EP0487698A1

EP0487698A1 - Novel 2,4-diamino 1,3,5-triazine derivatives and uses thereof for treating and preventing hair loss

Info

Publication number: EP0487698A1
Application number: EP91912033A
Authority: EP
Inventors: Michel Hocquaux; Jacqueline Dumats
Original assignee: LOreal SA
Current assignee: LOreal SA
Priority date: 1990-06-19
Filing date: 1991-06-17
Publication date: 1992-06-03
Also published as: WO1991019701A1; JPH05500819A; CA2064910A1; FR2663327A1; FR2663327B1

Abstract

L'invention est relative à des composés de formule (I) dans laquelle: R désigne un radical alkyle linéaire en C1-C12 pouvant porter un ou plusieurs atomes d'halogène; un radical alkyle ramifié en C3-C12 pouvant porter au moins un atome d'halogène; un radical alcényle en C2-C8; un radical alkyle en C1-C4 portant un noyau aromatique; R' désigne un atome d'hydrogène, un groupement alcoxycarbonyle de formule (a) dans lequel: R1 désigne un radical alkyle en C1-C6; X désigne un atome d'oxygène ou un groupement (b); ainsi que les sels d'addition d'acides cosmétiquement ou pharmaceutiquement acceptables et à leur utilisation dans le traitement de la chute des cheveux.The invention relates to compounds of formula (I) in which: R denotes a linear C1-C12 alkyl radical which can carry one or more halogen atoms; a branched C3-C12 alkyl radical which can carry at least one halogen atom; a C2-C8 alkenyl radical; a C1-C4 alkyl radical bearing an aromatic ring; R 'denotes a hydrogen atom, an alkoxycarbonyl group of formula (a) in which: R1 denotes a C1-C6 alkyl radical; X denotes an oxygen atom or a group (b); as well as cosmetically or pharmaceutically acceptable acid addition salts and their use in the treatment of hair loss.

Description

New derivatives of 2,4-diamino-triazine-1, 3, 5 and their use for the treatment and prevention of hair loss.

The invention relates to new derivatives of 2,4-diamino-triazine-1, 3, 5, to their preparation and to cosmetic or pharmaceutical compositions intended in particular for use in topical application in the treatment and prevention of hair loss. hair and stimulating its regrowth.

The Applicant has discovered that these new derivatives were particularly effective in inducing and stimulating hair growth and in curbing hair loss and that they could be used, in particular, in the treatment of diseases of the scalp, such as alopecia areata, scaling dermatitis. and alopecia.

The subject of the invention is therefore new derivatives of 2,4-diamino-triazine-1, 3, 5 substituted in position 6.

The invention also relates to cosmetic and / or pharmaceutical compositions comprising using these compounds.

Other objects of the invention will appear on reading the description and the examples which follow.

The compounds in accordance with the invention are essentially characterized by the fact that they correspond to formula (I):

in which :

R denotes a linear C ₁ -C ₁₂ alkyl radical which can carry one or more halogen atoms;

a branched C ₃ -C ₁₂ alkyl radical which can carry at least one halogen atom;

a C ₂ -C ₈ alkenyl radical;

a C ₁ -C ₄ alkyl radical bearing an aromatic ring;

R 'denotes a hydrogen atom, an alkoxycarbonyl group of formula:

in which :

R ₁ denotes a C ₁ -C ₆ alkyl radical;

X denotes an oxygen atom or an -OSO ₃ Θ group,

and their cosmetically or pharmaceutically acceptable acid addition salts.

The aromatic ring more particularly denotes a phenyl group; halogen designates in particular fluorine, chlorine or bromine; the alkoxy group preferably has 1 to 6 carbon atoms.

The 2,4-diamino-6 alkoxy-triazine-1,3,5 derivatives of formula (I) can be prepared according to the following reaction scheme:

The triazines of formula (II) for which R ′ denotes a hydrogen atom are known in themselves, in particular by Dudley et al., J. Amer. Chem. Soc. 73, 1951, p.2986, 298R; Contrachs, Banks, J. Amer. Chem. Soc. 67, 1945, p.1946. They can be prepared from 2,4-diamino-chloro-6 triazine-1, 3, 5 (of formula III) which are reacted with an alcoholate of formula , where R has the meaning given above and is an alkaline cation, such as sodium or potassium.

The compounds according to the invention of formula (I) are prepared by oxidation of the triazines of formula (II), for example by means of a perbenzoic acid of formula:

in which Z represents a halogen atom, a C ₁ -C ₄ alkyl or alkoxy group or a nitro group, in a suitable solvent, such as C ₁ -C ₄ alkanols, ethers derived from ethylene glycol, acetone or a mixture of these solvents. Other peracids can also be used to effect this oxidation.

The triazines of formula (II) can also be oxidized by means of magnesium monoperoxyphthalate (MMPP) in an appropriate solvent, such as C ₁ -C ₄ alcohols or a hydroalcoholic mixture.

The triazines of formula (I) for which

R 'denotes an alkoxycarbonyl group, are obtained from the 2,4-diamino-6 alkoxy-6 triazine-1, 3, 5 oxide-3 derivatives described above

Obtaining these derivatives is generally carried out by the action of an excess of chloroformic ester on the corresponding 2,4-diamino derivative by operating in a polar aprotic solvent, such as dichloromethane, in the presence of a tertiary amine. , such as triethylamine or pyridine, at a temperature between 0 and 50 ° C.

When X denotes an oxygen atom, the compounds of formula (I), in accordance with the invention, can coexist in their tautomeric forms of formulas (IA) and (IB) according to the following equilibrium:

Depending on the nature of the environment, one of the tautomeric forms can be predominant over the other.

The compounds of formula (I), in accordance with the invention, can be converted into their cosmetically or pharmaceutically acceptable acid addition salts, such as the salts of sulfuric, hydrochloric, hydrobromic, phosphoric, acetic, benzoic, salicylic acids. , glycolic, succinic, nicotinic, tartaric, maleic, pamoic, methane sulfonic, picric, lactic, etc.

Particularly preferred compounds are diamino-2,4 (n-butyloxy) -6 triazine-1, 3, 5 oxide-3, diamino-2,4 (methyl-6-triazine-1, 3, 5 oxide-3, diamino-2,4 (n-octyloxy) -6 triazine-1, 3, 5 oxide-3, diamino-2,4 (n-hexênyl-5 oxy) -6 triazine-1, 3, 5 oxide-3, 2,4-diamino (2-phenylethyloxy) -6 triazine-1, 3,5 oxide-3, 2,4-diamino isopropyloxy-6 triazine-1, 3,5 oxide-3, diamino hydroxide -2.4 n-butyloxy-6 sulfooxy-3 triazinium, di (ethyloxycarbamoyl) -2, 4 n-butyloxy-6 triazine-1, 3, 5 oxide-3.

The particular compounds in accordance with the invention and corresponding to formula (I) in which X denotes an oxygen atom, obtained according to the methods described above, can be transformed into their O-sulphate counterparts, by chemical sulphation, according to the classic methods described in the literature (J. Med. Chem. 1983, 26, p. 1791-1793).

The sulfur trioxide-pyridine, sulfur trioxide-triethylamine or sulfur trioxide-ethyl diisopropylamine complexes are used as the sulfation reagent.

The solvents used are preferably dimethylformamide, acetonitrile, chloroform or their binary mixtures. The temperature is of the order of 0 to 25ºC and the reaction time varies between 1 hour and 24 hours.

An advantage of these derivatives is a very weak antihypertensive activity (lower than that of Minoxidil).

The compositions in accordance with the invention contain, in a physiologically acceptable medium, at least one compound corresponding to formula (I) or one of its addition salts with physiologically acceptable acids, with a view to being applied in the cosmetic field or pharmaceutical, especially in topical application.

These compositions are intended for the treatment and prevention of hair loss and in particular of alopecia, alopecia as well as desquamating dermatitis.

These compositions may comprise, as physiologically acceptable medium, any medium suitable for topical application, either in cosmetics or in pharmacy, and which is compatible with the active substance.

The compounds according to the invention can be found in this medium, either in the dissolved state or in the dispersed state, in particular in micronized form.

The compositions intended for use in pharmacy are in the form of an ointment, a tincture, a cream, an ointment, a powder, a patch, a soaked tampon, a solution, an emulsion or a vesicular emulsion, a lotion, gel, spray or suspension. They can be either anhydrous or aqueous, depending on the clinical indication.

The compounds according to the invention are present in these pharmaceutical compositions at concentrations of between 0.1 and 10% by weight, and in particular of between 0.2 and 5% by weight.

The cosmetic compositions are in particular intended to be used in the form of a lotion, gel, soap, shampoo, aerosol or foam and contain, in a cosmetically acceptable carrier, at least one compound of formula (I) or the one of its acid addition salts.

The concentration of the compounds of formula (I) in these compositions is preferably between 0.01 and 5% by weight and in particular between 0.05 and 3% by weight.

The compositions in accordance with the invention may contain various additives usually used in cosmetics or in pharmacy and in particular active substances, such as hydrating agents such as thiamorpholine and its derivatives or urea; antiseborrhoeic agents such as S-carboxymethylcysteine, S-benzylcysteamine and their derivatives; thioxolone.

The compounds according to the invention can be combined with compounds which further improve their activity on regrowth and / or on the braking of hair loss, such as more particularly the following compounds:

- Nicotinic acid esters, including more particularly C ₁ -C ₆ alkyl nicotinates and in particular methyl nicotinate;

- steroidal and nonsteroidal anti-inflammatory agents well known in the state of the art and in particular hydrocortisone, its salts and derivatives, niflumic acid;

- the retinoids and more particularly the t-trans retinoic acid also called tretinoin, isotretinoin, retinol or vitamin A and its derivatives, such as acetate, palmitate or propionate, motretinide, etretinate, t-trans zinc retinoate;

- antibacterial agents chosen more particularly from macrolides, pyranosides and tetracyclines and in particular erythromycin;

- calcium antagonist agents, such as more particularly cinnarizine and diltiazem;

- hormones, such as estriol or analogues or thyroxine and its salts;

- antiandrogenic agents, such as oxendolone, spironolactone, diethylstilbestrol;

- OH radical scavengers, such as dimethylsulfoxide.

It is also possible to combine with the compounds of the invention, optionally in admixture with the others, compounds such as the diazoxide corresponding to methyl-3-chloro-7 2H-benzothiadiazine 1,2,4-dioxide1,1; spiroxazone or 7- (acetylthio) -4 ', 5'-dihydrospiro [androst 4-ene-17.2' - (3'H) furan] -3 one; phospholipids, such as lecithin; linoleic and linolenic acids; salicylic acid and its derivatives described more particularly in French patent 2,581,542, such as salicylic acid derivatives carrying an alkanoyl group having 2 to 12 carbon atoms in position 5 of the benzene ring; hydroxycarboxylic or ketocarboxylic acids and their esters, lactones and their corresponding salts; anthralin or trihydroxy-1,8,9 anthracene, carotenoids, eicosatetraynoic acids-5, 8, 11, 14 or eicosatriynoic-5, 8, 11, their esters and amides.

The compounds in accordance with the invention can also be combined with surfactants, more particularly those chosen from nonionic and amphoteric surfactants.

Among the nonionic surfactants, mention will be made in particular of the polyhydroxypropyl ethers described in French patents No. 1,477,048; 2,091,516; 2,169,787; 2,328,763; 2,574,786; oxyethylenated (C ₈ -C ₉ ) alkyl phenols containing from 1 to 100 moles of ethylene oxide and preferably 5 to 35 moles of ethylene oxide; the alkylpolyglycosides of formula:

C _n H _{2n + 1} (C ₆ H ₁₀ O ₅ ) _x H (A) in which n varies from 8 to 15 inclusive and x from 1 to 10 inclusive.

Among the amphoteric surfactants, are more particularly the amphocarboxyglycinates and amphocarboxypropionates defined in the CTFA dictionary, 3rd edition, 1982, and sold in particular under the name Miranol ^® by the company Miranol.

The compounds according to the invention can be introduced into carriers which further improve the activity at the regrowth level, while having both advantageous properties from a cosmetic point of view, such as volatile ternary mixtures of alkyl ether. alkylene, especially alkyl in C ₁ -C ₄ alkylene, C ₁ -C ₄ glycol or of dialkylene glycol, preferably dialkylene C ₁ -C ₄ glycol, ethyl alcohol and water , the glycolic solvent designating more particularly the monoethyl ethers of ethylene glycol, the monomethyl ether of propylene glycol, the monoethyl ether of diethylene glycol.

The compounds in accordance with the invention can also be introduced into gelled or thickened supports, such as essentially aqueous supports gelled with heterobiopolysaccharides, such as xanthan gum or cellulose derivatives, hydroalcoholic supports gelled with polyhydroxy ethylacrylate or methacrylate or essentially aqueous supports thickened, in particular by polyacrylic acids crosslinked with a polyfunctional agent, such as Carbopol sold by the company GOODRICH.

These compositions may also contain preserving agents, stabilizing agents, pH regulating agents, agents modifying osmotic pressure, emulsifying agents, UVA and UVB filters, antioxidant agents such as α-tocopherol, butylhydroxyanisole, butylhydroxytoluene.

The physiologically acceptable medium can consist of water or a mixture of water and a solvent or a mixture of solvents, the solvents being chosen from organic solvents acceptable from the cosmetic or pharmaceutical point of view and chosen more particularly from lower C ₁ -C ₄ alcohols, such as ethyl alcohol, isopropyl alcohol, tert-butyl alcohol, alkylene glycols, alkylene glycol and dialkylene glycol alkyl ethers, such as ethylene glycol monoethyl ether, propylene glycol monomethyl ether, diethylene glycol monoethyl ether. The solvents, when they are present, are present in proportions of between 1 and 80% by weight relative to the total weight of the composition.

Physiologically acceptable media can be thickened using thickening agents usually used in cosmetics or pharmacy, and there may be mentioned more particularly heterobiopolysaccharides such as xanthan gum, scleroglucans, cellulose derivatives such as cellulose ethers, acrylic polymers, crosslinked or not.

The thickeners are preferably present in proportions of between 0.1 and 5% by weight and in particular between 0.4 and 3% by weight relative to the total weight of the composition.

The subject of the invention is also a method of cosmetic treatment of the hair or the scalp, consisting in applying to them at least one composition as defined above, with a view to improving the aesthetics of the hair.

Another subject of the invention consists of the use of the composition containing the compounds of formula (I) defined above, for the preparation of a medicament having the effect of inducing or stimulating hair growth and to stop their fall.

The treatment consists mainly in applying to the alopecic areas of the scalp of an individual, the composition as defined above.

The preferred mode of application consists in applying 1 to 2 g of the composition to the alopecic zone, at a frequency of one to two applications per day, for 1 to 7 days per week and this for a period of 1 to 6 months.

The compositions can in particular be used in the treatment of alopecia areata, hair loss, flaking dermatitis.

The following examples are intended to illustrate the invention without, however, being limiting in nature.

PREPARATION EXAMPLES

EXAMPLE 1 2,4-Diamino-6-n-butyloxy-triazine-1,3,5 oxide-3.

PART A: Diamino-2,4 n-butyloxy-6 triazine-1,3,5.

4.3 g of sodium are dissolved in 250 ml of n-butanol.

125 ml of diglyme and 25 g of 2,4-diamino-chloro-6 triazine-1, 3, 5 are added.

The mixture is heated for 24 hours at 45 ° C., then the mixture is brought to dryness.

Precipitation is carried out by adding water, the precipitate obtained is filtered and washed with water.

Recrystallized from an ethanol and water mixture.

25 g of diamino-2,4 n-butyloxy-6 triazine-1, 3, 5 are obtained.

Yield = 80%

F = 180 ° C

Elementary analysis for C ₇ H ₁₃ N ₅ O; M = 183

C H N O

Calculated 45.9 7.1 38.25 8.75

Found 46.01 7.04 38.23 8.85 The 13c NMR spectrum is in agreement with the expected structure. PART B: Diamino-2,4 n-butyloxy-6 triazine-1,3,5 oxide-3.

47 g of 2,4-diamino-6-n-butyloxy-triazine-1, 3, 5 are mixed in 700 ml of absolute ethanol and 700 ml of ethylene glycol monomethyl ether.

160 g of 55% m-chloroperbenzoic acid are added at 15ºC.

Stirred at room temperature for 24 hours, then the mixture is dried.

250 ml of water acidified with concentrated hydrochloric acid are added.

The precipitate obtained is filtered.

The mother liquors are basified with soda. The precipitate obtained is filtered.

It is recrystallized from a mixture of water and methanol.

6.3 g of diamino-2,4 n-butyloxy-6 triazine-1,3,5 oxide-3 are obtained.

Yield = 12%

P = 197ºC

Elementary analysis for C ₇ H ₁₃ N ₅ O ₂ ; M = 199

C H N O

Calculated 42, 21 6, 53 35, 17 16, 1

Found 42, 22 6, 60 35, 28 16, 37

The 13 _C NMR and mass spectra are in agreement with the expected structure. EXAMPLE 2

Diamino-2,4-methyloxy-6 triazine-1,3,5 oxide-3. According to the procedure described in the example

1.

PART A: Diamino-2,4-methyloxy-6 triazine-1,3,5. In the presence of sodium methylate

Time = 24 hours t ° = 45 ° C

Recrystallization: ethanol and water mixture Yield = 51.5%.

Mp 265 ° C.

PART B: 2,4-Diamino-6-methyloxy-triazine-1, 3, 5

oxide-3.

Time = 24 hours t ° = 25ºC

Recrystallization: methanol and water mixture

Yield = 13.5%

M> 265 ° C.

Elementary analysis for C ₄ H ₇ N ₅ O ₂ ; M = 157

C H N O

Calculated 30.57 4.46 44.59 20.38

Found 30.34 4.40 44.50 20.47 The 1 H and 13 _C NMR and NMR spectra are in agreement with the expected structure. EXAMPLE 3

Diamino-2,4 isopropyloxy-6 triazine-1,3,5 oxide-3. According to the procedure described in Example 1.

PART A: Diamino-2,4-isopropyloxy-6 triazine-1,3,5. In the presence of Na isopropylate

Time = 24 hours tº = 25 ° C

Recrystallization: mixture of acetone and water Yield = 54%

F = 173ºC.

PART B: 2,4-Diamino-6-isopropyloxy-triazine-1, 3, 5

oxide-3.

Time = 24 hours tº = 25 ° C

Recrystallization: acetone and water mixture

Yield = 40%

M> 265 ° C.

Elementary analysis for C ₆ H ₁₁ N ₅ O ₂ 185

C H N O

Calculated 38.92 5.95 37.84 17.30

Found 38.79 5.96 37.84 17.49 The ¹ H NMR and mass spectra are in agreement with the expected structure. EXAMPLE 4

Diamino-2,4 (n-hexenyl-5-oxy) -6 triazine-1,3,5 oxide-3. According to the procedure described in Example 1.

PART A: Diamino-2,4 (n-hexenyl-5-oxy) -6 triazine- 1,3,5.

In the presence of 5-hexene-1-ol in the form of Na alcoholate

Time = 24 hours- t ° = 45ºC

Recrystallization from a mixture of water and methanol

Yield = 48%

Mp 140 ° C.

PART B: Diamino-2,4 (n-hexenyl-5-oxy) -6 triazine- 1,3,5 oxide-3.

Time = 24 hours t ° = 25 ° C

Recrystallization: mixture of water and methanol Yield = 9%

F = 180 ° C

Elementary analysis for C ₉ H ₁₅ N ₅ O ₂ ; M = 225

C H N O

Calculated 48 6.67 31.11 14, 22

Found 48.11 6.77 31.10 14.33

The 13 _C and 1 H NMR and mass spectra are in agreement with the expected structure. EXAMPLE 5

Diamino-2,4 (n-octyloxy) -6 triazine-1,3,5 oxide-3. According to the procedure described in Example 1.

PART A: Diamino-2,4 (n-octyloxy) -6 triazine-1,3,5. In the presence of n-octanol in the form of Na alcoholate

Time = 24 hours t ° = 45 ° C

Purified by precipitation: ether and petroleum ether

Yield = 60%

Mp 125 ° C.

PART B: Diamino-2,4 (n-octyloxy) -6 triazine-1,3,5

oxide-3.

Time = 24 hours tº = 25ºC

Recrystallization: mixture of acetone and

methanol

Yield = 15.5%

Mp 196 ° C.

Elementary analysis for C ₁₁ H ₂₁ N ₅ O ₂ ; 0.2 H ₂ O; M = 255

C H N O

Calculated 51, 04 8.27 27.07 13.61

Found 51.00 8.27 27.02 13.47

The 1H and 13 _C NMR and mass spectra are in agreement with the expected structure. EXAMPLE 6

Diamino-2,4 (phenyl 2-ethyloxy) -6 triazine-1,3,5 oxide-3 According to the procedure described in Example 1.

PART A: Diamino-2,4 (phenyl 2-ethyloxy) -6 triazine- 1,3,5.

In the presence of sodium phenylethyl-2 alcoholate

Time = 24 hours. t ° = 45 ° C

Purified by precipitation: ether and petroleum ether

Yield = 71%

Mp 172 ° C.

PART B: Diamino-2,4 (phenyl 2-ethyloxy) -6 triazine- 1,3,5 oxide-3.

Time = 24 hours t ° = 25 ° C

Recrystallization from methanol

Yield = 15.5%

F> 265ºC.

Elementary analysis for C ₁₁ H ₁₃ N ₅ O ₂ ; M = 247

C H N O

Calculated 53.44 5.26 28.34 12.95

Found 53.21 5.31 28.30 13.01

The 1H, 13 _C NMR and mass spectra are in agreement with the expected structure. EXAMPLE 7

Internal salt of 2,4-diamino-6-n-butyloxy-3-sulfooxy-triazinium hydroxide.

To a solution of 0.75 ml (0.0044 m) of N, N'-diisopropylethylamine in 10 ml of ice-cold chloroform is added with stirring, 0.132 ml (0.002 m) of chlorosulfonic acid. After waiting for 30 minutes, 0.199 g of 2,4-diamino-butyloxy-6, triazine-1,3,5 oxide-3, prepared according to Example 1, is added and the mixture is kept for 1 hour 30 minutes at 0-5 ° C. argon. The white precipitate which has appeared is filtered. Washed with ice water and 0.11 g of internal salt is obtained after drying.

The yield is 39.4%.

Mass spectrum: conforms to structure

expected.

EXAMPLE 8

Di (ethyloxycarbamoyl) -2.4 n-butyloxy-6 triazine-1,3,5oxide-3.

1 g of 2,4-diamino (n-butyloxy) -6 triazine-1,3,5 oxide-3 is placed in suspension in 20 ml of dried dichloromethane on a sieve.

2 g of triethylamine are added over KOH. After cooling to 0 ° C., 2.2 g of ethyl chloroformate are added.

The mixture is stirred for 1 hour at room temperature.

After adding 10 ml of methanol to the reaction medium, the organic phase is extracted with:

10 ml hydrochloric acid 1%

10 ml sodium carbonate 5%

20 ml water.

The organic phase is dried over sodium sulfate, then evaporated to dryness.

The precipitate obtained is recrystallized from a 1/1 hexane / acetone mixture.

Yield = 47%

F = 134 ° C

Elementary analysis for C ₁₃ H ₂₁ N ₅ O ₆ ; M = 343

1 C H Nr O

Calculated 45, 48 6, 12 20, 41 27, 99

Found 45, 47 6, 20 20, 31 28, 02

The 1H NMR and mass spectra are in accordance with the expected structure. COMPOSITION EXAMPLE 1 The following composition is prepared:

- 2,4-Diamino-butyloxy-6

triazine-1,3,5 oxide-3 2,0 g

- Propyleneglycol 6.45 g

98.0 g

Absolute ethyl alcohol qs 100.0 g

This composition is in the form of a lotion.

1 to 2 g of this composition are applied to the alopecic areas of the scalp, possibly accompanied by a massage to promote its penetration, at the rate of one to two applications per day, for three months of treatment.

EXAMPLE OF COMPOSIT ON 2

We prepare the following composition

- 2,4-Diamino-butyloxy-6

triazine-1,3,5 oxide-3 3,0 g - Propyleneglycol 22,8 g

97.0 g

Ethyl alcohol 55.1 g

Water qs 100.0 g This composition is in the form of a lotion. COMPOSITION EXAMPLE 3

A lotion of the following composition is prepared

Diamino-2,4 n-butyloxy-6

triazine-1,3,5 oxide-3 8,0 Ethyl alcohol 80 g

92.0 g

Water qs 100 g

COMPOSITION EXAMPLE 4

A lotion of the following composition is prepared

Diamino-2,4 n-butyloxy-6

triazine-1,3,5 oxide-3 7.0 Ethyl alcohol 50 g

93.0 g

Water qs 100 g

1 to 2 ml of these lotions are applied to the alopecic areas of the scalp; these applications, possibly accompanied by a massage to promote penetration, being carried out once or twice a day.

Claims

1. Compound characterized by the fact that it corresponds to the formula:

in which :

a C ₂ -C ₈ alkenyl radical;

a C ₁ -C ₄ alkyl radical bearing an aromatic ring;

R 'denotes a hydrogen atom, an alkoxycarbonyl group of formula:

in which :

R ₁ denotes a C ₁ -C ₆ alkyl radical;

X denotes an oxygen atom or an -OSO ₃ Θ group;

as well as the cosmetically or pharmaceutically acceptable acid addition salts.

2. Compound according to claim 1, characterized in that it is chosen from 2,4-diamino (n-butyloxy) -6 triazine-1,3,5 oxide-3, 2,4-diamino methyloxy- 6 triazine-1,3,5 oxide-3, diamino-2,4 (n-octyloxy) -6 triazine-1,3,5 oxide-3, diamino-2,4 (n-hexenyl-5 oxy) -6 triazine-1,3,5 oxide-3, 2,4-diamino (2-phenylethyloxy) -6 triazine-1,3,5 oxide-3, 2,4-diamino isopropyloxy-6 triazine-1,3,5 oxide-3, diamino hydroxide -2.4 n-butyloxy-6 sulfooxy-3 triazinium, di (ethyloxycarbamoyl) -2, 4 n-butyloxy-6 triazine-1,3,5 oxide-3, and their cosmetically or acid addition salts pharmaceutically acceptable.

3. Composition intended for use in topical application, characterized in that it contains in a physiologically acceptable medium, at least one compound as defined in any one of claims 1 or 2.

4. Composition according to claim 3, characterized in that it is in the form of ointment, tincture, cream, ointment, powder, patch, soaked tampon, solution, emulsion or d vesicular emulsion, lotion, gel, spray or anhydrous or aqueous suspension, for its pharmaceutical application and that it contains at least one compound as defined in claim 1 or 2.

5. Composition according to claim 3 or 4, characterized in that the compounds of formula (I) are present in concentrations of between 0.1 and 10% by weight, and in particular between 0.2 and 5% by weight relative to the total weight of the composition.

6. Composition intended for use in cosmetics, as defined in claim 3, characterized in that it is in the form of a lotion, gel, soap, shampoo, aerosol or foam and that it contains, in a cosmetically acceptable carrier, at least one compound as defined in any one of claims 1 to 2, in concentrations of between 0.01 and 5% by weight and in particular between 0.05 and 3% by weight.

7. Composition according to any one of claims 3 to 6, characterized in that it additionally contains hydrating agents or antiseborrhoeic agents.

8. Composition according to any one of claims 3 to 7, characterized in that it also contains agents further improving their activity on regrowth and / or on the braking of hair loss.

9. Composition according to Claim 8, characterized in that it contains, as agents further improving the activity of regrowth and / or of braking hair loss, nicotinic acid esters, anti agents -insteroidal or non-steroidal inflammatory, retinoids, antibacterial agents, calcium antagonists, hormones, antiandrogenic agents, OH radical scavengers.

10. Composition according to claim 8, characterized in that it contains, as compounds further improving the activity on hair regrowth and / or the braking of hair loss, compounds of formula (I), compounds chosen from diazoxide, spiroxazone, phospholipids, linoleic and linolenic acids, salicylic acid and its derivatives, hydroxycarboxylic or betocarboxylic acids and their esters, lactones and their corresponding salts, anthralin or trihydroxy1,8 , 9 anthracene, carotenoids, eicosatetraynoic acids-5, 8,11,14, eicosatriynoic-5, 8,11, their esters and amides.

11. Composition according to any one of claims 3 to 10, characterized in that the physiologically acceptable medium consists of water, a mixture of water and one or more solvents organic or by a mixture of non-aqueous organic solvents, the organic solvents being pharmaceutically and cosmetically acceptable.

12. Composition according to Claim 11, characterized in that the organic solvents are chosen from C ₁ -C ₄ lower alcohols, alkylene glycols, mono and dialkylene glycol alkyl ethers.

13. Composition according to any one of claims 3 to 12, characterized in that the physiologically acceptable medium is thickened by means of thickening and / or gelling agents and contains preserving agents, stabilizing agents, pH regulating agents , osmotic pressure modifying agents, emulsifying agents, UVA and UVB filters, antioxidant agents.

14. Composition according to any one of claims 3 to 13, characterized in that it also contains surfactants chosen from nonionic and amphoteric surfactants.

15. Composition according to any one of claims 3 to 14, for its application as a medicament intended for use in the therapeutic treatment of hair loss.

16. Cosmetic treatment process for the hair or scalp, characterized in that the composition as defined in any one of Claims 3 to 14 is applied.

17. Use of the composition as defined in any one of claims 3 to 14, for the preparation of a medicament intended to be used for the therapeutic treatment of hair loss.