Pyrimidine 3-oxide compounds for inducing/stimulating hair growth and/or retarding hair loss

• US 20010044444A1
• Filed: 06/06/2001
• Published: 11/22/2001
• Est. Priority Date: 07/24/1998
• Status: Active Grant

• Current Assignee: Jean-Baptiste Galey, Jean-Francois Michelet, Patrick Pichaud, Yann Mahe
• Original Assignee: Jean-Baptiste Galey, Jean-Francois Michelet, Patrick Pichaud, Yann Mahe
• Inventors: Mahe, Yann, Michelet, Jean-Francois, Pichaud, Patrick, Galey, Jean-Baptiste
• Granted Patent: US 6,511,659 B2
• Time in Patent Office: Days
• US Class Current: 514/269
• CPC Class Codes: A61K 8/4953 containing pyrimidine ring derivatives, e.g. minoxidil
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61Q 7/00 Preparations for affecting hair growth
• CPC Class Codes: C07D 239/48 Two nitrogen atoms

Abstract

Hair growth-/hair loss-affecting cosmetic/therapeutic compositions contain an effective amount of at least one 2-amino-4-alkylaminopyrimidine 3-oxide having the structural formula (I):

in which R₁ is an alkyl radical having from 5 to 20 carbon atoms, and Z is either a hydrogen atom or a radical —OR₂, wherein R₂ is an alkyl radical having from 1 to 12 carbon atoms, or an acyl derivative or acid addition salt thereof.

Claims

1. A 2-amino-4-alkylaminopyrimidine 3-oxide compound having the structural formula (I):

2. The compound as defined by

claim 1

, wherein formula (I), R₁ is an alkyl radical having from 6 to 12 carbon atoms.

3. A compound as defined by

claim 1

, wherein formula (I), Z is a radical —

OR₂ and R₂ is an alkyl radical having from 1 to 12 carbon atoms.

4. A compound as defined by

claim 1

, selected from among:

2-amino-4-pentylaminopyrimidine 3-oxide;

2-amino-4-hexylaminopyrimidine 3-oxide;

2-amino-4-heptylaminopyrimidine 3-oxide;

2-amino-4-octylaminopyrimidine 3-oxide;

2-amino-4-nonylaminopyrimidine 3-oxide;

2-amino-4-decylaminopyrimidine 3-oxide;

2-amino-4-undecylaminopyrimidine 3-oxide;

2-amino-4-dodecylaminopyrimidine 3-oxide;

2-amino-4-tridecylaminopyrimidine 3-oxide;

2-amino-4-tetradecylaminopyrimidine 3-oxide;

2-amino-4-pentadecylaminopyrimidine 3-oxide;

2-amino-4-hexadecylaminopyrimidine 3-oxide;

2-amino-4-heptadecylaminopyrimidine 3-oxide;

2-amino-4-octadecylaminopyrimidine 3-oxide;

2-amino-4-nonadecylaminopyrimidine 3-oxide;

2-amino-4-eicosadecylaminopyrimidine 3-oxide;

2-amino-4-pentylamino-6-methoxypyrieidine 3-oxide;

2-amino-4—

hexylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-heptylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-octylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-nonylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-decylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-undecylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-dodecylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-tridecylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-tetradecylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-pentadecylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-hexadecylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-heptadecylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-octadecylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-nonadecylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-eicosadecylamino-6-methoxypyrimidine 3-oxide;

2-amino-4-pentylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-hexylamino-6-ethoxypyri-oidine 3-oxide;

2-amino-4-heptylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-octylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-nonylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-decylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-undecylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-dodecylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-tridecylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-tetradecylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-pentadecylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-hexadecylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-heptadecylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-octadecylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-nonadecylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-eicosadecylamino-6-ethoxypyrimidine 3-oxide;

2-amino-4-pentylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-hexylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-heptylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-octylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-nonylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-decylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-undecylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-dodecylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-tridecylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-tetradecylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-pentadecylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-hexadecylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-heptadecy.amino-6-propyloxypyrimidine 3-oxide;

2-amino-4-octadecylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-nonadecylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-eicosadecylamino-6-propyloxypyrimidine 3-oxide;

2-amino-4-pentylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-hexylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-heptylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-octylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-nonylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-decylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-undecylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-dodecylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-tridecylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-tetradecylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-pentadecylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-hexadecylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-heptadecylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-octadecylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-nonadecylamino-6-butyloxypyrimidine 3-oxide;

2-amino-4-eicosadecylamino-6-butyloxypyrimidine 3-oxide;

and the branched isomers thereof.

5. A compound as defined by

claim 4

, selected from among

2-amino-4-hexylaminopyrimidine 3-oxide;

2-amino-4-octylaminopyrimidine 3-oxide;

2-amino-4-dodecylaminopyrimidine 3-oxide; and

2-amino-4-octylamino-6-butyloxypyrimidine 3-oxide.

6. A compound as defined by

claim 5

, comprising 2-amino-4-dodecylaminopyrimidine 3-oxide or 2-amino-4-octylamino-6-butyloxypyrimidine 3-oxide.

7. A process for the preparation of the 2-amino-4-alkylaminopyrimidine 3-oxide compound of formula (I) as defined by

claim 1

, comprising reacting an aliphatic amine with 2-amino-4,6-dichloropyrimidine in a solvent medium, next reacting the compound thus obtained with a urea/H₂O₂ complex and phthalic anhydride, also in a solvent medium, and thence reacting the compound obtained, in the presence of potassium hydroxide and palladium-on-charcoal, in a solvent medium under a high hydrogen pressure.

8. A process for the preparation of the 2-amino-4-alkylamino-6-alkyloxypyrimidine 3-oxide compound of formula (I) as defined by

claim 1

, comprising reacting an aliphatic amine with 2-amino-4,6-dichloropyrimidine in a solvent medium, next reacting the compound thus obtained with a urea/H₂O₂ complex and phthalic anhydride in the presence of isopropanol, and thence reacting the compound obtained with an excess of sodium alkoxide to provide the corresponding 2-amino-4-alkylamino-6-alkyloxypyrimidine 3-oxide.

9. A hair growth-/hair loss-affecting cosmetic/therapeutic composition of matter, comprising a hair growth stimulating and/or hair loss retarding effective amount of at least one 2-amino-4-alkylamino-6-alkyloxypyrimidine 3-oxide compound of formula (I), as defined in

claim 1

, formulated into a physiologically acceptable vehicle, diluent or carrier therefor.

10. The cosmetic/therapeutic composition as defined by

claim 9

, comprising from 0.001% to 10% by weight of said at least one 2-amino-4-alkylamino-6-alkyloxypyrimidine 3-oxide compound of formula (I).

11. The cosmetic/therapeutic composition as defined by

claim 10

, comprising from 0.01% to 2% by weight of said at least one 2-amino-4-alkylamino-6-alkyloxypyrimidine 3-oxide compound of formula (I).

12. The cosmetic/therapeutic composition as defined by

claim 9

, further comprising effective amount(s) of at least one antibacterial agent, antiparasitic agent, antifungal agent, antiviral agents, anti-inflammatory agent, antipruriginous agent, anaesthetics, keratolytic agent, anti-free-radical agent, antiseborrhoeic agent, antidandruff agent, antiacne agent and/or agent for reducing skin differentiation and/or proliferation and/or pigmentation, extract of plant, marine or bacterial origin, or mixture thereof.

13. The cosmetic/therapeutic composition as defined by

claim 12

, comprising an effective amount of at least one of an imidazole antifungal agent, or the antifungal agent ketoconazole.

14. The cosmetic/therapeutic composition as defined by

claim 9

, adopted for topical application.

15. The cosmetic/therapeutic composition as defined by

claim 9

, adopted for oral administration.

16. The cosmetic/therapeutic composition as defined by

claim 9

, adopted for systemic administration.

17. The cosmetic/therapeutic composition as defined by

claim 9

, further comprising at least one hydrophilic or lipophilic gelling agent, hydrophilic or lipophilic active agent, preservative, antioxidant, solvent, fragrance, filler, sunscreen, odor absorber, dyestuff, colorant, or mixture thereof.

18. The cosmetic/therapeutic composition as defined by

claim 9

, comprising an aqueous or oily solution, dispersion, lotion, serum, syrup, ointment, emulsion, suspension, cream, gel, mousse, spray, soap, or bar.

19. The cosmetic/therapeutic composition as defined by

claim 9

, comprising microcapsules, microparticles, a vesicle dispersion, capsules, granules, or tablets.

20. The cosmetic/therapeutic composition as defined by

claim 9

, comprising a shampoo, hairsetting lotion, hairstyling cream or gel hair restructuring lotion, or permanent-wave formulation.

21. A regime or regimen for inducing or stimulating the growth of hair or limiting the loss of hair on an individual subject in need of such treatment, comprising administering thereto, for such period of time as required to elicit the desired response, an effective amount of at least one 2-amino-4-alkylamino-6-alkyloxypyrimidine 3-oxide compound of formula (I) as defined by

claim 1

, or cosmetic/therapeutic composition comprised thereof.

22. The regime or regimen as defined by

claim 21

, comprising topically applying said at least one compound of formula (I), or composition comprised thereof, onto the head and/or hair of said individual subject in need of such treatment.