Bicyclic aromatic compounds

Abstract

The invention relates to novel bicyclic aromatic compounds which have the general formula (I): as well as to the use of these compounds in pharmaceutical compositions intended for use in human or veterinary medicine (dermatological, rheumatic, respiratory, cardiovascular and ophthalmological complaints in particular), or alternatively in cosmetic compositions.

1 . Bicyclic aromatic compounds, characterized in that they correspond to the general formula (I) below:  
       
         
           
           
               
               
           
         
       
       in which: 
 R 1  represents 
 (i) the —CH 3  radical  
 (ii) the radical —CH 2 OR 5    
 (iii) the radical —COR 6    
 
 R 5  and R 6  having the meaning given below  
 Ar represents a radical chosen from the radicals of formulae (a)-(e) below:  
                     
 R 5  and R 7  having the meaning given below,  
 X represents  
                     
 R 8  and R 9  having the meanings given below  
 R 2  and R 3 , which may be identical or different, represent 
 (i) a hydrogen atom,  
 (ii) an alkyl radical having at least 3 carbon atoms, among which the carbon attached to the phenyl radical is substituted with at least two carbon atoms,  
 (iii) a radical —OR 5 ,  
 (iv) a radical —SR 5 ,  
 
 R 5  having the meaning given below, it being understood that R 2  and R 3 , taken together, may form with the adjacent aromatic ring a 5- or 6-membered ring optionally substituted with methyl groups and/or optionally interrupted by an oxygen or sulphur atom,  
 and it being understood that R 2  and R 3  cannot at the same time have the meanings (i), (iii) and (iv) mentioned above,  
 R 4  and R 7 , which may be identical or different, represent a hydrogen atom, a halogen atom, a linear or branched alkyl radical having from 1 to 20 carbon atoms or a radical —OR 5 ,  
 R 5  represents a hydrogen atom, a lower alkyl radical or a radical —COR 10    
 R 10  having the meaning given below,  
 R 6  represents: 
 (a) a hydrogen atom  
 (b) a lower alkyl radical  
 (c) a radical of formula:  
                     
 
 R′ and R″ having the meaning given below, 
 (d) a radical —OR 11    
 
 R 11  having the meaning given below,  
 R 8  and R 9 , which may be identical or different, represent a hydrogen atom or a lower alkyl radical,  
 R 10  represents a lower alkyl radical,  
 R 11  represents 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, a sugar residue or an amino acid or peptide residue,  
 R′ and R″, which may be identical or different, represent a hydrogen atom, a lower alkyl radical, a mono- or polyhydroxyalkyl radical, an optionally substituted aryl radical or an amino acid or sugar residue, or alternatively, taken together form a heterocycle,  
 as well as the salts thereof and the optical and geometrical isomers thereof.  
 
     
     
         2 . Compounds according to  claim 1 , characterized in that they are in the form of salts of an alkali metal or alkaline-earth metal, or alternatively of zinc or of an organic amine.  
     
     
         3 . Compounds according to  claim 1 , characterized in that they are taken, alone or as mixtures, from the group consisting of: 
 5-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-acrylic acid,    5-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-propiolic acid,    2-(3-tert-Butyl-4-methoxyphenyl)-4-thiophene-acrylic acid,    4-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-acrylic acid,    5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneacrylic acid,    4-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophenepropiolic acid,    4-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-thiopheneacrylic acid,    5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophenepropiolic acid,    3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylpropiolic acid,    N-Methyl-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-pyrroleacrylic acid,    3-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylic acid,    N-Methyl-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylic acid,    4-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylic acid,    3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic acid,    3-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylpropiolic acid,    2-Methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic acid,    2-Propyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic acid,    2-Heptyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic acid,    2-Methoxymethoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic acid,    2-Hydroxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic acid,    3-(3-Methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylic acid,    3-(3-Propyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylic acid,    3-(3-Heptyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) phenylacrylic acid,    3-(3-Methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylic acid,    3-(3-Hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylic acid,    3-(4,4,7-Trimethylthiochroman-6-yl)-phenylacrylic acid,    N-Ethyl-3-(3,5,5,8,8-pentamethyl-5,6,7, tetrahydro-2-naphthyl)phenylacrylamide,    N-(4-Hydroxyphenyl)-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylamide,    3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic acid morpholide,    Ethyl 3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylate,    3-[3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]but-2-enoic acid,    4-Methoxymethoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic acid,    4-Hydroxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic acid,    4-Methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic acid,    4-Propyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic acid,    4-Heptyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic acid,    3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-phenyl]acrolein,    3-[3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]prop-2-en-1-ol,    cis-3-[3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]but-2-enoic acid,    cis-3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic acid,    5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-3-pyridineacrylic acid,    3-(3-Butyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylic acid,    6-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyridineacrylic acid.    
     
     
         4 . Compounds according to  claim 1 , characterized in that they have at least one, and preferably all, of the following characteristics: 
 R 1  represents the radical —COR 5      Ar represents the radicals of formula (a) or (d)    X represents the radical                          R 2  and R 3 , taken together, form, with the adjacent aromatic ring, a 5- or 6-membered ring optionally substituted with methyl groups and/or optionally interrupted by an oxygen or sulphur atom.    
     
     
         5 . Compounds according to any one of the preceding claims, for use as a medicinal product.  
     
     
         6 . Compounds according to  claim 5 , for use as a medicinal product intended for the treatment of dermatological complaints associated with a keratinization disorder which has a bearing on differentiation and on proliferation, in particular for treating common acne, comedones, polymorphonuclear leukocytes, rosacea, nodulocystic acne, acne conglobata, senile acne and secondary acnes such as solar, medication-related or profession-related acne; for treating other types of keratinization disorder, in particular ichthyosis, ichthyosiform states, Darier's disease, palmoplantar keratoderma, leucoplasias and leucoplasiform states, and cutaneous or mucous (buccal) lichen; for treating other dermatological complaints associated with a keratinization disorder with an inflammatory and/or immunoallergic component and, in particular, all forms of psoriasis, whether it is cutaneous, mucous or ungual psoriasis and even psoriatic rheumatism, or alternatively cutaneous atopy, such as eczema or respiratory atopy or alternatively gingival hypertrophy; the compounds may also be used for some inflammatory complaints which show no keratinization disorder; for treating all dermal or epidermal hyperproliferations, whether benign or malignant and whether they are of viral origin or otherwise, such as common warts, flat warts and verruciform epidermodysplasia, it being possible for the oral or florid papillomatoses and the hyperproliferations to be induced by ultraviolet radiation, in particular in the case of basocellular and spinocellular epithelioma; for treating other dermatological disorders such as bullosis and collagen diseases; for treating certain ophthalmological disorders, in particular 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 preventing or curing the stigmata of epidermal and/or dermal atrophy induced by local or systemic corticosteroids, or any other form of cutaneous atrophy; for preventing or treating cicatrization disorders or for preventing or repairing vibices; for favouring cicatrization, for combating disorders of sebaceous functioning such as the hyperseborrhoea of acne or simple seborrhoea; in the treatment or prevention of cancerous or precancerous states, more particularly promyelocytary leukemia; in the treatment of inflammatory complaints such as arthritis; in the treatment of any general or skin complaint of viral origin; in the prevention or treatment of alopecia; in the treatment of dermatological complaints having an immuological component; in the treatment of complaints of the cardiovascular system such as arteriosclerosis or hypertension, as well as insulin-independent diabetes, in the treatment of skin disorders caused by exposure to UV radiation.  
     
     
         7 . Pharmaceutical composition, characterized in that it comprises, in a pharmaceutically acceptable support, at least one of the compounds as defined in any of  claims 1  to  4 .  
     
     
         8 . Composition according to  claim 7 , characterized in that the concentration of compound(s) according to one of  claims 1  to  4  is between 0.001% and 5% by weight relative to the composition as a whole.  
     
     
         9 . Cosmetic composition, characterized in that it comprises, in a cosmetically acceptable support, at least one of the compounds as defined in any one of  claims 1  to  4 .  
     
     
         10 . Composition according to  claim 9 , characterized in that the concentration of compound(s) according to one of  claims 1  to  4  is between 0.001% and 3% by weight relative to the composition as a whole.  
     
     
         11 . Use of a cosmetic composition as defined in either of claims  9  and  10 , for body or hair hygiene.