SE459807B - 10-ARYL-1, 8-DIHYDROXY ANTRONES, PROCEDURES FOR PREPARING THEREOF AND PHARMACEUTICAL OR COSMETIC COMPOSITIONS - Google Patents

Description

10 15 20 30 35 459 807 wherein R 1, R 2, R 3, R 4 and R 5, the same or different, denote a hydrogen atom, a halogen atom, the group -CF3, a hydroxyl function, a lower alkyl group, a lower cycloalkyl group, a lower hydrogen oxyalkyl group. a lower alkoxy group, a nitrile function, QIUPP one IN -so N / r, -mn) -con / I '-mH) -N / I 2 \ r'l 237- \ rn '211 \ ru I' O----- -N-CO R '_ CH -CO' - than 1 (2) n ZR or (CH2) ¿§š N I'CCh I ", the same or different, denotes a hydrogen atom or a lower alkyl group, n is 0 or an integer from 1 p.m. 3, and R 'and R "represent a hydrogen atom, a lower alkyl group, straight or branched, the alkyl and aryl groups above optionally may be substituted, and wherein at least one of the groups R 1 to R5 is separated from a hydrogen atom, Re, / ' (ii) \\ N Ra (111) S R6 represents one of the meanings given to the groups R6 to R5 and 1 S / Q N and the mono-, di- and tri-esters thereof of formula II 10 15 20 25 30 35 s 459 807 (II) wherein Ar has the same meaning as given above for the associations of formula (I), p is 0 or 1.

When p = 0, R 8 represents a hydrogen atom or -COR and R 10 9 denotes -COR10 and p 'is 1, when p = 1, R 7 denotes: 1) a hydrogen atom, R 8 represents a hydrogen atom or the group -COR10, R9 represents the group -COR10 and p 'is 0, 2) or the group -COR 10, R 8 and R 9 represents the group -COR10 and p 'are 0, R10 represents a straight or branched alkyl group having from 1 to 10 carbon atoms, a cycloalkyl group, a 2-pyridyl group, a 2-thio- nyl group or a phenyl group optionally substituted by a lower alkyl group, a lower alkoxy group, a halogen atom, a nitrous oxide ro function, a group -CF3 or with a hydroxyl function and mixtures of these esters.

When the groups R1 to R5 represent a halogen atom, this is preferably a fluorine or chlorine atom.

By a lower alkyl group is meant according to the invention a group having from 1 to 6 carbon atoms, preferably a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl or hexyl group. 10 15 20 25 30 35 459 807 a 4 By lower alkoxy group is meant a group having from 1 to 4 carbon atoms, in particular a methoxy- , ethoxy, propoxy or iso- propoxy group.

By a lower cycloalkyl group is meant a cyclopropyl, cyclo- butyl, cyclopentyl or cyclohexyl group.

By lower hydroxyalkyl group is meant a group having from 1 to 3 carbon atoms and in particular a hydroxymethyl- , 2-hydroxy-ethyl- or 2,3-dihydroxypropyl group.

When in the compounds of formula (I) the group Ar represents a aromatic residue of the formula: R5 R4 Rs // RI Rz the preferred compounds are those in which: 1) R 1 (or R 5) represents a lower alkoxy group or group with the formula: -N - COR ' IN RI! R 'represents a straight or branched alkyl group having from 1 to 5 carbon atoms and R "represents a hydrogen atom, R3 represents a hydrogen atom atom or a lower alkoxy group and R 2, R 4 and R 5 (or R 1) denotes a hydrogen atom. 2) R 2 (or R 4) represents a group -CF 3, a lower alkoxy- group or a hydroxyl function and R 1, R 3, R 4 (or R 2) and RS denotes a hydrogen atom, and 3) R 3 represents a lower alkoxy group and R 1, R 2, R4 and R5 denotes a hydrogen atom. 10 15 20 25 30 35 459 807 According to a preferred embodiment, the group R 6 denotes a hydrogen atom.

Among the compounds of formula (I), mention may be made in particular following: 1,8-Dihydroxy-10- (N-2 ", 2" -dimethylpropanoyl) -2'-amino-phenyl-anthrone 1,8-Dihydroxy-10- (2 ', 4'-dimethoxy-phenyl) -anthrone 1,8-Dihydroxy-10- (4'-methoxy-phenyl) -anthrone 1,8-Dihydroxy-10 (3'-trifluoromethyl-phenyl) -antrone 1,8-Dihydroxy-10- (3'-methoxy-phenyl) -anthrone 1,8-dihydroxy-10% 3'-hydroxy-phenyl) -anthrone 1,8-Dihydroxy-10- (2'-methoxy-phenyl) -anthrone 1,8-Dihydroxy-10- (2-thienyl) -anthrone 1,8-dihydroxy-1042-thiazolyl) -antrone.

Among the straight or branched alkyl groups having from 1 to 10 carbon atoms include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, heptyl, the nonyl and decyl groups. l When the group R10 represents a cycloalkyl group, this is a cycloalkyl group. lopropyl, cyclobutyl, cyclopentyl or cyclohexyl group.

When the phenyl group is substituted with an alkyl group it is preferably a methyl, ethyl or t-butyl group.

When the phenyl group is substituted with an alkoxy group, this is preferably a methoxy or ethoxy group.

When the phenyl group is substituted with a halogen atom, this is preferably a chlorine or fluorine atom.

As can be seen from the general formula (II) above, the compounds according to the invention are in the form of mono- or di- esters of 10-acyl-1,8-dihydroxyanthron or their isomers, namely the mono- or di-esters of 10-acyl-1,8-dihydroxy-9- -anthranol or further in the form of triesters of 10-acyl-1,8-di- hydroxy-9-anthranol. 10 15 20 25 30 35 459 807 e Among the esters of formula (II), mention may be made in particular of the following jande: 10- (3'-methoxy-phenyl) -1.8.9-triacetoxy-anthracene 10- (3'-methoxy-phenyl) -1,8,9-tripropanoyloxy-anthracene 10- (2-thienyl) -1.8.9-triacetoxy-anthracene 10- (2-thienyl) -1.8.9-tripropanoyloxy anthracene 10- (2-thienyl) -1,8-dipivaloyloxy-anthrone Compounds of formula (I) according to the invention are obtained in two steps starting from 1,8-dihydroxyanthraquinone as follows reaction scheme: on o on on o o I) Ar- 2) n * ° Ar ou <9 <_2_> ou o ou Are U) The first step is to convert an aromatic carbonate with the 1,8-dihydroxy-anthraquinone (I) as. after acidification. to the compound of formula (II). leader The second step is to reduce the intermediate (2) in presence of metallic tin or tin (II) chloride. which leads to the compound of formula (I) according to the invention.

The supply of the aromatic carbonate can be provided either starting from an organometallic compound or a magnesium organic compound. 10 15 20 25 30 35 7 459 807 The aromatic lithium organic compounds can be obtained with two different methods: The first method consists in converting butyllithium or its complex with tetramethylethylenediamine with an aromatic compound. whose present substituent or substituents activate the carbon on which it is desired to perform the metal synthesis with it later.

In particular, the methods described by D.W.

SLOCUH et al. J.O.C., p. 3653, 1976 or by V. SNIECKUS et al. J.O.C .. 44. p. 4803. 1979.

The second method for producing aromatic lithium compounds consists in treating a halogenated aromatic derivative water, in particular a brominated derivative of butyllithium with de as described by P. BEAK et al., Ace. Chem. Res., 306. 1982 and H.E. PARHAH et al., Aco. Chem. Res. 1982. methods, sid. sid. 300, When it is desired to obtain the aromatic carbonate outgoing from a magnesium compound is used as in the foregoing the method a halogenated aromatic derivative. which one converts with the usual methods of magnesium compound in an aqueous free solvent such as tetrahydrofuran or ether.

That procedure. consisting of the conversion of an aromatic lithium compound with the 1,8-dinydroxy anthraquinone. especially preferred for in contrast to the aromatic magnesium compound leads this process to a selective addition of the carbonyl in 10-position in the anthraquinone core. which is not the case with those the aromatic magnesium compounds, for one observes in some case an addition 1 9 position ..

It has further been found that by using a large excess lithium aromatic compound of at least 4 molar equivalents in relation to the 1,8-dinydroxy anthraquinone is not necessary. as in the known methods. to hire one 10 15 20 25 30 35 459 807 8 protection of the hydroxyl function 1 or 8 position in order to needle aromatic derivatives in the 10-position in the anthron nucleus.

The addition reaction of the aromatic lithium compound on 1.8- The dihydroxy anthraquinone is generally carried out in an anhydrous solvents such as ethyl ether or tetranydrofuran at a temperature temperature between -B0 and 0 ° C by adding the aromatic lithium compound ' 1 ether or tetrahydrofuran to a solution in the same solvent of the 1,8-dihydroxy-anthraquinone.

After the addition, the reaction mixture is kept under stirring at the same temperature for a time between 30 minutes to 2 hours. The end of the reaction is determined by the absence of 1,8-di- hydroxyanthraquinone by thin layer chromatography.

The acidification of the reaction mixture is then continued at room temperature, after which it is washed with water and dried the organic phase over anhydrous magnesium sulphate.

After evaporation of the solvent, the intermediate is purified (2) or the 10-aryl-1,8,10-trihydroxy anthron by recrystallization from chromatography on silica gel.

When the reaction is carried out on the basis of an aromatic magnesium compound is similar to the reaction conditions. which was used going from an aromatic lithium compound, but after completion addition is allowed to return to room temperature and continues stirring for several hours. possibly during reflux of means. until the 1,8-dihydroxy anthraquinone disappears at thin layer chromatography.

The second step in the process is to reduce 10-aryl-1,8.10-trihydroxy-anthrone (II) to obtain the compounds of the invention of formula (I). whereby this re- production reaction is carried out in an acetic acid environment in the presence of stannous chloride or metallic tin and concentrated hydrochloric acid. 10 15 20 25 30 35 9 459 807 The reaction is generally carried out at room temperature below one time between 1/2 and 5 hours, the end point of the reaction being due to the absence of the starting product with the thin-film chromatography. F * if the reaction is not complete, the reaction mixture may held in water baths.

After returning to room temperature, the reaction mixture is kept in water, causing precipitation of the desired product, which is then purified by recrystallization into a suitable solution. means.

The esters of formula (II) are obtained by reacting a suitable acid anhydride with a 10-aryl-1,8-dihydroxy-anthraquinone with formula (I) in the presence of a few drops of pyridine and by to optionally bring the reaction mixture to a temperature between 50 and 130 ° C or by using an acid chloride in presence of pyridine in stoichiometric amount in an aromatic solution agents such as toluene.

The preparation of the mono-, di- or tri-esters is a functional the molar proportions of the acid anhydride reacted or the acid chloride and the reaction time.

The invention also relates to pharmaceutical and cosmetic compositions. characterized in that they contain as active ingredient at least one compound of formula I or II.

In these compositions, the concentration of active ingredient varies. dies 1 generally from 0.005 to 170 wt-2 as a function of method of administration.

These compositions may additionally contain inert or pharmaceutical compositions. codynamically active additives e.g. binder. fillers. out- additives, thickeners, preservatives, etc. 10 15 20 25 30 35 459 807 1 ° The compositions administered orally may also contain flavoring agents. average. the compositions administered topically may be present in the shape of pomaäor. salvor. creams. gels. tinctures. solutions. lotio- down. sprayer. suspensions, micronized powders or shampoos nutrients.

According to this embodiment, apply man on the zones of the skin. to be treated. í one or two administrations from 1 to S g of a composition containing from 0.01 to 5 g of the active substance per 100 g of composition.

The compositions. administered enterally or parenterally may be in the form of tablets. granules. gelatin capsules. capsules. sírupar. drinkable suspensions. bag or further í pensions. swallowable powder i in the form of injectable solutions or For enteral or parenteral administration, give in generally from 0.05 to 5 g of the active substance per day to the adult in one or two rounds.

The experiments performed have been able to show that the associations according to the invention has a good activity when incorporated into various pharmaceutical or cosmetic vehicles.

Below is shown by way of illustration and without any restrictive nature several examples of the production of according to the invention.

Example 1 Preparation of 1,8-dihydroxy-10-ERN-2 ", 2" -dimethyl-pro- panovyl) -2'-amino-phenyl] -antrone. a) To 18 g of N-pivaloylaniline in 100 cm 3 of tetrahydrofuran (THF) anhydrous is set at 0 ° C under inert atmosphere 100 cm 3 n-butyl-lithium (2.5 h). 10 15 20 25 30 35 n 459 807 After addition, the reaction mixture is left for 24 hours at room temperature. You then add drop by drop 0 ° C a solution of 5 g of 1,8-dihydroxy-anthraquinone in 100 cm: anhydrous tetrahydrofuran (THF). He touches for 4 hours room temperature. after which the solution is acidified down to 75 cm3 acetic acid. He pours in 500 cn3 of water and extracts using dichloromethane. The organic phase is dried over magnesium sulfate. then concentrated under reduced pressure. The desired product is purified by chronatography on silica gel. He thus obtaining 1 g of yellow crystals of 10 - [(N-2 ", 2" -di- methyl-propanoyl) -2'-amino-phenyl] -1,8,10-trihydroxy-anthrone with melting point 2s7_2s9 ° c.

The NHR spectrum is consistent with the structure of the expected the product.

Elemental analysis: C 25 H 21 O 5 N Calculated: C 71.92, H 5.55. 0 19.16. N 3.35 Found: 71.71 5.56 18.92 3.43 b) To a suspension of 250 mg of 10-f (N-2 ".2" -dimethyl-pro- panoyl) -2'-amino-phenyl -1] -1,8,10-trihydroxy-anthrone, obtained above under (a) in 25 cm3 of glacial acetic acid is placed under inert moss sphere 400 mg tin (II) chloride and a few drops concentrated hydrochloric acid.

Stir for 2 hours at room temperature. after which the reaction the mixture is poured into 100 cm3 of water. The desired product falls out and is filtered. then dried. He resume: then using 50 cn3 dichloromethane. which is stirred in the presence of 2 g silicic acid. The solution is filtered. then concentrated below reduced pressure. The desired product is precipitated by the addition of hexane. centrifuged. then dried. You thus obtain 100 mg of yellow crystals, m.p. 176 DEG-177 DEG.

The NHR spectrum corresponds to the structure of the desired one the product just like mass spectrum m / e 401. 10 15 20 25 30 35 459 807 12 Example 2 Preparation of 1,8-dihydroxy-10- (2 ', 4'-dinethoxy-phenyl) -anthrone a) To a solution of 22.1 g of 1,3-dimethoxybenzene in solution i 50 cm 3 of anhydrous ethyl ether are added 100 cnz of n-butyl ten (1.6 M) at room temperature under argon. After 24 hours this solution is rapidly added with a suspension of 5 g of 1.8- . . _ _ 3 _ _ -d1hydrox1-anthraclonone 1 150 cm 3 of anhydrous THF at a temperature temperature at -70 ° C. After the sale is completed, the reaction is acidified. the mixture with the aid of S0 one glacial acetic acid. After washing with water (200 cm) and drying over magnesium sulphate the organic phase is centered under reduced pressure. by chromatography of a yellow powder then cleaned on silica gel. He thus receives 200 mg of 10- (2 ', 4'-dimethoxy-phenyl) -1,8,10-tri- hydroxy-anthrone, m.p. 207 ° C.

NHR spectrum 1H 250 MH: corresponds to the structure of the expected product.

Elemental analysis: C H O 22 18 6 Calculated: C 69.85 H 4.79 Found: 70.54 4.85 b) To a solution of 100 mg of 10- (2'.4'-dinethoxy-phenyl) -1,8.10- -trihydroxy-anthron; as obtained in (a) above 25 cm of glacial acetic acid is placed under an inert atmosphere 200 mg tin (II) chloride and a few drops of concentrated hydrochloric acid. Reactive The mixture is stirred for 5 hours at room temperature. heel- then read in 100 cm3 of water, which results in the desired the product falls out. which is then filtered and dried. He thus obtaining 50 mg of a cream-colored powder. whose molten point is 15200.

Mass spectrum mle: 362.

Example 3 Preparation of 1,8-dihydroxy-10- (4'-methoxy-phenyl) -anthrone 10 15 20 25 30 '35 13 459 807 a) To a solution of 28 g of para-bromoanisole in 50 even aqueous free tetrahydrofuran is set at -78 ° C and below argon 100 cms N-hutyl-lithium (1.6 M). He lets the solution return to room temperature below 1 hour. You pour it into a hronan pull and a suspension of 7.2 g of 1,8-dihydroxy-anthra- quinone in 300 cm 3 of anhydrous THF at a temperature of -78 ° C and under argon. Upon completion of the addition, the reaction the mixture returns to room temperature below 24 tins. He then acidifies the reaction mixture with the aid of SO tíka and you pour in S00 cm3 of water.

After extraction with the aid of dichloromethane, the organic is dried phase over magnesium sulphate. then concentrated under lowered print.

He thus receives after chromatography on silica gel 3.4 g desired product. After recrystallization from a mixture of toluene-hexane to give yellow crystals of 10- (4'-methoxy- -phenyl) -1.8.10-trihydroxy-anthrone, m.p. 172-17300.

The NHR spectrum corresponds to the structure of the desired one the product.

Elemental analysis: C H 0 21 16 S Calculated: C 72.40 H 4.63 0 22.97 Found 72.47 4.61 22.87 b) To a suspension of 200 mg 10- (4-methoxy-phenyl) -1.8.10- -trihydroxy-anthron. as obtained under (a) above. i 10 cm3 of glacial acetic acid, 200 mg of stannous chloride and a few are added drops of concentrated hydrochloric acid. He continues the ol 'movement under an inert atmosphere for 2 hours. The desired product is obtained by precipitating the reaction medium in 100 units of water. ten. 150 mg of a yellow greenish powder are thus obtained. ver. which decomposes from 215 ° C. nun-Spectra: and mass spectra (m / e = 332) correspond to the structure of the desired product. 10 15 20 25 30 35 459 807 14 Elemental analysis: C 1 H 16 04 Calculated: C 75.89 H 4.85 O 19.25 Found: 75.78 4.80 19.26 Exemgel 4 Preparation of 1,8-dihydroxy-10- (3'-trifluoronethyl-phenyl) - -antron a) To a solution of 25 g of 3-trifluoromethyl-bronobenzene in 100 ml of anhydrous THF is added 100 cma n-butyl lithium (1.6 H) _ o v1d -78 ° C under argon.

After the addition is complete, the reaction medium is allowed to return to room temperature.

The resulting solution was then added. drop by drop un- inert atmosphere, with a suspension of 7.2 g of 1,8-dihydroxy -anthraquinone in 200 cm 3 of anhydrous THF at -78 ° C.

The reaction mixture is kept at this temperature for 1 hour. ma. then brought to room temperature. is then made by adding 50 cma of glacial acetic acid. Reaction the dium is washed with 200 cm 3 of water. torkas.

The reaction solutions are concentrated. then cleaned on silica gel column. Isolate 1.2 g desired product, which is recrystallized from a mixture of toluene -nexan. He receives yellow crystals of 10- (3'-trifluoro- methyl-phenyl) -1.8.10-trihydroxy-anthrone with melting point 222-223 ° C.

NHR spectrum fl 250 Mhz corresponds to its structure desired product.

Elemental analysis C F O 21 H13 3 4 'seräxnauz c 65.30 H 3.39 Found: 64.95 3.35 b) To a solution of 150 mg of 10- (3-trifluoromethyl-phenyl) - -1,8,10-trihydroxy-anthron, as obtained under (a) herein 10 15 20 25 30 35 OVBII, H 459 807 in 25 cm 3 of glacial acetic acid. placed under nitrogen. you put 200 mg of stannous chloride and a few drops of concentrated hydrochloric acid.

The reaction mixture is stirred for 3 hours at room temperature. lucky. after which the desired product is precipitated during batch of 100 one water. The product is filtered. then dried.

S0 mg of a yellow product is obtained. whose melting point is 210-211 ° C.

Mass spectrum: m / e: 370 Example 5 Preparation of 1,8-dihydroxy-10- (3'-methoxy-phenyl) -anthrone a) The organomagnesium method To 2.7 g of magnesium in 40 cm 3 of anhydrous THF is added nitrogen 20.8 g of m-bromoanisole under reflux of THF. The reflux is maintained for 1 hour after the addition is complete.

The reaction mixture is then added dropwise to one suspension of 5,9 1,8-dihydroxy-anthraquinone in 60 cm 3 of aqueous free THF under nitrogen and at 0 ° C. The reaction mixture is left overnight at room temperature. then heated for 8 hours at so ° c.

The reaction mixture is acidified by adding 9 cm3 of ice. vinegar, after which 150 cm3 of water are added. Man extrahe- the product with ethyl ether (100 cm 3). and the organic then dried. then concentrated in vacuo. Reaction mixture The residue is then purified by chromatography on silica gel to give contains 1.2 g of 10- (3'-methoxy-phenyl) -1,8,10-trihydroxy-anthrone.

NH spectra and mass spectra (m / e = 348) correspond to the structure of the desired product. a ') The organolithium compound method . . . 3.

To a solution of 28 g of m-bromoanisole 1 50 cm 3 of anhydrous THF at -78 ° C under argon 100 cm 3 of n-butyllithium are added 10 15 20 25 30 35 459 807 15 (1.6 H). The reaction solution is then allowed to return to room temperature. temperature below 1 hour. The solution obtained is transferred separately. and a suspension of 7.2 g 1,8-dihydroxy-anthraquinone in 300 cna of anhydrous THF at -7a ° c and under argon. After the addition is complete, you let go the reaction mixture is returned to room temperature for 24 hours. mar. He then acidifies with the help of 50 ones you wash with S00 cm3 of water. race, glacial acetic acid. after which The organic phase separates then dried over magnesium sulfate and concentrated reduced pressure. The desired product crystallizes by adding rate of toluene. He thus isolates 4.2 g of 10- (3'-methoxy) -phenyl) -1.8.10-trihydroxy-anthron with melting point 202 ° C.

The NHR spectrum corresponds to the structure of the desired one the product.

Elemental analysis C H O Zl 16 5 Calculated: C 72.40 H 4.63 0 22.97 Found: 72.73 4.61 22.62 b) To a solution of 3 g of 10- (3'-methoxy-phenyl) -1.8.10-trihydride oxy-anthron, as obtained by one of the above methods der (a) eller (a ') i ca 100 cma ísättíka. kept below inert . 3 atmosphere add 3 g of tin (II) chlor1d. then 3 cm hydrochloric acid. The reaction mixture is then stirred under 2 hours at room temperature. after which the desired product precipitate by adding 500 cm 3 of water. After drying, 2.7 g of a yellow powder with a melting point of 187 ° C are kept.

The NHR spectrum corresponds to the structure of the desired one the product.

Elemental analysis: 0 C21 H16 4 Calculated: C 75.89 H 4.85 O 19.25 Found: 75.71 4.92 19.24 Example 6 Preparation of 1,8-dihydroxy-10- (3'-hydroxy-phenyl) -anthrone 10 15 20 25 30 35 17 459 807 He puts 500 mg of 1,8-dihydroxy-10- (3'-netoxy-phenyl) -anthrone. eating tic acid and 17 cm3 of hydrobromic acid under an inert atmosphere. MAN warms to 100-110 ° C and the evolution of the reaction is followed. as obtained in Example 5 to a solution of 35 cm 3 by thin layer chromatography. Then the starting product completely disappeared, the solution is poured onto about 200 cn3 of water. and the precipitate is filtered. After drying, the product dissolves in 100 cm3 of dichloromethane. is then stirred in the presence of 3 g of silicon. acid. The solution is filtered, then concentrated under immersion print. The desired product crystallizes by adding hexane. There are thus obtained 310 mg of yellow crystals with molten point 2o4 ° c.

The NHR spectrum corresponds to the structure of the desired one the product.

Elemental analysis: C20 H14 04 Calculated: C 75.46 H 4.43 O 20.11 Found 75.57 4.37 19.96 Example 7 Preparation of 1,8-dihydroxy-10- (2'-methoxy-phenyl) -anthrone a) To 2.55 g of magnesium in 15 cm 3 of anhydrous THF is added under nitrogen 16.2 g of o-bromoanisole under reflux of THF. Re- the course is maintained for 1/2 hour after the addition is complete.

The resulting solution is then added drop by drop a suspension of 5 g of 1,8-dihydroxyanthraquinone in thien-free THF under nitrogen and at 0 ° C. The reaction mixture left overnight at room temperature. then acidified with 9 cm3 of glacial acetic acid, which was added with 150 units of water.

The organic phase is decanted. washed twice 'with water (100 cm 3) is then dried over magnesium sulphate. The solution con- then centered under vacuum. then resumed with toluene.

The solution is filtered by adding hexane. You get S g of a yellow precipitate. which is recrystallized from a mixture of 10 15 20 25 30 35 459 807 N luen-hexane. The resulting light yellow crystals of 10- (2 ' oxy-phenyl) -1.8.10-trihydroxy 220 DEG-21 DEG. -met- -antron has a melting point of Elemental analysis: 0 C21 H16 s aeraxnar: c 12.40 H 4.63 o 22.97 Found: 72.59 4.65 23.21 b) To a solution of 2.8 g of 10- (2'-methoxy-phenyl) -1.8.10-tri- hydroxy-anthron. as obtained under (a) above. i 90 3 cm glacial acetic acid. held under an inert atmosphere. you set 4.9 g of stannous chloride, then 14.5 cn3 of concentrated hydrochloric acid.

The reaction mixture is then stirred at room temperature for 3 hours hours. The desired product is precipitated by reacting the reaction medium with the dium is poured into 200 cm 3 of water. He thus obtains 1 g of pure product after chromatography on silica gel. The yellow obtained the crystals have a melting point of 191 ° C.

NHR spectra and mass spectra (mle = 332) correspond to the structure of the desired product.

Elemental analysis: C 0 21 H16 4 Calculated: C 75.89 H 4.85 0 19.25 Found: 75.96 4.92 19.30 Example 8 Preparation of 1,8-dihydroxy-10- (2-thienyl) -anthron a) To a solution of 12.7 one thiophene in 100 cm3 of anhydrous ethyl ether is added 100 cm 3 of n-butyl-lithium (1.6 H) at 0 ° C under argon. After addition, the solution is kept at 0 ° C der l hour, after which it is allowed to return to room temperature.

The resulting solution is then added dropwise to one suspension of 9.2 g of 1,8-dihydroxy-anthraquinone in 1000 cm3 of water tenfree THF at -78 ° C under argon. Reaction mixtures are allowed to return to room temperature. after which you acidify with 50 cm3 vinegar. 10 15 20 25 30 35 459 807 The solution is concentrated under reduced pressure. after which it taken up with ethyl ether. The brown precipitate formed is filtered then. then distributed in 100 cm3 of hot ethanol. He receives thus yellow crystals of 10- (2-thienyl) -1,8,10-trihydroxy- -antron with melting point 191-19200.

Elemental analysis: C H 04 S 18 12 Calculated: C 66.65 H 3.73 D 9.89 Found: 66.20 3.66 9.10 b) To a solution of 5 g of 10- (2-thienyl) -1,8-trihydroxy- -antron, as obtained in (a) above in 100 cm 3 of tic acid, 14.6 g of stannous chloride are placed under an inert atmosphere and 20 cm 3 of concentrated hydrochloric acid. He touches at room temperature for 2 hours. after which the solution is poured onto 200 cm3 water. It is filtered, then the product obtained is dried.

4.55 g of 1,8-dihydroxy-10- (2-thienyl) -antene are thus isolated. which, after recrystallization from toluene, has a melting point of 181-1a2 ° c.

NHR spectra and mass spectra (m / e = 308) correspond to the structure of the desired product.

Elemental analysis C18 H12 03 S Calculated: C 70.11 H 3.92 O 16.57 S 10.40 Found: 69.75 3.80 15.54 9.98 Example 9 Preparation of 1,8-dihydroxy-10- (2-thiazolyl) anthrone a) To a solution of 100 cm3 of n-butyl-lithium (1.S M) i l00 cm3 anhydrous ethyl ether is added drop by drop -4000 under inert atmosphere 24.6 g of 2-bromothiazole. After the reaction mixture is brought to -78 ° C and add 9.6 g of 1,89-dihydroxy-anthraquinone in solution in 1000 cm3 THF. The reaction medium is then allowed to stand for 48 hours room temperature, Acidification is carried out using 50 cm3 of acetic acid. _ U _ 3 after which the solution is poured onto 1000 cm of water. 10 15 20 25 30 35 459 807 2 ° The organic phase is dried over magnesium sulphate. concentrated then at reduced pressure. The desired product is purified by matography on silica gel. He thus isolates 3.5 g 10- (2 zolyl) -1.8.10-trihydroxy-anthron. contained in yellow solid. which is recrystallized in toluene-nexan. -ten- forn of one a mixture of The crystals have a melting point of 223-225 ° C, NHR spectra and mass spectra (nle = 325) correspond to the structure of the desired product.

Elemental analysis: C H 17 ll N 04 S Calculated: C 62.76 H 3.42 O 19.67 N 4.30 S 9.86 Funnett 62.85 3.41 19.63 4.39 9.66 b) To a suspension of 2 g of 10- (2-thiazolyl) -1,8,10-trihydrate oxy-anthron. as obtained under (a) above in 75 acetic acid add 2 g of metallic tin and 25 acid. He heats the mixture in a water bath for 1 hour, each at the starting product completely goes into solution. He pours on 200 cmz water. then filters the product obtained. thus gives 1 g of 1,8-dihydroxy-10- (2-thiazolyl) man recrystallizes in He -antron. as methanol. The recrystallized product melting point is 142 ° C.

Elemental analysis C N 0 S 17 H11 3 Calculated: C 66.00 H 3.58 N 4.52 O 15.51 S 10.35 Found: 66.15 3.60 4.60 15.92 10.15 Bxemgel 10 Preparation of 10- (3'-methoxy-phenyl) -1.8.9-triacetoxy-anthracene In a three-necked piston equipped with magnetour stirrer. nitrogen inlet. stir 200 mg of 10- (3'-methoxy-phenyl) -1,8-dihydroxy-anthron. your- held according to Example 5, in 5 cm 3 of anhydrous acetic acid and a few drops of pyridine. The mixture is stirred at 80 ° C for 3 hours hours, after which it is cooled. The desired triester crystallizes and centrifuged, after which it is washed with hexane. You are- holds 150 mg of light yellow crystals, m.p. 278 ° C. 10 15 20 25 30 35 21 459 807 Elemental analysis C H 0 27 22 7 Calculated: C 70.73 H 4.84 0 24.43 Found: 70.47 5.01 24.24 Example ll Preparation of 10- (3 '- methoxy-phenyl) -1.8.9-tripropanovloxy- -anthracene 4 In a three-necked flask equipped with a magnetic stirrer, stir 250 mg 10- (3'-methoxy-phenyl) -1,8-dihydroxy-anthrone. received a Example 5 in 5 cm 3 of propionic anhydride and a few drops pyridine. The mixture is stirred at 80 ° C for 6 hours inner atmosphere.

The solution is poured into 100 cm 3 of water, extracted with ether, with an aqueous solution of sodium bicarbonate. He dries se- over magnesium sulfate, then concentrate under lowered print. He isolates 200 mg of the desired triester through addition of hexane.

The yellow crystals obtained have a melting point of 177-178 ° C. NHR spectra and mass spectra (m / e: 500) correspond to the structure of the desired product.

Example 12 Preparation of 10- (2-thienyl) -1,8.9-triacetoxy-anthracene In a three-necked flask equipped with a magnetic stirrer, stir 250 mg 10- (2-thienyl) -1,8-dihydroxy-anthron. obtained according to examples 8. in S cm3 acetic anhydride and a few drops of pyridine.

The mixture is stirred for 3 hours at 80 ° C under an inert atmosphere. after which it is cooled. The desired triester ester crystallizes and then centrifuged and washed with hexane. He thus receives da 300 mg light yellow crystals, m.p. 260 ° C.

Elemental analysis: C24 H18 06 S Calculated: C 66.35 H 4.17 O 22.10 S 7.38 Found: 66.35 4.19 22.20 7.26 10 15 20 25 30 35 459 807 22 Example 13 Preparation of 10- (2-thienyl) -1,8,9-tripro Danoyloxy anthracene In a three-necked flask equipped with a magneton stirrer, stir 250 mg 10- (2-thienyl) -1,8-dihydroxy -antrons obtained according to examples 8 i 5 cm3 of propionic anhydride and a few drops of pyridine.

The mixture is stirred at 80 ° C for 6 hours under nitrogen.

Cooling results in the desired product. He isolates 120 mg yellow crystals. The filtrate is poured into 100 cn3 of water, ext- raheras with ether. washed with an aqueous solution of sodium carbonate. after which the ether phase is dried and concentrated underneath reduced pressure. By adding hexane to the residue obtained an additional 130 mg of the desired triester. The light yellow ones the crystals have a melting point of 192 ° C. NHR spectrum and mass spectrum (m / e: 476) corresponds to the structure of the desired one the product.

Example 14 Preparation of 1,8-dipivaloyloxy-10- (2'-thienyl) -anthrone To a solution stirred at normal temperature under the protection of light and humidity of 2 g of 10- (2'-thienyl) -1,8-dihydroxy- -antron 1 150 one anhydrous toluene one sets the fin equivalent- pyridine and immediately after five molar equivalents of pivaloyl chloride. The reaction mixture is then brought to reflux 8 hours, during which time the entire starting product is converted.

The reaction medium is then concentrated under reduced pressure. re- taken up with water and extracted with methylene chloride.

The methylene chloride phase is washed with water, magnesium sulfate and concentrated. decanted, dried over The resulting solid is recrystallized from a mixture of hexane-ethyl acetate. He receives 1.5 g of yellow crystals. as melts at 17 °. 10 15 20 25 30 35 23 459 807 The NM and mass spectra (m / e: 476) correspond to the structure of the desired product.

Pharmaceutical and cosmetic compositions Example 1 Kagslar containing 0.5 g of powder In capsules consisting of gelatin. titanium dioxide and preservatives conditioner: 0.5 g of the following powder: 1,8-Dihydroxy-10- (2'-methoxy-phenyl) -anthrone. . . . . . . . . .... 0.3 g - potatisstärke1se ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..0.1 g - lactose g.s.p. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..0.5 g Example 2 1 g tablets have been prepared from the mixture of the following ingredients: 1,8-Dihydroxy-10- (2-thienyl) -antrone. . . . . . . ............. 0.4 g - polyvinylpyrrolidone ........... . . . . . . . . . . . . . . . . . . . . . . ..0.0l3 g L crosslinked polyvinylpyrrolidone. . . . . . . . . . . ............. 0.0S g - talk ... . . . . _.... . . . . ................. . . . .............. 0.08 g silica "Aerosil 200" supplied by sté DEGUSSA0.001 g - lactose q.s.p .......................................... 100 g In this example, the 1,8-dihydoxy-10- (2-thienyl) anthrone can be replaced by taken with an equivalent amount of 1,8-dihydroxy-10 (3'-methoxy) -phenyl) -antron.

Exemgel 3 Komgositíon in the form of i sirag At the time of use, mix with stirring in 60 ml mineral water 30 g of a powder of the following composition: 10 15 20 25 30 35 459 807 24 1,8-Dihydroxy-10- (3'-hydroxy-phenyl) -antrone ............ 0.6 g - sodium benzoate . . . . _.......................... 0.l5 q - sodium chloride. . . . . _. ............ . . . . .................. o.23 g anhydrous sodium citrate. . . . . . . . . . . .................. l, l g - ammonium glycyrrhizinate. . . . . . . . . . . . . . . . . . _. ............ 0.06 g - arom q.s. - dye q.s.

- Sackaros q.s.p. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...... 3o g Once obtained, the syrup should be kept cool, whereby its stability does not exceed 7 days.

Exemgel 4 fl hydrophobic anhydrous gel 1,8-Dihydroxy-10- (3'-hydroxy-phenyl) -anthrone. . . . . . . . . . . . ..l g - silica “ABROSOL 200” supplied by sté DEGUSSA..7 g isopropyl myristate q.s.p. . . . . . . . . . . . . . . . _ ... . . . . . . . . . ..l00 g Example 5 fi hydrophobic, closing ointment 1,8-Dihydroxy-10- (2'-methoxy-phenyl) -anthrone. - ceresín ............................ . . . ............... 15 g - Vaseline oil. . . . . ........... . . . . . . .................... 35 g - Vaseline q.s.p ... . . . . . . . . . . _ ... . . . . . . . . ...... . . . . .... 100 g In this example, 1,8-dihydroxy-10- (2'-methoxy-phenyl) -anthro- is replaced by an equivalent amount of 1,8-dihydroxy-10- (3'- -methoxy-phenyl) -antrone.

Example 6 gygrophobic ointment in the form of pasta - 1,8-Dihydroxy-10- (2-thienyl} -antrone ._............... .1.5 g isopropyl myristate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..36.4 g silicone oil (dimethylpolysiloxane supplied by the company RHONE POULENC under the name RHODORSIL 47 V 300. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..36.4 g 5 10 15 20 25 30 35 25 459 807 - bivax ......... . . . ............... . . . . . . . . . . . . .... . . . ..l3.6 g silicone oil provided by sté GOLDSCHMIDT under the name "ABIL 300 000 est" q.s.p........ ...... l00 g Example 7 A dose of shampoo in two parts to mix at the moment l) Treating part in the form of suspension 1,8-Dihydroxy-10 - (3 '- methoxy-phenyl) -antrone. . . . . . . . . . . ..0.S g - Vaseline oil q.s.p ...... . . . .... . . . . . . . . . . . . . . . . . . . . ..100 g 2) Washing part dodecanediol polyglycerolated with 3.5 moles. . . . . . . ..... 20 g compound of the following form1: ......................... 1.75 g HO - (? H-CH 2 O) x - (CH 2 -CH 2 O) n - (CH 2 -EH) y -H R R = C H NJ 14 29 3 001111-70 .X-O-Y = - water q.s.p. . . . . . . . . . . ..... . . . . . . . . . . . . . ........... 100 g The treating part is mixed. after it has been stirred vigorously, i a bottle for application with that detergent portion in a pre- holding 10/90. Once the mixture is obtained, it should be turned immediately.

Exemgel 8 Anti-acne composition in the form of a cream _ magnesium lanolate. . . . . . . . . . . . . . . . . . . . . . .... . . . . . ....... 3.4 g - lanolin alcohol .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...... 2.8 g perhydrosvalence. . . . . . . . . . . . . . . . . . . . . . . . . . .... . . . . . . ._20 g isopropyl myristate. . . . .._.............................. 5 g - unprocessed sesame oil. . . . . ..... . . . . ......, ............ 10 g - Vaseline oil. . . . . . .f. . . . . . . . . . . . . . . . . . . . . . . . .... . . . . . ..8.8 g _ salicylic acid ........................................... l g - 10- (2-thienyl) -1.8.9-tripropanoyloxy-anthracene .......... 1 g methyl parahydroxybenzoate. . . . . . . . . . . . . . . . . . . . . . . . . . . . ..0.3 g - water q.s.p. . . . . . . . . . ...., ........; ................ 100 g 10 15 20 25 459 807 26 Example 9 Hair combination against hair loss and against dandruff 10- (3'-methoxy-phenyl) -1.8.9-triacetoxy-anthracene. . . . . . ..0.S 9 - salicylic acid. . . . . . . ......... . . . . . . . . . . . . . . . . . _ ... . . . ... 0.1 g benzyl salicylate. . . . . ...... . . . . . . . . . . . . . . . . . . . . . . . . ..100 g Bxemgel 10 Hair combination against hair loss and against dandruff 1,8-Dipivalovyloxy-10- (2'-thienyl) -antrone. . . . . . . . . . . . . ..0.8 g - tin (II) chloride. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..0.3 g - isopropyl myristate q.s.p ....... . . . . . . . . . . . . . . . . . . . . ..100 g Example 11 Lotions with seborrhea A solution consisting of 10 cm3 of ethanol 950 3 and 30 cm polyethylene glycol (PSG) 400 containing 30 mg of butyl hydroxy the cap was added with 0.2 g 1.8 -dipivalovyloxy-10- (2'-thienyl) - -antron.

After solubilization while stirring, apply lotion the whole man.

Preferably, this treatment should be performed twice a day.

Claims (14)

10 15 20 25 30 35 27 Patent claim 10-aryl-1,8-dihydroxy-anthrons. characterized in that they have the following general formula: OH O OH (I) Ar wherein: Ar denotes an aromatic radical having one of the following formulas: DU N 5 4 (i) Ra RI R2 wherein: R1. R2, R3. R4 and RS. l1ka or ollka. denotes a hydrogen atom, a halogen atom. the group -CF3. a hydroxyl function. a lower alkyl group. a lower cycloalkyl group, a lower hydroxyalkyl group. a lower alkoxy group. a nitrile function, a QIUPP SO zr 'z' r 'lr' 2 N \ r ", - (CH2) n-co N \ r", - (cH2) nN \ r ", o -N-co n '- CH -co '- å ", (2) n ZR or 1cHz) n- 10 15 20 25 30 35 459 807 28 r' and r". the same or different. lower alkyl group. and R 'represents a hydrogen atom or an n is 0 or an integer from l t.o.m. 3, and R "represents a hydrogen atom, a lower alkyl group. Straight or branched, at least one of the groups R 1 to R 6 does not represent a hydrogen atom, (ii) (iii) R 6 has one of the meanings given for the groups R 1 to R 5 and (iv) / <EN and the mono-, di- and tri-esters thereof of the formula (II) OR 8 Û H9 (II) Ar (H) p 'wherein: Ar has the same meaning as above, p is 0 or l. when p = 0 represents R, -CO R 18 represents a hydrogen atom or -CO R '10 and R 90 and p' is 1, when p = 1 represents R 7: (1) a RB represents a hydrogen atom or the group -CO R 10, R 9 represents the group -CO R 10 and p 'is 0. (2) or the group -CO R 10, Ra and R 9 represents the group -CO R 10 and p' is 0. H10 represents a straight or branched alkyl group having from 1 to 10 carbon atoms, a cycloalkyl group, a 2-pyridyl group, a 2-thienyl group or a phenyl group, optionally substituted by a lower alkyl group, a lower alkoxy group, a halogen atom, a nitro function, a group -CF3 or with a hydroxyl function, and mixtures of these esters. Compounds according to Claim 1, characterized in that the group Ar represents the aromatic radical of the formula: wherein 1: R 1 (or R 5) represents a lower alkoxy group or a group of the formula - N - CO-R 'IR ~ in R' a straight or branched alkyl group having from 1 to 5 carbon atoms and R "represents a hydrogen atom, R 3 represents a hydrogen atom or a lower alkoxy group. and R 2, R 4 and R 5 (or R 1) represent a hydrogen atom. Compounds according to claim 1, characterized in that the group Ar represents an aromatic radical of the formula: wherein: R 2 (or R 4) represents a group -CF 3. a lower alkoxy group or a hydroxyl function and R1. R3. R (or R2) and RS represent a hydrogen atom. Compounds according to claim 1, characterized in that the group Ar represents the aromatic radical of the formula: Rs Ra Ra RI Rzr wherein: a 3 represents a lower alkoxy group and RI. R2. R4, R5 denote a hydrogen atom. Compounds according to any one of claims 1 to 4, characterized in that they are selected from those consisting of: n QIUPP, 1,8-dihydroxy-10- (N-2 ".2" -dimethylpropanoyl) 2 ' -amino-2'-phenyl-anthrone 1,8-dihydroxy-10- (2'.4 *-dimethoxy-phenyl) -antrone 1,8-dihydroxy-10- (4'-methoxy-phenyl) -anthrone 1,3- Dihydroxy-10- (3'-trifluoromethyl-phenyl) 1,8-dihydroxy-10- (3'-methoxy-phenyl) -antrone 1,8-Dihydroxy-10- (3'-hydroxy-phenyl) -antrone 1,8-dihydroxy- 10- (2'-methoxy-phenyl) -anthrone 1,8-dihydroxy-10- (2-thienyl) -anthrone 1,8-dihydroxy-10- (2-thiazolyl) -anthrone. -antron a Compounds according to claim 1, characterized in that they are selected from that group. consisting of: 10- (3 '10- (3'-methoxy-phenyl) -1,8,9-triacetoxy-anthracene-methoxy-phenyl) -1.8.9-tripropanoyloxy-anthracene 10- (2-thienyl )- 1,8.9-Triacetoxy-anthracene 10 15 20 25 30 35 459 807 31 10- (2-thienyl) -1.8.9-Tripropanoyloxy-anthracene 10- (2-thienyl) -1,8-dipivalovyloxy-anthrone. A process for the preparation of the compounds of formula (I) OH 0 OH (I) Ar wherein: Ar represents an aromatic residue having one of the following formulas: 4 (1) Ra R1 R1 R2 wherein: R1. H2. R3. R4 and Rs. the same or different. denotes a hydrogen atom. a halogen atom. the group -CF3. a hydroxyl function. a lower alkyl group. a lower cycloalkyl group. a lower hydroxyalkyl group, a lower alkoxy group. and nitrile function, and QIUPP l II ,, r 1 ,: zlr soz nkr ". ~ (cH2) n-co lkr", - (cH2) nN \ I ", 0 _ _ I _ ._ I _ n co R, (c fl gn cozn or (cn2; n- RIU the same or different. denotes a hydrogen atom or a l to 3. straight r 'and r ". n is 0 or an integer from a lower alkyl group. lower alkyl group. and R' and R "denotes a hydrogen atom. Or branched. Wherein the at least one of the groups R1 to R is a hydrogen atom. (Ii) (iii) R6 has one of the meanings, to Rs and Åš and mono-, di- and tri-es OR8% (wherein: 32 N thereof thereof of formula (II) 217)? 0 119 (II) Ar has the same meaning as Above, p is 0 or 1. when p = 0 represents RB one represents -CO H10 when p = 1 represents R7: (1) a hydrogen atom, -CO R (2) or the group -CO H10 hydrogen atom or -CO R10 and R and p 'are 1, RB and R9 represent group 5 does not represent one given for the groups R1 9 Ra denote a hydrogen atom or the group -co '". lo, R9 denotes the group E10 and p ar 0 10 15 20 25 30 35 459 867 33 -CO H10 R10 denotes a straight el branched alkyl group having from 1 to 10 carbon atoms, a cycloalkyl group. and 2-pyridyl group. a 2-thienyl group or a phenyl group. optionally substituted with a lower alkyl group. a lower alkoxy group. a halogen atom. a nitro function. a group -CF 3 or having a hydroxyl function, and mixtures of these esters, and p 'is 0, characterized in that it comprises those steps. which consists in: a) reacting 1,8-dihydroxy-anthraquinone with at least 4 molar equivalents of an aromatic lithium compound (Ar Li) in anhydrous solvent and, after acidification, isolating the resulting 10-aryl-1,8,10-trihydroxy -antronen. and 2) reducing the 10-aryl-1,8,10-anthron in acetic acid environment in the presence of stannous chloride or metallic tin and concentrated hydrochloric acid and isolating the 10-aryl-1,8-dihydroxy anthron of formula (I) by precipitation in water. Process according to claim 7, characterized in that the first step is carried out in ethyl ether or tetrahydrofuran at a temperature between -80 and 0 ° C and for a time between 30 minutes. and 2 hours. 9. A method according to claim 7. CHARACTERIZED IN THAT the second step is performed at room temperature for a time between 0.5 and 5 hours. 10. Pharmaceutical or cosmetic compositions. characterized in that they contain as active substance at least one compound according to any one of claims 1 to 6 or obtained according to any one of claims 7-9, of the formula (I) Ar 10 15 20 25 30 35 459 807 Wherein: Ar represents an aromatic radical having one of the following formulas: RS Ra (1) 'R3 RI gz wherein: RI. R2. R 3, R 4 and R 5, a hydrogen atom, the same or different, represent a halogen atom, the group -CF 3. A hydroxyl function. a lower alkyl group, a lower cycloalkyl group PPP. a lower hydroxyalkyl group - a lower alkoxy group. and nitrile function. and QIUPP I 'f' r '_ O Z _ _ r' _ _ I s 2 N., (CH2) n CO N \\ r'¿ (cH2) n N \ H r I o-I-ï-I- _. _ _ _ z _ n co R. (cn2) n coza or (cn2) n- <Ru N __ 'r' and r ", the same or different. denotes a hydrogen atom or a lower alkyl group. n is 0 or a number from and R 'and R" denote a hydrogen atom. or branched. 1 p.m. 3, a lower alkyl group. straight wherein at least one of the groups R1 to RS does not represent a hydrogen atom. (ii) (iii) 10 15 20 25 30 35 35 R has one of the meanings given for the groups R / šï 1 s: '11 a N 1 and (iv) and the mono-, di- and tri-esters thereof with the formula (II) 0 R 8 Û X9 \ / (n) Ar (H) "'wherein: Ar has the same meaning as Above, p is 0 or 1. When p = 0, R 8 represents a hydrogen atom or -CO R 10 represents - CO E10 and p 'are 1. when p = 1 represents R7: (1) a hydrogen atom, R and R9 represent a hydrogen atom or the group 8 -CO R10, R9 represents the group -CO R10 and p' is 0, (2) or the group -CO R 10. R 8 and R 9 represent the group -CO R 10 and p 'is 0, R 10 represents a straight or branched alkyl group having from 1 to 10 carbon atoms. a cycloalkyl group, a 2-pyridyl group. a 2-thienyl group or a phenyl group, optionally substituted with a lower alkyl group - a lower alkoxy group. nitrofunction. a group -CF 3 or with a hydroxyl function. and mixtures of these esters. and HGIOQEIIBCOITI. one ll. Composition according to claim 10. characterized in that it contains the active compound in a concentration of between 0.005 and 70% by weight relative to the total weight of the composition. And R 'and R "represent a hydrogen atom. 459 807 36 Compounds of the formula (JH 0 OH (I) Ar wherein: Ar represents an aromatic radical having one of the following formulas: (i) wherein: R 1, R 2, R 3, R 4 and R 5, the same or different, represent a hydrogen atom. the halogen atom, the group -CF, a neutroxyl function, a lower alkyl group, a lower cycloalkyl group, a lower hydroxyalkyl group, a lower alkoxy group, a nitrile function, a QCUPP r 'r '50 N / f (fC fl) -CO N / _ (CH _ / r 2 \ rn 2 Il \ r "2) n N \ r" I -N-co R ', I 0 ~ (CH) -Co R' ell r - (CH Ru 2 n 2 e 2) n_ __ r 'and r ", the same or different, denote a hydrogen atom or a lower alkyl group. n is 0 or a number from 1 to 3. a lower alkyl group, straight or branched. wherein at least one of the groups R1 to R 6 does not represent a hydrogen atom, (ii) (iii) R 6 has one of the meanings given for the groups R 1 to R 5 and N (iv) and the mono-, di- and tri-esters thereof of the formula (II) 0 Ra 0: (R7) P o 119 (II) wherein: Ar has the same meaning as above, p is 0 or 1. when p = 0, RB represents a hydrogen empty or -CO R 10 and R 9 denote -CO R 10 and p 'is 1.' when p = 1 denotes R 7: (1) a hydrogen atom. Ra represents a hydrogen atom or the group -CO R 10. R 9 represents the group -CO R 10 (2) or the group -CO R 10, R 8 and R 9 -CO R 10 and p 'is O. represents the group and p' is 0. 10 15 20 25 30 35 459 807 38 310 represents a straight or branched alkyl group having from 1 to 10 carbon atoms, a cycloalkyl group. a 2-pyridyl group, a 2-thienyl group or a phenyl group. optionally substituted with a lower alkyl group. a lower alkoxy group. a halogen atom. a nitro function. a group -CF 3 or having a hydroxyl function, and mixtures of these esters for use as a therapeutic. Compounds according to claim 12 for the use of cancerous tumors, tumors. injuries. g as a remedy for psoriasis. vârtor. rheumatism, eczema, seborrheic dermatitis. derma- dandruff and sunburn l4. Compounds according to claim 12 for use in the treatment of acne, dandruff. seborrhea and hair loss.