Resorcinol derivatives for cosmetic use thereof
10457619 · 2019-10-29
Assignee
Inventors
Cpc classification
C07C39/11
CHEMISTRY; METALLURGY
International classification
C07C39/11
CHEMISTRY; METALLURGY
Abstract
The present invention relates to a compound of formula (I), in particular for the use thereof for depigmenting, lightering and/or bleaching the skin. (I) In which R.sub.1 and R.sub.2, which may be identical or different, denote hydrogen, or a COR5 radical in which R5 denotes a linear C.sub.1-C.sub.10 or branched C.sub.3-C.sub.10 alkyl radical, preferably a linear C.sub.1-C.sub.6 or branched C.sub.3-C.sub.6 alkyl radical, more preferentially a linear C.sub.1-C.sub.4 alkyl radical, R.sub.3 denotes a linear C.sub.1-C.sub.6 or branched C.sub.3-C.sub.6 alkyl radical, preferably a linear C.sub.1-C.sub.4 or branched C.sub.3-C.sub.4 alkyl radical, and R.sub.4 denotes H, a linear C.sub.1-C.sub.6 or branched C.sub.3-C.sub.6 alkyl radical, or a COR5 radical, and also the salts thereof, the solvates thereof and the optical isomers thereof, and the racemic mixtures thereof, alone or as a mixture. The present invention also relates to the novel compounds (I) and also to the process for preparing same and to a cosmetic process for depigmenting the skin using such compounds (I). ##STR00001##
Claims
1. A compound for depigmenting, lightening, and/or bleaching the skin, according to formula (I) below: ##STR00014## wherein: R.sub.1 and R.sub.2, which may be identical or different, are chosen from: a) hydrogen, or b) a radical COR.sub.5, wherein R.sub.5 is chosen from a linear C.sub.1-C.sub.10 or branched C.sub.3-C.sub.10 alkyl radical; R.sub.3 is chosen from a linear C.sub.1-C.sub.6 or branched C.sub.3-C.sub.6 alkyl radical; and R.sub.4 is chosen from: a) hydrogen, b) a linear C.sub.1-C.sub.6 or branched C.sub.3-C.sub.6 alkyl radical, or c) a radical COR.sub.5, or a salt thereof, a solvate thereof, an optical isomer thereof, a racemate thereof, or a mixture thereof.
2. The compound according to claim 1, wherein: R.sub.1 and R.sub.2, which may be identical or different, are chosen from a radical COR.sub.5, wherein R.sub.5 is chosen from a linear C.sub.1-C.sub.6 or branched C.sub.3-C.sub.6 alkyl radical; and R.sub.3 is chosen from a linear C.sub.1-C.sub.4 or branched C.sub.3-C.sub.4 alkyl radical.
3. The compound according to claim 1, wherein R.sub.1 and R.sub.2, which may be identical or different, are chosen from a radical COR.sub.5, wherein R.sub.5 is chosen from a linear C.sub.1-C.sub.4 alkyl radical.
4. The compound according to claim 1, wherein R.sub.4 is chosen from hydrogen, a linear C.sub.1-C.sub.4 alkyl radical, a branched C.sub.3-C.sub.4 alkyl radical, or a radical COR.sub.5.
5. The compound according to claim 1, wherein R.sub.4 is chosen from hydrogen or a radical COR.sub.5.
6. The compound according to claim 1, wherein: R.sub.1 and R.sub.2, which may be identical or different, are chosen from hydrogen or a COCH.sub.3 radical; R.sub.3 is chosen from methyl, ethyl or isopropyl; and R.sub.4 is chosen from hydrogen or a COCH.sub.3 radical, or a salt thereof, a solvate thereof, an optical isomer thereof, a racemate thereof.
7. The compound according to claim 1, wherein: R.sub.1 and R.sub.2, which may be identical or different, are chosen from hydrogen or a COCH.sub.3 radical; R.sub.3 is methyl; and R.sub.4 is chosen from hydrogen or a COCH.sub.3 radical, or a salt thereof, a solvate thereof, an optical isomer thereof, or a racemate thereof.
8. The compound according to claim 1, wherein the compound is chosen from: TABLE-US-00006 Compound Structure No. Chemical name
9. A cosmetic composition comprising, in a physiologically acceptable medium, at least one compound according to formula (I) below: ##STR00018## wherein: R.sub.1 and R.sub.2, which may be identical or different, are chosen from: a) hydrogen, or b) a radical COR.sub.5, wherein R.sub.5is chosen from a linear C.sub.1-C.sub.10 or branched C.sub.3-C.sub.10 alkyl radical; R.sub.3 is chosen from a linear C.sub.1-C.sub.6 or branched C.sub.3-C.sub.6 alkyl radical; and R.sub.4 is chosen from a) hydrogen, b) a linear C.sub.1-C.sub.6 or branched C.sub.3-C.sub.6 alkyl radical, or c) a radical COR.sub.5, or a salt thereof, a solvate thereof, an optical isomer thereof, a racemate thereof, or a mixture thereof.
10. The composition according to claim 9, wherein: R.sub.1 and R.sub.2, which may be identical or different, are chosen from hydrogen or a radical COR.sub.5, wherein R.sub.5 is chosen from a linear C.sub.1-C.sub.6 or branched C.sub.3-C.sub.6 alkyl radical; and R.sub.3 is chosen from a linear C.sub.1-C.sub.4 or branched C.sub.3-C.sub.4 alkyl radical.
11. The composition according to claim 9, wherein R.sub.1 and R.sub.2, which may be identical or different, are chosen from a radical COR.sub.5, wherein R.sub.5 is chosen from a linear C.sub.1-C.sub.4 alkyl radical.
12. The composition according to claim 9, wherein R.sub.4 is chosen from hydrogen, a linear C.sub.1-C.sub.4 alkyl radical, a branched C.sub.3-C.sub.4 alkyl radical, or a radical COR.sub.5.
13. The composition according to claim 9, wherein R.sub.4 is chosen from hydrogen or a radical COR.sub.5.
14. The composition according to claim 9, comprising at least one compound according to formula (I) wherein: R.sub.1 and R.sub.2, which may be identical or different, are chosen from hydrogen or a COCH.sub.3 radical; R.sub.3 is chosen from methyl, ethyl or isopropyl; and R.sub.4 is chosen from hydrogen or a COCH.sub.3 radical, or a salt thereof, a solvate thereof, an optical isomer thereof, a racemate thereof, or a mixture thereof.
15. The composition according to claim 9, comprising at least one compound according to formula (I) wherein: R.sub.1 and R.sub.2, which may be identical or different, are chosen from hydrogen or a COCH.sub.3 radical; R.sub.3 is methyl; and R.sub.4 is chosen from hydrogen or a COCH.sub.3 radical, or a salt thereof, a solvate thereof, an optical isomer thereof, a racemate thereof, or a mixture thereof.
16. The composition according to claim 9, wherein the composition comprises at least one compound chosen from: TABLE-US-00007 Compound Structure No. Chemical name
17. The composition according to claim 9, wherein the at least one compound according to formula (I) is present in an amount ranging from about 0.01% to about 10% by weight, relative to the total weight of the composition.
18. The composition according to claim 9, wherein the at least one compound according to formula (I) is present in an amount ranging from about 0.1% to about 5% by weight, relative to the total weight of the composition.
19. The composition according to claim 9, wherein the at least one compound according to formula (I) is present in an amount ranging from about 0.5% to about 3% by weight, relative to the total weight of the composition.
20. A nontherapeutic cosmetic process for depigmenting, lightening and/or bleaching keratin materials, wherein the method comprises applying to the keratin materials a cosmetic composition, the cosmetic composition comprising, in a physiologically acceptable medium, at least one compound according to formula (I) below: ##STR00022## wherein: R.sub.1 and R.sub.2, which may be identical or different, are chosen from: a) hydrogen, or b) a radical COR.sub.5, wherein R.sub.5is chosen from a linear C.sub.1-C.sub.10 or branched C.sub.3-C.sub.10 alkyl radical; R.sub.3 is chosen from a linear C.sub.1-C.sub.6 or branched C.sub.3-C.sub.6 alkyl radical; and R.sub.4 is chosen from a) hydrogen, b) a linear C.sub.1-C.sub.6 or branched C.sub.3-C.sub.6 alkyl radical, or c) a radical COR.sub.5, or a salt thereof, a solvate thereof, an optical isomer thereof, a racemate thereof, or a mixture thereof.
Description
EXAMPLE 1
Synthesis of Compound 1
(1) ##STR00010##
(2) Reagents: 7-hydroxy-4-methyl-3,4-dihydro-2H-1-benzopyran-2-one: 5.7 g LiAlH4 powder (3 eq): 3.7 g anhydrous THF: 250 ml
(3) Procedure:
(4) The LiAlH4 and the THF (part) were placed in a round-bottomed flask, and coumarin in solution was then added dropwise. The mixture was stirred overnight at room temperature.
(5) The reaction medium was cooled to 0 C. and 20 ml of water and then 250 ml of 1N HCl were added cautiously. The THF was evaporated off and the residue was then extracted three times with diethyl ether. The combined organic phases were washed with saturated NaCl solution and then dried with Na2SO4, filtered and evaporated.
(6) 5 g of a slightly pinkish powder corresponding to the expected compound (86% yield) were recovered.
(7) The 1H NMR and mass spectra are in accordance with the structure.
(8) Melting point: 128.8-129.4 C. (capillary tube)
EXAMPLE 2
Synthesis of Compound 2
(9) ##STR00011##
(10) Reagents: 4-(4-hydroxybut-2-yl)benzene-1,3-diol: 0.8 g acetic anhydride (3 eq): 1.2 ml pyridine: 5 ml
(11) Procedure:
(12) 4-(4-Hydroxybut-2-yl)benzene-1,3-diol and then pyridine were placed in a round-bottomed flask. The medium was cooled to 0 C. and acetic anhydride was then added. The mixture was stirred overnight at room temperature.
(13) 50 ml of ethyl acetate and 50 ml of 1N HCl were added. The organic phase was washed with twice 50 ml of 1N HCl and then 50 ml of water and 50 ml of saturated NaCl solution. The organic phase was dried with Na2SO4, filtered and evaporated.
(14) 1 g of a yellow oil corresponding to the expected compound (77% yield) was recovered.
(15) The 1H NMR and mass spectra are in accordance with the structure.
EXAMPLE 3
Synthesis of Compound 3
(16) ##STR00012##
(17) Reagents: 4-[4-(acetyloxy)but-2-yl]benzene-1,3-diyldiacetate: 0.4 g potassium hydrogen carbonate (2 eq): 260 mg water: 1 ml ethanol: 2 ml
(18) Procedure: 4-[4-(Acetyloxy)but-2-yl]benzene-1,3-diyl diacetate and ethanol were placed in a round-bottomed flask, and water and KHCO3 were then added.
(19) The mixture was left for 1 hour at room temperature. The ethanol was evaporated off and the residue was extracted with ethyl acetate. The organic phase was dried with Na2SO4 and then filtered and evaporated.
(20) 0.25 g of a yellow oil corresponding to the expected compound (86% yield) was recovered.
(21) The 1H NMR and mass spectra are in accordance with the expected structure.
EXAMPLE 4
Demonstration of the Activity on Constitutive Melanogenesis
(22) The efficacy was demonstrated on the basis of the following test:
(23) For the evaluations of the effect of preventing or decreasing pigmentation of the skin and/or of lightening of this skin, the examples are performed in the following manner.
(24) The measurement of the depigmenting activity (reduction of melanin production) of compounds of formula (I) was performed by assaying normal human melanocytes in vitro as follows.
(25) First of all, normal human melanocytes were cultured and dispensed into 384 wells. After 24 hours, the culture medium was replaced with a medium containing compounds of formula (I) to be evaluated. The cells were incubated for 72 hours before measurement of the final optical density, which measures the amount of melanin produced by the melanocytes. A dose effect was performed using a wide concentration range of the compounds evaluated. Thus, by making the concentrations and the melanin measurements correspond, it was possible to determine an IC50 in M: concentration at which a 50% decrease in melanin synthesis is achieved.
(26) The compounds of formula (I) showed a strong depigmenting effect.
(27) TABLE-US-00002 Maximum concentration Compound No. IC50 (M) tested (M) 1 3.61 200 2 4.08 200 3 4.96 200
(28) These results were compared with those obtained with the closest compound described in the prior art, in patent JP 2007186445 from Kuraray
(29) ##STR00013##
(30) For this compound (A), the IC50 value is 23.4 M: maximum concentration tested 200 M.
(31) The compounds of the invention have melanogenesis-reducing activity that is much greater than that of the compound (A) outside the invention.
EXAMPLE 5
Cosmetic Composition
(32) A skin depigmenting composition is prepared, comprising (in grams):
(33) TABLE-US-00003 Compound 1 2 g PEG400 68 g Ethanol 30 g
(34) The composition applied to the skin makes it possible to attenuate brown spots.
EXAMPLE 6
Gel
(35) A skin depigmenting gel is prepared, comprising (% by weight):
(36) TABLE-US-00004 Compound 2 0.25% Carbomer (Carbopol 981 from Lubrizol) 1% preserving agent qs Water qs 100%
(37) The composition applied to the skin makes it possible to attenuate brown spots.
EXAMPLE 7
Demonstration of the Depigmenting Activity on a Pigmented Reconstructed Epidermis
(38) The aim of this test is to evaluate the modulation of melanogenesis in pigmented reconstructed epidermides after systemic application of the products. The compounds are tested at 30 M in DMSO. The pigmented epidermides are reconstructed using keratinocytes and melanocytes of European origin seeded on the substrate BPER (Episkin). The test products are added to the culture medium immediately on seeding the cells and at all the changes of medium.
(39) The pigmented reconstructed epidermis standard study model was published by:
(40) Regnier M., Duval C., Galey J. B., Philippe M., Lagrange A., Tuloup R., Schmidt R., Cellular and Molecular Biology, 1999, 45, 7, 969-980: Keratinocyte-melanocyte co-cultures and pigmented reconstructed human epidermis: models to study modulation of melanogenesis.
(41) The melanin was quantified by image analysis on histological sections after revelation with Fontana-Masson stain. Each stained epidermis is photographed over its entire length using a camera connected to a microscope.
(42) The results are collated in the following table:
(43) The decrease in the amount of melanin is evaluated relative to the solvent (DMSO)
(44) TABLE-US-00005 Depigmentin g activity/DMSO Lucinol 41% Compound 1 59%
(45) The results obtained show that compound 1 according to the invention has greater depigmenting activity than that of lucinol.