Sulfonamidothiazolyl resorcinol derivative and application thereof in preparation of tyrosinase inhibitor and whitening cosmetics

Abstract

The invention discloses a sulfanilamide thiazolyl resorcinol derivative and application of the sulfanilamide thiazolyl resorcinol derivative in preparation of a tyrosinase inhibitor and whitening cosmetics. The structural formula of the derivative is # imgabs0 #, in the formula, R represents a fat (aromatic) group substituent, and R'represents a hydrogen atom or methyl; the preparation method comprises the following steps: taking 2-chloro-1-(2, 4-dimethoxyphenyl) ethanone as an initial raw material, carrying out cyclization condensation on the 2-chloro-1-(2, 4-dimethoxyphenyl) ethanone and thiourea to obtain 4-(2-amino-1, 3-thiazole-4-yl) benzene-1, 3-dimethanol, carrying out reaction on 2-amino of thiazole and different fat (aromatic) sulfonyl chloride, and then removing methyl to prepare the 4-(2-amino-1, 3-thiazole-4-yl) benzene-1, 3-dimethanol. Pharmacological activity tests show that the compound has good inhibitory activity on tyrosinase, which indicates that the sulfanilamide thiazolyl resorcinol derivative can be researched and utilized as a novel tyrosinase inhibitor and whitening cosmetics.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical drugs, and particularly relates to sulfamoylthiazolylresorcinol derivatives and their applications in preparing tyrosinase inhibitors and whitening cosmetics. Background Art

[0002] Hyperpigmentation, namely the excessive production of melanin in the skin, especially in people aged 40 to 45, is a particularly prominent problem and the most common skin disease. Hyperpigmentation not only affects the appearance of the skin, but may also lead to cosmetic disfigurement, change social and mental health, and have a serious adverse impact on the quality of life of patients. Currently, the treatment of hyperpigmentation mainly includes topical drug methods (such as hydroquinone, arbutin, and kojic acid), oral drug methods, chemical peeling methods, and laser treatment methods, etc. However, these treatment methods have certain side effects, which will cause adverse effects such as contact dermatitis and skin irritation, and even cause paradoxical exogenous hyperpigmentation (blue-gray or black hyperpigmentation). Due to different curative effects, it even takes a long treatment time to achieve the expected effect. Especially the drug hydroquinone, due to the limitation of these potential side effects, its addition or use in cosmetics has been prohibited in the European Union and can only be used as a prescription drug prescribed by physicians in hospitals for combined treatment. Therefore, finding a safer and more effective alternative treatment method for hyperpigmentation has become the focus of current research. Tyrosinase is the key enzyme for melanogenesis and an attractive inhibitory target for treating hyperpigmentation. Currently, inhibiting its activity is an important strategy for treating hyperpigmentation. In recent years, amidobenzoic acid (isobutyrylaminothiazolylresorcinol) as a new type of tyrosinase inhibitor has gradually become a research hotspot in the field of whitening skin care due to its high-efficiency whitening effect and low side effects.

[0003] There is no report on screening tyrosinase inhibitors for sulfamoylthiazolylresorcinol derivatives designed and synthesized on the basis of amidobenzoic acid in the prior art, especially the research on introducing aliphatic (aromatic) sulfonamide groups at the amino site of thiazolylresorcinol to carry out tyrosinase inhibitory activity has not been reported. Summary of the Invention

[0004] The purpose of the present invention is to provide a class of sulfamoylthiazolylresorcinol derivatives having good inhibitory activity against tyrosinase.

[0005] For the above purpose, the structural formula of the sulfamoylthiazolylresorcinol derivatives provided by the present invention is shown as follows:

[0006]

[0007] Among them, R is selected from any one of C1-C6 alkyl, C3-C6 cycloalkyl, benzyl, phenyl, biphenyl, C1-C4 alkyl-substituted phenyl, C1-C4 alkoxy-substituted phenyl, p-acetylphenyl, p-cyanophenyl, 2-naphthyl, 1-naphthyl, 2-thienyl, and R' is selected from a hydrogen atom or a methyl group.

[0008] Furthermore, when R' represents a methyl group, it is preferred that R is selected from any one of ethyl, n-propyl, n-butyl, isobutyl, isopropyl, cyclohexyl, benzyl, cyclopropyl, phenyl, biphenyl.

[0009] Furthermore, when R' represents a hydrogen atom, it is preferred that R is selected from any one of ethyl, n-propyl, n-butyl, isobutyl, isopropyl, cyclohexyl, benzyl, cyclopropyl.

[0010] The synthesis route and specific synthesis method of the sulfamoylthiazolylresorcinol derivative of the present invention are as follows:

[0011]

[0012] 1. Synthesis of thiazolylresorcinol intermediate 2

[0013] Using ethanol as a solvent, compound 1 (2-chloro-1-(2,4-dimethoxyphenyl)ethanone) and thiourea are reacted at a molar ratio of 1:1-3 by heating under reflux for 4-8 h; after the reaction is completed, the temperature is lowered and filtered by suction, and the filter cake is washed and then dried under vacuum to obtain thiazolylresorcinol intermediate 2 (4-(2-amino-1,3-thiazol-4-yl)benzene-1,3-dimethanol).

[0014] 2. Synthesis of sulfamoylthiazolylresorcinol derivative

[0015] Using dry dichloromethane as a solvent, thiazolylresorcinol intermediate 2, fatty (aromatic) sulfonyl chloride triethylamine (Et3N), and 4-dimethylaminopyridine (DMAP) are mixed at a molar ratio of 1:1-5:2-4:0.1-1, and stirred at 0-5 °C for 0.5-2 h; after the reaction is completed, concentrated under reduced pressure, and the concentrate is subjected to silica gel column chromatography to obtain the target compound A.

[0016] Using dry dichloromethane as a solvent, the target compound A and boron tribromide (BBr3) are mixed at a molar ratio of 1:4-8, stirred at -15--5 °C for 0.5-2 h, and then naturally raised to room temperature and continued to stir for 8-12 h; after the reaction is completed, concentrated under reduced pressure, and the concentrate is subjected to silica gel column chromatography to obtain the target compound B.

[0017] The present invention also provides the use of the above-mentioned sulfamoylthiazolylresorcinol derivative in the preparation of tyrosinase inhibitors and whitening cosmetics.

[0018] The beneficial effects of the present invention are as follows:

[0019] The present invention uses 2-chloro-1-(2,4-dimethoxyphenyl)ethanone as the starting material, which undergoes cyclization condensation with thiourea to obtain 4-(2-amino-1,3-thiazol-4-yl)benzene-1,3-dimethanol. The amine group at the 2-position of the thiazole reacts with different aliphatic (aromatic) sulfonyl chlorides, and then the methyl group is removed for preparation. Pharmacological activity tests show that this type of compound has good inhibitory activity against tyrosinase and can be used as a new type of tyrosinase inhibitor and whitening cosmetics. Detailed implementation manners

[0020] The following further elaborates on the present invention in conjunction with the embodiments, but the protection scope of the present invention is not limited to these embodiments.

[0021] Example 1

[0022] 1. Synthesis of thiazolyl resorcinol intermediate 2

[0023] Take 8.59 g (0.04 mol) of 2-chloro-1-(2,4-dimethoxyphenyl)ethanone in a 500 mL reaction flask, add 3.2 g (0.042 mol) of thiourea, add 200 mL of ethanol, and then heat up to 78 °C. After refluxing for 6 h, TLC detection shows that the raw materials have completely reacted. Cool down to 0 °C to precipitate white solids, filter by suction, wash the filter cake with ice ethanol, and collect the solids for vacuum drying to obtain thiazolyl resorcinol intermediate 2 (10.24 g, yield 94%).

[0024] The structural characterization data of compound 2 are as follows: 1 H NMR (400 MHz, DMSO-d6) δ 7.96–7.90 (m, 1H), 6.93 (d, J = 2.0 Hz, 1H), 6.89 (s, 2H), 6.60 (d, J = 2.6 Hz, 1H), 6.56 (dd, J = 8.7, 2.5 Hz, 1H), 3.86 (d, J = 2.2 Hz, 3H), 3.80–3.76 (m, 3H) ppm; 13 C NMR (101 MHz, DMSO-d6) δ 166.14, 159.39, 157.63, 145.76, 130.06, 116.47, 104.76, 103.25, 98.54, 55.40, 55.20 ppm; HRMS (ESI) m / z theoretical value C 11 H 12 N2O2S [M + H]+, 237.0692, measured value 237.0656.

[0025] 2. Synthesis of sulfonamide thiazolyl resorcinol derivatives A1 - A20

[0026] Dissolve 239 mg (1.0 mmol) of the thiazolyl resorcinol intermediate 2 in 5 mL of dry dichloromethane. Successively add 278 μL (2.0 mmol) of triethylamine and 12 mg (0.1 mmol) of 4-dimethylaminopyridine. Add 1.1 mmol of ethylsulfonyl chloride at 0 °C. After stirring the reaction at 0 °C for 1 h, concentrate under reduced pressure. The concentrate is subjected to silica gel column chromatography (the eluent is a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1) to obtain the sulfonamide thiazolyl resorcinol derivative A1.

[0027] Replace the above ethylsulfonyl chloride successively with equimolar n-propylsulfonyl chloride, n-butylsulfonyl chloride, isobutylsulfonyl chloride, isopropylsulfonyl chloride, cyclohexylsulfonyl chloride, benzylsulfonyl chloride, cyclopropylsulfonyl chloride, phenylsulfonyl chloride, biphenylsulfonyl chloride, 2-naphthalenesulfonyl chloride, 1-naphthalenesulfonyl chloride, 4-methylbenzenesulfonyl chloride, 2-methylbenzenesulfonyl chloride, 3-methylbenzenesulfonyl chloride, 4-ethylbenzenesulfonyl chloride, 4-methoxybenzenesulfonyl chloride, 4-acetylbenzenesulfonyl chloride, 4-cyanobenzenesulfonyl chloride, 2-thiophenesulfonyl chloride to obtain the sulfonamide thiazolyl resorcinol derivatives A2 - A20 in turn.

[0028] The structural characterization data of A1 are as follows: 1 H NMR (400 MHz, DMSO-d6) δ 12.59 (s, 1H), 7.49 (d, J = 8.5 Hz, 1H), 6.88 (s, 1H), 6.66 (d, J = 2.7 Hz, 1H), 6.60 (dd, J = 8.7, 2.6 Hz, 1H), 3.82 (dd, J = 15.4, 2.1 Hz, 6H), 3.02 (q, J = 7.9, 7.5 Hz, 2H), 1.22 (dt, J = 8.3, 4.2 Hz, 3H) ppm; 13 C NMR (101 MHz, DMSO) δ 168.26, 161.22, 157.78, 129.50, 110.31, 105.24, 103.81, 98.87, 55.74, 55.47, 47.06, 8.32 ppm; HRMS (ESI) m / z theoretical value C 13 H 16 N2O4S2 [M + H] + : 329.0624, measured value 329.0575.

[0029] The structural characterization data of A2 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.56 (s, 1H), 7.49 (d, J = 8.6 Hz, 1H), 6.89 (s, 1H), 6.66 (d, J = 2.7 Hz, 1H), 6.60 (dd, J = 8.5, 2.5 Hz, 1H), 3.84 (s, 3H), 3.81 (s, 3H), 3.00 (t, J = 7.7 Hz, 2H), 1.73–1.67 (m, 2H), 0.97 (t, J = 7.3 Hz, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 167.79, 161.22, 157.78, 129.50, 110.67, 105.24, 103.88, 98.87, 55.74, 55.47, 54.36, 17.18, 12.81 ppm; HRMS (ESI) m / z calcd for C 14 H 18 N2O4S2 [M+H] + : 343.0781, found 343.0729.

[0030] The structure characterization data of A3 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.57 (s, 1H), 7.49 (d, J = 8.6 Hz, 1H), 6.89 (s, 1H), 6.67 (d, J = 2.9 Hz, 1H), 6.60 (dd, J = 8.4, 2.3 Hz, 1H), 3.84 (s, 3H), 3.80 (s, 3H), 3.01 (t, J = 7.8 Hz, 2H), 1.65 (p, J = 7.8 Hz, 2H), 1.38 (h, J = 7.5 Hz, 2H), 0.86 (t, J = 7.2 Hz, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.70, 161.23, 157.79, 129.51, 110.68, 105.25, 103.87, 98.88, 55.75, 55.48, 52.36, 25.53, 20.95, 13.61 ppm; HRMS (ESI) m / z calcd for C 15 H 20 N2O4S2 [M+H] + : 357.0937, found 357.0885.

[0031] The structure characterization data of A4 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.57 (s, 1H), 7.49 (d, J = 8.6 Hz, 1H), 6.89 (s, 1H), 6.67 (s, 1H), 6.60 (d, J = 8.8 Hz, 1H), 3.84 (s, 3H), 3.81 (s, 3H), 2.92 (d, J = 5.1 Hz, 2H), 2.12 (hept, J = 6.7 Hz, 1H), 1.03 (d, J = 2.0 Hz, 3H), 1.01 (d, J = 2.2 Hz, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.04, 161.20, 157.76, 133.35, 129.48, 110.68, 105.21, 103.79, 98.86, 60.05, 55.72, 55.45, 24.52, 22.37 ppm; HRMS (ESI) m / z calculated for C 15 H 20 N2O4S2 [M+H] + : 357.0937, found 357.0929.

[0032] The structural characterization data of A5 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.57 (s, 1H), 7.50 (d, J = 8.5 Hz, 1H), 6.87 (s, 1H), 6.67 (s, 1H), 6.60 (d, J = 8.5 Hz, 1H), 3.84 (s, 3H), 3.81 (s, 3H), 3.14 (s, 1H), 1.25 (s, 3H), 1.23 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.06, 161.17, 157.76, 153.14, 132.15, 129.45, 105.20, 103.04, 98.86, 55.73, 55.45, 52.93, 16.42 ppm; HRMS (ESI) m / z calculated for C 14 H 18 N2O4S2 [M+H] + : 343.0781, found 343.0773.

[0033] The structural characterization data of A6 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.52 (s, 1H), 7.50 (d, J = 8.5 Hz, 1H), 6.87 (s, 1H), 6.67 (s, 1H), 6.60 (s, 1H), 3.84 (s, 3H), 3.81 (s, 3H), 2.87 (t, J = 11.0 Hz, 1H), 2.06 (d, J = 12.4 Hz, 2H), 1.76 (d, J = 12.2 Hz, 2H), 1.61 (d, J = 12.6 Hz, 1H), 1.38 (q, J = 13.0, 12.4 Hz, 2H), 1.24 (d, J = 12.7 Hz, 2H), 1.11 (q, J = 12.5 Hz, 1H) ppm; 13 13C NMR (101 MHz, DMSO) δ 166.19, 161.16, 159.43, 157.75, 129.42, 105.19, 104.77, 103.22, 98.86, 60.84, 55.72, 55.44, 26.15, 24.98, 24.53 ppm; HRMS (ESI) m / z calcd for C 17 H 22 N2O4S2 [M+H] + : 383.1094, found 383.1082.

[0034] The structural characterization data of A7 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.63 (s, 1H), 7.48 (d, J = 8.6 Hz, 1H), 7.37 (d, J = 6.0 Hz, 2H), 7.30 (d, J = 6.2 Hz, 3H), 6.83 (s, 1H), 6.67 (s, 1H), 6.60 (d, J = 8.6 Hz, 1H), 4.32 (s, 2H), 3.84 (s, 3H), 3.81 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.94, 161.23, 157.75, 130.99, 130.63, 129.43, 128.05, 127.78, 110.61, 105.24, 104.04, 98.87, 58.35, 55.73, 55.47 ppm; HRMS (ESI) m / z calcd for C 18 H 18 N2O4S2 [M+H] + : 391.0781, found 391.0771.

[0035] The structural characterization data of A8 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.58 (s, 1H), 7.50 (d, J = 8.6 Hz, 1H), 6.89 (s, 1H), 6.67 (s, 1H), 6.60 (d, J = 8.3 Hz, 1H), 3.84 (s, 3H), 3.81 (s, 3H), 2.62 (p, J = 7.0 Hz, 1H), 0.92 (s, 2H), 0.89 (s, 2H) ppm; 13 13C NMR (101 MHz, DMSO) δ 161.22, 157.77, 129.48, 105.24, 98.87, 55.74, 55.47, 32.06, 30.60, 5.02, 4.54 ppm; HRMS (ESI) m / z calcd for C 14 H 16 N2O4S2 [M+H] + : 341.0624, found 341.0619.

[0036] The structural characterization data of A9 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.81 (s, 1H), 7.84 (d, J = 7.4 Hz, 2H), 7.57 (dt, J = 14.8, 7.3 Hz, 3H), 7.44 (d, J = 8.6 Hz, 1H), 6.92 (s, 1H), 6.65 (s, 1H), 6.58 (dd, J = 8.5, 2.5 Hz, 1H), 3.82 (s, 3H), 3.79 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.24, 161.33, 157.74, 142.36, 132.08, 129.56, 129.00, 125.84, 110.35, 105.24, 104.28, 98.84, 55.72, 55.46 ppm; HRMS (ESI) m / z calcd for C 17 H 16 N2O4S2 [M+H] + : 377.0624, found 377.0617.

[0037] The structural characterization data of A10 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.84 (s, 1H), 7.94–7.82 (m, 4H), 7.70 (d, J = 7.6 Hz, 2H), 7.45 (dt, J = 28.1, 7.5 Hz, 4H), 6.93 (s, 1H), 6.65 (s, 1H), 6.58 (d, J = 8.7 Hz, 1H), 3.82 (s, 3H), 3.79 (s, 3H) ppm;13 13C NMR (101 MHz, DMSO) δ 168.39, 161.34, 157.74, 143.66, 141.14, 138.72, 129.58, 129.10, 128.38, 127.26, 127.04, 126.52, 110.37, 105.25, 104.36, 98.85, 55.72, 55.45 ppm; HRMS (ESI) m / z calcd for C 23 H 20 N2O4S2 [M + H] + : 453.0937, found 453.0931.

[0038] The structural characterization data of A11 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.84 (s, 1H), 8.50 (s, 1H), 8.16 (d, J = 7.7 Hz, 1H), 8.08 (d, J = 9.3 Hz, 1H), 8.00 (d, J = 7.7 Hz, 1H), 7.85 (d, J = 8.8 Hz, 1H), 7.64 (dd, J = 13.2, 6.2 Hz, 2H), 7.43 (d, J = 8.2 Hz, 1H), 6.91 (s, 1H), 6.63 (s, 1H), 6.56 (d, J = 8.4 Hz, 1H), 3.80 (s, 3H), 3.78 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.53, 161.34, 157.73, 139.21, 134.04, 133.43, 131.65, 129.59, 129.18, 129.15, 128.45, 127.79, 127.48, 126.22, 122.29, 110.35, 105.23, 104.36, 98.83, 55.71, 55.44 ppm; HRMS (ESI) m / z calcd for C 21 H 18 N2O4S2 [M + H] + : 427.0781, found 427.0772.

[0039] The structural characterization data of A12 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.81 (s, 1H), 8.77 (d, J = 8.5 Hz, 1H), 8.23 (d, J = 7.3 Hz, 1H), 8.17 (d, J = 8.3 Hz, 1H), 8.04 (d, J = 8.2 Hz, 1H), 7.66 (dq, J = 21.7, 7.3 Hz, 3H), 7.39 (d, J = 8.6 Hz, 1H), 6.87 (s, 1H), 6.62 (s, 1H), 6.54 (d, J = 8.7 Hz, 1H), 3.77 (s, 6H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.74, 161.33, 157.72, 136.76, 133.87, 133.52, 133.22, 129.67, 128.69, 127.86, 127.60, 127.49, 126.71, 125.86, 124.31, 110.28, 105.16, 104.44, 98.79, 55.69, 55.43 ppm; HRMS (ESI) m / z calcd for C 21 H 18 N2O4S2 [M + H] + : 427.0781, found 427.0771.

[0040] The structural characterization data of A13 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.76 (s, 1H), 7.72 (d, J = 7.6 Hz, 2H), 7.44 (d, J = 8.6 Hz, 1H), 7.34 (d, J = 7.9 Hz, 2H), 6.90 (s, 1H), 6.65 (s, 1H), 6.58 (dd, J = 8.6, 2.4 Hz, 1H), 3.81 (s, 3H), 3.79 (s, 3H), 2.35 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.14, 161.31, 157.73, 142.25, 139.54, 133.06, 129.55, 129.39, 125.93, 110.38, 105.24, 104.15, 98.84, 55.72, 55.45, 20.96 ppm; HRMS (ESI) m / z calcd for C 18 H 18 N2O4S2 [M + H] + : 391.0781, found 391.0770.

[0041] The structural characterization data of A14 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.74 (s, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.46 (dd, J = 8.2, 5.0 Hz, 2H), 7.36 (d, J = 7.1 Hz, 2H), 6.87 (s, 1H), 6.65 (s, 1H), 6.58 (d, J = 8.5 Hz, 1H), 3.82 (s, 3H), 3.79 (s, 3H), 2.61 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.02, 161.34, 157.74, 140.09, 136.54, 133.35, 132.21, 132.01, 129.65, 127.77, 125.69, 110.39, 105.22, 104.30, 98.83, 55.73, 55.46, 20.03 ppm; HRMS (ESI) m / z calcd for C 18 H 18 N2O4S2 [M+H] + : 391.0781, found 391.0773.

[0042] The structural characterization data of A15 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.76 (s, 1H), 7.63 (d, J = 8.0 Hz, 2H), 7.42 (q, J = 7.8, 7.3 Hz, 3H), 6.91 (s, 1H), 6.65 (d, J = 2.7 Hz, 1H), 6.58 (dd, J = 8.5, 2.9 Hz, 1H), 3.82 (s, 3H), 3.79 (s, 3H), 2.37 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.15, 161.33, 157.74, 142.30, 138.62, 133.29, 132.70, 129.57, 128.84, 126.12, 123.05, 110.38, 105.25, 104.25, 98.84, 55.72, 55.46, 20.89 ppm; HRMS (ESI) m / z calcd for C 18 H 18 N2O4S2 [M+H] + : 391.0781, found 391.0773.

[0043] The structural characterization data of A16 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.75 (s, 1H), 7.75 (d, J = 7.5 Hz, 2H), 7.44 (d, J = 8.7 Hz, 1H), 7.37 (d, J = 7.8 Hz, 2H), 6.90 (s, 1H), 6.65 (s, 1H), 6.57 (d, J = 8.6 Hz, 1H), 3.81 (s, 3H), 3.79 (s, 3H), 2.64 (q, J = 7.2 Hz, 2H), 1.17 (td, J = 7.7, 2.3 Hz, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.67, 161.31, 157.73, 148.30, 139.78, 133.31, 129.54, 128.26, 126.01, 110.39, 105.24, 104.17, 98.84, 55.71, 55.45, 28.01, 15.21 ppm; HRMS (ESI) m / z calculated for C 19 H 20 N2O4S2 [M+H] + : 405.0937, found 405.0929.

[0044] The structure characterization data of A17 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.71 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.6 Hz, 1H), 7.06 (d, J = 8.4 Hz, 2H), 6.89 (s, 1H), 6.65 (s, 1H), 6.58 (d, J = 8.5 Hz, 1H), 3.80 (d, J = 7.4 Hz, 9H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.07, 161.93, 161.30, 157.73, 134.25, 133.35, 129.54, 127.97, 114.09, 110.42, 105.24, 104.03, 98.84, 55.71, 55.57, 55.45 ppm; HRMS (ESI) m / z calculated for C 18 H 19 N2O5S2 [M+H] + : 407.0730, found 407.0724.

[0045] The structure characterization data of A18 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.94 (s, 1H), 8.10 (d, J = 7.9 Hz, 2H), 7.96 (d, J = 7.7 Hz, 2H), 7.44 (d, J = 8.5 Hz, 1H), 6.95 (s, 1H), 6.65 (s, 1H), 6.58 (d, J = 8.5 Hz, 1H), 3.81 (s, 3H), 3.79 (s, 3H), 2.61 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 197.32, 168.46, 161.40, 157.74, 145.93, 139.16, 133.58, 129.62, 128.90, 126.18, 110.26, 105.27, 104.63, 98.85, 55.73, 55.46, 27.00 ppm; HRMS (ESI) m / z calculated for C 19 H 18 N2O5S2 [M+H] + : 419.0730, found 419.0721.

[0046] The structure characterization data of A19 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 13.02 (s, 1H), 8.03 (d, J = 8.1 Hz, 2H), 7.98 (d, J = 8.1 Hz, 2H), 7.44 (d, J = 8.5 Hz, 1H), 6.97 (s, 1H), 6.65 (s, 1H), 6.58 (dd, J = 8.7, 2.4 Hz, 1H), 3.82 (s, 3H), 3.79 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.56, 161.43, 157.75, 146.34, 133.67, 133.31, 129.64, 126.56, 117.88, 114.50, 110.18, 105.28, 104.85, 98.85, 55.74, 55.47 ppm; HRMS (ESI) m / z calculated for C 18 H 15 N3O4S2 [M+H] + : 402.0577, found 402.0570.

[0047] The structure characterization data of A20 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 7.83 (d, J = 5.0 Hz, 1H), 7.59 (s, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.14–7.10 (m, 1H), 6.97 (s, 1H), 6.66 (s, 1H), 6.59 (d, J = 8.4 Hz, 1H), 3.82 (s, 3H), 3.80 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.49, 161.40, 157.75, 143.37, 133.68, 131.51, 130.34, 129.63, 127.20, 110.28, 105.28, 104.79, 98.86, 55.74, 55.47 ppm; HRMS (ESI) m / z calcd for C 15 H 14 N2O4S3 [M + H] + : 383.0188, found 383.0180.

[0048] 3. Synthesis of sulfonamido-thiazolyl resorcinol derivatives B1 - B20

[0049] Dissolve 66 mg (0.2 mmol) of A1 in 5 mL of dry dichloromethane. Add 116 μL (1.2 mmol) of boron tribromide at -10 °C. Stir the reaction mixture at -10 °C for 1 h, then allow it to warm to room temperature and continue the reaction for 10 h. After the reaction is complete, concentrate the mixture under reduced pressure. The concentrate is purified by silica gel column chromatography (eluent: a mixture of dichloromethane and methanol with a volume ratio of 20:1) to obtain sulfonamido-thiazolyl resorcinol derivative B1.

[0050] Replace A1 with an equimolar amount of A2 - A20 successively to obtain sulfonamido-thiazolyl resorcinol derivatives B2 - B20.

[0051] The structure characterization data of B1 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.43 (s, 1H), 10.21 (s, 1H), 9.67 (s, 1H), 7.34 (d, J = 8.7 Hz, 1H), 6.86 (s, 1H), 6.41 (s, 1H), 6.27 (d, J = 8.5 Hz, 1H), 3.01 (q, J = 7.4 Hz, 2H), 1.21 (t, J = 7.1 Hz, 3H) ppm; 1313C NMR (101 MHz, DMSO) δ 168.24, 159.00, 156.22, 128.87, 107.56, 106.93, 102.93, 102.19, 47.02, 8.34 ppm; HRMS (ESI) m / z calcd for C 11 H 12 N2O4S2 [M+H] + : 301.0311, found 301.0268.

[0052] The structure characterization data of B2 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.41 (s, 1H), 10.21 (s, 1H), 9.67 (s, 1H), 7.34 (d, J = 8.7 Hz, 1H), 6.86 (s, 1H), 6.41 (s, 1H), 6.27 (d, J = 8.6 Hz, 1H), 2.98 (t, J = 7.7 Hz, 2H), 1.69 (h, J = 7.7 Hz, 2H), 0.96 (t, J = 6.9 Hz, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.19, 159.00, 156.21, 128.86, 107.57, 106.92, 102.93, 102.17, 54.32, 17.20, 12.82 ppm; HRMS (ESI) m / z calcd for C 12 H 14 N2O4S2 [M+H] + : 315.0468, found 315.0418.

[0053] The structure characterization data of B3 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.07 (s, 1H), 10.10 (s, 2H), 7.33 (d, J = 8.6 Hz, 1H), 6.87 (s, 1H), 6.43 (s, 1H), 6.27 (d, J = 8.8 Hz, 1H), 3.00 (t, J = 7.8 Hz, 2H), 1.71–1.58 (m, 2H), 1.37 (h, J = 7.8 Hz, 2H), 0.85 (t, J = 7.4 Hz, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 159.03, 156.23, 128.87, 107.65, 106.96, 102.98, 102.34, 52.33, 25.56, 20.96, 13.64 ppm; HRMS (ESI) m / z calcd for C 13 H 16 N2O4S2 [M+H]+ : 329.0624, measured value 29.0617.

[0054] The structural characterization data of B4 are as follows: 1 H NMR (400 MHz, DMSO-d6) δ 7.33 (d, J = 8.6 Hz, 1H), 6.87 (s, 1H), 6.43 (s, 1H), 6.27 (d, J = 9.0 Hz, 1H), 2.90 (d, J = 6.7 Hz, 2H), 2.09 (d, J = 7.0 Hz, 1H), 1.01 (d, J = 6.7 Hz, 6H) ppm; 13 C NMR (101 MHz, DMSO) δ 159.04, 156.24, 128.89, 107.66, 106.96, 106.76, 102.98, 102.76, 102.35, 60.05, 24.58, 22.43, 22.37 ppm; HRMS (ESI) m / z theoretical value C 13 H 16 N2O4S2 [M+H] + : 329.0624, measured value 329.0618.

[0055] The structural characterization data of B5 are as follows: 1 H NMR (400 MHz, DMSO-d6) δ 12.57 (s, 1H), 7.50 (d, J = 8.5 Hz, 1H), 6.87 (s, 1H), 6.67 (s, 1H), 6.60 (d, J = 8.5 Hz, 1H), 3.14 (s, 1H), 1.25 (s, 3H), 1.23 (s, 3H) ppm; 13 C NMR (101 MHz, DMSO) δ 168.06, 161.17, 157.76, 153.14, 132.15, 129.45, 105.20, 103.04, 98.86, 55.73, 16.42 ppm; HRMS (ESI) m / z theoretical value C 12 H 15 N2O4S2 [M+H] + : 315.0468, measured value 315.0473.

[0056] The structural characterization data of B6 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.52 (s, 1H), 7.50 (d, J = 8.5 Hz, 1H), 6.87 (s, 1H), 6.67 (s, 1H), 6.60 (s, 1H), 2.87 (t, J = 11.0 Hz, 1H), 2.06 (d, J = 12.4 Hz, 2H), 1.76 (d, J = 12.2 Hz, 2H), 1.61 (d, J = 12.6 Hz, 1H), 1.38 (q, J = 13.0, 12.4 Hz, 2H), 1.24 (d, J = 12.7 Hz, 2H), 1.11 (q, J = 12.5 Hz, 1H) ppm; 13 13C NMR (101 MHz, DMSO) δ 166.19, 161.16, 159.43, 157.75, 129.42, 105.19, 104.77, 103.22, 98.86, 60.84, 26.15, 24.98, 24.53 ppm; HRMS (ESI) m / z calculated for C 15 H 19 N2O4S2 [M+H] + : 355.0781, found 355.0167.

[0057] The structural characterization data of B7 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.63 (s, 1H), 7.48 (d, J = 8.6 Hz, 1H), 7.37 (d, J = 6.0 Hz, 2H), 7.30 (d, J = 6.2 Hz, 3H), 6.83 (s, 1H), 6.67 (s, 1H), 6.60 (d, J = 8.6 Hz, 1H), 4.32 (s, 2H) ppm; 13 13C NMR (101 MHz, DMSO-d6) δ 168.94, 161.23, 157.75, 130.99, 130.63, 129.43, 128.05, 127.78, 110.61, 105.24, 104.04, 98.87, 55.47 ppm; HRMS (ESI) m / z calculated for C 16 H 14 N2O4S2 [M+H] + : 362.0395, found 362.0387.

[0058] The structural characterization data of B8 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.58 (s, 1H), 7.50 (d, J = 8.6 Hz, 1H), 6.89 (s, 1H), 6.67 (s, 1H), 6.60 (d, J = 8.3 Hz, 1H), 2.62 (p, J = 7.0 Hz, 1H), 0.92 (s, 2H), 0.89 (s, 2H) ppm; 13 13C NMR (101 MHz, DMSO-d6) δ 161.22, 157.77, 129.48, 105.24, 98.87, 32.06, 30.60, 5.02, 4.54 ppm; HRMS (ESI) m / z calculated for C 12 H 12 N2O4S2 [M + H] + : 312.0238, found 312.0249.

[0059] The structure characterization data of B9 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.65 (s, 1H), 10.21 (s, 1H), 9.67 (s, 1H), 7.83 (d, J = 7.2 Hz, 2H), 7.57 (dd, J = 12.5, 6.8 Hz, 3H), 7.30 (d, J = 8.3 Hz, 1H), 6.90 (s, 1H), 6.40 (s, 1H), 6.25 (d, J = 8.4 Hz, 1H) ppm; 13 13C NMR (101 MHz, DMSO-d6) δ 168.33, 159.12, 156.25, 142.43, 132.03, 128.97, 128.91, 125.85, 107.35, 106.92, 102.89, 102.74 ppm; HRMS (ESI) m / z calculated for C 15 H 12 N2O4S2 [M + H] + : 349.0311, found 349.0306.

[0060] The structure characterization data of B10 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.70 (s, 1H), 10.50 (s, 1H), 9.68 (s, 1H), 8.02–7.74 (m, 4H), 7.69 (t, J = 7.8 Hz, 2H), 7.57–7.24 (m, 4H), 6.91 (s, 1H), 6.41 (s, 1H), 6.26 (d, J = 8.3 Hz, 1H) ppm; 1313C NMR (101 MHz, DMSO) δ 159.13, 156.25, 155.52, 155.18, 143.61, 141.23, 138.76, 131.31, 129.10, 129.00, 128.91, 128.36, 127.69, 127.23, 127.05, 126.53, 106.91, 103.75, 102.88, 98.88 ppm; HRMS (ESI) m / z calcd for C 21 H 16 N2O4S2 [M+H] + : 425.0624, found 425.0615.

[0061] The structure characterization data of B11 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.68 (s, 1H), 10.36 (d, J = 99.7 Hz, 1H), 9.66 (s, 1H), 8.48 (s, 1H), 8.16 (d, J = 7.2 Hz, 1H), 8.07 (d, J = 8.5 Hz, 1H), 8.00 (d, J = 7.2 Hz, 1H), 7.84 (d, J = 8.5 Hz, 1H), 7.65 (s, 2H), 7.29 (d, J = 8.4 Hz, 1H), 6.90 (s, 1H), 6.39 (s, 1H), 6.24 (d, J = 8.5 Hz, 1H) ppm; 13 13C NMR (101 MHz, DMSO-d6) δ 168.28, 159.11, 156.25, 155.53, 139.31, 134.02, 131.64, 129.16, 129.11, 128.90, 128.41, 127.79, 127.47, 126.21, 122.32, 107.37, 106.89, 103.74, 102.87 ppm; HRMS (ESI) m / z calcd for C 19 H 14 N2O4S2 [M+H] + : 399.0468, found 399.0465.

[0062] The structure characterization data of B12 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.66 (s, 1H), 10.16 (s, 1H), 9.66 (s, 1H), 8.76 (d, J = 8.4 Hz, 1H), 8.22 (d, J = 7.1 Hz, 1H), 8.16 (d, J = 8.2 Hz, 1H), 8.04 (d, J = 7.9 Hz, 1H), 7.71–7.66 (m, 1H), 7.63 (s, 2H), 7.26 (d, J = 8.4 Hz, 1H), 6.86 (s, 1H), 6.37 (s, 1H), 6.23 (d, J = 8.3 Hz, 1H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.04, 159.11, 156.21, 136.86, 133.87, 133.16, 131.30, 128.99, 128.67, 127.89, 127.59, 127.46, 126.69, 125.90, 124.30, 107.28, 106.84, 102.84, 98.82 ppm; HRMS (ESI) m / z calcd for C 19 H 14 N2O4S2 [M+H] + : 399.0468, found 399.0460.

[0063] The structure characterization data of B13 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.78–12.54 (m, 1H), 10.48 (s, 1H), 10.19 (s, 1H), 7.71 (d, J = 7.9 Hz, 2H), 7.65 (s, 1H), 7.34 (d, J = 8.0 Hz, 2H), 6.63 (s, 1H), 6.40 (s, 1H), 6.25 (d, J = 8.6 Hz, 1H), 2.34 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO) δ 168.46, 159.09, 156.22, 155.47, 155.15, 141.85, 131.31, 129.38, 129.36, 128.89, 125.93, 106.90, 103.74, 102.87, 98.87, 20.97 ppm; HRMS (ESI) m / z calcd for C 16 H 14 N2O4S2 [M+H] + : 363.0468, found 362.0461.

[0064] The structure characterization data of B14 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.74 (s, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.46 (dd, J = 8.2, 5.0 Hz, 2H), 7.36 (d, J = 7.1 Hz, 2H), 6.87 (s, 1H), 6.65 (s, 1H), 6.58 (d, J = 8.5 Hz, 1H), 2.61 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO-d6) δ 168.02, 161.34, 157.74, 140.09, 136.54, 133.35, 132.21, 132.01, 129.65, 127.77, 125.69, 110.39, 105.22, 104.30, 98.83, 20.03 ppm; HRMS (ESI) m / z calcd for C 18 H 18 N2O4S2 [M+H] + , 391.0781; Found, 391.0773. HRMS (ESI) m / z calcd for C 16 H 14 N2O4S2 [M+H] + : 363.0468, found 363.0473.

[0065] The structure characterization data of B15 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.61 (s, 1H), 10.19 (s, 1H), 9.67 (s, 1H), 7.64 (s, 2H), 7.41 (d, J = 7.7 Hz, 2H), 7.30 (d, J = 8.5 Hz, 1H), 6.89 (s, 1H), 6.40 (s, 1H), 6.25 (d, J = 8.5 Hz, 1H), 2.37 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO-d6) δ 168.34, 159.10, 156.24, 142.27, 138.58, 132.64, 128.90, 128.80, 126.12, 123.05, 107.35, 106.90, 102.88, 98.83, 20.90 ppm; HRMS (ESI) m / z calcd for C 16 H 14 N2O4S2 [M+H] + : 363.0468, found 363.0461.

[0066] The structure characterization data of B16 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.75 (s, 1H), 7.75 (d, J = 7.5 Hz, 2H), 7.44 (d, J = 8.7 Hz, 1H), 7.37 (d, J = 7.8 Hz, 2H), 6.90 (s, 1H), 6.65 (s, 1H), 6.57 (d, J = 8.6 Hz, 1H), 2.64 (q, J = 7.2 Hz, 2H), 1.17 (td, J = 7.7, 2.3 Hz, 3H) ppm; 13 13C NMR (101 MHz, DMSO-d6) δ 168.67, 161.31, 157.73, 148.30, 139.78, 133.31, 129.54, 128.26, 126.01, 110.39, 105.24, 104.17, 98.84, 28.01, 15.21 ppm; HRMS (ESI) m / z calculated for C 17 H 17 N2O4S2 [M+H] + : 377.0624, found 377.0635.

[0067] The structure characterization data of B17 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.71 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.6 Hz, 1H), 7.06 (d, J = 8.4 Hz, 2H), 6.89 (s, 1H), 6.65 (s, 1H), 6.58 (d, J = 8.5 Hz, 1H), 3.80 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO-d6) δ 168.07, 161.93, 161.30, 157.73, 134.25, 133.35, 129.54, 127.97, 114.09, 110.42, 105.24, 104.03, 98.84, 55.45 ppm; HRMS (ESI) m / z calculated for C 16 H 15 N2O5S2 [M+H] + : 379.0417, found 379.0423.

[0068] The structure characterization data of B18 are as follows: 11H NMR (400 MHz, DMSO-d6) δ 12.73 (s, 1H), 10.21 (s, 1H), 9.67 (s, 1H), 8.23–7.93 (m, 2H), 7.90–7.71 (m, 2H), 7.29 (d, J = 8.4 Hz, 1H), 6.91 (s, 1H), 6.39 (s, 1H), 6.24 (d, J = 8.6 Hz, 1H), 1.22 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO-d6) δ 159.13, 156.29, 128.99, 126.21, 106.90, 102.87, 18.21 ppm; HRMS (ESI) m / z calcd for C 17 H 14 N2O5S2 [M+H] + : 391.0417, found 391.0411.

[0069] The structural characterization data of B19 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.77 (s, 1H), 10.48 (s, 1H), 9.67 (s, 1H), 7.98 (d, J = 7.9 Hz, 2H), 7.88 (d, J = 8.1 Hz, 2H), 7.56 (s, 1H), 6.96 (d, J = 42.0 Hz, 1H), 6.61 (s, 1H), 6.44–6.21 (m, 1H) ppm; 13 13C NMR (101 MHz, DMSO-d6) δ 166.94, 156.29, 155.59, 155.15, 137.39, 131.18, 128.10, 125.82, 106.91, 103.77, 102.88, 98.87 ppm; HRMS (ESI) m / z calcd for C 16 H 11 N3O4S2 [M+H] + : 374.0264, found 374.0249.

[0070] The structural characterization data of B20 are as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 10.22 (s, 1H), 9.69 (s, 1H), 7.82 (d, J = 4.9 Hz, 1H), 7.57 (s, 1H), 7.31 (d, J = 8.5 Hz, 1H), 7.11 (s, 1H), 6.96 (s, 1H), 6.41 (s, 1H), 6.26 (d, J = 8.8 Hz, 1H) ppm; 1313C NMR (101 MHz, DMSO-d6) δ 168.92, 159.20, 156.28, 143.46, 131.42, 130.30, 128.98, 127.17, 107.26, 106.94, 103.27, 102.90 ppm; HRMS (ESI) m / z calcd for C 13 H 10 N2O4S3 [M+H] + : 354.9875, found 354.9870.

[0071] Table 1 Substituents and yields of compounds A1 - A20 and B1 - B20

[0072]

[0073]

[0074]

[0075] Example 2

[0076] Compounds A1 - A20 and B1 - B20 above were used as test compounds respectively to test their inhibitory activities against tyrosinase. The specific test conditions are as follows:

[0077] Measurement of mushroom tyrosinase activity: Mushroom tyrosinase and L-tyrosine were purchased from Aladdin Reagent Co., Ltd. The reaction mixture for mushroom tyrosinase activity consisted of 150 μL of 0.1 M phosphate buffer (pH 6.5), 3 μL of sample solution, 8 μL of mushroom tyrosinase (2100 units / mL, 0.05 M phosphate buffer solution at pH 6.5), and 36 μL of 1.5 mM L-tyrosine. After incubation at 37 °C for 20 min, the tyrosinase activity was determined by reading the optical density at 490 nm on a microplate reader (Bio-Rad 3550, Richmond, CA, USA). The inhibitory activity of the sample was expressed as the concentration inhibiting 50% of the enzyme activity (IC 50 ).

[0078] The test results are shown in Table 2.

[0079] Table 2 Inhibitory activities of compounds A1 - A20 and B1 - B20 against tyrosinase

[0080]

[0081]

[0082] As can be seen from the activity results in Table 2, the sulfamoylthiazolylresorcinol derivatives A1-A10 and B1-B8 of the present invention showed excellent in vitro inhibitory activity against tyrosinase, all higher than the inhibitory activity of the positive control drug, pamidronic acid, indicating that such sulfamoylthiazolylresorcinol derivatives can be used to prepare tyrosinase inhibitors and whitening cosmetics.

Claims

1. A sulfonamido-thiazolyl resorcinol derivative, characterized in that The structural formula of the derivative is as follows: Wherein, R is selected from any one of C1-C6 alkyl, C3-C6 cycloalkyl, benzyl, phenyl, biphenyl, C1-C4 alkyl-substituted phenyl, C1-C4 alkoxy-substituted phenyl, p-acetylphenyl, p-cyanophenyl, 2-naphthyl, 1-naphthyl, 2-thienyl, and R' is selected from a hydrogen atom or a methyl group.

2. The sulfamoylthiazolylresorcinol derivative according to claim 1, characterized in that: R is selected from any one of ethyl, n-propyl, n-butyl, isobutyl, isopropyl, cyclohexyl, benzyl, cyclopropyl, phenyl, biphenyl, and R' represents a methyl group.

3. The sulfamoylthiazolylresorcinol derivative according to claim 1, characterized in that: R is selected from any one of ethyl, n-propyl, n-butyl, isobutyl, isopropyl, cyclohexyl, benzyl, cyclopropyl, and R' represents a hydrogen atom.

4. Use of the sulfamoylthiazolylresorcinol derivative according to claim 1 in the preparation of a tyrosinase inhibitor.

5. Use of the sulfamoylthiazolylresorcinol derivative according to claim 1 in the preparation of a whitening cosmetic.

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