Phenol derivatives and pharmaceutical or cosmetic use thereof

Patent metadata

Field	Value
Publication number	US-9505720-B2
Application number	US-201514707711-A
Country	US
Kind code	B2
Filing date	May 8, 2015
Priority date	Dec 23, 2009
Publication date	Nov 29, 2016
Grant date	Nov 29, 2016

Abstract

The present invention relates to novel compounds of general formula:

and to the cosmetic or pharmaceutical use thereof.

First claim

The invention claimed is:

1. A method of preparing 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 1-8 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 1-8 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 groups 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 8 , CN, NR 10 R 11 or NO 2 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) i —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, fluoroalkyl, —(CH 2 ) z —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,
the method comprising:
(a) reacting an aldehyde (II) or a benzyl ketone (II) with an amine (III) in the presence of a reducing agent;

(b) reacting a benzyl amine (VI) with a heterocycle (V) in the presence of a base; or

(c) reacting an amide intermediate (VII) with a reactive hydrogen donor

2. The method according to claim 1 , wherein the amide intermediate (VII) is prepared by reacting an acyl chloride (VI) with an amine (III)

3. The method according to claim 1 , wherein the reducing agent is sodium triacetoxyborohydride.

4. The method according to claim 1 , wherein the base is 1,8-diazabicyclo[5.4.0]undec-7-ene.

5. The method according to claim 1 , wherein the reactive hydrogen donor is lithium aluminum anhydride.

6. The method according to 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 .

7. The method according to claim 6 , wherein Y represents a carbon substituted with a member selected from the group consisting of a methyl, ethyl, isopropyl, cyclopropyl, CF 3 , CONH 2 , CO 2 CH 3 , CO 2 CH 2 CH 3 , CN, NO 2 , SCH 3 or SCH 2 CH 3 group, a hydrogen atom, a halogen, a OCF 3 , OCH 3 , OCH 2 CH 3 or OCH(CH 3 ) 2 group.

8. The method according to claim 1 , wherein R1 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.

9. The method according to claim 8 , wherein R1 represents a halogen, a methoxy, an ethoxy, a thiomethyl, a thioethyl or a trifluoromethyl group.

10. The method according to claim 1 , wherein the R2 and R3 groups can form tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, tetrahydro-1-oxythiopyran or tetrahydro-1,1-dioxythiopyran.

11. The method according to claim 1 , wherein the R8 and R9 groups can form azetidine, pyrrolidine, piperidine, azepane, morpholine or piperazine.

12. The method according to claim 1 , wherein the R10 and R11 groups can form azetidine, pyrrolidine, piperidine, azepane, morpholine or piperazine.

13. The method according to claim 1 , wherein the R12 and R13 groups can form azetidine, pyrrolidine, piperidine, azepane, morpholine or piperazine.

14. The method according to claim 1 , wherein the R14 and R15 groups can form azetidine, pyrrolidine, piperidine, azepane, morpholine or piperazine.

15. The method according to 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)met

Assignees

• Galderma Res & Dev

Inventors

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

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/08

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

• A61P17/00

  Drugs for dermatological disorders · CPC title

• A61P15/00

  Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives · CPC title

• A61P17/08

  Antiseborrheics · CPC title