Pyrazolone compounds and pyrazolonizing agents

Abstract

The purpose of the present invention is to provide a highly stable pyrazolone compound.　This problem can be solved by a pyrazolone compound represented by formula (1) of the present invention (in the formula, R1 is an electron-withdrawing group selected from the group consisting of halogen atoms, nitro groups, cyano groups, haloalkyl groups having 1 to 10 carbon atoms, perfluoropolyether groups having 2 to 10 carbon atoms, carboxy groups, substituted aryl groups having 6 to 60 carbon atoms, and groups represented by formulas (2) to (7), R2 is a hydrocarbon group that has 1 to 1000 carbon atoms and may contain a heteroatom, and n is an integer of 0 to 2).

Description

[Technical Field]

[0001] The present invention relates to a pyrazolone compound and a pyrazolating agent. [Background technology]

[0002] A method is known in which the formyl group of a protein such as an antibody is modified with a pyrazolone compound and a fluorescent molecule or the like is introduced (Patent Document 1 and Non-Patent Documents 1 to 3). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2014 / 074218 [Non-patent literature]

[0004] [Non-Patent Document 1] ACS Medicinal Chemistry Letters (USA) 2016, Vol. 7, pp. 994-998 [Non-patent document 2] ChemBioChem (Germany) 2020, Vol. 21, pp. 3580-3593 [Non-patent document 3] "ChemSusChem" (Germany) 2022, e202102592 Summary of the Invention [Problem to be solved by the invention]

[0005] The present inventors have modified the formyl group of sugars using 3-methyl-1-phenyl-5-pyrazolone as a pyrazolone compound to produce pyrazolonated compounds. However, the obtained pyrazolonated compounds were found to be easily decomposed and had low stability. Therefore, an object of the present invention is to provide a pyrazolonated compound having high stability. [Means for solving the problem]

[0006] The present inventors have conducted extensive research into highly stable pyrazolonated compounds and have surprisingly found that highly stable pyrazolonated compounds can be obtained by modifying a formyl group with a pyrazolone having an electron-withdrawing group introduced at a specific position. The present invention is based on this finding. Therefore, the present invention provides [1] Formula (1): [ka] (In the formula, R 1 is a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms (one or more halogen atoms bonded to the carbon atom at position 1), a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, a substituted aryl group having 6 to 60 carbon atoms (the benzene ring bonded to the pyrazolone skeleton side has at least one substituent, and the substituent is one or more selected from the group consisting of a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms (one or more halogen atoms bonded to the carbon atom at position 1), a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an acyl group having 2 to 61 carbon atoms, an alkoxycarbonyl group having 1 to 60 carbon atoms, an alkoxy group having 1 to 60 carbon atoms, and an alkyl group having 1 to 60 carbon atoms, provided that when the substituent is an alkoxy group having 1 to 60 carbon atoms or an alkyl group having 1 to 60 carbon atoms, the position of the substituent is the meta position of the benzene ring bonded to the pyrazolone skeleton side), and [ka] (In the formula, R 3represents a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms, a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an optionally substituted alkyl group having 1 to 60 carbon atoms, an optionally substituted alkenyl group having 1 to 60 carbon atoms, an optionally substituted alkynyl group having 1 to 60 carbon atoms, an optionally substituted aralkyl group having 1 to 60 carbon atoms, an optionally substituted aryl group having 6 to 60 carbon atoms, an optionally substituted alkoxy group having 1 to 60 carbon atoms, an optionally substituted alkenyloxy group having 1 to 60 carbon atoms, an optionally substituted alkynyloxy group having 1 to 60 carbon atoms, an optionally substituted aralkyloxy group having 1 to 60 carbon atoms, and / or an optionally substituted aryloxy group having 6 to 60 carbon atoms; R 4is a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms, a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an optionally substituted alkyl group having 1 to 60 carbon atoms, an optionally substituted alkenyl group having 1 to 60 carbon atoms, an optionally substituted alkynyl group having 1 to 60 carbon atoms, an optionally substituted aralkyl group having 1 to 60 carbon atoms, an optionally substituted aryl group having 6 to 60 carbon atoms, an optionally substituted alkoxy group having 1 to 60 carbon atoms, an optionally substituted alkenyloxy group having 1 to 60 carbon atoms, an optionally substituted alkynyloxy group having 1 to 60 carbon atoms, an optionally substituted aralkyloxy group having 1 to 60 carbon atoms, an optionally substituted aryloxy group having 6 to 60 carbon atoms, an optionally substituted alkylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkenylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkynylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted aralkylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted arylcarbonyl group having 6 to 60 carbon atoms, an optionally substituted alkoxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkenyloxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkynyloxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted aralkyloxycarbonyl group having 1 to 60 carbon atoms, and / or an optionally substituted aryloxycarbonyl group having 6 to 60 carbon atoms; and in the case of formula (4), R 4 is 0 to 4, and in the case of formulas (5) to (7), R 4 is 0 to 3), R 2 represents a hydrocarbon group having 1 to 1000 carbon atoms which may contain a heteroatom, and n is an integer from 0 to 2. a pyrazolone compound represented by the formula: [2] A pyrazolonization agent for a formyl group-containing compound, which comprises the pyrazolone compound according to [1]. [3] A method for pyrazolonizing a formyl group-containing compound, comprising contacting the pyrazolone compound according to [1] with a formyl group-containing compound. [4] A method for stabilizing a pyrazolone compound, comprising contacting the pyrazolone compound according to [1] with a formyl group-containing compound. [5] A method for producing a pyrazolone compound, comprising contacting the pyrazolone compound according to [1] with a formyl group-containing compound; and [6] A pyrazolone compound obtained by the production method described in [5]. Regarding. [Effects of the Invention]

[0007] According to the pyrazolone compound or pyrazolonating agent of the present invention, a pyrazolonated compound exhibiting high stability can be obtained. [Brief explanation of the drawings]

[0008] [Figure 1] 1 is a graph examining the stability of pyrazolonated compounds (compounds 5 to 10) produced using the pyrazolone compound of the present invention. [Figure 2] 1 is a graph examining the stability of pyrazolonated compounds (compounds 5 and 28 to 31) produced using the pyrazolone compound of the present invention. [Figure 3] 1 is a graph examining the stability of pyrazolonated compounds (compounds 5 and 32 to 36) produced using the pyrazolone compound of the present invention. [Figure 4] 1 is a graph examining the stability of pyrazolonated compounds (compounds 5 and 37 to 41) produced using the pyrazolone compound of the present invention. [Figure 5] 1 is a graph examining the stability of pyrazolonated compounds (compounds 5 and 42 to 45) produced using the pyrazolone compound of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0009] The pyrazolone compound of the present invention is represented by the following formula (1): [ka] It is a compound represented by the formula: R 1 is a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms (one or more halogen atoms bonded to the carbon atom at position 1), a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, a substituted aryl group having 6 to 60 carbon atoms (the benzene ring bonded to the pyrazolone skeleton side has at least one substituent, and the substituent is one or more selected from the group consisting of a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms (one or more halogen atoms bonded to the carbon atom at position 1), a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an acyl group having 2 to 61 carbon atoms, an alkoxycarbonyl group having 1 to 60 carbon atoms, an alkoxy group having 1 to 60 carbon atoms, and an alkyl group having 1 to 60 carbon atoms, provided that when the substituent is an alkoxy group having 1 to 60 carbon atoms or an alkyl group having 1 to 60 carbon atoms, the position of the substituent is the meta position of the benzene ring bonded to the pyrazolone skeleton side), and [ka] (In the formula, R 3represents a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms, a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an optionally substituted alkyl group having 1 to 60 carbon atoms, an optionally substituted alkenyl group having 1 to 60 carbon atoms, an optionally substituted alkynyl group having 1 to 60 carbon atoms, an optionally substituted aralkyl group having 1 to 60 carbon atoms, an optionally substituted aryl group having 6 to 60 carbon atoms, an optionally substituted alkoxy group having 1 to 60 carbon atoms, an optionally substituted alkenyloxy group having 1 to 60 carbon atoms, an optionally substituted alkynyloxy group having 1 to 60 carbon atoms, an optionally substituted aralkyloxy group having 1 to 60 carbon atoms, or an optionally substituted aryloxy group having 6 to 60 carbon atoms; R 4is a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms, a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an optionally substituted alkyl group having 1 to 60 carbon atoms, an optionally substituted alkenyl group having 1 to 60 carbon atoms, an optionally substituted alkynyl group having 1 to 60 carbon atoms, an optionally substituted aralkyl group having 1 to 60 carbon atoms, an optionally substituted aryl group having 6 to 60 carbon atoms, an optionally substituted alkoxy group having 1 to 60 carbon atoms, an optionally substituted alkenyloxy group having 1 to 60 carbon atoms, an optionally substituted alkynyloxy group having 1 to 60 carbon atoms, an optionally substituted aralkyloxy group having 1 to 60 carbon atoms, an optionally substituted aryloxy group having 6 to 60 carbon atoms a group, an optionally substituted alkylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkenylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkynylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted aralkylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted arylcarbonyl group having 6 to 60 carbon atoms, an optionally substituted alkoxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkenyloxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkynyloxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted aralkyloxycarbonyl group having 1 to 60 carbon atoms, or an optionally substituted aryloxycarbonyl group having 6 to 60 carbon atoms, and in the case of formula (4), R 4 is 0 to 4, and in the case of formulas (5) to (7), R 4 R is an electron-withdrawing group selected from the group consisting of groups represented by the formula (where R is 0 to 3). 2 is a hydrocarbon group having 1 to 1000 carbon atoms which may contain a heteroatom, and n is an integer of 0 to 2. The pyrazolone compound of the present invention can be used to pyrazoloneize a formyl group-containing compound.

[0010] The pyrazolone compound of the present invention may be a CH isomer of the formula (1), but may also be a compound of the following formula (8): [ka] or a structural isomer (OH form) represented by the following formula (9): [ka] It may also be a structural isomer (NH form) represented by the following formula: The R 1 However, because the group is an electron-withdrawing group, the pyrazolonated compound produced using the pyrazolone compound of the present invention is less likely to be decomposed and can be a stable pyrazolonated compound.

[0011] Examples of halogen atoms include fluorine, chlorine, bromine, and iodine atoms. 1 Examples of pyrazolone compounds in which is a halogen atom include, but are not limited to, [ka] Examples include:

[0012] The nitro group is represented by -NO2. 1 Examples of pyrazolone compounds in which is a nitro group include, but are not limited to, [ka] Examples include:

[0013] A cyano group is a group represented by -CN. 1 Examples of pyrazolone compounds in which is a cyano group include, but are not limited to, [ka] Examples include:

[0014] A haloalkyl group having 1 to 10 carbon atoms (one or more halogen atoms bonded to the carbon atom at position 1) refers to an alkyl group having 1 to 10 carbon atoms in which one or more hydrogen atoms of the alkyl group have been substituted with one or more halogen atoms such as fluorine, chlorine, bromine, or iodine atoms. The haloalkyl group is preferably a haloalkyl group having 1 to 8 carbon atoms, more preferably a haloalkyl group having 1 to 6 carbon atoms, and even more preferably a haloalkyl group having 1 to 4 carbon atoms. In this specification, the alkyl group may be a linear alkyl group, a branched alkyl group, or a cyclic alkyl group. A larger number of halogen atoms is preferred because it enhances the electron-withdrawing effect. However, by having one or more (preferably two or more) halogen atoms bonded to the carbon atom at position 1, the haloalkyl group can function as an electron-withdrawing group. In this specification, the "carbon atom at position 1" of a haloalkyl group refers to the carbon atom bonded to the -(CH)- of R. Furthermore, in a haloalkyl group having 2 to 10 carbon atoms, although not limited thereto, preferably one or more (preferably two or more) halogen atoms are bonded to the carbon atom at position 2. Examples of the haloalkyl group include a chloromethyl group, a 2,2,2-trichloroethyl group, and a 2,2,2-trifluoroethyl group. Furthermore, a group in which all hydrogen atoms of an alkyl group are substituted with halogen atoms is referred to as a perhalogenoalkyl group. For example, a perfluoroalkyl group means a group in which all hydrogen atoms of an alkyl group are substituted with fluorine atoms. Specific examples of perhalogenoalkyl groups include a trifluoromethyl group, a 2,2,2-trifluoro-1,1-dichloroethyl group, a perfluoroethyl group, a perfluoropropyl group, a perfluoroisopropyl group, a perfluorobutyl group, a perfluorosec-butyl group, a perfluorotert-butyl group, a perfluoropentyl group, a perfluorohexyl group, a trichloromethyl group, a tribromomethyl group, and a triiodomethyl group. R 1 is a haloalkyl group having 1 to 10 carbon atoms (one or more halogen atoms bonded to the carbon atom at the first position), but examples thereof include, but are not limited to, [ka] Examples include: A haloalkyl group having 1 to 10 carbon atoms (one or more halogen atoms bonded to the carbon atom at position 1) has a strong electron-withdrawing effect and can achieve the effects of the present invention as long as one or more halogen atoms are bonded to the carbon atom at position 1. Furthermore, a haloalkyl group having a total of two or more halogen atoms bonded to the carbon atom at position 1, or a haloalkyl group having a total of two or more halogen atoms bonded to the carbon atoms at positions 1 and 2, has an extremely strong electron-withdrawing effect and can achieve the effects of the present invention.

[0015] The perfluoropolyether group having 2 to 10 carbon atoms is a perfluoroalkyl group containing an ether group (—O—). Specific examples include, but are not limited to, [ka] Examples include:

[0016] A carboxy group is a group represented by -COOH. 1 Examples of pyrazolone compounds in which is a carboxy group include, but are not limited to, [ka] Examples include:

[0017] The substituted aryl group having 6 to 60 carbon atoms (wherein the benzene ring bonded to the pyrazolone skeleton has at least one substituent, and the substituent is one or more selected from the group consisting of a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms (wherein one or more halogen atoms are bonded to the carbon atom at position 1), a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an acyl group having 2 to 61 carbon atoms, an alkoxycarbonyl group having 1 to 60 carbon atoms, an alkoxy group having 1 to 60 carbon atoms, and an alkyl group having 1 to 60 carbon atoms, provided that when the substituent is an alkoxy group having 1 to 60 carbon atoms or an alkyl group having 1 to 60 carbon atoms, the substituent is located at the meta position of the benzene ring bonded to the pyrazolone skeleton) is essentially a group in which a hydrogen atom of the benzene ring bonded to the pyrazolone skeleton is substituted with a substituent that is an electron-withdrawing group. At least one hydrogen atom of the benzene ring bonded to the pyrazolone skeleton is substituted, and the group may have two, three, four, or five substituents. When two or more substituents are present, the substituents may be the same or a combination of two or more of the above-mentioned substituents. The position of the electron-withdrawing group is not limited, but is most preferably the para position. 1 Examples of pyrazolone compounds in which an aryl group having 6 to 60 carbon atoms is substituted with include, but are not limited to, [ka] Examples include:

[0018] The acyl group having 2 to 61 carbon atoms is R 5 is a group represented by -OC-, and R 5 is a hydrocarbon group. 5 Examples of the alkyl group include, but are not limited to, an optionally substituted alkyl group having 1 to 60 carbon atoms, an optionally substituted alkenyl group having 1 to 60 carbon atoms, an optionally substituted alkynyl group having 1 to 60 carbon atoms, an optionally substituted aralkyl group having 1 to 60 carbon atoms, and an optionally substituted aryl group having 6 to 60 carbon atoms.

[0019] R 1 is expressed by the following formula (2): [ka] R may be a group represented by 3 is a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms, a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an optionally substituted alkyl group having 1 to 60 carbon atoms, an optionally substituted alkenyl group having 1 to 60 carbon atoms, an optionally substituted alkynyl group having 1 to 60 carbon atoms, an optionally substituted aralkyl group having 1 to 60 carbon atoms, an optionally substituted aryl group having 6 to 60 carbon atoms, an optionally substituted alkoxy group having 1 to 60 carbon atoms, an optionally substituted alkenyloxy group having 1 to 60 carbon atoms, an optionally substituted alkynyloxy group having 1 to 60 carbon atoms, an optionally substituted aralkyloxy group having 1 to 60 carbon atoms, and / or an optionally substituted aryloxy group having 6 to 60 carbon atoms. R 3 Specific examples of the haloalkyl group having 1 to 10 carbon atoms include a trifluoromethanesulfonyl group and a pentafluoroethanesulfonyl group. 3 However, specific examples of the optionally substituted alkyl group having 1 to 60 carbon atoms include a methylsulfonyl group (mesyl group), an ethylsulfonyl group, an n-propylsulfonyl group, an isopropylsulfonyl group, an n-butylsulfonyl group, an isobutylsulfonyl group, a sec-butylsulfonyl group, and a tert-butylsulfonyl group. 3 However, specific examples of the optionally substituted aryl group having 6 to 60 carbon atoms include a phenylsulfonyl group, a methylphenylsulfonyl group, a methyl-para-tolylsulfonyl group, a methyl-metatolylsulfonyl group, a methyl-orthotolylsulfonyl group, a 1-naphthylsulfonyl group, a 2-naphthylsulfonyl group, and a 2-methylphenylsulfonyl group. The group represented by formula (2) functions as an electron-withdrawing group due to the sulfonyl group moiety close to the pyrazolone skeleton. 3 It is thought that R does not have a significant effect on the function as an electron-withdrawing group. 3 may be an alkyl or aryl group that is not an electron-withdrawing group, or may be a halogen atom, a nitro group, or the like that is an electron-withdrawing group. R 1 The pyrazolone compound in which is a group represented by formula (2) includes, but is not limited to, for example, [ka] Examples include:

[0020] R 1 is expressed by the following formula (3): [ka] R may be a group represented by 4is a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms, a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an optionally substituted alkyl group having 1 to 60 carbon atoms, an optionally substituted alkenyl group having 1 to 60 carbon atoms, an optionally substituted alkynyl group having 1 to 60 carbon atoms, an optionally substituted aralkyl group having 1 to 60 carbon atoms, an optionally substituted aryl group having 6 to 60 carbon atoms, an optionally substituted alkoxy group having 1 to 60 carbon atoms, an optionally substituted alkenyloxy group having 1 to 60 carbon atoms, an optionally substituted alkynyloxy group having 1 to 60 carbon atoms, an optionally substituted aralkyloxy group having 1 to 60 carbon atoms, an optionally substituted aryloxy group having 6 to 60 carbon atoms, and / or an optionally substituted aryloxycarbonyl group having 6 to 60 carbon atoms. R 4In the case of an alkoxy group having 1 to 60 carbon atoms, which may be substituted, in one embodiment it is an alkoxy group having 1 to 30 carbon atoms, in one embodiment it is an alkoxy group having 1 to 20 carbon atoms, and in one embodiment it is an alkoxy group having 1 to 10 carbon atoms. Specific examples of the group of formula (3) include a methoxycarbonyl group, an ethoxycarbonyl group, and a butoxycarbonyl group. An alkoxy group having 1 to 60 carbon atoms functions as an electron-withdrawing group due to the ester moiety (or carbonyl moiety) close to the pyrazolone skeleton. Therefore, it is believed that a group bonded via an ester moiety close to the pyrazolone skeleton does not significantly affect the function as an electron-withdrawing group. Therefore, for example, an alkoxy group having 60 carbon atoms can also function as an electron-withdrawing group. 1 is an optionally substituted alkoxy group having 1 to 60 carbon atoms, examples of which include, but are not limited to, [ka] Examples include:

[0021] R 4 In the case of an optionally substituted alkyl group having 1 to 60 carbon atoms, in one embodiment it is an alkyl group having 1 to 30 carbon atoms, in one embodiment it is an alkyl group having 1 to 20 carbon atoms, and in one embodiment it is an alkyl group having 1 to 10 carbon atoms. Specific examples of the group of formula (3) include an acetyl group, a propionyl group, a butanoyl group, a 2-methylpropionyl group, a heptanoyl group, a 2-methylbutanoyl group, a 3-methylbutanoyl group, an octanoyl group, a decanoyl group, a dodecanoyl group, and an octadecanoyl group. In the case of an optionally substituted alkyl group having 1 to 60 carbon atoms, the carbonyl group moiety close to the pyrazolone skeleton exerts its function as an electron-withdrawing group. Therefore, it is believed that a group bonded via a carbonyl group close to the pyrazolone skeleton does not significantly affect its function as an electron-withdrawing group. Therefore, an alkyl group having 60 carbon atoms can also exert its function as an electron-withdrawing group. 1is an optionally substituted alkyl group having 1 to 60 carbon atoms, but is not limited thereto. Examples of the pyrazolone compound include, but are not limited to, [ka] Examples include:

[0022] R 4 In the case of an optionally substituted aryl group having 6 to 60 carbon atoms, in one embodiment it is an aryl group having 6 to 30 carbon atoms, in one embodiment it is an aryl group having 6 to 22 carbon atoms, and in one embodiment it is an aryl group having 6 to 10 carbon atoms. Specific examples of the group of formula (3) include a benzoyl group, a methylbenzoyl group, an ethylbenzoyl group, a propylbenzoyl group, a butylbenzoyl group, a dimethylbenzoyl group, a 1-butylcarbonyl group, and a naphthylcarbonyl group. In the case of an optionally substituted aryl group having 6 to 60 carbon atoms, the carbonyl group moiety close to the pyrazolone skeleton exerts its function as an electron-withdrawing group. Therefore, it is believed that an aryl group bonded to the pyrazolone skeleton via a carbonyl group does not significantly affect its function as an electron-withdrawing group. Therefore, for example, an aryl group having 60 carbon atoms can also exert its function as an electron-withdrawing group. R 1 is an optionally substituted aryl group having 6 to 60 carbon atoms, examples of the pyrazolone compound include, but are not limited to, [ka] Examples include:

[0023] R 1 are expressed by the following equations (4) to (7): [ka] R may be a group represented by 4is a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms, a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an optionally substituted alkyl group having 1 to 60 carbon atoms, an optionally substituted alkenyl group having 1 to 60 carbon atoms, an optionally substituted alkynyl group having 1 to 60 carbon atoms, an optionally substituted aralkyl group having 1 to 60 carbon atoms, an optionally substituted aryl group having 6 to 60 carbon atoms, an optionally substituted alkoxy group having 1 to 60 carbon atoms, an optionally substituted alkenyloxy group having 1 to 60 carbon atoms, an optionally substituted alkynyloxy group having 1 to 60 carbon atoms, an optionally substituted aralkyloxy group having 1 to 60 carbon atoms, an optionally substituted aryloxy group having 6 to 60 carbon atoms, an optionally substituted alkylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkenylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkynylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted aralkylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted arylcarbonyl group having 6 to 60 carbon atoms, an optionally substituted alkoxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkenyloxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkynyloxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted aralkyloxycarbonyl group having 1 to 60 carbon atoms, and / or an optionally substituted aryloxycarbonyl group having 6 to 60 carbon atoms; and in the case of formula (4), R 4 is 0 to 4, and in the case of formulas (5) to (7), R 4 is 0 to 3.

[0024] The group represented by formula (4) is an optionally substituted pyridyl group, which is a residue formed by removing one hydrogen atom from pyridine (C5H5N). The position of the hydrogen atom removed on the pyridine ring may be any carbon atom in the ortho, meta, or para position relative to the nitrogen atom. That is, pyridyl groups include 2-pyridyl groups, 3-pyridyl groups, and 4-pyridyl groups. R 4 is a group in which one or more hydrogen atoms of the pyridyl group are substituted, and may have one, two, three, or four substituents. 4 When R is 0, it means a pyridyl group having no substituents. When R has two or more substituents, the substituents may be the same or may be a combination of two or more of the above-mentioned substituents. 1 The pyrazolone compound in which is a group represented by formula (4) includes, but is not limited to, for example, [ka] Examples include:

[0025] The groups represented by formulas (5) to (7) are optionally substituted diazine groups, which are the residues formed by removing one hydrogen atom from diazine (C4H4N2). Diazines include three isomers, namely, pyrazine, pyrimidine, and pyridazine, depending on the position of the nitrogen, but the removal of the hydrogen atom can be at any carbon atom. R 4 R is a group in which one or more hydrogen atoms of the diazine group are substituted, and may have one, two, or three substituents. 4 When R is 0, it means a pyrazine group, pyrimidine group, or pyridazine group that has no substituent. When R has two or more substituents, the substituents may be the same or a combination of two or more of the above substituents. 1 The pyrazolone compounds in which the group represented by formula (5) to (7) is a group include, but are not limited to, the following: [ka] Examples include:

[0026] In the formulas (2) to (7), R 3 and R 4 The halogen atom, nitro group, cyano group, haloalkyl group having 1 to 10 carbon atoms, or carboxy group is R 1 In addition, an optionally substituted alkyl group having 1 to 60 carbon atoms, an optionally substituted alkenyl group having 1 to 60 carbon atoms, an optionally substituted alkynyl group having 1 to 60 carbon atoms, an optionally substituted aralkyl group having 1 to 60 carbon atoms, an optionally substituted alkoxy group having 1 to 60 carbon atoms, an optionally substituted alkenyloxy group having 1 to 60 carbon atoms, an optionally substituted alkynyloxy group having 1 to 60 carbon atoms, an optionally substituted aralkyloxy group having 1 to 60 carbon atoms, an optionally substituted alkylcarbonyl group having 1 to 60 carbon atoms, and an optionally substituted alkenylcarbonyl group having 1 to 60 carbon atoms. In one embodiment, the number of carbon atoms in the optionally substituted alkynylcarbonyl group having 1 to 60 carbon atoms, the optionally substituted aralkylcarbonyl group having 1 to 60 carbon atoms, the optionally substituted alkoxycarbonyl group having 1 to 60 carbon atoms, the optionally substituted alkenyloxycarbonyl group having 1 to 60 carbon atoms, the optionally substituted alkynyloxycarbonyl group having 1 to 60 carbon atoms, the optionally substituted aralkyloxycarbonyl group having 1 to 60 carbon atoms, and / or the optionally substituted aryloxycarbonyl group having 6 to 60 carbon atoms is 1 to 30 carbon atoms, in one embodiment, 1 to 20 carbon atoms, and in one embodiment, 1 to 10 carbon atoms. Furthermore, the number of carbon atoms in the optionally substituted aryl group having 6 to 60 carbon atoms, the optionally substituted aryloxy group having 6 to 60 carbon atoms, or the optionally substituted arylcarbonyl group having 6 to 60 carbon atoms is 6 to 30 carbon atoms in one embodiment, 6 to 22 carbon atoms in one embodiment, and 6 to 10 carbon atoms in another embodiment.

[0027] The substituent of the hydrogen atom such as the optionally substituted alkyl group having 1 to 60 carbon atoms is not particularly limited as long as the effects of the present invention can be obtained, and examples thereof include a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms, a carboxy group, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 1 to 10 carbon atoms, an alkynyl group having 1 to 10 carbon atoms, an aralkyl group having 1 to 10 carbon atoms, an aryl group having 6 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, an alkenyloxy group having 1 to 10 carbon atoms, an alkynyloxy group having 1 to 10 carbon atoms, an aralkyl group having 1 to 10 carbon atoms, an aryl group having 6 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, an alkenyloxy group having 1 to 10 carbon atoms, an alkynyloxy group having 1 to 10 carbon atoms, an aralkyl group having 1 to 10 carbon atoms, an aryl group having 6 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, an aryl group having 6 ... Examples of the alkyloxy group include an aryloxy group having 6 to 10 carbon atoms, an alkylcarbonyl group having 1 to 10 carbon atoms, an alkenylcarbonyl group having 1 to 10 carbon atoms, an alkynylcarbonyl group having 1 to 10 carbon atoms, an aralkylcarbonyl group having 1 to 10 carbon atoms, an arylcarbonyl group having 6 to 10 carbon atoms, an alkoxycarbonyl group having 1 to 10 carbon atoms, an alkenyloxycarbonyl group having 1 to 10 carbon atoms, an alkynyloxycarbonyl group having 1 to 10 carbon atoms, an aralkyloxycarbonyl group having 1 to 10 carbon atoms, and / or an aryloxycarbonyl group having 6 to 10 carbon atoms. The 1 to 10 carbon atoms is preferably 1 to 6 carbon atoms, and more preferably 1 to 4 carbon atoms. The 6 to 10 carbon atoms is preferably 6 carbon atoms.

[0028] R in the pyrazolone compounds of the present invention 2 is not particularly limited as long as the effects of the present invention can be obtained, but is a hydrocarbon group having 1 to 1000 carbon atoms which may contain a heteroatom, in one embodiment a hydrocarbon group having 1 to 200 carbon atoms, and in another embodiment a hydrocarbon group having 1 to 100 carbon atoms. The heteroatom is not particularly limited, but includes a nitrogen atom (N), an oxygen atom (O), a sulfur atom (S), a phosphorus atom (P), a chlorine atom (Cl), an iodine atom (I), a bromine atom (Br), a fluorine atom (F), or a silicon atom (Si). The group R2 may contain one or more of the heteroatoms, or may contain two or more different types of heteroatoms. R 2 As will be described later, R does not affect the stability of the pyrazolonated compound produced using the pyrazolone compound of the present invention. 2is not limited in principle. Examples of the hydrocarbon group include saturated or unsaturated chain hydrocarbon groups, alicyclic hydrocarbon groups, aromatic groups, and polyethylene glycol groups. More specific examples of hydrocarbon groups having 1 to 1000 carbon atoms and which may contain heteroatoms include polymers containing polyethylene glycol, polyols, amino acids and derivatives thereof, peptides, proteins, nucleic acids, sugars and derivatives thereof, and the like.

[0029] n is an integer of 0 to 2. The -(CH2)n- group is a group that connects the pyrazolone skeleton and R 1 The electron-withdrawing group R 1 The effects of the present invention can be achieved as long as the distance between the -(CH2)n- group and the pyrazolone skeleton is equal to or less than a certain value. That is, the shorter the -(CH2)n- group, the better. Therefore, n is preferably an integer of 0 or 1, and more preferably 0. However, for electron-withdrawing groups with very strong electron-withdrawing properties (e.g., halogen atoms, nitro groups, cyano groups, haloalkyl groups having 1 to 10 carbon atoms (having one or more halogen atoms bonded to the carbon atom at the first position), and perfluoropolyether groups having 2 to 10 carbon atoms), the effects of the present invention can be sufficiently achieved even when n = 2. For electron-withdrawing groups with strong electron-withdrawing properties (e.g., carboxy groups and substituted aryl groups having 6 to 60 carbon atoms), the effects of the present invention can be achieved when n = 2, but preferably n = 1 or n = 0.

[0030] The pyrazolone compound of the present invention may take the form of a salt that is acceptable as a pyrazolonizing agent, as described below. That is, it may form an acid addition salt or a salt with a base. Specific salts with bases include salts with inorganic bases, organic bases, or metal alkoxides. The salt can be produced by mixing the pyrazolone compound of the present invention with an inorganic base, organic base, or metal alkoxide. Inorganic bases which can form salts include hydroxides, carbonates, bicarbonates, acetates, or hydrides of alkali metals (e.g., lithium, sodium, or potassium); hydroxides or hydrides of alkaline earth metals (e.g., magnesium, calcium, or barium); and the like. Examples of organic bases capable of forming salts include dimethylamine, triethylamine, piperazine, pyrrolidine, piperidine, 2-phenylethylamine, benzylamine, ethanolamine, diethanolamine, pyridine, and collidine; and examples of metal alkoxides include sodium methoxide, potassium tert-butoxide, and magnesium methoxide. Specific examples of the acid addition salt include salts with inorganic or organic acids, which can be produced by mixing the compound [1] of the present invention with an inorganic or organic acid. The inorganic acid may be hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, or phosphoric acid. Raise Examples of organic acids include formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, mandelic acid, tartaric acid, dibenzoyltartaric acid, ditoluoyltartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, aspartic acid, glutamic acid, benzoic acid, camphorsulfonic acid, ethenesulfonic acid, gluconic acid, hydrobromic acid, isethionic acid, mucic acid, pamoic acid, and pantothenic acid.

[0031] The method for producing the pyrazolone compound of the present invention is not particularly limited, and any method known in the art can be used without any restrictions.

[0032] The pyrazolonating agent of the present invention includes the pyrazolone compound of the present invention and can pyrazolonate the formyl group of a formyl group-containing compound. Specifically, as shown below, the pyrazolone compound of the present invention can be reacted with a formyl group-containing compound such as a protein, peptide, or sugar having a formyl group to obtain a pyrazolonated compound in which two molecules of the pyrazolone compound are bonded. [ka]

[0033] The pyrazolonating agent of the present invention may contain, as components other than the pyrazolone compound, a carrier (for example, water or a buffer solution), an excipient, a diluent, a preservative, a stabilizer, an antiseptic, an antioxidant, or the like. The formyl group-containing compound is not particularly limited as long as it contains a formyl group, and examples thereof include antibodies, drugs, peptides, amino acids and derivatives thereof, peptides, proteins, nucleic acids, sugars and derivatives thereof, and sugars into which a formyl group has been introduced.

[0034] In the method for pyrazolonating a formyl group-containing compound of the present invention, the pyrazolone compound of the present invention is brought into contact with a formyl group-containing compound. Specifically, the reaction is usually carried out in a solvent, and the reaction temperature is usually 0°C to 100°C, and preferably 10°C to 50°C from the viewpoint of reaction rate and reaction efficiency. The reaction time depends on the amount and type of substrate and solvent, the reaction temperature, etc., and is usually 5 minutes to 180 hours, and from the viewpoint of reaction rate and reaction efficiency, it is preferably 30 minutes to 48 hours. The theoretical amount of the pyrazolone compound is 2 moles per mole of the formyl group-containing compound, but this amount can be changed as desired depending on the reaction conditions. Usually, the amount of the pyrazolone compound is 1 to 20 moles, preferably 1 to 10 moles, per mole of the formyl group-containing compound. The reaction pressure is not particularly limited and may be increased, normal or reduced pressure, and is usually 0.01 to 10 MPa (hereinafter, pressure is expressed as absolute pressure), preferably 0.1 to 1 MPa.

[0035] The method for stabilizing a pyrazolone compound of the present invention involves contacting the pyrazolone compound with a formyl group-containing compound. The reaction conditions for the pyrazolone compound and the formyl group-containing compound can be the same as those for the method for pyrazolonizing a formyl group-containing compound. The resulting pyrazolone compound is stable and resistant to decomposition.

[0036] The method for producing a pyrazolone compound of the present invention comprises contacting a pyrazolone compound with a formyl group-containing compound. The reaction conditions for the pyrazolone compound and the formyl group-containing compound can be the same as those for the method for pyrazolonizing a formyl group-containing compound.

[0037] The pyrazolonated compound of the present invention can be produced by the method for producing a pyrazolonated compound of the present invention.

[0038] 《Action》 In the present invention, the mechanism by which the obtained pyrazolone compound is resistant to decomposition and stable has not been analyzed in detail, but can be assumed as follows: However, the present invention is not limited to the following assumption. As described above, pyrazolone compounds are a mixture of isomers of CH, OH, and NH. Therefore, pyrazolonated compounds obtained using pyrazolone compounds are also a mixture of isomers of CH, OH, and NH. Analysis by the present inventors has revealed that, among the isomer mixtures of pyrazolonated compounds, CH isomers are more likely to decompose. Here, R 1 However, if the group is an electron-withdrawing group, the pyrazolone ring will become a stable cyclic resonance structure, the OH form. 1 However, in the case of an electron-withdrawing group, the resulting pyrazolonated compound takes on a stable OH structure, which is thought to increase the stability of the pyrazolonated compound and prevent decomposition. On the other hand, in the formation of the cyclic resonance structure, R 2 Since R does not participate in the conjugated system, 1 If is an electron-withdrawing group, then R 2 Therefore, it is considered that R 2 The structure of R is expected to have no effect on the stability of the pyrazolone compound. 2 The structure of is not limited. [Example]

[0039] The present invention will be described in more detail below using examples, but these examples are intended to illustrate specific examples of the present invention and are not intended to limit the present invention in any way. Although the pyrazolone structure exists in equilibrium with tautomers such as those represented by formula (1), (8), or (9) in the specification, in these examples only the C-H isomer of formula (1) will be described.

[0040] Examples 1 to 4 In this example, a pyrazolone derivative was prepared. (Preparation of Compound 1) (Example 1) Ethyl 4,4,5,5,5-pentafluoro-3-oxovalerate (0.38 mL, 2.2 mmol) was dissolved in acetic acid (5 mL), and phenylhydrazine (0.26 mL, 2.6 mmol) was added. After stirring at 90°C for 23 hours, the reaction mixture was extracted with ethyl acetate. The organic phase was washed with water, saturated aqueous sodium bicarbonate, and saturated brine, and then dried over anhydrous magnesium sulfate. The extract was filtered and concentrated, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate = 10:1 to 2:1) with ethanol to obtain 428.3 mg of compound 1 (71% yield). [ka] compound 1 1 H-NMR( 600MHz, DMSO-d6):δ (ppm) =12.53(brs,1H),7.74-7.67(m,2H),7.56-7.49(m,2H),7.43-7.36(m,1H),5.93(s,1H).

[0041] (Preparation of Compound 2) (Example 2) Ethyl (2,4,5-trifluorobenzoyl)acetate (501.7 mg, 2.04 mmol) was dissolved in acetic acid (5 mL), and phenylhydrazine (0.22 mL, 2.2 mmol) was added. After stirring at 85°C for 24 hours, the reaction mixture was extracted with ethyl acetate. The organic phase was washed with water, saturated aqueous sodium bicarbonate, and saturated brine, and then dried over anhydrous magnesium sulfate. The extract was filtered and concentrated, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate = 6:1 to 3.5:1) with ethanol to give 482.3 mg of compound 2 (yield 81%). [ka] compound 2 1 H-NMR( 600MHz, DMSO-d6):δ (ppm) =12.01(m,1H),8.02-7.92(m,1H),7.87-7.78(m,2H),7.71-7.61(m,1H),7.54-7.46(m,2H),7.37-7.28(m,1H),6.00-5.94(m,1H).

[0042] (Preparation of Compound 3) (Example 3) Ethyl 2-(4-nitrobenzoyl)acetate (501.1 mg, 2.11 mmol) was dissolved in ethanol (5 mL), and phenylhydrazine (220 μL, 2.24 mmol) was added. After stirring under reflux for 22 hours, the solvent was removed under reduced pressure. The residue was extracted with ethyl acetate, and the organic phase was washed with saturated aqueous sodium bicarbonate and saturated brine, and then dried over anhydrous magnesium sulfate. The extract was filtered and concentrated, and the residue was recrystallized from ethanol to obtain 269.9 mg of compound 3 (45% yield). [ka] compound 3 1 H-NMR( 600MHz, DMSO-d6):δ (ppm)=12.11(brs,1H),8.31-8.25(m,2H),8.15-8.08(m,2H),7.85-7.80(m,2H),7.55-7.47(m,2H),7.37-7.31(m,1H),6.22(s,1H).

[0043] (Preparation of Compound 4) (Example 4) Ethyl 3-oxo-3-(4-pyridyl)propionate (414.8 mg, 2.15 mmol) was dissolved in acetic acid (5 mL) and phenylhydrazine (240 μL, 2.44 mmol) was added. After stirring at 85°C for 23 hours, the reaction mixture was extracted with ethyl acetate. The organic phase was washed with water, saturated aqueous sodium bicarbonate, and saturated brine, and then dried over anhydrous magnesium sulfate. The extract was filtered and concentrated, and the residue was purified by silica gel column chromatography (chloroform:methanol = 30:1 to 20:1) with ethanol to give 174.6 mg of compound 4 (yield 34%). [ka] compound 4 1 H-NMR( 600MHz, DMSO-d6):δ (ppm) =12.06(brs,1H),8.63-8.56(m,2H),7.85-7.76(m,4H),7.55-7.46(m,2H),7.36-7.29(m,1H),6.18(s,1H).

[0044] Comparative Example 1 and Examples 5 to 9 In this example, a pyrazolone derivative was introduced into a galactopyranoside. (Preparation of Compound 5) (Comparative Example 1) 4-Nitrophenyl β-D-galactohexodialdo-1,5-pyranoside (11.2 mg, 37.4 μmol) was added to water (3.7 mL) and 3-methyl-1-phenyl-5-pyrazolone (100 mM DMF solution, 1.5 mL, 150 μmol), in that order. After stirring at room temperature for 1 hour, the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol = 30:1 to 10:1) to give 18.4 mg of compound 5 (78% yield). [ka] Compound 5 MALDI-TOF MS(AXIMA-TOF2)m / z[M+H] + calcd for C 32 H 32 N5O9,630.22,found 630.25.

[0045] (Preparation of Compound 6) (Example 5) 4-Nitrophenyl β-D-galactohexodialdo-1,5-pyranoside (13.7 mg, 45.7 μmol) was added to water (4.6 mL), 3-trifluoromethyl-1-phenyl-5-pyrazolone (100 mM DMF solution, 1.9 mL, 190 μmol), and DMF (1.5 mL) in that order. After stirring at room temperature for 22 hours, the reaction mixture was concentrated under reduced pressure. The residue was purified by solid-phase extraction (Sep-Pak C18, methanol:HO = 1:4 to 4:1, Waters) and high-performance liquid chromatography (ODS column, 250 × 10 mm, 5 μm, eluent A: 0.1% aq. TFA, B: CHCN (0.1% TFA), B 55% to 70% (30 min), 30 °C, UV 240 nm) to obtain 0.7 mg of compound 6. [ka] Compound 6 MALDI-TOF MS(AXIMA-TOF2)m / z[M+H] + calcd for C 32 H 26 F6N5O9,738.16,found 737.97.

[0046] (Preparation of Compound 7) (Example 6) 4-Nitrophenyl β-D-galactohexodialdo-1,5-pyranoside (12.8 mg, 42.8 μmol) was added to water (4.3 mL), compound 1 (100 mM DMF solution, 1.8 mL, 180 μmol), and DMF (1.5 mL) in that order. After stirring at room temperature for 24 hours, the reaction mixture was concentrated under reduced pressure. The residue was purified by solid-phase extraction (Sep-Pak C18, methanol:HO = 1:4 to 3:2, Waters) and high-performance liquid chromatography (ODS column 250 × 10 mm, 5 μm, eluent A: 0.1% aq. TFA, B: CHCN (0.1% TFA), B 55% to 70% (30 min), 30 °C, UV 240 nm) to obtain 2.0 mg of compound 7. [ka] Compound 7 MALDI-TOFMS(AXIMA-TOF2)m / z[M+Na] + calcd for C 34 H 25 F 10 N5O9Na,860.14,found 860.24.

[0047] (Preparation of Compound 8) (Example 7) 4-Nitrophenyl β-D-galactohexodialdo-1,5-pyranoside (13.9 mg, 46.5 μmol) was added to water (4.6 mL), compound 2 (100 mM DMF solution, 1.9 mL, 190 μmol), and DMF (4.5 mL) in that order. After stirring at room temperature for 24 hours, the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol = 25:1 to 8:1) to give compound 8 (32.6 mg, 82% yield). [ka] compound 8 1 H-NMR( 600MHz, CD3OD):δ (ppm)=7.91-7.86(m,2H),7.82-7.77(m,2H),7.75-7.63(m,3H),7.59-7.53(m,2H),7.52-7.46(m,2H),7.44-7.39(m,1 H),7.38-7.33(m,1H),7.17-7.01(m,3H),7.00-6.95(m,2H),5.06(d,J=7.7Hz,1H),4.95-4.87(m,1H,overlapped with water signal),3.99(d,J=10.8Hz,1H),3.90(dd,J=7.8,9.5Hz,1H),3.81(d,J=3.2Hz,1H),3.71(dd,J=3.3,9.6,Hz,1H).

[0048] Preparation of Compound 9 (Example 8) 4-Nitrophenyl β-D-galactohexodialdo-1,5-pyranoside (13.4 mg, 44.8 μmol) was added to water (4.5 mL), compound 3 (100 mM DMF solution, 1.8 mL, 180 μmol), and DMF (4.5 mL) in that order. After stirring at room temperature for 22 hours, the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol = 25:1 to 6:1) to give compound 9 (31.9 mg, 84% yield). [ka] compound 9 1 H-NMR( 600MHz, CD3OD):δ (ppm) =8.03-7.97(m,2H),7.89-7.82(m,6H),7.80-7.75(m,2H),7.65-7.61(m,2H),7.58-7.51(m,4H),7.50-7.44(m,2H),7.42-7.37(m,1 H),7.35-7.30(m,1H),6.99-6.95(m,2H),5.09-5.03(m,2H),4.46(d,J=10.8Hz,1H),3.91-3.85(m,2H),3.74(dd,J=3.3,9.6Hz,1H).

[0049] Preparation of Compound 10 (Example 9) 4-Nitrophenyl β-D-galactohexodialdo-1,5-pyranoside (14.6 mg, 48.8 μmol) was added to water (4.9 mL), compound 4 (100 mM DMF solution, 1.96 mL, 196 μmol), and DMF (4.5 mL) in that order. After stirring at room temperature for 24 hours, the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol = 10:1 to 4:1, then chloroform:methanol:water = 12:8:1) to obtain 29.5 mg of compound 10 (80% yield). [ka] compound 10 1 H-NMR( 600MHz, CD3OD):δ (ppm) =8.31(d,J=5.8Hz,2H),8.23(d,J=5.5Hz,2H),7.96(d,J=7.9Hz,2H),7.90-7.84(m, 4H),7.57-7.50(m,4H),7.47-7.43(m,2H),7.39(d,J=5.9Hz,2H),7.34(t,J=7.4Hz, 1H),7.27(t,J=7.4Hz,1H),6.91(d,J=9.1Hz,2H),5.04(d,J=10.6Hz,1H),4.97(d,J =7.7Hz,1H),4.48(d,J=10.7Hz,1H),3.89-3.82(m,2H),3.73(dd,J=3.3,9.6Hz,1H).

[0050] In this example, the stability of pyrazolone derivative-introduced galactopyranosides (compounds 5 to 10) in phosphate buffer was examined. (Study on the stability of pyrazolone derivative-introduced galactopyranoside) Pyrazolone-introduced galactopyranosides (compounds 5–10) were dissolved in DMSO to prepare 5 mM solutions. To this 5 mM solution of compounds 5–10 (25 μL), 0.1 M pH 7.4 phosphate buffer (125 μL), water (62.5 μL), and DMSO (37.5 μL) were added and heated to 37°C. After 1–35 days, aliquots of the reaction mixture were analyzed by reverse-phase HPLC, and the remaining percentages of compounds 5–10 were calculated from the peak areas (Figure 1). As a result, R1 The pyrazolone compounds 6 to 10 obtained from the pyrazolone compounds having an electron-withdrawing group and the formyl group-containing compounds were compared with the control compound 5 (R 1 =Me), it was found that the stability was improved.

[0051] [HPLC analysis conditions using a reversed-phase column] HPLC: GL-7400 (GL Sciences Inc.) Column: Mightysil RP-18 GP Aqua, 5 μm, Φ2 × 250 mm (Kanto Chemical Co., Ltd.) Column temperature: 30℃ Mobile phase A: 0.1% TFA in HO (v / v) Mobile phase B: MeCN solution containing 0.1% TFA (v / v) Gradient (% mobile phase B): Compound 5, 30% (0 min), 60% (30 min); Compound 6, 45% (0 min), 80% (30 min); Compound 7, 60% (0 min), 90% (30 min); Compound 8, 50% (0 min), 80% (30 min); Compound 9, 50% (0 min), 80% (30 min); Compound 10, 30% (0 min), 80% (30 min). Flow rate: 0.2mL / min Detection wavelengths: compound 5, 240 nm; compound 6, 240 nm; compound 7, 240 nm; compound 8, 252 nm; compound 9, 250 nm; compound 10, 235 nm.

[0052] In the present invention, the compounds shown in the following Table 1 are preferred. Note that in the pyrazolone compounds in the following Table 1, n=0.

[0053] Examples 10 to 26 Preparation of Compound 11 (Example 10) Ethyl (4-fluorobenzoyl)acetate (300 μL, 1.70 mmol) was dissolved in acetic acid (3.0 mL) under an argon atmosphere, and phenylhydrazine (183 μL, 1.87 mmol) was added. After stirring at 85 °C for 17 hours, ethyl acetate was added to the reaction solution, and the organic layer was washed with water, saturated aqueous sodium bicarbonate, and saturated brine, and then dried over anhydrous magnesium sulfate. The solution was filtered and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate = 4:1) to obtain 206 mg of compound 11 (yield 95%). [ka] compound 11 1 H-NMR (600 MHz, CDCl3): δ (ppm) = 7.97(dd,J=1.2,9.0Hz,2H),7.80-7.77(m,2H),7.44(t,J=7.2Hz,2H),7.23(t,J=7.2Hz,1H),7.17-7.15(m,2H),3.85(s2H).

[0054] Preparation of Compound 12 (Example 11) Ethyl (4-chlorobenzoyl)acetate (150 mg, 0.66 mmol) was dissolved in acetic acid (1.5 mL) and phenylhydrazine (72 μL, 0.73 mmol) was added. After stirring at 85°C for 22 hours, ethyl acetate was added to the reaction mixture. The organic layer was washed with water, saturated aqueous sodium bicarbonate, and saturated brine, and then dried over anhydrous magnesium sulfate. The solution was filtered and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate = 3:1) to give 154 mg of compound 12 (yield 84%). [ka] compound 12 1 H-NMR (600 MHz, CDCl3): δ (ppm) = 7.93(d,J=7.8Hz,2H),7.68(d,J=8.4Hz,2H),7.43-7.40(m,4H),7.22(t,J=7.2Hz,1H),3.78(s,2H).

[0055] Preparation of Compound 13 (Example 12) Ethyl (4-cyanobenzoyl)acetate (300 mg, 1.38 mmol) was dissolved in acetic acid (3.0 mL) and phenylhydrazine (150 μL, 1.52 mmol) was added. After stirring at 85°C for 22 hours, ethyl acetate was added to the reaction mixture. The organic layer was washed with water, saturated aqueous sodium bicarbonate, and saturated brine, and then dried over anhydrous magnesium sulfate. The solution was filtered and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate = 3:1) to give 198 mg of compound 13 (yield 55%). [ka] compound 13 1 H-NMR (600 MHz, CDCl3): δ (ppm) = 7.92(d,J=7.8Hz,2H),7.87(d,J=7.8Hz,2H),7.74(d,J=8.4Hz,2H),7.44(t,J=7.8Hz,2H),7.25(t,J=7.8Hz,1H),3.86(s,2H).

[0056] Preparation of Compound 14 (Example 13) Ethyl 3-oxo-3-(pyridin-4-yl)propanoate (215 mg, 1.11 mmol) was dissolved in tetrahydrofuran (3.7 mL) under an argon atmosphere, and methylhydrazine (58.6 μL, 1.11 mmol) was added. After stirring at 65°C for 5 hours, the solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (chloroform:methanol = 30:1) to give 181 mg (93% yield) of compound 14. [ka] compound 14 1 H-NMR (600 MHz, CDCl3): δ (ppm) = 8.67(d,J=6.2Hz,2H),7.51(d,J=6.1Hz,2H),3.59(s,2H),3.44(s,3H).

[0057] Preparation of Compound 15 (Example 14) Ethyl 3-oxo-3-(pyridin-2-yl)propanoate (155 mg, 802 μmol) was dissolved in acetic acid (1.5 mL) under an argon atmosphere, and phenylhydrazine (86.8 μL, 883 μmol) was added. After stirring at 85 °C for 22 hours, the reaction mixture was diluted with methanol. The solvent was removed under reduced pressure by azeotropy with toluene, and the mixture was dried using a vacuum pump. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate = 1:1) to give 152 mg of compound 15 (80% yield). [ka] compound 15 1 H-NMR (600 MHz, CDCl3): δ (ppm) = 8.64(d,J=4.8Hz,1H),8.15(dd,J=1.2,8.4Hz,1H),7.97(d,J=8.4Hz,2H),7.80(t,J= 7.8Hz,1H),7.45(t,J=7.8Hz,2H),7.37-7.33(m,1H),7.25-7.22(m,1H),4.03(s,2H).

[0058] Preparation of Compound 16 (Example 15) 3-(2,6-Dichloro-5-fluoropyridin-3-yl)-3-oxopropanoic acid ethyl ester (202 mg, 721 μmol) was dissolved in acetic acid (2.0 mL) and phenylhydrazine (78.0 μL, 793 μmol) was added. After stirring at 85 °C for 22 hours, the reaction mixture was diluted with methanol. The solvent was removed under reduced pressure by azeotropy with toluene, and the mixture was dried using a vacuum pump. The residue was purified by silica gel column chromatography (hexane:ethyl acetate = 4:1) to give 176 mg of compound 16 (75% yield). [ka] compound 16 1 H-NMR (600 MHz, DMSO-d): δ (ppm) =12.13(brs,1H),8.41(d,J=8.8Hz,1H),7.81(dd,J=1.0,7.8Hz,2H),7.49(t,J=7.6Hz,2H),7.33(d,J=7.4Hz,1H),6.22(s,1H). Compound 16 was observed as the enol form in DMSO-d6. [ka]

[0059] Preparation of Compound 17 (Example 16) Ethyl 3-oxo-3-(pyridin-3-yl)propanoate (196 mg, 1.01 mmol) was dissolved in acetic acid (2.0 mL) and phenylhydrazine (110 μL, 1.12 mmol) was added. After stirring at 85 °C for 22 hours, the reaction mixture was diluted with methanol. The solvent was removed under reduced pressure by azeotropy with toluene, and the mixture was dried using a vacuum pump. The resulting residue was purified by silica gel column chromatography (chloroform:methanol = 50:1) to give 169 mg of compound 17 (70% yield). [ka] compound 17 1 H-NMR (600 MHz, CDCl3): δ (ppm) = 8.94(d,J=2.0Hz,1H),8.70(dd,J=1.1,4.8Hz,1H),8.16-8.14(m,1H),7.96(d,J=8.4Hz,2H),7.46-7.41(m,3H),7.25-7.23(m,1H),3.89(s,2H).

[0060] Preparation of Compound 18 (Example 17) [6-(Trifluoromethyl)nicotinyl]acetic acid methyl ester (144 mg, 582 μmol) was dissolved in acetic acid (1.4 mL) and phenylhydrazine (63.0 μL, 641 μmol) was added. After stirring at 85 °C for 22 hours, the reaction mixture was diluted with methanol. The solvent was removed under reduced pressure by azeotropy with toluene, and the mixture was dried using a vacuum pump. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate = 2:1) to give 167 mg of compound 18 (yield 94%). [ka] compound 18 1 H-NMR (600 MHz, CDCl3): δ (ppm) = 9.05(brs,1H),8.30(d,J=8.2Hz,1H),7.93(d,J=7.7Hz,2H),7.79(d,J=8.2Hz,1H),7.46(t,J=7.7Hz,2H),7.29-7.27(m,1H),3.91(s,2H).

[0061] Preparation of Compound 19 (Example 18) Ethyl 3-oxo-3-(pyrazin-2-yl)propionate (417 mg, 2.15 mmol) was dissolved in acetic acid (4.2 mL) and phenylhydrazine (232 μL, 2.32 mmol) was added. After stirring at 85 °C for 2 hours, the reaction mixture was diluted with ethyl acetate. The solvent was removed under reduced pressure by azeotropy with toluene, and the mixture was dried using a vacuum pump. The resulting residue was purified by silica gel column chromatography (chloroform:acetone = 5:1) to give 434 mg of compound 19 (85% yield). [ka] compound 19 1 H-NMR (600 MHz, DMSO-d): δ (ppm) =12.13(brs,1H),8.65(dd,J=1.6,2.4Hz,1H),8.57(d,J=2.5Hz,1H),7.84(d,J=8.1Hz,2H),7.53-7.50(m,2H),7.35(t,J=7.4Hz,1H),6.17(s,1H). Compound 19 was observed as the enol form in DMSO-d6. [ka]

[0062] Preparation of Compound 20 (Example 19) Ethyl (2,3,4,5,6-pentafluorobenzoyl)acetate (150 mg, 0.53 mmol) was dissolved in acetic acid (1.5 mL) and phenylhydrazine (57.0 μL, 0.58 mmol) was added. After stirring at 80 °C for 1 hour, the solvent was evaporated under reduced pressure using a toluene azeotropic distillation. The mixture was dried using a vacuum pump, and the resulting residue was purified by silica gel column chromatography (toluene:ethyl acetate = 30:1) to give 110 mg of compound 20 (yield 64%). [ka] compound 20 1 H-NMR (600 MHz, CDCl3): δ (ppm) = 7.89(d,J=8.2Hz,2H),7.43(t,J=8.6Hz,2H),7.26-7.23(m,1H),3.92(s,2H).

[0063] Preparation of Compound 21 (Example 20) Ethyl (4-chloro-2,3,5-trifluorobenzoyl)acetate (150 mg, 0.53 mmol) was dissolved in acetic acid (1.5 mL) and phenylhydrazine (58.0 μL, 0.59 mmol) was added. After stirring at 80 °C for 23 hours, the solvent was evaporated under reduced pressure using a toluene azeotropic distillation. The residue was dried using a vacuum pump, and purified by silica gel column chromatography (hexane:ethyl acetate = 6:1) to give 136 mg of compound 21 (79% yield). [ka] compound 21 1 H-NMR (600 MHz, CDCl3): δ (ppm) = 7.92-7.97(m,3H),7.43(t,J=7.8Hz,2H),7.26-7.23(m,1H),3.94(s,2H).

[0064] Preparation of Compound 22 (Example 21) Ethyl 5-[(4-methylphenyl)sulfonyl]-3-oxopentanoate (150 mg, 0.50 mmol) was dissolved in acetic acid (1.5 mL) and phenylhydrazine (54.0 μL, 0.55 mmol) was added. After stirring at 80 °C for 40 minutes, the solvent was evaporated under reduced pressure using a toluene azeotropic distillation. The mixture was dried using a vacuum pump, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate = 3:2) to give 75 mg of compound 22 (44% yield). [ka] compound 22 1 H-NMR (600 MHz, CDCl3): δ (ppm) = 7.78-7.72(m,4H),7.34-7.31(m,4H),7.14(t,J=7.2Hz,1H),3.50(t,J=7.2Hz,2H),3.34(s,2H),2.86(t,J=7.2Hz,2H),2.38(s,3H).

[0065] Preparation of Compound 23 (Example 22) Ethyl (3-methoxybenzoyl)acetate (43.6 μL, 0.23 mmol) was dissolved in acetic acid (563 μL) under an argon atmosphere, and phenylhydrazine (24.3 μL, 0.25 mmol) was added. After stirring at 85°C for 24 hours, the reaction solution was diluted with ethyl acetate and made basic by adding saturated aqueous sodium bicarbonate. The organic layer was washed with saturated aqueous sodium bicarbonate and dried over anhydrous sodium sulfate. The solution was filtered and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate = 6:1 to 4:1) to obtain 46 mg of compound 23 (76% yield). [ka] compound 23 1 H-NMR (600 MHz, CDCl3): δ (ppm) = 7.97(d,J=7.6Hz,2H),7.43(t,J=7.5Hz,2H),7.36-7.35(m,2H),7.28(d,J=7.6Hz, 1H),7.22(t,J=7.4Hz,1H),7.00(dd,J=2.6,8.0Hz,1H),3.88(s,3H),3.38(s,2H).

[0066] Preparation of Compound 24 (Example 23) Ethyl (2-nitrobenzoyl)acetate (600 mg, 2.53 mmol) was dissolved in acetic acid (6.0 mL) and phenylhydrazine (273 μL, 2.79 mmol) was added. After stirring at 80 °C for 21 hours, the solvent was evaporated under reduced pressure using a toluene azeotropic distillation. The mixture was dried using a vacuum pump, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate = 4:1) to give 104 mg of compound 24 (yield 15%). [ka] compound 24 1 H-NMR (600 MHz, DMSO-d): δ (ppm) = 12.04(brs,1H),7.85(dd,J=7.5 Hz,1H),7.7-7.69(m,3H),7.58(t,J=7.8Hz,1H),7.49(t,J=7.8Hz,2H),7.31(t,J=7.5Hz,1H),5.86(s,1H). Compound 24 was observed as the enol form in DMSO-d6. [ka]

[0067] Preparation of Compound 25 (Example 24) Ethyl (3-nitrobenzoyl)acetate (300 mg, 1.26 mmol) was dissolved in acetic acid (4.0 mL) and phenylhydrazine (137 μL, 1.39 mmol) was added. After stirring at 80 °C for 21 hours, the solvent was evaporated under reduced pressure using a toluene azeotropic distillation. The residue was dried using a vacuum pump, and purified by silica gel column chromatography (hexane:ethyl acetate = 3:1) to give 242 mg of compound 25 (yield 68%). [ka] compound 25 1 H-NMR (600 MHz, CDCl3): δ (ppm) = 7.94(d,J=7.8Hz,2H),7.69(t,J=8.4Hz,2H),7.44-7.41(m,4H),7.22(t,J=7.2Hz,1H),3.79(s,2H).

[0068] Preparation of Compound 26 (Example 25) Ethyl hydrazinoacetate hydrochloride (1.04 g, 6.74 mmol) and sodium acetate (615 mg, 7.50 mmol) were dissolved in absolute ethanol (10 mL) under an argon atmosphere. After stirring at room temperature for 5 minutes, ethyl 4,4,4-trifluoroacetoacetate (1.00 mL, 6.80 mmol) was added and the mixture was heated to reflux for 24 hours. Insoluble matter was filtered off, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol:acetic acid = 190:10:2) to give crude ethyl ester A. The crude product was dissolved in ethyl acetate with heating and precipitated with hexane to give 513 mg of ethyl ester A (32% yield). 242 mg (1.01 mmol) of ethyl ester A was dissolved in a mixed solvent of tetrahydrofuran (6.8 mL) and methanol (10.2 mL), and then aqueous sodium hydroxide solution (603 mM, 3.4 mL) was added and the mixture was stirred at room temperature for 19 hours. The reaction solution was adjusted to pH 6.0 with 4 M hydrochloric acid under ice cooling, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol = 2:1 to 1:4) to obtain crude carboxylic acid A (268 mg). The crude carboxylic acid A was dissolved in DMF (1 mL) under argon atmosphere, and a DMF solution (1.5 mL) of 1-hydroxy-7-azabenzotriazole (HOAt: 209 mg, 1.53 mmol), 11-azido-3,6,9-trioxaundecan-1-amine (250 μL, 1.26 mmol), N,N-diisopropylethylamine (260 μL, 1.53 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl: 300 mg, 1.57 mmol) was added. The mixture was stirred at room temperature for 23 hours. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (chloroform:methanol=40:1 to 35:1) to obtain 283 mg of compound 26 (yield 67%, two steps). [ka] compound 26 1 H-NMR (600 MHz, DMSO-D6): δ (ppm) =11.82(brs,1H),8.16(t,J=5.5Hz,1H),5.71(s,1H),4.59(s,2H),3.64-3.59(m, 2H),3.58-3.51(m,8H),3.47-3.43(m,2H),3.40-3.38(m,2H),3.28-3.22(m,2H).

[0069] (Preparation of Compound 27) (Example 26) Ethyl hydrazinoacetate hydrochloride (1.04 g, 6.72 mmol) and sodium acetate (607 mg, 7.40 mmol) were dissolved in absolute ethanol (20 mL) under an argon atmosphere. After stirring at room temperature for 5 minutes, ethyl 3-oxo-3-(4-pyridyl)propionate (1.43 g, 7.41 mmol) was added and the mixture was heated to reflux for 22 hours. Insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol = 40:1 to 25:1) to give 569 mg (34% yield) of ethyl ester C. 301 mg (1.22 mmol) of ethyl ester C was dissolved in a mixed solvent of tetrahydrofuran (8.2 mL) and methanol (12.3 mL). Aqueous sodium hydroxide solution (603 mM, 4.1 mL) was added and the mixture was stirred at room temperature for 19 hours. The reaction solution was adjusted to pH 6.0 by adding 4 M hydrochloric acid under ice cooling, and the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol = 3:1 to 1:1) to give a crude product (316 mg) of carboxylic acid C. The crude product was desalted using Diaion HP-20 to give 190 mg (yield 71%) of carboxylic acid C. A 98 mg (466 μmol) portion of the resulting carboxylic acid C was dissolved in DMF (1.0 mL) under an argon atmosphere. A DMF solution (1.5 mL) of 1-hydroxy-7-azabenzotriazole (HOAt: 100 mg, 735 μmol), 11-azido-3,6,9-trioxaundecan-1-amine (110 μL, 554 μmol), N,N-diisopropylethylamine (115 μL, 676 μmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl: 212 mg, 678 μmol) was added and stirred at room temperature for 19 h. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (chloroform:methanol = 40:1 to 10:1) to give crude compound 27. The crude product was purified again by silica gel column chromatography (chloroform:methanol:acetic acid=250:10:0.26 to 200:10:0.21) to obtain 43 mg of compound 27 (yield 23%). [ka] compound 27 1 H-NMR (600 MHz, CD3OD): δ (ppm) = 8.52(brs,2H),7.80-7.76(m,2H),4.72(s,2H),3.65-3.59(m,12H),3.59-3.55(m,2H),3.42(t,J=5.4Hz,2H),3.37-3.34(m,2H).

[0070] In the following examples, a pyrazolone compound was introduced into a galactopyranoside to synthesize a pyrazolone-galactose conjugate.

[0071] Examples 27 to 41 (General Synthesis Examples) The pyrazolone-galactose conjugates, Compounds 28 to 42, were synthesized according to the following procedure. A 50 mL polypropylene centrifuge tube was charged with an aqueous solution of 4-nitrophenyl β-D-galactopyranoside (50 mM, 720 μL), phosphate buffer (1.0 M, pH 7.0, 1.8 mL), water (32.5 mL), an aqueous solution of galactose oxidase (Worthington Biochemical Corporation, 90 units / mL, 623 μL), an aqueous solution of wasabi peroxidase (Oriental Yeast Co., Ltd., 3 units / mL, 396 μL), and a DMF solution of pyrazolone compound (25 mM, 5.76 mL). The mixture was then shaken in a constant temperature shaking bath at 30°C for 24 hours at a shaking speed of 165 rpm. The reaction solution was transferred to a 1 L recovery flask, methanol was added, and the solvent was concentrated under reduced pressure. After drying under vacuum, the residue was dissolved in methanol and insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the residue was purified to obtain the pyrazolone-galactose conjugate. [ka]

[0072] Preparation of Compound 28 (Example 27) [ka] Starting pyrazolone compound: Compound 11 Yield 22 mg (79%) Purification conditions: silica gel column chromatography (chloroform:methanol=20:1) compound 28 1 H-NMR (600 MHz, CD3OD): δ (ppm) = 7.85(d,J=7.8Hz,2H),7.83(d,J=7.8Hz,2H),7.75(d,J=7.8Hz,2H),7.55(t,J=7.8Hz,2H),7 .49-7.46(m,4H),7.38(t,J=7.8Hz,1H),7.32(t,J=7.8Hz,1H),7.22(dd,J=5.4,8.6Hz,2H),6 .95(d,J=9.3Hz,2H),6.91(t,J=8.8Hz,2H),6.88(t,J=8.8Hz,1H),5.01(d,J=7.8Hz,1H),4. 98(d,J=10.9Hz,1H),4.47(d,J=10.8Hz,1H),3.87-3.84(m,2H),3.70(dd,J=3.3,9.6Hz,1H).

[0073] Preparation of Compound 29 (Example 28) [ka] Starting pyrazolone compound: Compound 13 Yield 20mg (70%) Purification conditions: silica gel column chromatography (chloroform:methanol = 20:1 to 7:1) compound 29 1 H-NMR( 600MHz, CD3OD):δ(ppm) = 7.91-7.82(m,4H),7.78(d,J=7.5Hz,2H),7.62(d,J=8.1Hz,2H),7.58-7.53(m,4H),7.50-7.30(m,4H),6.99-6.92(m,1H),5.04(d ,J=7.8Hz,1H),5.03(d,J=10.5Hz,1H),4.45(d,J=10.8Hz,1H),3.90-3.85(m,2H),3.72(dd,J=9.6,3.3Hz,1H),3.64-3.59(m,1H).

[0074] Preparation of Compound 30 (Example 29) [ka] Starting pyrazolone compound: Compound 14 Yield 21 mg (91%) Purification conditions: silica gel column chromatography (chloroform:methanol = 5:1 to 1:1) compound 30 1 H-NMR( 600MHz, CD3OD):δ(ppm) = 8.31(d,J=5.5Hz,2H),8.19(d,J=5.6Hz,2H),8.03-8.01(m,2H),7.39(d,J=6.2Hz,2H),7.29(d,J=6.1Hz,2H),6.89(d,J=9.3Hz,2H),4.95(d,J =7.7Hz,1H),4.39(d,J=10.6Hz,1H),3.82(dd,J=7.8,9.6Hz,1H),3.74(s,3H),3.71(d,J=2.9Hz,1H),3.66(dd,J=3.3,9.6Hz,1H),3.63(s,3H).

[0075] Preparation of Compound 31 (Example 30) [ka] Yield 11 mg (52%) Starting pyrazolone compound: 1-methyl-3-trifluoromethyl-5-pyrazolone Purification conditions: silica gel column chromatography (chloroform:methanol = 5: After elution with chloroform and methanol (5:1 to 2:1), the crude product was purified by silica gel column chromatography (chloroform:methanol = 5:1 to 2:1). The crude product was purified by preparative thin-layer chromatography (20 × 20 cm, developing solvent: chloroform:methanol = 2:1). compound 31 1 H-NMR( 600MHz, CD3OD):δ(ppm) =8.02(d,J=9.2Hz,2H),6.84(d,J=9.2Hz,2H),4.82(d,J=7.8Hz,1H),4.68(d,J=10.7Hz,1H),4.52(d,J=10.7Hz,1H),3.82(dd ,J=7.8,9.6Hz,1H),3.67(s,3H),3.63(d,J=2.9Hz,1H),3.57(dd,J=3.2,9.5Hz,1H),3.54(s,3H),3.45(s,1H),3.35(s,1H).

[0076] Preparation of Compound 32 (Example 31) [ka] Starting pyrazolone compound: Compound 15 Yield 23 mg (85%) Purification conditions: silica gel column chromatography (chloroform:methanol = 20:1 to 8:1) Compound 32 MALDI-TOF MS.:Calcd for C 40 H 34 N7O9 m / z [M+H] + :756.241,Found 756.165.

[0077] Preparation of Compound 33 (Example 32) [ka] Starting pyrazolone compound: Compound 16 Yield 30 mg (89%) Purification conditions: silica gel column chromatography (chloroform:methanol = 20:1 to 8:1), followed by silica gel column chromatography (chloroform:methanol = 20:1 to 5:1) compound 33 1 H-NMR( 600MHz, CD3OD):δ(ppm) =8.16(d,J=8.1Hz,1H),7.88(d,J=7.8Hz,2H),7.84(d,J=8.0Hz,2H),7.77(d,J=8.0Hz,2H),7.56-7.29(m,9H),6.95(d,J=9.2Hz ,2H),5.03(d,J=7.8Hz,1H),3.86(dd,J=7.8,9.5Hz,1H),3.82(d,J=3.2Hz,1H),3.71(dd,J=3.4,9.6Hz,1H),3.64-3.59(m,3H).

[0078] Preparation of Compound 34 (Example 33) [ka] Starting pyrazolone compound: Compound 17 Yield 27 mg (99%) Purification conditions: silica gel column chromatography (chloroform:methanol:water=80:25:5) compound 34 1 H-NMR (600 MHz, CD3OD): δ (ppm) = 7.89-7.83(m,5H),7.79(d,J=7.2Hz,2H),7.59(d,J=7.8Hz,1H),7.52(t,J=7. 8Hz,2H),7.45(t,J=7.8Hz,2H),7.35(t,J=7.2Hz,1H),7.28(t,J=7.2Hz,1H),7 .18(brs,1H),7.08(brs,1H),6.92(d,J=9.0Hz,2H),5.00-4.98(m,2H),4.28( d,J=10.8Hz,1H),3.89-3.83(m,2H),3.70(dd,J=3.6,9.6Hz,1H),3.60(s,1H).

[0079] Preparation of Compound 35 (Example 34) [ka] Starting pyrazolone compound: Compound 18 Yield 16 mg (51%) Purification conditions: silica gel column chromatography (chloroform:methanol:water=85:20:1) Compound 35 1 H-NMR (600MHz, CD3OD): δ (ppm) = 8.81(d,J=1.2Hz,1H),8.62(d,J=1.2Hz,1H),7.98(dd,J=2.4,7.8Hz,1H),7.91-7.81(m,7H),7.55-7.52(m,3H),7.47-7.44(m,2H) ,7.37-7.34(m,2H),7.31-7.28(m,1H),5.01-4.99(m,2H),4.25(d,J=10.8Hz,1H),3.58-3.82(m,2H),3.71(dd,J=3.6,9.6Hz,1H).

[0080] (Preparation of Compound 36) (Example 35)

change

[0081] (Preparation of Compound 37) (Example 36) [ka] Starting pyrazolone compound: Compound 20 Yield 31 mg (92%) Purification conditions: silica gel column chromatography (chloroform:methanol:water=85:20:1) compound 37 1 H-NMR (600 MHz, CD3OD): δ (ppm) = 7.83-7.77(m,3H),7.73(d,J=7.8Hz,2H),7.60(d,J=7.8Hz,1H),7.51(t,J=7.8Hz,2H),7.46(t,J=7.8Hz,2H),7.43-7.35(m,2H)7.32-7.2 8(m,1H),6.92(d,J=9.6Hz,2H),4.89(d,J=7.8Hz,1H),4.67(d,J=10.8Hz,1H),3.72(d,J=7.8,9.6Hz,1H),3.64-3.56(m,5H),3.32(s,1H).

[0082] Preparation of Compound 38 (Example 37) [ka] Starting pyrazolone compound: Compound 21 Yield 26 mg (78%) Purification conditions: silica gel column chromatography (chloroform:methanol:water=85:15:1) compound 38 1 H-NMR (600 MHz, CD3OD): δ (ppm) =7.89-7.86(m,2H),7.79(d,J=7.8Hz,2H),7.74-7.70(m,3H),7.55(dd,J=1.2,7.2Hz ,2H),7.74(dd,J=1.2,7.2Hz,2H),7.40(t,J=7.8Hz,1H),7.34(t,J=7.8Hz,1H),7.05 (brs,1H),6.96-6.93(m,2H),5.04(d,J=10.8Hz,1H),3.99(d,J=7.8Hz,1H),3.85(dd ,J=1.8,9.6Hz,1H),3.74(d,J=3.0Hz,1H),3.67(dd,J=3.0,9.6Hz,1H),3.59(s,1H).

[0083] (Preparation of Compound 39) (Example 38)

change

[0084] Preparation of Compound 40 (Example 39) [ka] Starting pyrazolone compound: Compound 23 Yield 20mg (70%) Purification conditions: silica gel column chromatography (chloroform:methanol = 20:1), followed by silica gel column chromatography (chloroform:methanol = 50:1 to 30:1). The crude product was purified by preparative thin-layer chromatography (20 x 20 cm, developing solvent: chloroform:methanol = 7:1), followed by silica gel column chromatography (chloroform:methanol = 30:1 to 20:1). compound 40 1 H-NMR (600 MHz, CD3OD): δ (ppm) = 7.91-7.88(m,2H),7.85-7.84(m,2H),7.77-7.75(m,2H),7.57-7.54(m,2H),7.50-7.47(m,2H),7.4 0-7.38(m,1H),7.55-7.32(m,1H),7.30(brs,1H),7.02(t,J=7.7Hz,1H),6.98-6.96(m,2H),6.91-6 .90(m,1H),6.86-6.81(m,3H),6.68(d,J=7.5Hz,1H),5.02(d,J=7.8Hz,1H),4.98(d,J=10.9Hz,1H) ,4.72(d,J=10.9Hz,1H),3.87-3.84(m,2H),3.73(s,3H),3.70(dd,J=3.4,9.6Hz,1H),3.65(s,3H).

[0085] Preparation of Compound 41 (Example 40) [ka] Starting pyrazolone compound: Compound 24 Yield 15 mg (48%) Purification conditions: silica gel column chromatography (chloroform:methanol = 10:1 to 5:1), followed by silica gel column chromatography (chloroform:methanol = 10:1). The crude product was purified by silica gel column chromatography (chloroform:methanol = 50:1 to 20:1). compound 41 1 H-NMR (600 MHz, CD3OD): δ (ppm) = 7.99(d,J=8.1Hz,2H),7.93(d,J=7.9Hz,2H),7.82(d,J=9.3Hz,2H),7.69(d,J=7.5Hz ,2H),7.54(t,J=8.2Hz,3H),7.47(t,J=8.1Hz,3H),7.45-7.33(m,5H),7.05(brs,1H), 6.99(d,J=7.7Hz,2H),5.04(d,J=7.8Hz,1H),4.95(d,J=10.9Hz,1H),4.16(d,J=10.9H) z,1H),3.91(d,J=3.0Hz,1H),3.83(dd,J=7.8,9.6Hz,1H)3.70(dd,J=3.4,9.6Hz,1H).

[0086] Preparation of Compound 42 (Example 41) [ka] Starting pyrazolone compound: Compound 25 Yield 21 mg (68%) Purification conditions: silica gel column chromatography (chloroform:methanol = 20:1 to 10:1) Compound 42 MALDI-TOF MS.:calcd. for C 42 H 33 N7NaO 13 ,866.203,m / z[M+Na] + found 866.206.

[0087] Examples 42 to 44 (Other Manufacturing Methods) (Synthesis of Compound 43) (Example 42) [ka] Compound 12 (32.4 mg, 120 μmol) and DMF (1.0 mL) were added to 4-nitrophenyl β-D-galactohexodialdo-1,5-pyranoside (9.5 mg, 29.9 μmol), in that order. After stirring at room temperature for 1 hour, the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol = 15:15) to obtain 23 mg of compound 43 (yield 92%). compound 43 1 H-NMR (600 MHz, CD3OD): δ (ppm) = 7.86(d,J=9.3Hz,2H),7.83(d,J=7.6Hz,2H),7.75(d,J=7.6Hz,2H),7.55(t,J=8.0 Hz,2H),7.56-7.43(m,4H),7.38(t,J=7.5Hz,1H),7.32(t,J=6.5Hz,1H),7.19-7.1 4(m,6H),6.96-6.93(m,2H),5.00(d,J=7.7Hz,1H),4.97(d,J=10.8Hz,1H),4.45(d ,J=10.8Hz,1H),3.87-3.82(m,2H),3.70(dd,J=3.4,9.7Hz,1H),3.62-3.59(m,1H).

[0088] Preparation of Compound 44 (Example 43) [ka] 4-Nitrophenyl β-D-galactohexodialdo-1,5-pyranoside (23.0 mg, 72.5 μmol) was dissolved in water (7.1 mL) and compound 26 (117.1 mg, 285 μmol) in DMF (4.6 mL) was added. After stirring at 37°C for 25 hours, the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol = 10:1 to 3:1) to give compound 44 (21 mg, 27% yield). Compound 44 MALDI-TOF MS.:calcd. for C 40 H 53 F6N 13 NaO 17 ,1124.348,m / z[M+Na] +found 1124.272.

[0089] Preparation of Compound 45 (Example 44) [ka] Compound 27 (25.1 mg, 59.8 μmol) and DMF (1.0 mL) were added to 4-nitrophenyl β-D-galactohexodialdo-1,5-pyranoside (4.8 mg, 15.0 μmol), in that order. After stirring at room temperature for 24 hours, the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol = 10:1 to 3:2) to give 17 mg of compound 45 (yield 99%). Compound 45 MALDI-TOF MS.:calcd. for C 48 H 61 N 15 NaO 17 ,1142.426,m / z[M+Na] + found 1142.337.

[0090] <Stability test> The stability of the pyrazolone derivative-introduced galactopyranosides (compounds 28 to 45) obtained in Examples 27 to 44 in phosphate buffer was examined. (Study on the stability of pyrazolone derivative-introduced galactopyranoside) Pyrazolone-introduced galactopyranosides (compounds 28-45) were dissolved in DMSO to prepare a 5 mM solution. To this 5 mM solution (75 μL), 0.1 M pH 7.4 phosphate buffer (375 μL), water (187.5 μL), and DMSO (112.5 μL) were added and heated to 37°C. After 1 to 14 days, a portion of the reaction mixture was analyzed by reverse-phase HPLC, and the remaining percentages of compounds 28-45 were calculated from the peak areas (Figures 2 to 5). As a result, R 1 The pyrazolone compounds 28 to 45 obtained from the pyrazolone compounds having an electron-withdrawing group and the formyl group-containing compounds were compared with the control compound 5 (R 1 =Me), it was found that the stability was improved.

[0091] [HPLC analysis conditions using a reversed-phase column] (Compounds 28~45) HPLC: GL-7700 (GL Sciences Inc.) Column: Inert sustain AQ-18, 5 μm, Φ4.6 × 250 mm (GL Sciences Inc.) Column temperature: 30℃ Mobile phase A: 0.1% TFA in HO (v / v) Mobile phase B: MeCN solution containing 0.1% TFA (v / v) Gradient (mobile phase B%): Compound 28, Compound 29, Compound 35, Compound 39, Compound 40, Compound 42, Compound 43, 50% (0 min), 80% (30 min), Compound 30, 10% (0 min), 40% (30 min), Compound 31, Compound 45, 20% (0 min), 50% ( 30 minutes) Compound 32, Compound 34, Compound 44, 30% (0 minutes), 60% (30 minutes), Compound 33, 60% (0 minutes), 90% (30 minutes), Compound 36, Compound 41, 40% (0 minutes), 70% (30 minutes), Compound 37, Compound 38, 65% (0 minutes), 95% (30 minutes). Flow rate: 1.0mL / min Detection wavelengths: Compound 28, 262 nm; Compound 29, 277 nm; Compound 30, 270 nm; Compound 31, 226 nm; Compound 32, 288 nm; Compound 33, 283 nm; Compound 34, 274 nm; Compound 35, 275 nm; Compound 36, 290 nm; Compound 37, 245 nm; Compound 38, 252 nm; Compound 39, 250 nm; Compound 40, 262 nm; Compound 41, 250 nm; Compound 42, 260 nm; Compound 43, 265 nm; Compound 44, 303 nm; Compound 45, 295 nm.

[0092] [Table 1-1]

[0093] [Table 1-2]

[0094] Table 1-3

[0095] Table 1-4

[0096] Table 1-5

[0097] Table 1-6

[0098] Table 1-7

[0099] Table 1-8

[0100] Table 1-9

[0101] Table 1-10

[0102] Table 1-11

[0103] Table 1-12

[0104] Table 1-13

[0105] [Table 1-14]

[0106] [Table 1-15]

[0107] [Table 1-16]

[0108] [Table 1-17]

[0109] [Table 1-18]

[0110] [Table 1-19]

[0111] [Table 1-20]

[0112] [Table 1-21] [Industrial Applicability]

[0113] The pyrazolone compounds of the present invention enable the introduction of drugs into formyl groups on antibodies under mild conditions and the production of chemically and biochemically stable antibody-drug conjugates, which are expected to contribute to pharmaceutical development. Furthermore, the pyrazolone compounds of the present invention can form stable modified forms with the formyl groups at the reducing ends of glycans, enabling quantitative and qualitative analysis of glycans and detailed structural analysis by enzymatic reactions. These compounds are expected to contribute to biology and medicine, particularly to diagnosis and pathological analysis.

Claims

1. The following formula (1): 【Chemistry 1】 (In the formula, R 1 is a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms (one or more halogen atoms bonded to the carbon atom at position 1), a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, a substituted aryl group having 6 to 60 carbon atoms (the benzene ring bonded to the pyrazolone skeleton has at least one substituent, and the substituent is one or more selected from the group consisting of a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms (one or more halogen atoms bonded to the carbon atom at position 1), a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an acyl group having 2 to 61 carbon atoms, an alkoxycarbonyl group having 1 to 60 carbon atoms, an alkoxy group having 1 to 60 carbon atoms, and an alkyl group having 1 to 60 carbon atoms, provided that when the substituent is an alkoxy group having 1 to 60 carbon atoms or an alkyl group having 1 to 60 carbon atoms, the position of the substituent is the meta position of the benzene ring bonded to the pyrazolone skeleton), and the following formulas (2) to (7): 【Chemistry 2】 (wherein R 3 represents a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms, a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an alkyl group having 1 to 60 carbon atoms which may be substituted, an alkenyl group having 1 to 60 carbon atoms which may be substituted, an alkynyl group having 1 to 60 carbon atoms which may be substituted, an aralkyl group having 1 to 60 carbon atoms, an aryl group having 6 to 60 carbon atoms which may be substituted, an alkoxy group having 1 to 60 carbon atoms which may be substituted, an alkenyloxy group having 1 to 60 carbon atoms which may be substituted, an alkynyloxy group having 1 to 60 carbon atoms which may be substituted, an aralkyloxy group having 1 to 60 carbon atoms, and / or an aryloxy group having 6 to 60 carbon atoms which may be substituted; and R 4is a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms, a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an optionally substituted alkyl group having 1 to 60 carbon atoms, an optionally substituted alkenyl group having 1 to 60 carbon atoms, an optionally substituted alkynyl group having 1 to 60 carbon atoms, an optionally substituted aralkyl group having 1 to 60 carbon atoms, an optionally substituted aryl group having 6 to 60 carbon atoms, an optionally substituted alkoxy group having 1 to 60 carbon atoms, an optionally substituted alkenyloxy group having 1 to 60 carbon atoms, an optionally substituted alkynyloxy group having 1 to 60 carbon atoms, an optionally substituted aralkyloxy group having 1 to 60 carbon atoms, an optionally substituted aryloxy group having 6 to 60 carbon atoms, and / or an optionally substituted alkylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkenylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkynylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted aralkylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted arylcarbonyl group having 6 to 60 carbon atoms, an optionally substituted alkoxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkenyloxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkynyloxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted aralkyloxycarbonyl group having 1 to 60 carbon atoms, and / or an optionally substituted aryloxycarbonyl group having 6 to 60 carbon atoms, and in the case of formula (4), R 4 is 0 to 4, and in the case of formulas (5) to (7), R 4 is 0 to 3; R 2 is a hydrocarbon group having 1 to 1000 carbon atoms which may contain a heteroatom, and n is an integer from 0 to 2. A pyrazolonizing agent for a formyl group-containing sugar compound, comprising a pyrazolone compound represented by the following formula:

2. A method for pyrazolonizing a formyl group-containing sugar compound, comprising contacting the pyrazolonizing agent described in claim 1 with a formyl group-containing sugar compound to obtain a pyrazolonized sugar compound in which two molecules of the pyrazolone compound and one molecule of the formyl group-containing sugar compound are bonded.

3. A method for stabilizing a pyrazolonized sugar compound, comprising contacting the pyrazolonizing agent described in claim 1 with a formyl group-containing sugar chain to obtain a pyrazolonized sugar compound in which two molecules of the pyrazolone compound and one molecule of the formyl group-containing sugar compound are bonded.

4. A method for producing a pyrazolonized sugar compound, comprising contacting the pyrazolonizing agent according to claim 1 with a formyl group-containing sugar compound to obtain a pyrazolonized sugar compound in which two molecules of the pyrazolone compound and one molecule of the formyl group-containing sugar compound are bonded.

5. The following formula (1): 【Chemistry 1】 (In the formula, R 1 is a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms (one or more halogen atoms bonded to the carbon atom at position 1), a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, a substituted aryl group having 6 to 60 carbon atoms (the benzene ring bonded to the pyrazolone skeleton has at least one substituent, and the substituent is one or more selected from the group consisting of a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms (one or more halogen atoms bonded to the carbon atom at position 1), a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an acyl group having 2 to 61 carbon atoms, an alkoxycarbonyl group having 1 to 60 carbon atoms, an alkoxy group having 1 to 60 carbon atoms, and an alkyl group having 1 to 60 carbon atoms, provided that when the substituent is an alkoxy group having 1 to 60 carbon atoms or an alkyl group having 1 to 60 carbon atoms, the position of the substituent is the meta position of the benzene ring bonded to the pyrazolone skeleton), and the following formulas (2) to (7): 【Chemistry 2】 (wherein R 3 represents a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms, a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an alkyl group having 1 to 60 carbon atoms which may be substituted, an alkenyl group having 1 to 60 carbon atoms which may be substituted, an alkynyl group having 1 to 60 carbon atoms which may be substituted, an aralkyl group having 1 to 60 carbon atoms, an aryl group having 6 to 60 carbon atoms which may be substituted, an alkoxy group having 1 to 60 carbon atoms which may be substituted, an alkenyloxy group having 1 to 60 carbon atoms which may be substituted, an alkynyloxy group having 1 to 60 carbon atoms which may be substituted, an aralkyloxy group having 1 to 60 carbon atoms, and / or an aryloxy group having 6 to 60 carbon atoms which may be substituted; and R 4is a halogen atom, a nitro group, a cyano group, a haloalkyl group having 1 to 10 carbon atoms, a perfluoropolyether group having 2 to 10 carbon atoms, a carboxy group, an optionally substituted alkyl group having 1 to 60 carbon atoms, an optionally substituted alkenyl group having 1 to 60 carbon atoms, an optionally substituted alkynyl group having 1 to 60 carbon atoms, an optionally substituted aralkyl group having 1 to 60 carbon atoms, an optionally substituted aryl group having 6 to 60 carbon atoms, an optionally substituted alkoxy group having 1 to 60 carbon atoms, an optionally substituted alkenyloxy group having 1 to 60 carbon atoms, an optionally substituted alkynyloxy group having 1 to 60 carbon atoms, an optionally substituted aralkyloxy group having 1 to 60 carbon atoms, an optionally substituted aryloxy group having 6 to 60 carbon atoms, and / or an optionally substituted alkylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkenylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkynylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted aralkylcarbonyl group having 1 to 60 carbon atoms, an optionally substituted arylcarbonyl group having 6 to 60 carbon atoms, an optionally substituted alkoxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkenyloxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted alkynyloxycarbonyl group having 1 to 60 carbon atoms, an optionally substituted aralkyloxycarbonyl group having 1 to 60 carbon atoms, and / or an optionally substituted aryloxycarbonyl group having 6 to 60 carbon atoms, and in the case of formula (4), R 4 is 0 to 4, and in the case of formulas (5) to (7), R 4 is 0 to 3; R 2 is a hydrocarbon group having 1 to 1000 carbon atoms which may contain a heteroatom, and n is an integer from 0 to 2. A pyrazolonized sugar compound having two pyrazolone motif molecules derived from a pyrazolone compound represented by the formula (I) and one sugar motif molecule derived from a formyl group-containing sugar compound.

Images