Selective compounds inhibiting CYP26A1 useful in cosmetic and pharmaceutical compositions

Patent metadata

Field	Value
Publication number	US-9408793-B2
Application number	US-201314417035-A
Country	US
Kind code	B2
Filing date	Jul 23, 2013
Priority date	Jul 23, 2012
Publication date	Aug 9, 2016
Grant date	Aug 9, 2016

Abstract

Compounds or salts thereof are described that correspond to general formula (I) below:

Also described, are pharmaceutical and cosmetic compositions that include these compounds. Methods of using these compounds and compositions for the treatment of pathological conditions are also described.

First claim

The invention claimed is:

1. A compound or a salt thereof of general formula (I) below:

in which:
R1 represents a hydrogen atom or a C 1 -C 3 alkyl;
R2 represents a hydrogen, a C 1 -C 3 alkyl, a fluorine, or a CF 3 radical;
R3 represents a hydrogen, a C 1 -C 3 alkyl, a fluorine, or a CF 3 radical; and
R4 represents a hydrogen, a C 1 -C 3 alkyl, or a CF 3 radical.

2. The compound according to claim 1 , wherein:
R1 is selected from the group consisting of a hydrogen, a methyl and an ethyl;
R2 is selected from the group consisting of a hydrogen, a methyl, a fluorine, or a CF 3 radical;
R3 is selected from the group consisting of a hydrogen, a methyl, a fluorine, or a CF 3 radical; and
R4 is selected from the group consisting of a hydrogen, a methyl, and a CF 3 radical.

3. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoic acid;
4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]-3-trifluoromethylbenzoic acid;
4-[2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]-3-trifluoromethylbenzoic acid;
methyl 4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoate;
ethyl 4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoate;
methyl 4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]-3-trifluoromethyl benzoate;
ethyl 4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]-3-trifluoromethyl benzoate;
2-methyl-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoic acid;
2-fluoro-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoic acid;
4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]-2-trifluoromethyl benzoic acid;
3-methyl-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoic acid;
3-fluoro-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoic acid;
4-[2-(5,5,8,8-tetramethyl-3-trifluoromethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoic acid;
3-methyl-4-[2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoic acid;
2-methyl-4-[2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoic acid;
2,3-dimethyl-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoic acid;
2,3-difluoro-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoic acid; and
methyl 2-methyl-4-[2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoate.

4. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoic acid;
4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]-3-trifluoromethylbenzoic acid; and
4-[2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]-3-trifluoromethylbenzoic acid.

5. The compound according to claim 1 , wherein the compound is 4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-sulphonyl)ethyl]benzoic acid.

6. A composition comprising a compound according to claim 1 , in combination with a solvent or a support.

7. The composition according to claim 6 , l wherein the solvent or support is dermatologically acceptable.

8. The compound according to claim 1 , wherein the compound is formulated for use as a medicament.

9. A method of treating a pathological condition, the method comprising administering an effective amount of the compound according to claim 1 to an individual subject in need thereof, wherein the pathological condition is selected from:
1) common acne, comedonal acne, polymorphic acne, acne rosacea, nodulocystic acne, acne conglobata, senile acne, solar acne, acne medicamentosa or occupational acne;
2) ichthyosis, ichthyosiform conditions, lamellar ichthyosis, Darier's disease, palmoplantar keratodermia, leukoplakia, pityriasis rubra pilaris and leucoplasiform conditions, or cutaneous or mucosal (buccal) lichen;
3) cutaneous, mucosal or ungueal psoriasis, psoriatic arthritis, atopic dermatitis or various forms of eczema;
4) skin disorders caused by exposure to UV radiation for reducing actinic keratoses and pigmentations;
5) any pathological conditions associated with chronological or actinic ageing;
6) common warts, flat warts, molluscum contagiosum and epidermodysplasia verruciformis, or oral or floride papillomatoses;
7) lupus erythematosus, bullous immune diseases or collagen diseases;
8) stigmata of epidermal and/or dermal atrophy induced by local or systemic corticosteroids, or any other form of cutaneous atrophy;
9) healing disorders, treating or repairing stretch marks, or promoting healing;
10) tinea pedis or tinea versicolor;
11) hyperpigmentation, melasma, hypopigmentation or vitiligo;
12) actinic keratoses, Bowen's disease, in-situ carcinomas, keratoacanthoma and skin cancers optionally basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous lymphomas, acute promyelocytic leukaemia, neuroblastomas, acute myeloid leukaemias, prostate cancer or breast cancer.

10. The method according to claim 9 , wherein the pathological condition is selected from the group consisting of acne, ichthyosis, ichthyosiform conditions, palmoplantar hyperkeratosis and psoriasis.

11. A method of treating skin ageing, the method comprising administering an effective amount of the compound of claim 1 to an individual subject in need thereof.

12. The method according to claim 11 , for treating cutaneous atrophy, pigmentation spots, skin dryness, skin roughness, solar elastosis or telangiectasia.

13. A cosmetic method comprising administering an effective amount of the compound of claim 1 to an individual subject in need thereof to maintain and/or stimulate the moisture of the skin, to treat dry skin, to treat ageing of the skin or skin appendages and/or photoageing, to treat pigmentation spots or wrinkles, for reducing ptosis, for improving quality and/or transparency of the skin, for improving or restoring suppleness, elasticity and/or tonicity of the skin, or for firming the skin.

14. The composition according to claim 6 , wherein the composition comprises a dose ranging from 0.000001% to 10% by total weight of the compound relative to the total weight of the composition.

15. The compound according to claim 2 , wherein R1 is a hydrogen.

16. The composition according to claim 14 , wherein the dose ranges from 0.001% to 5% by total weight of the compound relative to the total weight of the composition.

17. The composition of claim 15 , wherein the dose ranges from 0.1% to 3% by total weight of the compound relative to the total weight of the composition.

18. The method of claim 9 , wherein the cutaneous lymphoma is T lymphoma.

Assignees

• Galderma Res & Dev

Inventors

• Boiteau Jean-Guy
• Rivier Michel
• Feraille Gérard
• JOMARD ANDRé

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07C317/44

  having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton · CPC title

• A61Q19/08

  Anti-ageing preparations · CPC title

• A61K8/46 Primary

  containing sulfur (A61K8/44 takes precedence) · CPC title

• A61Q19/02

  for chemically bleaching or whitening the skin · CPC title