JPH02765A - Aminoguanidine derivative and maillard reaction inhibitor containing the same derivative as active component - Google Patents

Abstract

NEW MATERIAL:The compound of formula I (R<1a> is halogen, 1-4C alkyl, alkoxy, etc.; Xa is single bond, 1-4C alkylene or 2-4C alkenylene; R<2a> is H, 1-4C alkyl, etc.) and its acid addition salt. EXAMPLE:1-Anilinoguanidine sulfate. USE:A Maillard reaction inhibitor. PREPARATION:The compound of formula I can be produced by reacting a compound of formula II with a salt of a compound of formula III (R<a> is 1-4C alkyl) in water at room temperature to 80 deg.C. The compound of formula I has low toxicity and can be safely used. It is especially useful as a remedy and/or preventive for diseases caused by Maillard reaction of human.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to aminoguanidine derivatives useful as pharmaceuticals and pharmaceuticals containing them.

More specifically, the present invention provides compounds of the general formula (formula During,
All symbols have the same meaning as below. ) The present invention relates to a Maillard reaction inhibitor containing a compound represented by the following as an active ingredient.

[Background of the Invention] In 1912, Maillard noticed and reported the phenomenon that a mixed solution of amino acids and reducing sugars was colored brown when heated [Haillard, L., C.
Complete.

Rend, Soc, Biol, 72,599 (19
[12)], suggesting that this reaction may also occur in vivo.

In 1968, Rahbar et al. reported that tlbAIc, a minor component of clobin, was increased in diabetic patients.
, , CI in, Chim.

8cta, 22.296 (1968)]. In general, the chemical structure of tlbAIc is that glucose is bound to the N-terminal valine of the β chain in the form of Amadori rearrangement [Koe-ni (1, R, J, ,
BIObStein, S., Il., & Cer.
ami,^,,J,Biol.

Chem,,2! b2.2992 (1977)], and this reaction is non-enzymatic (nonenzymatic).
) happens to [5tevens, V, J,.

Vlassara, tl., Abati, A., & C.
erami, A., J., Biol.

Chem, 252.2998 (1977)], it was confirmed that the Maillard reaction occurs in vivo.

In the initial stage of the Maillard reaction, reducing sugars and protein amino groups undergo glycosylation (glycosylation).
sylation) and the formation of Amatoli rearrangement products. When this progresses further, a crosslinked compound is called an advanced glycosylation product (abbreviated as AGE). ] The solubility of the protein decreases, making it less susceptible to the action of proteases, and eventually fluorescence is generated and the product becomes brown in color.

Various mechanisms of AGE production have been proposed, for example, according to Brownlee et al. [Brownlee, H. et al., 5
science.

Nmu 1629 (1986)].

Glucose protein Schiff base Maillard reaction is a phenomenon observed in healthy individuals, but it is more prominent in diabetic patients with elevated blood sugar levels and in protein sites with slow turnover. For example, hemoglobin is 2.7 times more glycosylated in diabetic mice than in normal mice.
at,, the Maillard Reacti
on+n Foods and Nutrition,
8cs symposium 5eries.

215, 432. Am, Chem, Soc, ,
Washington, D.C. (1983)
[Guthrow, C,E
.

et al, , Proc, Natl, Acad, Sci.
, U.S., 76.4258 (1979)]. Furthermore, when glycosylated serum proteins are repeatedly administered intravenously to mice over a period of 12 weeks, typical diabetic kidney disease is observed! l
The appearance of ia disorders [Honnler, V., M.
, et al., , CI in, Endocr.
inol, Hetab, .

11, 431 (1982)].

Crystallin in the eye lens is a special protein that does not undergo any turnover once biosynthesized. It was observed that when glycosylation occurs in this crystallin, a change occurs in the three-dimensional structure, and an enzyme participates in the intramolecular SH group to form an S-8 bond, resulting in polymerization. In the case of diabetic cataracts in rats, the binding with glucose is 10
The group onnie has doubled in size and the number of intramolecular S-8 bonds has also increased.
r.

V., H., & Cerami, A., Cl1n, Endoc.
Rinol, Hetab, 11, 431 (1982)
].

Due to glycosylation of crystallin, polymerization, insolubility,
Fluorescence and yellow to brown coloration occur, and these changes are consistent with age-related changes in the lens.

[Chiou, S., H., Chylack, L.

Ding, , Jr., , Ding, W., ll2. & Bunn
,r,,J,Biol,Chem, 256°517
6 (1981)].

Collagen and elastin present in connective tissue are proteins rich in lysine and hydroxylysine, and their turnover is slow, and the presence of substances bound to glucose in the renal glomerular basement membrane, skin, skin, etc. ,
V, H,, 5tevens, V, J, , &
Cerami.

8. Ha+1Iard Reactions i
n Food, Prog, FoodNutr, Sci
, 5,315. Pergamon Press, Lo
It is also thought to be related to stiffness of blood vessel walls [RO3e-nburg, H, Hodrak, J
,B., ,Hassing, J.) f, ,AI-Dingurk.

W, A, & 5tohs, S, J,, Bioche
m, Biophys, Res, Com-mun, child;
49B (1979)].

Furthermore, non-enzymatic glycosylation of neuromyelin proteins is thought to be a cause of diabetic neurological disease.
er, V, H, et al,, Cl1n, Endocr
inol.

) 1etab, 11.431 (1982)].

Thus, the Maillard reaction is thought to be involved not only in various complications of diabetes but also in various diseases associated with aging.

[Prior Art] Based on the background described above, a search for a substance that inhibits the Maillard reaction has recently been conducted. For example, Brownlee et al.
o>, the Maillard reaction was inhibited, and when aminogranisin was administered to diabetic rats, AGE (AdVanCed GIycosyla) in the arterial wall was inhibited.
[Brownlee, ) f, et a
T.

5science, 232.1629 (1986)],
The mechanism of action is that the amino group (bonded to the guanidino group) of aminoguanidine, a nucleophilic hydrazine compound, blocks the active carbonyl group in the Amatoli rearrangement product, and the Amatoli rearrangement product is further crosslinked and polymerized. It is said that this is to prevent it.

Zarani JP-A No. 62-142114 discloses a secondary glycosylation final product consisting of a compound having an active nitrogen-containing group (an amino group bonded to a guanidino group) that can react with the active carbonyl group in the Amatoli rearrangement product. Compositions have been suggested that suppress the production of , specifically aminoguanidine, α-hydrazinohistidine, and lysine.

Also, recently, in Japanese Patent Application Laid-Open No. 62-249908,
Specifically, urea, guanidine, and salts thereof have been disclosed as compositions that suppress collagen crosslink formation.

In addition, compounds having the same structure as the compound of the present invention or structurally similar to the compound of the present invention include British Patent No. 12
No. 59568 specifies the general formula [wherein Rlc represents a nitro group, alkyl, alkoxy, alkylbΔ, or haloalkyl, R2c and R3c may be the same or different, and hydrogen atom, halogen, water r! iM represents either alkyl or alkoxy, R4c and R5C
may be the same or different and represent either a hydrogen atom or an alkyl having 3 or more carbon atoms. ] It is disclosed that the compound represented by the following is useful as an antihypertensive agent. This British patent specifies that (2゜4-dimethylanilino)guanidine, (2,3-dimethylanilino)
Guanidine, (3,4-dimethylanilino)guanidine, (2,6-dimethylanilino)guanidine, (2-methyl-6-chloroanilino)guanidine, (2-methyl-3-chloroanilino)guanidine, (2-methyl -4
-chloroanilino)guanidine, (3-chloro-4-methylanilino)guanidine, (2-methyl-5-chloroanilino)guanidine, (3-chloro-4-methoxyanilino)guanidine, (2-methoxy-5-chloroanilino)guanidine , (2-methoxy-4-chloro-5-
Specific examples include methylanilino)guanidine, (2-trifluoromethylanilino)guanidine, (3-trifluoromethylanilino)guanidine, (4-nitroanilino)guanidine, and (4-methylthioanilino)guanidine.

[Disclosure of the Invention] The present invention has the following features: 1) General formula (wherein Rla is a halogen atom, an alkyl group or alkoxy group having 1 to 4 carbon atoms, a nitro group, a phenoxy group, an amino group, a hydroxyl group, or a 2-carbon number group) ~ Represents a carbon ring or polycyclic ring substituted with 1 to 3 acylamino groups or unsubstituted, ×a is a single bond, alkylene having 1 to 4 carbon atoms, or alkylene having 2 to 4 carbon atoms represents an alkenylene, and Rla and X are -
Together, they represent an alkyl group having 1 to 4 carbon atoms, and R2a is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a halogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group, a hydroxyl group, or a nitro group. It represents a phenyl group substituted with 1 to 3 groups or unsubstituted.

However, the group represented by -x-Rla is a 3-nitrophenyl group, 4-nitrophenyl group, 3-chloro-4-methoxyphenyl group, 2-methoxy-5-chlorophenyl group, 2,4-dimedylphenyl group, 2,3-dimedylphenyl group, 3,4-dimedylphenyl group, 2,6-dimedylphenyl group, 2-methyl-6-chlorophenyl group,
2-methyl-3-chlorophenyl group, 2-methyl-4-
Chlorophenyl group, 3-chloro-4-methylphenyl group, 2-methyl-5-chlorophenyl group, 2-methoxy-
4-chloro-5-methylphenyl group, 2-trifluoromethylphenyl group, 3-trifluoro[1-mebruphenyl group and 4-methylthiophenyl group, and R2
Excludes compounds where a represents a hydrogen atom. ) or an acid addition salt thereof, and a compound represented by the general formula (wherein,
Rlb is a halogen atom, an alkyl group or alkoxy group having 1 to 4 carbon atoms, a nitro group, a phenoxy group, an amino group, a hydroxyl group, or an acylamino group having 2 to 4 carbon atoms.
Xb represents a single bond, alkylene having 1 to 4 carbon atoms or alkenylene having 2 to 4 carbon atoms, Rlb and Xb together represent an alkyl group having 1 to 4 carbon atoms, R2b is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a halogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group, a hydroxyl group, or It represents a phenyl group substituted with 1 to 3 nitro groups or unsubstituted. ) The present invention relates to a Maillard reaction inhibitor containing a compound represented by the following formula or an acid addition salt thereof as an active ingredient.

[Comparison with Prior Art] Aminoguanidine was thought to inhibit the Maillard reaction by reacting the active nitrogen-containing group (amine group bonded to the guanidino group) with the active carbonyl group in the Amatoli rearrangement product. Therefore, it is completely unexpected that the compound of the present invention in which the amino group is blocked has Maillard reaction inhibitory activity. Moreover, some of the compounds of the present invention have the same structure as the compound represented by general formula (C). However, the compound represented by general formula (C) has been disclosed to be useful as an antihypertensive agent, and therefore, it is completely unpredictable that the compound of the present invention would have Maillard reaction inhibitory activity from these medicinal effects and uses.

In the present invention, all isomers are included unless otherwise specified. For example, alkyl groups, alkoxy groups,
Alkylene groups and alkenylene groups include straight chain and branched chains, and the double bond in the alkenylene group is
Including those that are E, Z and EZ mixtures. It also includes isomers resulting from the presence of asymmetric carbon atoms, such as when a branched alkyl group is present.

fe, formula (IA); 13yoU (IB>, Rlal
The halogen atom represented by the substituent in RlbR and R2b is a fluorine atom, chlorine atom, bromine atom, and iodine atom, and the substituent in R and R1b is an acylamino group having 2 to 4 carbon atoms and is an acetamide, propionamide, butyramide group or an isomer group thereof, and any group is preferable.

Type 11 (IA) and U (IB> Medium, Rla, Rlb
, 2a 21) laR and substituents in R, groups represented together such as R and x, R2b and Xb, and groups represented by R2a and R2b having 1 to 1 carbon atoms
The four alkyl groups are methyl, 1pu, propyl, butyl groups and their isomer groups, Rla, Rlb
, carbon v11 represented by the substituent in R2a and R2b
The four alkoxy groups are methoxy, ethoxy, propoxy, buty-oxy groups, and isomer groups thereof, and any group is preferable. Substituent a in R and R1b is preferably a nitro group, phenoxy group, amino group or hydroxyl group, particularly preferably a chlorine atom, fluorine atom, methyl group, methoxy group or nitro group, and Rla and Rlb are unsubstituted It is also preferred that a carbocycle or a heterocycle is not represented.

f'lst formula (IA) c9 and (TB), R1ao,
J:, carbocycle in R1b is a monocyclic, bicyclic or bicyclic ring having 1 carbon atoms, which may be partially or completely saturated.
Refers to 5 or less aromatic rings.

Examples of these rings include benzene, naphthalene, indene, azulene, fluorene, phenanthrene, anthracene, acenaphthylene, biphenylene rings, and rings in which some or all of these are saturated,
Particularly preferred are benzene and naphthalene rings.

W1 formula (IA) and (f (IB>), R1acl
'j, Jl: The heterocycle in R1b refers to a monocyclic, bicyclic or bicyclic heterocyclic ring having 15 or less carbon atoms and heteroatoms which may be partially or fully saturated.

These rings include, for example, furan, thiophene, pyrrole, oxylysyl, isoxazole, thiazole, isothiazole, imidazole, pyrazole, furazane, pyran, pyridine, pyridazine, pyrimidine, pyrazine, indole, isoindole, benzofuran, penzodiophene, indole, etc. lysine, chromene, quinoline,
Examples include isoquinoline, quinolidine, purine, indazole, quinazoline, cinnoline, quinoxaline, phthalazine, pteridine, carbazolene, phenanthrene, xanthine, phenazine, phenothiazine rings and rings thereof that are partially or fully saturated.

The substituents in R2a and R2b are preferably a hydroxyl group or a nitro group, and R2a and R2b are preferably a hydrogen atom or an unsubstituted phenyl group, and particularly preferred R and R2b are a hydrogen atom, a methyl group, and a phenyl group.

In general formulas (IA) and (IB), the alkylene group having 1 to 4 carbon atoms represented by Xa and The four alkenylene groups are vinylene, propenylene, butenylene groups and isomer groups thereof, and particularly preferred Xa and Xb are single bonds.

The compounds represented by formulas (IA) and (IB) can be converted into acid addition salts by known methods, if desired. Preferably, the acid addition salt is non-toxic and water soluble. Suitable acid addition salts include, for example, inorganic acid salts such as hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, nitrate;
or acetate, lactate, tartrate, benzoate, citrate, methanesulfonate, ethanesulfonate, benzenesulfonate, toluenesulfonate, isethionate, glucuronate, gluconate. Examples include organic acid salts such as Acid addition salts have general formulas (IA) and (I
1q can be obtained by reacting the compound represented by B) with a desired acid by a theoretical amount of Φ in a known manner, for example, in an appropriate solvent.

[Method for producing the compound of the present invention] The compound of general formula (TA) can be produced by the method described below, but it can also be produced by the method described in British Patent No. 1259568 @ specification.

The compound of the general formula (IA) is a compound represented by the general formula (in the formula, all symbols have the same meanings as above) and -Noshiro (in the formula, R3 is an alkyl having 11 to 4 carbon atoms) It can be produced by reacting a salt of a compound represented by (representing a group) in water at room temperature to 80°C.

-Noshiro (IB> compound) can also be produced by the same method as the compound of general formula (IA).

[Starting Materials] The IM complex represented by formulas (n) and (III) and each reagent in the present invention are all known per se, or can be produced by known methods.

The reaction product is purified by conventional purification means, such as distillation under normal pressure or reduced pressure, high performance liquid chromatography using silica gel or magnesium silicate, thin layer chromatography, column chromatography, washing, recrystallization, etc. be able to. Purification may be performed for each reaction or after completion of several reactions.

[Effects] The compounds of the present invention represented by general formulas (IA> and (IB)) and acid addition salts thereof inhibit Maillard reaction, and therefore are effective against various diabetic complications, such as coronary heart disease, peripheral circulatory disorders, Cerebrovascular disorders, diabetic neuropathy, nephropathy, arteriosclerosis, arthrsclerosis, cataracts and retinopathy, as well as diseases caused by aging, such as atherosclerosis,
Useful in the treatment and/or prevention of senile cataracts and cancer.

The inhibitory effect of the Maillard reaction of the compounds of the present invention was confirmed by the screening system described below.

(1) Experimental Method In order to measure the effect of the drug of the present invention in suppressing the Maillard reaction in a test tube, a reaction was carried out under the following conditions.

100 m'j/dl bovine serum albumin, 200 m)i
Glucose, 6+nH test drug at pH 7,38 0.5
The cells were dissolved in 8-phosphate buffer and cultured at 37°C for one week.

After culturing, the culture solution was diluted 100 times with the same phosphate buffer, and fluorescence was measured at an excitation wavelength of 360 nm and a fluorescence wavelength of 450 nm.

The inhibition rate (%) was calculated using the following formula.

Inhibition rate (%) = [ΔI-(Δl4-(Δ11+Δ■2+
Δl3))]/(ΔI) Δ11: Fluorescence of the compound of the present invention, Δ■: Fluorescence of (the compound of the present invention, dried glucose), ΔI
: Fluorescence of (the compound of the present invention, calf serum albumin), Δ■4: Fluorescence of (the compound of the present invention, calf serum albumin + glucose), ΔI: Fluorescence of (the compound of the present invention, calf serum albumin + glucose).

(2) Results The results are shown in Table I.

It is understood from Table 1 that the compounds of the present invention and their acid addition salts have Maillard reaction inhibiting action.

It has been confirmed that the toxicity of the compounds of the present invention is sufficiently low, that they can be used safely as pharmaceuticals, and that they are particularly useful for the treatment and/or prevention of diseases caused by Maillard reactions in humans.

[Dosage 1] In order to use the compounds of the present invention represented by the general formulas (IA> and (IB>) and their acid addition salts for the above purposes, they are usually administered systemically or locally, orally or parenterally. The dosage varies depending on age, body weight, symptoms, therapeutic effect, administration method, treatment time, etc., but it is usually orally administered once to several times a day in the range of 1 ml to 7000 my per dose per adult. Alternatively, it is administered parenterally (preferably intravenously) once to several times a day in the range of 0.1 mg to 100 mg per adult.Of course, as mentioned above, the dosage may vary. Because it changes depending on the conditions,
In some cases, a whistle less than the above dosage range may be sufficient, and in other cases, more than the above range may be necessary.

Solid compositions for oral administration according to the present invention include tablets, pills, powders, granules, and the like.

In such solid compositions, one or more active substances are present in at least one inert diluent,
For example, it is mixed with hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, magnesium aluminate metasilicate. The composition may be prepared in accordance with conventional methods by adding additives other than inert diluents, such as lubricants such as magnesium stearate, disintegrants such as calcium glycolate, and solubilizing agents such as glutamic acid or aspartic acid. May contain. Tablets or gun powder may be coated with a film of gastric or enteric substances such as white sugar, gelatin, hydroxypropyl cellulose, hydroxypropyl methyl cellulose phthalate, or may be coated with two or more layers, if necessary. . Also included are capsules of absorbable materials such as pyratine.

Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs, etc. - inert diluents used in the membrane, e.g. Contains water and ethanol. In addition to inert diluents, this composition may contain adjuvants such as wetting agents and suspending agents, sweetening agents, flavoring agents,
It may contain aromatics and preservatives.

Other compositions for oral administration include sprays containing one or more active substances and formulated in a manner known per se. In addition to inert diluents, the compositions may also contain stabilizers such as sodium bisulfite and isotonic buffers, such as sodium chloride, sodium citrate, or citric acid.

A method for producing a spray agent is described, for example, in US Pat. No. 28686.
91@ and the specification of the same No. 3095355.

Copper pours for parenteral administration according to the present invention include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Aqueous solutions and suspensions include, for example, distilled water for injection and physiological saline. Examples of non-aqueous solutions and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, alcohols such as ethanol, and polysorbate 80.

Such compositions may further contain preservatives, wetting agents, emulsifying agents,
Adjuvants such as dispersants, stabilizers (e.g. lactose), solubilizers (e.g. glutamic acid, aspartic acid) may also be included. They can also be sterilized by preparing sterile solid compositions and dissolving them in sterile water or sterile injectable solvents before use.

The compositions for parenteral administration include topical solutions containing one or more active substances and formulated in a manner known per se, liniments such as ointments, and for rectal administration. Includes pessaries for sentencing and intravaginal administration.

[Example] The compound of the present invention and the method for producing the same will be explained in detail with reference to the following example, but the present invention is of course not limited thereto.

The solvent in parentheses listed in the section for separation by TLC indicates the developing solvent used, and the proportions indicate volume ratios. Moreover, IR was measured by the KBr tablet method.

Example 1 Phenylhydrazine (1,83d) was added to an aqueous solution (10d) of 1-anilinoguanidine sulfate S-methylisothiourea sulfate (2,0g). After stirring the mixture at 80°C for 3 hours, it was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in hot ethanol, the insoluble matter was removed, and the filtrate was concentrated to obtain crystals. The obtained crystals were recrystallized from water to obtain the title compound (698 my) having the following tit value. It's 19.

TLC: Rf O, 41 (ethyl acetate: acetic acid: water = 3:
1:1); ■R Niji 3100.1640.1590.1490.
1100.750゜610cm'' Working Example 11(a) to 1 (,1) Using the compound represented by the general formula (in which all symbols have the same meanings as above) as a raw material, the same procedure as in Example 1 was carried out. ,
The compound of the present invention shown in Robe ■ was obtained.

Formulation Example The following ingredients were mixed in a conventional manner and then tableted to obtain 100 tablets each containing 50 mg of the active ingredient.

・1-anilinoguanidine sulfate...5g・
mM elementary calcium glycolate (disintegrant)...0.2
g ・Magnesium stearate (lubricant) ・・・0.1
(1. Microcrystalline cellulose...4
．． 7g patent applicant Ono Pharmaceutical Co., Ltd.

Claims (1)

[Claims] 1) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I A) (In the formula, R^1^a is a halogen atom, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group, Represents a carbocyclic or heterocyclic ring substituted or unsubstituted with a nitro group, phenoxy group, amino group, hydroxyl group, or 1 to 3 acylamino groups having 2 to 4 carbon atoms, and X_a is a single bond, a carbon Represents alkylene having 1 to 4 carbon atoms or alkenylene having 2 to 4 carbon atoms, and R^1^a and X
_a together represent an alkyl group having 1 to 4 carbon atoms, and R^2^a is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a halogen atom, an alkyl group having 1 to 4 carbon atoms, or It represents a phenyl group substituted with 1 to 3 alkoxy groups, hydroxyl groups, or nitro groups or unsubstituted. However, the group represented by -X_a-R^1^a is a 3-nitrophenyl group, 4-nitrophenyl group, 3-chloro-
4-methoxyphenyl group, 2-methoxy-5-chlorophenyl group, 2,4-dimethylphenyl group, 2,3-dimethylphenyl group, 3,4-dimethylphenyl group, 2,6
-dimethylphenyl group, 2-methyl-6-chlorophenyl group, 2-methyl-3-chlorophenyl group, 2-methyl-4-chlorophenyl group, 3-chloro-4-methylphenyl group, 2-methyl-5-chlorophenyl group , represents a 4-methylthiophenyl group, a 2-methoxy-4-chloro-5-methylphenyl group, a 2-trifluoromethylphenyl group and a 3-trifluoromethylphenyl group, and R^2^a represents a hydrogen atom Excludes compounds. ) or their acid addition salts. 2) The compound according to claim 1, wherein X_a is a single bond. 3) The compound according to claim 2, wherein the carbon ring in R^1^a is a benzene ring or a naphthalene ring. 4) The compound according to claim 1, wherein R^1^a is substituted with a chlorine atom, a fluorine atom, a methyl group, a methoxy group, or a nitro group, or is an unsubstituted carbocyclic or heterocyclic ring. 5) The compound according to claim 1, wherein R^2^a is a hydrogen atom, a methyl group, or a phenyl group. 6) The compound is 1-anilinoguanidine, 1-(2-chloroanilino)guanidine, 1-(4-chloroanilino)guanidine, 1-(4-fluoroanilino)guanidine, 1-(4-
methoxyanilino)guanidine, 1-(1-naphthylamino)guanidine, 1-(N,N-diphenylamino)guanidine, 1-(
N-methyl-N-phenylamino)guanidine, 1-(4-methylanilino)guanidine or 1-(2
-Nitroanilino)guanidine. 7) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I B) (In the formula, R^1^b is a halogen atom, an alkyl group or alkoxy group having 1 to 4 carbon atoms, a nitro group, a phenoxy group, represents a carbocyclic or heterocyclic ring substituted or unsubstituted with 1 to 3 amino groups, hydroxyl groups, or acylamino groups having 2 to 4 carbon atoms; X_b is a single bond; Represents alkylene or alkenylene having 2 to 4 carbon atoms, and R^1^b and X
_b together represent an alkyl group having 1 to 4 carbon atoms, and R^2^b is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a halogen atom, an alkyl group having 1 to 4 carbon atoms, or It represents a phenyl group substituted with 1 to 3 alkoxy groups, hydroxyl groups, or nitro groups or unsubstituted. ) A Maillard reaction inhibitor containing a compound shown in (a) or an acid addition salt thereof as an active ingredient.