I) 顺 — Η τ . . Chen ¾ί
•(sj Ήΐ)ε ΐ '(sj Ήΐ)8·π Ή • (sj Ήΐ) ε ΐ '(sj Ήΐ) 8π Ή
'Ηΐ)98·8 '(saq 'Ηΐ)69·8 '(ω 'HI)SS'8— 3Γ8 '(ω 'H2)0Z"Z-09"Z '(ω Ήΐ) νί-0£Ί 'Ηΐ) 98 · 8' (saq 'Ηΐ) 69 · 8' (ω 'HI) SS'8— 3Γ8' (ω 'H2) 0Z "Z-09" Z' (ω Ήΐ) νί-0 £ Ί
Figure imgf000184_0002
'； 'HS) I 9 :( OSWa) 顺— HT °%IS ¾ί
Figure imgf000184_0003
Figure imgf000184_0002
'HS' I 9 :( OSWa) 顺 — H T °% IS '
Figure imgf000184_0003
•(zHS'9=f 'P Ήΐ)Γ2ΐ '(s Ήΐ) 9·6 '(zHS"9=f 'P Ήΐ)Ζ8"8 '(ω 'Ηΐ)0ε·8— '(ω 'H SI'8— 00·8 '(ω 'H SZ'Z— 09·  • (zHS'9 = f 'P Ήΐ) Γ2ΐ' (s Ήΐ) 9.6 '(zHS "9 = f' P Ήΐ) Ζ8" 8 '(ω' Ηΐ) 0ε8 — '(ω' H SI '8— 00 · 8' (ω 'H SZ'Z— 09 ·
'(ω
Figure imgf000184_0004
9 :(9p— oswa) 顺— HT °%ZZ ¾T '(ω
Figure imgf000184_0004
9 :( 9 p—oswa) 顺 — H T °% ZZ ¾T
"(zH9=f 'P 'Ηΐ) ΐ '( q Ήΐ)ε ΐ
Figure imgf000184_0005
' 'HT)SZ"Z "( z H9 = f 'P' Ηΐ) ΐ '(q Ήΐ) ε ΐ
Figure imgf000184_0005
'' HT) SZ "Z
'P 'Ηΐ)99· '(zH8=f ' 'H\)ZVL '(s 'HZ)ZVZ 9 :( OSWa) N— HT °%S8 ? φ 'P' Ηΐ) 99 '' (zH8 = f '' H \) ZVL '(s' HZ) ZVZ 9 :( OSWa) N— H T °% S8? Φ
οιε各粱呦^ -oim οιε each siang 呦 ^ -oim
Xs Ήΐ)3 ΐ '(s 'Ηΐ)88·6 '(s 'HI)S9'8 '(ω 'Η 0ε·8— SI'8 '(ω 'Ηΐ)0ΐ·8- 00·8 '(zHS"S=f 'Ρ 'HT)S6"Z '(ω 'HT)06"Z-S8"Z '(zHS"S=f 'Ρ 'Ηΐ) 9·Ζ '(ω 'H )09 —S 'Z 9 :( OSWa) Ν— Ητ °% ε ¾ί X s Ήΐ) 3 ΐ '( s ' Ηΐ) 886 '( s ' HI) S9'8 '(ω' Η 0ε8— SI'8 '(ω' Ηΐ) 0ΐ8-00 (zHS "S = f 'Ρ' HT) S6" Z '(ω' HT) 06 "Z-S8" Z '(zHS "S = f' Ρ 'Ηΐ) 9 · Ζ' (ω 'H) 09 — S 'Z 9 :( OSWa) Ν— Η τ °% ε ¾ί
6οε各粱呦 -eom  6οε each siang 呦 -eom
•(s 'Ηΐ) ·0ΐ• ( s ' Ηΐ) · 0ΐ
'(s Ήΐ)6Ζ·6 '(s 'Ηΐ) Ζ·8 '(ω 'Ηΐ)09·8— '(ω 'Ηΐ)0ε·8— '(ω 'Ηΐ)3ΐ·8— Ζ0·8 '( s Ήΐ) 6Ζ6' ( s 'Ηΐ) 88' (ω 'Ηΐ) 09 · 8''(ω' Ηΐ) 0ε8― '(ω' Ηΐ) 3ΐ8― Ζ0.8
'(ω 'HT)06"Z-S8"Z '(ω 'Η9)09·Ζ— S ·Ζ 9 :( OSWa) 顺— Ητ °%0S ¾ί '(ω' HT) 06 "Z-S8" Z '(ω' Η9) 09 · Ζ— S · Ζ 9 :( OSWa) 顺 — Η τ °% 0S ¾ί
8οε各粱呦 -som 8οε each siang 呦 -som
•(s 'Ηΐ)66·6 '(s Ήΐ)ΖΖ·6• ( s 'Ηΐ) 66 · 6' ( s Ήΐ) ΖΖ6
'(ω 'HT)82"8-02"8 '(ω 'Ηΐ)0ΐ·8- S0'8 '(ω 'HT)S0"8-S6"Z '(ω 'HT)06"Z-S8"Z '(ω '(ω' HT) 82 "8-02" 8 '(ω' Ηΐ) 0ΐ8-S0'8 '(ω' HT) S0 "8-S6" Z '(ω' HT) 06 "Z-S8 "Z '(ω
'HT)OZ"Z-S9"Z '(ω 'He)ee" -e^" Ήε) s 9 :(9p— oswa) 顺— HT °%9ε ¾T 'HT) OZ "Z-S9"Z' (ω 'He) ee "-e ^" Ήε) s 9 :( 9 p— oswa) 顺 — H T °% 9ε ¾T
οε各粱呦 -Lom  οε each siang 呦 -Lom
'Ηΐ)ε ΐ
Figure imgf000184_0006
Figure imgf000184_0007
381- S081760/S00Z OAV ' 'HZ)OVZ '(zHS'Z=f '； u!nb )88·ΐ '(zH =f '； Ήε)8Γΐ 9 :( OSW I) 顺— Η 'Ηΐ) ε ΐ
Figure imgf000184_0006
Figure imgf000184_0007
381- S081760 / S00Z OAV '' HZ) OVZ '(zHS'Z = f'; u! Nb) 88 · ΐ '(zH = f'; Ήε) 8Γΐ 9 :( OSW I) 顺 — Η
τ °%96 ¾τ ^m^ ^mm^ ^ mo^ m-m-
Figure imgf000185_0001
τ °% 96 ¾τ ^ m ^ ^ mm ^ ^ mo ^ mm-
Figure imgf000185_0001
'b 'HZ)£V '(s Ήε)68"ε '(s 'HS)SS'S '(S Ήε)εε·ε '(zHs- =f Ήζ)ίνζ '(zHs- =f' b ' HZ) £ V '(s Ήε) 68 "ε' (s 'HS) SS'S' (S Ήε) εε · ε '(zHs- = f Ήζ) ίνζ' (zHs- = f
' 'HZ)OVZ
Figure imgf000185_0002
'； 'HS)Z2"T 9 :(¾aつ) 顺— H ベ - S- /— : ό ΰ、'' HZ) OVZ
Figure imgf000185_0002
'HS) Z2 "T 9: (¾a)) 顺 — H -S- / —: ό ΰ,
；^、— s' — ^ — τ—[ 。 ( - ^ / 、^^ェ)— ε]— ε—ベ ^ , - ^ «、— (2)
Figure imgf000185_0003
; ^, — S '— ^ — τ — [. (-^ /, ^^ ェ) — ε ] — ε —Ba ^,-^ «, — (2)
Figure imgf000185_0003
Figure imgf000185_0004
Figure imgf000185_0004
"(ζΗ2ΐ=Γ 'Ρ 'Ηΐ) ΐ '(ζΗ2ΐ=Γ 'Ρ Ήΐ)2ΐ ΐ '(zH8=f 'Ρ Ήΐ)02"8 '(ω 'H2)06"Z-08"Z '(zH8=f 'Ρ Ήΐ)89"Ζ '(ω 'ΗΖ)09Ί- νί
Figure imgf000185_0005
' Ήΐ)ΐΓΖ 9 :( Ν— Ητ °%6 ¾ί "( ζ Η2ΐ = Γ 'Ρ' Ηΐ) ΐ '( ζ Η2ΐ = Γ' Ρ Ήΐ) 2ΐ ΐ '(zH8 = f' Ρ Ήΐ) 02" 8 '(ω' H2) 06 "Z-08" Z ' (zH8 = f 'Ρ Ήΐ) 89 "Ζ' (ω 'ΗΖ) 09Ί- νί
Figure imgf000185_0005
'Ήΐ) ΐΓΖ 9 :( Ν— Η τ °% 6 ¾ί
•(sjq Ήΐ)0 ·2ΐ '(ω Ήΐ)38 ΐ-3Ζ ΐ '(ω 'HI)0S'8- 0 ·8 '(zH8=f 'Ρ 'Ηΐ) 8 '(zH8=f 'Ρ Ήΐ)96"Ζ '(ω 'HS)00"8-SZ"Z '(ω 'H2)09"Z-0^"Z '(ω 'HT)S0"Z-06"9 '(s Ή Ζ'Ζ 9 :( OSWa) 顺- Ητ °%SS ¾ί • (sjq Ήΐ) 0 2ΐ '(ω Ήΐ) 38 ΐ-3Ζ ΐ' (ω 'HI) 0S'8-0 8' (zH8 = f 'Ρ' Ηΐ) 8 '(zH8 = f' Ρ Ήΐ ) 96 "Ζ '(ω' HS) 00" 8-SZ "Z '(ω' H2) 09" Z-0 ^ "Z '(ω' HT) S0" Z-06 "9 '( s Ζ Ζ' Ζ 9 :( OSWa) 顺-Η τ °% SS ¾ί
SIS各粱呦  SIS
•(sjq Ήΐ)^εΐ '( q Ήΐ)06 ΐ '( q 'Ηΐ)6 ·8 '(zH8=f 'P 'Ηΐ) 8 '(ΖΗ6
Figure imgf000185_0006
• (sjq Ήΐ) ^ εΐ '(q Ήΐ) 06 ΐ' (q 'Ηΐ) 6 · 8' ( z H8 = f 'P' Ηΐ) 8 '( Ζ Η6
Figure imgf000185_0006
'HT)W '(zH6=f ' 'HZ)^L '(s 'HZ)WZ 9 :( OSWa) 顺— HT °%08 ¾T 'HT) W' (zH6 = f '' HZ) ^ L '(s' HZ) WZ 9 :( OSWa) 顺 — H T °% 08 ¾T
"(s-i 'Ηΐ)ε ΐ '(ω 'Ηΐ)0 ΐ— Γΐΐ '(saq Ήΐ)3ε·6 '(ΖΗ8=Γ 'Ρ Ήΐ)8Γ8
Figure imgf000185_0007
Figure imgf000185_0008
881- S081760/S00Z OAV
Figure imgf000186_0001
"(si 'Ηΐ) ε ΐ' (ω 'Ηΐ) 0 ΐ— Γΐΐ' (saq Ήΐ) 3ε6 '( Ζ Η8 = Γ' Ρ Ήΐ) 8Γ8
Figure imgf000185_0007
Figure imgf000185_0008
881- S081760 / S00Z OAV
Figure imgf000186_0001
•(s 'HT)½"9 '(s Ήε)68·ε '(zHZ=f 'b 'H2)9Z"S '(s 'HS)62"S '(s '\ Ζ)\ΥΖ '(zHZ=f '； 'HS)Z2"T 9 :( OSW I) 顺— H • (s 'HT) ½ " 9' (s Ήε) 68 · ε '(z HZ = f' b 'H2) 9Z"S' (s 'HS) 62 "S' (s '\ Ζ) \ ΥΖ' (zHZ = f ';' HS) Z2 "T 9 :( OSW I) 顺 — H
T °w¥¾ :*¾i °^ ¾^^®^ τ^)¾^ )#^^ Θ ^ ^ - T ° w ¥ ¾ : * ¾i ° ^ ¾ ^^ ® ^ τ ^) ¾ ^) # ^^ Θ ^ ^-
•(sjq 'Ηΐ)09·0ΐ '(s Ήΐ)0Γ3 • (sjq 'Ηΐ) 09 · 0''( s Ήΐ) 0Γ3
'(zHZ=f 'b 'HZ)fL'£ '(s Ήε)66·ΐ '(zH =f '； Ήε)8Γΐ 9 :( P-OS^a)H N-H
Figure imgf000186_0002
(ΐ) '(zHZ = f' b 'HZ) fL' £ '(s Ήε) 66ΐ ΐ' (zH = f '; Ήε) 8Γΐ 9 :( P-OS ^ a) H NH
Figure imgf000186_0002
(ΐ)
"(s-i 'HDZ Zl '(sj Ήΐ)98 ΐ '(s-i 'Ηΐ)Ζ ·8 '(zH8=f 'P 'Ηΐ) 8 '(zH6=f 'P 'H2)S0"8 '(zH8=f 'P Ήΐ)96"Ζ '(zH8=f ' 'HT)S8"Z '(zH8=f ^ Ήΐ)33· '(zH6=f 'P 'HZ)LVL '(s 'HZ)WZ 9 :( OSWd) N— HT °%6S ? φ "(si 'HDZ Zl' (sj Ήΐ) 98 ΐ '(si' Ηΐ) Ζ8 '( z H8 = f' P 'Ηΐ) 8' (zH6 = f 'P' H2) S0" 8 '(zH8 = f 'P Ήΐ) 96 "Ζ' (zH8 = f '' HT) S8" Z '(zH8 = f ^ Ήΐ) 33 ·' (zH6 = f 'P' HZ) LVL '(s' HZ) WZ 9 :( OSWd) N— H T °% 6S? Φ
OSS各粱呦^ -OZm [S TO]
Figure imgf000186_0003
OSS each 呦 呦 -OZm [S TO]
Figure imgf000186_0003
'P Ήΐ)06 ΐ '(ζΗ0ΐ=Γ 'Ρ 'Ηΐ)9 ·8 '(ΖΗ8=Γ 'Ρ Ήΐ)^·8 '(s Ήΐ)0Γ8 '(ΖΗ6=Γ 'Ρ Ήΐ)Ζ6"Ζ
Figure imgf000186_0004
' 'HT)eS"Z 'P Ήΐ) 06 ΐ' ( ζ Η0ΐ = Γ 'Ρ' Ηΐ) 9 8 '( Ζ Η8 = Γ' Ρ Ήΐ) ^ 8 '( s Ήΐ) 0Γ8' ( Ζ Η6 = Γ 'Ρ Ήΐ) Ζ6 "Ζ
Figure imgf000186_0004
'' HT) eS "Z
' 'H\)WL '(zH6=f 'P Ήΐ)6ΓΖ '(s 'HZ)ZZ'Z 9 :( OSWa) 顺— HT °%8 ¾T '' H \) WL '(zH6 = f' P Ήΐ) 6ΓΖ '(s' HZ) ZZ'Z 9 :( OSWa) 顺 — H T °% 8 ¾T
6ΐε各粱呦^ -eim  6ΐεEach 呦 ^ -eim
"(s-i 'HT)Z9"2T  "(s-i 'HT) Z9" 2T
'(saq Ήΐ)3Ζ ΐ '(s 'Ηΐ)ε ·8
Figure imgf000186_0005
'(saq Ήΐ) 3Ζ ΐ'(s' Ηΐ) ε8
Figure imgf000186_0005
' Ήΐ)ε8"ζ '(ω 'Hs)e9" -es" Ήε) Γ2 9 :(9ρ— oswa) 顺— Ht °%S8 ？ Φ 'Ήΐ) ε8 "ζ' (ω 'Hs) e9" -es "Ήε) Γ2 9 :( 9 ρ— oswa) 顺 — H t °% S8? Φ
•(ζΗετ=Γ• ( ζ Ηετ = Γ
'Ρ 'Ηΐ)96·ΐΐ '(s Ήΐ)92 ΐ '(zHST=f 'Ρ 'Ηΐ)89·8 '(zHS'Z=f 'Ρ 'HT)02"8 '(ΖΗ6=Γ 'Ρ 'Ρ' Ηΐ) 96ΐΐ '( s Ήΐ) 92 ΐ' ( z HST = f 'Ρ' Ηΐ) 89Ηΐ8 '(zHS'Z = f' Ρ 'HT) 02 "8' ( Ζ Η6 = Γ 'Ρ
Ηΐ)Ζ6·Ηΐ) Ζ6
Figure imgf000186_0006
Figure imgf000186_0007
S081760/S00Z OAV zzz^ ^ (ε)
Figure imgf000186_0006
Figure imgf000186_0007
S081760 / S00Z OAV zzz ^ ^ (ε)
•(s 'Ηΐ)ΐΟ· '(ω 'Η8)00· — S8'S '(s 'ΗΖ)Ζ^Ζ '(s Ήε)0Γ2 9 :( <3つ) Η顺— Η ベ - s- /
Figure imgf000187_0001
• ( s 'Ηΐ) ΐΟ ·' (ω 'Η8) 00 · — S8'S' ( s 'ΗΖ) Ζ ^ Ζ' ( s Ήε) 0Γ2 9 :( <3) Η 顺 — Η-s- /
Figure imgf000187_0001
'H2)6S"S '(sjq 'HI)SS'S '(sjq 'HI) '(s Ήε)66·ΐ 9 :( P- OSW I) 顺- H 'H2) 6S "S' (sjq 'HI) SS'S' (sjq 'HI)' (s Ήε) 66ΐ 9 :( P- OSW I) 顺-H
T °W¥¾ °^ ¾^^®^ τ^)¾^ )#^^ん ¾¾t ^ 一
Figure imgf000187_0002
(ΐ) T ° W ¥ ¾ ° ^ ¾ ^^ ® ^ τ ^) ¾ ^) # ^^ ん ^ t ^ one
Figure imgf000187_0002
(ΐ)
(sjq Ήΐ)36·Π '(s Ήΐ)02 ΐ (s-iq 'HT)^9"8 '(zH8=f 'P Ήΐ)6Γ8 '(zH6=f 'P Ήΐ)86"Ζ '(zH8=f 'P Ήΐ)88"Ζ '(zH6=f 'P 'HI)6S'Z
Figure imgf000187_0003
(sjq Ήΐ) 36 · Π '( s Ήΐ) 02 ΐ (s-iq' HT) ^ 9 "8 '(zH8 = f' P Ήΐ) 6Γ8 '(zH6 = f' P Ήΐ) 86" Ζ '(zH8 = f 'P Ήΐ) 88 "Ζ' (zH6 = f 'P' HI) 6S'Z
Figure imgf000187_0003
'b 'H2)29"2 '(zHS"Z=f '； 'Η£)ΟΖΊ '(zH =f '； Ήε)6Γΐ 9 :( P- OSWa) 顺- H ' b ' H2) 29 "2 '(zHS" Z = f';'Η £) ΟΖΊ' (zH = f '; Ήε) 6Γΐ 9 :( P- OSWa) 顺-H
T °%S8 ¾i ^m^ ^mm^ ^ mo^ m-m- zzz^ ^ (ε) T °% S8 ¾i ^ m ^ ^ mm ^ ^ mo ^ mm- zzz ^ ^ (ε)
•(s Ήΐ)Ζ6"9 '(s Ήε)88·ε '(zHZ=f 'b 'H2)ZZ"S '(s 'HS)62"S
Figure imgf000187_0004
'； 'HS)22"T 9 :( Iつ dつ) WN— H • (s Ήΐ) Ζ6 "9 '(s Ήε) 88 · ε' (zHZ = f 'b' H2) ZZ" S '(s' HS) 62 "S
Figure imgf000187_0004
';' HS) 22 "T 9 :( I d d) WN— H
T :*¾i °^ ¾^^®^ τ^)¾^ )#^^ Θ ^ ^ - T : * ¾i ° ^ ¾ ^^ ® ^ τ ^) ¾ ^) # ^^ Θ ^ ^-
0% 8*¾i。 呦^ 遨 C)Tコ 翁^; ん¾¾ ^^ 一 0 % 8 * ¾i. C 呦 T
Figure imgf000187_0005
Figure imgf000187_0005
ε各粱呦 ： ε εEach 呦: ε
•(ΖΗΠ=Γ 'Ρ 'Ηΐ)88·ΐΐ• ( Ζ ΗΠ = Γ 'Ρ' Ηΐ) 88
'(s Ήΐ)22 ΐ '(ΖΗΠ=Γ 'Ρ 'Ηΐ) 9·8 '(ΖΗ8=Γ 'Ρ Ήΐ)6Γ8 '(ΖΗ6=Γ 'Ρ 'Ηΐ)Ζ6· '(ZH8=f 'Ρ Ήΐ)88"Ζ '(ZH6=f 'Ρ 'HI)6S'Z
Figure imgf000187_0006
' 'HT)SS"Z ' 'HD VL '(zHZ=f 'b 'H2)99"S '(s Ήε)6Γ2 '(zH =f '； Ήε)6Γΐ 9 :( P— OS ) 顺— H
Figure imgf000187_0007
981- S081760/S00Z OAV '( s Ήΐ) 22 ΐ' ( Ζ ΗΠ = Γ 'Ρ' Ηΐ) 9.8 '( Ζ Η8 = Γ' Ρ Ήΐ) 6Γ8 '( Ζ Η6 = Γ' Ρ 'Ηΐ) Ζ6' (ZH8 = f 'Ρ Ήΐ) 88 "Ζ' (ZH6 = f 'Ρ' HI) 6S'Z
Figure imgf000187_0006
'' HT) SS "Z '' HD VL '(zHZ = f' b 'H2) 99"S' (s Ήε) 6Γ2 '(zH = f'; Ήε) 6Γΐ 9 :( P— OS) 顺 — H
Figure imgf000187_0007
981- S081760 / S00Z OAV
ベ,ェ cH-— - ΰ — (ΐ) C, cH-—-ΰ — (ΐ)
各粱呦 - zm Each siang 呦-zm
•(zHST=f 'P 'HT)S6"n '(s Ήΐ)22 ΐ '(zHS'SI=f 'P 'HI)S9'8 '(zH8=f 'P Ήΐ)6Γ8 '(zH6=f 'P Ήΐ)86"Ζ '(zH8=f 'P Ήΐ)88"Ζ '(zH6=f 'P 'HT)6S"Z
Figure imgf000188_0001
' 'HT)SS"Z ' 'Ηΐ) ·Ζ '(sjq 'Ηΐ) ( Z HST = f 'P' HT) S6 "n '( s Ήΐ) 22 ΐ'(zHS'SI = f 'P' HI) S9'8 '(zH8 = f' P Ήΐ) 6Γ8 '(zH6 = f 'P Ήΐ) 86 "Ζ' (zH8 = f 'P Ήΐ) 88"Ζ' (zH6 = f 'P' HT) 6S "Z
Figure imgf000188_0001
'' HT) SS "Z '' Ηΐ) · Ζ '(sjq' Ηΐ)
' 'ΗΖ)Ζ9'£ '(zHS"Z=f 'b ΉΖ)£9'Ζ '(zH =f '； Ήε)ΖΓΐ 9 :( P- OSW I) 顺- H
Figure imgf000188_0002
'' ΗΖ) Ζ9 '£' (zHS "Z = f 'b ΉΖ) £ 9'Ζ' (zH = f '; Ήε) ΖΓΐ 9 :( P- OSW I) 顺-H
Figure imgf000188_0002
•(s Ήΐ)εο·• ( s Ήΐ) εο ·
'(ω 'Η8)00· S8'S '(s Ή£ :('(ω' Η8) 00S8'S '(s Ή £ :(
DaD)H N-HT °% 6 ¾τ
Figure imgf000188_0003
DaD) H NH T °% 6 ¾τ
Figure imgf000188_0003
ベ - s- /
Figure imgf000188_0004
(ζ)Ba-s- /
Figure imgf000188_0004
(ζ)
•(s Ήΐ)ΐΓ3
Figure imgf000188_0005
' 'H2)6S"S '(saq ΉΖ)Ζ£'£
Figure imgf000188_0006
Ήε)60·ΐ 9 :( P- OSW I) 顺- H • (s Ήΐ) ΐΓ3
Figure imgf000188_0005
'' H2) 6S "S '(saq ΉΖ) Ζ £' £
Figure imgf000188_0006
Ήε) 60ΐ 9 :( P- OSW I) 顺-H
T :*¾i ^ ^ ^mm^m^ mん ^ 一 ベ - s - /— ½。 Ei、 ¾^- s' ( ^エ 、^ 、 - s)- ΐ- ^エ- ε (ΐ) T : * ¾i ^ ^ ^ mm ^ m ^ m ^ ^-s-/ — ½. Ei, ¾ ^-s' (^ e, ^,-s)-ΐ- ^ e- ε (ΐ)
"(ζΗ2ΐ=Γ 'Ρ 'Ηΐ)88·ΐΐ '(s Ήΐ)ε2 ΐ '(ζ =1" 'Ρ 'HT)S9"8 '(ZH8=f 'Ρ 'Ηΐ ·8
Figure imgf000188_0007
'Ρ Ήΐ)88"Ζ
Figure imgf000188_0008
' 'HT)SS"Z ' 'HD VL (s-iq 'Ηΐ)9 "( ζ Η2ΐ = Γ 'Ρ' Ηΐ) 88 · ΐΐ '( s Ήΐ) ε2 ΐ' (ζ = 1"'Ρ' HT) S9 "8 '(ZH8 = f' Ρ 'Ηΐ · 8
Figure imgf000188_0007
'Ρ Ήΐ) 88 "Ζ
Figure imgf000188_0008
'' HT) SS "Z '' HD VL (s-iq 'Ηΐ) 9
'(zH8=f ' 'HZ)£L'£ '(zH8=f ' 'ΗΖ)£9'£ '(s 'H£)6VZ 9 :( P- OS ) 顺- H
Figure imgf000188_0009
981· S081760/S00Z OAV (sjq 'HI)S9 ΐ '(wq Ήΐ)03·Π 'Ηΐ)ΖΖ·8 '(zH8=f 'P 'HI)ZS'8 '(zH8 = f''HZ) £ L' £ '(zH8 = f''ΗΖ) £ 9' £ '( s ' H £) 6VZ 9 :( P- OS) 顺-H
Figure imgf000188_0009
981S081760 / S00Z OAV (sjq 'HI) S9 ΐ' (wq Ήΐ) 03Π Π 'Ηΐ) ΖΖ8' ( z H8 = f 'P' HI) ZS'8
'(ZH8=f 'P Ήΐ)66"Ζ '(ΖΗΖ·Ζ=ί" 'HZ)£6'L
Figure imgf000189_0001
' 'HI)8S'Z '(ZH8 = f' P Ήΐ) 66 "Ζ '(ΖΗΖ · Ζ = ί"' HZ) £ 6'L
Figure imgf000189_0001
'' HI) 8S'Z
'(zHZ"Z=f 'HZ)6VL '(zHZ"Z=f Ήΐ)62"Ζ 9 :(9p— OSW I) 顺— HT °%SZ ¾T '(zHZ "Z = f' HZ) 6VL '(zHZ" Z = f Ήΐ) 62 "Ζ 9 :( 9 p— OSW I) 顺 — H T °% SZ ¾T
•(saq 'HI)SS ΐ '(saq Ήΐ)36 ΐ '(ω 'HI)0S'8- 0 ·8 '(ω 'HI)SS'8- SI'8 • (saq 'HI) SS ΐ' (saq Ήΐ) 36 ΐ '(ω' HI) 0S'8-0 8 '(ω' HI) SS'8- SI'8
Ήΐ)66"Ζ
Figure imgf000189_0002
4 'HT)S8"Z '(ω 'HT)e9"Z-0S Ήΐ) 66 "Ζ
Figure imgf000189_0002
4 'HT) S8 "Z' (ω 'HT) e9" Z-0S
' 'H ·ζ '(ZHS'Z=1" '； ' )fVL '(s Ήε)ΐΓ2 9 :(9p— oswa) 顺— HT °% 9 ¾T '' H · ζ '(ZHS'Z = 1 "';')fVL' ( s Ήε) ΐΓ2 9 :( 9 p—oswa) 顺 — H T °% 9 ¾T
^ ^ ^mm^m^ mつ ^ ^ - ^ ^ ^ mm ^ m ^ m ^ ^-
ベ,ェ cH-— / ^ / ( ^エ ci / ベ )— (ΐ) C, cH- — / ^ / (^ d ci / be) — (—)
各粱呦 ^ -SZ [8ΖΪ0] "(s-i Ήΐ)22·2ΐ '(saq 'Ηΐ)Μ) ΐ Ή 'Ηΐ)0 ·6
Figure imgf000189_0003
'Ρ Ήΐ)8Γ8
Figure imgf000189_0004
Each beam ^ -SZ [8ΖΪ0] "(si Ήΐ) 222ΐ '(saq' Ηΐ) Μ) ΐ Ή 'Ηΐ) 0
Figure imgf000189_0003
'Ρ Ήΐ) 8Γ8
Figure imgf000189_0004
'(zHS"Z=f 'b 'H2)06"2 '(zHS" =f 'HS "T 9 :(9p—〇SWa) 顺— HT °%S9 ？ φ '(zHS "Z = f' b 'H2) 06"2' (zHS "= f 'HS" T 9 :( 9 p—〇SWa) 顺 — H T °% S9?
•(s Ή\)^Ζ\ '(zHST=f 'P 'Ηΐ)86·ΐΐ '(zHST=f 'P 'Ηΐ)9 ·6 '(ZH8=f 'P Ήΐ)02"8
Figure imgf000189_0005
' 'Ηΐ)9ΓΖ
Figure imgf000189_0006
' Ήΐ)ΖΥί Ήΐ)82"Ζ • ( s Ή \) ^ Ζ \ '( z HST = f' P 'Ηΐ) 86ΐΐ' ( z HST = f 'P' Ηΐ) 9Ηΐ6 '(ZH8 = f' P Ήΐ) 02 "8
Figure imgf000189_0005
'' Ηΐ) 9ΓΖ
Figure imgf000189_0006
'Ήΐ) ΖΥί Ήΐ) 82 "Ζ
'(zHS"Z=f 'b ΉΖ)£6'Ζ '(zHS"Z=f 'HS)9S"T 9 :(9p— OSWa) 顺— HT °% 9 ¾T '(zHS "Z = f' b ΉΖ) £ 6'Ζ '(zHS" Z = f' HS) 9S "T 9 :( 9 p— OSWa) 顺 — H T °% 9 ¾T
各粱呦 -9zm •(S 'HI) 90 ΐ '(ζΗετ=Γ 'ρ 'ΗΪ) ernEach beam -9zm • ( S 'HI) 90 ΐ' ( ζ Ηετ = Γ 'ρ' ΗΪ) ern
)
Figure imgf000189_0007
)
Figure imgf000189_0007
'b Ήζ) LS'Z '(s Ήε) LZ'Z '(zHS" =f Ήε) ε·ΐ 9 :(9p— oswa) 顺— HT °%S ¾T
Figure imgf000189_0008
Z8I- S081760/S00Z OAV -(mv9=i 'P 'Ηΐ)ΐ ΐ' b Ήζ) LS'Z' (s Ήε) LZ'Z '(zHS "= f Ήε) εΐ ΐ 9 :( 9 p— oswa) 顺 — H T °% S ¾T
Figure imgf000189_0008
Z8I- S081760 / S00Z OAV -(mv9 = i 'P' Ηΐ) ΐ ΐ
'(ζ服 =f 'Ρ 'HWU '(ΖΗ ·9=ί" 'Ρ 'Ηΐ)ΐΖ·8 '(ζ服 =1" 'Ρ 'Ηΐ)89·8 '(ΖΗ8=Γ 'Ρ 'Ηΐ) ·8 '(ZH6=f 'Ρ 'H¾S0"8
Figure imgf000190_0001
'(ζ clothes = f' Ρ 'HWU' ( ΖΗ · 9 = ί "'Ρ' Ηΐ) ΐΖ · 8 '(ζ clothes = 1"' Ρ 'Ηΐ) 89 · 8' (Ζ Η8 = Γ 'Ρ' Ηΐ) 8 '(ZH6 = f' Ρ 'H¾S0 "8
Figure imgf000190_0001
'p Ήζ) η '(zH8=f ' ' )ovL '(s 'u z'z 9 :(9p— OSW I) 顺— HT °%S8 ? ill 'p Ήζ) η' ( z H8 = f '') ovL '( s ' u z'z 9 :( 9 p— OSW I) 顺 — H T °% S8? ill
SSS各粱呦  SSS
•(zHS-9=f 'P 'H\)ZVZ\ '{ =[ 'P 'H\)W\\ '(ζΗε·9=ί" 'P Ήΐ)2 ·8 =[ 'P 'Ηΐ)69·8 '(zW8=f 'P 'Ηΐ) ·8 '(s Ήΐ)^Γ8 '(zHS'8=f 'P 'Ηΐ)66· '(zW8=f ' 'HT)2Z"Z '(zW8=f 'Ρ 'HT)S9"Z '(zH2"8=f ' 'HDW L '(zW8=f ' 'Ηΐ)ΐ ·
Figure imgf000190_0002
• ( z HS-9 = f 'P' H \) ZVZ \ '{= [' P 'H \) W \\' (ζΗε9 = ί "'P Ήΐ) 2 · 8 = [' P 'Ηΐ ) 698 '(zW8 = f'P'Ηΐ) 8' ( s Ήΐ) ^ Γ8 '(zHS'8 = f'P'Ηΐ) 66 · '(zW8 = f''HT) 2Z "Z' (zW8 = f 'Ρ' HT) S9 "Z '(zH2" 8 = f''HDWL' (zW8 = f '' Ηΐ) ΐ
Figure imgf000190_0002
εε各粱呦^ - m εεEach 呦 ^-m
•(ΖΗε·9=ί" 'P 'HI)ZS ΐ '(zHW=f 'P 'HI ·ΐΐ '(ζΗε·9=ί" 'P 'Ηΐ)69·8 '(ζ服 =f 'P 'Ηΐ)ε9·8 '(zHS'Z=f 'P 'HI ·8 '(ω • (ΖΗε · 9 = ί "'P' HI) ZS ΐ '(z HW = f' P 'HI · ΐΐ' (ζΗε · 9 = ί"'P' Ηΐ) 69 · 8 '(ζ clothes = f' P 'Ηΐ) ε9.8'(zHS'Z = f 'P' HI
'Hs)ez"z-ee"z '(ω 'H )OS'Z ss'z Ή£)9ζτ 9 :(9p— oswa) N— HT °%S6 ？ Φ 'Hs) ez "z-ee"z'(ω'H)OS'Zss'z Ή £) 9ζτ 9 :( 9 p—oswa) N—H T °% S6? Φ
εεε各粱呦 ： εεείϋ εεε each beam: εεείϋ
•(zW9=f 'P 'HI)8S ΐ '(ζΗ8·εΐ=ί" 'Ρ 'Ηΐ)½·ΐΐ '(zW9=f 'Ρ Ήΐ)2 ·8 '(zH8"ST=f 'Ρ 'Ηΐ)89·8 '(zHS" =f 'Ρ 'ΗΙ)£Ζ'8 '(zH8=f 'Ρ 'H2)S0"8 '(zHS" =f 'ΗΙ)ΖίΊ
Figure imgf000190_0003
' Ήΐ)εΓΖ '(zHS"Z=f 'b 'H2)69"2 '(zHS" =f 'HS)82"T 9 :(9p—〇SWa) 顺— HT °%98 ¾T
Figure imgf000190_0004
• (zW9 = f 'P' HI) 8S ΐ '(ζΗ8 · εΐ = ί "' Ρ 'Ηΐ) ½ · ΐΐ' (zW9 = f 'Ρ Ήΐ) 2 · 8'(zH8" ST = f 'Ρ' Ηΐ) 89 · 8 '(zHS "= f' Ρ 'ΗΙ) £ Ζ'8' (zH8 = f 'Ρ' H2) S0" 8 '(zHS "= f' ΗΙ) ΖίΊ
Figure imgf000190_0003
'Ήΐ) εΓΖ' (zHS "Z = f 'b' H2) 69" 2 '(zHS "= f' HS) 82" T 9 :( 9 p—〇SWa) 顺 — H T °% 98 ¾T
Figure imgf000190_0004
•(zH8'SI=f 'P 'H\)ZVZ\ • (zH8'SI = f 'P' H \) ZVZ \
'(s Ήΐ)^ ΐ '(ζΗ8·εΐ=ί" 'P 'Ηΐ)06·8 '(zH6=f 'P 'HI)W8 '(zHS'Z=f 'P 'H2)20"8 '(ω 'H2)86"Z-08"Z
Figure imgf000190_0005
'( s Ήΐ) ^ ΐ' (ζΗ8 · εΐ = ί "'P' Ηΐ) 068 '( z H6 = f' P 'HI) W8'(zHS'Z = f 'P' H2) 20" 8 '(ω' H2) 86 "Z-08" Z
Figure imgf000190_0005
'(zHS"Z=f ^ Ήΐ)ΖΓΖ '(s 'Η 06·ε '(s 'HS)69"S 9 :(9p— OSWa) 顺— HT °%S9 ? φ '(zHS "Z = f ^ Ήΐ) ΖΓΖ'(s' Η 06 · ε '( s ' HS) 69" S 9 :( 9 p— OSWa) 顺 — H T °% S9? φ
•(sj Ήΐ)ε9 ΐ• (sj Ήΐ) ε9 ΐ
'(saq 'Ηΐ)θε·ΐΐ '(s 'HI)S9'8
Figure imgf000190_0006
'(saq' Ηΐ) θεΐΐ '(s' HI) S9'8
Figure imgf000190_0006
Figure imgf000190_0007
' 'HT)6S"Z '(s 'Η£)£Υ£ g :(9p— OSW I) 顺— HT °%08 ¾T οεε各粱呦^ -ozm
Figure imgf000190_0008
881· S081760/S00Z OAV z ^ ^ '-z [ΐ8ΐθ]
Figure imgf000190_0007
'' HT) 6S "Z '(s' Η £) £ Υ £ g :( 9 p— OSW I) 顺 — H T °% 08 ¾T οεε each beam 呦 ^ -ozm
Figure imgf000190_0008
881S081760 / S00Z OAV z ^ ^ '-z [ΐ8ΐθ]
•(sjq 'HI)6S ΐ
Figure imgf000191_0001
'Ρ 'Ηΐ)ΐε· ΐ ΐ Ή 'Ηΐ)69·8 • (sjq 'HI) 6S ΐ
Figure imgf000191_0001
'Ρ' Ηΐ) ΐε · ΐ ΐ 'Ηΐ) 69
'Ρ
Figure imgf000191_0002
'Ρ
Figure imgf000191_0002
Ήΐ)03·Ζ '(ω 'Hf) VL-0Z-L '(s 'HS)92"2 9 :( OSW I) 顺— Ητ °%ZZ ¾ί
Figure imgf000191_0003
Ήΐ) 03 · Ζ '(ω' Hf) VL-0Z-L '( s ' HS) 92 "2 9 :( OSW I) 顺 — Η τ °% ZZ ¾ί
Figure imgf000191_0003
'P 'H\)LV \ \ '(ζΗε·9=ί" 'P 'Ηΐ)69·8 '(zHW=f 'P 'Ηΐ) 9·8 '(zH8=f 'P 'Ηΐ) ·8 'P' H \) LV \ \ '(ζΗε9 = ί "' P 'Ηΐ) 698' ( z HW = f 'P' Ηΐ) 9.8 '( z H8 = f' P 'Ηΐ) · 8
(zHS"8=f 'P Ή2)68"Ζ '(zH8=f 'P Ήΐ)69"Ζ '(zH8=f ' Ήΐ)99"Ζ '(zH8=f ' Ήΐ)0^"Ζ (zHS "8 = f 'P Ή2) 68" Ζ' (zH8 = f 'P Ήΐ) 69 "Ζ' (zH8 = f 'Ήΐ) 99" Ζ' (zH8 = f 'Ήΐ) 0 ^ "Ζ
'ρ 'HZ)WL '(s Ήε)οε '(s 'm z'z 9 :(9p— oswa) 顺— HT °%68 ¾T 'ρ' HZ) WL '(s Ήε) οε' ( s ' m z'z 9 :( 9 p— oswa) 顺 — H T °% 68 ¾T
•(zHS-9=f 'P 'HI)6S ΐ =[ 'P 'Ηΐ)6 · ΐ ΐ '(ζΗε·9=ί" 'P Ήΐ)0Ζ·8 '(zHW=f 'P 'Ηΐ)99·8 '(ΖΗε·8=ί" 'P 'Ηΐ) ·8 '(s Ήΐ)98"Ζ '(ΖΗΖ·Ζ=ί" 'Ρ 'HT)S8"Z
Figure imgf000191_0004
• ( z HS-9 = f 'P' HI) 6S ΐ = ['P' Ηΐ) 6 · ΐ ΐ '(ζΗε9 = ί "' P Ήΐ) 0Ζ8 '( z HW = f' P ' Ηΐ) 99 · 8 '(ΖΗε · 8 = ί "' P 'Ηΐ) · 8' ( s Ήΐ) 98" Ζ '(ΖΗΖ · Ζ = ί "' Ρ 'HT) S8" Z
Figure imgf000191_0004
'HT)2Z"Z '(ΖΗε·8=ί" 'Ρ 'HT)S9"Z
Figure imgf000191_0005
' Ήΐ)ΟΥί '(ΖΗΖ·Ζ=ί" Ήΐ)82"Ζ 'HT) 2Z "Z' (ΖΗε · 8 = ί"'Ρ' HT) S9 "Z
Figure imgf000191_0005
'Ήΐ) ΟΥί' (ΖΗΖ · Ζ = ί "Ήΐ) 82" Ζ
:(ΖΗΖ·Ζ=1" 'Ρ 'HT)S6"9 '(s 'HS)SS"2 '(s 'U£)SZ'Z 9 :(9p— OSWa) N— HT °% ¾T : (ΖΗΖ · Ζ = 1 "'Ρ' HT) S6" 9 '( s ' HS) SS "2 '(s' U £) SZ'Z 9 :( 9 p— OSWa) N— H T °% ¾T
6εε各粱呦 -ezm •(sj Ήΐ)ΐ ΐ '(zHs'si=f 'p Ήΐ)3ε·π  6εε each beam 呦 -ezm • (sj Ήΐ) ΐ ΐ '(zHs'si = f' p Ήΐ) 3ε
'(s 'Ηΐ)89·8 '(zHS"ST=f 'P Ήΐ)29"8 '(zH8=f 'P Ήΐ)02"8 '(ω 'H SZ'Z— 09·  '(s' Ηΐ) 89 · 8 '(zHS "ST = f' P Ήΐ) 29" 8 '(zH8 = f' P Ήΐ) 02 "8 '(ω' H SZ'Z— 09
'(ui 'HS)e^- -S2" '(s 'U£) Z'Z '(s 'H£)£Z'Z 9 :(9p— OSWa) 顺— HT °%9 ¾T '(ui' HS) e ^--S2 "'(s' U £) Z'Z '( s ' H £) £ Z'Z 9 :( 9 p— OSWa) 顺 — H T °% 9 ¾T
8εε各粱呦 -szm 8εε each siang 呦 -szm
•(sjq 'Ηΐ)09 ΐ
Figure imgf000191_0006
'P Ήΐ)ΐ Γ2ΐ '(sjq 'm)SV0l • (sjq 'Ηΐ) 09 ΐ
Figure imgf000191_0006
'P Ήΐ) ΐ Γ2ΐ' (sjq 'm) SV0l
'P 'Ηΐ)06·8 '(zH6=f 'P 'Ηΐ) 8 '(zH8=f 'P 'HZ)WS '(zH8=f 'P 'Ηΐ)εθ·8 '(zH8=f 'P' Ηΐ) 068 '( z H6 = f' P 'Ηΐ) 8' ( z H8 = f 'P' HZ) WS '( z H8 = f' P 'Ηΐ) εθ8' ( z H8 = f
'P Ήΐ)ΐ6"Ζ
Figure imgf000191_0007
'P Ήΐ) ΐ6 "Ζ
Figure imgf000191_0007
' 'HZ)ZVL '(zH8=f ' Ήΐ)ΖΓ ΉΖ)6∑τ 9 :( OSWa) 顺— Ητ °%Ζΐ ¾ί '' HZ) ZVL '(zH8 = f' Ήΐ) ΖΓ ΉΖ) 6∑τ 9 :( OSWa) 顺 — Η τ °% Ζΐ ¾ί
εε各粱呦^ ： ssp } [osio] εε each siang 呦 ^: ssp} [osio]
•(sjq 'HWZl '(s 'Ηΐ)ε6·8 '(zH6=f 'P Ήΐ)32·8
Figure imgf000191_0008
(Sjq 'HWZl' ( s ' Ηΐ) ε6.8 '( z H6 = f' P Ήΐ) 32
Figure imgf000191_0008
'(zH8=f Ήΐ)83· '(s Ήε)8 ·ε '(s Ήε)99 9 :(9p— oswa) 顺— HT ¾ί '( z H8 = f Ήΐ) 83''(s Ήε) 8 · ε' ( s Ήε) 99 9 :( 9 p— oswa) 顺 — H T ¾ί
9εε各粱呦 -9zm
Figure imgf000191_0009
681· S081760/S00Z OAV 収率 77%。 H-NMR(DMSO-d ): δ 2.29(3H, s), 6.90— 7.00(1H, m), 7.35— 7.50(2H,9εε each beam -9zm
Figure imgf000191_0009
681S081760 / S00Z OAV Yield 77%. H-NMR (DMSO-d): δ 2.29 (3H, s), 6.90-7.00 (1H, m), 7.35-7.50 (2H,
6 6
m), 7.64(1H, d, J=8Hz), 7.72(1H, t, J=8Hz), 7.85- 7.95(2H, m), 8.22(1H, d, J=8Hz), 8.70(1H, d, J=14Hz), 8.71(1H, d, J=6.5Hz), 11.44(1H, d, J=14Hz), 12.42(1H, d, J=6.5Hz). m), 7.64 (1H, d, J = 8Hz), 7.72 (1H, t, J = 8Hz), 7.85- 7.95 (2H, m), 8.22 (1H, d, J = 8Hz), 8.70 (1H, d , J = 14Hz), 8.71 (1H, d, J = 6.5Hz), 11.44 (1H, d, J = 14Hz), 12.42 (1H, d, J = 6.5Hz).
例 343:化合物番号 343 Example 343: Compound number 343
収率 74%。 'H-NMRCDMSO-d ): δ 2.28(3Η, s), 7.24(2Η, t, J=9Hz), 7.41(1Η, t, Yield 74%. 'H-NMRCDMSO-d): δ 2.28 (3Η, s), 7.24 (2Η, t, J = 9Hz), 7.41 (1Η, t,
6  6
J=7.7Hz), 7.65(1H, d, J=7.7Hz), 7.72(1H, t, J=7.7Hz), 8.02(2H, dd, J=9, 5Hz), 8.22(1H, d, J=7.7Hz), 8.67(1H, d, J=14Hz), 8.71(1H, d, J=6Hz), 11.43(1H, d, J=14Hz), 12.40(1H, d, J=6Hz).  J = 7.7Hz), 7.65 (1H, d, J = 7.7Hz), 7.72 (1H, t, J = 7.7Hz), 8.02 (2H, dd, J = 9, 5Hz), 8.22 (1H, d, J = 7.7Hz), 8.67 (1H, d, J = 14Hz), 8.71 (1H, d, J = 6Hz), 11.43 (1H, d, J = 14Hz), 12.40 (1H, d, J = 6Hz).
例 344:化合物番号 344 Example 344: Compound number 344
収率 78%。 'H-NMRCDMSO-d ): δ 2.24(3Η, s), 3.77(3Η, s), 6.97(2Η, d, J=9Hz), Yield 78%. 'H-NMRCDMSO-d): δ 2.24 (3Η, s), 3.77 (3Η, s), 6.97 (2Η, d, J = 9Hz),
6  6
7.40(1Η, td, J=7.5, 1.5Hz), 7.65(1H, dd, J=7.5, 1.5Hz), 7.72(1H, td, J=7.5, 1.5Hz), 7.89(2H, d, J=9Hz), 8.22(1H, dd, J=7.5, 1.5Hz), 8.63(1H, d, J=14Hz), 8.69(1H, d, J=6.5Hz), 11.46(1H, d, J=14Hz), 12.39(1H, d, J=6.5Hz).  7.40 (1Η, td, J = 7.5, 1.5Hz), 7.65 (1H, dd, J = 7.5, 1.5Hz), 7.72 (1H, td, J = 7.5, 1.5Hz), 7.89 (2H, d, J = 9Hz), 8.22 (1H, dd, J = 7.5, 1.5Hz), 8.63 (1H, d, J = 14Hz), 8.69 (1H, d, J = 6.5Hz), 11.46 (1H, d, J = 14Hz) , 12.39 (1H, d, J = 6.5Hz).
例 345:化合物番号 345 Example 345: Compound number 345
収率 78%。 ^-NMRCDMSO-d ): δ 2.28(3Η, s), 7.15(1Η, t, J=7.5Hz), 7.42(2Η, t, Yield 78%. ^ -NMRCDMSO-d): δ 2.28 (3Η, s), 7.15 (1Η, t, J = 7.5Hz), 7.42 (2Η, t,
6  6
J=7.5Hz), 7.58(1H, t, J=8Hz), 7.78(1H, d, J=8Hz), 7.88(1H, t, J=8Hz), 7.99(2H, d, J=7.5Hz), 8.19(1H, d, J=8Hz), 8.50- 8.60(1H, m), 9.10(1H, s), 11.08- 11.18(1H, m). 3-ァミノ- 4H-クロメン- 4-オン： Journal of Chemical Research (M), p.0882- 0890(1978) 参照。  J = 7.5Hz), 7.58 (1H, t, J = 8Hz), 7.78 (1H, d, J = 8Hz), 7.88 (1H, t, J = 8Hz), 7.99 (2H, d, J = 7.5Hz) , 8.19 (1H, d, J = 8Hz), 8.50- 8.60 (1H, m), 9.10 (1H, s), 11.08- 11.18 (1H, m). 3-Amino-4H-chromen-4-one: Journal See Chemical Research (M), pp. 0882-0890 (1978).
例 346:化合物番号 346 Example 346: Compound number 346
(1) 2'-メチルァミノ- 2-二トロアセトフエノン  (1) 2'-Methylamino-2-nitroacetophenone
一般合成法 Κと同様の方法により標題ィ匕合物を得た。収率 81%。 1 To give the title I匕合product by the general synthetic methods Κ the same way. Yield 81%. 1
H-NMR(DMSO-d ): δ 2.88(3H, d, J=5Hz), 6.42(2H, s), 6.63(1H, t, J=8Hz), H-NMR (DMSO-d): δ 2.88 (3H, d, J = 5Hz), 6.42 (2H, s), 6.63 (1H, t, J = 8Hz),
6  6
6.82(1H, d, J=8Hz), 7.50(1H, t, J=8Hz), 7.56(1H, d, J=8Hz), 8.46(1H, d, J=5Hz). 6.82 (1H, d, J = 8Hz), 7.50 (1H, t, J = 8Hz), 7.56 (1H, d, J = 8Hz), 8.46 (1H, d, J = 5Hz).
(2) 1-メチル -3-二トロ- 1,4-ジヒドロキノリン- 4-オン (一般合成法 V ) (2) 1-methyl-3-nitro-1,4-dihydroquinolin-4-one (General synthesis method V)
2しメチルァミノ- 2-二トロアセトフエノン (lg, 5.15mmol)、オルトギ酸ェチル (0.94ml, 5.70mmol)及びトルエン (5ml)の混合物を 3時間加熱還流した。反応混合物を室温まで ΐδε各粱呦^A mixture of methylamino-2-nitroacetophenone (lg, 5.15 mmol), ethyl ethyl formate (0.94 ml, 5.70 mmol) and toluene (5 ml) was heated to reflux for 3 hours. Bring the reaction mixture to room temperature ΐδε each beam 呦 ^
Figure imgf000193_0001
Figure imgf000193_0001
'(s 'HT)02"6 '(s 'HT)29"8 '(zH8=f 'P Ήΐ)8Γ8 '(zH8=f ' 'HT)06"Z '(zH8=f 'P 'HT)8Z"Z
Figure imgf000193_0002
' 'HT)ZS"Z '(s Ήε Τ 9 :( P-OS a)H N-HT °%SZ ¾T '( s ' HT) 02 "6 '( s ' HT) 29" 8 '( z H8 = f' P Ήΐ) 8Γ8 '( z H8 = f''HT) 06 "Z' (zH8 = f 'P' HT) 8Z "Z
Figure imgf000193_0002
'' HT) ZS "Z '(s Ήε Τ 9 :( P-OS a) H NH T °% SZ ¾T
OSS各粱呦^ -0 m •(sjq 'HT)S8"n '(s 'Ηΐ) 6 '(s 'HI)SZ'8 '(zH8=f 'P Ήΐ)6Γ8
Figure imgf000193_0003
' 'HT)6S"Z OSS each 呦 ^ -0 m • (sjq 'HT) S8 "n' ( s ' Ηΐ) 6 '( s ' HI) SZ'8' ( z H8 = f 'P Ήΐ) 6Γ8
Figure imgf000193_0003
'' HT) 6S "Z
'(zHS"Z=f ^ 'H2)0S"Z '(zHS"Z=f ^ Ήΐ)62"Ζ 9 :( P-OS a)H N-HT °%8 ¾T
Figure imgf000193_0004
'(zHS "Z = f ^' H2) 0S" Z '(zHS "Z = f ^ Ήΐ) 62" Ζ 9 :( P-OS a) H NH T °% 8 ¾T
Figure imgf000193_0004
'(saq 'Ηΐ)68·8
Figure imgf000193_0005
'P 'H2)86"Z '(ω 'H2)S8"Z-SZ"Z '(ω '(saq' Ηΐ) 68
Figure imgf000193_0005
'P' H2) 86 "Z '(ω' H2) S8" Z-SZ "Z '(ω
'HS)eS" -e^" '(zH8=f ' Ήΐ)82"Ζ '(s Ήε)66·ε 9 :( P-OS a)H N-HT °%9S ¾ί 'HS) eS "-e ^"' (zH8 = f 'Ήΐ) 82 "Ζ' (s Ήε) 66 · 9 :( P-OS a) H NH T °% 9S ¾ί
"(s-i 'Ηΐ)^ ΐ '(s 'Ηΐ) 6·8 '(s Ήΐ)ε ·8 '(zH8=f 'P 'HT)62"8 '(^ 'HS)06'Z- SZ'Z "(si 'Ηΐ) ^ ΐ' ( s ' Ηΐ) 6.8 '( s Ήΐ) ε · 8' ( z H8 = f 'P' HT) 62" 8 '(^' HS) 06'Z- SZ 'Z
'(in 'HWL-OVL '(s Ήε) 6"ε '(s Ήε)ε ·ε 9 :( p-os a)H N-HT °%08 ¾i '(in' HWL-OVL '( s Ήε) 6 "ε' ( s Ήε) ε · ε 9 :( p-os a) H NH T °% 08 ¾i
ε各粱呦^ -m Κ8ΐθ] ε each beam 呦 ^ -m Κ8ΐθ]
•(z服 =f 'P 'Ηΐ)ΐ ·ΐΐ '(s 'HT)28"8 '(z服 =f 'P 'HI)8S'8 '(zH8=f 'P 'Ηΐ) 8
Figure imgf000193_0006
'P 'H2)00"8 '(ω 'H2)S8"Z-SZ"Z '(ω 'HI)SS'Z— S 'Z ' 'HZ)IVL • (z clothing = f 'P' Ηΐ) ΐ · ΐΐ '(s' HT) 28 "8 '( z clothing = f' P 'HI) 8S'8' ( z H8 = f 'P' Ηΐ) 8
Figure imgf000193_0006
'P' H2) 00 "8 '(ω' H2) S8" Z-SZ "Z '(ω' HI) SS'Z— S 'Z''HZ) IVL
'(ZH8=f ' Ήΐ)εΓ '(s Ήε)2ε·ε 'HS)SS 9 :( p-os a)H N-HT °%08 ¾τ '( Z H8 = f' Ήΐ) εΓ '(s Ήε) 2ε ·' HS) SS 9 :( p-os a) H NH T °% 08 ¾τ
"(zH8=f 'P 'HT)02"8 '(ω "( z H8 = f 'P' HT) 02" 8 '(ω
'HS)09"Z-SS"Z '(ω Ήΐ)οε· -θ2" Ή 'H S ' '(s Ήε)ΐ8·ε 9 :( oswa) 顺— H ベ - べ fl,^ci、 ¾、— ΐ— ^ — ΐ— — ε (ε)'HS) 09 "Z-SS"Z' (ω Ήΐ) οε-θ2 "Ή 'HS''( s Ήε) ΐ8 · ε 9 :( oswa) 顺 — H be-be fl, ^ ci, ¾, — Ϊ́— ^ — ΐ— — ε (ε)
•(s 'Ηΐ)6ε·6 '(ZHS'I 'S"Z=f 'PP 'HT)SS"8 '(ZHS'I 'S"Z=f 'P^ Ήΐ)ΐ6"Ζ '(ZHS'I • (s' Ηΐ) 6ε · 6 '(ZHS'I' S "Z = f 'PP' HT) SS" 8 '(ZHS'I' S "Z = f 'P ^ Ήΐ) ΐ6" Ζ' (ZHS 'I
'S"Z=f 'PP Ήΐ)98"Ζ '(ZHS'I 'S"Z=f 'P; Ήΐ)ΐ9"Ζ '(s 'HS)S0' 9 '·( P-OS a)H N-HT 'S "Z = f' PP Ήΐ) 98" Ζ '(ZHS'I' S "Z = f 'P; Ήΐ) ΐ9"Ζ'(s' HS) S0 '9' · (P-OS a) H NH T
。 %89
Figure imgf000193_0007
. % 89
Figure imgf000193_0007
^^mn、ェっ ¾ ^ 一ェ 厶 mm^^^ ΨΜ^
Figure imgf000193_0008
1-61. S081760/S00Z OAV sss各粱呦 ： eesp} ^^ mn, ^^^^^^^^ ^
Figure imgf000193_0008
1-61. S081760 / S00Z OAV sss each sword: eesp}
•(z服 =f• ( z clothes = f
'P Ήΐ)ΐ3·Π '(s Ήΐ)88·8 '(ζ服 =f 'P 'Ηΐ)89·8 'd8- f 'P 'HI)SS'8 '(zHS'8=f 'P 'P Ήΐ) ΐ3 · Π' (s Ήΐ) 88 · 8 '(ζ clothes = f' P 'Ηΐ) 89 · 8' d8- f 'P' HI) SS'8 '(zHS'8 = f' P
'H2)00"8 '(ω 'H9)08"Z-09"Z '(zH2"8=f ' 'HDLVL '(zHS"8=f ' 'HZ)IVL '(zHS"8=f ' Ήΐ)εΓΖ 'P ' )WL '(s 'U Z'Z 9 :( P-OS a)H N-HT °%Z9 ? ill
Figure imgf000194_0001
(ε) ベ - べ fl,^cl、 ¾、— ΐ— / ェ — ΐ— cH — ε (Z) ベ,ェ cH-— -ェ — (ΐ) 'H2) 00 "8' (ω 'H9) 08" Z-09 "Z'(zH2" 8 = f '' HDLVL '(zHS "8 = f''HZ)IVL'(zHS" 8 = f 'Ήΐ ) εΓΖ 'P') WL '( s ' U Z'Z 9 :( P-OS a) H NH T °% Z9? ill
Figure imgf000194_0001
(ε) be-be fl, ^ cl, ¾, — ΐ— / —— c— cH — ε (Z) be, c cH -—-— — (ΐ)
各粱呦^
Figure imgf000194_0002
Each saga 呦 ^
Figure imgf000194_0002
^HVZ\=[ 'P 'H\)\VZ\  ^ HVZ \ = ['P' H \) \ VZ \
'(sj 'Ηΐ)Ζε·Οΐ 'WZ\=[ 'P 'Ηΐ)ε8·8 '(zH8=f 'P Ή\)ΖΖ^ '(zH8=f 'p Ή εο·8
Figure imgf000194_0003
' 'HT)SS"Z
Figure imgf000194_0004
' 'HDSVL 'H '(sj' Ηΐ) ΖεΟΐ 'WZ \ = [' P 'Ηΐ) ε888' ( z H8 = f 'P Ή \) ΖΖ ^' ( z H8 = f 'p Ή εο8
Figure imgf000194_0003
'' HT) SS "Z
Figure imgf000194_0004
'' HDSVL 'H
(zHS"Z=f ΉΖ)ΟΥΖ '(zHS"Z=f '^m )96·ΐ 9 :(9p—〇SWa) 顺— HT °%8S ¾T (zHS "Z = f ΉΖ) ΟΥΖ '(zHS" Z = f' ^ m) 96ΐ 9 :( 9 p—〇SWa) 顺 — H T °% 8S ¾T
SSS各粱呦^ ： SSSp} 810] SSS each 呦: SSSp} 810]
•(zH9=f 'p Ήΐ)εε ΐ '( q ' )zvn '(zH9=f 'p 'ΗΪ) 9·8 ( Z H9 = f 'p Ήΐ) εε ΐ' (q ') zvn' ( z H9 = f 'p' ΗΪ) 9.8
'(saq 'HT)SS"8
Figure imgf000194_0005
'P 'HT)S9"Z '(saq' HT) SS "8
Figure imgf000194_0005
'P' HT) S9 "Z
'(ω 'H9)S 'Z— 0 '(s 'HZ)W '(s Ήε)3Γ2 9 :( OSWa) 顺— HT °%9 ¾T '(ω' H9) S 'Z— 0' (s 'HZ) W' ( s Ήε) 3Γ2 9 :( OSWa) 顺 — H T °% 9 ¾T
SSS各粱呦 -z^m SSS each 呦 -z ^ m
Figure imgf000194_0006
Figure imgf000194_0006
'P 'Ηΐ)ΐΟ ΐ '(s 'Ηΐ)6ε·0ΐ '(zHS-ST=f 'Ρ 'HT)28"8 '(ΖΗ6=Γ 'Ρ 'HWS '(ΖΗ6=Γ 'Ρ Ήΐ)06"Ζ '(ω 'HS)S9"Z-09"Z
Figure imgf000194_0007
'Ρ 'HI)9S'Z '(ω 'HS)SS'Z— 'P' Ηΐ) ΐΟ ΐ '( s ' Ηΐ) 6ε0ΐ '(zHS-ST = f' Ρ 'HT) 28 "8' ( Ζ Η6 = Γ 'Ρ' HWS '( Ζ Η6 = Γ' Ρ Ήΐ ) 06 "Ζ '(ω' HS) S9" Z-09 "Z
Figure imgf000194_0007
'Ρ' HI) 9S'Z '(ω' HS) SS'Z—
' Ήΐ)3ΓΖ
Figure imgf000194_0008
'HS)S 'Ήΐ) 3ΓΖ
Figure imgf000194_0008
'HS) S
(zHS"Z=f 'W!nb 'H2)66"T '(zHS" =f ^ Ήε)ΖΓΐ 9 :(9p— OSWa) 顺— HT °%0S ¾T
Figure imgf000194_0009
361- S081760/S00Z OAV 収率 46%。 H-NMR(DMSO-d ): δ 7.06(1H, d, J=8Hz), 7.29(1H, t, J=8Hz), (zHS "Z = f 'W! nb' H2) 66" T '(zHS "= f ^ Ήε) ΖΓΐ 9 :( 9 p— OSWa) 顺 — H T °% 0S ¾T
Figure imgf000194_0009
361- S081760 / S00Z OAV Yield 46%. H-NMR (DMSO-d): δ 7.06 (1H, d, J = 8Hz), 7.29 (1H, t, J = 8Hz),
6  6
7.48(2H, t, J=7.5Hz), 7.49(1H, t, J=8Hz), 7.60— 7.80(6H, m), 7.98(2H, d, J=7.5Hz), 8.37(1H, d, J=8Hz), 8.95(1H, brs), 9.15(1H, s), 12.38(1H, brs).  7.48 (2H, t, J = 7.5Hz), 7.49 (1H, t, J = 8Hz), 7.60-7.80 (6H, m), 7.98 (2H, d, J = 7.5Hz), 8.37 (1H, d, J = 8Hz), 8.95 (1H, brs), 9.15 (1H, s), 12.38 (1H, brs).
例 356:化合物番号 356 Example 356: Compound number 356
収率 80%。 'H-NMRCDMSO-d ): δ 3.43(3Η, s), 7.05(1Η, d, J=8Hz), 7.49(1Η, t, Yield 80%. 'H-NMRCDMSO-d): δ 3.43 (3Η, s), 7.05 (1Η, d, J = 8Hz), 7.49 (1Η, t,
6  6
J=8Hz), 7.60-7.75(6H, m), 8.35(1H, d, J=8Hz), 8.82(1H, brs), 9.08(1H, s), 12.43(1H, brs).  J = 8Hz), 7.60-7.75 (6H, m), 8.35 (1H, d, J = 8Hz), 8.82 (1H, brs), 9.08 (1H, s), 12.43 (1H, brs).
例 357:化合物番号 357 Example 357: Compound number 357
収率 38%。 ^-NMRCDMSO-d ): δ 1.92(2Η, quint, J=7.3Hz), 2.33(2Η, t, J=7.3Hz), Yield 38%. ^ -NMRCDMSO-d): δ 1.92 (2Η, quint, J = 7.3Hz), 2.33 (2Η, t, J = 7.3Hz),
6  6
2.68(2H, t, J=7.3Hz), 7.12(1H, t, J=7.5Hz), 7.35- 7.45(3H, m), 7.60-7.70(2H, m), 8.02(2H, d, J=8Hz), 8.20(1H, d, J=7.5Hz), 8.70- 8.85(2H, m), 11.55(1H, brs).  2.68 (2H, t, J = 7.3Hz), 7.12 (1H, t, J = 7.5Hz), 7.35- 7.45 (3H, m), 7.60-7.70 (2H, m), 8.02 (2H, d, J = 8Hz), 8.20 (1H, d, J = 7.5Hz), 8.70- 8.85 (2H, m), 11.55 (1H, brs).
例 358:化合物番号 358 Example 358: Compound number 358
収率 24%。 ^-NMRCDMSO-d ): δ 1.93(2Η, quint, J=7.3Hz), 2.33(2Η, t, J=7.3Hz), Yield 24%. ^ -NMRCDMSO-d): δ 1.93 (2Η, quint, J = 7.3Hz), 2.33 (2Η, t, J = 7.3Hz),
6  6
2.64(2H, t, J=7.3Hz), 7.03(1H, d, J=8Hz), 7.14(1H, t, J=7.5Hz), 7.42(2H, t, J=7.5Hz), 7.48(1H, t, J=8Hz), 7.60— 7.80(6H, m), 8.01(2H, d, J=7.5Hz), 8.35(1H, d J=8Hz), 8.70(1H, d, J=13.5Hz), 8.89(1H, s), 11.63(1H, d, J=13.5Hz), 12.03(1H, brs).  2.64 (2H, t, J = 7.3Hz), 7.03 (1H, d, J = 8Hz), 7.14 (1H, t, J = 7.5Hz), 7.42 (2H, t, J = 7.5Hz), 7.48 (1H , t, J = 8Hz), 7.60-7.80 (6H, m), 8.01 (2H, d, J = 7.5Hz), 8.35 (1H, d J = 8Hz), 8.70 (1H, d, J = 13.5Hz) , 8.89 (1H, s), 11.63 (1H, d, J = 13.5Hz), 12.03 (1H, brs).
例 359:化合物番号 359 Example 359: Compound number 359
収率 94%。 ^-NMRCDMSO-d ): δ 2.17(3H,s), 7.15(1Η, t, J=7.5Hz), 7.42(2H, t, 94% yield. ^ -NMRCDMSO-d): δ 2.17 (3H, s), 7.15 (1Η, t, J = 7.5Hz), 7.42 (2H, t,
6  6
J=7.5Hz), 7.90-8.10(7H, m), 8.21(1H, s).  J = 7.5Hz), 7.90-8.10 (7H, m), 8.21 (1H, s).
例 360:化合物番号 360 Example 360: Compound number 360
(1) 2-ァミノ- 3-ヒドロキシ- 1-ォキソイソインドリン  (1) 2-amino-3-hydroxy-1-oxoisoindoline
原料として 2-ァミノフタルイミドを用いて一般合成法 ξと同様の反応を行い、標題ィ匕 合物を得た。収率 9%。 1H-NMR(CDC1 ): δ 3.74(1H, d, J=8Hz), 4.18(2H, brs), The same reaction as in the general synthesis method II was carried out using 2-aminophthalimide as a starting material to obtain the title compound. 9% yield. 1H-NMR (CDC1): δ 3.74 (1H, d, J = 8Hz), 4.18 (2H, brs),
3  Three
5.78(1H, d, J=8Hz), 7.45- 7.55(1H, brs), 7.55- 7.65(2H, m), 7.74(1H, d, J=7.5Hz). 5.78 (1H, d, J = 8Hz), 7.45-7.55 (1H, brs), 7.55- 7.65 (2H, m), 7.74 (1H, d, J = 7.5Hz).
(2)化合物番号 360 (2) Compound No. 360
収率 42%。 'H-NMRCDMSO-d ): δ 2.20(3H, s), 5.95— 6.05(1H, m), 7.13(1H, t, Yield 42%. 'H-NMRCDMSO-d): δ 2.20 (3H, s), 5.95-6.05 (1H, m), 7.13 (1H, t,
6  6
J=8.5Hz), 7.20-7.30(lH, m), 7.41(2H, t, J=8.5Hz), 7.60-7.70(2H, m), 'P 'H\)WZ\ '(ζ服 =f 'P 'H\)ZV\\ '(zH9=f 'P 'Ηΐ)0Γ8 '(ζ服 =f 'P 'Ηΐ)ε9·8
Figure imgf000196_0001
J = 8.5Hz), 7.20-7.30 (lH, m), 7.41 (2H, t, J = 8.5Hz), 7.60-7.70 (2H, m), 'P' H \) WZ \ '( ζ服 = f' P 'H \) ZV \\' ( z H9 = f 'P' Ηΐ) 0Γ8 '( ζ服 = f' P 'Ηΐ) ε9.8
Figure imgf000196_0001
'(zHS"Z=f '； Ήΐ)εΓΖ '(s 'HS)82"2 9 :( OSW I) 顺— HT °%ZZ ¾T '(zHS "Z = f'; Ήΐ) εΓΖ '(s' HS) 82" 2 9 :( OSW I) 顺 — H T °% ZZ ¾T
9S各粱呦 -L9m 9S each 呦 -L9m
•(s 'HT)S2"8
Figure imgf000196_0002
'HT)W • (s' HT) S2 "8
Figure imgf000196_0002
'HT) W
'( 'HI)0S'9— 00·9 '(s 'H S8' '(s 'HS)S9"S 9 :( P-OS a)H N-HT °%S8 ? φ '(' HI) 0S'9— 009 '( s ' H S8''( s ' HS) S9 "S 9 :( P-OS a) H NH T °% S8? Φ
99S各粱呦 -99m •(s 'HT)Z2"8
Figure imgf000196_0003
99S each 呦 -99m • (s' HT) Z2 "8
Figure imgf000196_0003
P 'HT)6Z"Z '(ω 'H2)SZ"Z-S9"Z
Figure imgf000196_0004
4 lWZ)LY L P 'HT) 6Z "Z' (ω 'H2) SZ" Z-S9 "Z
Figure imgf000196_0004
4 l WZ) LY L
' 'HT)92" q 'Ηΐ)00·9— S6'S '(s 'H2) 8^ 9 :( P-OS a)H N-HT °%ZZ ¾T '' HT) 92 "q 'Ηΐ) 009—S6'S'(s' H2) 8 ^ 9 :( P-OS a) H NH T °% ZZ ¾T
S9S各粱呦 :S9Sp} S9S each beam: S9Sp}
。^拳 (696ΐ)Ρΐ9ε^ΐ 'ΐΖΊ。Λ 's ^sqy iBO!uisqつ：べ fi、ベ ^ ί^Ρ — ΐ— — S . ^ Fist (696ΐ) Ρΐ9ε ^ ΐ 'ΐΖΊ. Λ 's ^ sqy iBO! Uisq: be fi, be ^ ί ^ Ρ — ΐ— — S
•  •
' 'Ηΐ)ΐΖ·
Figure imgf000196_0005
'' Ηΐ) ΐΖ
Figure imgf000196_0005
'(zHZ=f '； Ήΐ)3ΓΖ '(s 'HS)08' '(s 'm)ZZ'Z 9 :( P-OS a)H N-HT °% 9 ¾T'( z HZ = f'; Ήΐ) 3ΓΖ '(s' HS) 08''( s ' m) ZZ'Z 9 :( P-OS a) H NH T °% 9 ¾T
9S各粱呦^ -f9m  9S each siang 呦 ^ -f9m
"(s-i 'Ηΐ)Ζ6 ΐ '(s 'Ηΐ)66·6 '(s Ήΐ)3Γ8 '(s 'Ηΐ)Μ)·8 '(zHZ=f 'P 'HDWL
Figure imgf000196_0006
"(si 'Ηΐ) Ζ6 ΐ' ( s ' Ηΐ) 666 '( s Ήΐ) 3Γ8' ( s ' Ηΐ) Μ) 8 '( z HZ = f' P 'HDWL
Figure imgf000196_0006
'P Ήΐ)3Ζ·9 '(zH8=f ' 'Ηΐ)09·9 '(S 'ΗΖ '9 9 :( P-OS a)H N-HT °% ¾1 'P Ήΐ) 3Ζ9' ( z H8 = f '' Ηΐ) 099 '( S ' ΗΖ '9 9 :( P-OS a) H NH T °% ¾1
ε9ε各粱呦 ： S9sp} ε9ε each beam: S9sp}
•(sjq 'Ηΐ)ΜΤεΐ '( q 'HI)0S ΐ • (sjq 'Ηΐ) ΜΤεΐ' (q 'HI) 0S ΐ
'(sjq Ήΐ)Ζ^ ΐ '(s Ήΐ)9Γ8 '(s 'Ηΐ)80·8 '(zHS'Z=f ·Ρ 'Ηΐ)ΐΟ·8 '(ω 'HS)09' - OS'Z '(sjq Ήΐ) Ζ ^ ΐ' ( s Ήΐ) 9Γ8 '( s ' Ηΐ) 808'(zHS'Z = f · Ρ 'Ηΐ) ΐΟ8' (ω 'HS) 09'-OS'Z
'(ZHS-Z=f '； 'H\)WL '(ω 'H2)00"Z-06"9 9 :( P-OS a)H N-HT °%ΐΐ ¾ί '( Z HS-Z = f';'H \) WL' (ω 'H2) 00 "Z-06" 9 9 :( P-OS a) H NH T °% ΐΐ ¾ί
各粱呦^ -Z9 [9810] •(s 'Ηΐ)00·εΐ '(s Ήΐ)32 ΐ '(ζΗ3·ΐ=Γ 'Ρ Ήΐ^ '(s 'Ηΐ)90·8 Each beam 呦 ^ -Z9 [9810] • ( s 'Ηΐ) 00 · εΐ' ( s Ήΐ) 32 ΐ '( ζ Η3ΐ ΐ = Γ' Ρ Ήΐ ^ '( s ' Ηΐ) 90 · 8
'(ΖΗΖ·Ϊ '8=f 'ΡΡ Ή2)86"Ζ '(ω 'HS)0Z"Z-0S"Z 9 :( OSWa) 顺— ΗΤ °%ΖΖ ¾ί '(ΖΗΖ · Ϊ' 8 = f 'ΡΡ Ή2) 86 "Ζ' (ω 'HS) 0Z" Z-0S "Z 9 :( OSWa) 顺 — Η Τ °% ΖΖ ¾ί
"(ω 'HS)00"8-06"Z '(ω 'H2)S8"Z-0Z"Z
Figure imgf000196_0007
S081760/S00Z OAV •(sjq 'Ηΐ)69·ΐΐ '(ZHS Όΐ=Γ 'PP 'Ηΐ)ΟΓΖ "(ω 'HS) 00" 8-06 "Z' (ω 'H2) S8" Z-0Z "Z
Figure imgf000196_0007
S081760 / S00Z OAV • (sjq 'Ηΐ) 69ΐΐ' ( Z HS Όΐ = Γ 'PP' Ηΐ) ΟΓΖ
'(ω 'H2)S9"Z-0S"Z '(ZHS 'Ζ=Γ 'Ρ; Ήΐ)ΟΥί '(sjq ΉΖ)Ζ^ 9 :( OSW I) 顺— Η ベ - べ fi,^ci、 ¾、— i— ΰ / — 9— — ε (ε)  '(ω' H2) S9 "Z-0S" Z '(ZHS' Ζ = Γ 'Ρ; Ήΐ) ΟΥί' (sjq ΉΖ) Ζ ^ 9 :( OSW I) 顺 — Η be-be fi, ^ ci, ¾, — i— ΰ / — 9— — ε (ε)
"(s-i 'Ηΐ) ·εΐ '(s 'Ηΐ) 6 '(ZHS '6=f 'PP "(si 'Ηΐ) · εΐ' ( s 'Ηΐ) 6' (ZHS '6 = f' PP
Ήΐ)26"Ζ '(ZHS '6=f 'PP Ήΐ)28"Ζ '(ZHS '6=f 'P 'HT)SZ"Z 9 :( P- OSWa) 顺- H ベ - べ fl,^ci、 ¾、— ΐ— cH — ε— ΰ / — 9 (Ζ) ベ,ェ cH-— ΰ / — <S— — (ΐ) Ήΐ) 26''Ζ '(ZHS' 6 = f 'PP Ήΐ) 28''Ζ' (ZHS '6 = f' P 'HT) SZ''Z 9 :( P- OSWa) 顺-H be-be fl, ^ ci, ¾, — ΐ— cH — ε— ΰ / — 9 (Ζ) ,, ェ cH-— ΰ / — <S— — (ΐ)
69ε各粱呦 :69ε 69ε each sword: 69ε
•(zH9=f 'Ρ 'H\)ZVZ\ '(zHW=f 'Ρ Ή\)Ζν\\ '(ΖΗ9=Γ 'Ρ 'Ηΐ)69·8 '(ζ服 =1" 'Ρ 'Ηΐ)ε9·8 '(ΖΗ9 '6=Γ 'PP 'Ηΐ) 8
Figure imgf000197_0001
• ( z H9 = f 'Ρ' H \) ZVZ \ '( z HW = f' Ρ Ή \) Ζν \\ '( Ζ Η9 = Γ' Ρ 'Ηΐ) 69 · 8' ( ζ服 = 1 ”' Ρ 'Ηΐ) ε9 8' ( Ζ Η9 '6 = Γ' PP 'Ηΐ) 8
Figure imgf000197_0001
Ήΐ) 2· '(zHS'8=f ' Ήΐ)εΓΖ '(s 'HZ)LZ'Z 9 :( OSWd) N— HT °% Z ¾T Ήΐ) 2 '(zHS'8 = f' Ήΐ) εΓΖ '(s' HZ) LZ'Z 9 :( OSWd) N-- H T °% Z ¾T
89S-^ i¾J^ (f) 89S- ^ i¾J ^ (f)
•(ω 'Ηΐ)9 ·ΐΐ- SS'II '(ΖΗ9 '6=f 'PP 'Ηΐ) ΐ·8 '(zH9=f 'P 'HI)IS'Z 'WZ • (ω 'Ηΐ) 9 ΐΐ SS SS'II' ( Ζ Η9 '6 = f' PP 'Ηΐ) ΐ8' ( z H9 = f 'P' HI) IS'Z 'WZ
'6=f 'PP Ήΐ)6ΓΖ '(ZHS '6=f 'P; 'HT)S0"Z '(sjq Ήζ)ΖΥ 9 :( P- OSW I) 顺- H  '6 = f' PP Ήΐ) 6ΓΖ '(ZHS' 6 = f 'P;' HT) S0 "Z '(sjq Ήζ) ΖΥ 9 :( P- OSW I) 顺-H
T °%68 ¾i
Figure imgf000197_0002
 T °% 68 ¾i
Figure imgf000197_0002
"(s-i 'HT)20"ST '(s Ήΐ)32·6 '(ΖΗ9 '6=f 'PP 'Ηΐ)0ε·8 "(si 'HT) 20"ST' ( s Ήΐ) 326 '( Ζ Η9' 6 = f 'PP' Ηΐ) 0ε8
'(ZHS Όΐ=Γ 'PP Ήΐ)8^"Ζ '(ZHS Όΐ=Γ 'Ρ; Ήΐ)0Υί 9 :( Ρ- OSWa) 顺- Η ベ - べ fl,^ci、 ¾、— ΐ— cH — ε— ΰ / — Ζ (Ζ) ベ,ェ cH-— ΰ / — —, ^ — (ΐ)  '(ZHS Όΐ = Γ' PP Ήΐ) 8 ^ "Ζ '(ZHS Όΐ = Γ' Ρ; Ήΐ) 0Υί 9 :( Ρ- OSWa) 顺-Η be-be fl, ^ ci, ¾, — ΐ— cH — Ε— ΰ / — Ζ (Ζ) Ba, e cH-— ΰ / — —, ^ — (ΐ)
89S各粱呦 ^ :89Sp } [Ζ8Ϊ0] •(zH9=f
Figure imgf000197_0003
961- S081760/S00Z OAV
Figure imgf000198_0001
89S each beam ^: 89Sp} [Ζ8Ϊ0] • (zH9 = f
Figure imgf000197_0003
961- S081760 / S00Z OAV
Figure imgf000198_0001
'HT)S2"6 '(ΖΗ6 Όΐ=Γ 'PP 'Ηΐ) ΐ·8 '(ΖΗΖ '6=f 'ΡΡ 'Ηΐ) Ζ 9 :(9ρ— OSW I) 顺— Η 'HT) S2 "6' ( Ζ Η6 Όΐ = Γ 'PP' Ηΐ) ΐ8 '( Ζ ΗΖ' 6 = f 'ΡΡ' Ηΐ) Ζ 9 :( 9 ρ— OSW I) 顺 — Η
ベ,ェ cH-— ΰ / s'' ,^ — (ΐ) C, cH-— — / s '', ^ — (ΐ)
•(zH8"9=f 'P Ήΐ)39·Π '(ζΗ^ΐ=Γ 'P 'ΗΙ)6¥Π '(z服 • ( z H8 "9 = f 'P Ήΐ) 39 · Π' ( ζ Η ^ ΐ = Γ 'P' ΗΙ) 6 ¥ Π '(z clothes
'P 'H2
Figure imgf000198_0002
'P' H2
Figure imgf000198_0002
'(ZHS'Z=1" '； Ήΐ)εΓ '(s Ήε)εε·ε '(s Ήε)οε 9 :(9p— oswa) N— Ht °%Z8 ? Φ '(ZHS'Z = 1 "'; Ήΐ) εΓ '(s Ήε) εε · ε' ( s Ήε) οε 9 :( 9 p— oswa) N— H t °% Z8? Φ
"(ω Ήΐ)0Ζ ΐ-33 ΐ
Figure imgf000198_0003
'P Ήΐ)86"Ζ 'P 'HT)TS"Z "(ω Ήΐ) 0Ζ ΐ-33 ΐ
Figure imgf000198_0003
'P Ήΐ) 86 "Ζ' P 'HT) TS" Z
P 'Ηΐ) Ζ
Figure imgf000198_0004
9 :( P- OSW I) 顺- H P 'Ηΐ) Ζ
Figure imgf000198_0004
9 :( P- OSW I) 顺-H
T °%68 ¾i T °% 68 ¾i
Figure imgf000198_0005
Figure imgf000198_0005
•(sjq 'm)0VZl '(s 'Ηΐ)68·8
Figure imgf000198_0006
'P 'Ηΐ)εΐ·8
Figure imgf000198_0007
'； Ήΐ)ΖΥί '(s 'HS)SS"2 9 :( P- OSW I) 顺- H • (sjq 'm) 0VZl' ( s ' Ηΐ) 68
Figure imgf000198_0006
'P' Ηΐ) εΐ8
Figure imgf000198_0007
'; Ήΐ) ΖΥί' ( s ' HS) SS "2 9 :( P- OSW I) 顺-H
ベ,ェ CH ^ — 'ε— — (ΐ)
Figure imgf000198_0008
Ba, e CH ^ — 'ε— — (ΐ)
Figure imgf000198_0008
'P 'HWU '(zHS'9=f 'P Ήΐ)3Ζ·8 '(ζ服 =f 'P 'HI)S9'8 '(zH8=f 'P 'H2)20"8
Figure imgf000198_0009
'P' HWU '(zHS'9 = f' P Ήΐ) 3Ζ · 8 '(ζ clothes = f' P 'HI) S9'8 ' (z H8 = f 'P' H2) 20 "8
Figure imgf000198_0009
' 'HZ)\VL '(zH8=f ' Ήΐ)εΓΖ '(s 'HS)82"2 9 :( OSWa) 顺— HT °% 9 ¾T '' HZ) \ VL '(zH8 = f' Ήΐ) εΓΖ '(s' HS) 82 "2 9 :( OSWa) 顺 — H T °% 9 ¾T
69S-^ i¾J^ (f)
Figure imgf000198_0010
961· S081760/S00Z OAV ベ,ェ cH-— ^ —' s— — (ΐ)
Figure imgf000199_0001
69S- ^ i¾J ^ (f)
Figure imgf000198_0010
961S081760 / S00Z OAV Bae, cH-— ^ — 's— — (ΐ)
Figure imgf000199_0001
'P 'H\)W\\ '(z服 =f 'P 'Ηΐ)ε9·8 '(ζ服 =f 'P 'HT)29"8 '(zH8=f 'P Ήΐ)0Γ8
Figure imgf000199_0002
L (zHS'8=f ' Ήΐ)εΓΖ '(s 'HZ)WZ '(s 'HS)82"2 9 :( OSW I) 顺— HT °%6 ¾T
Figure imgf000199_0003
'P' H \) W \\ '( z clothes = f' P 'Ηΐ) ε9 8' ( ζ clothes = f 'P' HT) 29 "8 '( z H8 = f' P Ήΐ) 0Γ8
Figure imgf000199_0002
L (zHS'8 = f 'Ήΐ) εΓΖ'(s' HZ) WZ '( s ' HS) 82 "2 9 :( OSW I) 顺 — H T °% 6 ¾T
Figure imgf000199_0003
•(sj Ήΐ)εε·π '(zHe-8=f 'p 'ΗΪ)86· 'H\)LVL 'Wi=i 'p 'HWL(Sj Ήΐ) εεπ '( z He-8 = f' p 'ΗΪ) 86H') LVL 'Wi = i' p 'HWL
'(ZHS'I 'S'8=f 'PP 'Ηΐ)66·9 '(sjq 'UZ)Z£'f '(s 'H£)S£'Z 9 :(9p— OSW I) N— H '(ZHS'I'S'8 = f 'PP' Ηΐ) 669 '(sjq' UZ) Z £ 'f' ( s 'H £) S £' Z 9 :( 9 p— OSW I) N — H
T °%96 ¾i T °% 96 ¾i
Figure imgf000199_0004
Figure imgf000199_0004
•(sjq 'HI)S8 ΐ '(s Ήΐ)2Γ6 '(zH8=f 'P 'Ηΐ)εΐ·8(Sjq 'HI) S8 ΐ' ( s Ήΐ) 2Γ6 '( z H8 = f' P 'Ηΐ) εΐ8
'(ζΗΐ=Γ 'p 'HDSVL '(ζΗΐ '8=f 'pp Ήΐ · '(s Ή νζ 9 :(9p— oswa) N— H '( ζ Ηΐ = Γ' p 'HDSVL' ( ζ Ηΐ '8 = f' pp Ήΐ · '(s Ή νζ 9 :( 9 p— oswa) N— H
ベ,ェ cH-— ^ —^—,^ — (ΐ) Ba, e cH-— ^ — ^ —, ^ — (ΐ)
•(zHS"9=f 'P• (zHS "9 = f 'P
'HI)SS ΐ
Figure imgf000199_0005
'P 'Ηΐ)6ε·ΐΐ "P 'HT)S9"8 (ZH6 'S"6=f 'PP 'Ηΐ)90·8 '(zH8=f 'P 'H2)00"8 '(ZHS'9 'Π=Γ 'PP Ήΐ)29"Ζ '(zH8=f'HI) SS ΐ
Figure imgf000199_0005
'P' Ηΐ) 6ε · ΐΐ "P 'HT) S9" 8 (ZH6' S "6 = f 'PP' Ηΐ) 90 · 8 '(zH8 = f' P 'H2) 00"8'(ZHS'9'Π = Γ' PP Ήΐ) 29 "Ζ '(zH8 = f
' Ήζ)οη '(zH8=f ' Ήΐ)εΓ 'm z'z 9 :(9p— oswa) 顺— Ht °% ε ¾T 'Ήζ) οη' ( z H8 = f 'Ήΐ) εΓ' m z'z 9 :( 9 p— oswa) 顺 — H t °% ε ¾T
"(ω 'H2)S6"Z-08"Z"(ω 'H2) S6" Z-08 "Z
'(saq 'HT)ZS"Z '(ω 'HT)0S"Z-eS"Z '(sjq 'H2)0S"S 9 :(9p—〇SW I) 顺— H ベ - べ fi,^ci、 ¾、- 卜 ΰ / 、- z'9- - ε (ε)
Figure imgf000199_0006
Ζ6Ι- S081760/S00Z OAV (2) 6-メチル -3--トロ- 1,4-ジヒドロキノリン- 4-オン '(saq' HT) ZS "Z '(ω' HT) 0S" Z-eS "Z '(sjq' H2) 0S" S 9 :( 9 p—〇SW I) 顺 — H be-be fi, ^ ci, ¾,-ΰ /, -z'9--ε (ε)
Figure imgf000199_0006
Ζ6Ι- S081760 / S00Z OAV (2) 6-methyl-3--toro-1,4-dihydroquinolin-4-one
一般合成法 Vと同様の方法により標題化合物を得た。収率 79%。 1 The title compound was obtained in the same manner as in General Synthesis Method V. 79% yield. 1
H-NMR(DMSO-d ): δ 2.45(3H, s), 7.61— 7.65(2H, m), 8.05(1H, d, J=lHz), 9.15(1H, H-NMR (DMSO-d): δ 2.45 (3H, s), 7.61-7.65 (2H, m), 8.05 (1H, d, J = 1 Hz), 9.15 (1H,
6  6
s), 13.0K1H, brs).  s), 13.0K1H, brs).
(3) 3-ァミノ- 6-メチル -1,4-ジヒドロキノリン- 4-オン  (3) 3-amino-6-methyl-1,4-dihydroquinolin-4-one
一般合成法 tと同様の方法により標題ィ匕合物を得た。収率 61%。 1 The title compound was obtained in the same manner as in the general synthesis method t . Yield 61%. 1
H-NMR(DMSO-d ): δ 2.38(3H, s), 4.42(2H, brs), 7.30(1H, d, J=8.5Hz), 7.37(1H, H-NMR (DMSO-d): δ 2.38 (3H, s), 4.42 (2H, brs), 7.30 (1H, d, J = 8.5Hz), 7.37 (1H,
6  6
d, J=8.5Hz), 7.48-7.52(lH, m), 7.88(1H, s), 11.37(1H, brs). d, J = 8.5Hz), 7.48-7.52 (lH, m), 7.88 (1H, s), 11.37 (1H, brs).
(4)化合物番号 373  (4) Compound No. 373
収率 74%。 'H-NMRCDMSO-d ): δ 2.28(3H, s), 2.45(3H, s), 7.13(1H, t, J=7.5Hz), Yield 74%. 'H-NMRCDMSO-d): δ 2.28 (3H, s), 2.45 (3H, s), 7.13 (1H, t, J = 7.5Hz),
6  6
7.40(2H, t, J=7.5Hz), 7.50— 7.60(2H, m), 7.95— 8.10(3H, m), 8.60— 8.75(2H, m), 11.45(1H, d, J=14Hz), 12.34(1H, d, J=6Hz).  7.40 (2H, t, J = 7.5Hz), 7.50-7.60 (2H, m), 7.95-8.10 (3H, m), 8.60-8.75 (2H, m), 11.45 (1H, d, J = 14Hz), 12.34 (1H, d, J = 6Hz).
例 374:化合物番号 374 Example 374: Compound number 374
収率 44%。 'H-NMRCDMSO-d ): δ 2.17(3Η, s), 3.10(2Η, dd, J=16, 6.5Hz), Yield 44%. 'H-NMRCDMSO-d): δ 2.17 (3Η, s), 3.10 (2Η, dd, J = 16, 6.5Hz),
6  6
3.30(2Η, dd, J=16, 6.5Hz), 4.42— 4.80(1Η, m), 7.34(1Η, t, J=8Hz), 7.15-7.23(2Η, m), 7.25-7.30(2Η, m), 7.34(2Η, t, J=8Hz), 7.95(2H, d, J=8Hz), 8.17(1H, d,  3.30 (2Η, dd, J = 16, 6.5Hz), 4.42― 4.80 (1Η, m), 7.34 (1Η, t, J = 8Hz), 7.15-7.23 (2Η, m), 7.25-7.30 (2Η, m ), 7.34 (2Η, t, J = 8Hz), 7.95 (2H, d, J = 8Hz), 8.17 (1H, d,
J=14Hz), 9.70-9.85(lH, m). J = 14Hz), 9.70-9.85 (lH, m).
例 375:化合物番号 375 Example 375: Compound number 375
収率 56%。 ^-NMRCDMSO-d ): δ 7.29(1Η, t, J=7.5Hz), 7.50(2Η, t, J=7.5Hz), Yield 56%. ^ -NMRCDMSO-d): δ 7.29 (1Η, t, J = 7.5Hz), 7.50 (2Η, t, J = 7.5Hz),
6  6
7.90-8.10(7H, m), 8.58(1H, s).  7.90-8.10 (7H, m), 8.58 (1H, s).
例 376:化合物番号 376 Example 376: Compound number 376
収率 85%。 ^-NMRCDMSO-d ): δ 1.21(3Η, t, J=7.5Hz), 2.56(2Η, q, J=7.5Hz), Yield 85%. ^ -NMRCDMSO-d): δ 1.21 (3Η, t, J = 7.5Hz), 2.56 (2Η, q, J = 7.5Hz),
6  6
7.16(1H, t, J=7.5Hz), 7.42(2H, t, J=7.5Hz), 7.95— 8.05(7H, m), 8.25(1H, s).  7.16 (1H, t, J = 7.5Hz), 7.42 (2H, t, J = 7.5Hz), 7.95― 8.05 (7H, m), 8.25 (1H, s).
例 377:化合物番号 377 Example 377: Compound number 377
(1) 2-ァミノ- 1,3-ジォキソ -1,2,3,4-テトラヒドロイソキノリン  (1) 2-amino-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline
ホモフタル酸無水物 (lg, 6.168mmol)、抱水ヒドラジン (1.5ml, 30.8mmol)及びェタノ ール (5ml)の混合物を 1.5時間加熱還流した。反応混合物を室温まで冷却後、減圧濃 縮した。得られた残渣に水を加え、酢酸ェチルで抽出した。酢酸ェチル層を飽和食 塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去して得られた残渣を ジイソプロピルエーテルで洗净して、標題ィ匕合物の淡緑色結晶 (0.3 lmg, 29%)を得た A mixture of homophthalic anhydride (lg, 6.168 mmol), hydrazine hydrate (1.5 ml, 30.8 mmol) and ethanol (5 ml) was heated under reflux for 1.5 hours. After the reaction mixture was cooled to room temperature, it was concentrated under reduced pressure. Water was added to the obtained residue and extracted with ethyl acetate. Ethyl acetate layer saturated diet Washed with brine and dried over anhydrous sodium sulfate. The residue obtained by evaporating the solvent under reduced pressure was washed with diisopropyl ether to obtain pale green crystals (0.3 lmg, 29%) of the title compound.
H-NMR(DMSO-d ): δ 4.21(2H, s), 5.53(2H, brs), 7.39(1H, d, J=7.5Hz), 7.47(1H H-NMR (DMSO-d): δ 4.21 (2H, s), 5.53 (2H, brs), 7.39 (1H, d, J = 7.5Hz), 7.47 (1H
6  6
t, J=7.5Hz), 7.65(1H, t, J=7.5Hz), 8.03(1H, d, J=7.5Hz). t, J = 7.5Hz), 7.65 (1H, t, J = 7.5Hz), 8.03 (1H, d, J = 7.5Hz).
(2)化合物番号 377  (2) Compound No. 377
収率 29%。 'H-NMRCDMSO-d ): δ 2.15(3H, s), 4.39(2H, s), 7.14(1H, t, J=7.5Hz), Yield 29%. 'H-NMRCDMSO-d): δ 2.15 (3H, s), 4.39 (2H, s), 7.14 (1H, t, J = 7.5Hz),
6  6
7.41(2H, t, J=7.5Hz), 7.49(1H, d, J=8Hz), 7.56(1H, t, J=8Hz), 7.76(1H, t, J=8Hz), 7.95(2H, d, J=7.5Hz), 8.03(1H, s), 8.10(1H, d, J=8Hz).  7.41 (2H, t, J = 7.5Hz), 7.49 (1H, d, J = 8Hz), 7.56 (1H, t, J = 8Hz), 7.76 (1H, t, J = 8Hz), 7.95 (2H, d , J = 7.5Hz), 8.03 (1H, s), 8.10 (1H, d, J = 8Hz).
例 378:化合物番号 378 Example 378: Compound number 378
(1) 2'-ァミノ- 4'-トリフルォロメチル- 2-二トロアセトフエノン  (1) 2'-amino-4'-trifluoromethyl-2-nitroacetophenone
一般合成法 κと同様の方法により標題ィ匕合物を得た。  The title compound was obtained in the same manner as in the general synthesis method κ.
(2) 3-二トロ- 7-トリフルォロメチル- 1,4-ジヒドロキノリン- 4-オン  (2) 3-Nitro-7-trifluoromethyl-1,4-dihydroquinolin-4-one
一般合成法 Vと同様の方法により標題化合物を得た。収率 85%。 1 The title compound was obtained in the same manner as in General Synthesis Method V. Yield 85%. 1
H-NMR(DMSO-d ): δ 7.82(1H, d, J=8.5Hz), 8.08(1H, s), 8.45(1H, d, J=8.5Hz), H-NMR (DMSO-d): δ 7.82 (1H, d, J = 8.5Hz), 8.08 (1H, s), 8.45 (1H, d, J = 8.5Hz),
6  6
9.35(1H, s), 13.16(1H, brs).  9.35 (1H, s), 13.16 (1H, brs).
(3) 3-ァミノ- 7-トリフルォロメチル- 1,4-ジヒドロキノリン- 4-オン  (3) 3-amino-7-trifluoromethyl-1,4-dihydroquinolin-4-one
一般合成法 tと同様の方法により標題化合物を得た。収率 60%。 1 The title compound was obtained in the same manner as in General Synthesis Method t. Yield 60%. 1
H-NMR(DMSO-d ): δ 4.67(2H, brs), 7.39(1H, d, J=9Hz), 7.86(1H, s), 7.99(1H, s), H-NMR (DMSO-d): δ 4.67 (2H, brs), 7.39 (1H, d, J = 9 Hz), 7.86 (1H, s), 7.99 (1H, s),
6  6
8.26(1H, d, J=9Hz), 11.92(1H, brs).  8.26 (1H, d, J = 9Hz), 11.92 (1H, brs).
(4)化合物番号 378  (4) Compound No. 378
収率 71%。 'H-NMRCDMSO-d ): δ 2.29(3H, s), 7.14(1H, t, J=7.5Hz), 7.41(2H, t, Yield 71%. 'H-NMRCDMSO-d): δ 2.29 (3H, s), 7.14 (1H, t, J = 7.5Hz), 7.41 (2H, t,
6  6
J=7.5Hz), 7.67(1H, d, J=9Hz), 7.99(1H, s), 8.01(2H, d, J=7.5Hz), 8.42(1H, d, J=9Hz), 8.67(1H, d, J=13.5Hz), 8.83(1H, d, J=6Hz), 11.46(1H, d, J=13.5Hz), 12.69(1H, d, J=6Hz).  J = 7.5Hz), 7.67 (1H, d, J = 9Hz), 7.99 (1H, s), 8.01 (2H, d, J = 7.5Hz), 8.42 (1H, d, J = 9Hz), 8.67 (1H , d, J = 13.5Hz), 8.83 (1H, d, J = 6Hz), 11.46 (1H, d, J = 13.5Hz), 12.69 (1H, d, J = 6Hz).
例 379:化合物番号 379 Example 379: Compound number 379
収率 53%。 ^-NMRCDMSO-d ): δ 1.20(3Η, t, J=7.5Hz), 2.52(2Η, q, J=7.5Hz), Yield 53%. ^ -NMRCDMSO-d): δ 1.20 (3Η, t, J = 7.5Hz), 2.52 (2Η, q, J = 7.5Hz),
6  6
4.38(2H, s), 7.14(1H, t, J=8Hz), 7.41(2H, t, J=8Hz), 7.48(1H, d, J=7.5Hz), 7.55(1H, t, J=7.5Hz), 7.76(1H, t, J=7.5Hz), 7.99(2H, d, J=8Hz), 8.07(1H, s), 8.10(1H, d, J=7.5Hz). 4.38 (2H, s), 7.14 (1H, t, J = 8Hz), 7.41 (2H, t, J = 8Hz), 7.48 (1H, d, J = 7.5Hz), 7.55 (1H, t, J = 7.5Hz), 7.76 (1H, t, J = 7.5Hz), 7.99 (2H, d, J = 8Hz), 8.07 (1H, s), 8.10 (1H, d, J = 7.5Hz).
例 380:化合物番号 380 Example 380: Compound number 380
収率 43%。 ^-NMRCDMSO-d ): δ 1.22(3Η, t, J=7Hz), 2.61(2Η, q, J=7Hz), Yield 43%. ^ -NMRCDMSO-d): δ 1.22 (3Η, t, J = 7Hz), 2.61 (2Η, q, J = 7Hz),
6  6
4.22(1H, brs), 4.80(2H, s), 7.16(1H, t, J=7Hz), 7.42(2H, t, J=7Hz), 7.57(1H, t, J=7Hz), 7.67(1H, t, J=7Hz), 7.70(1H, d, J=7Hz), 7.80(1H, d, J=7Hz), 7.96(2H, d, J=7Hz), 8.23(1H, s).  4.22 (1H, brs), 4.80 (2H, s), 7.16 (1H, t, J = 7Hz), 7.42 (2H, t, J = 7Hz), 7.57 (1H, t, J = 7Hz), 7.67 (1H , t, J = 7Hz), 7.70 (1H, d, J = 7Hz), 7.80 (1H, d, J = 7Hz), 7.96 (2H, d, J = 7Hz), 8.23 (1H, s).
例 381:化合物番号 381 Example 381: Compound number 381
収率 63%。 'H-NMRCDMSO-d ): δ 2.21(3Η, s), 4.80(3Η, s), 7.26(2Η, t, J=8.5Hz), 63% yield. 'H-NMRCDMSO-d): δ 2.21 (3Η, s), 4.80 (3Η, s), 7.26 (2Η, t, J = 8.5Hz),
6  6
7.57(1Η, t, J=7Hz), 7.65-7.75(2H, m), 7.80(1H, d, J=7Hz), 7.85— 8.10(2H, m), 8.21(1H, s).  7.57 (1Η, t, J = 7Hz), 7.65-7.75 (2H, m), 7.80 (1H, d, J = 7Hz), 7.85― 8.10 (2H, m), 8.21 (1H, s).
例 382:化合物番号 382 Example 382: Compound number 382
収率 28%。 'H-NMRCDMSO-d ): δ 2.18(3Η, s), 2.21(3Η, s), 3.51(1Η, brs), Yield 28%. 'H-NMRCDMSO-d): δ 2.18 (3Η, s), 2.21 (3Η, s), 3.51 (1Η, brs),
6  6
4.85(2Η, s), 7.05-7.30(4Η, m), 7.45— 7.58(1Η, m), 7.59-7.70(2Η, m), 7.70— 7.80(1Η, m), 7.97(1Η, s).  4.85 (2Η, s), 7.05-7.30 (4Η, m), 7.45-7.58 (1Η, m), 7.59-7.70 (2Η, m), 7.70-7.80 (1Η, m), 7.97 (1Η, s).
例 383:化合物番号 383 Example 383: Compound number 383
収率 16%。 'H-NMRCDMSO-d ): δ 3.47(1H, brs), 6.34(1H, d, J=8.5Hz), 6.95(1H, d Yield 16%. 'H-NMRCDMSO-d): δ 3.47 (1H, brs), 6.34 (1H, d, J = 8.5Hz), 6.95 (1H, d
6  6
J=8.5Hz), 7.16(1H, t, J=7.5Hz), 7.40(2H, t, J=7.5Hz), 7.55- 7.80(4H, m), 8.07(2H, d, J=7.5Hz), 8.37(1H, s).  J = 8.5Hz), 7.16 (1H, t, J = 7.5Hz), 7.40 (2H, t, J = 7.5Hz), 7.55- 7.80 (4H, m), 8.07 (2H, d, J = 7.5Hz) , 8.37 (1H, s).
例 384:化合物番号 384 Example 384: Compound number 384
収率 81%。 ^-NMRCDMSO-d ): δ 1.21(3Η, t, J=7.5Hz), 2.59(2Η, q, J=7.5Hz), Yield 81%. ^ -NMRCDMSO-d): δ 1.21 (3Η, t, J = 7.5Hz), 2.59 (2Η, q, J = 7.5Hz),
6  6
5.99(1H, d, J=8Hz), 7.14(1H, t, J=7.5Hz), 7.24(1H, d, J=8Hz), 7.41(2H, t,  5.99 (1H, d, J = 8Hz), 7.14 (1H, t, J = 7.5Hz), 7.24 (1H, d, J = 8Hz), 7.41 (2H, t,
J=7.5Hz), 7.63(1H, t, J=7.5Hz), 7.67(1H, d, J=7.5Hz), 7.75(1H, d, J=7.5Hz), 7.79(1H, t, J=7.5Hz), 7.98(2H, d, J=7.5Hz), 8.01(1H, s). J = 7.5Hz), 7.63 (1H, t, J = 7.5Hz), 7.67 (1H, d, J = 7.5Hz), 7.75 (1H, d, J = 7.5Hz), 7.79 (1H, t, J = 7.5Hz), 7.98 (2H, d, J = 7.5Hz), 8.01 (1H, s).
例 385:化合物番号 385 Example 385: Compound number 385
収率 85%。 ^-NMRCDMSO-d ): δ 2.19(3Η, s), 5.99(1Η, d, J=7Hz), 7.20- 7.35(3Η, Yield 85%. ^ -NMRCDMSO-d): δ 2.19 (3Η, s), 5.99 (1Η, d, J = 7Hz), 7.20- 7.35 (3Η,
6  6
m), 7.63(1Η, t, J=7.5Hz), 7.67(1H, d, J=7.5Hz), 7.75(1H, d, J=7.5Hz), 7.79(1H, t, J=7.5Hz), 7.95-8.05(3H, m).
Figure imgf000203_0001
'； 'ΗΖ)6 'Ζ m), 7.63 (1Η, t, J = 7.5Hz), 7.67 (1H, d, J = 7.5Hz), 7.75 (1H, d, J = 7.5Hz), 7.79 (1H, t, J = 7.5Hz) , 7.95-8.05 (3H, m).
Figure imgf000203_0001
';' ΗΖ) 6 'Ζ
'(zHS"Z=f ΉΖ) £τ '(zHS"Z=f '^m )88·ΐ 9 :(9p—〇SW I) 顺— HT ¾T '(zHS "Z = f ΉΖ) £ τ'(zHS" Z = f '^ m) 88 · ΐ 9 :( 9 p—〇SW I) 顺 — H T ¾T
68ε各粱呦 -esm 68ε each siang 呦 -esm
•(s Ήΐ)62"8 '(zH8=f 'P 'HZ)£VS '(ω 'H^)SZ"Z-OS"Z
Figure imgf000203_0002
' Ήΐ)Ζ6"9 '(sjq 'Ηΐ)8ε·9 'H2)8S"2 • (s Ήΐ) 62 "8 '(zH8 = f' P 'HZ) £ VS' (ω 'H ^) SZ" Z-OS "Z
Figure imgf000203_0002
'Ήΐ) Ζ6 "9' (sjq 'Ηΐ) 8ε9' H2) 8S" 2
'(zHS"Z=f 'Η εε '(zHS"Z=f ';u!nb )88·ΐ 9 :(9p— OSWa) 顺— HT °%SS ¾ί '(zHS "Z = f' Η εε '(zHS" Z = f'; u! nb) 88 · ΐ 9 :( 9 p— OSWa) 顺 — H T °% SS ¾ί
88ε各粱呦 -ssm 88ε each siang 呦 -ssm
•(s 'Ηΐ)00·6 '(s 'Ηΐ)ΐΐ·8
Figure imgf000203_0003
'P 'Ηΐ)Ζ9·
Figure imgf000203_0004
• ( s ' Ηΐ) 00 · 6 '( s ' Ηΐ) ΐΐ · 8
Figure imgf000203_0003
'P' Ηΐ) Ζ9
Figure imgf000203_0004
'(zHZ=f '； 'H2)S2"2 '(zHZ=f '^m 'H2)S6"T 9 :( OSWd) N— HT °%6S ¾T '(zHZ = f';'H2) S2 "2' (zHZ = f '^ m' H2) S6" T 9 :( OSWd) N— H T °% 6S ¾T
8S各粱呦^ -LS Κ6Ϊ0] •(zHS'9=f 'P 'H\)ZVZ\
Figure imgf000203_0005
8S each beam 呦 ^ -LS Κ6Ϊ0] • (zHS'9 = f 'P' H \) ZVZ \
Figure imgf000203_0005
'P 'H2)20"8
Figure imgf000203_0006
'(ω 'H2)SS"Z-S2"Z 'P' H2) 20 "8
Figure imgf000203_0006
'(ω' H2) SS "Z-S2" Z
'(ZHS'Z=1" '； Ήΐ)εΓ '(s Ήε) ο· '(s 'HS)6S 9 :(9p— oswa) N— ΗΤ °%ΐΖ ¾T '(ZHS'Z = 1 "'; Ήΐ) εΓ '(s Ήε) ο ·' ( s ' HS) 6S 9 :( 9 p— oswa) N— Η Τ °% ΐΖ ¾T
'P 'Ηΐ)εθ·ΐΐ '(ZHS'I
Figure imgf000203_0007
'P' Ηΐ) εθΐΐ ΐΐ '(ZHS'I
Figure imgf000203_0007
'(ZHS'I '8=f 'PP 'HT)S0"Z '(saq '^W '(S 'HS)Z6"S 9 :(9p— OSW I) 顺— H
Figure imgf000203_0008
(ε) '(ZHS'I' 8 = f 'PP' HT) S0 "Z '(saq' ^ W '( S ' HS) Z6" S 9 :( 9 p— OSW I) 顺 — H
Figure imgf000203_0008
(ε)
•(s_iq Ήΐ)63·2ΐ '(s  • (s_iq Ήΐ) 632ΐ '(s
Ηΐ)6Γ8 'Ρ Ήΐ)08"Ζ '(ω 'H SS'Z— SS' '(s Ήε) 0· 9 :( OSWa) 顺— Η
Figure imgf000203_0009
） ベ,ェ CH-— ^^ — 'ε— — ) Ηΐ) 6Γ8 'Ρ Ήΐ) 08 "Ζ' (ω 'H SS'Z— SS''(s Ήε) 0 · 9 :( OSWa) 顺 — Η
Figure imgf000203_0009
) Eh, e CH-— ^^ — 'ε— —)
98ε各粱呦 m
Figure imgf000203_0010
1-03 S081760/S00Z OAV ' Ή ε6·ε '(zHs-9=f ' Ήζ)οζτ '(s 'm)svz 9 :(9p— oswa) 顺— HT ¾T 98ε each 呦
Figure imgf000203_0010
1-03 S081760 / S00Z OAV 'Ή ε6 · ε' ( z Hs-9 = f 'Ήζ) οζτ' ( s ' m) svz 9 :( 9 p— oswa) 顺 — H T ¾T
ε6ε各粱呦 -zem 'Ηΐ)ΐΖ·Ζ ε6ε each beam -zem 'Ηΐ) ΐΖ
Figure imgf000204_0001
'Ηΐ)εε· '(s )98· 9 :(9p— OSW I) 顺— HT °%SZ ¾T
Figure imgf000204_0001
'Ηΐ) εε ·' (s) 98 · 9 :( 9 p— OSW I) 顺 — H T °% SZ ¾T
各粱呦^ -Z6 i 610]
Figure imgf000204_0002
Each sliver 呦 ^ -Z6 i 610]
Figure imgf000204_0002
'P 'HWU '(zHS'9=f 'P 'HI) 8 '(ζ服 =f 'Ρ 'Ηΐ)99·8 'WZ=i 'P 'Ηΐ) ΐ·8
Figure imgf000204_0003
'P' HWU '(zHS'9 = f' P 'HI) 8' (ζ clothes = f 'Ρ' Ηΐ) 99 · 8 'WZ = i' P 'Ηΐ) ΐ · 8
Figure imgf000204_0003
' 'HZ)WL '(ZHS'Z=1" '； Ήΐ)εΓ 'u z'z 9 :(9p— oswa) N— Ht °% 9 ¾T '' HZ) WL '(ZHS'Z = 1 "'; Ήΐ) εΓ 'u z'z 9 :( 9 p— oswa) N— H t °% 9 ¾T
ΐ6ε各粱呦 (f) ΐ6ε each beam 呦 (f)
Figure imgf000204_0004
Figure imgf000204_0004
'p Ήΐ)εο·8 '(s Ήΐ)ε9" '(ω 'H2)es" -oe" Ή 'H ·ε 9 :(9p— oswa) N— H
Figure imgf000204_0005
(ε) 'p Ήΐ) εο · 8' (s Ήΐ) ε9 "'(ω' H2) es" -oe "Ή 'H · ε 9 :( 9 p— oswa) N— H
Figure imgf000204_0005
(ε)
"(s-i 'Ηΐ)9ΐ·εΐ '(s Ήΐ)32·6 '(ZHS =f 'Ρ Ήΐ)8Γ8 '(ZHS '6=f 'PP 'HT)S8"Z '(zH6=f 'P 'Ηΐ)9ΓΖ 9 :(9p— OSWd) N— H "(si 'Ηΐ) 9ΐεΐ' ( s Ήΐ) 326 '(ZHS = f' Ρ Ήΐ) 8Γ8 '(ZHS' 6 = f 'PP' HT) S8" Z '(zH6 = f' P ' Ηΐ) 9ΓΖ 9 :( 9 p— OSWd) N— H
ベ,ェ cH-— crn^— <S— — (ΐ) C, cH-— crn ^ — <S— — (ΐ)
ΐ6ε各粱呦  呦 6ε each 呦
•(zHS'9=f 'P Ήΐ)ΐ^2ΐ '{ =[ 'P 'H\)W\\ '(zHS-9=f 'P 'Ηΐ)99·
Figure imgf000204_0006
'P 'H2)20"8 '(ω 'H2)S9"Z-eS"Z '(ω 'HS)0S"Z-0S"Z
Figure imgf000204_0007
(ZHS'9 = f 'P Ηΐ) ΐ ^ 2ΐ' {= ['P' H \) W \\ '( z HS-9 = f' P 'Ηΐ) 99
Figure imgf000204_0006
'P' H2) 20 "8 '(ω' H2) S9" Z-eS "Z '(ω' HS) 0S" Z-0S "Z
Figure imgf000204_0007
06ε各粱呦^ m 06ε each 呦 ^ m
•(saq 'Ηΐ)60 ΐ
Figure imgf000204_0008
'P
Figure imgf000204_0009
Figure imgf000204_0010
303 S081760/S00Z OAV
Figure imgf000205_0001
'P Ήΐ)29"Ζ• (saq 'Ηΐ) 60 ΐ
Figure imgf000204_0008
'P
Figure imgf000204_0009
Figure imgf000204_0010
303 S081760 / S00Z OAV
Figure imgf000205_0001
'P Ήΐ) 29 "Ζ
ZVL 'P 'HT)0Z"9
Figure imgf000205_0002
'HS)02"T 9 :( P-OS a)H N-HT °%S ¾T ZVL 'P' HT) 0Z "9
Figure imgf000205_0002
'HS) 02 "T 9 :( P-OS a) H NH T °% S ¾T
86ε各粱呦 -sem 86ε each siang 呦 -sem
。^拳餱 980S9— SSgH |;
Figure imgf000205_0003
. ^ Ken 餱 980S9— SSgH |;
Figure imgf000205_0003
•(zH =f • (zH = f
'P 'HT)Z2"8 '(s 'HT)92"8
Figure imgf000205_0004
'P 'P' HT) Z2 "8 '(s' HT) 92" 8
Figure imgf000205_0004
'P
'HT)9Z"Z
Figure imgf000205_0005
'HT) 9Z "Z
Figure imgf000205_0005
' 'Ηΐ) ΐ·Ζ '(zHS'Z=f 'P 'Ηΐ)0Γ9 '(s Ήε)8Γ2 9 :( P- OS 顺- HT °% ¾T '' Ηΐ) ΐ Ζ '(zHS'Z = f' P 'Ηΐ) 0Γ9' ( s Ήε) 8Γ2 9 :( P- OS 顺-H T °% ¾T
6S各粱呦^ -L6m [36 TO]  6S each 呦 ^ -L6m [36 TO]
•(s 'Ηΐ)90·8 '(ω 'HS)00"8-S6"Z
Figure imgf000205_0006
• (s' Ηΐ) 90 · 8 '(ω' HS) 00 "8-S6" Z
Figure imgf000205_0006
' Ήΐ)εΓΖ
Figure imgf000205_0007
'ΡΡ 'HT)0S"S 'Ήΐ) εΓΖ
Figure imgf000205_0007
'ΡΡ' HT) 0S "S
'(ZHS '3·9ΐ=Γ 'ΡΡ Ήΐ)2Γε 'm)evz 9 :( p-os a)H N-HT °%6ε ? Φ '( Z HS' 3.9ΐ = Γ 'ΡΡ Ήΐ) 2Γε' m) evz 9 :( p-os a) H NH T °% 6ε? Φ
96S各粱呦 -96m •(s Ήΐ)02"8 '(ω 'HS)S0"8-S6"Z '(zHS" =f 'HT)8S"Z  96S each 呦 -96m • (s Ήΐ) 02 "8 '(ω'HS) S0" 8-S6 "Z' (zHS" = f'HT) 8S "Z
'(in
Figure imgf000205_0008
' 'H2)2"S '(in
Figure imgf000205_0008
'' H2) 2 "S
'(zHS"Z=f 'b 'H2)8S"2 '(zHS" =f ΉΖ)ΖΖ'\ 9 :( P-OS a)H N-HT °%S8 ¾T '(zHS "Z = f' b 'H2) 8S"2' (zHS "= f ΉΖ) ΖΖ '\ 9 :( P-OS a) H NH T °% S8 ¾T
S6S各粱呦 - 6m S6S each 呦-6m
•(s 'Ηΐ) Γ8
Figure imgf000205_0009
'HT)ZS"Z
Figure imgf000205_0010
• (s' Ηΐ) Γ8
Figure imgf000205_0009
'HT) ZS "Z
Figure imgf000205_0010
'(zHS"9=f ' 'H2)Z6"S '(zHS"9=f ' 'ΗΖ)ΙΖ'£ 9 :( P-OS a)H N-HT °%6 ¾ί'(zHS "9 = f''H2)Z6"S' (zHS "9 = f '' ΗΖ) ΙΖ '£ 9 :( P-OS a) H NH T °% 6 ¾ί
6ε各粱呦^ -fem 6ε each siang 呦 ^ -fem
。^拳 (ZZ6T)2ZT-6Srd
Figure imgf000205_0011
. ^ Fist (ZZ6T) 2ZT-6Srd
Figure imgf000205_0011
•(s Ήΐ)ΖΓ8 '(ω 'HS)S0"8-S6"Z
Figure imgf000205_0012
Figure imgf000205_0013
SOS S081760/S00Z OAV 'Ρ Ήΐ)8ΓΖ
Figure imgf000206_0001
' 'HDfVL '(saq 'ΗΙ) Ζ' '； 'HI)OS ' '(s 'HS)0S"2 • (s Ήΐ) ΖΓ8 '(ω' HS) S0 "8-S6" Z
Figure imgf000205_0012
Figure imgf000205_0013
SOS S081760 / S00Z OAV 'Ρ Ήΐ) 8ΓΖ
Figure imgf000206_0001
'' HDfVL '(saq' ΗΙ) Ζ '';'HI)OS''(s' HS) 0S "2
'(HZ=f '； u!nb 'Η 99·ΐ '(zH =f '； Ήε)98 9 :( OSW I) 顺— HT °%89 ¾T '(HZ = f'; u! Nb 'Η 99 · ΐ' (zH = f '; Ήε) 98 9 :( OSW I) 顺 — H T °% 89 ¾T
SO 粱呦^ -ZOf [96 TO] •(zHS'9=f  SO Siang 呦 ^ -ZOf [96 TO] • (zHS'9 = f
P Ήΐ)^Γ2ΐ 'WZl=i 'P 'HWU 'WZl=i 'P Ήΐ)83·8 '(zHS'9=f 'P 'HI)SS'8
Figure imgf000206_0002
Ήΐ)3ΓΖ '(sP Ήΐ) ^ Γ2ΐ 'WZl = i' P 'HWU' WZl = i 'P Ήΐ) 83 · 8'(zHS'9 = f 'P' HI) SS'8
Figure imgf000206_0002
Ήΐ) 3ΓΖ '(s
'ΗΪ)ΟΟ· '(s Ήε)68·ε '(s Ήε)88·ε '(s Ή ζ'ζ 9 :(9p— oswa) 顺— Ht °%ΐ ¾τ 'ΗΪ) ΟΟ' (s Ήε) 68 · '' ( s Ήε) 88 · ε '( s Ή ζ''ζ 9 :( 9 p— oswa) 顺 — H t °% ΐ ¾τ
ΐΟ^ ί¾?^ (f)  ΐΟ ^ ί¾? ^ (f)
•(s Ήΐ)6ΓΠ '(s • ( s Ήΐ) 6ΓΠ '( s
' )0VL '(s 'Ηΐ)Ζ8·9 '(s 'HI)S8'9 '(s 'HS)S8"S '(s 'HS)T8"S 9 :(9p— OSWa) N— H :-f- i ^A^- 'i-^i^^-i' - ^ .-z (ε) ') 0VL' ( s ' Ηΐ) Ζ8.9 · ' s ' HI) S8'9' ( s ' HS) S8 "S '( s ' HS) T8" S 9 :( 9 p— OSWa) N— H : -f- i ^ A ^-'i- ^ i ^^-i'-^ .-z (ε)
.(s . (s
Ήΐ)Ζ0"6 '(s 'HI)6S'Z '(s Ήΐ)3Γ 'HS)06"S '(s 'HS)88"S 9 :(9p— OSWa) N— H Ήΐ) Ζ0 "6 '(s ' HI) 6S'Z '(s Ήΐ) 3Γ' HS) 06" S '(s' HS) 88 "S 9 :( 9 p- OSWa) N- H
T °%88 ¾i ^m^ ^mm^ ^ m λ ^ m-m-
Figure imgf000206_0003
(ΐ) T °% 88 ¾i ^ m ^ ^ mm ^ ^ m λ ^ mm-
Figure imgf000206_0003
(ΐ)
•(s 'HT)S6"Z
Figure imgf000206_0004
'P 'Ηΐ)ΐ6·
Figure imgf000206_0005
'(ω 'HS)S 'Z— OS' '(ω 'HS)0S"Z-0rZ '(s 'UZ)6L'f • (s' HT) S6 " Z
Figure imgf000206_0004
'P' Ηΐ) ΐ6
Figure imgf000206_0005
'(ω' HS) S 'Z— OS''(ω' HS) 0S "Z-0rZ '(s' UZ) 6L'f
' ) 6·ε '(zHz=f Ηζ) ΐτ '(s Ήε) ο 9 :(9p— oswa) 顺— HT °%9S ? Φ ') 6 · ε' ( z Hz = f Ηζ) ΐτ '( s Ήε) ο 9 :( 9 p— oswa) 顺 — H T °% 9S? Φ
•(s 'HIW8 '(zH8=f• ( s 'HIW8' ( z H8 = f
'P 'HT)S6"Z '(ZH8=f ' 'HI)ZS'Z
Figure imgf000206_0006
'P' HT) S6 "Z '(ZH8 = f''HI)ZS'Z
Figure imgf000206_0006
^ 'H2)s6"s '(s Ήε) ·ε '(zHS"9=f ' Ήζ)6ΐ 9 :(9p— oswa) 顺— HT °%SS ¾T ^ 'H2) s6 "s' (s Ήε) · ε '(zHS" 9 = f' Ήζ) 6ΐ 9 :( 9 p—oswa) 顺 — H T °% SS ¾T
66S各粱呦 -66m •(s Ήΐ)2ε·8 '(zH8=f 'P Ήΐ) 2·8
Figure imgf000206_0007
S081760/S00Z OAV J=6.5Hz), 7.30-7.55(5H, m), 8.00(2H, d, J=8Hz), 8.63(1H, d, J=12Hz), 11.40(1H, d, J=12Hz). 66S each 呦 -66m • ( s Ήΐ) 2ε · 8 ′ ( z H8 = f 'P 2) 2.8
Figure imgf000206_0007
S081760 / S00Z OAV J = 6.5Hz), 7.30-7.55 (5H, m), 8.00 (2H, d, J = 8Hz), 8.63 (1H, d, J = 12Hz), 11.40 (1H, d, J = 12Hz).
例 403:化合物番号 403 Example 403: Compound number 403
(1) 3- (フラン- 2-ィル) -1- (3-二トロフエ-ル)- 2-プロペン- 1-オール  (1) 3- (furan-2-yl) -1- (3-ditrophenyl) -2-propen-1-ol
3- (フラン- 2-ィル) -1- (3--トロフエ-ル)- 2-プロペン- 1-オン (0.92g, 3.766mmol)のメ タノール (10ml)溶液に、水素化ホウ素ナトリウム (0.28g, 7.53mmol)をカ卩え、室温で 30分 間攪拌した。反応混合物を減圧濃縮し、水を加え、酢酸ェチルで抽出した。酢酸ェ チル層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去して 得られた残渣をシリカゲルカラムクロマトグラフィー (n-へキサン Z酢酸ェチル =1Z で精製して、標題ィ匕合物の褐色液体 (0.90g, 97%)を得た。  To a solution of 3- (furan-2-yl) -1- (3--trophenyl) -2-propen-1-one (0.92 g, 3.766 mmol) in methanol (10 ml) was added sodium borohydride ( (0.28 g, 7.53 mmol) were stirred and stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, water was added, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated saline and dried over anhydrous sodium sulfate. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (n-hexane Z ethyl acetate = 1Z) to obtain a brown liquid (0.90 g, 97%) of the title compound.
^-NMRCCDCl ): δ 2.24(1H, d, J=3Hz), 5.45(1H, dd, J=7, 3Hz), 6.27(1H, dd, J=15,  ^ -NMRCCDCl): δ 2.24 (1H, d, J = 3Hz), 5.45 (1H, dd, J = 7, 3Hz), 6.27 (1H, dd, J = 15,
3  Three
7Hz), 6.30(1H, d, J=3Hz), 6.38(1H, dd, J=3, 2Hz), 6.55(1H, d, J=15Hz), 7.35(1H, d, J=2Hz), 7.55(1H, t, J=8Hz), 7.75(1H, d, J=8Hz), 8.15(1H, dd, J=8, 2Hz),  7Hz), 6.30 (1H, d, J = 3Hz), 6.38 (1H, dd, J = 3, 2Hz), 6.55 (1H, d, J = 15Hz), 7.35 (1H, d, J = 2Hz), 7.55 (1H, t, J = 8Hz), 7.75 (1H, d, J = 8Hz), 8.15 (1H, dd, J = 8, 2Hz),
8.30(1H, t, J=2Hz). 8.30 (1H, t, J = 2Hz).
3- (フラン- 2-ィル) -1- (3-二トロフエ-ル)- 2-プロペン- 1-オン： Synthetic  3- (furan-2-yl) -1- (3-ditrophenyl) -2-propen-1-one: Synthetic
Communication, Vol.29, No.6, p.965- 971(1999)参照。 See Communication, Vol. 29, No. 6, p. 965-971 (1999).
(2) 1- (3-ァミノフエ-ル)- 3- (フラン- 2-ィル) -1-プロパノール  (2) 1- (3-aminophenol) -3- (furan-2-yl) -1-propanol
3- (フラン- 2-ィル) -1- (3--トロフエ-ル)- 2-プロペン- 1-オール (lOOmg, 0.36mmol) のメタノール溶液 (10ml)に 5%パラジウム/炭素 (0.025g)をカ卩え、水素雰囲気下、室温 で 14.5時間攪拌した。不溶物をセライト濾過し、濾液を減圧濃縮して得られた残渣を シリカゲルカラムクロマトグラフィー (n-へキサン Z酢酸ェチル = 1Z1)で精製して、標 題ィ匕合物の無色液体 (0.14g, 63%)を得た。  3- (furan-2-yl) -1- (3-trophenyl) -2-propen-1-ol (100 mg, 0.36 mmol) in methanol (10 ml) was treated with 5% palladium / carbon (0.025 g ) And stirred under a hydrogen atmosphere at room temperature for 14.5 hours. The insoluble material was filtered through celite, and the filtrate was concentrated under reduced pressure.The residue obtained was purified by silica gel column chromatography (n-hexane Z ethyl acetate = 1Z1) to give a colorless liquid (0.14 g) of the title compound. , 63%).
1H-NMR(CDC1 ): δ 1.90(1H, brs), 2.00-2.20(2H, m), 2.60-2.80(2H, m), 3.69(2H,  1H-NMR (CDC1): δ 1.90 (1H, brs), 2.00-2.20 (2H, m), 2.60-2.80 (2H, m), 3.69 (2H,
3  Three
brs), 4.62(1H, t, J=6.5Hz), 5.95— 6.05(1H, m), 6.25— 6.35(1H, m), 6.55— 6.65(1H, m), 6.70-6.85(2H, m), 7.13(1H, t, J=7.5Hz), 7.28(1H, d, J=7.5Hz). brs), 4.62 (1H, t, J = 6.5Hz), 5.95― 6.05 (1H, m), 6.25― 6.35 (1H, m), 6.55-6.65 (1H, m), 6.70-6.85 (2H, m) , 7.13 (1H, t, J = 7.5Hz), 7.28 (1H, d, J = 7.5Hz).
(3)化合物番号 403  (3) Compound No. 403
収率 46%。 'H-NMRCDMSO-d ): δ 1.85-2.00(2H, m), 2.30(3H, s), 2.60-2.75(2H, Yield 46%. 'H-NMRCDMSO-d): δ 1.85-2.00 (2H, m), 2.30 (3H, s), 2.60-2.75 (2H,
6  6
m), 4.55-4.75(lH, m), 5.45(1H, d, J=5Hz), 6.11(1H, d, J=3Hz), 6.34(1H, t, J=3Hz), 7.14(1H, t, J=7.5Hz), 7.21(1H, d, J=7Hz), 7.35- 7.55(6H, m), 8.00(2H, d, J=7.5Hz), 8.62(1H, d, J=10Hz), 11.40(1H, d, J=10Hz). m), 4.55-4.75 (lH, m), 5.45 (1H, d, J = 5Hz), 6.11 (1H, d, J = 3Hz), 6.34 (1H, t, J = 3Hz), 7.14 (1H, t, J = 7.5Hz), 7.21 (1H, d, J = 7Hz), 7.35- 7.55 (6H, m), 8.00 (2H, d, J = 7.5Hz), 8.62 (1H, d, J = 10Hz), 11.40 (1H, d, J = 10Hz).
[0197] 例 404:化合物番号 404 [0197] Example 404: Compound number 404
収率 71%。 'H-NMRCDMSO-d ): δ 1.85-2.00(2Η, m), 2.60-2.75(2Η, m), 3.43(3Η,  Yield 71%. 'H-NMRCDMSO-d): δ 1.85-2.00 (2Η, m), 2.60-2.75 (2Η, m), 3.43 (3Η,
6  6
s), 4.55-4.65(1Η, m), 5.45(1Η, d, J=4.5Hz), 6.08(1Η, d, J=4Hz), 6.33(1H, t, J=4Hz), 7.25-7.35(lH, m), 7.35— 7.60(4H, m), 8.61(1H, s).  s), 4.55-4.65 (1Η, m), 5.45 (1Η, d, J = 4.5Hz), 6.08 (1Η, d, J = 4Hz), 6.33 (1H, t, J = 4Hz), 7.25-7.35 ( lH, m), 7.35-7.60 (4H, m), 8.61 (1H, s).
例 405:化合物番号 405  Example 405: Compound number 405
(1) 3-ァミノ- 1,2, 3,4-テトラヒドロキナゾリン- 4-オン  (1) 3-amino-1,2,3,4-tetrahydroquinazolin-4-one
原料として 3-ァミノ- 3,4-ジヒドロキナゾリン- 4-オンを用いて一般合成法 ξと同様の 反応を行い、標題化合物を得た。収率 99%。 'H-NMRCDMSO-d ): δ 4.60(2H, d,  Using 3-amino-3,4-dihydroquinazolin-4-one as a starting material, the same reaction as in general synthesis method II was carried out to obtain the title compound. Yield 99%. 'H-NMRCDMSO-d): δ 4.60 (2H, d,
6  6
J=2Hz), 4.98(2H, brs), 6.71(1H, t, J=7.5Hz), 6.72(1H, d, J=7.5Hz), 6.80(1H, brs), 7.24(1H, t, J=7.5Hz), 7.63(1H, d, J=7.5Hz).  J = 2Hz), 4.98 (2H, brs), 6.71 (1H, t, J = 7.5Hz), 6.72 (1H, d, J = 7.5Hz), 6.80 (1H, brs), 7.24 (1H, t, J = 7.5Hz), 7.63 (1H, d, J = 7.5Hz).
(2)化合物番号 405  (2) Compound No. 405
収率 66%。 'H-NMRCDMSO-d ): δ 2.18(3H, s), 4.89(2H, d, J=2Hz), 6.78(1H, t,  Yield 66%. 'H-NMRCDMSO-d): δ 2.18 (3H, s), 4.89 (2H, d, J = 2Hz), 6.78 (1H, t,
6  6
J=8Hz), 6.80(1H, d, J=8Hz), 7.11(1H, t, J=8Hz), 7.14(1H, brs), 7.38(1H, t, J=8Hz), 7.39(2H, t, J=8Hz), 7.71(1H, d, J=8Hz), 7.98(2H, d, J=8Hz), 8.09(1H, s).  J = 8Hz), 6.80 (1H, d, J = 8Hz), 7.11 (1H, t, J = 8Hz), 7.14 (1H, brs), 7.38 (1H, t, J = 8Hz), 7.39 (2H, t , J = 8Hz), 7.71 (1H, d, J = 8Hz), 7.98 (2H, d, J = 8Hz), 8.09 (1H, s).
例 406:化合物番号 406  Example 406: Compound number 406
収率 45%。 ^-NMRCDMSO-d ): δ 1.20(3Η, t, J=7.5Hz), 2.56(2Η, q, J=7.5Hz),  Yield 45%. ^ -NMRCDMSO-d): δ 1.20 (3Η, t, J = 7.5Hz), 2.56 (2Η, q, J = 7.5Hz),
6  6
4.90(2H, d, J=2Hz), 6.78(1H, t, J=7.5Hz), 6.79(1H, d, J=8Hz), 7.08-7.16(2H, m), 7.32(1H, t, J=8Hz), 7.40(2H, t, J=7.5Hz), 7.70(1H, d, J=8Hz), 7.99(2H, d,  4.90 (2H, d, J = 2Hz), 6.78 (1H, t, J = 7.5Hz), 6.79 (1H, d, J = 8Hz), 7.08-7.16 (2H, m), 7.32 (1H, t, J = 8Hz), 7.40 (2H, t, J = 7.5Hz), 7.70 (1H, d, J = 8Hz), 7.99 (2H, d,
J=7.5Hz), 8.13(1H, s).  J = 7.5Hz), 8.13 (1H, s).
[0198] 試験例 1：細胞を用いた PGD2産生抑制試験 Test Example 1: PGD2 production suppression test using cells
造血器型 PGD2合成酵素を発現するラット好塩基球性白血病細胞、 RBL-2H3を 24 ゥエルプレートに 2.5 X 105cells/well播種し、 CO インキュベータ内で 1晚培養後、被 Rat basophil leukemia cells expressing hematopoietic PGD2 synthase, RBL-2H3, were seeded at 2.5 × 10 5 cells / well on a 24-well plate, cultured in a CO incubator for 1 μm, and cultured.
2  2
験化合物含有又は非含有の培地に置換し 37°Cで 1時間プレインキュベーションした。 細胞を PBS (-)で洗浄後、被験化合物含有又は非含有の Hepes緩衝液 (pH7.4)に置換 し、 37°Cで 15分間インキュベーション後、終濃度 2.5 Mのカルシウムィオノフォア (A23187)を添カ卩し 37°Cで 15分間インキュベーションし PGD2産生を惹起させた。細胞 上清を回収し、上清へ流出した PGD2量を Cayman社製の PGD2-MOX EIAキットによ り測定した。被験化合物の PGD2産生阻害率は被験化合物非存在下における A23187による PGD2産生量を 100%として算出した。被験化合物 10 Mにおける結果 を以下に示す。 The medium was replaced with a medium containing or not containing the test compound, and preincubation was performed at 37 ° C for 1 hour. After washing the cells with PBS (-), replace the cells with Hepes buffer (pH 7.4) containing or not containing the test compound, and incubate at 37 ° C for 15 minutes.Then, a final concentration of 2.5 M calcium ionophore (A23187) Was added and incubated at 37 ° C for 15 minutes to induce PGD2 production. cell The supernatant was collected, and the amount of PGD2 that had flowed into the supernatant was measured with a Cayman PGD2-MOX EIA kit. The PGD2 production inhibition rate of the test compound was calculated assuming that the amount of PGD2 produced by A23187 in the absence of the test compound was 100%. The results for the test compound at 10 M are shown below.
[表 3] [Table 3]
化合物 PGD2産生 化合物 PGD2産生 化合物 PGD2産生 番号 阻害率 (％) 番号 阻害率(％) 番号 阻害率(％)Compound PGD2 production Compound PGD2 production Compound PGD2 production No. Inhibition rate (%) No. Inhibition rate (%) No. Inhibition rate (%)
1 >99 71 43 142 951> 99 71 43 142 95
2 88 72 〉99 143 >992 88 72〉 99 143> 99
3 >99 73 83 144 983> 99 73 83 144 98
4 83 74 19 145 954 83 74 19 145 95
5 63 75 56 146 435 63 75 56 146 43
6 32 76 94 147 736 32 76 94 147 73
7 27 77 >99 148 367 27 77> 99 148 36
8 59 78 98 149 588 59 78 98 149 58
9 4 79 >99 150 859 4 79> 99 150 85
10 7 80 34 151 3310 7 80 34 151 33
11 48 81 >99 152 5611 48 81> 99 152 56
12 >99 82 >99 153 7212> 99 82> 99 153 72
13 20 83 >99 154 9413 20 83> 99 154 94
14 29 84 88 155 5014 29 84 88 155 50
15 31 85 73 156 6015 31 85 73 156 60
16 30 86 97 157 4316 30 86 97 157 43
17 53 87 68 158 >9917 53 87 68 158> 99
18 13 88 >99 159 9418 13 88> 99 159 94
19 8 89 99 160 9719 8 89 99 160 97
20 28 90 89 161 9820 28 90 89 161 98
21 47 91 59 162 99 2 80 92 61 163 83 3 19 93 94 164 >99 4 95 94 94 165 93 5 88 95 98 166 61 6 >99 96 69 167 64 7 86 97 85 168 13 8 36 98 58 169 89 9 81 99 57 170 87 0 81 101 87 171 88 1 99 102 93 172 86 /vu/ O oosooifcldS0sAV 60S 21 47 91 59 162 99 2 80 92 61 163 83 3 19 93 94 164> 99 4 95 94 94 165 93 5 88 95 98 166 61 6> 99 96 69 167 64 7 86 97 85 168 13 8 36 98 58 169 89 9 81 99 57 170 87 0 81 101 87 171 88 1 99 102 93 172 86 / vu / O oosooifcldS0sAV 60S
Figure imgf000211_0001
Figure imgf000211_0001
7 49 138 88 208 >997 49 138 88 208> 99
8 >99 139 538> 99 139 53
9 41 140 >999 41 140> 99
0 31 141 92 4] 化合物 PGD2産生 化合物 PGD2産生 化合物 PGD2産生 番号 阻害率 (％) 番号 阻害率 (％) 番号 阻害率(％)0 31 141 92 4] Compound PGD2 production Compound PGD2 production Compound PGD2 production No. Inhibition rate (%) No. Inhibition rate (%) No. Inhibition rate (%)
209 85 272 25 341 64209 85 272 25 341 64
210 43 273 7 342 76210 43 273 7 342 76
211 >99 274 83 343 83211> 99 274 83 343 83
212 98 275 90 344 80212 98 275 90 344 80
213 55 276 57 345 38213 55 276 57 345 38
214 〉99 277 75 346 61214〉 99 277 75 346 61
215 92 278 98 347 3215 92 278 98 347 3
216 >99 279 >99 348 64216> 99 279> 99 348 64
217 94 280 93 349 79217 94 280 93 349 79
218 99 281 72 350 22218 99 281 72 350 22
219 91 282 98 351 98219 91 282 98 351 98
220 92 283 96 352 44220 92 283 96 352 44
221 99 284 99 353 94221 99 284 99 353 94
222 99 285 99 354 90222 99 285 99 354 90
223 69 286 >99 355 36223 69 286> 99 355 36
224 34 287 98 356 19224 34 287 98 356 19
225 29 288 97 357 10225 29 288 97 357 10
226 28 289 77 358 23226 28 289 77 358 23
227 40 290 88 359 19227 40 290 88 359 19
228 >99 291 98 360 74228> 99 291 98 360 74
229 93 292 98 361 5229 93 292 98 361 5
230 74 293 99 364 35230 74 293 99 364 35
231 23 294 >99 365 57231 23 294> 99 365 57
232 40 295 >99 366 13232 40 295> 99 366 13
233 47 296 >99 367 86233 47 296> 99 367 86
234 46 297 >99 368 88234 46 297> 99 368 88
235 60 298 〉99 369 86235 60 298〉 99 369 86
236 99 299 >99 370 47236 99 299> 99 370 47
237 >99 300 99 371 57 238 96 301 >99 372 95237> 99 300 99 371 57 238 96 301> 99 372 95
239 76 302 1 373 87239 76 302 1 373 87
240 27 303 8 374 38240 27 303 8 374 38
241 >99 304 34 375 6241> 99 304 34 375 6
242 29 305 13 376 3242 29 305 13 376 3
243 95 306 65 377 93243 95 306 65 377 93
244 91 307 >99 378 46244 91 307> 99 378 46
245 59 308 99 379 91245 59 308 99 379 91
246 69 309 >99 380 39246 69 309> 99 380 39
247 >99 310 26 381 27247> 99 310 26 381 27
248 >99 311 34 382 11248> 99 311 34 382 11
249 >99 312 27 383 6249> 99 312 27 383 6
250 99 314 7 384 33250 99 314 7 384 33
251 >99 315 17 385 29251> 99 315 17 385 29
252 >99 316 19 386 75252> 99 316 19 386 75
253 >99 317 >99 387 40253> 99 317> 99 387 40
254 >99 320 2 388 15254> 99 320 2 388 15
255 >99 321 >99 390 75255> 99 321> 99 390 75
256 >99 322 >99 391 72256> 99 322> 99 391 72
257 >99 323 >99 392 60257> 99 323> 99 392 60
258 >99 324 >99 393 94258> 99 324> 99 393 94
259 36 326 77 394 93259 36 326 77 394 93
260 5 328 4 395 99260 5 328 4 395 99
261 >99 329 3 396 43261> 99 329 3 396 43
262 >99 331 >99 397 52262> 99 331> 99 397 52
263 99 332 75 398 95263 99 332 75 398 95
264 65 333 59 399 64264 65 333 59 399 64
265 69 334 65 400 20265 69 334 65 400 20
266 43 335 81 401 38266 43 335 81 401 38
267 6 336 95 402 21267 6 336 95 402 21
268 >99 337 99 403 23268> 99 337 99 403 23
269 >99 338 70 404 31269> 99 338 70 404 31
270 >99 339 87 405 83270> 99 339 87 405 83
271 >99 340 78 406 75 試験例 2：細胞の lysateを用いた PGD2産生抑制試験 271> 99 340 78 406 75 Test Example 2: PGD2 production inhibition test using cell lysate
造血器型 PGD2合成酵素を発現するラット好塩基球性白血病細胞、 RBL-2H3を 10cm dishに 2.5 X 105cells播種し、 CO インキュベータ内で 1晚培養後、終濃度 RBL-2H3, a rat basophil leukemia cell expressing hematopoietic PGD2 synthase Seed 2.5 X 10 5 cells in a 10 cm dish, culture 1 晚 in a CO incubator,
2  2
ΙΟΟηΜのインドメタシン含有の培地に置換し 37°Cで 1時間プレインキュベーションした ンキュベーシヨンし、細胞を PBS (-)で洗浄後、セルスクレーパーにより細胞を遠心チュ ーブに回収した。 8500rpm、 4°Cで 5分間遠心しペレツトイ匕した細胞にインドメタシン (100nM)、 GSH(lmM)含有の Tris緩衝液を加え、 Pestleにより細胞をホモジナイズし、 14500rpm、 4°Cで 10分間遠心し細胞抽出液を得た。タンパク質定量後、 10 gを被験 化合物含有又は非含有の Tris/インドメタシン/ GSH緩衝液に加え 25°Cで 1分間及び 10分間インキュベートし PGD2を産生させ、終濃度 10mMの FeClを加え反応を停止さ  The medium was replaced with a medium containing indomethacin ({η}), incubated at 37 ° C for 1 hour, incubated, the cells were washed with PBS (-), and the cells were collected in a centrifuge tube using a cell scraper. Centrifuge at 8500 rpm at 4 ° C for 5 minutes, add Tris buffer containing indomethacin (100 nM) and GSH (lmM) to the pelleted cells, homogenize the cells with Pestle, and centrifuge at 14500 rpm for 10 minutes at 4 ° C. An extract was obtained. After protein quantification, 10 g was added to Tris / indomethacin / GSH buffer containing or not containing the test compound, and incubated at 25 ° C for 1 minute and 10 minutes to produce PGD2, and the reaction was stopped by adding 10 mM final concentration of FeCl.
2  2
せた。 PGD2産生量を Cayman社製の PGD2-MOX EIAキットにより測定した。被験化 合物の PGD2産生阻害率は被験化合物非存在下における PGH添カ卩による PGD2産 I let you. The amount of PGD2 production was measured using a Cayman PGD2-MOX EIA kit. The PGD2 production inhibition rate of the test compound was determined by the PGD2
2  2
生量を 100%として算出した。被験化合物 10 M、インキュベート時間 1分間における 結果を以下に示す。 It was calculated assuming that the amount of production was 100%. The results at 10 M of the test compound and an incubation time of 1 minute are shown below.
[表 5] [Table 5]
化合物 PGD2産生 化合物 PGD2産生 化合物 PGD2産生 番号 阻害率(％) 番号 阻害率(％) 番号 阻害率(％)Compound PGD2 production Compound PGD2 production Compound PGD2 production No Inhibition rate (%) No Inhibition rate (%) No Inhibition rate (%)
1 90 86 8 164 201 90 86 8 164 20
2 92 93 4 165 732 92 93 4 165 73
3 74 95 18 166 813 74 95 18 166 81
4 26 102 15 169 44 26 102 15 169 4
12 41 108 14 170 5712 41 108 14 170 57
24 11 116 1 171 1224 11 116 1 171 12
26 50 117 3 172 2026 50 117 3 172 20
27 80 119 8 174 9027 80 119 8 174 90
29 10 120 7 178 1529 10 120 7 178 15
36 63 122 90 184 3236 63 122 90 184 32
37 6 123 19 185 1137 6 123 19 185 11
46 59 124 29 187 9146 59 124 29 187 91
47 46 129 19 188 9047 46 129 19 188 90
48 33 130 1 189 8348 33 130 1 189 83
51 27 135 19 190 9351 27 135 19 190 93
52 24 136 23 191 8652 24 136 23 191 86
53 94 140 23 192 1253 94 140 23 192 12
54 24 141 19 193 254 24 141 19 193 2
55 37 142 18 194 155 37 142 18 194 1
60 80 143 74 195 9460 80 143 74 195 94
64 41 144 17 196 8964 41 144 17 196 89
68 1 147 19 197 2168 1 147 19 197 21
76 13 150 38 198 5476 13 150 38 198 54
77 72 154 91 199 777 72 154 91 199 7
78 2 158 96 205 5378 2 158 96 205 53
79 39 159 2 206 979 39 159 2 206 9
81 40 160 1 208 9281 40 160 1 208 92
82 4 161 11 82 4 161 11
83 90 163 17 6] 化合物 PGD2産生 化合物 PGD2産生 化合物 PGD2産生 番号 阻害率 (％) 番号 阻害率(％) 番号 阻害率(％)83 90 163 17 6] Compound PGD2 production Compound PGD2 production Compound PGD2 production No. Inhibition rate (%) No. Inhibition rate (%) No. Inhibition rate (%)
209 10 289 51 349 68209 10 289 51 349 68
211 95 290 55 350 33211 95 290 55 350 33
212 91 291 4 351 95212 91 291 4 351 95
214 92 292 39 352 82214 92 292 39 352 82
215 5 293 11 353 92215 5 293 11 353 92
216 53 294 98 354 17216 53 294 98 354 17
218 92 295 95 355 51218 92 295 95 355 51
219 92 296 52 356 63219 92 296 52 356 63
220 11 297 96 357 84220 11 297 96 357 84
221 76 298 94 358 33221 76 298 94 358 33
222 86 299 95 359 82222 86 299 95 359 82
228 99 300 97 360 90228 99 300 97 360 90
229 20 301 93 361 37229 20 301 93 361 37
230 7 302 88 362 21230 7 302 88 362 21
236 92 303 82 363 23236 92 303 82 363 23
237 93 304 70 364 92237 93 304 70 364 92
238 94 305 39 365 89238 94 305 39 365 89
241 91 306 34 366 71241 91 306 34 366 71
243 90 307 19 367 75243 90 307 19 367 75
244 54 308 10 368 84244 54 308 10 368 84
247 93 309 19 369 91247 93 309 19 369 91
248 39 310 94 370 41248 39 310 94 370 41
249 36 312 83 371 89249 36 312 83 371 89
250 63 313 8 372 33250 63 313 8 372 33
251 >99 314 77 373 86251> 99 314 77 373 86
253 >99 315 89 374 29253> 99 315 89 374 29
254 40 316 74 375 68254 40 316 74 375 68
255 91 317 91 376 84255 91 317 91 376 84
256 93 318 70 377 85256 93 318 70 377 85
257 43 319 84 378 47257 43 319 84 378 47
258 83 320 80 379 95258 83 320 80 379 95
261 95 321 90 380 22 262 89 322 93 381 90261 95 321 90 380 22 262 89 322 93 381 90
263 59 323 93 382 91263 59 323 93 382 91
264 24 324 91 383 65264 24 324 91 383 65
265 36 325 48 384 81265 36 325 48 384 81
266 43 326 18 385 92266 43 326 18 385 92
267 91 327 22 386 92267 91 327 22 386 92
268 90 328 73 387 91268 90 328 73 387 91
269 78 329 24 388 90269 78 329 24 388 90
270 33 330 5 389 93270 33 330 5 389 93
271 67 331 94 390 86271 67 331 94 390 86
272 73 332 50 391 67272 73 332 50 391 67
273 95 333 92 392 53273 95 333 92 392 53
274 46 334 79 393 93274 46 334 79 393 93
275 83 335 88 394 49275 83 335 88 394 49
276 26 336 70 395 89276 26 336 70 395 89
277 26 337 98 396 88277 26 337 98 396 88
278 31 338 95 397 91278 31 338 95 397 91
279 88 339 80 398 89279 88 339 80 398 89
280 94 340 71 399 70280 94 340 71 399 70
281 96 341 93 400 53281 96 341 93 400 53
282 8 342 86 401 78282 8 342 86 401 78
283 19 343 94 402 26283 19 343 94 402 26
284 92 344 92 403 52284 92 344 92 403 52
285 93 345 62 404 1285 93 345 62 404 1
286 90 346 82 405 89286 90 346 82 405 89
287 90 347 71 287 90 347 71
288 49 348 53 産業上の利用可能性  288 49 348 53 Industrial applicability
本発明の医薬は、 PGD2の産生及び Z又は造血器型 PGD2合成酵素に対して強力 な阻害作用を有することから、アレルギー、アレルギー性炎症、及び喘息などの疾患 の予防及び Z又は治療のための医薬として有用である。また、脳損傷の増悪の予防 及び Z又は予後の改善、組織損傷保護、性周期調節、睡眠調節、体温調節、鎮痛、 又は嗅覚調節などの作用を有する医薬としても有用である。  Since the medicament of the present invention has a strong inhibitory action on PGD2 production and Z or hematopoietic PGD2 synthase, it is useful for prevention and Z or treatment of diseases such as allergy, allergic inflammation and asthma. Useful as a medicine. It is also useful as a medicament having effects such as prevention of exacerbation of brain damage and improvement of Z or prognosis, protection of tissue damage, estrous cycle regulation, sleep regulation, body temperature regulation, analgesia, or olfactory regulation.

Claims

請求の範囲 下記一般式 (I): A-Y-B (I) [式中、 A及び Bはそれぞれ独立して置換基を有していてもよい炭化水素環基又は置 換基を有していてもよいへテロ環基を表し； Yは- CH=N -、 - N=CH -、 - CONH-又は - NHCO-を表す。 但し、下記一般式 (1-1): Claims The following general formula (I): AYB (I) wherein A and B each independently may have a hydrocarbon ring group or a substituent which may have a substituent. Y represents -CH = N-, -N = CH-, -CONH- or -NHCO-. However, the following general formula (1-1):
[化 1]
Figure imgf000218_0001
[Chemical 1]
Figure imgf000218_0001
[式中、 Xは式- N=C(R5)- (式中、左側の結合手がベンゼン環に結合し、右側の結合 手が窒素原子に結合する)、又は式- NH-CH(R5)- (式中、左側の結合手がベンゼン 環に結合し、右側の結合手が窒素原子に結合する)を表し；
Figure imgf000218_0002
R3及び R4はそれ ぞれ独立して水素原子、ハロゲン原子、置換基を有していてもよい C - Cアルキル基 Wherein, X is the formula - N = C (R 5) - ( wherein the left bond is attached to the benzene ring, right bond is attached to the nitrogen atom), or the formula - NH-CH ( R 5 )-(where the left hand is bonded to the benzene ring and the right hand is bonded to the nitrogen atom);
Figure imgf000218_0002
R 3 and R 4 are each independently a hydrogen atom, a halogen atom, and a C -C alkyl group which may have a substituent.
1 6 1 6
、又は置換基を有していてもよいヒドロキシ基を表し； R5は置換基を有していてもよい C - Cアルキル基、又は置換基を有していてもよい C - C ァリール基を表し； RはOr a hydroxy group which may have a substituent; R 5 represents a C -C alkyl group which may have a substituent, or a C -C aryl group which may have a substituent Represents; R is
1 6 6 10 置換 基を有して 、てもよ 、アミノ基を表す]で表される化合物は除く] A compound having a 16610 substituent and which may represent an amino group]
で表される化合物及び薬理学的に許容されるその塩、並びにそれらの水和物及び 溶媒和物からなる群から選択される物質を有効成分として含み、プロスタグランジンAnd a pharmacologically acceptable salt thereof, and a substance selected from the group consisting of hydrates and solvates thereof, as a prostaglandin,
D2D2
(PGD2)産生抑制作用を有する医薬。 (PGD2) A drug having an activity of suppressing production.
Yカ CH=N―、— N=CH―、— CONH—又は— NHCO—であり；  Y is CH = N-, -N = CH-, -CONH- or -NHCO-;
Aが置換基を有していてもよい C - C ァリール基、置換基を有していてもよい 6ないし  A may have a substituent C-C aryl group, may have a substituent 6 or more
6 10  6 10
13員のへテロアリール基、或 、は置換基を有して 、てもよ 、9又は 10員の部分飽和 ヘテロ環基であり；  A 13-membered heteroaryl group or is a 9- or 10-membered partially saturated heterocyclic group having a substituent, and
Bが置換基を有していてもよい C - C ァリール基、置換基を有していてもよい 5ないし  B may have a substituent C-C aryl group, optionally having a substituent 5 to
6 10  6 10
13員のへテロアリール基、或 、は置換基を有して 、てもよ 、5な 、し 10員の部分飽和 ヘテロ環基である請求の範囲第 1項に記載の医薬。 2. The medicament according to claim 1, wherein the drug is a 13-membered heteroaryl group or a 5- or 10-membered partially saturated heterocyclic group having a substituent.
[3] A力ヒドロキシ置換 C - C ァリール基 (該ァリール基はヒドロキシ基のほかに更に置換 [3] Hydroxy-substituted C-C aryl group (the aryl group is further substituted in addition to the hydroxy group)
6 10  6 10
基を有して 、てもよ 、；)であり；  Having a group, may be;));
Yカ CH=N―、— N=CH―、— CONH—又は— NHCO—であり；  Y is CH = N-, -N = CH-, -CONH- or -NHCO-;
Bが置換基を有して 、てもよ 、5な 、し 13員のへテロアリール基である請求の範囲第 2 項に記載の医薬。  3. The medicament according to claim 2, wherein B has a substituent, and may be a 5- to 13-membered heteroaryl group.
[4] A力ヒドロキシ置換ナフチル基 (該ナフチル基はヒドロキシ基のほかに更に置換基を有 していてもよい)であり；  [4] A-hydroxy-substituted naphthyl group (the naphthyl group may have a substituent in addition to the hydroxy group);
Yカ CH=N―、— N=CH―、— CONH—又は— NHCO—であり；  Y is CH = N-, -N = CH-, -CONH- or -NHCO-;
Bが置換基を有していてもよいピラゾリル基である請求の範囲第 3項に記載の医薬。  4. The medicament according to claim 3, wherein B is a pyrazolyl group which may have a substituent.
[5] Aが 1-ヒドロキシ- 2-ナフチル基であり； [5] A is a 1-hydroxy-2-naphthyl group;
(a) Yカ N=CH-であり； B力 1位が水素原子、置換基を有していてもよい C - Cアル  (a) Y is N = CH-; B force is a hydrogen atom at position 1 and may have a substituent.
1 6 キル基、置換基を有していてもよい C - C ァリール基、置換基を有していてもよい C  16-C hyl group, C-C aryl group optionally having substituent (s) C-C aryl group, C group optionally having substituent (s)
6 10 7 6 10 7
- C ァラルキル基、又は置換基を有していてもよい 9員のへテロアリール基であり、 3-A C aralkyl group or a 9-membered heteroaryl group which may have a substituent,
12 12
位が置換基を有していてもよい C - Cアルキル基、又は置換基を有していてもよい C  C-C alkyl group which may have a substituent at the position, or C which may have a substituent
1 6 6 1 6 6
- C ァリール基であり、 5位力 Sヒドロキシ基であるピラゾール -4-ィル基； -A pyrazole-4-yl group which is a C aryl group and is a 5-position S hydroxy group;
10  Ten
(b) Yが- CH=N -であり； Bが、 1位が置換基を有していてもよい C - Cアルキル基、置  (b) Y is -CH = N-; B is a C-C alkyl group optionally substituted at the 1-position,
1 6  1 6
換基を有していてもよい C -C ァリール基、置換基を有していてもよい C -C ァラル  C -C aryl group which may have a substituent, C -C aryl which may have a substituent
6 10 7 12 キル基、又は置換基を有していてもよい C - Cアルコキシカルボニル基であり、 3位が  6 10 7 12 alkyl group or a C-C alkoxycarbonyl group which may have a substituent,
2 7  2 7
水素原子、置換基を有していてもよい C - Cアルキル基、又は置換基を有していても  Hydrogen atom, optionally substituted C-C alkyl group, or optionally substituted
1 6  1 6
よい C - C ァリール基であり、 4位が水素原子又は置換基を有していてもよい C - C了 A good C-C aryl group, which may have a hydrogen atom or a substituent at the 4-position.
6 10 2 7 ルコキシカルボ-ル基であるピラゾール -5-ィル基；或 、は 6 10 2 7 a pyrazole-5-yl group which is a alkoxycarbyl group;
(c) Yが- CH=N-であり； Bが、 1位が水素原子又は置換基を有していてもよい C - C 了  (c) Y is -CH = N-; B is a C-C atom which may have a hydrogen atom or a substituent at the 1-position.
6 10 リール基であり、 4位が水素原子であり、 5位が置換基を有していてもよい C - C ァリー  6 10 reel group, 4-position is hydrogen atom, 5-position may have a substituent C-C aryl
6 10 ル基、又はヒドロキシ基であるピラゾール -3-ィル基  6 10-pyrazole-3-yl group or hydroxy group
である請求の範囲第 4項に記載の医薬。  5. The medicament according to claim 4, which is:
[6] A力 Sヒドロキシ基で置換された 6な 、し 10員のへテロアリール基 (該ヘテロァリール基は ヒドロキシ基のほかに更に置換基を有して 、てもよ 、；)であり； [6] A force A 6- or 10-membered heteroaryl group substituted with an S-hydroxy group (the heteroaryl group may further have a substituent in addition to the hydroxy group;);
Yカ N=CH-又は- CONH-であり； Bが置換基を有して 、てもよ 、5員のへテロアリール基である請求の範囲第 2項に記 載の医薬。 Y is N = CH- or -CONH-; 3. The medicament according to claim 2, wherein B has a substituent and may be a 5-membered heteroaryl group.
[7] A力ヒドロキシ置換キノリル基 (該キノリル基はヒドロキシ基のほかに更に置換基を有し ていてもよい)であり；  [7] A-hydroxy-substituted quinolyl group (the quinolyl group may have a substituent in addition to the hydroxy group);
Yカ N=CH-又は- CONH-であり；  Y is N = CH- or -CONH-;
Bが置換基を有していてもよいピラゾリル基である請求の範囲第 6項に記載の医薬。  7. The medicament according to claim 6, wherein B is a pyrazolyl group which may have a substituent.
[8] Aが 4-ヒドロキシ -3-キノリル基 (該キノリル基はヒドロキシ基のほかに更に置換基を有 していてもよい)であり； [8] A is a 4-hydroxy-3-quinolyl group (the quinolyl group may have a substituent in addition to the hydroxy group);
Yカ N=CH—であり；  Y = N—CH—
Bが、 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよい  B is a C-C alkyl group which may have a substituent at the 1-position, and may have a substituent
1 6  1 6
C -C ァリール基、又は置換基を有していてもよい C -C ァラルキル基であり、 3位が A C -C aryl group or a C -C aralkyl group which may have a substituent, wherein the 3-position is
6 10 7 12 6 10 7 12
置換基を有していてもよい C - Cアルキル基であり、 5位がヒドロキシ基であるピラゾー  A pyrazole having an optionally substituted C-C alkyl group, wherein the 5-position is a hydroxy group
1 6  1 6
ル -4-ィル基；  Le-4-yl group;
である請求の範囲第 7項に記載の医薬。  8. The medicament according to claim 7, which is:
[9] Aが、 1又は 2個の窒素原子を環構成原子として含有する 9又は 10員の部分飽和へテ 口環基 (該部分飽和へテロ環基は置換基を有して ヽてもよく、 Yとの結合位置は環構 成原子である窒素原子の位置である)であり； [9] A is a 9- or 10-membered partially saturated heterocyclic group containing 1 or 2 nitrogen atoms as a ring-constituting atom (the partially saturated heterocyclic group may have a substituent Often, the bonding position with Y is the position of a nitrogen atom which is a ring-constituting atom);
Yカ N=CH—であり；  Y = N—CH—
Bが置換基を有して 、てもよ 、5員のへテロアリール基である請求の範囲第 2項に記 載の医薬。  3. The medicament according to claim 2, wherein B has a substituent and may be a 5-membered heteroaryl group.
[10] A力 置換基を有して!/、てもよ 、イソインドリン- 2-ィル基、置換基を有して!/、てもよ!/ヽ 1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、置換基を有していてもよい 1,2-ジヒドロイソ キノリン- 2-ィル基及び置換基を有していてもよい 1,2,3,4-テトラヒドロキナゾリン- 3-ィ ル基からなる群から選択される基であり；  [10] A force Having a substituent! /, May have an isoindoline-2-yl group, having a substituent! /, May have /! Tetrahydroisoquinoline-2-yl group, optionally substituted 1,2-dihydroisoquinolin-2-yl group and optionally substituted 1,2,3,4-tetrahydroquinazoline -A group selected from the group consisting of 3-yl groups;
Yカ N=CH—であり；  Y = N—CH—
Bが置換基を有していてもよいピラゾリル基である請求の範囲第 9項に記載の医薬。  10. The medicament according to claim 9, wherein B is a pyrazolyl group which may have a substituent.
[11] Aが、下記環群 α -3-1から選択される基であり； [11] A is a group selected from the following ring group α-3-1;
Υカ N=CH—であり； Bが、 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよい Υka N = CH—; B is a C-C alkyl group which may have a substituent at the 1-position, and may have a substituent
1 6  1 6
C -C ァリール基、又は置換基を有していてもよい C -C ァラルキル基であり、 3位が A C -C aryl group or a C -C aralkyl group which may have a substituent, wherein the 3-position is
6 10 7 12 6 10 7 12
置換基を有していてもよい C - Cアルキル基であり、 5位がヒドロキシ基であるピラゾー  A pyrazole having an optionally substituted C-C alkyl group, wherein the 5-position is a hydroxy group
1 6  1 6
ル -4-ィル基；  Le-4-yl group;
である請求の範囲第 10項に記載の医薬。  11. The medicament according to claim 10, which is:
[環群 α - 3-1] 1,3-ジォキソイソインドリン- 2-ィル基、 3-ヒドロキシ- 1-ォキソイソインド リン- 2-ィル基、 1-ォキソイソインドリン- 2-ィル基、 1,3-ジォキソ- 1,2,3,4-テトラヒドロイ ソキノリン- 2-ィル基、 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 3-ヒドロキ シ- 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 1-ォキソ -1,2-ジヒドロイソキノ リン- 2-ィル基、 4-ォキソ -1,2,3,4-テトラヒドロキナゾリン- 3-ィル基  [Ring group α-3-1] 1,3-Dioxoisoindoline-2-yl group, 3-hydroxy-1-oxoisoindoline-2-yl group, 1-oxoisoindoline-2-yl 1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 3- Hydroxy-1-oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2-dihydroisoquinolin-2-yl group, 4-oxo-1,2 , 3,4-tetrahydroquinazoline-3-yl group
[12] 一般式 (I)で表される化合物が、本明細書に記載されたィ匕合物番号 1ないし 406で表さ れる化合物からなる群力 選択される化合物である請求の範囲第 1項に記載の医薬 [12] The compound according to claim 1, wherein the compound represented by the general formula (I) is a compound selected from the group consisting of the compounds represented by Compound Nos. 1 to 406 described in the present specification. Pharmaceuticals described in item
[13] 造血器型 PGD2合成酵素阻害作用を有する請求の範囲第 1項ないし第 12項のいず れか 1項に記載の医薬。 [13] The medicament according to any one of claims 1 to 12, which has a hematopoietic PGD2 synthase inhibitory action.
[14] 抗アレルギー作用、抗アレルギー性炎症作用、及び抗喘息作用力 なる群力 選択 される 1以上の作用を有する請求の範囲第 1項ないし第 13項のいずれ力 1項に記載 の医薬。 [14] The medicament according to any one of claims 1 to 13, which has one or more actions selected from the group consisting of an antiallergic action, an antiallergic inflammatory action, and an antiasthmatic action.
[15] 脳損傷の増悪の予防作用及び Ζ又は脳損傷の予後の改善作用を有する請求の範 囲第 1項ないし第 13項のいずれ力 1項に記載の医薬。  [15] The medicament according to any one of claims 1 to 13, which has a preventive action for exacerbation of brain damage and an action for improving prognosis of brain damage.
[16] 脳保護作用を有する請求の範囲第 1項ないし第 13項のいずれか 1項に記載の医薬 [16] The medicament according to any one of claims 1 to 13, which has a brain protective effect.
[17] 性周期調節作用、睡眠調節作用、体温調節作用、鎮痛作用及び嗅覚調節作用から なる群力 選択される 1以上の作用を有する請求の範囲第 1項ないし第 13項のいず れか 1項に記載の医薬。 [17] any one of claims 1 to 13 having at least one action selected from the group consisting of an estrous cycle controlling action, a sleep controlling action, a body temperature controlling action, an analgesic action and an olfactory controlling action; The medicament according to item 1.
[18] 下記一般式 (II):  [18] The following general formula (II):
Α101 - Υ101 - Β101 (II) Α 101 -Υ 101 -Β 101 (II)
中、 A1Q1及び Β1Μはそれぞれ独立して置換基を有していてもよい炭化水素環基又 は置換基を有していてもよいへテロ環基を表し； Y は- CH=N -、 - N=CH -、 -CONH- 又は- NHCO-を表す。 Wherein A 1Q1 and {1} are each independently an optionally substituted hydrocarbon ring group or Represents a heterocyclic group which may have a substituent; Y represents -CH = N-, -N = CH-, -CONH- or -NHCO-.
但し、下記一般式 (II-1):  However, the following general formula (II-1):
[化 2]  [Formula 2]
Figure imgf000222_0001
Figure imgf000222_0001
[式中、 X1U1は式- N=C(RbU1)_ (式中、左側の結合手がベンゼン環に結合し、右側の結 合手が窒素原子に結合する)、又は式- NH-CH(R5Q1)- (式中、左側の結合手がベンゼ ン環に結合し、右側の結合手が窒素原子に結合する)を表し； R1M、 R2M、 R3M及び R4M はそれぞれ独立して水素原子、ハロゲン原子、置換基を有していてもよい C - Cアル Wherein X 1U1 is a compound of the formula -N = C (R bU1 ) _ (where the bond on the left is bonded to a benzene ring and the bond on the right is bonded to a nitrogen atom), or the formula -NH- CH (R 5Q1 )-(where the bond on the left is bonded to the benzene ring and the bond on the right is bonded to the nitrogen atom); R 1M , R 2M , R 3M and R 4M are each independently A hydrogen atom, a halogen atom, and a C-C
1 6 キル基、又は置換基を有していてもよいヒドロキシ基を表し； R5Q1は置換基を有してい てもよい C - Cアルキル基、又は置換基を有していてもよい C - C ァリール基を表し； Represents a 16- alkyl group or a hydroxy group which may have a substituent; R 5Q1 represents a C-C alkyl group which may have a substituent or a C- which may have a substituent; Represents a C aryl group;
1 6 6 10 1 6 6 10
R1QQ1は置換基を有していてもよいアミノ基を表す]で表される化合物、並びに Y1Mが - CH=N -又は- CONH-であり； A1()1が 2-ヒドロキシ- 1-ナフチル基であり； Βωιが 2-ヒドロ キシ -4-スルホ -1-ナフチル基である化合物は除く] R 1QQ1 represents an amino group which may have a substituent], and Y 1M is —CH = N— or —CONH—; and A 1 () 1 is 2-hydroxy-1 -A naphthyl group; excluding compounds where ωωι is a 2-hydroxy-4-sulfo-1-naphthyl group]
で表される化合物若しくはその塩、又はそれらの水和物若しくはそれらの溶媒和物。  Or a salt thereof, or a hydrate or solvate thereof.
[19] Αωιがヒドロキシ置換ナフチル基 (該ナフチル基はヒドロキシ基のほかに更に置換基を 有していてもよい)であり； [19] Αωι is a hydroxy-substituted naphthyl group (the naphthyl group may further have a substituent in addition to the hydroxy group);
Y101が— CH=N―、— N=CH―、— CONH—又は— NHCO—であり； Y 101 is —CH = N—, —N = CH—, —CONH— or —NHCO—;
B1Q1が置換基を有していてもよいピラゾリル基である請求の範囲第 18項に記載の化 合物若しくはその塩、又はそれらの水和物若しくはそれらの溶媒和物。 19. The compound according to claim 18, wherein B 1Q1 is a pyrazolyl group which may have a substituent, a salt thereof, or a hydrate or solvate thereof.
[20] Αωιが 1-ヒドロキシ- 2-ナフチル基であり； [20] Αωι is a 1-hydroxy-2-naphthyl group;
(a) Y1Mが- N=CH-であり； B1Mが、 1位が水素原子、置換基を有していてもよい C - Cァ (a) Y 1M is -N = CH-; B 1M is a hydrogen atom at the 1-position, which may have a substituent.
1 6 ルキル基、置換基を有していてもよい C - C ァリール基、置換基を有していてもよい C  16 alkyl group, optionally substituted C-C aryl group, optionally substituted C
6 10  6 10
- C ァラルキル基、又は置換基を有していてもよい 9員のへテロアリール基であり、 3 -A C aralkyl group or a 9-membered heteroaryl group which may have a substituent,
7 12 7 12
位が置換基を有していてもよい C - Cアルキル基、又は置換基を有していてもよい C  C-C alkyl group which may have a substituent at the position, or C which may have a substituent
1 6 6 1 6 6
- C ァリール基であり、 5位力 Sヒドロキシ基であるピラゾール -4-ィル基； (b) Y1Mが- CH=N -であり； B1()1が、 1位が置換基を有していてもよい C - Cアルキル基、 -A pyrazole-4-yl group which is a C aryl group and is a 5-position S hydroxy group; (b) Y 1M is -CH = N-; B 1 () 1 is a C-C alkyl group optionally substituted at the 1-position,
1 6  1 6
置換基を有していてもよい C -C ァリール基、置換基を有していてもよい C -C ァラ  C -C aryl group which may have a substituent, C -C aryl group which may have a substituent
6 10 7 12 ルキル基、又は置換基を有していてもよい C - Cアルコキシカルボニル基であり、 3位  6 10 7 12 alkyl group, or an optionally substituted C-C alkoxycarbonyl group, 3-position
2 7  2 7
が水素原子、置換基を有していてもよい C - Cアルキル基、又は置換基を有していて  Has a hydrogen atom, a C-C alkyl group which may have a substituent, or a substituent
1 6  1 6
もよい C - C ァリール基であり、 4位が水素原子又は置換基を有していてもよい C - C Is a C-C aryl group, and the C-C may have a hydrogen atom or a substituent at the 4-position.
6 10 2 7 アルコキシカルボ-ル基であるピラゾール -5-ィル基；或いは 6 10 2 7 a pyrazole-5-yl group which is an alkoxycarbol group; or
(c) Y1Q1が- CH=N-であり； Βωΐが、 1位が水素原子又は置換基を有していてもよい C (c) Y 1Q1 is -CH = N-; ΒωΒ is a hydrogen atom or a substituent which may have a substituent at the 1-position
6 6
- C ァリール基であり、 4位が水素原子であり、 5位が置換基を有していてもよい C - C-C aryl group, the 4-position is a hydrogen atom, and the 5-position may have a substituent C-C
10 6 ァリール基、又はヒドロキシ基であるピラゾール -3-ィル基 10 6 Aryl group or pyrazole-3-yl group which is hydroxy group
10  Ten
である請求の範囲第 19項に記載の化合物若しくはその塩、又はそれらの水和物若 しくはそれらの溶媒和物。  20. The compound according to claim 19 or a salt thereof, or a hydrate or solvate thereof.
[21] Αωιがヒドロキシ置換キノリル基 (該キノリル基はヒドロキシ基のほかに更に置換基を有 していてもよい)であり； [21] Αωι is a hydroxy-substituted quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group);
Y101が- N=CH-又は- CONH-であり； Y 101 is -N = CH- or -CONH-;
B1Q1が置換基を有していてもよいピラゾリル基である請求の範囲第 18項に記載の化 合物若しくはその塩、又はそれらの水和物若しくはそれらの溶媒和物。 19. The compound according to claim 18, wherein B 1Q1 is a pyrazolyl group which may have a substituent, a salt thereof, or a hydrate or solvate thereof.
[22] Αωιが 4-ヒドロキシ -3-キノリル基 (該キノリル基はヒドロキシ基のほかに更に置換基を 有していてもよい)であり； [22] Αωι is a 4-hydroxy-3-quinolyl group (the quinolyl group may further have a substituent in addition to the hydroxy group);
Y101が— N=CH—であり； Y 101 is —N = CH—;
B1Q1が、 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよ B 1Q1 may have a C-C alkyl group optionally having a substituent at the 1-position, or a substituent
1 6  1 6
い C - C ァリール基、又は置換基を有していてもよい C -C ァラルキル基であり、 3位 A C-Caryl group or a C-Caralkyl group which may have a substituent,
6 10 7 12 6 10 7 12
が置換基を有していてもよい C - Cアルキル基であり、 5位力ヒドロキシ基であるピラゾ  Is a C-C alkyl group which may have a substituent, and pyrazo is a 5-position hydroxy group.
1 6  1 6
ール -4-ィル基；  -4-yl group;
である請求の範囲第 21項に記載の化合物若しくはその塩、又はそれらの水和物若 しくはそれらの溶媒和物。  22. The compound according to claim 21 or a salt thereof, or a hydrate or solvate thereof.
[23] Αωιが、 1又は 2個の窒素原子を環構成原子として含有する 9又は 10員の部分飽和へ テロ環基 (該部分飽和へテロ環基は置換基を有していてもよぐ Y1Mとの結合位置は 環構成原子である窒素原子の位置である)であり； Y が- N=CH-であり； [23] ωωι is a 9- or 10-membered partially saturated heterocyclic group containing 1 or 2 nitrogen atoms as ring constituent atoms (the partially saturated heterocyclic group may have a substituent. The position of the bond to Y 1M is the position of the nitrogen atom which is a ring-constituting atom); Y is -N = CH-;
B1Q1が置換基を有していてもよいピラゾリル基である請求の範囲第 18項に記載の化 合物若しくはその塩、又はそれらの水和物若しくはそれらの溶媒和物。 19. The compound according to claim 18, wherein B 1Q1 is a pyrazolyl group which may have a substituent, a salt thereof, or a hydrate or solvate thereof.
[24] Αωιが下記環群 oc ωι-3-1から選択される基であり； [24] Αωι is a group selected from the following ring group oc ωι- 3-1;
Y101が- N=CH-であり； Y 101 is -N = CH-;
B1Q1が、 1位が置換基を有していてもよい C - Cアルキル基、置換基を有していてもよ B 1Q1 may have a C-C alkyl group optionally having a substituent at the 1-position, or a substituent
1 6  1 6
い C - C ァリール基、又は置換基を有していてもよい C -C ァラルキル基であり、 3位 A C-Caryl group or a C-Caralkyl group which may have a substituent,
6 10 7 12 6 10 7 12
が置換基を有していてもよい C - Cアルキル基であり、 5位力ヒドロキシ基であるピラゾ  Is a C-C alkyl group which may have a substituent, and pyrazo is a 5-position hydroxy group.
1 6  1 6
ール -4-ィル基；  -4-yl group;
である請求の範囲第 23項に記載の化合物若しくはその塩、又はそれらの水和物若 しくはそれらの溶媒和物。  24. The compound according to claim 23, or a salt thereof, or a hydrate or solvate thereof.
[環群ひ1。1- 3-1] 1,3-ジォキソイソインドリン- 2-ィル基、 3-ヒドロキシ- 1-ォキソイソイン ドリン- 2-ィル基、 1-ォキソイソインドリン- 2-ィル基、 1,3-ジォキソ- 1,2,3,4-テトラヒドロ イソキノリン- 2-ィル基、 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 3-ヒドロキ シ- 1-ォキソ -1,2,3,4-テトラヒドロイソキノリン- 2-ィル基、 1-ォキソ -1,2-ジヒドロイソキノ リン- 2-ィル基、 4-ォキソ -1,2,3,4-テトラヒドロキナゾリン- 3-ィル基 [Ring group 1 . 1 - 3-1] 1,3-O Kiso isoindoline - 2 I group, 3-hydroxy - 1-Okisoisoin Dorin - 2 I group, 1-O Kiso isoindoline - 2 I group, 1,3-Dioxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 3-hydroxy-1 -Oxo-1,2,3,4-tetrahydroisoquinolin-2-yl group, 1-oxo-1,2-dihydroisoquinolin-2-yl group, 4-oxo-1,2,3,4 -Tetrahydroquinazoline-3-yl group
[25] 一般式 (II)で表される化合物力 本明細書に記載された化合物番号 1ないし 406で表 される化合物力 なる群力 選択される化合物である請求の範囲第 18項に記載の化 合物若しくはその塩、又はそれらの水和物若しくはそれらの溶媒和物。 [25] The compound represented by the general formula (II): The compound represented by the compound number 1 to 406 described in the present specification. Compounds or salts thereof, or hydrates or solvates thereof.
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