Phenol derivatives and the pharmaceutical or cosmetic use thereof

Abstract

The use of compounds in the treatment of skin disorders is described. In particular, use of a compound of formula (I): or one of its pharmaceutically acceptable salts, solvates or hydrates in the preparation of a medicament to treat skin pathologies is described.

1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
         in which: 
         R 1  represents a C 1-6  alkyl, C 3-7  cycloalkyl, C 1-6  alkyloxy, —S(O) m —C 1-6  alkyl, C 1-6  fluoroalkyl, C 1-6  fluoroalkyloxy, —(CH 2 ) n —C 3-9  cycloalkyl, —(CH 2 ) n —C 3-9  cycloalkyl, C 2-6  alkyl-OH, —(CH 2 ) n —C 1-6  alkyloxy, —(CH 2 ) n —C 1-6  fluoroalkyl, —(CH 2 ) p —O—C 1-6  fluoroalkyl, COR a , CN, NO 2  or NR 9 R 10  group, a halogen or a phenyl or heteroaryl group comprising either a) from 1 to 4 nitrogen atoms or b) an oxygen or sulphur atom and 1 or 2 nitrogen atom(s), wherein the phenyl and heteroaryl groups can optionally be substituted with one to three identical or different R b  groups; 
         R 2  represents a C 1-6  alkyl, C 3-7  cycloalkyl, C 1-6  alkyloxy, —S(O) f —C 1-6  alkyl, C 1-6  fluoroalkyl, C 1-6  fluoroalkyloxy, —(CH 2 ) 1 —C 3-9  cycloalkyl, —(CH 2 ) 1 —C 3-9  cycloalkyl, C 2-6  alkyl-OH, —(CH 2 ) 1 —C 1-6  alkyloxy, —(CH 2 ) 1 —C 1-6  fluoroalkyl, —(CH 2 ) q —O—C 1-6  fluoroalkyl, COR d , CN, NO 2  or NR 9′ R 10′  group, a hydrogen, a halogen or a phenyl or heteroaryl group comprising either a) from 1 to 4 nitrogen atoms or b) an oxygen or sulphur atom and 1 or 2 nitrogen atom(s), wherein the phenyl and heteroaryl groups can optionally be substituted with one to three identical or different R b  groups; 
         R 3  and R 4  are identical or different and represent a hydrogen atom or a C 1-9  alkyl, C 3-9  cycloalkyl, C 1-6  fluoroalkyl, —(CH 2 ) k —C 3-9  cycloalkyl, —C 2-6  alkyl-OH, —(CH 2 ) p —C 1-6  alkyloxy, —(CH 2 ) k —C 3-7  cycloalkyl, —(CH 2 ) k —C 1-6  fluoroalkyl or —(CH 2 ) r —O—C 1-6  fluoroalkyl group, 
         Optionally, the R 3  and R 4  groups can form, with the carbon atom which bears them, a C 3-9  cycloalkyl group or a heterocycle such as tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, tetrahydro-1-oxythiopyran or tetrahydro-1,1-dioxythiopyran; 
         R 5 , R 6 , R 7  and R 8  are identical or different and represent either a hydrogen atom or a C 1-6  alkyl, C 3-7  cycloalkyl, C 1-6  alkyloxy, —S(O) g —C 1-6  alkyl, C 1-6  fluoroalkyl, C 1-6  fluoroalkyloxy, —(CH 2 ) j —C 3-9  cycloalkyl, —(CH 2 ) j —C 3-9  cycloalkyl, —C 1-6  alkyl-OH, —(CH 2 ) j —C 1-6  alkyloxy, —(CH 2 ) j —C 1-6  fluoroalkyl, —(CH 2 ) s —O—C 1-6  fluoroalkyl, COR e , CN or NR 11 R 12  group, or a halogen or a phenyl or heteroaryl group comprising either a) from 1 to 4 nitrogen atoms or b) an oxygen or sulphur atom and 1 or 2 nitrogen atom(s), wherein the phenyl and heteroaryl groups can optionally be substituted with one to three identical or different R c  groups; 
         R a , R d  and R e  are identical or different and represent a C 1-6  alkyl, C 1-6  alkyloxy or NR 13 R 14  group; 
         R b  and R c  are identical or different and represent a halogen, or a C 1-6  alkyl, C 3-7  cycloalkyl, C 1-6  alkyloxy, —S(O) u —C 1-6  alkyl, C 1-6  fluoroalkyl, C 1-6  fluoroalkyloxy, —(CH 2 ) i —C 3-7  cycloalkyl, OH, —(CH 2 ) i —C 3-7  cycloalkyl, C 1-6  alkyl-OH, —(CH 2 ) i —C 1-6  alkyloxy, —(CH 2 ) i —C 1-6  fluoroalkyl, —(CH 2 ) t —O—C 1-6  fluoroalkyl, COR a , CN, or NR 15 R 16  group; 
         R 9 , R 9′ , R 10 , R 10′ , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are identical or different and represent a hydrogen atom, or a C 1-6  alkyl, C 3-7  cycloalkyl, —(CH 2 ) h —C 3-7  cycloalkyl or —(CH 2 ) h —C 1-6  fluoroalkyl group; 
         optionally, the R 9  and R 10  groups can form, with the nitrogen atom which bears them, a heterocycle; 
         optionally, the R 9′  and R 10′  groups can form, with the nitrogen atom which bears them, a heterocycle; 
         optionally, the R 11  and R 12  groups can form, with the nitrogen atom which bears them, a heterocycle; 
         optionally, the R 13  and R 14  groups can form, with the nitrogen atom which bears them, a heterocycle; 
         optionally, the R 15  and R 16  groups can form, with the nitrogen atom which bears them, a heterocycle; 
         h, i, j, k, l and n are different or identical and are equal to 1, 2 or 3; 
         f, g, m and u are different or identical and are equal to 0, 1 or 2; 
         p, q, r, s and t are different or identical and are equal to 2, 3 or 4; 
         and also a pharmaceutically acceptable salt, solvate or hydrate thereof and the conformer or rotamer thereof. 
       
     
     
         2 . The compound as defined by  claim 1 , wherein:
 R 1  represents a halogen, a methyl, an ethyl, an isopropyl, a trifluoromethyl, a nitrile, a nitro, a methoxy, a ethoxy, an isopropoxy, a thiomethyl, a thioethyl or a thioisopropyl group, and   R 2  represents a hydrogen atom, a halogen, a methyl, an ethyl, an isopropyl, a trifluoromethyl, a nitrile, a nitro, a methoxy, an ethoxy, an isopropoxy, a thiomethyl, a thioethyl or a thioisopropyl group.   
     
     
         3 . The compound as defined in  claim 2 , wherein:
 R 1  represents a halogen, a methyl, an ethyl, a methoxy, an ethoxy, a thiomethyl, a thioethyl or a trifluoromethyl group, and   R 2  represents a hydrogen atom, a halogen, a methoxy, an ethoxy, a thiomethyl, a thioethyl or a trifluoromethyl group.   
     
     
         4 . The compound as defined by  claim 1 , wherein the compound is selected from the group consisting of:
 2-[(2-Bromo-6-methoxypyridin-4-ylamino)methyl]phenol;   2-[(2-Chloropyridin-4-ylamino)methyl]phenol;   2-[(2-Bromopyridin-4-ylamino)methyl]phenol;   2-[(2-Bromopyridin-4-ylamino)methyl]-4-fluorophenol;   2-[(2-Methoxypyridin-4-ylamino)methyl]phenol;   2-[(2-Trifluoromethylpyridin-4-ylamino)methyl]phenol;   4-Fluoro-2-[(2-methoxypyridin-4-ylamino)methyl]phenol;   2-[(2-Bromo-6-methoxypyridin-4-ylamino)methyl]-4-fluorophenol;   2-[(2-Bromo-6-methoxypyridin-4-ylamino)methyl]-6-fluorophenol;   2-[(2-Bromo-6-methoxypyridin-4-ylamino)methyl]-6-methylphenol;   2-[(2-Bromo-6-methoxypyridin-4-ylamino)methyl]-5-fluorophenol;   2-[(2-Bromo-6-methoxypyridin-4-ylamino)methyl]-3-fluorophenol;   2-[(2-Bromo-6-methoxypyridin-4-ylamino)methyl]-3-fluorophenol;   2-[(2-Chloro-6-methoxypyridin-4-ylamino)methyl]phenol;   2-[(2-Bromo-6-methoxypyridin-4-ylamino)methyl]-5-methylphenol;   2-[(2-Chloro-6-methoxypyridin-4-ylamino)methyl]-4-fluorophenol;   2-[(2-Bromo-6-methylpyridin-4-ylamino)methyl]phenol;   2-[(2-Bromo-6-methylpyridin-4-ylamino)methyl]-4-fluorophenol;   2-[1-(2-Bromo-6-methoxypyridin-4-ylamino)ethyl]phenol;   2-[1-(2-Bromo-6-methoxypyridin-4-ylamino)propyl]phenol;   2-[(2-Bromo-6-ethoxypyridin-4-ylamino)methyl]phenol;   2-[1-(2-Bromo-6-methoxypyridin-4-ylamino)-1-methylethyl]phenol; and   2-[(2-Bromo-6-methylpyridin-4-ylamino)methyl]-5-fluorophenol and a pharmaceutically acceptable salt, solvate, hydrate, conformer or rotamer thereof.   
     
     
         5 . The compound as defined by  claim 1 , wherein the compound is a medicinal product. 
     
     
         6 . A method of manufacturing a cosmetic composition, the method comprising manufacturing the composition with an effective amount of the compound as defined by  claim 1  for body or hair hygiene. 
     
     
         7 . A method of producing a medicament, the method comprising producing the medicament with an effective amount of the compound as defined by  claim 1  for treating hirsutism, androgenic alopecia, hyperpilosity, atopic dermatitis, a sebaceous gland disorder, acne, oily skin or seborrhoeic dermatitis. 
     
     
         9 . A method of producing a medicament for treating acne, the method comprising producing the medicament with an effective amount of the compound as defined by  claim 1  for treating acne. 
     
     
         10 . The compound as defined by  claim 1 , wherein the R 8  and R 9  groups can form azetidine, pyrrolidine, piperidine, azepane, morpholine or piperazine. 
     
     
         11 . The compound as defined by  claim 1 , wherein the R 8′  and R 9′  groups can form azetidine, pyrrolidine, piperidine, azepane, morpholine or piperazine. 
     
     
         12 . The compound as defined by  claim 1 , wherein the R 10  and R 11  groups can form azetidine, pyrrolidine, piperidine, azepane, morpholine or piperazine. 
     
     
         13 . The compound as defined by  claim 1 , wherein the R 12  and R 13  groups can form azetidine, pyrrolidine, piperidine, azepane, morpholine or piperazine. 
     
     
         14 . The compound as defined by  claim 1 , wherein the R 14  and R 15  groups can form azetidine, pyrrolidine, piperidine, azepane, morpholine or piperazine. 
     
     
         15 . The method of  claim 9 , wherein the sebaceous gland disorder is hyperseborrhoea.