1-(3,4-DISUBSTITUTED)PHENYL-2-(3,4-DISUBSTITUTED)PHENYLETHANE COMPOUNDS AND USE THEREOF

Abstract

The present invention relates to the cosmetic use, in a composition containing a physiologically acceptable medium, of at least one compound of formula (I) in which: —R.sub.3 means a hydrogen atom or a hydroxyl radical, —R.sub.1 and R.sub.2 mean, independently of each other, a hydrogen atom, a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, and/or of an isomer and/or of a salt and/or of a solvate of said compound of formula (1), for preventing and/or treating the signs of ageing of the skin and its appendages.

##STR00001##

Claims

1. A cosmetic method for preventing and/or treating the signs of ageing of the skin and its appendages comprising, in a composition containing a physiologically acceptable medium, using at least one compound of formula (I): ##STR00023## in which: R.sub.3 means a hydrogen atom or a hydroxyl radical, R.sub.1 and R.sub.2 mean, independently of each other, a hydrogen atom, a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, and/or of an isomer and/or of a salt and/or of a solvate of said compound of formula (I).

2. The method as claimed in claim 1, wherein in the compound of formula (I): R.sub.1 means a hydrogen atom; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl, or a linear or branched C1-C6 alkoxycarbonyl radical, and R.sub.2 means a linear or branched C1-C6 alkyl radical.

3. The method as claimed in claim 1, wherein in the compound of formula (I): R.sub.1 means a hydrogen atom; and R.sub.2 means a linear or branched C1-C6 alkyl radical.

4. The method as claimed in claim 1, wherein in the compound of formula (I): R.sub.1 means a hydrogen atom; and R.sub.2 means a methyl radical.

5. Compound of formula (Ia): ##STR00024## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C2-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical.

6. Compound of formula (Ib): ##STR00025## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom or an ethyl radical, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C3-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a benzyl radical or an acetyl, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; D. R.sub.1 means a linear or branched C3-C6 alkyl radical; a linear or branched C2-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, on the understanding that: R.sub.1 and R.sub.2 cannot simultaneously denote a hydrogen atom, or a methyl, allyl, n-butyl, n-pentyl or acetyl radical.

7. A composition, comprising, in a physiologically acceptable medium, at least one compound chosen from: the compound of formula (I) ##STR00026## in which: R.sub.3 means a hydrogen atom or a hydroxyl radical, R.sub.1 and R.sub.2 mean, independently of each other, a hydrogen atom, a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, and/or of an isomer and/or of a salt and/or of a solvate of said compound of formula (I), the compound of formula (Ia) ##STR00027## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C2-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and the compound of formula (Ib) ##STR00028## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom or an ethyl radical, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C3-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a benzyl radical or an acetyl, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; D. R.sub.1 means a linear or branched C3-C6 alkyl radical; a linear or branched C2-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, on the understanding that: R.sub.1 and R.sub.2 cannot simultaneously denote a hydrogen atom, or a methyl, allyl, n-butyl, n-pentyl or acetyl radical.

8. The composition as claimed in claim 7, in which the compound of formula (I), (Ia) or (Ib) is present, alone or as a mixture, in an amount of between 0.001% and 30% by weight relative to the total weight of the composition.

9. The composition according to claim 7, in which the physiologically acceptable medium comprises at least one cosmetic adjuvant chosen from water; organic solvents; hydrocarbon-based oils, silicone oils, fluoro oils, waxes, pigments, fillers, dyes, surfactants, emulsifiers, cosmetic or dermatological active agents, UV-screening agents, film-forming polymers, hydrophilic or lipophilic gelling agents, thickeners, preserving agents, fragrances, bactericides, odour absorbers and antioxidants.

10. The composition according to claim 7, in which the physiologically acceptable medium comprises at least one compound chosen from: desquamating agents; moisturizers; depigmenting or propigmenting agents; anti-glycation agents; NO-synthase inhibitors; agents for stimulating the synthesis of dermal or epidermal macromolecules and/or for preventing their degradation; agents for stimulating fibroblast and/or keratinocyte proliferation or for stimulating keratinocyte differentiation; muscle relaxants and/or dermo-decontracting agents; tensioning agents; anti-pollution agents and/or free-radical scavengers; agents acting on the capillary circulation; agents acting on the energy metabolism of cells; and mixtures thereof.

11. The composition according to claim 7, which is in the form of an anti-ageing composition for combating the outer signs of ageing of the skin.

12. A non-therapeutic cosmetic process for treating the skin, comprising the application to the skin of a cosmetic composition comprising, in a physiologically acceptable medium, at least one compound chosen from: the compound of formula (I) ##STR00029## in which: R.sub.3 means a hydrogen atom or a hydroxyl radical, R.sub.1 and R.sub.2 mean, independently of each other, a hydrogen atom, a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, and/or of an isomer and/or of a salt and/or of a solvate of said compound of formula (I), the compound of formula (Ia) ##STR00030## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C2-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and the compound of formula (Ib) ##STR00031## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom or an ethyl radical, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C3-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a benzyl radical or an acetyl, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; D. R.sub.1 means a linear or branched C3-C6 alkyl radical; a linear or branched C2-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, on the understanding that: R.sub.1 and R.sub.2 cannot simultaneously denote a hydrogen atom, or a methyl, allyl, n-butyl, n-pentyl or acetyl radical.

13. A cosmetic process for treating and/or preventing the onset of the signs of ageing, of the skin, the nails and/or the hair, comprising applying to the skin, the nails and/or the hair a cosmetic composition comprising, in a physiologically acceptable medium, at least one compound chosen from: the compound of formula (I) ##STR00032## in which: R.sub.3 means a hydrogen atom or a hydroxyl radical, R.sub.1 and R.sub.2 mean, independently of each other, a hydrogen atom, a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, and/or of an isomer and/or of a salt and/or of a solvate of said compound of formula (I), the compound of formula (Ia) ##STR00033## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C2-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and the compound of formula (Ib) ##STR00034## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom or an ethyl radical, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C3-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a benzyl radical or an acetyl, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; D. R.sub.1 means a linear or branched C3-C6 alkyl radical; a linear or branched C2-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, on the understanding that: R.sub.1 and R.sub.2 cannot simultaneously denote a hydrogen atom, or a methyl, allyl, n-butyl, n-pentyl or acetyl radical.

14. A process according to claim 12, in which the composition is applied to mature and/or wrinkled skin.

15. A non-therapeutic method for cosmetically preventing and/or treating the signs of ageing of the skin and its appendages using a cosmetic composition comprising, in a physiologically acceptable medium, at least one compound chosen from: the compound of formula (I) ##STR00035## in which: R.sub.3 means a hydrogen atom or a hydroxyl radical, R.sub.1 and R.sub.2 mean, independently of each other, a hydrogen atom, a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, and/or of an isomer and/or of a salt and/or of a solvate of said compound of formula (I), the compound of formula (Ia) ##STR00036## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C2-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and the compound of formula (Ib) ##STR00037## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom or an ethyl radical, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C3-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a benzyl radical or an acetyl, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; D. R.sub.1 means a linear or branched C3-C6 alkyl radical; a linear or branched C2-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, on the understanding that: R.sub.1 and R.sub.2 cannot simultaneously denote a hydrogen atom, or a methyl, allyl, n-butyl, n-pentyl or acetyl radical.

16. A non-therapeutic method for improving the firmness of the skin using a cosmetic composition comprising, in a physiologically acceptable medium, at least one compound chosen from: the compound of formula (I) ##STR00038## in which: R.sub.3 means a hydrogen atom or a hydroxyl radical, R.sub.1 and R.sub.2 mean, independently of each other, a hydrogen atom, a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, and/or of an isomer and/or of a salt and/or of a solvate of said compound of formula (I), the compound of formula (Ia) ##STR00039## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C2-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and the compound of formula (Ib) ##STR00040## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom or an ethyl radical, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C3-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a benzyl radical or an acetyl, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; D. R.sub.1 means a linear or branched C3-C6 alkyl radical; a linear or branched C2-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, on the understanding that: R.sub.1 and R.sub.2 cannot simultaneously denote a hydrogen atom, or a methyl, allyl, n-butyl, n-pentyl or acetyl radical.

17. A non-therapeutic method for reducing, or even inhibiting, the glycation of proteins of the skin, the nails and/or the hair using a cosmetic composition comprising, in a physiologically acceptable medium, at least one compound chosen from: the compound of formula (I) ##STR00041## in which: R.sub.3 means a hydrogen atom or a hydroxyl radical, R.sub.1 and R.sub.2 mean, independently of each other, a hydrogen atom, a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, and/or of an isomer and/or of a salt and/or of a solvate of said compound of formula (I), the compound of formula (Ia) ##STR00042## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C2-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and the compound of formula (Ib) ##STR00043## isomers thereof, salts thereof and solvates thereof, in which the meaning of R.sub.1 and R.sub.2 is chosen from the following combinations: A. R.sub.1 means a hydrogen atom or an ethyl radical, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; B. R.sub.1 means a methyl radical and R.sub.2 means a linear or branched C3-C6 alkyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; C. R.sub.1 means a benzyl radical or an acetyl, and R.sub.2 means a hydrogen atom; a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; D. R.sub.1 means a linear or branched C3-C6 alkyl radical; a linear or branched C2-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical; and R.sub.2 means a hydrogen atom; a linear or branched C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C1-C6 alkoxycarbonyl radical, on the understanding that: R.sub.1 and R.sub.2 cannot simultaneously denote a hydrogen atom, or a methyl, allyl, n-butyl, n-pentyl or acetyl radical.

18. The method as claimed in claim 17, for reducing, or even inhibiting, the glycation of dermal proteins.

19. The method as claimed in claim 17, for reducing, or even inhibiting, the glycation of keratins.

Description

EXAMPLES

Example 1. Synthesis of the Common Precursors of Formula (II)

[0162] The ethylenic precursors of formula (II) may be obtained in various ways, either via an olefination of Wittig type (1) and variants thereof, or via a coupling of McMurry type starting with the aldehyde (2), or via a metathesis starting with the styrene derivative (3), according to the following scheme:

##STR00015##

[0163] The possible hydroxyl groups of the reagents may, if necessary, be protected beforehand with a suitable protecting group, as reviewed by Peter G. M. Wuts and Theodora W. Greene, in Greene's Protective Groups in Organic Synthesis, Fourth Edition, Wiley, 2006.

[0164] 1.1. Wittig-Horner Reaction

[0165] The phosphonate derivative may be obtained from the corresponding benzyl halide via the standard procedures. By way of example, the following protocol may be used: [0166] a mixture of benzyl halide (1 eq.) and of trimethyl or triethyl phosphite (2 eq.) in a high-boiling apolar solvent such as toluene is heated at 110° C. for 4-16 hours. [0167] The product is then purified either by distillation or via standard techniques such as chromatography on a column of silica. [0168] Under anhydrous conditions and under an inert atmosphere, a solution of the phosphonate derivative (1-1.3 eq.) in a polar aprotic solvent such as THF is treated at 0° C. with a strong base (1.1-2 eq.) such as sodium hydride (NaH), lithium diisopropylamide (LDA) or n-butyllithium (BuLi), followed by dropwise addition of a solution of the aldehyde (1 eq.) in the same solvent. [0169] Stirring is continued at room temperature overnight, until the aldehyde has disappeared, and the mixture is then cooled to 0° C. [0170] Water is added dropwise with stirring, followed by dilute aqueous hydrochloric acid solution. [0171] The mixture is then extracted using an organic solvent such as ether, CH.sub.2Cl.sub.2 or EtOAc. [0172] The organic phases are combined, dried and concentrated under reduced pressure. [0173] The residue may be purified by chromatography on a column of silica.

[0174] 1.2. McMurry Reaction

[0175] The following protocol may be used for the preparation of the activated titanium: [0176] Under anhydrous conditions and under an inert atmosphere, a mixture of TiCl.sub.3 or TiCl.sub.4 (5-6 eq.) with a reductive basic metal, such as Li, Mg, Zn, Zn—Cu (10-20 eq.), optionally combined with an arene such as naphthalene (1 eq.) in a polar aprotic solvent such as THF, is stirred at a temperature of between −5 and 20° C. depending on the procedure.

[0177] The coupling step may thus be performed: [0178] To the solution of freshly prepared activated titanium is added the solution of the aldehyde (1-2 eq.) in the same solvent. [0179] The reaction mixture is stirred at room temperature or heated to reflux until the aldehyde has disappeared, and is then neutralized with saturated aqueous NH.sub.4Cl solution or 10% K.sub.2CO.sub.3 solution depending on the procedure, and extracted using an organic solvent such as CH.sub.2Cl.sub.2 or EtOAc. The organic phases are combined, dried and concentrated under reduced pressure. [0180] The residue may be purified by chromatography on a column of silica.

[0181] 1.3. Metathesis

[0182] The following protocol is applied:

[0183] Under anhydrous conditions and under an inert atmosphere, a mixture of a catalyst such as the Grubbs catalyst (1-2 mol %) and of the styrene derivative (1 eq.) in an apolar solvent such as CH.sub.2Cl.sub.2 is heated to reflux until the styrene has disappeared. [0184] The mixture is then filtered, concentrated under reduced pressure and purified by chromatography on a column of silica.

Example 2. Synthesis of the Compounds of Formula (Ia)

[0185] 2.1. The compounds of formula (Ia) may be obtained in two steps from the corresponding ethylenic derivatives of formula (II), the possible free hydroxyl groups of which are protected beforehand with compatible protecting groups, according to the following scheme:

##STR00016##

[0186] The protocol for the epoxidation of the ethylenic precursors (II) is as follows:

[0187] Step 1: Epoxidation [0188] The compound of formula (II) (I eq.) in an apolar solvent such as dichloromethane is treated with an oxidizing agent (1.5-5 eq.) such as mCPBA or H.sub.2O.sub.2 at room temperature. [0189] The reaction mixture is stirred for 20 hours and then diluted by adding saturated NaHCO.sub.3 solution. [0190] After settling, the phases are separated and the aqueous phase is extracted with an organic solvent such as dichloromethane. [0191] The organic phases are combined and then dried. [0192] After evaporating off the solvent, the residue is purified by chromatography on a column of silica.

[0193] Step 2: Reduction [0194] The intermediate derived from step 1 (I eq.) is dissolved in a polar solvent such as methanol, ethanol or ethyl acetate. [0195] A heterogeneous catalyst of Pd/C type (5-10 mol %) is suspended in this mixture. [0196] The reaction mixture is stirred at room temperature under an atmosphere of dihydrogen for 1-24 hours. [0197] The catalyst is then removed by filtration and the filtrate is concentrated under reduced pressure. [0198] The residue is purified by chromatography on a column of silica. [0199] The product obtained is then optionally deprotected in a third step.

[0200] 2.2. The compounds of formula (Ia) may be obtained from the benzyl halide derivative and from the aldehyde via a reaction of Nozaki-Hiyama, Grignard or Barbier type, according to the following scheme:

##STR00017##

[0201] The possible hydroxyl groups of the reagents may, if necessary, be protected beforehand with a suitable protecting group.

[0202] 2.2.1. Reaction of Grignard Type

[0203] Step 1: Preparation of the Grignard Reagent: [0204] Under anhydrous conditions and under an inert atmosphere, magnesium turnings (1.5 eq.) are introduced into a three-necked pear-shaped flask and then heated under vacuum (0.5 mmHg) at 70° C. for 30 min. [0205] The flask is then filled again with argon, and an anhydrous polar aprotic solvent, such as THF or diethyl ether, is added via a syringe, followed by 1,2-dibromoethane (a few drops) to initiate the reaction. [0206] The benzyl halide (1.2-1.3 eq.) in solution in the same solvent is added slowly via a syringe so as to maintain a gentle reflux (15 mL/h). [0207] After the addition, the mixture is refluxed for 2 hours.

[0208] Step 2 of Coupling: [0209] In another three-necked round-bottomed flask under anhydrous conditions and under an inert atmosphere, a solution of the aldehyde (1 eq.) in the same solvent or in an apolar solvent such as toluene is cooled to 0° C., then the magnesium solution is added slowly via a syringe or a cannula. [0210] After the addition, the reaction mixture is stirred at between 0 and 20° C. for 2 hours until the aldehyde has disappeared, and then diluted in saturated NH.sub.4Cl solution cooled to 0° C. [0211] The aqueous phase is separated and re-extracted with an organic solvent such as diethyl ether (2×). [0212] The organic phases are combined, washed with saturated NaCl solution, dried and concentrated under reduced pressure. [0213] The residue is purified by chromatography on a column of silica. [0214] The product obtained is then optionally deprotected in a second step.

[0215] 2.2.2. Reaction of Barbier Type [0216] Zinc powder (2 eq.), CdCl2 (1 eq.) and InCl3 (0.1 eq.). are added to a mixture of the aldehyde (1 eq.) and of the halide (2 eq.) in water. [0217] The reaction mixture is stirred at room temperature until the reagents have disappeared, and then extracted using an organic solvent such as ethyl acetate (3×). [0218] The organic phases are combined, dried and concentrated under reduced pressure. [0219] The residue is purified by chromatography on a column of silica. [0220] The product obtained is then optionally deprotected in a second step.

[0221] 2.3. Introduction of the Desired Substituents

[0222] The groups incompatible with the key reactions for formation of the target compounds will have to be introduced during a subsequent step according to standard procedures. Similarly, if the reagents are not commercially available, the substituents will have to be introduced onto the corresponding phenolic derivatives, before or after the coupling step, depending on the chemical compatibility.

[0223] The reactions described below are common for introducing substituents onto the precursors of formula (II) and the novel compounds of formulae (Ia) and (Ib).

[0224] 2.3.1. Alkylation/Benzylation of Phenols

##STR00018##

[0225] The following protocol is applied: [0226] The phenolic derivative to be substituted (1 eq./phenol) in a polar aprotic solvent such as DMF or DMSO is deprotonated by adding a weak base (1-2 eq.) such as potassium carbonate or caesium carbonate. [0227] The reaction mixture is stirred at 0-80° C. and the alkylating agent RX (1-2 eq.) is introduced dropwise. For example, the alkylating agent is an alkyl halide and preferentially an alkyl iodide, or benzyl bromide or iodide. [0228] Stirring is continued for 1-96 hours. [0229] The reaction mixture is diluted by adding saturated aqueous NH.sub.4Cl solution and extracted using an organic solvent such as ethyl acetate. [0230] The organic phases are combined, dried and concentrated under reduced pressure. [0231] The residue may be purified by chromatography on a column of silica.

[0232] 2.3.2. Acylation of Phenols

##STR00019## [0233] A solution of the phenolic derivative to be substituted (1 eq./phenol) and of an organic base such as triethylamine, diisopropylethylamine or pyridine (1.2-1.5 eq.), in a polar aprotic solvent such as dichloromethane, acetone, acetonitrile or THF at 0° C., is treated dropwise with a solution of the acid chloride or the corresponding anhydride (1.1-1.5 eq.) in the same solvent. [0234] The reaction mixture is stirred at room temperature for 3-18 hours and then diluted with water. [0235] After settling and phase separation, the organic phase is washed with saturated NaCl solution, dried and concentrated under reduced pressure. [0236] The residue is purified by chromatography on a column of silica.

[0237] 2.3.3. Carbonatation of Phenols

##STR00020##

[0238] The procedure is similar to that of the acylation using an alkyl chloroformate or alkyl dicarbonate (1.1-2 eq.).

Example 3. Synthesis of the Compounds of Formula (Ib)

[0239] 3.1. The compounds of formula (Ib) may be obtained via a reduction reaction starting with the ethylenic precursors of formula (II).

[0240] The hydrogenation of the ethylenic derivatives of formula (II) is represented according to the following scheme:

##STR00021##

[0241] The protocol for the catalytic hydrogenation of the ethylenic precursors (II) is as follows: [0242] The ethylenic derivative (II) is dissolved in a polar solvent such as methanol, ethanol, THF or ethyl acetate. [0243] A heterogeneous catalyst of Pd/C or PtO.sub.2 type is suspended in this mixture. [0244] The reaction medium is stirred at 20-90° C. under dihydrogen (1-40 bar) for 1-24 hours. [0245] The catalyst is removed by filtration and the filtrate is concentrated under reduced pressure. [0246] The residue may be purified by chromatography on a column of silica.

[0247] The groups incompatible with this reaction, such as the benzyl groups, will have to be introduced during a subsequent step according to standard procedures.

[0248] 3.2. The compounds of formula (Ib) may be obtained from the benzyl halide derivative via a metallo-catalysed coupling reaction of Wurtz or Negishi type, according to the following scheme:

##STR00022##

[0249] The possible hydroxyl groups of the reagents may, if necessary, be protected beforehand with a suitable protecting group.

[0250] The compounds of formula (Ib) may be obtained in particular from the benzyl halide derivative via a Negishi-type reaction, the experimental protocol for which is presented below:

[0251] Step 1—Preparation of the Zinc Derivative: [0252] Under anhydrous conditions and under an inert atmosphere, zinc powder (1.5 eq.) is placed in a pear-shaped Schlenk tube and then heated under vacuum (0.5 mmHg) at 70° C. for 30 min. [0253] The tube is then filled again with argon, and an anhydrous polar aprotic solvent such as THF, DMA (N,N-dimethylacetamide) or DMI (1,3-dimethyl-2-imidazolidinone), is added via a syringe, followed by iodine (12, 0.025 eq.). [0254] The reaction mixture is stirred at 70° C. until the red colour turns pale (˜5 min). [0255] The benzyl halide (1 eq.) in solution in the same solvent is added slowly via a syringe. [0256] The mixture is stirred at 70° C. for 12 hours and then left to cool to room temperature for 1 hour without stirring, in order for the unreacted zinc particles to become deposited at the bottom of the flask. [0257] The mixture is filtered under argon through a sinter equipped with a two-necked pear-shaped flask in which the solution of the zinc derivative is recovered.

[0258] Step 2—Coupling: [0259] In a three-necked round-bottomed flask, under anhydrous conditions and under an inert atmosphere, a mixture of the catalytic system (catalyst optionally coupled to a ligand), such as NiCl.sub.2.glyme (0.05-0.07 eq.)/ligand of the type Pybox (0.055-0.09 eq.), NiBr.sub.2.diglyme (0.1 eq.)/ligand of the type Pybox (0.13 eq.), Pd.sub.2(dba).sub.3 (0.02 eq.)/IPr.HCl (0.08 eq.), Pd.sub.2(dba).sub.3 (0.005 eq.)/tri-o-tolylphosphine (0.02 eq.), or Pd(OAc).sub.2 (1 mol %)/CPhos (2 mol %), and halogenated derivative (1 eq.) in a polar aprotic solvent such as DMI, DMA, DMF, NMP or THF, is stirred for 5-10 minutes at room temperature, and the organozinc solution (1.2-1.6 eq.) is then added slowly via a syringe or a cannula, while keeping the internal temperature below 0 to 30° C. [0260] The reaction mixture is stirred at between 0 and 75° C. for 5-24 hours, until the halogenated derivative has disappeared. [0261] The excess zinc reagent is then neutralized by adding ethanol, and the mixture is diluted with an organic solvent such as diethyl ether. [0262] This solution is washed with water (3×), dried and concentrated under reduced pressure. [0263] The residue is purified by chromatography on a column of silica.

[0264] The steps for the introduction of the desired substituents are then performed, as presented in Example 2.

Example 4. Biological Activity of Compounds (A) and (B)

[0265] Compound A is synthesized, for example, according to the following reference: Synthetic Communications 1987, 17(7), 877-92.

[0266] Compound B is synthesized for example according to: Harvery, Benjamin G. et al., Polymer Preprints (American Chemical Society, Division of Polymer Chemistry) 2011, 52(1).

[0267] The anti-ageing effect of the compounds of formula (I) is illustrated by the capacity of these compounds (A) and (B) to inhibit the protein glycation activity, according to the conventional test of inhibition of the glycation of bovine serum albumin (or BSA).

[0268] A. Materials and Methods

[0269] The test compounds are placed in contact with BSA and ribose, and incubation is maintained for 15 days. The fluorescence due to the glycation of BSA by the ribose is measured at T0 and at T15 days. 1 mM aminoguanidine is used as positive control and corresponds to 100% inhibition. The effective doses allowing a 25% inhibition of glycation are determined by means of the dose-response curves.

[0270] B. Results

[0271] The capacity of each of the compounds of formula (I) A and B to inhibit the glycation of BSA was tested, by means of the test described in the Materials and Methods section.

[0272] The results are reported in Table 1 below.

TABLE-US-00001 TABLE 1 compound IC.sub.25 % inhibition at 100 μM A 17 μM 37% B 17 μM 39%

[0273] In Table 1, the IC.sub.25 value represents the concentration of each compound that induces 25% inhibition of BSA glycation.

[0274] Table 1 also presents the percentage values for the inhibition of BSA glycation which is induced by a concentration of 100 μM of each of the indicated compounds.

[0275] The results of Table 1 show that the compounds of formula (I) are capable of inhibiting the glycation reaction in the model test.

[0276] As active agents in cosmetic formulations, these compounds are thus effective in helping to prevent and/or delay the onset of the signs of ageing that are characteristic of glycation: slackened appearance, flaccid skin, fine wrinkles.

Example 5. Example of Composition in Accordance with the Invention

[0277] The percentages of compounds shown are percentages by weight, relatively to the total weight of the composition in which they are present.

TABLE-US-00002 Compound A  1% Glycerol  12% Polyacrylamide at 40% AM* (Sepigel 305 from SEPPIC) 1% AM* Preserving agents qs Fragrance qs Water qs 100% *AM meaning active material

[0278] The above composition, applied topically to the skin, makes it possible to combat the signs of ageing, such as wrinkles and fine lines, or also withered, flabby and/or thinned skin.

Example 6: Example of Composition in Accordance with the Invention

[0279] The percentages of compounds shown are percentages by weight, relative to the total weight of the composition in which they are present.

TABLE-US-00003 Compound (A) 1% Glycerol 12%  Polyacrylamide at 40% AM (Sepigel 305 from SEPPIC) 1% AM Mixture of polydimethylsiloxane containing α,ω- 2% hydroxyl and cyclopentadimethylsiloxane groups (15/85) Preserving agents qs Fragrance qs Water qs 100%

[0280] The same types of results are obtained by replacing compound A with compound B.