Phenol derivatives and pharmaceutical or cosmetic use thereof

Patent metadata

Field	Value
Publication number	US-9050266-B2
Application number	US-201013519100-A
Country	US
Kind code	B2
Filing date	Dec 22, 2010
Priority date	Dec 23, 2009
Publication date	Jun 9, 2015
Grant date	Jun 9, 2015

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.

First claim

The invention claimed is:

1. A compound of formula (I):

in which:
R 1 represents a C 2-6 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 8 R 9 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 can optionally be substituted with one to three identical or different R b groups,
R 2 and R 3 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 ) r —C 3-9 cycloalkyl, —C 2-6 alkyl-OH, —(CH 2 ) r —C 1-6 alkyloxy, —(CH 2 ) r —C 3-7 cycloalkyl, —(CH 2 ) r —C 1-6 fluoroalkyl, or —(CH 2 ) q —O—C 1-6 fluoroalkyl group,
optionally, the R 2 and R 3 groups can form, with the carbon atom which bears them, a C 3-9 cycloalkyl group or a heterocycle,
R 4 , R 5 , R 6 , R 7 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) s —C 1-6 alkyl, C 1-6 fluoroalkyl, C 1-6 fluoroalkyloxy, —(CH 2 ) t —C 3-9 cycloalkyl, —(CH 2 ) t —C 3-9 cycloalkyl, —C 1-6 alkyl-OH, —(CH 2 ) t C 1-6 alkyloxy, —(CH 2 ) t —C 1-6 fluoroalkyl, —(CH 2 ) u —O—C 1-6 fluoroalkyl, COR d , CN or NR 8′ R 9′ 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); these phenyl and heteroaryl groups can optionally be substituted with one to three identical or different R c groups,
X represents CH or N;
Y represents either a nitrogen atom, or a carbon atom substituted with a C 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkyloxy, —S(O) v —C 1-6 alkyl, C 1-6 fluoroalkyl, C 1-6 fluoroalkyloxy, —(CH 2 ) l —C 3-9 cycloalkyl, —(CH 2 ) l —C 3-9 cycloalkyl, —C 1-6 alkyl-OH, —(CH 2 ) l —C 1-6 alkyloxy, —(CH 2 ) l —C 1-6 fluoroalkyl, —(CH 2 ) w —O—C 1-6 fluoroalkyl, COR e , CN, or NR 10 R 11 group, a hydrogen atom 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); these phenyl and heteroaryl groups can optionally be substituted with one to three identical or different R b 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 12 R 13 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) j —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 )—O—C 1-6 fluoroalkyl, COR a , CN or NR 14 R 15 group;
R 8 and R 8′ are identical or different and represent a C 1-6 alkyl, C 3-7 cycloalkyl, —(CH 2 ) f —C 3-7 cycloalkyl or —(CH 2 ) f —C 1-6 fluoroalkyl group;
R 9 , R 9′ , R 10 , R 11 , R 12 , R 13 , R 14 and R 15 are identical or different and represent a hydrogen atom or a C 1-6 alkyl, C 3-7 cycloalkyl, —(CH 2 ) g —C 3-7 cycloalkyl or —(CH 2 ) g —C 1-6 fluoroalkyl group;
optionally, the R 8 and R 9 groups can form, with the nitrogen atom which bears them, a heterocycle;
optionally, the R 8′ and R 9′ groups can form, with the nitrogen atom which bears them, a heterocycle;
optionally, the R 10 and R 11 groups can form, with the nitrogen atom which bears them, a heterocycle;
optionally, the R 12 and R 13 groups can form, with the nitrogen atom which bears them, a heterocycle;
optionally, the R 14 and R 15 groups can form, with the nitrogen atom which bears them, a heterocycle;
f, g, i, l, n, r and t are different or identical and are equal to 1, 2 or 3;
j, m, s and v are different or identical and are equal to 0, 1 or 2;
p, q, u, w and z are different or identical and are equal to 2, 3 or 4;
and also a pharmaceutically acceptable salt, solvate, hydrate, conformer or rotamer thereof.

2. The compound as defined by claim 1 , wherein:
X represents a carbon atom and Y represents a carbon atom optionally substituted with one of the groups as defined in claim 1 .

3. The compound as defined in claim 1 , wherein R 1 represents a halogen, an ethyl, an isopropyl, a trifluoromethyl, a nitrile, a nitro, a methoxy, an ethoxy, an isopropoxy, a thiomethyl, a thioethyl or a thioisopropyl group.

4. The compound as defined by claim 3 , wherein R 1 represents a halogen, a methoxy, an ethoxy, a thiomethyl, a thioethyl or a trifluoromethyl group.

5. The compound as defined by claim 1 , wherein the compound is selected from the group consisting of:
2-[(6-Methoxypyridin-2-ylamino)methyl]phenol;
2-[(6-Bromopyridin-2-ylamino)methyl]phenol;
2-[(6-Bromopyridin-2-ylamino)methyl]-4-fluorophenol;
6-(2-Hydroxybenzylamino)pyridine-2-carbonitrile;
2-[1-(6-Methoxypyridin-2-ylamino)ethyl]phenol;
2-[(6-Trifluoromethylpyridin-2-ylamino)methyl]phenol;
2-[(6-Chloropyridin-2-ylamino)methyl]phenol;
2-[(6-Ethylpyridin-2-ylamino)methyl]phenol;
2-[(6-Ethoxypyridin-2-ylamino)methyl]phenol;
2-[(6-Isopropoxypyridin-2-ylamino)methyl]phenol;
5-Chloro-2-[(6-methoxypyridin-2-ylamino)methyl]phenol;
2-[(2-Trifluoromethylpyrimidin-4-ylamino)methyl]phenol;
2-[(6-Bromopyrazin-2-ylamino)methyl]phenol;
2-[(2-Chloropyrimidin-4-ylamino)methyl]phenol;
2-[(2-Bromopyrimidin-4-ylamino)methyl]phenol;
2-[(2-Chloro-6-methylpyrimidin-4-ylamino)methyl]phenol;
2-[(6-Chloro-4-trifluoromethylpyridin-2-ylamino)methyl]phenol;
2-[(6-Chloro-4-methylpyridin-2-ylamino)methyl]phenol;
2-[(6-Methoxypyrazin-2-ylamino)methyl]phenol;
2-[(2-Methoxypyrimidin-4-ylamino)methyl]phenol;
2-[(2-Methoxy-6-methylpyrimidin-4-ylamino)methyl]phenol;
2-[(6-Methylsulphanylpyridin-2-ylamino)methyl]phenol;
2-[(6-Methanesulphinylpyridin-2-ylamino)methyl]phenol;
2-[(6-Methanesulphonylpyridin-2-ylamino)methyl]phenol;
2-[(6-Methoxypyridin-2-ylamino)methyl]-6-methylphenol;
2-[(4-Bromo-6-methoxypyridin-2-ylamino)methyl]phenol;
2-[(6-Bromo-2-methoxypyrimidin-4-ylamino)methyl]phenol;
2-[(4-Chloro-6-methoxypyridin-2-ylamino)methyl]phenol;
2-[(6-Bromo-2-methoxypyrimidin-4-ylamino)methyl]phenol;
2-[(4-Bromo-6-methoxypyridin-2-ylamino)methyl]-6-fluorophenol;
2-[(4-Bromo-6-methoxypyridin-2-ylamino)methyl]-5-fluorophenol;
2-[(4-Bromo-6-methoxypyridin-2-ylamino)methyl]-3-fluorophenol;
2-[(4-Bromo-6-methoxypyridin-2-ylamino)methyl]-4-fluorophenol;
2-[(6-Bromo-2-methoxypyrimidin-4-ylamino)methyl]-4-fluorophenol;
2-[(4-Chloro-6-methoxypyridin-2-ylamino)methyl]-4-fluorophenol;
2-[(6-Chloro-2-methoxypyrimidin-4-ylamino)methyl]-4-fluorophenol;
2-[1-(4-Bromo-6-methoxypyridin-2-ylamino)ethyl]phenol;
2-[1-(4-Bromo-6-methoxypyridin-2-ylamino)propyl]phenol;
2-[1-(6-Bromo-4-methylpyridin-2-ylamino)-1-methylethyl]phenol;
2-[1-(4-Bromo-6-methoxypyridin-2-ylamino)propyl]-4-fluorophenol;
2-[1-(6-Bromopyridin-2-ylamino)propyl]-4-fluorophenol;
4-Fluoro-2-[(6-methoxypyridin-2-ylamino)methyl]phenol;
4-Fluoro-2-[1-(6-methoxypyridin-2-ylamino)ethyl]phenol;
4-Fluoro-2-[1-(6-methoxypyridin-2-ylamino)propyl]phenol;
2-[(6-Bromo-4-methoxypyridin-2-ylamino)methyl]phenol;
2-[(6-Bromo-4-methylpyridin-2-ylamino)methyl]phenol; and
2-[(6-Chloro-4-methoxypyridin-2-ylamino)methyl]phenol and a pharmaceutically acceptable salt, solvate, hydrate or rotamer thereof.

6. The compound as defined by claim 1 , wherein the compound is a medicinal product.

Assignees

• Poinsard Cédric
• Linget Jean-Michel
• Rethore Sandrine
• Mauvais Pascale
• Collette Patrice Lucien Maurice
• Collette Isabelle Marie Joëlle Martine
• Galderma Res & Dev

Inventors

• Poinsard Cédric
• Collette Pascal
• Linget Jean-Michel
• Rethore Sandrine
• Mauvais Pascale

Classifications

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P17/14

  for baldness or alopecia · CPC title

• A61P17/10

  Anti-acne agents · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title