Α-keto acid amide or substituted oxalic acid amide ester compound and composition thereof

Abstract

The present invention relates to the technical field of chemical synthesis, in particular to an α-keto acid amide or substituted oxalic acid amide ester compound and a composition thereof. The general structural formula of the compound is as shown in formula I: wherein R1 is C1-C6 alkyl or cycloalkyl, or OR2, where R2 is C1-C8 alkyl or cycloalkyl, or NR3R4, R3 and R4 each independently being C1-C6 alkyl or cycloalkyl, or amido with the following structure: wherein X and Y are each independently C1-C5 methylene, and Z represents one of CH2, O, S and NH. The compound in the present invention can effectively inhibit the activity of tyrosinase and inhibit the synthesis of melanin, and has a good skin whitening effect; and compared with the prior art, the compound provided in the present invention is greatly changed in terms of the molecular space structure, has increased targets that interact with tyrosinase and improved dissolving properties, and achieves a better effect.

Description

Alpha-keto acid amide or substituted oxalic acid amide ester compounds and compositions thereof Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, in particular to an alpha-keto acid amide or substituted oxalic acid amide ester compound and a composition thereof. Background Art

[0002] Skin pigmentation, typically characterized by melasma, freckles, and post-inflammatory hyperpigmentation, is a major cosmetic concern for many patients seeking medical attention. Melanin, a pigment found in human epidermal cells, is the primary cause of endogenous skin pigmentation. Under normal physiological conditions, melanin production protects the skin from UV rays and prevents DNA damage from radiation. However, excessive melanin production can lead to skin hyperpigmentation.

[0003] Melanogenesis is a complex pathway involving a combination of enzymatic and chemical reactions. Melanin is primarily synthesized and secreted by melanocytes. Melanocytes aggregate with surrounding keratinocytes to form dendritic structures. Melanosomes are specialized organelles within melanocytes that contain melanin granules. Melanin granule synthesis, storage, and transport occur within melanosomes. After melanin production, it is transported from the dendritic tips of melanocytes to keratinocytes. Melanocytes produce two types of melanin: eumelanin and pheomelanin. Melanogenesis begins with the oxidation of tyrosine to dopaquinone by tyrosinase (TYR), and dopaquinone formation is the rate-limiting step in melanin synthesis. Once formed, dopaquinone can be further converted in the presence of cysteine ​​or glutathione to produce pheomelanin. Alternatively, it can undergo intramolecular cyclization and further oxidation via cyclodopa to produce dopachrome, which is ultimately converted to eumelanin by the action of the tyrosine-related proteins TRP-1 and TRP-2. Among them, although TYR, TRP-1 and TRP-2 are all involved in the melanogenesis pathway, TYR is the only essential enzyme for melanogenesis. Inhibiting the activity of this enzyme will directly affect the rate and amount of melanin synthesis and reduce pigmentation. It is the main research direction of whitening agents on the current market.

[0004] Currently, many topical products are available for the treatment of hyperpigmentation disorders. These products contain a variety of active ingredients to reduce the production and / or distribution of melanin. Among them, hydroquinone, kojic acid, and arbutin are more common. However, existing common technical solutions often have safety risks that cannot be ignored. For example, hydroquinone may cause exogenous chloasma and permanent white spots on the skin. As a derivative of hydroquinone, arbutin also has the risk of releasing hydroquinone under certain conditions. The use of kojic acid has been controversial due to its potential endocrine disrupting properties. In 2013, the Japanese cosmetics company Kanebo added rhododendron alcohol to its products to reduce melanin production, but it caused serious side effects such as white spots, which led to the recall and withdrawal of the products. A considerable number of victims of its products have not yet recovered.

[0005] Many compounds containing resorcinol structural units also inhibit tyrosinase and reduce melanin production, and are used in various commercial whitening products. Examples include isobutyrylaminothiazolylresorcinol, dimethoxytolyl-4-propylresorcinol, phenylethylresorcinol, butylresorcinol, and hexylresorcinol. These compounds generally exhibit strong in vitro tyrosinase inhibitory activity, but often suffer from disadvantages such as poor water solubility, easy degradation and discoloration / odor generation, and strong irritation.

[0006] Therefore, it is urgent to develop new whitening products that are safe, efficient and easy to use.

[0007] Summary of the Invention

[0008] The purpose of the present invention is to overcome the deficiencies in the prior art and provide an α-keto acid amide or substituted oxalic acid amide ester compound that can effectively inhibit the activity of tyrosinase and inhibit the synthesis of melanin.

[0009] To achieve the above purpose, the technical solutions adopted in the present invention are as follows:

[0010] α-keto acid amide or substituted oxalic acid amide ester compounds, the general structural formula of which is shown in Formula I:

[0011] wherein R1 is a C1-C6 alkyl or cycloalkyl group, or is OR2, wherein R2 is a C1-C8 alkyl or cycloalkyl group, or is NR3R4, wherein R3 and R4 are each independently a C1-C6 alkyl or cycloalkyl group;

[0012] Or an amine group having the following structure: Wherein, X and Y are each independently a C1-C5 methylene group, and Z represents one of CH2, O, S, and NH.

[0013] Furthermore, the compound exists in a free form, or in the form of a pharmaceutically acceptable salt or ester.

[0014] A composition containing the aforementioned α-keto acid amide or substituted oxalic acid amide ester compound is a cosmetic or dermatological preparation.

[0015] Furthermore, the added amount of the α-keto acid amide or substituted oxalic acid amide ester compound in the composition is 0.000001% to 10% of the total weight of the preparation.

[0016] The technical solution of the present invention has the following beneficial effects:

[0017] (1) The compounds of the present invention can effectively inhibit the activity of tyrosinase and the synthesis of melanin, and have a good skin whitening effect.

[0018] (2) The compounds of the present invention have undergone technical improvements, and compared with the prior art, the molecular spatial structure has undergone significant changes, the number of targets for tyrosinase action has increased, the solubility performance has been improved, and better effects have been achieved. DETAILED DESCRIPTION

[0019] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[0020] 4-(2,4-Dimethoxyphenyl)-1,3-thiazol-2-amine can also be conveniently prepared by a published method (document US2011 / 0230486) or directly using commercially available reagents.

[0021] Embodiment 1:

[0022] Under nitrogen, 4-(2,4-dimethoxyphenyl)-1,3-thiazol-2-amine (1.5 g) was dispersed in dry dichloromethane (30 mL), cooled to -5-10°C, and a 2.0 M dichloromethane solution of boron tribromide (19 mL) was added dropwise. The reaction was incubated for 24 hours. After completion, methanol was added dropwise to quench the reaction. The reaction solution was concentrated and dispersed with ethyl acetate (100 mL). The organic phase was washed with saturated sodium bicarbonate and saturated brine, then dried over anhydrous sodium sulfate. The organic phase was concentrated, filtered, and washed with a small amount of cold isopropyl acetate. The product was then dried under vacuum at 20-30°C to yield 0.69 g of 4-(2-aminothiazol-4-yl)benzene-1,3-diphenol as a brown solid, which was used directly in the subsequent reaction without purification.

[0023] Example 2:

[0024] 4-(2-Aminothiazol-4-yl)benzene-1,3-diol (0.50 g) was dissolved in anhydrous THF (10 mL). A solution of 2-oxopropionyl chloride (0.42 g, obtained by the method in Org. Synth. 1983, 61, 1) in anhydrous THF (1.6 mL) was added dropwise at 0-10°C. After the addition was complete, the reaction was allowed to proceed overnight. Methylamine (33% in ethanol, 3 mL) was then added and stirred for 2 hours. After concentration under vacuum to remove the solvent, the mixture was acidified with 1N HCl and recrystallized from isopropanol-water to obtain 0.28 g of N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-2-oxopropionamide as an off-white solid. ESI-MS: m / z 301.1 [M+Na] + ; 1 H NMR (400MHz, DMSO-d6): 12.05(s,1H),10.97(s,1H),9.71(s,1H),7.57(m,1H),7.43(s,1H),6.44(m,1H),6.35(m,1H),2.15(s,3H).

[0025] Example 3:

[0026] 4-(2-Aminothiazol-4-yl)benzene-1,3-diol (0.43 g) was dissolved in anhydrous THF (8 mL), and a solution of ethyl oxalyl chloride (0.50 g) in anhydrous THF (2 mL) was added dropwise at 0-10°C. After the addition was complete, the reaction was allowed to proceed overnight, followed by the addition of methylamine (33% ethanol solution, 2.5 mL) and stirring for 2 h. After vacuum concentration to remove the solvent, the mixture was separated by column chromatography (silica gel, dichloromethane-methanol) to obtain 0.38 g of ethyl 2-((4-(2,4-dihydroxyphenyl)thiazol-2-yl)amino)-2-oxoacetate as a white solid. ESI-MS: m / z 309.0 [M+H] + ， 331.0[M+Na] + ; 1 H NMR (400MHz, DMSO-d6): 12.13(s,1H),10.20(s,1H),9.64(s,1H),7.55(m,1H),7.44(s,1H),6.50(m,1H),6.44(m,1H),4.30(s,2H),1.30(t,3H).

[0027] Embodiment 4:

[0028] 2-Cyclopropyl-2-oxoacetic acid (0.21 g) was dispersed in dry acetonitrile (15 mL), followed by the addition of DIPEA (0.55 g) and HATU (0.72 g). After stirring at room temperature for 30 min, 4-(2-aminothiazol-4-yl)benzene-1,3-diol (0.30 g) was added and the reaction stirred for 12-24 h. After completion of the reaction, 1N NaOH (15 mL) was added and the mixture was stirred at 5-15°C overnight. The resulting reddish-brown mixture was neutralized with 1N HCl to a pH of 5-6. Extraction was performed with ethyl acetate (3 × 20 mL). The organic phases were combined and concentrated, and the crude product was purified by column chromatography (silica gel, dichloromethane-methanol) to yield 0.14 g of 2-cyclopropyl-N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-2-oxoacetamide as an off-white solid. ESI-MS: m / z 327.1[M+Na] + ; 1 H NMR(400MHz, DMSO-d6):12.01(s,1H),10.10(s,1H),9.71(s,1H),7.53(m,1H),7.40(s,1H),6.45(m,1H), 6.34(m,1H),1.81(m,1H),0.97(m,2H),0.75(m,2H).

[0029] Example 5:

[0030] 2-Cyclohexyl-2-oxoacetic acid (0.28 g) was dispersed in dry acetonitrile (15 mL), followed by the addition of DIPEA (0.55 g) and HATU (0.72 g). After stirring at room temperature for 30 min, 4-(2-aminothiazol-4-yl)benzene-1,3-diol (0.30 g) was added and the reaction was stirred for 12-24 h. After completion of the reaction, 1N NaOH (15 mL) was added and the mixture was stirred at 5-15°C overnight. The resulting reddish-brown mixture was neutralized with 1N HCl to a pH of 5-6. Extraction was performed with ethyl acetate (3 x 20 mL). The organic phases were combined and concentrated, and the crude product was purified by column chromatography (silica gel, dichloromethane-methanol) to yield 0.23 g of 2-cyclohexyl-N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-2-oxoacetamide as a white solid. ESI-MS: m / z 369.1 [M+Na] + ; 1 H NMR(400MHz,DMSO-d6):12.09(s,1H),10.13(s,1H),9.64(s,1H),7.60(m,1H),7. 43(s,1H),6.42(m,1H),6.33(m,1H),2.31(m,1H)1.80(m,2H),1.62-1.37(m,8H).

[0031] Example 6:

[0032] 2-Oxo-2-(propan-2-ylamino)acetic acid (0.24 g) was dispersed in dry acetonitrile (15 mL), followed by the addition of DIPEA (0.55 g) and HATU (0.72 g). After stirring at room temperature for 30 minutes, 4-(2-aminothiazol-4-yl)benzene-1,3-diol (0.30 g) was added and the reaction was stirred for 12-24 hours. After completion of the reaction, 1N NaOH (15 mL) was added and stirred at 5-15°C overnight. The resulting reddish-brown mixture was neutralized with 1N HCl to a pH of 5-6. The mixture was then extracted with ethyl acetate (3 x 20 mL). The organic phases were combined and concentrated, and the crude product was purified using prepHPLC (ACCQPrep HP150, Welch Ultimate Polar-RP 5μm 21.2×150mm, (A) 0.1% TFA aq., (B) CH3CN). The product was collected and lyophilized to yield 0.16 g of N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-N'-isopropyloxamide as a white powder. ESI-MS: m / z 322.1 [M+H] + ,344.1[M+Na] + ; 1 H NMR(400MHz,DMSO-d6):11.99(s,1H),10.23(s,1H),9.68(s,1H),7.97(s,1 H),7.45(m,1H),7.33(s,1H),6.38-6.32(m,2H),4.07(m,1H),1.24(d,6H).

[0033] Example 7:

[0034] Oxo(1-pyrrolidinyl)acetic acid (0.26 g) was dispersed in dry acetonitrile (15 mL), followed by the addition of DIPEA (0.55 g) and HATU (0.72 g). After stirring at room temperature for 30 min, 4-(2-aminothiazol-4-yl)benzene-1,3-diol (0.30 g) was added and the reaction was stirred for 12-24 h. After completion of the reaction, 1N NaOH (15 mL) was added and stirred at 5-15°C overnight. The resulting reddish-brown mixture was neutralized with 1N HCl to a pH of 5-6. The mixture was extracted with ethyl acetate (3 x 20 mL). The organic phases were combined and concentrated, and the crude product was purified using prepHPLC (ACCQPrep HP150, Welch Ultimate Polar-RP 5μm 21.2×150mm, (A) 0.1% TFA aq., (B) CH3CN). The product was collected and lyophilized to yield 0.25 g of N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-N'-isopropyloxamide as a white powder. ESI-MS: m / z 334.1 [M+H] + ,356.1[M+Na] + ; 1 HNMR(400MHz,DMSO-d6):12.13(s,1H),10.30(s,1H),9.86(s,1H),7.53(s,1H),7.45(s,1H),6.51(m,1H),6.43(m,1H),3.42(m,4H),1.81(m,4H).

[0035] Example 8:

[0036] 4-(2-Aminothiazol-4-yl)benzene-1,3-diol (0.50 g) was dissolved in anhydrous THF (10 mL), and a solution of 2-oxobutyryl chloride (0.49 g) in anhydrous THF (1.6 mL) was added dropwise at 0-10°C. After the addition was complete, the reaction was allowed to proceed overnight, followed by the addition of methylamine (33% in ethanol, 3 mL) and stirring for 2 h. After vacuum concentration to remove the solvent, the mixture was acidified with 1N HCl and recrystallized from isopropanol-water to obtain 0.22 g of N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-2-oxobutyramide as an off-white solid. ESI-MS: m / z 315.1 [M+Na] + ; 1H NMR(400MHz,DMSO-d6):12.25(s,1H),11.03(s,1H),9.72(s,1H),7.60(m,1H),7. 43(s,1H),6.44(m,1H),6.35(m,1H),2.39(q,J=7.2Hz,2H),1.06(t,J=7.2Hz,2H).

[0037] Example 9:

[0038] 4-(2-Aminothiazol-4-yl)benzene-1,3-diol (0.50 g) was dissolved in anhydrous THF (10 mL), and a solution of 3-methyl-2-oxobutyryl chloride (0.55 g) in anhydrous THF (1.6 mL) was added dropwise at 0-10°C. After the addition was complete, the reaction was allowed to proceed overnight, followed by the addition of methylamine (33% ethanol solution, 3 mL) and stirring for 2 hours. After vacuum concentration to remove the solvent, the mixture was separated by column chromatography (dichloromethane-methanol) to obtain 0.18 g of N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-3-methyl-2-oxobutyramide. ESI-MS: m / z 328.9 [M+Na] + ; 1 H NMR(400MHz,DMSO-d6):12.11(s,1H),11.07(s,1H),9.71(s,1H),7.62(m,1H ),7.43(s,1H),6.42(m,1H),6.34(m,1H),3.11(m,1H),1.04(d,J=6.9Hz,6H).

[0039] Embodiment 10:

[0040] 4-(2-Aminothiazol-4-yl)benzene-1,3-diol (0.43 g) was dissolved in anhydrous THF (8 mL), and a solution of monomethyl oxalyl chloride (0.47 g) in anhydrous THF (2 mL) was added dropwise at 0-10°C. After the addition was complete, the reaction was allowed to proceed overnight, followed by the addition of methylamine (33% ethanol solution, 2.5 mL) and stirring for 2 h. After vacuum concentration to remove the solvent, the mixture was separated by column chromatography (silica gel, dichloromethane-methanol) to obtain 0.32 g of methyl 2-((4-(2,4-dihydroxyphenyl)thiazol-2-yl)amino)-2-oxoacetate. ESI-MS: m / z 294.9 [M+H] + ， 316.9[M+Na] + ; 1H NMR (400MHz, DMSO-d6): 12.07(s,1H),10.33(s,1H),9.67(s,1H),7.61(m,1H),7.46(s,1H),6.45(m,1H),6.36(m,1H),3.58(s,3H).

[0041] Example 11:

[0042] 2-Cyclopropyloxy-2-oxoacetic acid (0.24 g) was dispersed in dry acetonitrile (15 mL), followed by the addition of DIPEA (0.55 g) and HATU (0.72 g). After stirring at room temperature for 30 min, 4-(2-aminothiazol-4-yl)benzene-1,3-diol (0.30 g) was added and the reaction was stirred for 12-24 h. After completion of the reaction, 1N NaOH (15 mL) was added and stirred at 5-15°C overnight. The resulting reddish-brown mixture was neutralized with 1N HCl to a pH of 5-6. The mixture was extracted with ethyl acetate (3 x 20 mL). The organic phases were combined and concentrated, and the crude product was purified using prepHPLC (ACCQPrep HP150, Welch Ultimate Polar-RP 5μm 21.2×150mm, (A) 0.1% TFA aq., (B) CH3CN). The product was collected and lyophilized to yield 0.22 g of cyclopropyl 2-((4-(2,4-dihydroxyphenyl)thiazol-2-yl)amino)-2-oxoacetate. ESI-MS: m / z 342.9 [M+Na] + ; 1 H NMR (400MHz, DMSO-d6): 12.12(s,1H),10.24(s,1H),9.68(s,1H),7.63(m,1H),7.51(s,1H),6.47(m,1H),6.35(m,1H),0.66-0.25(m,4H).

[0043] Example 12:

[0044] N,N-dimethyloxamic acid (0.21 g) was dispersed in dry acetonitrile (15 mL), followed by the addition of DIPEA (0.55 g) and HATU (0.72 g). After stirring at room temperature for 30 minutes, 4-(2-aminothiazol-4-yl)benzene-1,3-diol (0.30 g) was added and the reaction was stirred for 12-24 hours. After completion of the reaction, 1N NaOH (15 mL) was added and stirred at 5-15°C overnight. The resulting reddish-brown mixture was neutralized with 1N HCl to a pH of 5-6. The mixture was then extracted with ethyl acetate (3 x 20 mL). The organic phases were combined and concentrated, and the crude product was purified using prepHPLC (ACCQPrep HP150, Welch Ultimate Polar-RP 5μm 21.2×150mm, (A) 0.1% TFA aq., (B) CH3CN). The product was collected and lyophilized to yield 0.28 g of N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-N',N'-dimethyloxamide. ESI-MS: m / z 308.1 [M+H] + ,330.1[M+Na] + ; 1 H NMR (400MHz, DMSO-d6): 12.11(s,1H),10.27(s,1H),9.87(s,1H),7.58(s,1H),7.42(s,1H),6.46(m,1H),6.33(m,1H),2.98(s,6H).

[0045] Example 13:

[0046] N,N-Diethyloxamic acid (0.32 g) was dispersed in dry acetonitrile (15 mL), followed by the addition of DIPEA (0.55 g) and HATU (0.72 g). After stirring at room temperature for 30 minutes, 4-(2-aminothiazol-4-yl)benzene-1,3-diol (0.30 g) was added and the reaction was stirred for 12-24 hours. After completion of the reaction, 1N NaOH (15 mL) was added and stirred at 5-15°C overnight. The resulting reddish-brown mixture was neutralized with 1N HCl to a pH of 5-6. The mixture was then extracted with ethyl acetate (3 x 20 mL). The organic phases were combined and concentrated, and the crude product was purified using prepHPLC (ACCQPrep HP150, Welch Ultimate Polar-RP 5μm 21.2×150mm, (A) 0.1% TFA aq., (B) CH3CN). The product was collected and lyophilized to yield 0.31 g of N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-N',N'-diethyloxamide. ESI-MS: m / z 358.1 [M+Na] + ; 1H NMR(400MHz,DMSO-d6):12.34(s,1H),10.31(s,1H),9.89(s,1H),7.56(s,1H),7. 45(s,1H),6.44(m,1H),6.35(m,1H),3.05(q,J=7.1Hz,4H),1.15(t,J=7.1Hz,6H).

[0047] Example 14:

[0048] 2-Morpholin-4-yl-2-oxoacetic acid (0.35 g) was dispersed in dry acetonitrile (15 mL), followed by the addition of DIPEA (0.55 g) and HATU (0.72 g). After stirring at room temperature for 30 min, 4-(2-aminothiazol-4-yl)benzene-1,3-diol (0.30 g) was added and the reaction was stirred for 12-24 h. After completion of the reaction, 1N NaOH (15 mL) was added and stirred at 5-15°C overnight. The resulting reddish-brown mixture was neutralized with 1N HCl to a pH of 5-6. The mixture was extracted with ethyl acetate (3 x 20 mL). The organic phases were combined and concentrated, and the crude product was purified using prepHPLC (ACCQPrep HP150, Welch Ultimate Polar-RP 5μm 21.2×150mm, (A) 0.1% TFA aq., (B) CH3CN). The product was collected and lyophilized to yield 0.29 g of N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-2-morpholinyl-2-oxoacetamide. ESI-MS: m / z 372.1 [M+Na] + ; 1 H NMR (400MHz, DMSO-d6): 12.22(s,1H),10.27(s,1H),9.76(s,1H),7.55(s,1H),7.37(s,1H),6.42(m,1H),6.31(m,1H),3.65(d,4H),3.44(d,4H).

[0049] Example 15:

[0050] Oxo(thiomorpholin-4-yl)acetic acid (0.38 g) was dispersed in dry acetonitrile (15 mL), followed by the addition of DIPEA (0.55 g) and HATU (0.72 g). After stirring at room temperature for 30 min, 4-(2-aminothiazol-4-yl)benzene-1,3-diol (0.30 g) was added and the reaction was stirred for 12-24 h. After completion of the reaction, 1N NaOH (15 mL) was added and stirred at 5-15°C overnight. The resulting reddish-brown mixture was neutralized with 1N HCl to a pH of 5-6. The mixture was extracted with ethyl acetate (3 x 20 mL). The organic phases were combined and concentrated, and the crude product was purified using prepHPLC (ACCQPrep HP150, Welch Ultimate Polar-RP 5μm 21.2×150mm, (A) 0.1% TFA aq., (B) CH3CN). The product was collected and lyophilized to yield 0.28 g of N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-2-thiomorpholinyl-2-oxoacetamide. ESI-MS: m / z 388.1 [M+Na] + ; 1 H NMR (400MHz, DMSO-d6): 12.26(s,1H),10.21(s,1H),9.78(s,1H),7.62(s,1H),7.44(s,1H),6.39(m,1H),6.28(m,1H),3.37(d,4H),2.68(d,4H).

[0051] The inhibitory activity of the compounds against tyrosinase was determined using a modified MBTH method, as reported previously (Journal of biochemical and biophysical methods, 1994, 28(3):173-183). Using 3-methyl-2-benzothiazolinone (MBTH) as a colorimetric reagent, human tyrosinase oxidizes L-dopa to L-dopaquinone, which then reacts with MBTH to produce a colored product. The reaction is terminated, and the inhibitory activity of the compounds against human tyrosinase is determined by measuring the specific absorbance of the resulting product at 505 nm.

[0052] Application examples:

[0053] According to the mass fraction of each component in the formula example in the table below, the required emulsion can be prepared by referring to the following formula production process steps.

[0054] Preparation method:

[0055] Taking Recipe 1 as an example,

[0056] Add polyglyceryl-3-methylglucose distearate, hydrogenated polydecene, oleyl erucate, ethyl palmitate, polydimethylsiloxane, methyl parahydroxybenzoate, and butylated hydroxytoluene as the oil phase into the oil phase preparation tank, heat until dissolved, add cyclopentasiloxane, and stir to disperse.

[0057] Add water, glycerin, propylene glycol, butylene glycol, dipropylene glycol, betaine salicylate, trisodium EDTA, ammonium acryloyldimethyltaurate / beheneth-25 methacrylate crosspolymer, and carbomer to the aqueous phase mixing tank and heat and stir until completely dissolved.

[0058] First draw the water phase into the emulsification kettle, add the oil phase and stir thoroughly to homogenize, and keep stirring while keeping warm.

[0059] Cool the mixture and add a mixture of glycerol polymethacrylate, C12-C15 alcohol benzoate, and aminomethyl propanol. Mix thoroughly, then add a mixture of N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-2-oxopropionamide, fragrance, bis-diethoxydiglycol cyclohexane-1,4-dicarboxylate, and phenoxyethanol. Homogenize thoroughly, cool to room temperature, and allow to stand to obtain the desired emulsion.

[0060] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the present invention shall be determined by the appended claims.

Claims

1. α-keto acid amide or substituted oxalic acid amide ester compound, characterized in that: The general structural formula is shown in Formula I: wherein R1 is a C1-C6 alkyl or cycloalkyl group, or is OR2, wherein R2 is a C1-C8 alkyl or cycloalkyl group, or is NR3R4, wherein R3 and R4 are each independently a C1-C6 alkyl or cycloalkyl group; Or an amine group having the following structure: Wherein, X and Y are each independently a C1-C5 methylene group, and Z represents one of CH2, O, S, and NH.

2. The α-keto acid amide or substituted oxalic acid amide ester compound according to claim 1, characterized in that: The compound exists in free form, or in the form of a pharmaceutically acceptable salt or ester.

3. A composition comprising the α-keto acid amide or substituted oxalic acid amide ester compound according to any one of claims 1 to 2.

4. The composition according to claim 3, characterized in that The added amount of the α-keto acid amide or substituted oxalic acid amide ester compound in the composition is 0.000001% to 10% of the total weight of the preparation.

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