WO2016104451A1 - Nouveau dérivé hétérocyclique - Google Patents

Nouveau dérivé hétérocyclique Download PDF

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Publication number
WO2016104451A1
WO2016104451A1 PCT/JP2015/085718 JP2015085718W WO2016104451A1 WO 2016104451 A1 WO2016104451 A1 WO 2016104451A1 JP 2015085718 W JP2015085718 W JP 2015085718W WO 2016104451 A1 WO2016104451 A1 WO 2016104451A1
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group
triazolo
pyridine
amino
anemia
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PCT/JP2015/085718
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English (en)
Japanese (ja)
Inventor
隆弘 佐藤
幸帆 永山
泰裕 吉野
勗 井上
宏茂 加藤
淳一郎 雨田
真里 稲葉
典子 矢本
哲也 谷口
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株式会社富士薬品
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Publication of WO2016104451A1 publication Critical patent/WO2016104451A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Definitions

  • the present invention relates to a novel heterocyclic derivative having an erythropoietin (EPO) production promoting action.
  • EPO erythropoietin
  • EPO is a glycoprotein hormone consisting of 165 amino acids produced mainly in the kidney and partly in the liver, and promotes differentiation induction of erythroid stem cells (progenitor cells) to produce mature erythrocytes.
  • erythroid stem cells progenitor cells
  • HIF hypoxia-inducible factor
  • HIF- ⁇ ⁇ subunit
  • HIF- ⁇ ⁇ subunit
  • PHD prolyl hydroxylase
  • Non-patent Documents 2 and 3 It has been reported that PHD has 1 to 3 isoforms, and each has different intracellular localization, oxygen partial pressure response, reactivity to HIF isoform, etc. (Non-patent Documents 2 and 3). HIF- ⁇ also has several isoforms. Although HIF-1 ⁇ and HIF-2 ⁇ are very similar in structure, their expression levels and localization are different (Non-patent Document 3). HIF has also been suggested to affect hypoxia-inducible factors other than EPO (glucose transporters 1 and 3, lactate dehydrogenase, hepcidin, etc.) (Non-Patent Documents 3 and 4). It is not fully understood.
  • HIF- ⁇ is stabilized without being degraded by PHD, and moves from the cytoplasm into the nucleus to form a dimer with HIF- ⁇ .
  • the heterodimer of HIF- ⁇ and ⁇ binds to the hypoxia responsive element sequence of the EPO gene to enhance transcription and promote EPO production. It has been confirmed in mammals such as rodents, monkeys, and humans that stabilization of HIF based on PHD inhibition promotes EPO production and increases erythrocytes with increasing EPO concentration.
  • EPO production promoter by PHD inhibition Has been shown to be useful as a therapeutic agent for anemia (Patent Documents 1, 2, 3 and Non-Patent Documents 5, 6).
  • EPO production decreases in the kidney due to kidney damage or the like
  • the EPO concentration in the blood decreases
  • red blood cell production is suppressed
  • anemia renal anemia
  • acute kidney diseases such as renal failure
  • renal anemia with a high probability
  • anemia resulting from a decrease in EPO production is also known regardless of kidney damage or the like.
  • the main treatments for these diseases include anemia treatment in patients with chronic kidney disease (CKD) using genetically modified human EPO preparation (hereinafter referred to as EPO preparation), treatment of self-accumulation and premature infant anemia, AIDS and chemistry. Treatment of anemia for cancer patients undergoing therapy is known.
  • EPO preparation genetically modified human EPO preparation
  • ischemic heart disease such as angina pectoris, myocardial infarction
  • ischemic cerebrovascular disorder cerebral embolism, cerebral infarction, etc.
  • ischemic kidney disease such as ischemic renal failure
  • Ischemic diseases such as lower limb ischemia (obstructive arteriosclerosis, Buerger's disease, diabetic gangrene, etc.), ischemic enteritis (such as ischemic colitis), and metabolic diseases such as fatty liver are also low in the target organ or tissue. Under the oxygen environment, stabilization of HIF based on PHD inhibition is expected to have a preventive or therapeutic effect on these diseases (Non-patent Documents 7 and 8).
  • the above-mentioned EPO preparation has drastically reduced the number of patients who require regular blood transfusion, has improved various symptoms associated with anemia, and has greatly contributed to the improvement of QOL (Quality of life) of anemia patients.
  • the EPO preparation is a glycoprotein, the structure of the sugar chain attached to the EPO surface is complex, and its glycosylation is extensive and diverse. It was difficult to produce human serum EPO with good reproducibility.
  • it since it is a biologic, it is expensive, and it is a burden on the patient from the viewpoint of medical costs.
  • the route of administration is injection, a method and / or compound for increasing endogenous EPO that can be administered orally is also desired from the viewpoint of preventing medical accidents and reducing patient burden.
  • Patent Document 1 triazolopyridine derivatives
  • Patent Documents 4 and 5 pyrimidine derivatives
  • isoquinoline derivatives Patent Documents 3 and 6
  • bicyclic pyridine derivatives Patent Document 7)
  • Bicyclic heteroaromatic N-substituted glycine derivatives Patent Document 8 and the like have been developed.
  • JP 2011-37841 A JP 2006-137763 A Special table 2008-546644 JP2011-88840 Special table 2009-541351 JP2011-148810A Special table 2009-541486 Special table 2009-537558
  • An object of the present invention is to provide a novel compound having an EPO production promoting action, and is useful for the prevention or treatment of a symptom of a disease in which a hypoxic environment occurs in a target organ or tissue, particularly for the prevention or treatment of anemia. Providing a good medicine.
  • the present invention provides the following [1] to [10].
  • X represents an oxygen atom, an imino group, a sulfur atom, sulfinyl or sulfonyl
  • R 1 , R 2 and R 3 each independently represents a hydrogen atom or a C 1 -C 6 alkyl group
  • R 4 represents a hydrogen atom, a C 1 -C 6 alkyl group or an arylalkyl group
  • R 5 is an alkyl group which may be substituted with a group selected from the substituent group, an alkenyl group which may be substituted with a group selected from the substituent group, or a group selected from the substituent group.
  • the substituent group includes an aryl group which may have 1 to 7 substituents (the substituent on the aryl group includes a C 1 -C 6 alkyl group, a trifluoromethyl group, a halogen atom, a methoxy group, A heteromethoxy group which may have 1 to 7 substituents (the substituent on the heteroaryl group includes a C 1 -C 6 alkyl group, trifluoro; Methyl group, halogen atom, methoxy group, trifluoromethoxy group, cyano group or phenyl group), C 1 -C 6 alkyl group (in the case of C 3 -C 6 alkyl group, carbon atoms are bonded to each other) A 3- to 6-membered saturated ring may
  • a pharmaceutical composition comprising the compound according to [1] or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • a medicament comprising the compound according to [1] above or a pharmaceutically acceptable salt thereof as an active ingredient.
  • An EPO production promoter comprising the compound according to [1] or a pharmaceutically acceptable salt thereof as an active ingredient.
  • a method for promoting EPO production comprising administering the compound according to [1] or a pharmaceutically acceptable salt thereof.
  • anemia self-blood storage, premature infant anemia, AIDS or cancer receiving chemotherapy in a patient with chronic renal failure, characterized by administering the compound according to [1] or a pharmaceutically acceptable salt thereof
  • a method for preventing and / or treating anemia selected from patient anemia, chronic anemia, iron deficiency anemia, aplastic anemia, hemolytic anemia and megaloblastic anemia.
  • the compound of the present invention Since the compound of the present invention has a sustained and superior EPO production promoting effect than the compound described in Patent Document 1, it has undergone anemia, self-accumulation and premature infant anemia, AIDS and chemotherapy in patients with chronic renal failure. It is useful as a prophylactic and / or therapeutic agent for anemia such as anemia, chronic anemia, iron deficiency anemia, aplastic anemia, hemolytic anemia, megaloblastic anemia in cancer patients.
  • alkyl group means a saturated hydrocarbon chain that may be linear, branched, cyclic, or a combination thereof.
  • a C 1 -C 18 linear or branched alkyl group, a C 3 -C 18 cyclic alkyl group, or a combination thereof is preferred, and a C 1 -C 4 linear or branched alkyl group, C 3 A —C 12 cyclic alkyl group or a combination thereof is more preferred.
  • alkenyl group means an unsaturated hydrocarbon chain having a double bond, which may be linear, branched, cyclic, or a combination thereof.
  • n-propenyl, n-butenyl, n-pentenyl, n-hexenyl, n-heptenyl, n-octenyl and the like can be mentioned.
  • a C 2 -C 18 linear or branched alkenyl group is preferable, and a C 2 -C 14 linear or branched alkenyl group is more preferable.
  • alkynyl group described in the present specification means an unsaturated hydrocarbon chain having a triple bond which may be linear, branched, cyclic, or a combination thereof.
  • n-pentynyl, n-hexynyl and the like can be mentioned.
  • a C 2 -C 8 linear or branched alkynyl group is preferred.
  • the “aryl group” described in the present specification is a monocyclic, bicyclic or tricyclic aryl group, and includes an aryl group in which some of the rings have an aromatic ring.
  • a monocyclic, bicyclic or tricyclic aryl group having 6 to 14 carbon atoms is used.
  • Specific examples include phenyl group, naphthyl group, tetrahydronaphthyl group, indenyl group, indanyl group, phenanthrenyl group, fluorenyl group and the like.
  • heteroaryl group is a monocyclic, bicyclic or tricyclic heteroaryl group, for example, a monocyclic ring having 1 to 4 heteroatoms (nitrogen atom, oxygen atom or sulfur atom) , Bicyclic or tricyclic heteroaryl groups.
  • Specific examples include pyrrolyl, furanyl, thienyl, pyridyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, pyrazyl, quinolyl, isoquinolyl, quinazolyl, indolyl, benzothiophenyl, benzofuranyl.
  • benzoimidazolyl group benzoxazolyl group, benzothiazolyl group, benzodioxanyl group, dibenzothiophenyl group, dibenzofuranyl group, carbazolyl group and the like.
  • the substituent group includes an aryl group which may have 1 to 7 substituents (the substituent on the aryl group includes a C 1 -C 6 alkyl group, a halogen atom, a methoxy group, A heteromethoxy group optionally having 1 to 7 substituents (a substituent on the heteroaryl group includes a C 1 -C 6 alkyl group, a halogen atom) , A methoxy group, a trifluoromethoxy group, a cyano group and a phenyl group), a C 1 -C 6 alkyl group (in the case of a C 3 -C 6 alkyl group, carbon atoms are bonded to each other to form a 3- to 6-membered saturated group) A C 2 -C 6 alkenyl group, a C 2 -C 6 alkynyl group, an arylalkyl group, a C 2 -C 6 alkoxycarbonyl group, a halogen atom
  • X is preferably an oxygen atom, a sulfur atom, sulfinyl or sulfonyl, more preferably an oxygen atom or a sulfur atom.
  • R 1 , R 2 and R 3 each independently represent a hydrogen atom or a C 1 -C 6 alkyl group, and among these, a hydrogen atom is more preferred.
  • C 1 -C 6 alkyl group means a saturated hydrocarbon chain that may be linear, branched, cyclic, or a combination thereof. Preferably, it is a C 1 -C 6 linear or branched alkyl group or a C 3 -C 6 cyclic alkyl group.
  • Specific examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.
  • R 4 represents a hydrogen atom, a C 1 -C 6 alkyl group or an arylalkyl group, and more preferably a hydrogen atom.
  • the “arylalkyl group” is a group in which a C 1 -C 6 alkyl group is bonded to the aryl group, and examples thereof include a C 6 -C 14 aryl-C 1 -C 6 alkyl group. Specifically, a phenyl-C 1 -C 6 alkyl group is preferable, and a benzyl group and a phenethyl group are more preferable.
  • Examples of the alkyl group, alkenyl group, aryl group or heteroaryl group represented by R 5 include a C 1 -C 18 linear or branched alkyl group, a C 3 -C 8 cyclic alkyl group, or a combination thereof.
  • Monocyclic, bicyclic or tricyclic heteroaryl groups having 1 heteroatom (nitrogen atom, oxygen atom or sulfur atom) are preferred.
  • the substituent group which can be substituted with 1 to 7 substituents for R 5 includes a monocyclic, bicyclic or tricyclic aryl group having 6 to 14 carbon atoms which may have 1 to 7 substitutions (on the aryl group).
  • the substituent is a C 1 -C 6 alkyl group, a trifluoromethyl group, a halogen atom, a methoxy group, a trifluoromethoxy group, a cyano group or a phenyl group) and may have 1 to 7 substituents.
  • halogen atom examples include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • aryl group examples include phenyl, naphthyl, tetrahydronaphthyl, indanyl, phenanthrenyl, fluorenyl and the like.
  • C 1 -C 6 alkyl group examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, n-hexyl, cyclopropyl, And cyclobutyl, cyclopentyl, cyclohexyl and the like.
  • heteroaryl group examples include pyrrolyl, furanyl, thiophenyl, pyridyl, quinolyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, benzothiazolyl, pyrazyl, benzodioxanyl and the like.
  • alkenyl group examples include vinyl, propenyl, butenyl and the like.
  • C 2 -C 6 alkynyl group examples include ethynyl, propynyl, pentynyl and the like.
  • arylalkyl group examples include benzyl.
  • Examples of the “C 2 -C 6 alkoxycarbonyl group” include methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl and the like.
  • Examples of the “C 1 -C 6 halogenated alkyl group” include trifluoromethyl, trifluoroethyl and the like.
  • Examples of the “C 1 -C 6 alkoxy group” include methoxy, ethoxy, isopropoxy, t-butoxy and the like.
  • Examples of the “C 1 -C 6 halogenated alkoxy group” include trifluoromethoxy, trifluoroethoxy and the like.
  • Examples of the “aryloxy group, carbamoyl group” include phenoxy, t-butoxycarbamoyl, benzylcarbamoyl and the like.
  • Examples of the “C 2 -C 6 alkylcarbonyl group” include methylcarbonyl and the like.
  • Examples of the “C 1 -C 6 alkylamino group” include dimethylamino, benzylamino and the like.
  • Examples of the “C 1 -C 6 alkylaminocarbonyl group” include dimethylaminocarbonyl and the like.
  • Examples of the “C 1 -C 6 alkylcarbonylamino group” include acetylamino and the like.
  • Examples of the “arylamino group” include phenylamino, diphenylamino and the like.
  • Examples of the “C 1 -C 6 alkylsulfonyl group” include methanesulfonyl and the like.
  • Examples of the “C 1 -C 6 halogenated alkylsulfonyl group” include trifluoromethanesulfonyl and the like.
  • Examples of the “arylsulfonyl group” include phenylsulfonyl and the like.
  • Examples of the “C 1 -C 6 alkylsulfanyl group” include methylsulfanyl, isopropylsulfanyl and the like.
  • C 1 -C 6 halogenated alkylsulfanyl group examples include trifluoromethanesulfanyl and the like.
  • arylsulfanyl group examples include phenylsulfanyl and the like.
  • a preferred embodiment of the general formula (1) is a compound comprising a combination of each of the above-mentioned preferred groups.
  • the compounds described in the examples, their pharmaceutically acceptable salts, or their hydrates, or solvents Japanese products are listed.
  • the compound of the present invention represented by the general formula (1) or a pharmaceutically acceptable salt, hydrate, or solvate thereof is a geometric isomer or tautomer based on a double bond depending on the type of substituent.
  • optical isomers and diastereomers may exist due to the presence of an asymmetric carbon atom.
  • all isolated isomers or mixtures thereof are included.
  • the production method of the compound of the present invention and pharmaceutically acceptable salts, hydrates and solvates can be produced by various known techniques.
  • the functional group is replaced with an appropriate protective group at the stage of the raw material or intermediate, which is effective in terms of production technology.
  • functional groups include amino groups, hydroxy groups, and carboxy groups.
  • the desired compound can be obtained by removing the protecting group at the appropriate time in each production stage.
  • protective group types and desorption methods include the methods described in Protective Groups In Organic Synthesis: Third Edition (by Greene, Wuts).
  • representative production methods of the compound (1) of the present invention will be described.
  • the production method of the compound of the present invention is not particularly limited, and can be produced, for example, according to the following production method.
  • Y represents a protecting group for a carboxyl group such as a methyl group or a tert-butyl group, and other symbols are as defined above.
  • a compound (3) can be obtained by introduce
  • X is S
  • the compound (2) is heated under a palladium catalyst such as palladium acetate, tris (dibenzylideneacetone) dipalladium, xanthophos, 1,1-bis (di-tert-butylphosphino) ferrocene under heating conditions.
  • a palladium catalyst such as palladium acetate, tris (dibenzylideneacetone) dipalladium, xanthophos, 1,1-bis (di-tert-butylphosphino) ferrocene under heating conditions.
  • a ligand such as bis [2- (diphenylphosphino) phenyl] ether
  • a base such as diisopropylethylamine, potassium carbonate, cesium carbonate, sodium carbonate, potassium phosphate, potassium t-butoxide
  • Compound (3) can be obtained by reacting with thiol (R 5 SH) in a solvent such as N, N-dimethylformamide, toluene, cyclopentyl methyl ether and the like.
  • the compound (2) is subjected to a copper catalyst such as copper iodide, copper bromide, copper chloride, copper oxide, ethyl 2-cyclohexanone carboxylate, 1,10-phenanthroline under low temperature to warming conditions. , Dimethyl sulfoxide, N, N-dimethylformamide, acetonitrile, 1,4-dioxane, toluene, etc. in the presence of a ligand such as (2-pyridyl) acetone and picolinic acid and a base such as potassium carbonate, cesium carbonate and potassium phosphate
  • a ligand such as (2-pyridyl) acetone and picolinic acid
  • a base such as potassium carbonate, cesium carbonate and potassium phosphate
  • the compound (3) can be obtained by reacting with phenol (R 5 OH) in the solvent.
  • Second step Compound (4) can be obtained by deprotecting the t-butoxycarbonyl group of compound (3) according to a conventional method.
  • the compound (3) is hexane, chloroform, methylene chloride, ethyl acetate, toluene, 1,2-dimethoxyethane, 1,4-dioxane, tetrahydrofuran, methanol, ethanol, 2-propanol, dimethyl under low temperature to warming conditions.
  • Compound (4) can be obtained by reacting with an acid such as aluminum trichloride, hydrogen chloride, hydrogen bromide, phosphoric acid, sulfuric acid, acetic acid or trifluoroacetic acid.
  • Compound (4) can be obtained by reacting with a base such as sodium hydroxide, potassium hydroxide or lithium hydroxide in a mixed solvent.
  • Compound (5) can be obtained by condensing compound (4) with a glycine derivative represented by H 2 NCH 2 COOY according to a conventional method.
  • the compound (4) is subjected to dicyclohexylcarbodiimide, 1,1′-carbonyldiimidazole in a solvent such as N, N-dimethylformamide, acetonitrile, tetrahydrofuran, chloroform, ethyl acetate, methylene chloride, toluene and the like under low temperature to warming conditions.
  • a condensing agent such as diphenylphosphoryl azide and optionally N-hydroxysuccinimide, 1-hydroxybenzotriazole, dimethylaminopyridine and the like
  • potassium carbonate if desired, sodium bicarbonate, cesium carbonate
  • triethylamine, diisopropylethylamine, morpholine a base such as
  • Compound (1) can be obtained by deprotecting the protecting group for the benzyl group and carboxyl group of compound (5) according to a conventional method.
  • Y is a methyl group
  • the compound (5) is reacted in an acid solvent such as trifluoroacetic acid under heating conditions in the presence of anisole, thioanisole, dimethyl sulfide, etc.
  • the group can be deprotected.
  • the compound (5) is heated at room temperature to warming, in a hydrogen atmosphere, at normal pressure to under pressure, hexane, methanol, ethanol, 2-propanol, tetrahydrofuran, N, N-dimethylformamide, N, N-dimethyl.
  • a catalyst such as palladium carbon, palladium hydroxide, platinum oxide, platinum carbon, Raney nickel in a single or mixed solvent such as acetamide, ethyl acetate, acetic acid, water, etc.
  • a mixed solvent of water and a solvent such as methanol, ethanol, 2-propanol, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N, N-dimethylformamide, acetonitrile under low temperature to warming conditions
  • the compound (1) can be obtained by reacting with a base such as sodium hydroxide, potassium hydroxide or lithium hydroxide.
  • First step When X is S, compound (2) can be reacted with sodium sulfide or the like in a solvent such as N, N-dimethylformamide under low temperature to warming conditions to obtain compound (6). it can.
  • X When X is O, the compound (2) is reacted with a sodium hydroxide aqueous solution, a potassium hydroxide aqueous solution or the like in a solvent such as diethylene glycol monoethyl ether under low temperature to warming conditions to obtain the compound (6).
  • a solvent such as N, N-dimethylformamide
  • Second Step When X is S and O, compound (6) is mixed with azodicarboxylic acid ester such as diethyl azodicarboxylate or diisopropyl azodicarboxylate, triphenylphosphine, alcohol (R 5 OH) in a solvent such as tetrahydrofuran or toluene. ) Can be reacted to give compound (3).
  • azodicarboxylic acid ester such as diethyl azodicarboxylate or diisopropyl azodicarboxylate, triphenylphosphine, alcohol (R 5 OH)
  • R 5 OH a solvent
  • the compound (6) is subjected to low temperature to warming conditions such as triethylamine, diisopropylethylamine, potassium carbonate, cesium carbonate, sodium carbonate, potassium phosphate, potassium t-butoxide, sodium hydride and the like.
  • the type of the salt is not particularly limited as long as it is a pharmaceutically acceptable salt.
  • Examples of the pharmaceutically acceptable hydrate of the compound of the general formula (1) include 1/2 hydrate, monohydrate, dihydrate and the like. Moreover, since the compound of General formula (1) may exist as a solvate, a solvate is also included.
  • the compound represented by the general formula (1) of the present invention produced as described above is in a free state or as a salt thereof, which is extraction, concentration, distillation, crystallization, filtration, recrystallization, which is a normal chemical operation. It can be isolated and purified by various chromatographies.
  • compound (1) contains an optical isomer, a stereoisomer, or a regioisomer, each can be isolated by a fractional recrystallization method, a chiral column method, a diastereomer method, or the like.
  • anemia self-blood storage, premature infant anemia in patients with chronic renal failure
  • anemia such as anemia, chronic anemia, iron deficiency anemia, aplastic anemia, hemolytic anemia, megaloblastic anemia, etc. in cancer patients undergoing chemotherapy It is.
  • a pharmaceutical composition comprising a compound represented by the general formula (1) or a pharmaceutically acceptable salt, hydrate or solvate thereof is carried out in the form of tablets, pills, capsules, granules, powders, liquids Oral administration, etc., or intravenous, intramuscular injections, suppositories, eye drops, eye ointments, transdermal solutions, ointments, transdermal patches, transmucosal solutions, transmucosal patches, inhalation Any form of parenteral administration by an agent or the like may be used.
  • the kind of additive for the preparation is pharmaceutically acceptable
  • the carrier is not particularly limited as long as it is a carrier, excipient, lubricant, coating agent, sugar coating, wetting agent, binder, disintegrant, solvent, solubilizer, solubilizer, solubilizer, Suspending agents, dispersing agents, emulsifiers, surfactants, tonicity agents, buffers, pH regulators, soothing agents, preservatives, preservatives, stabilizers, antioxidants, coloring agents, sweeteners, etc. It can be used alone or in appropriate combination.
  • the dose and frequency of administration of the compound of the present invention or the pharmaceutical composition containing the compound can be appropriately selected according to symptoms, age, sex, dosage form, type of concomitant drug, etc., but usually 0.1 to 1000 mg / day / person
  • the dose can be administered in the range of 1 to 500 mg / day / person once a day or divided into several times.
  • the pharmaceutical composition of the present invention may be used not only alone but also in combination with other drugs having the same drug effect and / or other drugs having another drug effect.
  • NMR showed a 270 MHz nuclear magnetic resonance spectrum
  • TMS tetramethylsilane
  • MS showed mass spectrometry
  • ESI electrospray ionization method
  • Reference Example 1 7-benzyloxy-5-phenylsulfanyl [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester benzenethiol (54 mg), 7-benzyloxy-5 -Iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg), tris (dibenzylideneacetone) dipalladium (10 mg), xanthophos (13 mg), N, N-diisopropylethylamine (120 mg) was mixed in a dioxane solvent (2.0 mL), and heated and stirred at 100 ° C.
  • Reference Example 2 7-Benzyloxy-5-phenylsulfanyl [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid
  • the compound (484 mg) obtained in Reference Example 1 was dissolved in toluene (3. 8 mL) and ethyl acetate (1.2 mL) were dissolved, and methanesulfonic acid (429 mg) dissolved in ethyl acetate (0.5 mL) was added over 10 minutes at room temperature. After stirring at room temperature for 3 hours, the precipitated crystals were collected by filtration.
  • Example 1 Methyl [(7-benzyloxy-5-phenylsulfanyl [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetate
  • Compound (309 mg) obtained in Reference Example 2 ) was dissolved in DMF (3.0 mL), and glycine methyl ester hydrochloride (113 mg), 1-hydroxybenzotriazole (138 mg) and triethylamine (99 mg) were added at room temperature.
  • To this mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (173 mg), and the mixture was stirred overnight at room temperature.
  • Example 2 Methyl [(7-hydroxy-5-phenylsulfanyl [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetate
  • Example 3 [(7-Hydroxy-5-phenylsulfanyl [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid
  • the compound (210 mg) obtained in Example 2 was obtained.
  • the suspension was suspended in isopropyl alcohol (4.0 mL), 4 M aqueous lithium hydroxide solution (0.6 mL) was added, and the mixture was heated with stirring at 70 ° C. for 2 hours. After completion of the reaction, the reaction solution was neutralized with 6M hydrochloric acid (0.4 mL) and stirred while gradually cooling. When crystals began to precipitate, water (2.0 mL) was added and collected by filtration to obtain the title compound (189 mg).
  • Reference example 3 ⁇ [7-benzyloxy-5- (3,4-dichlorophenoxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester copper bromide ( 14 mg), ethyl 2-cyclohexanonecarboxylate (36 mg) and cesium carbonate (684 mg) were mixed in DMSO (3 mL) and stirred at room temperature for 30 minutes. 3,4-Dichlorophenol (99 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (452 mg) were added to DMSO (5 mL).
  • Example 4 ⁇ [7-Benzyloxy-5- (3,4-dichlorophenoxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid t-butyl ester Reference The compound (377 mg) obtained in Example 3 was converted to a carboxylic acid in the same manner as in Reference Example 2, and then the title compound (183 mg) was obtained in the same manner as in Example 1 using glycine t-butyl ester hydrochloride. .
  • Example 5 ⁇ [5- (3,4-Dichlorophenoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid obtained in Example 4
  • the compound (183 mg) was dissolved in trifluoroacetic acid (2 mL), thioanisole (83 mg) was added, and the mixture was stirred at 80 ° C. for 2 hr.
  • the solvent was distilled off under reduced pressure, and methanol (0.5 mL) and water (2 mL) were added.
  • Example 6 ⁇ [5- (3,5-Dimethylphenylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3,5-dimethyl Benzenethiol (182 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (500 mg) were used in Reference Example 1 and Example 4. In the same manner as in 5, the title compound (160 mg) was obtained.
  • Example 7 ⁇ [5- (2,3-Dimethylphenylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2,3-dimethyl Benzenethiol (138 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (226 mg) were used in Reference Example 1 and Example 4. In the same manner as in 5, the title compound (55 mg) was obtained.
  • Example 8 ⁇ [5- (3-Fluorophenylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3-fluorobenzenethiol (62 mg ) And 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg), Reference Examples 1, 2, and Examples 1-3 In the same manner as the above, the title compound (160 mg) was obtained.
  • Example 9 ⁇ [5- (3,5-Difluorophenylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3,5-difluoro Reference Examples 1 and 2 were carried out using benzenethiol (65 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg). In the same manner as in Examples 1 to 3, the title compound (85 mg) was obtained.
  • Example 10 ⁇ [5- (3,4-Difluorophenylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3,4-difluoro Benzenethiol (77 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) were used in Reference Example 1 and Example 4. In the same manner as in 5, the title compound (55 mg) was obtained.
  • Example 11 ⁇ [5- (3,5-Dichlorophenylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3,5-dichlorobenzene Thiol (83 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (199 mg) were used as Reference Examples 1, 2, and Examples. The title compound (112 mg) was obtained in the same manner as in 1-3.
  • Example 12 ⁇ [7-Hydroxy-5- (4-trifluoromethoxyphenylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 4-trifluoromethoxy Reference Examples 1, 2 were carried out using benzenethiol (86 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg). In the same manner as in Examples 1 to 3, the title compound (107 mg) was obtained.
  • Example 13 ⁇ [5- (biphenyl-3-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3-phenylbenzenethiol ( 104 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg). In the same manner as in 3, the title compound (99 mg) was obtained.
  • Example 14 ⁇ [5- (2-Chloro-5-fluorophenylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-chloro Reference Example 1 was prepared using -5-fluorobenzenethiol (93 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (226 mg). 2, In the same manner as in Examples 1 to 3, the title compound (72 mg) was obtained.
  • Example 15 ⁇ [5- (3-Chloro-5-fluorophenylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3-chloro Reference Example 1 -5-fluorobenzenethiol (85 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) 2. In the same manner as in Examples 1 to 3, the title compound (30 mg) was obtained.
  • Example 16 ⁇ [5- (3-Chloro-5-methylphenylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3-chloro Reference Example 1 -5-methylbenzenethiol (85 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) 2. In the same manner as in Examples 1 to 3, the title compound (104 mg) was obtained.
  • Example 17 ⁇ [5- (3-Fluoro-5-methylphenylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3-fluoro Reference Example 1 using -5-methylbenzenethiol (71 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (201 mg) 2, In the same manner as in Examples 1 to 3, the title compound (103 mg) was obtained.
  • Example 18 ⁇ [5- (3-Fluoro-5-trifluoromethylphenylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3 -Fluoro-5- (trifluoromethyl) benzenethiol (72 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester ( 166 mg) in the same manner as in Reference Examples 1 and 2 and Examples 1 to 3, to obtain the title compound (87 mg).
  • Example 19 ( ⁇ 5- [3-Chloro-5- (trifluoromethyl) phenylsulfanyl] -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl ⁇ amino) Acetic acid
  • the title compound (48 mg) was obtained.
  • Example 20 ⁇ [5- (2,3-Dimethylphenoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2,3-dimethylphenol (119 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (400 mg), Reference Example 3, Example 4 In the same manner as in 5, the title compound (125 mg) was obtained.
  • Example 21 ⁇ [5- (3,5-dichlorophenoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3,5-dichlorophenol Reference Example 3, Example 4 using (72 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (238 mg). In the same manner as in 5, the title compound (42 mg) was obtained.
  • Example 22 ⁇ [5- (biphenyl-3-yloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3-phenylphenol (135 mg) And 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (300 mg) as in Reference Example 3, Examples 4 and 5. To give the title compound (75 mg).
  • Example 23 ⁇ [5- (3-Chloro-4-fluorophenoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3-chloro- Reference Example 3 was carried out using 4-fluorophenol (110 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (226 mg). In the same manner as in Examples 4 and 5, the title compound (90 mg) was obtained.
  • Example 24 ⁇ [5- (4-Chloro-2-methylphenoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 4-chloro- Reference Example 3 using 2-methylphenol (113 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (300 mg) In the same manner as in Examples 4 and 5, the title compound (30 mg) was obtained.
  • Example 25 ⁇ [5- (4-Fluoro-3-trifluoromethylphenoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 4- Using fluoro-3-trifluoromethylphenol (144 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (300 mg) In the same manner as in Reference Example 3 and Examples 4 and 5, the title compound (86 mg) was obtained.
  • Example 26 ⁇ [7-hydroxy-5- (naphthalen-1-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 1-naphthalenethiol (99 mg ) And 7-benzyloxy-5-iodo [1,2,4] triazolo “1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg), Reference Examples 1, 2, and Examples 1-3 In the same manner as the above, the title compound (31 mg) was obtained.
  • Example 27 ⁇ [5- (4-Chloronaphthalen-1-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 4-chloro Reference Example 4 was conducted using 1-naphthol (730 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo “1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (304 mg). In the same manner as in Example 19, the title compound (50 mg) was obtained.
  • Example 28 ⁇ [7-Hydroxy-5- (naphthalen-1-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 1-naphthol (192 mg) and 7-Benzyloxy-5-iodo [1,2,4] triazolo “1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) was prepared in the same manner as in Reference Example 3 and Examples 4 and 5. To give the title compound (86 mg).
  • Example 29 ⁇ [7-Hydroxy-5- (5,6,7,8-tetrahydronaphthalen-1-ylsulfanyl) [1,2,4] -triazolo [1,5- ⁇ ] pyridine-8-carbonyl Amino ⁇ acetic acid 5,6,7,8-tetrahydronaphthalene-1-thiol (220 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carvone The title compound (215 mg) was obtained using acid t-butyl ester (500 mg) in the same manner as in Reference Examples 1 and 2 and Examples 1 to 3.
  • Example 30 ⁇ [7-Hydroxy-5- (indan-4-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid
  • Reference Example 7 Reference example of synthesized indan-4-thiol (100 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (250 mg) 1, 2
  • the title compound (74 mg) was obtained.
  • Example 31 ⁇ [7-Hydroxy-5- (7-trifluoromethylquinolin-4-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridin-8-carbonyl] amino ⁇ acetic acid 7 -Trifluoromethylquinoline-4-thiophenol (183 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (300 mg) In the same manner as in Reference Example 1 and Example 4, the title compound (59 mg) was obtained.
  • Reference Example 5 Bis (4-isoquinoline) disulfide 4-bromoisoquinoline (504 mg), 2-ethylhexyl 3-mercaptopropionate (532 mg), tris (dibenzylideneacetone) dipalladium (43 mg), xanthophos (55 mg), N, N-diisopropylethylamine (0.85 mL) was mixed in a dioxane solvent (2.5 mL), and heated and stirred at 100 ° C. for 3.5 hours under an argon atmosphere. After completion of the reaction, insoluble materials were removed by filtration, and the solvent was distilled off under reduced pressure.
  • Example 32 ⁇ [7-Hydroxy-5- (isoquinolin-4-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid obtained in Reference Example 6
  • the title compound (168 mg) was obtained in the same manner as in Reference Example 2 and Examples 1 to 3 using the compound (297 mg).
  • Reference Example 8 Bis (5-fluoro-1,2,3-trimethyl-1H-indol-7-yl) disulfide Dissolve the compound (310 mg) obtained in Reference Example 7 in N, N-dimethylformamide (3 mL) Under ice-cooling, sodium hydride (60%, 77 mg) and methyl iodide (96 ⁇ L) were added, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate.
  • Example 33 ⁇ [5- (5-Fluoro-1,2,3-trimethyl-1H-indol-7-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine -8-Carbonyl] amino ⁇ acetic acid
  • the compound (436 mg) obtained in Reference Example 8 and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t -Butyl ester (521 mg) was obtained in the same manner as in Reference Example 6 and Example 32 to obtain the title compound (230 mg).
  • Example 34 ⁇ [7-Hydroxy-5- (thiophen-2-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-thiophenethiol (116 mg ) And 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (421 mg), Reference Examples 1, 2, and Examples 1-3 In the same manner as the above, the title compound (194 mg) was obtained.
  • Example 35 ⁇ [5- (5-chlorothiophen-2-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 5-chloro Thiophene-2-thiol (117 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (181 mg) were used in Reference Example 1, 2. The title compound (79 mg) was obtained in the same manner as in Examples 1 to 3.
  • Example 36 ⁇ [5- (Benzo [b] thiophen-3-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid Benzo [ b] Thiophene-3-thiol (89 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (201 mg) 1, 2 In the same manner as in Examples 1 to 3, the title compound (109 mg) was obtained.
  • Example 37 ⁇ [5- (Benzo [b] thiophen-4-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid Benzo [ b] Thiophene-4-thiol (76 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (188 mg) 1, 2 In the same manner as in Examples 1 to 3, the title compound (90 mg) was obtained.
  • Example 38 ⁇ [7-hydroxy-5- (2-methylfuran-3-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-methyl Furan-3-thiol (75 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo “1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) were used in Reference Example 1, 2. In the same manner as in Examples 1 to 3, the title compound (48 mg) was obtained.
  • Example 39 ⁇ [5- (5-Chloronaphthalen-1-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 5-chloro Reference Example 4 was carried out using 1-naphthol (168 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (250 mg). In the same manner as in Example 19, the title compound (128 mg) was obtained.
  • Example 40 ⁇ [5- (6-Chloronaphthalen-1-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 6-chloro Reference Example 4 was carried out using 1-naphthol (120 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (250 mg). In the same manner as in Example 19, the title compound (109 mg) was obtained.
  • Example 41 ⁇ [5- (5-Chloronaphthalen-1-yloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 5-chloro- Reference Example 3, Example 1-naphthol (388 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (400 mg) In the same manner as in 4 and 5, the title compound (75 mg) was obtained.
  • Example 42 ⁇ [7-Hydroxy-5- (8-trifluoromethylquinolin-4-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 4 -Hydroxy-8-trifluoromethylquinoline (739 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (180 mg) In the same manner as in Reference Example 4 and Example 19, the title compound (140 mg) was obtained.
  • Example 43 ⁇ [5- (Dibenzothiophen-4-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid dibenzothiophene-4- All (165 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (379 mg) were used as Reference Example 4, Example 19 and In the same manner, the title compound (73 mg) was obtained.
  • Example 44 ⁇ [5-hydroxy-5- (1-trifluoromethylisoquinolin-5-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 1 Using trifluoromethyl-5-hydroxyisoquinoline (183 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (300 mg) In the same manner as in Reference Example 3 and Examples 4 and 5, the title compound (58 mg) was obtained.
  • Example 45 [7-Hydroxy-5- (5-trifluoromethylnaphthalen-1-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 5- See trifluoromethylnaphthalene-1-thiol (219 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (433 mg) In the same manner as in Examples 1, 2, and Examples 4, 5, the title compound (195 mg) was obtained.
  • Example 46 [7-hydroxy-5- (5-methylnaphthalen-1-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 5-methylnaphthalene See 1-thiol (0.58 g) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (1.6 g) In the same manner as in Examples 1 and 2, and Examples 4 and 5, the title compound (141 mg) was obtained.
  • Example 47 [[5- (5-Cyanonaphthalen-1-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 5-cyano Reference examples: naphthalen-1-ol (2 g) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (1.2 g) 4. In the same manner as in Example 19, the title compound (199 mg) was obtained.
  • Example 48 ⁇ [7-Hydroxy-5- (6-trifluoromethylnaphthalen-1-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 6 -Trifluoromethylnaphthalene-1-thiol (603 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo “1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (300 mg) In the same manner as in Reference Example 1 and Examples 4 and 5, the title compound (150 mg) was obtained.
  • Example 49 ⁇ [7-Hydroxy-5- (7-trifluoromethylnaphthalen-1-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 7 -Trifluoromethylnaphthalene-1-thiol (603.6 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo “1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (300 mg) The title compound (198 mg) was obtained in the same manner as in Reference Example 1, Examples 4 and 5.
  • Example 50 ⁇ [7-Hydroxy-5- (5-trifluoromethylnaphthalen-1-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 5- See trifluoromethylnaphthalen-1-ol (80 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (208 mg) In the same manner as in Example 9 and Examples 4 and 5, the title compound (68 mg) was obtained.
  • Example 51 ⁇ [7-Hydroxy-5- (5-methoxynaphthalen-1-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 5-methoxynaphthalene
  • Reference Example 9 was carried out using 1-ol (106 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (329 mg). In the same manner as in Examples 4 and 5, the title compound (45 mg) was obtained.
  • Example 52 ⁇ [7-hydroxy-5- (5-methylnaphthalen-1-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 5-methylnaphthalene
  • Reference Example 9 was carried out using 1-ol (146 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (487 mg). In the same manner as in Examples 4 and 5, the title compound (50 mg) was obtained.
  • Example 53 ⁇ [7-hydroxy-5- (6-methylnaphthalen-1-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 6-methylnaphthalene
  • Reference Example 9 was carried out using 1-ol (100 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (316 mg). In the same manner as in Examples 4 and 5, the title compound (97 mg) was obtained.
  • Example 54 ⁇ [7-hydroxy-5- (6-trifluoromethylnaphthalen-1-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 6- Using trifluoromethylnaphthalen-1-ol (189 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (400 mg) In the same manner as in Reference Example 3 and Examples 4 and 5, the title compound (98 mg) was obtained.
  • Example 55 ⁇ [5- (6-Chloronaphthalen-1-yloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 6-chloronaphthalene
  • Reference Example 3 using 1-ol (121 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (300 mg) In the same manner as in Examples 4 and 5, the title compound (73 mg) was obtained.
  • Example 56 ⁇ [7-Hydroxy-5- (8-trifluoromethylisoquinolin-4-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 8 Trifluoromethylisoquinoline-4-thiol (307 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (252 mg) The title compound (159 mg) was obtained in the same manner as in Reference Examples 2 and 3 and Examples 1 to 3.
  • Example 57 ⁇ [7-Hydroxy-5- (8-methylisoquinolin-4-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 8-methyl
  • isoquinoline-4-thiol 64 mg
  • Example 58 ⁇ [5- (8-Fluoroisoquinolin-4-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 8-fluoro Reference example using isoquinoline-4-thiol (70 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (202 mg) 1, In the same manner as in Examples 4 and 5, the title compound (24 mg) was obtained.
  • Example 59 ⁇ [5- (8-chloroisoquinolin-4-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 8-chloro Reference example using isoquinoline-4-thiol (152 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (404 mg) 1, In the same manner as in Examples 4 and 5, the title compound (125 mg) was obtained.
  • Example 60 ⁇ [7-Hydroxy-5- (7-trifluoromethylisoquinolin-4-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridin-8-carbonyl] amino ⁇ acetic acid 7 -Trifluoromethylisoquinoline-4-thiol (642 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (339 mg) In the same manner as in Reference Example 1 and Examples 4 and 5, the title compound (40 mg) was obtained.
  • Example 61 ⁇ [7-Hydroxy-5- (8-methylisoquinolin-4-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 8-methylisoquinoline Reference Example 2 using -4-ol (78 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) 3. In the same manner as in Examples 1 to 3, the title compound (25 mg) was obtained.
  • Example 62 ⁇ [5- (8-Fluoroisoquinolin-4-yloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 8-fluoroisoquinoline Reference Example 3 using -4-ol (152 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (420 mg) In the same manner as in Examples 4 and 5, the title compound (46 mg) was obtained.
  • Example 63 ⁇ [5- (8-Chloroisoquinolin-4-yloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 8-chloroisoquinoline Reference Example 3 using 4-ol (250 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (690 mg) In the same manner as in Examples 4 and 5, the title compound (90 mg) was obtained.
  • Example 64 ⁇ [5- (7-chloroquinolin-4-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 7-chloro Reference example using quinoline-4-thiol (120 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (300 mg) 3. In the same manner as in Examples 4 and 5, the title compound (55 mg) was obtained.
  • Example 65 ⁇ [7-hydroxy-5- (2-trifluoromethylquinazolin-5-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2 -Trifluoromethylquinazoline-5-thiol (155 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (334 mg) And the title compound (135 mg) was obtained in the same manner as in Reference Example 1, Examples 4 and 5.
  • Example 66 ⁇ [5- (2-Chlorobenzo [b] thiophen-4-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-chlorobenzo [b] thiophene-4-thiol (87 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (180 mg)
  • the title compound (92 mg) was obtained in the same manner as in Reference Examples 1 and 2 and Examples 1 to 3.
  • Example 67 ⁇ [7-Hydroxy-5- (2-trifluoromethylbenzo [b] thiophen-4-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] Amino ⁇ acetic acid 2-trifluoromethylbenzo [b] thiophene-4-thiol (186 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid The title compound (190 mg) was obtained using t-butyl ester (249 mg) in the same manner as in Reference Examples 1 and 2 and Examples 1 to 3.
  • Example 68 ⁇ [5- (Benzo [b] thiophen-4-yloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid Reference Example 9 The title compound (146 mg) was obtained in the same manner as in Reference Example 2 and Examples 1 to 3 using the compound obtained in step (220 mg).
  • Example 69 ⁇ [7-Hydroxy-5- (3-methylbenzo [b] thiophen-7-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3-methylbenzo [b] thiophene-7-thiol (108 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (213 mg)
  • the title compound (155 mg) was obtained in the same manner as in Reference Examples 1 and 2 and Examples 1 to 3.
  • Example 70 ⁇ [7-hydroxy-5- (3-trifluoromethylbenzo [b] thiophen-7-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] Amino ⁇ acetic acid 3-trifluoromethylbenzo [b] thiophene-7-thiol (404 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid The title compound (155 mg) was obtained using t-butyl ester (231 mg) in the same manner as in Reference Examples 1 and 2 and Examples 1 to 3.
  • Example 71 ⁇ [5- (Benzo [b] thiophen-7-yloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid Benzo [b ] Using thiophen-7-ol (110 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (255 mg) In the same manner as in Examples 9 and 2 and Examples 1 to 3, the title compound (91 mg) was obtained.
  • Example 72 ⁇ [7-hydroxy-5- (3-methylbenzo [b] thiophen-7-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3 -Methylbenzo [b] thiophen-7-ol (117 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (247 mg) In the same manner as in Reference Examples 9 and 2 and Examples 1 to 3, the title compound (105 mg) was obtained.
  • Example 73 ⁇ [7-Hydroxy-5- (3-trifluoromethylbenzo [b] thiophen-7-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ Acetic acid 3-trifluoromethylbenzo [b] thiophen-7-ol (227 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t Using butyl ester (246 mg), the title compound (88 mg) was obtained in the same manner as in Reference Examples 9 and 2 and Examples 1 to 3.
  • Example 74 ⁇ [5- (4-Chlorobenzo [b] thiophen-7-yloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 4 -Chlorobenzo [b] thiophen-7-ol (123 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (252 mg) In the same manner as in Reference Examples 9 and 2 and Examples 1 to 3, the title compound (114 mg) was obtained.
  • Example 75 ⁇ [7-hydroxy-5- (7-trifluoromethylbenzo [b] thiophen-3-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] Amino ⁇ acetic acid 7-trifluoromethylbenzo [b] thiophene-3-thiol (201 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid Using the t-butyl ester (301 mg), the title compound (214 mg) was obtained in the same manner as in Reference Examples 1 and 2 and Examples 1 to 3.
  • Example 76 ⁇ [5- (Benzo [b] thiophen-3-yloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid Benzo [b ] Using thiophen-3-one (554 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (987 mg) In the same manner as in Example 9 and Examples 4 and 5, the title compound (76 mg) was obtained.
  • Example 77 ⁇ [5- (6-Chlorobenzofuran-3-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 6-chloro Reference example using benzofuran-3-thiol (113 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (214 mg) 1, In the same manner as in Examples 4 and 5, the title compound (136 mg) was obtained.
  • Example 78 ⁇ [7-Hydroxy-5- (1,2,3-trimethyl-1H-indol-7-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl Amino ⁇ acetic acid 1,2,3-trimethyl-1H-indole-7-thiol (138 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8- The title compound (111 mg) was obtained in the same manner as in Reference Examples 1 and 2 and Examples 1 to 3, using carboxylic acid t-butyl ester (288 mg).
  • Example 79 ⁇ [5- (3-Chloro-1-methyl-1H-indol-7-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl Amino ⁇ acetic acid 3-chloro-1-methyl-1H-indole-7-thiol (198 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8- The title compound (90 mg) was obtained in the same manner as in Reference Example 1, Example 4, and 5 using carboxylic acid t-butyl ester (200 mg).
  • Example 80 ⁇ [7-Hydroxy-5- (1,2,3-trimethyl-1H-indol-4-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl Amino ⁇ acetic acid 1,2,3-trimethyl-1H-indole-4-thiol (132 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8- The title compound (159 mg) was obtained in the same manner as in Reference Examples 1 and 2 and Examples 1 to 3, using carboxylic acid t-butyl ester (279 mg).
  • Example 81 ⁇ [7-Hydroxy-5- (1,2,3-trimethyl-1H-indol-4-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] Amino ⁇ acetic acid 1,2,3-trimethyl-1H-indole-4-ol (254 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carvone
  • the title compound (41 mg) was obtained in the same manner as in Reference Examples 2 and 3, and Examples 1 to 3, using acid t-butyl ester (550 mg).
  • Example 82 ⁇ [5- (9H-fluoren-1-yloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 9H-fluorene-1 -Ol (165 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (474 mg) were used in Reference Example 9 and Example 4. In the same manner as in 5, the title compound (31 mg) was obtained.
  • Example 83 ⁇ [5- (Dibenzofuran-4-yloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid dibenzofuran-4-ol (164 mg ) And 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (400 mg), Reference Example 3, Examples 4, 5 In the same manner as the above, the title compound (177 mg) was obtained.
  • Example 84 ⁇ [5- (Dibenzothiophen-4-yloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid dibenzothiophen-4-ol (178 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (400 mg), Reference Example 3, Example 4 In the same manner as in 5, the title compound (78 mg) was obtained.
  • Example 85 ⁇ [5- (dibenzofuran-4-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid dibenzofuran-4-thiol ( 603 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo “1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (300 mg) In the same manner, the title compound (78 mg) was obtained.
  • Example 86 ⁇ [7-hydroxy-5- (phenanthren-1-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid phenanthren-1-ol (173 mg ) And 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (400 mg), Reference Example 3, Examples 4, 5 In the same manner as the above, the title compound (125 mg) was obtained.
  • Example 87 ⁇ [7-Hydroxy-5- (5,6,7,8-tetrahydronaphthalen-1-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ Acetic acid 5,6,7,8-tetrahydronaphthalen-1-ol (1 g) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t -The title compound (667 mg) was obtained by treating the butyl ester (2 g) in the same manner as in Reference Example 9, Examples 4 and 5.
  • Example 88 ⁇ [7-hydroxy-5- (5-methyl-5,6,7,8-tetrahydronaphthalen-1-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8 -Carbonyl] amino ⁇ acetic acid 5-methyl-5,6,7,8-tetrahydronaphthalen-1-ol (100 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] Pyridine-8-carboxylic acid t-butyl ester (316 mg) was treated in the same manner as in Reference Example 9, Examples 4 and 5 to give the title compound (97 mg).
  • Example 89 ⁇ [7-hydroxy-5- (indan-4-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid indan-4-ol (120 mg ) And 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (350 mg), and Reference Example 3, Examples 4, 5 In the same manner as described above, the title compound (149 mg) was obtained.
  • Example 90 ⁇ [5- (3,5-dimethylphenoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3,5-dimethylphenol (81 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (250 mg) were used. In the same manner as in Examples 1 to 3, the title compound (70 mg) was obtained.
  • Example 91 ⁇ [5- (5-Fluorobiphenyl-3-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 5-fluoro Biphenyl-3-thiol (135 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) were used in Reference Example 1, In the same manner as in Examples 4 and 5, the title compound (55 mg) was obtained.
  • Reference Example 11 7-Benzyloxy-5- (2-cyclopentylethoxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester
  • Compound obtained in Reference Example 10 200 mg was mixed with tetrahydrofuran (10 mL), and 2-cyclopentaneethanol (114 ⁇ l), diisopropyl azodicarboxylate (235 ⁇ l), and triphenylphosphine (315 mg) were sequentially added under ice cooling. After stirring at room temperature for 2 hours, the solvent was distilled under reduced pressure.
  • Example 92 [[7-Hydroxy-5- (2-methylbutylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2-methylbutanethiol (63 mg ) And 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (250 mg) in the same manner as in Example 8, Compound (71 mg) was obtained.
  • Example 93 (S)-[[7-hydroxy-5- (2-methylbutylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid (S) After using -2-methylbutanol (71 mg) and the compound (200 mg) obtained in Reference Example 15 in the same manner as in Reference Example 11 and Example 2, the resulting residue was placed in isopropyl alcohol (1.5 mL). Suspended, 4M aqueous lithium hydroxide solution (0.5 mL) was added, and the mixture was stirred at room temperature for 4 hours.
  • reaction mixture was neutralized with 2M hydrochloric acid, and the organic layer extracted with ethyl acetate was washed with water and saturated brine. After washing with water, drying over anhydrous sodium sulfate and filtration, the solvent was distilled off under reduced pressure to obtain the title compound (35 mg).
  • Example 94 [[7-Hydroxy-5-methylsulfanyl [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid obtained in methanol (1 mL) and Reference Example 15 Using the compound (200 mg), the title compound (42 mg) was obtained in the same manner as in Reference Example 11, Examples 2 and 3.
  • Example 95 [(7-hydroxy-5-propylsulfanyl [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid propanethiol (40 mg) and 7-benzyloxy-5 Using the iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg), the title compound (28 mg) was obtained in the same manner as in Example 8.
  • Example 96 ⁇ [7-hydroxy-5- (3,3,3-trifluoropropylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3, Using 3,3-trifluoropropanethiol (173 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (201 mg) In the same manner as in Example 8, the title compound (74 mg) was obtained.
  • Example 97 [(7-hydroxy-5-butylsulfanyl [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid obtained in butanol (80 mg) and Reference Example 15 The title compound (117 mg) was obtained in the same manner as in Example 94, using the compound (200 mg).
  • Example 98 [[7-Hydroxy-5- (3-methylbutylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 3-methylbutanethiol (55 mg ) And 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) in the same manner as in Example 8, Compound (40 mg) was obtained.
  • Example 99 ⁇ [5- (3,3-dimethylbutylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3,3-dimethyl
  • the title compound (39 mg) was obtained in the same manner as in Example 152, using butyl-4-methylbenzenesulfonate (95 mg) and the compound (125 mg) obtained in Reference Example 15.
  • Example 100 [[7-Hydroxy-5- (2,2-dimethylbutylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2,2-dimethyl
  • the title compound (95 mg) was obtained in the same manner as in Reference Example 11 and Example 5, using butanol (110 mg) and the compound (200 mg) obtained in Reference Example 13.
  • Reference Example 13 [(7-Benzyloxy-5-mercapto [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid t-butyl ester
  • Compound obtained in Reference Example 12 (15.7 g) was dissolved in methanol (60 mL) and stirred at 0 ° C. for 30 minutes. Thereafter, sodium methoxide (2.6 g) was added, the mixture was further stirred for 30 minutes, and aqueous citric acid was added. The precipitated crystals were collected by filtration and washed with water to give the title compound (8.0 g).
  • Reference Example 14 3- [7-Benzyloxy-8- (methoxycarbonylmethylcarbamoyl)-[1,2,4] triazolo [1,5- ⁇ ] pyridin-5-ylsulfanyl] propionic acid 3-ethylhexyl ester 3 -Mercaptopropionic acid 3-ethylhexyl ester (2.7 g) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (5.
  • the title compound (3.85 g) was obtained in the same manner as in Reference Examples 1 and 2 and Example 1.
  • Example 101 [[5- (2-Ethylbutylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2-ethylbutanol (87 mg)
  • the title compound (48 mg) was obtained in the same manner as in Example 93, using the compound (250 mg) obtained in Reference Example 15.
  • Example 102 [[5- (1,3-Dimethylbutylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 4-methyl-2 -The title compound (30 mg) was obtained in the same manner as in Example 100 using pentanol (105 mg) and the compound (200 mg) obtained in Reference Example 13.
  • Example 103 [[7-hydroxy-5- (4,4,4-trifluorobutylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid methanesulfone Using the acid 4,4,4-trifluoro-butyl ester (309 mg) and the compound (279 mg) obtained in Reference Example 15, the title compound (104 mg) was obtained in the same manner as in Example 152.
  • Example 104 [(7-Hydroxy-5-pentylsulfanyl [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid pentanethiol (125 mg) and 7-benzyloxy-5 Using iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (451 mg), the title compound (48 mg) was obtained in the same manner as in Example 6.
  • Example 105 [(7-hydroxy-5- (4-methylpentylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid 4-methylpentanol (100 mg ) And the compound (200 mg) obtained in Reference Example 13 were used in the same manner as in Example 100 to obtain the title compound (100 mg).
  • Example 106 [(7-Hydroxy-5- (3-methylpentylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid 3-methylpentanol (100 mg ) And the compound (200 mg) obtained in Reference Example 13 were used in the same manner as in Example 100 to obtain the title compound (70 mg).
  • Example 107 [[7-Hydroxy-5- (2-propylpentylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2-propylpentene-1-
  • the title compound (102 mg) was obtained in the same manner as in Example 100, using all (147 mg) and the compound (311 mg) obtained in Reference Example 13.
  • Example 108 [[5- (3-Ethylpentylsulfanyl) -7-hydroxy- [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 3-ethylpentane-1 Using the ol (131 mg) and the compound (311 mg) obtained in Reference Example 13, the title compound (135 mg) was obtained in the same manner as in Example 100.
  • Example 109 [[7-Hydroxy-5- (pent-3-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 3-pentyne-1- Using all (32 mg) and the compound (130 mg) obtained in Reference Example 15, the title compound (69 mg) was obtained in the same manner as in Reference Example 11, Example 5, and 3.
  • Example 110 [[7-Hydroxy-5- (4,4,5,5,5-pentafluoropentylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ] Acetic acid Toluenesulfonic acid 4,4,5,5,5-pentafluoropentane ester (332 mg) and the compound obtained in Reference Example 15 (279 mg) were used in the same manner as in Example 152 to give the titled compound (210 mg) Got.
  • Example 111 [(5-Hexylsulfanyl-7-hydroxy- [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid hexanethiol (88 mg) and 7-benzyloxy-
  • the title compound (60 mg) was obtained in the same manner as in Example 8 using 5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg). .
  • Example 112 [(5-hex-3-yn-1-ylsulfanyl-7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid 3-hexyne-
  • the title compound (57 mg) was obtained in the same manner as in Example 152, using 1-hydroxymethanesulfonic acid ester (143 mg) and the compound (350 mg) obtained in Reference Example 15.
  • Example 113 [(7-Hydroxy-5-isopropylsulfanyl [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid 2-propanethiol (92 mg) and 7-benzyloxy Using -5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (250 mg), the title compound (32 mg) was obtained in the same manner as in Example 8. It was.
  • Example 114 [(5-tert-butylsulfanyl-7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid 2-methylpropane-2-thiol (48 mg ) And 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) in the same manner as in Example 8, Compound (60 mg) was obtained.
  • Example 115 [(7-hydroxy-5-isobutylsulfanyl [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid 2-methylpropane-1-thiol (48 mg) and Using 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) in the same manner as in Example 8, the title compound ( 73 mg) was obtained.
  • Example 116 [[5- (1,2-Dimethylpropylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 1,2-dimethyl
  • the title compound (40 mg) was obtained.
  • Example 117 [(5-allylsulfanyl-7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid allyl mercaptan (53.8 mg) and 7-benzyloxy Using 5--5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid methyl ester (300 mg) in the same manner as in Reference Examples 1, 2, and Example 1, 5-allyl Sulfanyl-7-benzyloxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonylaminoacetic acid methyl ester (104 mg) was obtained.
  • Example 118 [(5-Cyclopentylsulfanyl-7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid cyclopentanethiol (45 mg) and 7-benzyloxy- Using 5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) in the same manner as in Example 8, the title compound (72 mg) was obtained. .
  • Example 119 [(5-cyclohexylsulfanyl-7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid cyclohexanethiol (61 mg) and 7-benzyloxy-5
  • the title compound (55 mg) was obtained in the same manner as in Example 8 using iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (250 mg).
  • Example 120 [[5- (adamantan-1-ylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 1-adamantanethiol (400 mg ) And 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (400 mg) in the same manner as in Example 8, Compound (110 mg) was obtained.
  • Example 121 ⁇ [5-Cyclopropylmethylsulfanyl-7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid Bromomethylcyclopropane (87 mg) and Reference Example The title compound (56 mg) was obtained in the same manner as in Example 152, using the compound (81 mg) obtained in 15.
  • Example 122 ⁇ [5-cyclobutylmethylsulfanyl-7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid Bromomethylcyclobutane (39 mg) and Reference Example 15 The title compound (50 mg) was obtained in the same manner as in Example 152 using the compound obtained in (76 mg).
  • Example 123 ⁇ [5-Cyclopentylmethylsulfanyl-7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid Toluene-4-sulfonic acid cyclopentylmethyl ester (254 mg ) And the compound (250 mg) obtained in Reference Example 15 were used to obtain the title compound (111 mg) in the same manner as in Example 152.
  • Example 124 ⁇ [5-cyclohexylmethylsulfanyl-7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid toluene-4-sulfonic acid cyclohexylmethyl ester (75 ⁇ L ) And the compound (200 mg) obtained in Reference Example 15 were used to obtain the title compound (85 mg) in the same manner as in Example 152.
  • Example 125 ⁇ [5- (2-cyclohexylethylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid toluene-4-sulfonic acid cyclohexyl
  • the title compound (136 mg) was obtained in the same manner as in Example 152, using ethyl ester (251 mg) and the compound (300 mg) obtained in Reference Example 15.
  • Example 126 ⁇ [5- (2-cyclohexylpropylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-cyclohexylpropanol ( 102 mg) and the compound obtained in Reference Example 13 (200 mg) were used in the same manner as in Example 100 to obtain the title compound (119 mg).
  • Example 127 [[5- (2-Cyclopropylethylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid Toluene-4-sulfonic acid
  • the title compound (95 mg) was obtained in the same manner as in Example 152, using 2-cyclopropylethyl ester (132 mg) and the compound (207 mg) obtained in Reference Example 15.
  • Example 128 ⁇ [5- (2-cyclobutylethylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid Toluene-4-sulfonic acid
  • the title compound (40 mg) was obtained in the same manner as in Example 152, using -2-cyclobutylethyl ester (165 mg) and the compound (200 mg) obtained in Reference Example 15.
  • Example 129 ⁇ [5- (2-Cyclopentylethylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid Toluene-4-sulfonic acid
  • the title compound (56 mg) was obtained in the same manner as in Example 152, using 2-cyclopentylethyl ester (217 mg) and the compound (200 mg) obtained in Reference Example 15.
  • Example 130 ⁇ [5- (2-bicyclo [2.2.1] hept-2-ylethylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8- Carbonyl] amino ⁇ acetic acid
  • (2-bicyclo [2,2,1] hept-2-ylethanol (144 mg) and triethylamine (101 mg) was dissolved in THF (2 mL), and mesyl chloride (112 mg) was added under ice cooling. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, and dried over anhydrous magnesium sulfate.
  • Example 131 ⁇ [5- (2-adamantan-1-ylethyl) sulfanyl-7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid Toluene-4-
  • the title compound (71 mg) was obtained in the same manner as in Example 152, using sulfonic acid-2-adamantan-1-ylethyl ester (234 mg) and the compound (200 mg) obtained in Reference Example 15.
  • Example 132 ⁇ (7-hydroxy-5-phenethylsulfanyl [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino ⁇ acetic acid 2-phenylethanethiol (92 mg) and 7-benzyl Using oxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (250 mg) in the same manner as in Reference Example 3 and Example 32, the title compound ( 60 mg) was obtained.
  • Example 133 ([5- [2- (3,4-Dichlorophenyl) ethylsulfanyl] -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino) acetic acid 3 , 4-Dichlorophenylethanol (110 mg) and the compound obtained in Reference Example 13 (200 mg) were used in the same manner as in Example 100 to obtain the title compound (120 mg).
  • Example 134 ([7-hydroxy-5- [2- (4-methoxyphenyl) ethylsulfanyl] [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino) acetic acid 2-
  • the title compound (100 mg) was obtained in the same manner as in Example 100, using (4-methoxyphenyl) ethanol (150 mg) and the compound (200 mg) obtained in Reference Example 13.
  • Example 135 [(7-hydroxy-5- (2-phenylpropylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid 2-phenylpropanol (90 mg)
  • the title compound (90 mg) was obtained in the same manner as in Example 94, using the compound (200 mg) obtained in Reference Example 15.
  • Example 136 [(7-Hydroxy-5- (2-methyl-2-phenylpropylsulfanyl)-[1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid 2-
  • the title compound (90 mg) was obtained in the same manner as in Example 94, using methyl-2-phenylpropanol (90 mg) and the compound (200 mg) obtained in Reference Example 15.
  • Example 137 [(7-hydroxy-5- (2-thiophen-2-ylethylsulfanyl)-[1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid 2-
  • the title compound (84 mg) was obtained in the same manner as in Example 94, using thiophene ethanol (71 mg) and the compound (200 mg) obtained in Reference Example 15.
  • Example 138 ⁇ [5- (3-cyclohexylpropylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid toluene-4-sulfonic acid 3 -
  • the title compound (50 mg) was obtained in the same manner as in Example 152, using cyclohexylpropyl ester (112 mg) and the compound (200 mg) obtained in Reference Example 15.
  • Example 139 [[7-hydroxy-5- (3-phenylpropylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 3-phenylpropanol (110 mg)
  • the title compound (89 mg) was obtained in the same manner as in Example 100 using the compound (200 mg) obtained in Reference Example 13.
  • Example 140 ⁇ [7-hydroxy-5- (2-methoxyethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 1-bromo-2-methoxy
  • the title compound (105 mg) was obtained in the same manner as in Example 152, using ethane (76 ⁇ L) and the compound (200 mg) obtained in Reference Example 15.
  • Example 141 [[7-Hydroxy-5- (2-isopropoxyethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2-isopropoxyethanol ( 73 mg) and the compound obtained in Reference Example 17 (200 mg) were used in the same manner as in Reference Examples 11 and 2 and Examples 1 to 3, to obtain the title compound (44 mg).
  • Example 142 [(7-hydroxy-5- (2-phenoxyethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid 2-phenoxyethanol (90 mg) and The title compound (40 mg) was obtained in the same manner as in Example 94, using the compound (200 mg) obtained in Reference Example 15.
  • Example 143 [[5- (2,3-dihydrobenzo [b] [1,4] dioxin-2-ylmethylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] [Pyridine-8-carbonyl] amino] acetic acid 2-hydroxymethyl-1,4-benzodioxane (150 mg) and the compound obtained in Reference Example 15 (200 mg) were used in the same manner as in Example 94 to obtain the title compound (20 mg )
  • Example 144 ⁇ [5- (2,3-diphenylpropylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2,3-diphenyl 2,3-Diphenylpropanol methanesulfonate (1.4 g) was obtained in the same manner as in Example 130, using propanol (1.0 g). Using this compound (190 mg) and the compound (200 mg) obtained in Reference Example 17, the title compound (55 mg) was obtained in the same manner as in Reference Example 16 and Example 32.
  • Example 145 ( ⁇ 5- [2- (2-ethylhexyloxycarbonyl) ethylsulfanyl] -7-hydroxy [1,2,4] triazolo [1,5, ⁇ ] pyridine-8-carbonyl] amino) acetic acid 3 -Using mercaptopropanoic acid 2-ethylhexyl ester (72 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (137 mg) In the same manner as in Example 94, the title compound (90 mg) was obtained.
  • Example 146 [(5-Benzylsulfanyl-7-hydroxy- [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid benzyl mercaptan (49 mg) and 7-benzyloxy- Use 5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (150 mg) in the same manner as Reference Example 3, Reference Example 2, and Examples 1 to 3. To give the title compound (21 mg).
  • Example 147 ⁇ [7-hydroxy-5- (2-methylbenzylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid (2-methylphenyl) methane Using thiol (67 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) as in Example 8. To give the title compound (44 mg).
  • Example 148 ⁇ [7-hydroxy-5- (2-trifluoromethylbenzylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2- (trifluoro
  • the title compound (46 mg) was obtained in the same manner as in Example 152, using methyl) benzyl bromide (57 mg) and the compound (80 mg) obtained in Reference Example 15.
  • Example 149 ⁇ [5- (2-Fluorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-fluorobenzyl bromide (45 mg ) And the compound (80 mg) obtained in Reference Example 15 were used to obtain the title compound (56 mg) in the same manner as in Example 152.
  • Example 150 ⁇ [5- (2-chlorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid (2-chlorophenyl) methanethiol (77 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) as in Example 8. The title compound (66 mg) was obtained.
  • Example 151 1 [[7-Hydroxy-5- (2-methoxybenzylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid obtained in Reference Example 16
  • the title compound (48 mg) was obtained in the same manner as in Examples 2 and 3 using the compound (100 mg).
  • Example 152 [[7-hydroxy-5- (2-trifluoromethoxybenzylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2- (trifluoro
  • the title compound (70 mg) was obtained in the same manner as in Reference Example 16 and Example 151 using (methoxy) benzyl bromide (65 mg) and the compound (80 mg) obtained in Reference Example 15.
  • Example 153 ⁇ [7-Hydroxy-5- (3-methylbenzylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3-methylbenzyl bromide (44 mg ) And the compound (80 mg) obtained in Reference Example 15 were used to obtain the title compound (51 mg) in the same manner as in Example 152.
  • Example 154 ⁇ [7-hydroxy-5- (3-trifluoromethylbenzylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3- (trifluoro
  • the title compound (60 mg) was obtained in the same manner as in Example 152, using (methyl) benzyl bromide (57 mg) and the compound (80 mg) obtained in Reference Example 15.
  • Example 155 ⁇ [5- (3-Fluorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3-fluorobenzyl bromide (45 mg ) And the compound (80 mg) obtained in Reference Example 15 were used to obtain the title compound (60 mg) in the same manner as in Example 152.
  • Example 156 ⁇ [5- (3-chlorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3-chlorobenzyl bromide (49 mg ) And the compound (80 mg) obtained in Reference Example 15 were used to obtain the title compound (60 mg) in the same manner as in Example 152.
  • Example 157 [[7-hydroxy-5- (4-methylbenzylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 4-methylbenzyl mercaptan (66 mg ) And 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) in the same manner as in Example 8, Compound (66 mg) was obtained.
  • Example 158 ⁇ [7-hydroxy-5- (4-trifluoromethylbenzylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid [4- (tri Fluoromethyl) phenyl] methanethiol (108 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (230 mg) In the same manner as in Example 8, the title compound (89 mg) was obtained.
  • Example 159 ⁇ [5- (4-Fluorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid (4-fluorophenyl) methane Using thiol (69 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) as in Example 8. To give the title compound (88 mg).
  • Example 160 [[5- (4-Chlorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 4-chlorobenzyl mercaptan (168 mg ) And 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (400 mg) in the same manner as in Example 6, Compound (48 mg) was obtained.
  • Example 161 ⁇ [5- (4-Cyanobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 4- (mercaptomethyl) benzo Similar to Example 6 using nitrile (73 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg). To give the title compound (97 mg).
  • Example 162 ⁇ [5- (4-t-butylbenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid (4-t- Examples using butylphenyl) methanethiol (144 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (300 mg) In the same manner as 146, the title compound (24 mg) was obtained.
  • Example 163 ⁇ [5- (biphenyl-4-ylmethylsulfanyl) -7-hydroxy- [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid biphenyl-4-
  • Example 146 with ylmethanethiol (117 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (220 mg) In the same manner, the title compound (42 mg) was obtained.
  • Example 164 ⁇ [7-hydroxy-5- (4-methoxybenzylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 4-methoxybenzyl alcohol (134 mg ) And the compound (300 mg) obtained in Reference Example 15 were used to obtain the title compound (53 mg) in the same manner as in Reference Example 11, Examples 2 and 3.
  • Example 165 ⁇ [5- (2-Fluoro-3-methylbenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-fluoro
  • the title compound (47 mg) was obtained in the same manner as in Example 152, using -3-methylbenzyl bromide (48 mg) and the compound (80 mg) obtained in Reference Example 15.
  • Example 166 ⁇ [5- (2,3-difluorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2,3-difluoro
  • the title compound (56 mg) was obtained in the same manner as in Example 152, using benzyl bromide (49 mg) and the compound (80 mg) obtained in Reference Example 15.
  • Example 167 ⁇ [5- (2,4-dichlorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid (2,4- Example 8 using dichlorophenyl) methanethiol (94 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg) To give the title compound (65 mg).
  • Example 168 ⁇ [5- (2,4-dimethylbenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2,4-dimethyl Benzyl alcohol (50 mg) and tetrahydrofuran (2.0 mL) were mixed, and triethylamine (45 mg) and methanesulfonyl chloride (42 mg) were sequentially added under ice cooling. After stirring at the same temperature for 2 hours and confirming the completion of the reaction, triethylamine (45 mg) and the compound obtained in Reference Example 13 (152 mg) were further added. After stirring for 1 hour at room temperature, the completion of the reaction was confirmed.
  • Example 169 ⁇ [5- (2,5-dimethylbenzylsulfanyl) -7-hydroxy- [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2,5-
  • the title compound (71 mg) was obtained in the same manner as in Example 152, using dimethylphenylmethyl methanesulfonate (57 mg) and the compound (90 mg) obtained in Reference Example 15.
  • Example 170 ⁇ [5- (2,5-difluorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2,5-difluoro
  • the title compound (50 mg) was obtained in the same manner as in Example 152, using benzyl bromide (43 mg) and the compound (70 mg) obtained in Reference Example 15.
  • Example 171 ⁇ [5- (2,5-dichlorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2,5-dichloro
  • the title compound (52 mg) was obtained in the same manner as in Example 152, using benzyl bromide (57 mg) and the compound (80 mg) obtained in Reference Example 15.
  • Example 172 ⁇ [5- (5-chloro-2-fluorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 5-chloro
  • the title compound (57 mg) was obtained in the same manner as in Example 152, using -2-fluorobenzyl bromide (53 mg) and the compound (80 mg) obtained in Reference Example 15.
  • Example 173 ⁇ [5- (2-chloro-5-fluorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-chloro
  • the title compound (51 mg) was obtained in the same manner as in Example 152, using -5-fluorobenzyl bromide (53 mg) and the compound (80 mg) obtained in Reference Example 15.
  • Example 174 ⁇ [5- (2-Fluoro-5-methylbenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-fluoro
  • the title compound (70 mg) was obtained in the same manner as in Example 130, using -5-methylbenzyl alcohol (80 mg) and the compound (90 mg) obtained in Reference Example 15.
  • Example 175 ⁇ [5- (2-Chloro-3,6-difluorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2
  • the title compound (63 mg) was obtained in the same manner as in Example 152, using -chloro-3,6-difluorobenzyl bromide (57 mg) and the compound (80 mg) obtained in Reference Example 15.
  • Example 176 ⁇ [5- (2,6-dichlorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2,6-dichloro
  • the title compound (56 mg) was obtained in the same manner as in Example 152, using benzyl bromide (50 mg) and the compound (70 mg) obtained in Reference Example 15.
  • Example 177 ⁇ [5- (3-Chloro-4-fluorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3-chloro
  • the title compound (68 mg) was obtained in the same manner as in Example 152, using -4-fluorobenzyl bromide (53 mg) and the compound obtained in Reference Example 15 (80 mg).
  • Example 178 ⁇ [5- (3,5-bistrifluoromethylbenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3,5 Using the bis (trifluoromethyl) benzyl bromide (95 mg) and the compound (92 mg) obtained in Reference Example 17, the title compound (67 mg) was obtained in the same manner as in Example 32.
  • Example 179 [[5- (2,6-dimethylbenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2,6-dimethyl
  • the title compound (75 mg) was obtained in the same manner as in Example 152, using benzyl iodide (159 mg) and the compound (200 mg) obtained in Reference Example 15.
  • Example 180 ⁇ [7-hydroxy-5- (2,4,6-trimethylbenzylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid (2, 4,6-trimethylphenyl) methanethiol (81 mg) and 7-benzyloxy-5-iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (200 mg). And the title compound (64 mg) was obtained as in Example 8.
  • Example 181 ⁇ [7-hydroxy-5- (2,3,6-trifluorobenzylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2,
  • the title compound (48 mg) was obtained in the same manner as in Example 152, using 3,6-trifluorobenzyl bromide (53 mg) and the compound (80 mg) obtained in Reference Example 15.
  • Example 182 ⁇ [7-hydroxy-5- (2,3,4,5,6-pentafluorobenzylsulfanyl)-[1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] Amino ⁇ acetic acid 2,3,4,5,6-pentafluorobenzyl bromide (46 mg) and the compound obtained in Reference Example 15 (60 mg) were used in the same manner as in Example 152 to obtain the title compound (33 mg). .
  • Example 183 ⁇ [5- (3,6-difluoro-2-methylbenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 1 , 4-Difluoro-2,3-dimethylbenzene (100 mg) and monochlorobenzene (1.0 mL) were added, and N-bromosuccinimide (150 mg) and azobisisobutyronitrile (6 mg) were added to the mixture. Stir at 4 ° C. for 4 hours. After completion of the reaction, the insoluble material was filtered through Celite, and the solvent was concentrated under reduced pressure. The title compound (73 mg) was obtained in the same manner as in Example 152, using the obtained 2-bromomethyl-1,4-difluoro-3-methylbenzene and the compound (80 mg) obtained in Reference Example 15.
  • Example 184 ⁇ [5- (2,6-difluorobenzylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2,6-difluoro
  • the title compound (30 mg) was obtained in the same manner as in Example 100 using benzyl alcohol (110 mg) and the compound (200 mg) obtained in Reference Example 13.
  • Example 185 ( ⁇ )-[[7-hydroxy-5- (1-phenylethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid ( ⁇ )
  • the title compound (113 mg) was obtained in the same manner as in Example 152, using 1-phenylethyl chloride (106 mg) and the compound (140 mg) obtained in Reference Example 15.
  • Example 186 [[7-hydroxy-5- (1,2,3,4-tetrahydronaphthalen-1-ylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] Amino] acetic acid 1-chloro-1,2,3,4-tetrahydronaphthalene (80 mg) and the compound obtained in Reference Example 15 (94 mg) were used in the same manner as in Example 152 to obtain the title compound (40 mg). It was.
  • Example 187 ⁇ [7-Hydroxy-5- (5,6,7,8-tetrahydronaphthalen-2-ylmethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl Amino ⁇ acetic acid 5,6,7,8-tetrahydronaphthalen-2-ylmethanol (274 mg)
  • the title compound (65 mg) was obtained in the same manner as in Example 130, using the compound (80 mg) obtained in Reference Example 15. It was.
  • Example 188 ⁇ [5- (benzothiazol-2-ylmethylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-benzothiazole
  • the title compound (62 mg) was obtained in the same manner as in Example 152, using methanol 2-methanesulfonate (57 mg) and the compound (80 mg) obtained in Reference Example 15.
  • Example 189 ⁇ [7-hydroxy-5- (pyridin-2-ylmethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-bromomethylpyridine
  • the title compound (53 mg) was obtained in the same manner as in Example 152, using bromate (112 mg) and the compound (150 mg) obtained in Reference Example 15.
  • Example 190 ⁇ [7-Hydroxy-5- (pyridin-3-ylmethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid Pyridin-3-yl
  • the title compound (35 mg) was obtained in the same manner as in Example 152, using methylmethanesulfonate (83 mg) and the compound (150 mg) obtained in Reference Example 15.
  • Example 191 1 ⁇ [7-Hydroxy-5- (pyridin-4-ylmethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 4-Bromomethylpyridine
  • the title compound (101 mg) was obtained in the same manner as in Example 152, using bromate (136 mg) and the compound (200 mg) obtained in Reference Example 15.
  • Example 192 ⁇ [7-hydroxy-5- (6-methylpyridin-2-ylmethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 6- ⁇ [7-Benzyloxy-5- (6-methylpyridin-2-ylmethyl) was prepared in the same manner as in Example 168 using methyl-2-pyridinemethanol (49 mg) and the compound obtained in Reference Example 15 (135 mg). Sulfanyl)-[1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid methyl ester was obtained. The title compound (70 mg) was obtained from the obtained compound in the same manner as in Examples 2 and 3.
  • Example 193 [[7-hydroxy-5- (6-trifluoromethylpyridin-3-ylmethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid
  • the title compound (109 mg) was obtained in the same manner as in Example 130, using 6-trifluoromethylpyridin-3-ylmethanol (255 mg) and the compound (311 mg) obtained in Reference Example 15.
  • Example 194 [[5- (2,6-dichloropyridin-3-ylmethylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid
  • the title compound (185 mg) was obtained in the same manner as in Example 152, using methanesulfonic acid 2,6-dichloropyridin-3-ylmethyl ester (256 mg) and the compound (311 mg) obtained in Reference Example 15.
  • Example 195 [[7-hydroxy-5- (2-trifluoromethylpyridin-4-ylmethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid
  • the title compound (160 mg) was obtained in the same manner as in Example 130, using (2-trifluoromethylpyridin-4-yl) methanol (177 mg) and the compound (311 mg) obtained in Reference Example 15.
  • Example 196 [[5- (2,6-Dimethylpyridin-4-ylmethylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid Using the methanesulfonic acid 2,6-dimethylpyridin-4-ylmethyl ester (161 mg) and the compound obtained in Reference Example 15 (250 mg), the title compound (120 mg) was obtained in the same manner as in Example 152.
  • Example 197 [[5- (2,6-dichloropyridin-4-ylmethylsulfanyl) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid
  • the title compound (180 mg) was obtained in the same manner as in Example 152, using methanesulfonic acid 2,6-dichloropyridin-4-ylmethyl ester (256 mg) and the compound (311 mg) obtained in Reference Example 15.
  • Example 198 ⁇ [7-Hydroxy-5- (quinolin-4-ylmethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridin-8-carbonyl] amino ⁇ acetic acid quinolin-4-yl
  • the title compound (70 mg) was obtained in the same manner as Example 192 using methanol (94 mg) and the compound (200 mg) obtained in Reference Example 15.
  • Example 199 [[7-Hydroxy-5- (8-trifluoromethylquinolin-4-ylmethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid Sodium borohydride (86 mg) was added to a methanol solution (4 mL) of 8-trifluoromethylquinoline-4-carbaldehyde (341 mg), and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the mixture was extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, and dried over anhydrous magnesium sulfate.
  • Example 200 [[7-Hydroxy-5- (quinolin-2-ylmethylsulfanyl) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2-quinoline methanol ( 230 mg) and the compound obtained in Reference Example 15 (300 mg) were used in the same manner as in Example 94 to obtain the title compound (130 mg).
  • Example 201 [[7-Hydroxy-5- (2-methylbutoxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2-methylbutanol (22 mg) and The title compound (50 mg) was obtained in the same manner as in Reference Example 11, Example 4 and 5, using the compound (93.7 mg) obtained in Reference Example 10.
  • Example 202 (S)-[(7-hydroxy-5- (2-methylbutoxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid (S)-
  • the title compound (35 mg) was obtained in the same manner as in Example 201, using 2-methylbutanol (22 mg) and the compound (94 mg) obtained in Reference Example 10.
  • Example 203 [(5-butoxy-7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid obtained in n-butanol (108 mg) and Reference Example 10
  • the title compound (123 mg) was obtained in the same manner as in Example 201 using the obtained compound (250 mg).
  • Example 204 ⁇ [5- (3,3-dimethylbutoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3,3-dimethylbutanol (72 mg) and the compound obtained in Reference Example 10 (200 mg) were used in the same manner as Reference Example 11, Reference Example 2 and Example 1, ⁇ [7-benzyloxy-5- (3,3-dimethylbutoxy) -[1,2,4] Triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid methyl ester was obtained.
  • Example 205 [[5- (2-Ethylbutoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2-ethylbutanol (90 mg) and The title compound (90 mg) was obtained in the same manner as in Example 201 using the compound (200 mg) obtained in Reference Example 10.
  • Example 206 [[5- (2,3-Dimethylbutoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2,3-dimethylbutane
  • the title compound (35 mg) was obtained in the same manner as in Example 201, using -1-ol (77 mg) and the compound (200 mg) obtained in Reference Example 10.
  • Example 207 [[5- (1,2-dimethylbutoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 1,2-dimethylbutanol (185 mg) and the compound (500 mg) obtained in Reference Example 10 were used in the same manner as in Reference Example 11 to obtain an ether form (216 mg). Subsequently, it melt
  • Example 208 [[7-Hydroxy-5- (4-methylpentyloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 4-methylpentanol (72 mg ) And the compound (200 mg) obtained in Reference Example 10 were used in the same manner as in Example 201 to obtain the title compound (83 mg).
  • Example 209 [[7-Hydroxy-5- (3-methylpentyloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid-methylpentan-1-ol (72 mg) and the compound (200 mg) obtained in Reference Example 10 were used, and the title compound (75 mg) was obtained in the same manner as in Example 201.
  • Example 210 [(7-Hydroxy-5- (pent-3-ynyloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid 3-pentyn-1-ol (59 mg) and the compound (200 mg) obtained in Reference Example 10 were used, and the title compound (36 mg) was obtained in the same manner as in Example 201.
  • Example 211 [[5- (1,4-Dimethylpentyloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 1,4-dimethyl
  • the title compound (50 mg) was obtained in the same manner as in Example 201, using -1-pentanol (116 mg) and the compound (300 mg) obtained in Reference Example 10.
  • Example 212 [(5-Hexyloxy-7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid 1-hexanol (85 mg) and Reference Example 10
  • the title compound (25 mg) was obtained in the same manner as in Example 201 using the obtained compound (122 mg).
  • Example 213 [[5- (Hex-4-en-1-yloxy) -7-hydroxy- [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid cis- Using 4-hexen-1-ol (70.3 mg) and the compound obtained in Reference Example 10 (200 mg), the title compound (57 mg) was obtained in the same manner as in Example 201.
  • Example 214 [[7-Hydroxy-5- (oct-3-en-1-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid cis-3 Using the -octen-1-ol (90 mg) and the compound (250 mg) obtained in Reference Example 10, the title compound (310 mg) was obtained in the same manner as in Example 201.
  • Example 215 [[7-hydroxy-5- (non-3-yn-1-yloxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 3-nonine
  • the title compound (35 mg) was obtained in the same manner as in Example 201, using -1-ol (98.5 mg) and the compound (200 mg) obtained in Reference Example 10.
  • Example 216 ([5- [2- (2-ethoxyethoxy) ethoxy] -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino) acetic acid diethylene glycol monoethyl
  • the title compound (40 mg) was obtained in the same manner as in Example 201 using ether (100 mg) and the compound (200 mg) obtained in Reference Example 10.
  • Example 217 [[5- (2-cyclohexylethoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2-cyclohexane-1-ethanol ( The title compound (44 mg) was obtained in the same manner as in Example 201 using 46 mg) and the compound (102 mg) obtained in Reference Example 10.
  • Example 218 ⁇ [5- (2-cyclobutylethoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-cyclobutylethanol (60 mg ) And the compound (200 mg) obtained in Reference Example 10 were used in the same manner as in Example 201 to obtain the title compound (25 mg).
  • Example 219 ⁇ [5- (2-Cyclopentylethoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-cyclopentylethanol (114 mg) and The title compound (66 mg) was obtained in the same manner as in Example 201 using the compound (200 mg) obtained in Reference Example 10.
  • Example 220 [[5- (2-bicyclo [2.2.1] hept-2-ylethoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] Amino ⁇ acetic acid 2-bicyclo [2,2,1] hept-2-ylethanol (164 mg) and the compound obtained in Reference Example 10 (200 mg) were used in the same manner as in Example 201 to give the title compound (40 mg). Got.
  • Example 221 [[5- (2-adamantan-1-ylethoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 2-adamantane-1 -The title compound (67 mg) was obtained in the same manner as in Example 201 using ylethanol (128 mg) and the compound (200 mg) obtained in Reference Example 10.
  • Example 222 [(7-hydroxy-5-phenethyloxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl) amino] acetic acid obtained in 2-phenylethanol (90 mg) and Reference Example 10 Using the obtained compound (200 mg), the title compound (70 mg) was obtained in the same manner as in Example 201.
  • Example 223 ([5- [2- (2-Fluorophenyl) ethoxy] -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino) acetic acid 2- ( Using 2-fluorophenyl) -1-ethanol (139 mg) and the compound (300 mg) obtained in Reference Example 10, the title compound (73 mg) was obtained in the same manner as in Example 201.
  • Example 224 [[7-hydroxy-5- (2-thiophen-2-ylethoxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2-thiophene ethanol ( 81 mg) and the compound (200 mg) obtained in Reference Example 10 were used, and the title compound (35 mg) was obtained in the same manner as in Example 201.
  • Example 225 ⁇ [5- (3-cyclohexylpropoxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino ⁇ acetic acid 3-cyclohexylpropanol (139 ⁇ L) and Using the compound (200 mg) obtained in Reference Example 10, the title compound (60 mg) was obtained in the same manner as in Reference Example 11, Example 4 and Example 5.
  • Example 226 [[7-Hydroxy-5- (2-phenoxyethoxy) [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2-phenoxyethanol (90 mg) and reference Using the compound (200 mg) obtained in Example 10, the title compound (70 mg) was obtained in the same manner as in Example 201.
  • Example 227 [[5- (2,6-Dimethylbenzyloxy) -7-hydroxy [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carbonyl] amino] acetic acid 2-fluoro-5 -Methylbenzyl alcohol (3.34 g) was dissolved in HMPA (35 mL), NaH (866 mg) was added with stirring in an ice bath, stirred at 65 ° C. for 2 hours, and cooled in an ice bath with cooling and stirring.
  • 5-Iodo [1,2,4] triazolo [1,5- ⁇ ] pyridine-8-carboxylic acid t-butyl ester (3.26 g) was added, and the mixture was stirred at 15 ° C.
  • Tables 1 to 35 below list the chemical structural formulas and physical property data in the above examples for the compounds represented by the general formula (1).
  • EPO increase rate (%) (EPO concentration when test substance is added / EPO concentration when medium is added ⁇ 1) ⁇ 100
  • the compound of the present invention has a sustained and strong EPO production promoting action at a concentration of 1 ⁇ M, and is significantly superior to the compound described in Patent Document 1.
  • Formulation example (tablet manufacturing method) 1) Example 11 5.0 mg 2) Lactose 94.0mg 3) Corn starch 20.0mg 4) Hydroxypropylcellulose 4.0mg 5) Magnesium stearate 0.5mg 6) Carboxymethylcellulose 6.5mg Total (1 tablet) 130.0mg
  • the above 1), 2) and 3) are dispersed with a stirring granulator, the aqueous solution of 4) is added to this powder, kneaded, dried and sized, and 5) and 6) are added and mixed. Tablet using a tablet machine.
  • the compound of the present invention has a sustained and excellent EPO production-promoting action, and is useful for the prevention or treatment of diseases in which a hypoxic environment occurs in a target organ or tissue, particularly for the prevention or treatment of anemia.

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Abstract

La présente invention concerne un composé représenté par la formule générale suivante (1) [dans laquelle X représente un atome d'oxygène, un groupe imino, un atome de soufre, un sulfinyle, ou un sulfonyle, R1, R2 et R3 représentent chacun indépendamment un atome d'hydrogène ou un groupe alkyle en C1-6, R4 représente un atome d'hydrogène, un groupe alkyle en C1-6, ou un groupe arylalkyle, R5 représente un groupe alkyle, alcényle, alcynyle, aryle, ou hétéroaryle]. Ce composé présente une excellente activité d'accélération de la production de l'EPO et est utile comme produit pharmaceutique.
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* Cited by examiner, † Cited by third party
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CN113387948A (zh) * 2021-02-06 2021-09-14 成都诺和晟泰生物科技有限公司 一种稠环杂芳基衍生物及其药物组合物和治疗方法及用途
WO2024061172A1 (fr) * 2022-09-19 2024-03-28 苏中药业集团股份有限公司 Inhibiteur de la prolyl hydroxylase et son utilisation

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009537558A (ja) * 2006-05-16 2009-10-29 スミスクライン・ビーチャム・コーポレイション プロリルヒドロキシラーゼ阻害剤
JP2009541351A (ja) * 2006-06-23 2009-11-26 スミスクライン・ビーチャム・コーポレイション プロリルヒドロキシラーゼ阻害剤
JP2009541486A (ja) * 2006-06-26 2009-11-26 ザ プロクター アンド ギャンブル カンパニー プロリルヒドロキシラーゼ阻害剤および使用方法
JP2011037841A (ja) * 2009-07-17 2011-02-24 Japan Tobacco Inc トリアゾロピリジン化合物、ならびにそのプロリル水酸化酵素阻害剤およびエリスロポエチン産生誘導剤としての作用
JP2011508725A (ja) * 2007-11-30 2011-03-17 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー プロリルヒドロキシラーゼ阻害剤
JP2011088840A (ja) * 2009-10-21 2011-05-06 Daiichi Sankyo Co Ltd ５−ヒドロキシピリミジン−４−カルボキサミド化合物を含有する医薬組成物
JP2011525924A (ja) * 2008-06-25 2011-09-29 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー プロリルヒドロキシラーゼ阻害剤

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009537558A (ja) * 2006-05-16 2009-10-29 スミスクライン・ビーチャム・コーポレイション プロリルヒドロキシラーゼ阻害剤
JP2009541351A (ja) * 2006-06-23 2009-11-26 スミスクライン・ビーチャム・コーポレイション プロリルヒドロキシラーゼ阻害剤
JP2009541486A (ja) * 2006-06-26 2009-11-26 ザ プロクター アンド ギャンブル カンパニー プロリルヒドロキシラーゼ阻害剤および使用方法
JP2011508725A (ja) * 2007-11-30 2011-03-17 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー プロリルヒドロキシラーゼ阻害剤
JP2011525924A (ja) * 2008-06-25 2011-09-29 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー プロリルヒドロキシラーゼ阻害剤
JP2011037841A (ja) * 2009-07-17 2011-02-24 Japan Tobacco Inc トリアゾロピリジン化合物、ならびにそのプロリル水酸化酵素阻害剤およびエリスロポエチン産生誘導剤としての作用
JP2011088840A (ja) * 2009-10-21 2011-05-06 Daiichi Sankyo Co Ltd ５−ヒドロキシピリミジン−４−カルボキサミド化合物を含有する医薬組成物

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113387948A (zh) * 2021-02-06 2021-09-14 成都诺和晟泰生物科技有限公司 一种稠环杂芳基衍生物及其药物组合物和治疗方法及用途
WO2024061172A1 (fr) * 2022-09-19 2024-03-28 苏中药业集团股份有限公司 Inhibiteur de la prolyl hydroxylase et son utilisation

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