Selective 11-beta-hydroxysteroid dehydrogenase type 1 inhibitors

Patent metadata

Field	Value
Publication number	US-10550097-B2
Application number	US-201615745754-A
Country	US
Kind code	B2
Filing date	Jul 7, 2016
Priority date	Jul 23, 2015
Publication date	Feb 4, 2020
Grant date	Feb 4, 2020

Abstract

The present invention relates to novel selective 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors and the use thereof to prevent age-induced skin structure and function defects.

First claim

The invention claimed is:

1. A cosmetic composition comprising:
(i) a compound of formula (I):

wherein X is CH or N,
Y is CHR 8 or O,
n is 0, 1 or 2,
R 1 , R 2 and R 3 are independently of each other selected from the group consisting of H, OH, a halogen atom, a carbamoyl group and C 1 -C 6 alkyl group, and
R 4 , R 5 , R 6 , R 7 and R 8 are independently of each other H or a C 1 -C 6 alkyl group, and

(ii) a cosmetically acceptable carrier.

2. The cosmetic composition according to claim 1 , wherein the compound of formula (I) is present in an amount within a range of about 0.00001 to 0.5 wt.-%, based on total weight of the cosmetic composition.

3. The cosmetic composition according to claim 1 , wherein the compound of formula (I) is a compound of formula (Ia):

wherein X is CH or N,
Y is CHR 8 or O,
n is 1 or 2,
R 1 , R 2 and R 3 are independently of each other selected from the group consisting of H, OH, a halogen atom, a carbamoyl group and a C 1 -C 6 alkyl group, and
R 4 , R 5 , R 6 , R 7 and R 8 are independently of each other H or a C 1 -C 6 alkyl group,
with the proviso that if
(i) n is 1 and Y is CHR 8 , then at least one of R 4 , R 5 or R 8 is a C 1-6 alkyl group; or
(ii) n is 2, Y is CHR 8 , X is CH and R 1 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are H, then R 2 is not F; or
(iii) n is 1 and Y is O, then R 2 and at least one of R 4 or R 5 are a C 1 -C 6 alkyl group.

4. The cosmetic composition according to claim 1 , wherein the compound of formula (I) contains only one residue selected from the group consisting of OH, a halogen atom and a carbamoyl group.

5. The cosmetic composition according to claim 1 , wherein the C 1 -C 6 alkyl group is an unbranched C 1 -C 3 alkyl group.

6. The cosmetic composition according to claim 1 , wherein the halogen atom is F or Cl.

7. The cosmetic composition according to claim 1 , wherein the compound of formula (I) is a compound of formula (II):

wherein X is CH or N,
R 1 , R 2 and R 3 are independently of each other selected from the group consisting of H, OH, a halogen atom, a carbamoyl group and a C 1 -C 6 alkyl group, and
R 4 , R 5 and R 8 are independently of each other H or a C 1 -C 6 alkyl group,
with the proviso that at least one of R 4 , R 5 and R 8 is a C 1-6 alkyl group.

8. The cosmetic composition according claim 7 , wherein the compound of formula (II) is a compound selected from the group consisting of (4-methylpiperidin-1-yl) (3-(6-methylpyridin-3-yl)phenyl)methanone (II-a), (4′-hydroxy-[1,1′-biphenyl]-3-yl)(4-methylpiperidin-1-yl)methanone (II-b), (4′-fluoro-[1,1′-biphenyl]-3-yl)(4-methylpiperidin-1-yl)methanone (III-c), (3′-fluoro-4′-methyl-[1,1′-biphenyl]-3-yl)(4-methylpiperidin-1-yl)methanone (III-d), (2′-chloro-[1,1′-biphenyl]-3-yl)(4-methylpiperidin-1-yl)methanone (II-e), (4′-methyl-[1,1′-biphenyl]-3-yl)(4-methylpiperidin-1-yl)methanone (II-f), (4′-chloro-[1,1′-biphenyl]-3-yl)(4-methylpiperidin-1-yl)methanone (II-g), (3,3-dimethylpiperidin-1-yl)(3′-fluoro-4′-methyl-[1,1′-biphenyl]-3-yl)methanone (II-h), 3′-(4-methylpiperidine-1-carbonyl)-[1,1′-biphenyl]-4-carboxamide (II-i), (3′-hydroxy-[1,1′-biphenyl]-3-yl)(4-methylpiperidin-1-yl)methanone (II-j), and 3′-(4-methylpiperidine-1-carbonyl)-[1,1′-biphenyl]-3-carboxamide (II-k).

9. The cosmetic composition according to claim 1 , wherein the compound of formula (I) is a compound of formula (III):

wherein R 1 and R 3 are independently of each other selected from the group consisting of H, OH, a halogen atom and a C 1 -C 6 alkyl group,
R 2 is a C 1 -C 6 alkyl group, and
R 4 , R 5 , R 6 and R 7 are independently of each H or a C 1 -C 6 alkyl group, with the proviso that at least one of R 4 or R 5 are a C 1 -C 6 alkyl group.

10. The cosmetic composition according claim 9 , wherein the compound of formula (III) is a compound selected from the group consisting of (2,2-dimethylmorpholino) (3′-fluoro-4′-methyl-[1,1′-biphenyl]-3-yl)methanone (III-a), (2,6-dimethylmorpholino) (3′-fluoro-4′-methyl-[1,1′-biphenyl]-3-yl)methanone (III-b) and (2,6-dimethylmorpholino) (4′-methyl-[1,1′-biphenyl]-3-yl)methanone (III-c).

11. The cosmetic composition according to claim 1 , wherein the compound of formula (I) is a compound of formula (IV):

wherein X is CH or N, and
R 1 , R 2 and R 3 are independently of each other selected from the group consisting of H, OH, a halogen atom and a C 1 -C 6 alkyl group,
with the proviso that if X is CH and R 1 and R 3 are H, then R 2 is not a F atom.

12. The cosmetic composition or the compound according claim 11 , wherein the compound of formula (IV) is a compound selected from the group consisting of azepan-1-yl(3′-fluoro-4′-methyl-[1,1′-biphenyl]-3-yl)methanone (IV-a), azepan-1-yl(4′-chloro-[1,1′-biphenyl]-3-yl)methanone (IV-b), azepan-1-yl(4′-methyl-[1,1′-biphenyl]-3-yl)methanone (IV-c), azepan-1-yl(4′-hydroxy-[1,1′-biphenyl]-3-yl)methanone (IV-d), azepan-1-yl(3-(6-methylpyridin-3-yl)phenyl)methanone (IV-e), [1,1′-biphenyl]-3-yl(azepan-1-yl)methanone (IV-f), and azepan-1-yl(3′,4′-dimethyl-[1,1′-biphenyl]-3-yl)methanone (IV-g).

13. The cosmetic composition according to claim 1 , wherein n is 1 or 2.

14. The cosmetic composition according to claim 2 , wherein the compound of formula (I) is present in an amount with a range of 0.0001 to 0.25 wt.-%, based on the total weight of the cosmetic composition.

15. The cosmetic composition according to claim 2 , wherein the compound of formula (I) is present in an amount with a range of 0.0001 to 0.1 wt.-%, based on the total weight of the cosmetic composition.

16. The cosmetic composition according to claim 5 , wherein the C 1 -C 6 alkyl group is a C 1 -C 2 alkyl group.

17. The cosmetic composition according to claim 5 , wherein the C 1 -C 6 alkyl group is a methyl group.

18. A method to smoothen wrinkles and fine lines and/or to decrease volume and depth of wrinkles and fine lines, wherein the method comprises the step of applying to an area of skin affected by wrinkles and fine lines an effective amount of the cosmetic composition according to claim 1 .

19. The method according to claim 18 , wherein the cosmetic composition is applied to the area of skin in an amount of between 0.1 to 3 mg/cm 2 of skin.

20. A method for the treatment of (photo)age-induced skin structure and function defects which comprises applying to an area of skin affected by (photo)age-induced skin structure and function defects an effective amount of the cosmetic composition according to claim 1 .

21. The method according to claim 4 , wherein the cosmetic composition is applied to the area of skin in an amount of between 0.1 to 3 mg/cm 2 of skin.

Assignees

• Dsm Ip Assets Bv

Inventors

• Boudon Stéphanie
• Geotti-Bianchini Piero
• Heidl Marc
• Jackson Eileen
• Schlifke-Poschalko Alexander

Classifications

• A61K8/4906

  with one nitrogen as the only hetero atom · CPC title

• A61K8/49 Primary

  containing heterocyclic compounds · CPC title

• A61Q19/08

  Anti-ageing preparations · CPC title

• C07D223/04

  with only hydrogen atoms, halogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07D401/10 Primary

  linked by a carbon chain containing aromatic rings · CPC title