Biphenyl compound selective agonists of gamma RAR receptors

• US 20090023811A1
• Filed: 06/16/2008
• Published: 01/22/2009
• Est. Priority Date: 12/15/2005
• Status: Active Grant

• Current Assignee: Galderma Research And Development Snc (Galderma Holding SA)
• Original Assignee: Galderma Research And Development Snc (Galderma Holding SA)
• Inventors: Thoreau, Etienne, Biadatti, Thibaud
• Granted Patent: US 8,049,034 B2
• Time in Patent Office: Days
• US Class Current: 514/569
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07C 51/09 from carboxylic acid esters or lactones
• CPC Class Codes: C07C 65/26 containing rings other than six-membered aromatic rings

Abstract

Biphenyl compounds having the formula (I):

are useful for preventing/treating pathologies linked to a deficiency of the activation of the RAR gamma receptor, e.g., for treating a pathology linked to a cell differentiation and/or proliferation disorder, for treating acne, for treating psoriasis.

Claims

1. A biphenyl compound of formula (I)

in which n is an integer ranging from 1 to 3 inclusive, or salt thereof.

2. A compound as defined by claim 1, the same being 4′

-(3-hydroxypropoxy)-3′

-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)biphenyl-4-carboxylic acid.

3. A compound as defined by claim 1, the same being 4′

-(4-hydroxybutoxy)-3′

-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)biphenyl-4-carboxylic acid.

4. A medicament comprising a compound as defined by claim 1.

5. A pharmaceutical or cosmetic composition, which comprises, formulated into a pharmaceutically or cosmetically acceptable carrier, at least one compound of formula (I) as defined by claim 1.

6. The pharmaceutical or cosmetic composition as defined by claim 5, formulated for topical administration.

7. The pharmaceutical or cosmetic composition as defined by claim 5, wherein the amount of compound of formula (I) ranges from 0.001% to 3% by weight, relative to the total weight thereof.

8. A regime or regimen for the prevention and/or treatment of pathologies linked to a deficiency of the activation of the RAR gamma receptor, comprising administering to an individual in need of such treatment, a thus effective amount of a compound of formula (I) as defined by claim 1.

9. A regime or regimen for the treatment of a pathology linked to a cell differentiation and/or proliferation disorder, comprising administering to an individual in need of such treatment, a thus effective amount of a compound of formula (I) as defined by claim 1.

10. A regime or regimen for the treatment of acne, comprising administering to an individual in need of such treatment, a thus effective amount of a compound of formula (I) as defined by claim 1.

11. A regime or regimen for the treatment of psoriasis, comprising administering to an individual in need of such treatment, a thus effective amount of a compound of formula (I) as defined by claim 1.

12. A process for preparing a compound of formula (I) as defined by claim 1, comprising the following steps:

i) Suzuki reaction from the compound of formula 1

and the compound of formula 2

to produce the compound of formula 3

ii) etherification of the compound of formula 3 with the compound of formula 4

in which X represents a leaving group permitting a nucleophilic substitution, R represents a hydrogen or a protective group, and n is an integer ranging from 1 to 3, to produce the compound of formula 5

iv) saponification of the ester function of the compound obtained in the preceding step.

13. The process for preparing a compound of formula (I) as defined by claim 12, wherein it comprises, from steps ii) and iv), in the event that the group R is other than H, a step iii) for deprotection of the alcohol function of the compound of formula 5, to produce the compound of formula 6:

14. The process as defined by claim 12, wherein X is a halogen.

15. The process as defined by claim 12, wherein R is a protective group selected from acetyl and dimethyl-tert-butylsilyl.