Ligand activators of the RAR receptors and pharmaceutical/cosmetic applications thereof

1. A compound having the following structural formula (I):

in which:

Ar is a radical of formulae (a) below:

wherein R 7 is as defined below;

R 1 is:

(a) a hydrogen atom,

(b) an alkyl radical having from 1 to 6 carbon atoms,

(c) a radical of formula:

(d) a radical —OR 8 ,

wherein R′, R″ and R 8 are as defined below;

R 2 is a hydrogen atom or an alkyl radical having from 1 to 6 carbon atoms;

R 3 is a hydrogen atom, an alkyl radical having from 1 to 6 carbon atoms or a radical —CO—R 9 ,

wherein R 9 is as defined below;

R 4 and R 5 together form, with the adjacent aromatic ring from which they depend, a 5- or 6-membered ring optionally substituted with methyl groups;

R 6 is an alkyl radical having from 1 to 6 carbon atoms or a radical —CO)R 10 ,

wherein R 10 is as defined below;

R 7 is a hydrogen atom, a halogen atom, an alkyl radical having from 1 to 6 carbon atoms or a radical —OR 11 ,

wherein R 11 is as defined below;

R 8 is a hydrogen atom, a linear or branched alkyl radical having from 1 to 20 carbon atoms, an alkenyl radical, a mono- or polyhydroxyalkyl radical, an optionally substituted aryl or aralkyl radical or a sugar residue or an amino acid or peptide residue;

R 9 and R 10 are each CF 3 or an alkyl radical having from 1 to 6 carbon atoms;

R 11 is H, an alkyl radical having from 1 to 6 carbon atoms or a radical —(CO)—R 12 ,

wherein R 12 is as defined below;

R 12 is an alkyl radical having from 1 to 6 carbon atoms;

R′ and R″ are each a hydrogen atom, an alkyl radical having from 1 to 6 carbon atoms, a mono- or polyhydroxyalkyl radical, an aryl radical or an amino acid, peptide or sugar residue;

n is an integer ranging from 2 to 6;

and the salts of the compounds of formula (I) when R 1 is a hydroxyl group, and also the optical and geometrical isomers of the compounds of formula (I).

2. An alkali metal or alkaline-earth metal, zinc or organic amine salt of the compound as defined by claim 1 .

3. The compound as defined by claim 1 , bearing at least one substituent selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, i-butyl, t-butyl, n-pentyl and n-hexyl radicals.

4. The compound as defined by claim 1 , bearing at least one substituent selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, i-butyl, t-butyl, n-pentyl, n-hexyl, 2-ethylhexyl, octyl, dodecyl, hexadecyl and octadecyl radicals.

5. The compound as defined by claim 1 , bearing at least one substituent selected from the group consisting of 2-hydroxyethyl, 2-hydroxypropyl and 3-hydroxypropyl radicals.

6. The compound as defined by claim 1 , bearing at least one substituent selected from the group consisting of 2,3-dihydroxypropyl, 2,3,4-trihydroxybutyl and 2,3,4,5-tetrahydroxypentyl radicals, or a pentaerythritol residue.

7. The compound as defined by claim 1 , bearing at least one substituent selected from the group consisting of a phenyl radical optionally substituted with at least one halogen, a hydroxyl or a nitro substituent.

8. The compound as defined by claim 1 , bearing at least one substituent selected from the group consisting of benzyl and phenethyl radicals optionally substituted with at least one halogen, a hydroxyl group or a nitro substituent.

9. The compound as defined by claim 1 , bearing at least one substituent selected from the group consisting of alkenyl radicals having from 2 to 5 carbon atoms and one or more sites of ethylenic unsaturation.

10. The compound as defined by claim 1 , bearing at least one substituent selected from the group consisting of residues derived from glucose, galactose, mannose and glucuronic acid.

11. The compound as defined by claim 1 , bearing at least one substituent selected from the group consisting of residues derived from lysine, glycine and aspartic acid.

12. The compound as defined by claim 1 , bearing at least one substituent selected from the group consisting of dipeptide and tripeptide residues resulting from the combination of amino acids.

13. The compound as defined by claim 1 , bearing at least one substituent selected from the group consisting of fluorine, chlorine and bromine atoms.

14. The compound as defined by claim 1 , wherein at least one of the following conditions is satisfied:

n is 2 or 3,

R 2 is a hydrogen atom,

R 4 and R 5 form, with the adjacent aromatic ring, a 6-membered ring,

R 6 is an alkyl radical.

15. The compound as defined by claim 1 , selected from the group consisting of:

4-{3-Hydroxy-3-[4-(2-methoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]prop-1-ynyl}benzoic acid;

4-{3-Hydroxy-3-[4-(2-ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]prop-1-ynyl}benzoic acid;

4-{3-Hydroxy-3-[4-(2-ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]prop-1-ynyl}-2-hydroxybenzoic acid;

4-{3-Hydroxy-3-[4-(2-ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]prop-1-ynyl}benzoic (S)-acid;

4-{3-Hydroxy-3-[4-(2-ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]prop-1-ynyl}benzoic (R)-acid;

4-{3-[4-(3-Ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoic acid;

4-{3-[4-(3-Methoxypropoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoic acid;

4-{3-[4-(4-Methoxybutoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoic acid;

4-{3-[4-(5-Methoxypentoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoic acid;

4-{3-[4-(6-Methoxyhexyloxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoic acid;

4-{3-[4-(2-Ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxybut-1-ynyl}benzoic acid;

4-{3-[4-(2-Ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxypent-1-ynyl}benzoic acid;

4-{3-[4-(2-Ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-acetoxyprop-1-ynyl}benzoic acid;

4-{3-[4-(2-Acetoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoic acid;

4-(3-Hydroxy-3-{5,5,8,8-tetramethyl-4-[2-(2,2,2-trifluoroacetoxy)ethoxy]-5,6,7,8-tetrahydronaphth-2-yl}prop-1-ynyl}benzoic acid;

4-(3-Hydroxy-3-[5,5,8,8-tetramethyl-4-(2-propionyloxyethoxy)-5,6,7,8-tetrahydronaphth-2-yl]prop-1-ynyl)benzoic acid;

2-Chloro-4-{3-[4-(ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoic acid;

4-{3-[4-(2-Ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}-2-fluorobenzoic acid;

4-{3-[4-(2-Ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}-3-fluorobenzoic acid;

4-{3-[4-(2-Ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}-3-methylbenzoic acid;

Ethyl 4-{3-[4-(2-ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoate;

Isopropyl 4-{3-[4-(2-ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoate;

Isobutyl 4-{3-[4-(2-ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoate;

2,3-Dihydroxypropyl 4-{3-[4-(2-ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoate;

6-Glucosyl 4-{3-[4-(2-ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoate;

6-Galactosyl 4-{3-[4-(2-ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoate;

4-{3-[4-(2-Ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}-N,N-dimethylbenzamide;

4-{3-[4-(2-Ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}-N,N-diethylbenzamide;

(4-{3-[4-(2-Ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}-N-ethylbenzamide;

(4-{3-[4-(2-Ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoylamino)acetic acid; and

2-(4-{3-[4-(2-Ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl]-3-hydroxyprop-1-ynyl}benzoylamino)-3-phenylpropionic acid.

16. A pharmaceutical composition comprising a thus effective amounts of at least one ligand compound as defined by claim 1 , formulated into a physiologically acceptable medium therefor.

17. The pharmaceutical composition as defined by claim 16 , said at least one ligand compound comprising from 0.001% to 10% by weight thereof.

18. The pharmaceutical composition as defined by claim 16 , said at least one ligand compound comprising from 0.01% to 1% by weight thereof.