Biphenyl compound selective agonists of gamma RAR receptors
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.
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 method for exercising a selective agonist activity on the RAR gamma receptor, the method comprising contacting said receptor with an effective amount of a compound of formula (I) as defined by claim 1 .
9. A method for the treatment of acne or psoriasis, the method 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 method for the treatment of acne, the method 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 method for the treatment of psoriasis, the method 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 , said process comprising the following steps:
i) conducting a Suzuki reaction between the compound of formula 1
and the compound of formula 2
to produce the compound of formula 3
ii) etherifying 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) saponifying the ester function of the compound obtained in the preceding step to afford the compound of formula (I).
13. The process for preparing a compound of formula (I) as defined by claim 12 , said process comprising, when the group R is other than H, between steps ii and iv, conducting a step iii) of deprotecting 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 the group consisting of acetyl and dimethyl-tert-butylsilyl.