7-Oxo-DHEA compounds for treating keratinous conditions/afflictions

Abstract

7-Oxo-DHEA derivatives, various of which are themselves novel compounds, are well suited for cosmetically/therapeutically treating adverse conditions/afflictions of a keratinous substrate/material, notably of human skin, hair, eyelashes and nails, to improve the appearance thereof, in particular to prevent or treat signs of aging of the skin and/or a dull complexion and/or skin or hair pigmentation disorders and/or dryness of the skin and/or hyperseborrhoea and/or hyperseborrhoea-related imperfections and/or sensitive skin and/or dandruff and/or natural hair loss and/or baldness.

1 . A method for cosmetically/therapeutically treating an adverse condition/affliction of a keratinous substrate/material to improve the appearance thereof, comprising topically applying onto such keratinous substrate/material, an appearance-enhancing effective amount of at least one 7-oxo-DHEA compound having the structural formula (I):  
       
         
           
           
               
               
           
         
       
       in which R is a saturated or unsaturated, linear or branched, or cyclic C 1 -C 12  alkyl radical optionally containing one or more hetero atoms and optionally substituted with one or more substituents selected from among —OR′ and/or —SR′ and/or —COOR′ and/or —NR′R′ and/or halogen and/or sulfate and/or phosphate and/or aryl and/or heterocycle; 
 a group O═P(OH)OR′ a group (O) 2 SOR′ a trialkylsilyl radical (SiR′ 3 ) in which the 3 groups R′ may be identical or different; an alkyloxycarbonyl group (R′OCO); an alkylaminocarbonyl group (R′NHCO); wherein R′ is a hydrogen atom, a saturated or unsaturated, linear or branched, or cyclic C 1 -C 12  alkyl radical, which may optionally contain one or more hetero atoms, optionally functionalized with one or more of the groups —OR″, —COOR″, halogen, —NR″R″, or with an aryl group, optionally functionalized with one or more of the groups —OR″, —COOR″, halogen or —NR″R″; and R″ is a hydrogen atom or a saturated or unsaturated, linear or branched or cyclic alkyl radical; with the proviso that, in each of the groups —NR′R′ and —NR″R″, the substituents R′ and R″, respectively, are identical or different.  
 
     
     
         2 . The method as defined by  claim 1 , wherein formula (I), R is a C 1 -C 6 , saturated or unsaturated, linear or branched, or cyclic alkyl radical optionally containing one or more hetero atoms, and optionally substituted with one or more groups selected from among —OR′ and/or —SR′ and/or —COOR′ and/or —NR′R′ and/or halogen.  
     
     
         3 - 4 . (canceled)  
     
     
         5 . The method as defined by  claim 1 , wherein formula (I), each of the groups R″ and R″ is a hydrogen atom or a C 1 -C 6  alkyl radical.  
     
     
         6 . The method as defined by  claim 1 , wherein formula (I), each of the groups R′ and R″ is a hydrogen atom, or a methyl, ethyl, butyl, propyl or isopropyl radical.  
     
     
         7 . The method as defined by  claim 1 , wherein formula (I), at least one R′ is an amino acid group —NR′R′ or —NR″R″ selected from among L-alanine, L-arginine, L-asparagine, L-aspartic acid, L-cysteine, L-glutamine, L-glutamic acid, glycine, L-histidine, L-isoleucine, L-leucine, L-lysine, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L-tryptophan, L-tyrosine and/or L-valine.  
     
     
         8 . The method as defined by  claim 1 , said at least one 7-oxo-DHEA compound comprising: 
 3β-O-methyl-7-oxo-dehydroepiandrosterone;    3β-O-ethyl-7-oxo-dehydroepiandrosterone;    3β-O-glucosyl-7-oxo-dehydroepiandrosterone;    3β-O-glucoronyl-7-oxo-dehydroepiandrosterone;    3β-O-(2-tetrahydropyranyl)-7-oxo-dehydroepiandrosterone;    3β-O-(2-tetrahydrofuranyl)-7-oxo-dehydroepiandrosterone; and/or    3β-O-(2-hydroxymalonyl)-7-oxo-dehydropiandrosterone.    
     
     
         9 . The method as defined by  claim 1 , said at least one 7-oxo-DHEA compound comprising: 
 3β-O-(2-malonylaminocarbonyl)-7-oxo-dehydroepiandrosterone;    3β-O-(2-succinylaminocarbonyl)-7-oxo-dehydroepiandrosterone;    3β-O-(2-glutarylaminocarbonyl)-7-oxo-dehydroepiandrosterone;    3β-O-benzoyl-7-oxo-dehydroepiandrosterone;    3β-O-(3,4-dihydroxybenzoyl)-7-oxo-dehydroepiandrosterone;    3β-O-phosphonyl-7-oxo-dehydroepiandrosterone;    3β-O-monoacetylphosphonyl-7-oxo-dehydroepiandrosterone;    3β-O-sulfonyl-7-oxo-dehydroepiandrosterone;    3β-O-(tert-butyldimethylsilyl)-7-oxo-dehydroepiandrosterone;    3β-O-(tert-butyldiphenylsilyl)-7-oxo-dehydroepiandrosterone; and/or    3β-O-(trimethylsilyl)-7-oxo-dehydroepiandrosterone.    
     
     
         10 . The method as defined by  claim 1 , for preventing or treating the signs of aging of the skin and/or a dull complexion and/or skin or hair pigmentation disorders and/or skin dryness and/or hyperseborrhoea and/or hyperseborrhoea-related imperfections and/or sensitive skin and/or dandruff and/or natural hair loss and/or baldness.  
     
     
         11 . The method as defined by  claim 10 , comprising treating wrinkles and fine lines, cutaneous atrophy, loss of firmness and/or elasticity of the skin, an irregular skin grain with presence of dilated pores, loss of radiance of the skin and/or pigmentary marks.  
     
     
         12 . The method as defined by  claim 1 , comprising topically co-applying onto such keratinous substrate/material, an effective amount of at least one other active agent compound selected from the group consisting of desquamating agents, moisturizers, depigmenting or propigmenting agents, anti-glycation agents, NO-synthase inhibitors, 5α-reductase inhibitors, lysyl and/or prolyl hydroxylase inhibitors, agents for stimulating the synthesis of dermal or epidermal macromolecules or for preventing their degradation, agents for stimulating the proliferation of fibroblasts and keratinocytes and/or keratinocyte differentiation, muscle relaxants, compounds for reducing irritation of neurogenic origin, antimicrobial agents, tensioning agents, anti-pollution agents, and free-radical scavengers.  
     
     
         13 . The method as defined by  claim 1 , comprising topically co-applying onto such keratinous substrate/material, an effective amount of at least one optionally coated inorganic pigment and/or at least one UV-screening agent selected from the group consisting of: 
 (a) a benzophenone derivative;    (b) a triazine derivative;    (c) benzene-1,4-bis(3-methylidene-10-camphorsulfonic acid), optionally in partially or totally neutralized state;    (d) a salicylic acid derivative;    (e) a cinnamic acid derivative;    (f) a liquid β,β′-diphenylacrylate derivative;    (g) a p-aminobenzoic acid derivative;    (h) 4-methylbenzylidenecamphor;    (i) 2-phenylbenzimidazole-5-sulfonic acid;    (j) a 1,3,5-triazine derivative;    (k) a plant extract which comprises an extract of  Rosmarinus officinalis, Leontopodium alpinum  and/or  Leontopodium stracheyi ; and    (l) a benzotriazole silicone having the formula:                          
     
     
         14 . The method as defined by  claim 1 , said keratinous substrate/material comprising human skin, hair, eyelashes and/or nails.  
     
     
         15 . A 7-oxo-DHEA compound having the formula (I) as defined by  claim 1 , in which R is: 
 a group O═P(OH)OR′ with the exception of the O═P(OH) 2  group and the O═P(OH)OCOCH 3  group;    a group (O) 2 SOR′ with the exception of the Na.SO 3 H group and the SO 3 H group;    a trialkylsilyl group (SiR′ 3 ) in which the 3 groups R′ may be identical or different, with the exception of the tBu Si(Me) 2  group; or    an alkylaminocarbonyl group (R′NHCO) wherein the alkyl moiety is necessarily substituted with one or more of the groups selected from among —OR′ and/or —SR′ and/or —COOR′ and/or —NR′R′ and/or halogen and/or sulfate and/or phosphate and/or glycoside and/or aryl and/or heterocycle, said heterocycle being an indole, a pyrimidine, a piperidine, a morpholine, a pyran, a furan, a piperazine, or a pyridine.    
     
     
         16 . A 7-oxo-DHEA compound selected from the group consisting of: 
 3β-O-methyl-7-oxo-dehydroepiandrosterone;    3β-O-ethyl-7-oxo-dehydroepiandrosterone;    3β-O-glucosyl-7-oxo-dehydroepiandrosterone; and    3β-O-(2-tetrahydrofuranyl)-7-oxo-dehydroepiandrosterone.    
     
     
         17 . A 7-oxo-DHEA compound selected from the group consisting of: 
 3β-O-(2-hydroxymalonyl)-7-oxo-dehydroepiandrosterone;    3β-O-(2-malonylaminocarbonyl)-7-oxo-dehydroepiandrosterone;    3β-O-(2-succinylaminocarbonyl)-7-oxo-dehydroepiandrosterone;    3β-O-(2-glutarylaminocarbonyl)-7-oxo-dehydroepiandrosterone;    3β-O-(t-butyldiphenylsilyl)-7-oxo-dehydroepiandrosterone; and    3β-O-(trimethylsilyl)-7-oxo-dehydroepiandrosterone.    
     
     
         18 . A process for synthesizing the 3β-O-alkylcarbonyl-7-oxo-DHEA compound as defined by  claim 16 , comprising introducing 7-oxo-DHEA into a polar aprotic solvent, adding an organic base and an acid chloride thereto and then, after reaction of same, the residue obtained is then recrystallized or purified.  
     
     
         19 . A process for synthesizing the 3β-O-alkyl-carbonyl-7-oxo-DHEA compounds as defined by claims  16  or  17 , comprising adding a carbonyldiimidazole dissolved in a polar aprotic solvent to carboxylic acid dissolved in the same solvent, and then, to the solution stirred without heating, adding 7-oxo-DHEA dissolved in the same solvent, stirring the mixture under cold conditions and then at room temperature and then, after reaction of same, the residue is then purified.  
     
     
         20 . A process for synthesizing the 3β-O-alkyl-7-oxo-DHEA compounds as defined by claims  16  or  17 , comprising introducing 7-oxo-DHEA into a polar aprotic solvent and then adding an alkali metal hydride under cold conditions, stirring the reaction medium and then, after adding an alkyl halide, maintaining the reaction medium at room temperature, and, after reaction, the residue obtained is then recrystallized or purified.  
     
     
         21 . A process for synthesizing the 7-keto-DHEA carbamates as defined by claims  16  or  17 , comprising introducing 7-oxo-DHEA into an anhydrous aprotic solvent, heating the reaction medium after addition, under inert atmosphere, of an isocyanate and an organic base, and, after reaction thereof, the residue obtained is then recrystallized or purified.  
     
     
         22 . A topically applicable cosmetic/therapeutic composition suited for treating an adverse condition/affliction of a keratinous substrate/material to improve the appearance thereof, comprising (1) an appearance-enhancing effective amount of at least one 7-oxo-DHEA compound having the structural formula (I):  
       
         
           
           
               
               
           
         
       
       in which R is a saturated or unsaturated, linear or branched, or cyclic C 1 -C 12  alkyl radical optionally containing one or more hetero atoms and optionally substituted with one or more substituents selected from among —OR′ and/or —SR′ and/or —COOR′ and/or —NR′R′and/or halogen and/or sulfate and/or phosphate and/or aryl and/or heterocycle; 
 a group O═P(OH)OR′; a group (O) 2 SOR′ a trialkylsilyl radical (SiR′ 3 ) in which the 3 groups R′ may be identical or different; an alkyloxycarbonyl group (R′OCO); an alkylaminocarbonyl group (R′NHCO); wherein R′ is a hydrogen atom, a saturated or unsaturated, linear or branched, or cyclic C 1 -C 12  alkyl radical, which may optionally contain one or more hetero atoms, optionally functionalized with one or more of the groups —OR″, —COOR″, halogen, —NR″R″, or with an aryl group, optionally functionalized with one or more of the groups —OR″, —COOR″, halogen or —NR″R″; and R″ is a hydrogen atom or a saturated or unsaturated, linear or branched or cyclic alkyl radical; with the proviso that, in each of the groups —NR′R′ and —NR″R″, the substituents R′ and R″, respectively, are identical or different, formulated into a (2) topically applicable, physiologically acceptable vehicle, diluent or carrier therefor.  
 
     
     
         23 . The topically applicable cosmetic/therapeutic composition as defined by  claim 22 , further comprising an effective amount of at least one other active agent compound selected from the group consisting of desquamating agents, moisturizers, depigmenting or propigmenting agents, anti-glycation agents, NO-synthase inhibitors, 5α-reductase inhibitors, lysyl and/or prolyl hydroxylase inhibitors, agents for stimulating the synthesis of dermal or epidermal macromolecules or for preventing their degradation, agents for stimulating the proliferation of fibroblasts and keratinocytes and/or keratinocyte differentiation, muscle relaxants, compounds for reducing irritation of neurogenic origin, antimicrobial agents, tensioning agents, anti-pollution agents, and/or and free-radical scavengers.  
     
     
         24 . The topically applicable cosmetic/therapeutic composition as defined by  claim 22 , further comprising an effective amount of at least one optionally coated inorganic pigment and/or at least one UV-screening agent selected from the group consisting of: 
 (a) a benzophenone derivative;    (b) a triazine derivative;    (c) benzene-1,4-bis(3-methylidene-10-camphorsulfonic acid), optionally in partially or totally neutralized state;    (d) a salicylic acid derivative;    (e) a cinnamic acid derivative;    (f) a liquid β,β′-diphenylacrylate derivative;    (g) a p-aminobenzoic acid derivative;    (h) 4-methylbenzylidenecamphor;    (i) 2-phenylbenzimidazole-5-sulfonic acid;    (j) a 1,3,5-triazine derivative;    (k) a plant extract which comprises an extract of  Rosmarinus officinalis, Leontopodium alpinum  and/or  Leontopodium stracheyi ; and    (l) a benzotriazole silicone having the formula:                          
     
     
         25 . The topically applicable cosmetic/therapeutic composition as defined by  claim 22 , comprising from 0.00001% to 10% by weight of said at least one 7-oxo-DHEA compound.  
     
     
         26 . The topically applicable cosmetic/therapeutic composition as defined by  claim 22 , comprising from 0.001% to 5% by weight of said at least one 7-oxo-DHEA compound.