Novel biaromatic propynyl compounds, pharmaceutical and cosmetic compositions containing same, and uses thereof

Abstract

The invention relates to new compounds of the general formula (I):as well as the use thereof in pharmaceutical compositions intended for use in human or veterinary medicine (dermatological, rheumatic, respiratory, cardiovascular and ophthalmological disorders, in particular), or in the use of cosmetic compositions.

1 .- 17 . (canceled) 
     
     
         18 . A method of treating a keratinization disorder, a dermatological condition linked to a keratinization disorder pertaining to cellular differentiation and proliferation, or a dermatological condition associated with a keratinization disorder with an inflammatory or immunoallergenic component, the method comprising:
 administering to a human subject in need thereof a pharmaceutical composition comprising:   (a) an effective amount of a compound having the structure of formula (I) below:   
       
         
           
           
               
               
           
         
         
           wherein: 
           Ar is a radical selected from the group of radicals of formula (α) or (b) below: 
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
         
           wherein R 5  is OH; 
           R 1  is:
 (i) a hydrogen atom, 
 (ii) a —CH 3  radical, 
 (iii) a —CH 2 —O—R 6  radical, 
 (iv) an —O—R 6  radical, 
 (v) a —CO—R 7  radical, or 
 (vi) an —S(O) t R 9  radical; 
 
           R 2  and R 3 , together with the carbon atoms to which they are attached, form a 5- or 6-membered ring optionally substituted by methyl groups and includes only carbon atoms; 
           R 4  is a halogen atom or an —OR 6  radical; 
           R 6  is a hydrogen atom, a lower alkyl radical, a linear or branched alkyl radical having 1 to 20 carbon atoms, or a —CO—R 9  radical; 
           R 7  is a hydrogen atom, a lower alkyl radical, a radical of formula: 
         
       
       
         
           
           
               
               
           
         
         
           
             or an —OR 8  radical; 
           
           R 8  is a hydrogen atom, a linear or branched alkyl radical having 1 to 20 carbon atoms, an alkenyl radical, a mono- or polyhydroxyalkyl radical, an optionally substituted aryl or aralkyl radical, a sugar residue, an amino acid, or a peptide residue; 
           R 9  represents a lower alkyl radical, or a linear or branched alkyl radical having 1 to 20 carbon atoms; 
           each of R′ and R″ is a hydrogen atom, a lower alkyl radical, a mono- or polyhydroxyalkyl radical, an optionally substituted aryl radical, an amino acid, a peptide residue, or a sugar residue; or R′ and R″, together with the nitrogen atom to which they are attached, form a heterocycle; and 
           t is 0, 1 or 2, 
         
         or a salt, or an optical or geometric isomer thereof; and 
         (b) a pharmaceutically acceptable carrier. 
       
     
     
         19 . The method of  claim 18 , wherein the compound is an alkali metal or alkaline earth metal salt, a zinc salt, or an organic amine salt. 
     
     
         20 . The method of  claim 18 , wherein the lower alkyl radicals are selected from the group consisting of methyl, ethyl, isopropyl, butyl, tert-butyl, and hexyl radicals. 
     
     
         21 . The method of  claim 18 , wherein the linear or branched alkyl radicals having 1 to 20 carbon atoms are selected from the group consisting of methyl, ethyl, propyl, cyclopropyl, cyclobutyl, and cyclopentyl radicals. 
     
     
         22 . The method of  claim 18 , wherein the monohydroxyalkyl radicals are selected from the group consisting of 2-hydroxyethyl, 2-hydroxypropyl, and 3-hydroxypropyl radicals. 
     
     
         23 . The method of  claim 18 , wherein the polyhydroxyalkyl radicals are selected from the group consisting of 2,3-dihydroxypropyl, 2,3,4-trihydroxybutyl, 2,3,4,5-tetrahydroxypentyl radicals, and a pentaerythritol residue. 
     
     
         24 . The method of  claim 18 , wherein the aryl radical is a phenyl radical optionally substituted with at least one halogen atom, hydroxyl, or nitro. 
     
     
         25 . The method of  claim 18 , wherein the aralkyl radicals are selected from the group consisting of benzyl or phenethyl radicals optionally substituted by at least one halogen atom, hydroxyl, or nitro. 
     
     
         26 . The method of  claim 18 , wherein the alkenyl radicals are selected from the group consisting of radicals containing 2 to 5 carbon atoms and having one or more double bonds. 
     
     
         27 . The method of  claim 18 , wherein the sugar residues are selected from the group consisting of glucose, galactose, mannose, and glucuronic acid residues. 
     
     
         28 . The method of  claim 18 , wherein the amino acid residues are selected from the group consisting of residues deriving from lysine, glycine, and aspartic acid. 
     
     
         29 . The method of  claim 18 , wherein the peptide residues are selected from the group consisting of dipeptide and tripeptide residues. 
     
     
         30 . The method of  claim 18 , wherein the heterocyclic radicals are selected from the group consisting of piperidino, morpholino, pyrrolidino, and piperazino radicals, optionally substituted in position 4 by a C1-C6 alkyl or mono- or polyhydroxyalkyl radical. 
     
     
         31 . The method of  claim 18 , wherein the compound is an alkali metal salt, an alkaline earth metal salt, a zinc salt, or an organic amine salt of compound 1 or 2: 
       
         
           
           
               
               
           
         
       
     
     
         32 . The method of  claim 18 , wherein the administering comprises enteral, parenteral, topical, or ocular administration. 
     
     
         33 . The method of  claim 18 , wherein the keratinization disorder is selected from the group consisting of: ichthyosis; ichthyosiform states; Darier's disease; palmoplantar keratoderma; leukoplakia and leukoplakiform conditions; and cutaneous or mucosal (buccal) lichen. 
     
     
         34 . The method of  claim 18 , wherein the dermatological condition linked to a keratinization disorder is selected from the group consisting of: acne vulgaris; comedonic or polymorphic acne; rosacea; nodulocystic acne; acne conglobate; senile acne; solar acne; drug-induced acne; and occupational acne. 
     
     
         35 . The method of  claim 18 , wherein the dermatological condition associated with a keratinization disorder with an inflammatory or immunoallergenic component is selected from the group consisting of: psoriasis; psoriatic arthritis; eczema; respiratory atopy; and gingival hypertrophy. 
     
     
         36 . The method of  claim 18 , wherein the administering is performed using a daily dosage of the compound having the structure of formula (I) of approximately 0.01 mg/kg to 100 mg/kg of bodyweight in 1 to 3 doses. 
     
     
         37 . The method of  claim 18 , wherein the administering comprises ocular administration and the pharmaceutical composition comprises the compound having the structure of formula (I) at a concentration of between 0.001% and 5% by weight, relative to the total weight of the composition.