LU86388A1 - NOVEL CHROMANE AND THIOCHROMANE DERIVATIVES, PREPARATION METHOD THEREOF, AND MEDICINAL AND COSMETIC COMPOSITIONS CONTAINING THEM - Google Patents

Description

"'* * NEW DERIVATIVES OF CHROMANE AND THIOCHROMANE, THEIR PREPARATION PROCESS AND MEDICINAL COMPOSITIONS h AND COSMETICS CONTAINING THEM -

The present invention relates to new chemical compounds composed of derivatives of chroman and thiochroman, as well as the preparation process making it possible to obtain these new compounds. The present invention also relates to the use of these new compounds either in cosmetics, or in human and veterinary medicine, as pharmaceutical preparations, in particular in the treatment of dermatological conditions linked to a disorder of keratinization (differentiation, proliferation: tion), in the treatment of dermatological, or other, inflammatory and / or immunoallergic conditions, in the treatment of certain rheumatic-like diseases such as rheumatoid psoriasis, in the treatment of cutaneous atopy or respiratory, degenerative diseases of connective tissue and tumors, as well as in ophthalmology, especially in the treatment of corneopathies.

The therapeutic action of vitamin A in its acid, aldehyde or alcohol form is well known in dermatology (see, in this regard, the publication "EXPERIENTIA", volume 34, pages 1105-1119 (1978)); this action in the treatment of cutaneous proliferations, acne, psoriasis and similar affections will be designated hereinafter by the generic expression "action of retinoid type"

It has been found that products having a structure similar to vitamin A also exhibit a retinoid-like action, but that the side effect of toxic hypervitaminosis ^ could, for certain compounds, be multiplied N: 30 by a factor smaller than the multiplicative factor of the retinoic effect sought (see, in this regard, "EUR. J.

MED. CHEM. - CHIMICA THERAPEUTICA, January-February 1980, 15, n ° 1, pages 9-15); P. Loeliger et al. have described, in this last publication, a derivative of formula (a).

J 2 Λ Cïî3 (3)

It has been found, according to the invention, that it was possible to replace the benzene nucleus of the above-mentioned compound with a chroman or thiochroman nucleus and that other substitutions could be provided on the side chain of said compound, without losing for that the benefit of retinoid-like action.

The present invention therefore firstly relates to the new industrial product which constitutes a new chemical compound K corresponding to the general formula (I) ^ (I) r2 r4 25 formula in which: - X represents -O- or -S -; - R ^, R £ / R ^, and R ^ independently represent a hydrogen atom or an alkyl radical, linear or branched, C ^ -Cg; and A represents A: either a radical of formula (II): (ii) 3 * formula in which Rg represents: a radical -CSN; - an oxazolinyl radical; * ’- a radical of formula (III): 5 - CH2OR1q (III) * formula in which R ^ q represents: - a hydrogen atom; - a C ^ -C ^ alkyl radical; - a mono- or polyhydroxyalkyl radical in; - a cyclopentyl radical; - a cyclohexyl radical; or - a tetrahydropyranyl radical; - a radical of formula (IV) * 15 -ij-RU (IV)

O

formula in which R represents: - a hydrogen atom; - an alkyl radical in C ^ -C ^. ; 20 / R '- a radical -N, where R' and R "^ R" identical or different, represent a hydrogen atom, an alkyl radical - Ci-C6 7 a ra ~ 25 dical alkenyl - C ^ -C ^, a cyclopentyl or cyclohexyl radical, or alternatively an aralkyl or aryl radical optionally substituted, R 'and R "can form a heterocycle with the nitrogen atom y 30 to which they are attached, the radical -N ^ t ^ \ u can, moreover, be the residue of an amino acid or of an amino sugar; or 35 - a radical -OR. ^ 'oa Ri2 represents a atom k ί

AT

hydrogen, an alkyl radical - Ci “C2Q '1111 res_ te mono- or polyhydroxyalkyle - C ^ -C ^, the group -0Rj_2 can also be derived from a sugar; 5 b) or a radical of formula (V): (v)

10 R

R6 formula in which: - Rg has the meaning indicated above; and - R ,, and R. independently represent a hydrogen atom or a linear or branched C 1 -C 4 alkyl radical; v 1 oc) or a radical of formula (VI): R5 R7 20 1 (VI) \ R8 25 formula in which: - Rç, Rg and Rg have the meaning indicated above 7 and - and Rg independently represent an atom of hydrogen or an alkyl radical, linear or branched, in C3_-Cg * and the geometric or optical isomers of the compounds of formula (I), as well as their salts.

Among the C 1 -C 4 alkyl radicals which are particularly ς which can be used in the meanings of the radicals R 1 to R 4, R 3 and R 3, mention may be made of the methyl, ethyl, isopropyl, butyl and tert-butyl radicals , and, preferably, for R1 to Rg, the methyl radical.

Among the alkyl radicals in particular ci ”c2o - ζ. ment usable in the meanings of the radical 1 ^ 2 '5 there may be mentioned, preferably, the methyl, ethyl, propyl, 2-ethyl hexyl, octyl, dodecyl, hexadecyl and octadecyl radicals.

Among the substituted or unsubstituted aryl radicals which are particularly usable in the meanings of the R ′ and R ″ radicals, the phenyl radical optionally substituted by a halogen atom, a hydroxyl or a C 1 -C 4 alkoxy radical is preferred. .

Among the substituted or unsubstituted aralkyl radicals, which can be particularly used in the meanings of the radicals R 'and R ", benzyl or phenethyl radicals are preferred, optionally substituted by a hydroxyl group or a C 1 -C 6 alkoxy group, . v 1 6

When the radicals R ′, R ″ and R12 represent a mono- or polyhydroxyalkyl radical C 1 -C 4, this is,

Δ O

Preferably, the 2-hydroxyethyl radical, the 2,3-dihydroxy propyl radical or the pentaerythritol residue.

Among the C 1 -C alkenyl radicals which can be used

O O

in the meanings of the radicals R 'and R ", mention will be made, in particular, of the propenyl, butenyl and iso-pentenyl radicals.

When the radicals R 'and R "form a hetero-cycle with the nitrogen atom to which they are attached, the latter is preferably a radical ion piperidino, morpholino, pipérazino, pyrrolidino or (2-hydroxy-ethyl) -4 30 piperazino.

When the group -OR ^ is derived from a sugar, the latter is, for example, glucose, mannitol or erythritol.

v. The compounds of formula (I) or their isomers can be in the form of their salts; they may be either zinc salts, an alkali or alkaline-earth metal or an organic amine when they contain at least one free acid function, or salts of a mineral acid or organic, in particular hydrochloride, bromhy-t. drate or citrate, when they contain at least one amine function.

Among the particularly preferred compounds according to the invention, mention may be made of those corresponding to the following general formulas: 10 0 Χχ / ΑΑ (Ia) 20

æ A

3 (Ib) it

30 kJ

oXn 35 7 "(le) 10 5 nY5] 2 ° k

/ 'S

CH- (Id)

= S

R11 8 * * 5 (le) formulas in which: - X represents -0- or -S-; and R '10 “* n represents a radical or a rat ^ lcal _0 ~ Ri2' R" R ', R "representing a hydrogen atom or an alkyl radical C ^ -Cg and R12 representing a hydrogen atom, a alkyl radical C ^ -C ^ q or a mono- or polyhydroxyalkyls C2-Cg "* 9

Among the preferred compounds of formula (la), mention may be made of the following compounds: - £ (methoxycarbonyl-4'-phenyl) -4-methyl-3-butadiene-1E, 3eJ- * yl-6-dimethyl-4,4 -chroman5 - £ (methoxycarbonyl-4'-phenyl) -4-methyl-3-butadiene-1E-3Ej-v yl-6-dimethyl-4,4-thiochroman; - | (carboxy-41-phenyl) -4-methyl-3-butadiene-1E, 3E ^ -yl-6-dimethyl-4,4-chroman; - £ (4-carboxy-phenyl) -4-raethyl-3-butadiene-1E-3Ej-yl-6-10 dimethyl-4,4-thiochroman; and - £ (ethylaminocarbonyl-4'-phenyl) -4-methyl-3-butadiene-lE-, 3ej-y1-6-dimethyl-4,4-chroman.

Among the preferred compounds of formula (Ib), mention may be made of the following compounds: - J (4-methoxycarbonyl-phenyl) -4-methyl-3-butadiene-1Z, 3eJ - y1-6-dimethyl-4, 4-chroman; V - | (4 1-methoxycarbonyl-phenyl) -4-methyl-3-butadiene-1Z, 3eJ - yl-6-dimethyl-4,4-thiochroman; - j (carboxy-41-phenyl) -4-methyl-3-butadiene-1Z, 3Ej-yl-6-dimethyl-4,4-chroman; and - | (4-carboxy-phenyl) -4-methyl-3-butadiene-1Z, 3El-yl-6-dimethyl-4,4-thiochroman.

10 "

Among the preferred compounds of formula (Ie), the following compounds may be cited: - [efehoxycarbonyl-8-dimethyl-3,7-octatetraene-1E, 3E, 5E, 7eJ-y1-6-dimethyl-4,4-chromane ; and 5 - £ carboxy-8-dimethyl-3,7-octatetraene-1, 3E, 5E, 7e - yl_6-dimethyl-4,4-chroman.

Among the preferred compounds of formula (id), the following compounds may be mentioned: - £ ethoxycarbonyl-8-dimethyl-3,7-octatetraene-lZ, 3E, 5Ξ, 7e1-

Yl-6-dimethyl-4,4-chroman; and J

- £ carboxy-8-dimethyl-3,7-octatetraene-lZ, 3e, 5E, 7E -yl_6_ dimethyl-4,4-chromane.

Among the preferred compounds of formula (Ic), mention may be made of the following compounds: ethoxycarbonyl-6-dimethyl-1,5-hexatriene-1E, 3e, 5e1-yl-6-dimethyl-4,4-chromane; and - £ carboxy-6-dimethyl-1,5-hexatriene-lE, 3Ε, 5Εj -y1-6-dimethyl-4,4-chromane.

The present invention also relates to a process for the preparation of the new compounds of formula (I), including their geometric and optical isomers, and their salts. According to the invention, the synthesis of the compounds of formula (I) consists in reacting a compound of formula (VII): * 1 25 \> / (VH) on a compound of formula (VIII): 30 R3 35

P P

K2 _ J 4 (VIII) "11 formulas in which R1, R2, R3, r and A have the meanings indicated above, provided that R cannot represent the group of formula (IV) there: -c- Rn (IV)

5 U

- when R ^ is a hydrogen atom or an alkyl radical Cl-C6 'the groups B1 and B2, in the formulas respectively (VII) and (VIII) above, representing, one, an oxo group, 10 while the other is: a) either a triarylohosphonium group of formula (IX): -P Qf Y® dx) formula in which: - Q is an aryl group; and - 1 ^ - Y is a monovalent anion of an organic or inorganic acid; ^ b) or a dialkoxyphosphinyl group of formula (X): -P [zj2 (X, formula in which Z represents an alkoxy residue

Cl-C6 ’

In the case where. and B ^ represent, one, an oxo group, and the other, a triarylphosphonium group of formula (IX), the condensation of the compounds of formulas (VII) and fylll) is carried out in the presence of an alcohol alkali metalate, such as sodium methylate, in the presence of an alkali metal hydride, such as sodium hydride, or in the presence of butyllithium, in a solvent such as tetrahydrofuran or dimethylformamide, 30 condensation which can also be carried out in the presence of an alkaline carbonate, such as potassium carbonate, in an alcohol, such as isopropanol, or in the presence of an alkylene oxide optionally substituted by an alkyl group, optionally in a solvent such as dichlo-35-romethane, the reaction temperature being between -80 ° C. and the boiling temperature of the reaction mixture.

<κ 12

When and Β2 represent, one, an oxo group, and the other, a dialkoxyphosphinyl group of formula (X), the condensation of the compounds of formulas (VII) and ^ (VIII) is carried out in the presence of a base and preferably, in the presence of an inert organic solvent, for example, by means of sodium hydride in benzene, toluene, dimethylformamide, tetrahydrofuran, dioxane or 1,2-dimethoxyethane or also by means of an alcoholate, for example, by means of sodium methoxide, in methanol. This condensation can also be carried out using a mineral base, such as potassium hydroxide or sodium hydroxide, in an organic solvent such as tetrahydrofuran or also by means of an alkali carbonate ion, for example by means of potassium carbonate in water, or by means of butyllithium in tetrahydrofuran. It is possible to add to the reaction mixture a crown ether capable of complexing the metal cation contained in the base and thus making it possible to increase the strength of the latter. The reaction temperature is between -80 ° C and the boiling temperature of the reaction mixture.

The compounds of formulas (VII) and (VIII) are known compounds or which can be prepared by known methods.

The compound of formula (I), obtained by the preparation process according to the invention, can undergo functional modifications of the substituent Rg. Among the functional modifications of this substituent, mention will be made, for example, of the saponification of a carboxylic acid ester or the reduction of the carboxylic acid ester group to the hydroxymethyl group. The hydroxymethyl group can also be oxidized to formyl group, or else be esterified or etherified. On the other hand, a carboxyl group can be converted to a salt, an ester, an amide, an alcohol, an acetyl group or to the corresponding acid chloride. A carboxylic acid ester group can be converted to an acetyl group. The acetyl group can be converted to the secondary alcohol group by reduction, and the secondary alcohol group itself can be alkylated or acylated by known procedures. All of these functional modifications can be accomplished by procedures known per se.

The compounds of formula (I) are obtained in the cis / trans mixture state which can be separated, if desired, in a manner known per se, into pure compounds of the cis or trans type.

The compounds of formula (I) according to the present invention, including their isomers and their salts, have an activity ranging from "good" to "excellent" in the test for inhibition of ornithine decarboxylase after induction, by "tape 15 Stripping ", in the naked rat (M. BOUCLIER et al. Dermatologi-ca, p.159, n ° 4 (1984)). This test is accepted as a measure of the action of retinoids on cell proliferation phenomena.

The compounds according to the invention also exhibit enhanced activity in the differentiation test of mouse embryonic teratocarcinoma cells (F9 cells: Cancer Research 43 p.5268, 1983).

These compounds are particularly suitable for treating dermatological affections linked to a disorder of keratinization (differentiation, proliferation), as well as dermatological affections, or others, with an inflammatory and / or immunoallergic component, in particular: - acne vulgaris, comedonian or polymorphic, senile, solar acne, and medical or professional acne; 30 - widespread and / or severe forms of psoriasis, and other keratinization disorders, and in particular ichthyosis and ichthyosiform states, - - Darier's disease, - - palmoplantar keratoderma; 35 - leukoplakias and leukoplasiform states, lichen planus 7 14 - all benign or malignant, severe or extensive dermatological proliferations.

They can also be recommended in dystrophic epidermis bullosa and in the molecular pathology of collagen. They still find application in carcinomas induced by ultraviolet rays (solar carcinogenesis), in epidermodisplasia verruci-form and related forms.

They are also active for certain umat0 rheumatic affections in particular rheumatoid psoriasis, as well as in the treatment of atopy, whether it is cutaneous or respiratory. These compounds also find application in the ophthalmological field, in particular, in the treatment of corneopathies.

The present invention therefore also relates to medicinal compositions containing at least one compound of formula (I) as defined above and / or one of its isomers, and / or one of its salts.

The present invention thus relates to a new 2o medicinal composition, intended in particular for the treatment of the aforementioned conditions, characterized in that it comprises, in a pharmaceutically acceptable carrier, at least one compound of formula (I) and / or one of its salts and / or one of its.isomers ^.

The compounds according to the invention are generally administered at a daily dose of approximately 2 g / kg to 2 mg / kg of body weight.

As support for the compositions, any conventional support can be used, the active compound being either in the dissolved state or in the state dispersed in the support.

2q The administration of the compositions according to the invention can be carried out by enteral, parenteral, topical or ocular route. For the enteral route, the drugs can be in the form of tablets, capsules, dragees, syrups, suspensions, solutions, powders, granules, emulsions. For the parenteral route, the compositions may be in the form of solutions or suspensions for infusion or for injection. >

For the topical route, the pharmaceutical compositions based on compounds according to the invention are in the form of ointments, tinctures, creams, ointments, powders, patches, soaked tampons, solutions, lotions, gels, sprays or suspensions or emulsions.

These compositions preferably contain from 0.0005 to about 2% by weight of compound (s) of formula (I).

The compositions which can be used topically can be presented either in anhydrous form or in aqueous form according to the clinical indication.

For the ocular route, the compositions are mainly eye drops.

The compounds of formula (I) according to the invention also find application in the cosmetic field, in particular in body and hair hygiene, and in particular in the treatment of acne-prone skin, for hair regrowth or action against hair loss, to combat the oily appearance of the skin or hair, as well as for the treatment of physiologically dry skin. Finally, they have a preventive and curative power against the harmful effects of the sun.

The present invention therefore also relates to a cosmetic composition containing, in a cosmetically acceptable carrier, at least one compound of formula (I) and / or one of its salts and / or one of its isomers, this composition being in particular in the form of lotion, gel, cream, soap, shampoo or the like.

The concentration of compound (s) of formula (I) in the cosmetic compositions according to the invention is between 0.0005 and 2% by weight and, preferably, between 0.01 and 1% by weight.

The medicinal and cosmetic compositions according to the invention can contain inert or even pharmacodynamically or cosmetically active additives and in particular: hydrating agents such as thiamorpholinone and its derivatives or urea; antiseborrhoeic or anti-acene agents such as S-carboxymethylcysteine, S-benzyl-cysteamine and their derivatives, tioxolone or even benzoyl peroxide; antibiotics, such as erythromycin and its esters, neomycin, tetracyclines or polymethylene-4,5-isothiazolinones-3; agents promoting hair regrowth, such as "Minoxidil" (2,4-diamino-piperidino-6 pyrimidine oxide-3) and its derivatives, anthralin and its derivatives, Diazoxide (chloro-7 methyl-3 benzothiadiazine-1 , 2,4 10 dioxide-1, 1) and Phenytoin (diphenyl-5,5 imidazolidinedione-2,4); steroidal and nonsteroidal anti-inflammatory agents; carotenoids and, in particular, ^ -carotene; anti-psoriatic agents such as anthralin and its derivatives and eicosatetraynoic-5,8,11,14 and -triynoic-5,8,11 acids, their esters and their amides.

The compositions according to the invention may also contain flavor enhancers, preserving agents, stabilizing agents, humidity regulating agents, pH regulating agents, osmotic pressure modifying agents, emulsifying agents , UV-A and UV-B filters, antioxidants such as 1 '-tocopherol, butylhydroxyanisole or butylhydroxytoluene.

To better understand the subject of the invention, several embodiments will now be described.

EXAMPLE 1

Preparation of a compound of formula: ^ * c ° 2CH3 3b '30 | A) 4.85 g of trimethyl 1,4,4,6 chromane are dissolved in 3,150 cm of anhydrous carbon tetrachloride. 5 g of N-bromosuccinimide and 0.05 g of azobisisobutyronitrile are added. The mixture is heated for one hour at reflux under UV irradiation. After cooling, the succinimide formed is filtered and the solution is washed with 150 cm of a saturated solution of sodium bicarbonate. After drying the organic phase, the solvent is evaporated. 4.59 g of 6-bromomethyl-4,4-dimethyl-chroman are obtained.

B) 5.8 g of 6-bromomethyl-4,4-dimethyl-chroman 3 obtained above are dissolved in 150 cm of toluene. 6.6 g of triphenylphosphine are added. The reaction mixture is heated at 100 ° C for 6 hours. After evaporation of the solvent, the solid residue is reduced to powder and washed several times with ether. 10.64 g of 4-methyl-4,4-chromanyl-6) methyl bromide is obtained (methylj triphenyl phosphonium in the form of a white powder), c) 15.4 g of the phosphonium bromide obtained above is suspended in 250 cm ^ of tetrahydrofuran anhy-20 are. 1.1 equivalent of n-butyl lithium in 1.6 N solution in hexane are added at 0 ° C. After 15 minutes at 0 ° C., the excess butyl lithium is destroyed by the addition of 20 cm of di ch 1 anhydrous oromethane. The mixture is then cooled to -78 ° C. and 0.95 equivalent of (methoxycarbonyl-4-phenyl) - 3-methyl-2-propene-2-al dissolved in 15 cm is added to protect from light. anhydrous dichloromethane. It is left to react for 30 min at -78 ° C. and finally, the temperature is allowed to rise to room temperature in two hours. The reaction mixture is poured onto 3 2q 200 cm of a saturated solution of ammonium chloride.

After dilution with 50 cm of water, the aqueous solution 3 is extracted with 2 times 100 cm of ether. The organic phase is dried over sodium sulphate and quickly filtered through silica gel. After evaporation of the solvent and recrystallization from hexane, 18 3.58 g of expected product is obtained, having the following characteristics:

- melting point: 113 ° C

- the nuclear magnetic resonance spectrum - 5 (200 MHz, CDCl ^) corresponds to the expected structure.

- elementary analysis:

C H

10 calculated for 79.53 7.23 found 79.69 7.37 15 EXAMPLE 2

Preparation of a compound of formula: 20 | ίΊ

25 I

C02CH3

This compound is obtained from the mother liquors of re-crystallization of the compound of Example 1C.

It has the following characteristics:

- melting point: 83 ° C

- the 1 H nuclear magnetic resonance spectrum (200 MHz, CDCl ^) corresponds to the expected structure.

35 <c - elementary analysis: 19

C H

calculated for C2AH26 ° 3 79.53 7> 1 2 3 4 5 6 7 8 9 10 11 found 79.77 7.51 EXAMPLE 3 10,.

Preparation of a compound of formula:

15 ^^ C02H

35 2

2.17 g of the compound obtained in Example IC is heated for 1 hour at 50 ° C. in a mixture containing 70cin 3 4 of water, 50 cm of ethanol and 20 g of sodium hydroxide. After cooling, the mixture is diluted by adding 300 cm of water and the ethanol is distilled under reduced pressure. The residual aqueous solution 7 is acidified to pH 2 with a 10% hydrochloric acid solution 8. The acid which precipitates is filtered, 9 then washed with water. After recrystallization from acetone, the expected product is obtained in the form of a yellow solid 11 having the following characteristics: _ - melting point: 188 ° C. (with decomposition) - the nuclear magnetic resonance spectrum (200 MHz, CDCl ^) corresponds to the expected structure.

* »20 - elementary analysis: --—;

_ c H

5 calculated for C23 h24 03 79.28 · 6.94 found_ 79.20 7.02 EXAMPLE 4

Preparation of a compound of formula 1 ° A.

15

U

20

co2H

This compound is obtained according to the procedure described in Example 3 in which the compound of Example IC 2 ^ is replaced by the compound of Example 2. After recrystallization from acetone, the expected product is obtained in the form of a yellow solid having the following characteristics: - melting point: 150 ° C (with decomposition) 2q - the nuclear magnetic resonance spectrum (200 MHz, CDC1_) corresponds to the expected structure.

O

35 - elementary analysis: 21

C H

calculated for C23 H24 03 79.28 6.94 5 found 79.24 7.07 EXAMPLE 5

Preparation of a compound of formula: 1 ° 15

This compound is obtained according to the procedure described in Example IC in which the (methoxycarbonyl-4-phe-nyl) -3-methyl-2-propene-2-al is replaced by formyl-7-methyl-3- ethyl octatriene-2,4,6-oate. After chromatography-2q graphed on silica gel, using a hexane-ethyl acetate mixture (99/1) as eluent, the expected product is obtained in the form of yellow crystals having the following characteristics:

- melting point: 27-29 ° C

2 ^ - the nuclear magnetic resonance spectrum (200 MHz, CDC13) corresponds to the expected structure.

- elementary analysis:

C H

30 - calculated for C24H30 ° 3 78.58 8.19 found 78.46 8.23 35 "22 EXAMPLE 6 '

Preparation of a compound of formula: k 10 Ί C02C2H5 15 This compound is obtained during the purification by chromatography of the compound described in Example 5. It is obtained in the form of a yellow oil having the following characteristics:

- melting point: 7 ° C

20 - the nuclear magnetic resonance spectrum (200 MHz, CDCl ^) corresponds to the expected structure.

- elementary analysis:

C H

Calculated for C24H30 ° 3 78.58 8.19 found 78.73 8.15 EXAMPLE 7 Preparation of a compound of formula; 35 23

This compound is obtained according to the procedure described in Example 3 in which the compound of Example 1C is replaced by the compound of Example 5. After recrystallization from hexane, the expected product is obtained in the form of '' a yellow solid with the following characteristics:

- melting point: 178 ° C

- the nuclear magnetic resonance spectrum H (200 MHz, CDCI ^) corresponds to the expected structure.

10 - elementary analysis:

C H

calculated for C22H26 ° 3 78.00 7.68 15 found 78.18 7.53 EXAMPLE 8

Preparation of a compound of formula: 20

Q

VS

30

1.2 g of the compound obtained in Example 3 3 are dissolved in 80 cm of tetrahydrofuran. Cool to 0 ° C and introduce, under argon, about 1.5 equivalent of diimida-zole sulfonyl in solution in tetrahydrofuran. The mixture is left at 0 ° C. for 5 min, then 10 cm of ethylamine are added. The mixture is stirred for 30 min at room temperature. The reaction mixture is washed twice with 80 cm of water. The organic phase is dried over magnesium sulfate. After evaporation of the solvent and recrystallization from acetone, 670 mg of expected product is obtained which has the following characteristics:

- melting point: 186-187 ° C

- the nuclear magnetic resonance spectrum (200 MHz, CDCl ^) corresponds to the expected structure.

- elementary analysis: 10 _ — _— d ---

C H N

calculated for C ^ H ^ g N02 73.96 7.78 3.73 found 79.79 7.92 3.74 1 5 1 ------ EXAMPLE 9

Preparation of the compounds of formula 20 25 Çi C02CH3 35 Μ 25 CÏÎ3

These Compounds are obtained according to the procedure described in Example IC in which the bromide of 1Q ^ (dimethyl-4,4-chromanyl-6) -methyl J triphenyl phosphonium is replaced by the bromide of £ (dimethyl-4,4 -thiochromanyl- 6) -methylJ triphenylphosphonium. The products are obtained with a yield of 80% in the form of a mixture of Z, E (45%) and E, Ξ (5.5%) isomers, the proportions of which were determined by nuclear magnetic resonance H.

The E, E isomer is isolated from the reaction mixture by crystallization and has the following characteristics:

- melting point: 110-112 ° C

- the 1H nuclear magnetic resonance spectrum (200 MHz, 20 CDC13) conforms to the expected structure.

- elementary analysis:

C H

25 calculated for C24H2602S 76.15 6.92 found 76.19 7.19 * - - _________ - —- - - | _____ I - The Z, E isomer is obtained from the mother liquors of crystallization by chromatography on silica gel using a mixture of hexane and ethyl acetate as eluent; it has the following characteristics:

- melting point: 84-86 ° C

- the 1H nuclear magnetic resonance spectrum (200 MHz, CDC1-) conforms to the expected structure.

35 ‘'26 - elementary analysis:

C H

: 5 calculated for 76.15 6.92 found 76.20 7.13 EXAMPLE 10

Preparation of a compound of formula: 10 15

This compound is obtained according to the procedure described in Example 3 in which the compound of Example 1 C is replaced by the compound of Example 9 in the form of the E, E isomer.

The product obtained has the following characteristics: 25 - melting point: 178 ° C. (with decomposition) - the 1 H nuclear magnetic resonance spectrum (200 MHz, CDCl 4) corresponds to the expected structure.

- elementary analysis: 30 C H 0 s calculated for C ^ H ^ O ^ 75.82 6.59 8.79 8.79; found 75.31 6.77 8.94 8.17 35% 27 EXAMPLE 11

Preparation of a compound of formula: 5

ÖTX

Λ

: - V

co2h. This compound is obtained according to the procedure described in Example 3 in which the compound of Example IC is replaced by the compound of Example 9 in the form of the Z, S isomer.

The product obtained has the following characteristics: - melting point: 160 ° C-165 ° C (with decomposition) - the nuclear magnetic resonance spectrum (200 MHz, CDCl ^) corresponds to the expected structure.

- elementary analysis: s 28

C H

calculated for C ^ H ^ C ^ S 75.72 6.58 found 75.65 6.55 5 EXAMPLE 12

Preparation of a compound of formula XVvvV “2" 10 a) 10/2 g of aluminum chloride are added in small portions to a solution of 12 g of dimethyl-4,4-chroman 15 and 6 g of chloride d acetyl in 105 cm of nitro-methane under argon After 6 hours of reaction at room temperature, 100 cm of 6N hydrochloric acid are slowly added, the mixture is stirred for 10 min and then 120 cm of ether are added. organic is washed with water, 2Q then with a saturated aqueous solution of sodium bicarbonate and again with water After drying the organic phase and distilling off the solvent under reduced pressure, 8.5 g of 'acety1-6-dimethyl-4,4-chroman.

b) a solution of 8 g of acetyl-6-dimethyl-4,4-chroman 3 2! _ in 50 cm of anhydrous ether is slowly added under argon to a suspension of 6 g of aluminum hydride and 3 of lithium in 150 cm of anhydrous ether. The reaction mixture is left under stirring at room temperature for 20 hours. 3 cm ^ of ethyl acetate are added, 3 „then 10 cm of 5¾ hydrochloric acid. After 5 minutes of stirring, the organic phase is decanted. The aqueous phase is washed twice with 150 cm 3 of ether. The organic phases are combined and then washed with 200 cm of 5¾ potassium carbonate solution, then with 3 295 150 cm of saturated aqueous sodium chloride solution.

After drying over sodium sulfate, the solvent is distilled under reduced pressure. The residue is purified by crystallization from hexane. 6.3 g of dimethyl-4,4-hydroxyethyl-6-chroman are obtained.

Q

c) 10 g of triphenylphosphine are dissolved in 100 cm of ether. Passage of hydrobromic acid gas causes precipitation of hydrobromide. triphenylphosphine, which is filtered and used without further purification.

A solution of 6 g of 4,4-dimethyl-6-hydroxyethyl chroman and 10.3 g of triphenylphosphine hydrobromide in 250 cm of methanol is stirred for 24 hours under argon. The solvent is distilled under reduced pressure. The oily residue is washed with ether until crystallization. After filtration and drying, 13.15 g of the expected phosphonium bromide are obtained.

d) The phosphonium bromide obtained above is condensed on ethoxycarbonyl-5-methyl-4-pentadiene-2E, 4E-al-1 under the same conditions as those described in Example IC. The crude product is separated from the triphenylphosphine oxide by treatment with hexane. The expected product is obtained, after evaporation of the solvent (£ 6-ethoxy-carbonyl-dimethyl-1,5 hexatriene-1,3,5j-yl-6 dimethyl- 4,4 chromane) in the form of a mixture of 1Z isomers , 3E, 25 5E (33¾) and 1E, 3E, 5E (66¾) The proportions of each of the two isomers were determined by nuclear magnetic resonance ^ H.

e) the hydrolysis of the mixture of isomeric esters obtained in 12d) is carried out according to the same procedure as that described in Example 3. After recrystallization from acetone, the expected compound is obtained wholly of structure trans. It has the following characteristics: -melting point: 175 ° C (with decomposition) £ - the nuclear magnetic resonance spectrum 35 (200 MHz, CDCl ^) corresponds to the expected structure.

- elementary analysis: 30

C H

calculated for ConHo / 0 ^ 76.89 7.74 5 20 24 3 found 76.81 8.01 31

EXAMPLE A

Preparation of 0.5 g insoluble tablets having the following formulation: - Compound of Example 3 .................. 0.050 g 5 - Lactose ..... ............................ 0.082 g - Stearic acid ................. ........ 0.003 g - Purified talc ............................ 0.015 g - Sweetener ..... ..................... qs

- Colorant ............................ q.s.

10 - Rice starch ....................... q.s. 0.500 g

These tablets, containing 0.05 g of active compound (compound of Example 3), are obtained by direct dry compression of the mixture of the various constituents above. These tablets are administered 2 to A per day in the treatment of psoriasis.

EXAMPLE B

Preparation of a gel for topical application having the following formulation: 20 - Compound of Example 8 ................. 0.05 g - Ethanol ...... .......................... 43.00 g -d-tocopherol ................ ........... 0.05 g - Carboxyvinyl polymer

crosslinked sold under the trade name 25 "CARB0P0L 941" by the company "GOODRICH

CHEMICAL "............................. 0.50 g - Triethanolamine in 20% aqueous solution ....... ........................... 3.80 g - Water ................. ................... 9.30 g 30 - Propylene glycol .................... qs 100, 00 g ii This gel is applied to dermatosis or acne-prone skin 1 to 3 times a day.

35> »·» 32

EXAMPLE C

Preparation of a salt for topical application having the following formulation: - Compound of Example 9 ................. 0.025 g 5 - Erythromycin base ...... .............. 4, 000 g - Buthylhydroxytoluène ................... 0.050 g - Hydroxypropyl cellulose sold under the trade name " KLUCEL HF ”by the company" HERCULES ".............. 2,000 g 10 - Ethanol (at 95 °) ................. ... qs 100,000 g

This gel is applied to acne skin 1 to 2 times a day.

EXAMPLE D

Preparation of a 0.3 g capsule having the following formulation 1 5: - Compound of Example 5 ................. 0.05 g - Corn starch. ........................ 0.06 g - Lactose .................... ...... qs 0.3 g

The capsules used consist of gelatin, - titanium oxide and a preservative; they are administered at a rate of 2 to 4 per day in the treatment of psoriasis.

EXAMPLE E

Preparation of an anti-sun cosmetic composition 25 having the following formulation: - compound of Example 1 ................. 1.00 g - benzylidene camphor .... ................ 4.00 g - Triglycerides of fatty acids (CgàC18) ... 31.00 g - Glycerol monostearate .......... ..... 6.00 g 30 - Stearic acid ........................ 2.00 gw - Cetyl alcohol ...... ................. 1.20 g - Lanolin ........................... .... 4.00 g - Preservatives .......................... 0.30 g - Propanediol ........ .................... 2.00 g 35 - Triethanolamine ....................... .50 g - Perfume ................................. 0.40 g * 33 - Demineralized water. ................. qs 100.00 g

EXAMPLE F

Preparation of an anti-seborrhoeic cream having the following formulation: 5 - Polyoxyethylene stearate (40 moles of ethylene oxide) sold under the trade name "MYRJ 52" by the company "ATLAS" ....... ......... 4 g - Mixture of lauric esters of sorbitol Ίο and sorbitan, polyoxyethylenated with 20 moles of ethylene oxide sold under the trade name "TWEEN 20" by the company "ATLAS." ................ 1.8 g - Mixture of mono and distearate of gly-15 cerol sold under the trade name "GELE0L" by the company "" GATTEF0SSE ".... ...................... 4.2 g - Propylene glycol ...................... .10 g - Buthylhydroxyanisole .................. 0.01 g 20 - Butylhydroxytoluene ................... 0 , 02 g - Keto-stearyl alcohol ............... 6.2 g - Preservatives ...............'..... ..qs - Perhydrosqualene ...................... 18 g - Mixture of caprylic triglycerides - 25 capric sold under the trade name "MIGLY0L 812" by the company " DYNAMIT NOB EL "........................ 4 g - S-carboxymethyl cysteine .............. 3 g - Triethanolamine 99% ................... 2.5 g 30 - Compound of Example 4 ................ 0.02 gi - Water ......................... qs .... 100 g Λ 34

EXAMPLE G

Preparation of an anti-acne cream having the following formulation: - Mixture of glycerol stearates and of polyethylene glycol (75 moles) sold under the trade name "GELOT 64" by the company "GATTEFOSSE" ........ .... 15 g - Polyoxyethylenated core oil containing 6 moles of ethylene oxide sold 10 under the trade name "LABRAFIL M 2130 CS" by the company "GATTEFOSSE" ............ .............. 8 g - Perhydrosqualene ...................... 10 g - Colorant ...... .................. q. s. . .

15 - Preservatives ................... q.s ...

- Perfumes ......................... q.s ...

- Tioxolone ............................. 0.4 g - Polyethylene glycol 400 ............ .... 8 g - Purified water .......................... 58.5 g 20 - Disodium salt of ethylenededia mine acid tetracetic ..................... 0.05 g - Compound of Example 4 ................ 0 0.05 g

EXAMPLE H

Preparation of a hair lotion for the regrowth of 25 hairs having the following formulation: - Propylene glycol ....................... 20 g - Ethanol .... ........................... 34.92 g - Polyethylene glycol 400 ................ 40 g - Water .................................. 4 g 30 - Butylhydroxyanisole ....... ............ 0.01 g - Butylhydroxytoluene ................... 0.02 g - Compound of Example 7 .. .............. 0.05 g - Minoxidil ............................. 1 g "35

EXAMPLE I

Preparation of an anti-acne cream having the following formulation: - Polyoxyethylene stearate (40 Moles of ethylene oxide) sold under the trade name "MYRJ 52" by the company "ATLAS" ....... A g - Mixture of lauric esters of sorbitol and sorbitan, polyoxyethylenated with 20 moles of ethylene oxide sold under the trade name "TWEEN 20" by the company "ATLAS" ......... ....... 1.8 g - Mixture of mono and glycerol distearate ............................. .... 4.2 g - Propylene glycol ....................... 10 g 15 Butylhydroxyanisole ............. ...... 0.01 g - Eutylhydroxytoluene ................... 0.02 g - Keto-stearyl alcohol .......... ..... 6.2 g - Preservatives ................. qs ....

- Polytetrahydrofuran dimethyl ether 18 g 20 - Mixture of caprylic-caprylic triglycerides sold under the trade name "MIGLY0L 812" by the company "DYNAMIT NOBEL" ................. A g - Compound of example 12 ............... 0.02 g 25 - Water ...................... .... qsp ---- 100 g

EXAMPLE J

It is an anti-acne kit comprising two parts: a) A gel is prepared having the following formulation: - Ethyl alcohol ..................... 48, A g 30 - Propylene glycol ....................... 50 g - Crosslinked carboxyvinyl polymer sold under the trade name "CARB0P0L, 940" by the company "GOODRICH CHEMICAL Co." ......... 1 g 35 - Diisopropanolamine 99% ................ 0.3 g

H

36 - Butylhydroxyanisole ................... 0.05 g - Butylhydroxytoluene ................... 0.05 g - £ locopherol ............................ 0.1 g - Compound of Example 7 ....... ......... 0.1 g 5 b) A gel is prepared having the following formulation: - Ethyl alcohol ...................... 5 g - Propylene glycol ....................... 5 g - Disodium salt of ethylenediaminetetraacetic acid ......... .............. 0.05 g - Crosslinked carboxyvinyl polymer -------- sold under the name "CARB0P0L 940" by the company "GOODRICH CHEMICAL Co." .. .......... 1 g 15 - Triethanolamine 99% ................... 1 g - Sodium lauryl sulfate ........ ....... 0.1 g '- Purified water .......................... 75.05 g - Hydrated benzoyl peroxide at 25% .... 12.8g

The two gels 20 are mixed extemporaneously, weight for weight.

Claims (26)

37 1. Chemical compound corresponding to general formula * (I): r2 r4 (i) 10 formula in which: - X represents -O- or -S-; - R ^ / ^ 2 '^ 3' ^ 4 represent, independently, a hydrogen atom or an alkyl radical, linear or branched, in 15 Cl-C6 * and - A represents: a) either a radical of formula (II): X (III) formula in which Rg represents: - a radical -C ^ N; Z 3 - an oxazolinyl radical; - a radical of formula (III): - ch2or10 (III) formula in which R ^ q represents: 30. a hydrogen atom; - a C 1 -C 4 alkyl radical; - - a mono- or polyhydroxyalkyl radical in Cn-C,, · 2 6 - a cyclopentyl radical; - a cyclohexyl radical; or 38 - a tetrahydropyranyl radical 7 - a radical of formula (IV) ifRu (IV) 0 5 formula in which R1; L represents: - a hydrogen atom; - a C ^ -C ^ alkyl radical; - a radical -N, where R 'and R ", 10 V ', identical or different, represent a hydrogen atom, a C 1 -C 4 alkyl radical, a C 1 -C 4 alkenyl radical, a cyclopentyl or cyclo-hexyl radical, or an aralkyl or aryl radical optionally substituted (s), R 'and R "being able to form a heterocycle with the nitrogen atom to which they ^ R' are attached, the radical -N being able, in addition, ^ R" 20 to be the remainder of an amino acid or an amino sugar, · or - a radical -0- ^ 27 where R12 represents a hydrogen atom, an alkyl radical in Cj_-C20 '1111 remains Mono- or polyhydroxyalkyl in C ^ -C ^, the group 25 -0R12 P ° can also be derived from a sugar; b) or a radical of formula (V): R, "30 * 6 5 formula in which: - Rg has the meaning indicated above? and - R, - and Rg represent, independently, a hydrogen atom or an alkyl radical, linear or branched, in C ^ -Cg, * 39 c) or a radical of formula (VI): R5 R7 < vi> R6 R8 formula in which; - Rg / Rg and Rg have the meaning indicated above; 10 and - and Rg independently represent a hydrogen atom or a linear or branched C - C £ alkyl radical; i O and the geometric or optical isomers of the compounds of formula (I), as well as their salts, j 2 - Compound according to: claim 1, characterized in that the C 1 -C 4 alkyl radicals involved therein for the meanings of the radicals R ^ to R ^, R 'and R ", are chosen from the group formed by methyl, ethyl, isopropyl, butyl and tert-butyl radicals. 3. Compound according to Claim 1, characterized in that the C1-C20 alkyl radical which intervenes therein for the meaning of R12, is chosen from the group consisting of the methyl, ethyl, propyl and 2-ethylhexyl radicals , octyl, dodecyl, hexadecyl and octadecyl. 's- ^ _ 6 "* AO A - Compound according to claim 1, characterized in that the mono- or polyhydroxyalkyl radicals C ^ -Cg, which are involved for the definitions of R', R" and R12> are chosen from the radicals hydroxy-2 ethyl, dihy-5 droxy-2,3 propyl and the rest of pentaerythritol. 5. Compound according to one of claims 1 to A, in the form of a salt, characterized in that, if the compound of formula (I) comprises at least one free acid function, said salt is chosen from the group formed by 10 the salts of zinc, of an alkali or alkaline earth metal or of an organic amine, and that, if the compound of formula (I) contains at least one amine function, said salt is chosen from the group formed by the salts of a mineral or organic acid and, in particular, the hydrochloride, the hydrobromide and the citrate. The " 6. Compound according to claim 1, characterized in that it corresponds to one of the following general formulas (la) to (le): 20 \ 25 \ 30 \> '\ 35 \ _ 41 (la) 10; > w% 15 X ^ X ^ AT CH ^ 3 (Ib) il 20 o ^ S * 11 25 30 | ^ ^ R11 (le) 35 42 '5 rVv ^ A ch3 10 CH ^^ l (ld) 15 A f 0 R11 20 25 Xq ^ uOIA ,, 30 Ax (le) Π · ν '35 V 43 formulas in which: - X represents -0- or -S-; and / * '* - ^ 11 represents a radical -N or a radical -OR ^ "5 ^ R" - R *, R "representing a hydrogen atom or an alkyl radical C ^ -C ^ and R ^ representing a hydrogen atom, an alkyl radical C ^ - ^ q or a ra ^^ cal mono_ or polyhydroxy-alkyl C2-Cg. 7 - Compound according to claim 6, characterized in that it is chosen from the following compounds: - £ (methoxycarbonyl-4 '-phenyl) -4-methyl-3-butadiene-lE, 3eJ -yl-6- dimethyl-4,4-chroman; - £ (methoxycarbonyl-41-phenyl) -4-methyl-3-butadiene-1E-3Ej- * ^ yl-6-dimethyl-4,4-thiochroman; - | (4-carboxy-phenyl) -4-methyl-3-butadiene-1E, 3E] -yl-6-dimethyl-4,4-chroman; - | (4-carboxy-phenyl) -4-methyl-3-butadiene-1E-3Ej-yl-6-dimethyl-4,4-thiochroman? 2C r - | (ethylaminocarbonyl-4'-phenyl) -4-methyl-3-butadiene-1E-, 3ej-yl-6-dimethyl-4,4-chroman. - | (4-methoxycarbonyl-phenyl) -4-methyl-3-butadiene-1Z, 3e] -yl-6-dimethyl-4,4-chromane, · - - (methoxycarbony 1-4 '-phenyl) - 4-methyl-3-butadiene-1Z, 3eJ -yl-6-dimethyl-4,4-thiochroman; - | (4-carboxy-phenyl) -4-methyl-3-butadiene-1Z, 3e j-yl-6-dimethyl-4,4-chroman; | (4-carboxy-phenyl) -4-methyl-3-butadiene-1Z, 3El-yl-6-2 dimethyl-4,4-thiochroman. - [ethoxycarbonyl-8-dimethyl-3,7-octatetraene-1E, 3E, 5E, 7EJ-yl-6-dimethyl-4, 4-chroman; - £ carboxy-8-dimethyl-3,7-octatetraene-lE, 3E, 5E, 7eJ-yl-6-dimethyl-4,4-chroman ^. 35% 44 - £ ethoxycarbonyl-8-dimethyl ~ 3,7-octatetraene-lZ, 3E, 5e, 7e1-yl-6-diinethyl-4,4-chroman? ^ - £ carboxy-8-dimethyl-3,7-octatetraene-lZ, 3Ε, 5E, 7Ε -yi_6- s dimethyl-4,4-chromane ^, '> - [ethoxycarbonyl-6-dimethyl-1,5-hexatriene -El, 3rd, 5th - yl-6-dimethyl-4,4-chroman; - j ^ carboxy-6-dimethyl-l, 5-hexatriene-lE, 3E, 5E J -yl-6-dimethyl-4,4-chromane. 10 -: - 1 15 \ 20 \ 25 \ 30 \ 35> - * 45 8. Process for the preparation of a compound as defined in one of claims 1 to 7, characterized in that a compound of formula (VII) is reacted: 1 '> vA I ^ (VII) 10 on a compound of formula (VIII): * 3 'nA, / 1 5 15 k2 ft4 formulas in which R ^, R2 / R ^, R ^ and A have the meanings indicated in claim 1, provided that Rg cannot represent the group of formula (IV): 20,, -fi- Ru tIV) when -R ^ is a hydrogen atom or an alkyl radical W 25 the groups and B2 / in the formulas respectively (VII) and (VIII) ci above, representing, one, an oxo group, while the other is: a) either a triarylphosphonium group of formula (IX): * 46% -p [q | Ç y 0 (ix) formula in which: * - Q is an aryl group; and 5. Y is a monovalent anion of an organic or inorganic acid · b) or a dialkoxyphosphinyl group of formula (X): -P [z] 2 (X) “* formula in which Z represents an alkoxy residue Cl'C6 ' 9. The process as claimed in claim 8 / in which 11 represents an oxo group and the other represents a triarylphosphonium group of formula (IX), characterized in that the condensation of the compounds of formula Λ 8 mules (VII) and (VIII) is carried out in the presence of an alkali metal alcoholate, in the presence of an alkali metal hydride, or in the presence of butyllithium, in a solvent such as tetrahydrofuran or dimethylformamide, or else in the presence of an alkali carbonate, in an alcohol, or in the presence of an alkylene oxide optionally substituted with an alkyl group, optionally in a solvent such as dichloride, the reaction temperature - 25 tion being between - 80 ° C and the boiling temperature of the reaction mixture. 10. The method of claim 8, wherein and represent, one, an oxo group, and the other, a dialkoxyphosphinyl group of formula (X), ca-30 characterized by the fact that the condensation of the compounds of formulas ( VII) and (VIII) is carried out in the presence of a base and, preferably, in the presence of an inert organic solvent "·", the reaction temperature being between y - 80 ° C and the boiling temperature of the reaction mixture. »47 11. Method according to one of claims 8 to 10, characterized in that the compound obtained by reaction of the compounds of formulas (VII) and (VIII) subsequently undergoes * = functional modifications of the substituent RQ. J "· 5 12 - Medicinal composition, characterized in that - it comprises, in a pharmaceutically acceptable carrier, at least one compound as defined in one of claims 1 to 7. 13. Composition according to claim 12, character-ized by the fact that it is intended for the treatment of dermatological conditions linked to a disorder of keratinization (differentiation, proliferation), dermatological conditions, or others, with an inflammatory component and / or immunoallergic, of all benign - malignant or malignant, severe or extensive dermatological proliferations, epidermolysis bullosa / dystrophic and molecular pathology of collagen, b Carcinomas Induced by ultraviolet (solar carcinogenesis), epidermodisplasia verruciformis and related forms, of rheumatic affections like the psoriasis rhuma-20 tïde, to the ophthalmological treatments, as well as to the treatment of atopy. 14. Composition according to one of claims 12 and 13, characterized in that it is administered in an amount of approximately 2 jig up to 2 mg of compound (s) according to one of claims 1 to 7, per day and per kg of body weight of the subject treated. 15. Composition according to one of claims 12 to 14, usable by enteral route, characterized in that it is in the form of tablets, capsules, dragees, syrup, suspension, solution, powder , granules or emulsion, ft. 16 - Composition according to one of claims 12 ^ to 14, usable parenterally, characterized in that it is in the form of solution or suspension for infusion or for injection. t 48 17. Composition according to one of claims 12 to 14, usable topically, characterized in that it is in the form of ointment, tincture, * cream, ointment, powder, patch, soaked tampon, 5 solution, lotion, gel, spray, suspension or emulsion. 18. Composition according to Claim 17, characterized in that the concentration of compound (s) according to one of Claims 1 to 7 is between 0.0005 and 10 2% by weight. 19. Composition according to one of claims 12 to 14, usable by eye, characterized in that it is in the form of eye drops. 20. Cosmetic composition, characterized in that it contains, in a cosmetically acceptable carrier, f at least one compound according to one of claims 1 to 7- 21. Composition according to claim 20, characterized in that it finds an application for the treatment of acne-prone skin, for hair regrowth, for action against hair loss, for combating the appearance oily skin or hair, for the treatment of physiologically dry skin as well as in the treatment and prevention against the harmful effects of the sun. 25 22 - Composition according to one of claims 20 and 21, characterized in that the compound (s) according to one of claims 1 to 7 is (or are) present (s) at a concentration included between 0.0005 and 2% by weight and preferably between 0.01 and 1% by weight. 23 23 - Composition according to one of claims 20 to 22, characterized in that it is in the form of lotion, gel, cream, soap or shampoo. 24. Composition according to one of claims 12 to 23, characterized in that it contains inert or pharmacodynamically or cosmetically active additives. * v- * 49% 25. A composition according to claim 24, characterized in that the additives are taken from the group formed by moisturizing agents, anti-seborrheic agents, anti-acne agents, antibiotics, favoka agents '' 5 risking hair regrowth, anti-inflammatory agents, carotenoids, anti-psoriatic agents, flavor enhancers, preservatives, stabilizers, moisture regulators, regulators pH, osmotic pressure modifiers, emulsifiers, UV-A and UV-B filters, and antioxidants. J * V "Drawings: ..........." dL 5o plates ..... pages of which ........ j ....... cover page ... .... 36 ..... pages of description ........ A & .. pages of claim ....... short description Luxembourg, le ^ / R. "The representative: Me Alain Rukavina i .- ^ ·