Diarylselenide compounds and their use in human or veterinary medicine and in cosmetics

Abstract

The invention concerns novel diarylselenide compounds corresponding to formula (I): and the use thereof in pharmaceutical compositions in human or veterinary medicine (in the treatment of dermatological, rheumatic, cardiovascular and ophthalmologic pathologies in particular), or in cosmetic compositions.

1 . A compound having the formula (I):  
       
         
           
           
               
               
           
         
       
       in which: 
 R 1  represents  
 (i) —CH 3 ,  
 (ii) —CH 2 —O—R 5 , or  
 (iii) —COR 6 ;  
 Ar is a radical selected from the group consisting of radicals of formula (a)-(e):  
                     
 R 2  and R 3 , which are identical or different, independently are a radical selected from the group consisting of:  
 (i) hydrogen,  
 (ii) tert-butyl, 1-methylcyclohexyl or 1-adamantyl,  
 (iii) —OR 8 , and  
 (iv) a polyether radical, it being understood that at least one of the radicals R 2  or R 3  is (ii), or  
 R 2  and R 3  taken together form, with the adjacent aromatic ring, a 5- or 6-membered saturated ring optionally substituted with methyl groups and/or optionally interrupted with an oxygen or sulphur atom;  
 R 4  is hydrogen, halogen, lower alkyl, OR 9 , a polyether radical or COR 10 ;  
 R 5  is hydrogen, lower alkyl or COR 11 ;  
 R 6  is a radical selected from the group consisting of:  
 (i) hydrogen,  
 (ii) lower alkyl,  
 (iii) OR 12 , and  
 (iv) a radical of formula  
                     
 R 7  is hydrogen, halogen, lower alkyl, nitro, OR 13 , a polyether radical or a radical of the formula:  
                     
 R 8  is hydrogen, lower alkyl, optionally substituted aryl, optionally substituted aralkyl, monohydroxyalkyl, polyhydroxyalkyl or lower acyl;  
 R 9  is hydrogen, lower alkyl, optionally substituted aryl, optionally substituted aralkyl, monohydroxyalkyl, polyhydroxyalkyl, lower acyl, —(CH 2 ) n —COOR 16  or —(CH 2 ) n —X;  
 R 10  and R 11 , which are identical or different, are lower alkyl;  
 R 12  is hydrogen, lower alkyl, optionally substituted aryl or aralkyl, monohydroxyalkyl or polyhydroxyalkyl;  
 R′ and R″, which are identical or different, represent hydrogen, lower alkyl, or optionally substituted aryl or an amino acid residue, or alternatively R′ and R″ taken together form, with the nitrogen atom, a heterocycle;  
 R 13  is hydrogen or lower alkyl;  
 R 14  and R 15 , which are identical or different, represent hydrogen or lower alkyl;  
 R 16  is hydrogen or lower alkyl;  
 n is an integer between 1 and 12 inclusive; and  
 X is halogen;  
 or a salt, or an optical or geometrical isomer thereof;  
 with the proviso that when Ar is a radical of formula (b), R 1  is COOH and R 2  and R 3 , with the carbon atoms to which they are attached, form a 6-membered saturated ring, then R 4  cannot be lower alkyl.  
 
     
     
         2 . A salt of a compound according to  claim 1 , said salt being an alkali metal or alkaline-earth metal salt, a zinc salt, an organic amine salt or a salt of an inorganic or organic acid.  
     
     
         3 . A compound according to  claim 1 , containing a lower alkyl radical selected from the group consisting of methyl, ethyl, isopropyl, butyl and tert-butyl.  
     
     
         4 . A compound according to  claim 1 , containing a monohydroxyalkyl radical having 2 or 3 carbon atoms, the monohydroxyalkyl radical optionally being protected in the form of acetyl or tertbutyldimethylsilyl.  
     
     
         5 . A compound according to  claim 1 , containing a polyhydroxyalkyl radical selected from the group consisting of 2,3-dihydroxypropyl, 2,3,4-trihydroxybutyl and 2,3,4,5-tetrahydroxypentyl radicals and a pentaerythritol residue, the hydroxyl group optionally being protected in the form of acetyl or tert-butyldimethylsilyl.  
     
     
         6 . A compound according to  claim 1 , containing an aryl radical which is a phenyl radical, optionally substituted with at least one halogen or one hydroxyl function.  
     
     
         7 . A compound according to  claim 1 , containing an aralkyl radical selected from the group consisting of benzyl and phenethyl optionally substituted with at least one halogen or one hydroxyl function.  
     
     
         8 . A compound according to  claim 1 , containing a lower acyl radical selected from the group consisting of acetyl and propionyl.  
     
     
         9 . A compound according to  claim 1 , containing a polyether radical selected from the group consisting of methoxymethyl ether, methoxyethoxymethyl ether and methylthiomethyl ether.  
     
     
         10 . A compound according to  claim 1 , containing an amino acid residue selected from the group consisting of residues derived from lysine, glycine and aspartic acid.  
     
     
         11 . A compound according to  claim 1 , containing an heterocyclic radical selected from the group consisting of piperidino, morpholino, pyrrolidino and piperazino radicals, optionally substituted in position 4 with a C 1 -C 6  alkyl radical or with a mono- or polyhydroxyalkyl radical.  
     
     
         12 . A compound according to  claim 1 , selected from the group consisting of: 
 ethyl 4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)benzoate, 4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)benzoic acid, ethyl 6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)nicotinate, ethyl 6-(5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-2-naphthylselanyl)nicotinate, 3-(4-tert-butylphenylselanyl)benzoic acid, 6-(4-tert-butylphenylselanyl)nicotinic acid, 4-(4-tert-butylphenylselanyl)benzoic acid, 4-(4,4-dimethylthiochroman-8-ylselanyl) benzoic acid, 3-(4,4-dimethylthiochroman-8-ylselanyl)benzoic acid, 6-(4,4-dimethylthiochroman-8-ylselanyl)nicotinic acid, 4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)benzoic acid, 3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)benzoic acid, 4-[5-adamantan-1-yl-4-(2-methoxyethoxymethoxy)-2-methylphenylselanyl]benzoic acid, 3-[5-adamantan- 1 -yl-4-(2-methoxyethoxymethoxy)-2-methylphenylselanyl]benzoic acid, 3-(4-methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl) benzoic acid, 4-(4-methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)-3-methoxybenzoic acid, 3-(4-methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)-4-methoxybenzoic acid, 4-(3-methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)benzoic acid, 3-(3-methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)benzoic acid, 6-(3,5-di-tert-butyl-2-methoxymethoxyphenylselanyl)-nicotinic acid, 2-(3,5-di-tert-butyl-2-methoxymethoxyphenylselanyl) nicotinic acid, 4-(3,5-di-tert-butyl-2-methoxymethoxyphenylselanyl) benzoic acid, 3-(3,5-di-tert-butyl-2-methoxymethoxyphenylselanyl) benzoic acid, 6-(4-adamantan-1-yl-3-benzyloxyphenylselanyl) nicotinic acid, 6-(3,5-di-tert-butyl-2-benzyloxyphenylselanyl) nicotinic acid, 3-methoxy-4-(4-benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylselanyl)benzoic acid, 4-(4-benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylselanyl)benzoic acid, 6-(4-benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylselanyl)nicotinic acid, 3-methoxy-4-(3-benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylselanyl) benzoic acid, 6-(3-benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylselanyl)nicotinic acid, 4-(3-hexyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylselanyl)-3-methoxybenzoic acid, 6-(3-hexyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylselanyl)nicotinic acid, 4-(5-adamantan-1-yl-4-benzyloxy-2-methylphenylselanyl)-benzoic acid, ethyl 4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)benzoate, ethyl 4-(3-methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl) benzoate, ethyl 4-(3-hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)benzoate, 4-(3-hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)benzoic acid, ethyl 6-(3-methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)nicotinate, ethyl 6-(3-hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)nicotinate, ethyl 6-[3-(3-ethoxycarbonylpropoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl]nicotinate, ethyl 4-[3-(3-ethoxycarbonylpropoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)benzoate, 4-[3-(3-carboxypropoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl]benzoic acid, ethyl 4-[3-(7-methoxycarbonylheptyloxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl]benzoate, 4-[3-(7-carboxyheptyloxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl]benzoic acid, ethyl 6-[3-(7-methoxycarbonylheptyloxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl]nicotinate, ethyl 6-[3-(2-acetoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl]nicotinate, ethyl 4-[3-(2-acetoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl]benzoate, 4-[3-(2-hydroxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl]benzoic acid, 6-(3-adamantan-1-yl-4-methoxyphenylselanyl)nicotinic acid, [6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)-3-pyridyl]methanol, N-ethyl-6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)nicotinamide, morpholin-4-yl-[6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)-3-pyridyl]methanone, N-(4-hydroxyphenyl)-6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylselanyl)nicotinamide and 6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylselanyl) pyridine-3-carbaldehyde.    
     
     
         13 . A compound according to  claim 1 , having at least one of the following characteristics: 
 R 1  is a radical COR 6 ;    Ar is a radical of formula (a) or (b);    R 2  or R 3  is adamantyl or R 2  and R 3  taken together form, with the adjacent aromatic ring, a 5- or 6-membered saturated ring optionally substituted with methyl groups and/or optionally interrupted with an oxygen or sulphur atom.    
     
     
         14 . A method for treating dermatological complaints associated with a keratinization disorder which has a bearing on differentiation and on proliferation including common acne, comedones, palmorphonuclear leukocytes, rosacea, nodulocystic acne, acne conglobata, senile acne, or secondary acne including solar acne, medication-related acne or occupational acne; for treating other types of keratinization disorder including ichthyosis, ichthyosiform states, Darier's disease, palmoplantar keroderma, leucoplasias and leucoplasiform states, cutaneous or mucous (buccal) lichen; for treating other dermatological complaints associated with a keratinization disorder with an inflammatory and/or immunoallergic component including psoriasis, including cutaneous, mucous or ungal psoriasis or psoriatic rheumatism, cutaneous atopy, such as eczema, respiratory atopy or gingival hypertrophy; for treating inflammatory complaints which have no keratinization disorder; for treating all dermal or epidermal proliferations, whether benign or malignant and regardless of whether they are of viral origin including common warts, flat warts, verruciform epidermodysplasia, oral or florid papillomatoses or proliferations induced by ultraviolet radiation, in particular in the case of basocellular and spinocellular epitheliomia; for treating other dermatological disorders including bullosis and collagen diseases; for treating ophthalmological disorders including corneopathies; for repairing or combating ageing of the skin, whether this is light induced or chronological ageing, or for reducing actinic keratoses and pigmentations, or any pathologies associated with chronological or actinic ageing; for treating the stigmata of epidermal and/or dermal atrophy induced by local or systemic corticosteroids, or any other form of cutaneous atrophy; for treating cicatrization disorders or repairing stretchmarks, or for promoting cicatrization; for combating disorders of sebaceous functioning including the hyperseborrhoea of acne or simple seborrhoea; for treating or inhibiting cancerous or precancerous states including promyelocyte leukaemias; for the treatment of inflammatory complaints including arthritis; for the treatment of any general or skin complaint of viral origin; for the prevention or treatment of alopecia; for the treatment of dermatological complaints having an immunological component; for the treatment of complaints of the cardiovascular system including arteriosclerosis, hypertension, non-insulin-dependent diabetes and obesity; or for the treatment of skin disorders due to an exposure to U.V. radiation; comprising administering to a subject an effective amount of at least one compound of formula (I) as defined in  claim 1 .  
     
     
         15 . A method for treating dermatological complaints associated with a keratinization disorder which has a bearing on differentiation and on proliferation including common acne, comedones, palmorphonuclear leukocytes, rosacea, nodulocystic acne, acne conglobata, senile acne, or secondary acne including solar acne, medication-related acne or occupational acne; for treating other types of keratinization disorder including ichthyosis, ichthyosiform states, Darier's disease, palmoplantar keroderma, leucoplasias and leucoplasiform states, cutaneous or mucous (buccal) lichen; for treating other dermatological complaints associated with a keratinization disorder with an inflammatory and/or immunoallergic component including psoriasis, including cutaneous, mucous or ungal psoriasis or psoriatic rheumatism, cutaneous atopy, such as eczema, respiratory atopy or gingival hypertrophy; for treating inflammatory complaints which have no keratinization disorder; for treating all dermal or epidermal proliferations, whether benign or malignant and regardless of whether they are of viral origin including common warts, flat warts, verruciform epidermodysplasia, oral or florid papillomatoses or proliferations induced by ultraviolet radiation, in particular in the case of basocellular and spinocellular epitheliomia; for treating other dermatological disorders including bullosis and collagen diseases; for treating ophthalmological disorders including comeopathies; for repairing or combating ageing of the skin, whether this is light induced or chronological ageing, or for reducing actinic keratoses and pigmentations, or any pathologies associated with chronological or actinic ageing; for treating the stigmata of epidermal and/or dermal atrophy induced by local or systemic corticosteroids, or any other form of cutaneous atrophy; for treating cicatrization disorders or repairing stretchmarks, or for promoting cicatrization; for combating disorders of sebaceous functioning including the hyperseborrhoea of acne or simple seborrhoea; for treating or inhibiting cancerous or precancerous states including promyelocyte leukaemias; for the treatment of inflammatory complaints including arthritis; for the treatment of any general or skin complaint of viral origin; for the prevention or treatment of alopecia; for the treatment of dermatological complaints having an immunological component; for the treatment of complaints of the cardiovascular system including arteriosclerosis, hypertension, non-insulin-dependent diabetes and obesity; or for the treatment of skin disorders due to an exposure to U.V. radiation; comprising administering to a subject an effective amount of at least one compound having the formula (I):  
       
         
           
           
               
               
           
         
       
       in which: 
 R 1  represents  
 (i) —CH 3 ,  
 (ii) —CH 2 —O—R 5 , or  
 (iii) —COR 6 ;  
 Ar is a radical selected from the group consisting of radicals of formula (a)-(e):  
                     
 R 2  and R 3 , which are identical or different, independently are a radical selected from the group consisting of:  
 (i) hydrogen,  
 (ii) tert-butyl, 1-methylcyclohexyl or 1-adamantyl,  
 (iii) —OR 8 , and  
 (iv) a polyether radical, it being understood that at least one of the radicals R 2  or R 3  is (ii), or  
 R 2  and R 3  taken together form, with the adjacent aromatic ring, a 5- or 6-membered saturated ring optionally substituted with methyl groups and/or optionally interrupted with an oxygen or sulphur atom;  
 R 4  is hydrogen, halogen, lower alkyl, OR 9 , a polyether radical or COR 10 ;  
 R 5  is hydrogen, lower alkyl or COR 11 ;  
 R 6  is a radical selected from the group consisting of:  
 (i) hydrogen,  
 (ii) lower alkyl,  
 (iii) OR 2 , and  
 (iv) a radical of formula  
                     
 R 7  is hydrogen, halogen, lower alkyl, nitro, OR 13 , a polyether radical or a radical of the formula:  
                     
 R 8  is hydrogen, lower alkyl, optionally substituted aryl, optionally substituted aralkyl, monohydroxyalkyl, polyhydroxyalkyl or lower acyl;  
 R 9  is hydrogen, lower alkyl, optionally substituted aryl, optionally substituted aralkyl, monohydroxyalkyl, polyhydroxyalkyl, lower acyl, —(CH 2 ) n —COOR 16  or —(CH 2 ) n —X;  
 R 10  and R 11 , which are identical or different, are lower alkyl;  
 R 12  is hydrogen, lower alkyl, optionally substituted aryl or aralkyl, monohydroxyalkyl or polyhydroxyalkyl;  
 R′ and R″, which are identical or different, represent hydrogen, lower alkyl, or optionally substituted aryl or an amino acid residue, or alternatively R′ and R″ taken together form, with the nitrogen atom, a heterocycle;  
 R 13  is hydrogen or lower alkyl;  
 R 14  and R 15 , which are identical or different, represent hydrogen or lower alkyl;  
 R 16  is hydrogen or lower alkyl;  
 n is an integer between 1 and 12 inclusive; and  
 X is halogen;  
 or a salt, or an optical or geometrical isomer thereof.  
 
     
     
         16 . A method for treating dermatological complaints associated with a keratinization disorder which has a bearing on differentiation and on proliferation including common acne, comedones, palmorphonuclear leukocytes, rosacea, nodulocystic acne, acne conglobata, senile acne, or secondary acne including solar acne, medication-related acne or occupational acne; for treating other types of keratinization disorder including ichthyosis, ichthyosiform states, Darier's disease, palmoplantar keroderma, leucoplasias and leucoplasiform states, cutaneous or mucous (buccal) lichen; for treating other dermatological complaints associated with a keratinization disorder with an inflammatory and/or immunoallergic component including psoriasis, including cutaneous, mucous or ungal psoriasis or psoriatic rheumatism, cutaneous atopy, such as eczema, respiratory atopy or gingival hypertrophy; for treating inflammatory complaints which have no keratinization disorder; for treating all dermal or epidermal proliferations, whether benign or malignant and regardless of whether they are of viral origin including common warts, flat warts, verruciform epidermodysplasia,oral or florid papillomatoses or proliferations induced by ultraviolet radiation, in particular in the case of basocellular and spinocellular epitheliomia; for treating other dermatological disorders including bullosis and collagen diseases; for treating ophthalmological disorders including corneopathies; for repairing or combating ageing of the skin, whether this is light induced or chronological ageing, or for reducing actinic keratoses and pigmentations, or any pathologies associated with chronological or actinic ageing; for treating the stigmata of epidermal and/or dermal atrophy induced by local or systemic corticosteroids, or any other form of cutaneous atrophy; for treating cicatrization disorders or repairing stretchmarks, or for promoting cicatrization; for combating disorders of sebaceous functioning including the hyperseborrhoea of acne or simple seborrhoea; for treating or inhibiting cancerous or precancerous states including promyelocyte leukaemias; for the treatment of inflammatory complaints including arthritis; for the treatment of any general or skin complaint of viral origin; for the prevention or treatment of alopecia; for the treatment of dermatological complaints having an immunological component; for the treatment of complaints of the cardiovascular system including arteriosclerosis, hypertension, non-insulin-dependent diabetes and obesity; or for the treatment of skin disorders due to an exposure to U.V. radiation; comprising administering to a subject an effective amount of at least one compound having the formula (I):  
       
         
           
           
               
               
           
         
       
       in which: 
 R 1  is COOH;  
 Ar is  
                     
 R 2  and R 3 , taken together with the carbon atoms to which they are attached, form a 6-membered saturated ring; R 7  represents a hydrogen atom, a halogen atom, a lower alkyl radical, a nitro radical, a radical OR 13 , a polyether radical or a radical having the formula:  
                     
 R 13  is a hydrogen atom or a lower alkyl radical; and  
 R 14  and R 15 , which are identical or different, are hydrogen or lower alkyl;  
 or a salt thereof.  
 
     
     
         17 . A pharmaceutical composition comprising, in a pharmaceutically acceptable support, at least one compound of formula (I) as defined in  claim 1 .  
     
     
         18 . A pharmaceutical composition comprising, in a pharmaceutically acceptable support, at least one compound having the formula (I):  
       
         
           
           
               
               
           
         
       
       in which: 
 R 1  represents  
 (i) —CH 3 ,  
 (ii) —CH 2 —O—R 5 , or  
 (iii) —COR 6 ;  
 Ar is a radical selected from the group consisting of radicals of formula (a)-(e):  
                     
 R 2  and R 3 , which are identical or different, independently are a radical selected from the group consisting of:  
 (i) hydrogen,  
 (ii) tert-butyl, 1-methylcyclohexyl or 1-adamantyl,  
 (iii) —OR 8 , and  
 (iv) a polyether radical, it being understood that at least one of the radicals R 2  or R 3  is (ii), or  
 R 2  and R 3  taken together form, with the adjacent aromatic ring, a 5- or 6-membered saturated ring optionally substituted with methyl groups and/or optionally interrupted with an oxygen or sulphur atom;  
 R 4  is hydrogen, halogen, lower alkyl, OR 9 , a polyether radical or COR 10 ;  
 R 5  is hydrogen, lower alkyl or COR 11 ;  
 R 6  is a radical selected from the group consisting of:  
 (i) hydrogen,  
 (ii) lower alkyl,  
 (iii) OR 12 , and  
 (iv) a radical of formula  
                     
 R 7  is hydrogen, halogen, lower alkyl, nitro, OR 13 , a polyether radical or a radical of the formula:  
                     
 R 8  is hydrogen, lower alkyl, optionally substituted aryl, optionally substituted aralkyl, monohydroxyalkyl, polyhydroxyalkyl or lower acyl;  
 R 9  is hydrogen, lower alkyl, optionally substituted aryl, optionally substituted aralkyl, monohydroxyalkyl, polyhydroxyalkyl, lower acyl, —(CH 2 ) n —COOR 16  or —(CH 2 ) n —X;  
 R 10  and R 11 , which are identical or different, are lower alkyl;  
 R 12  is hydrogen, lower alkyl, optionally substituted aryl or aralkyl, monohydroxyalkyl or polyhydroxyalkyl;  
 R′ and R″, which are identical or different, represent hydrogen, lower alkyl, or optionally substituted aryl or an amino acid residue, or alternatively R′ and R″ taken together form, with the nitrogen atom, a heterocycle;  
 R 13  is hydrogen or lower alkyl;  
 R 14  and R 15 , which are identical or different, represent hydrogen or lower alkyl;  
 R 16  is hydrogen or lower alkyl;  
 n is an integer between 1 and 12 inclusive; and  
 X is halogen;  
 or a salt, or an optical or geometrical isomer thereof.  
 
     
     
         19 . A pharmaceutical composition comprising, in a pharmaceutically acceptable support, at least one compound having the formula (I):  
       
         
           
           
               
               
           
         
       
       in which: R 1  is COOH; 
 Ar is  
                     
 R 2  and R 3 , taken together with the carbon atoms to which they are attached, form a 6-membered saturated ring; R 7  represents a hydrogen atom, a halogen atom, a lower alkyl radical, a nitro radical, a radical OR 13 , a polyether radical or a radical having the formula:  
                     
 R 13  is a hydrogen atom or a lower alkyl radical; and  
 R 14  and R 15 , which are identical or different, are hydrogen or lower alkyl;  
 or a salt thereof.  
 
     
     
         20 . A composition according to  claim 17 , wherein the concentration of compound(s) of formula (I) is between 0.001% and 5% by weight relative to the composition as a whole.  
     
     
         21 . A composition according to  claim 18 , wherein the concentration of compound(s) of formula (I) is between 0.001% and 5% by weight relative to the composition as a whole.  
     
     
         22 . A composition according to  claim 19 , wherein the concentration of compound(s) of formula (I) is between 0.001% and 5% by weight relative to the composition as a whole.  
     
     
         23 . A cosmetic composition comprising, in a cosmetically acceptable support, at least one compound as defined in  claim 1 .  
     
     
         24 . A composition according to  claim 23 , wherein the concentration of compound(s) of formula (I) is between 0.001% and 3% by weight relative to the composition as a whole.  
     
     
         25 . A method for body or hair hygiene comprising administering an effective amount of a cosmetic composition according to  claim 20  to a subject.