MXPA00012229A - Diarylselenide compounds and their use in human or veterinary medicine and in cosmetics - Google Patents

Abstract

The invention concerns novel diarylselenide compounds corresponding to the general formula (I) and the use thereof in pharmaceutical compositions in human or veterinary medicine (in the treatment of dermatological, rheumatic, cardiovascular and ophthalmologic pathologies in particular), or in cosmetic compositions.

Description

COMPOUNDS DIARILSELENUROS AND ITS USE IN HUMAN OR VETERINARY MEDICINE AS WELL AS IN COSMETOLOGY DESCRIPTION OF THE INVENTION The invention relates, as new and useful industrial products, to diaryl selenide compounds. It also relates to the use of these new compounds in pharmaceutical compositions intended for use in human or veterinary medicine, or even in cosmetic compositions. The compounds according to the invention have a marked activity in the fields of cell differentiation and proliferation, and find applications more particularly in the topical and systemic treatment of dermatological conditions linked to a keratinization disorder, dermatological (or other) affections of inflammatory and / or immunoallergic component and dermal or epidermal proliferations, whether benign or malignant. These compounds can also be used in the treatment of diseases of connective tissue degeneration, to combat skin aging, whether photoinductive or chronological and to treat healing disorders. They find, on the other hand, an application in the ophthalmological field, mainly in the treatment of corneopathies.

Ref: 125322 The compounds according to the invention can also be used in cosmetic compositions for body and hair hygiene. The present invention relates to compounds that can be represented by the following general formula (I): (i) wherein: Ri represents: (i) the radical -CH3 (ii) the radical -CH2-0-R5 (iii) the radical -COR6 having R5 and Re the meanings given below, - Ar represents a radical selected from the radicals of formulas (a) - (e) below: (a) (b) (c) (d) (e) having R the meaning given below, R2 and R3 identical or different independently represent a radical selected from: (i) a hydrogen atom, (ü) a selected radical between the tert.-butyl, 1-methylcyclohexyl or 1- adamantyl radicals, (iii) a radical -0R8, the meaning given below having R?, (iv) a radical p-lister, it being understood that at least one of the radicals R2 or R3 represents a radical (ii), - R2 and R3 taken together can form with the adjacent aromatic ring a saturated cycle of 5 or 6 links optionally substituted by methyl groups and / or optionally interrupted by an oxygen or sulfur atom, R4 represents a hydrogen atom, a halogen atom, a lower alkyl radical, an ORg radical, a polyether radical, or a CORIO radical, Rg and R10 having the meanings given below, R5 represents a hydrogen atom, a lower alkyl radical, or a radical COR n having the meaning given below Rn - R6 represents a radical chosen from: (i) a hydrogen atom (ii) a lower alkyl radical (iii) a radical 0R12 having Ri2 the meaning given below, \ / N I. R " having R 'and R "the meanings given below, R7 represents a hydrogen atom, a halogen atom, a lower alkyl radical, a nitro radical, an ORi3 radical, a polyether radical or a radical of the following formula: NEITHER having R? 3, R? , R15 the meanings given below, R8 represents a hydrogen atom, a lower alkyl radical, an optionally substituted aryl radical, an optionally substituted aralkyl radical, a monohydroxyalkyl or polyhydroxyalkyl radical, or a lower acyl radical, R9 represents a hydrogen atom , a lower alkyl radical, an optionally substituted aryl radical, an optionally substituted aralkyl radical, a monohydroxyalkyl or polyhydroxyalkyl radical, a lower acyl radical, a radical - (CH2) n-C00Ri6, or a radical - (CH2) nX, having n , Ri6 and X the meanings given below, Rio and Rn identical or different represent a lower alkyl radical, R? 2 represents a hydrogen atom, a lower alkyl radical, an optionally substituted aryl or aralkyl radical, a monohydroxyalkyl radical or a polyhydroxyalkyl radical, -R 'and R "identical or different represent a hydrogen atom, a lower alkyl radical, an optionally substituted aryl radical, or a amino acid residue, or even R 'and R "taken together can form with the nitrogen atom a heterocycle, - Ri3 represents a hydrogen atom, or a lower alkyl radical, - R? 4 and R15 identical or different represent an atom of hydrogen, or a lower alkyl radical, -R 6 represents a hydrogen atom, or a lower alkyl radical, n represents an integer comprised between 1 and 12 included, X represents a halogen atom. The invention also relates to the salts of the compounds of formula (I), when Ri represents a carboxylic acid function and the geometric and optical isomers of the compounds of formula (I) • When the compounds according to the invention are in the form of salts, they are preferably salts of an alkali metal or alkaline earth metal, or even of zinc or of an organic amine. According to the present invention, the term "lower alkyl radical" means a radical having from 1 to 6 carbon atoms and preferably the methyl, ethyl, isopropyl, butyl and tert-butyl radicals. By monohydroxyalkyl radical is meant a radical having from 1 to 6 carbon atoms, in particular a 2-hydroxyethyl, 2-hydroxy-propyl or 3-hydroxypropyl radical, the monohydroxyalkyl radical being protected in the form of acetyl or tert-butyl dimethylsilyl. By "polyhydroxyalkyl radical" is meant a radical containing from 2 to 6 carbon atoms and from 2 to 5 hydroxyl groups such as, in particular, 2, 3-dihydroxypropyl radicals, 2, 3, 4, -trihydroxybutyl, 2, 3, 4 , 5-tetrahydroxypentyl or the rest of the pentaerythritol, the hydroxyl groups may be protected in the form of acetyl or of tert-butyldimethylsilyls. By optionally substituted aryl radical is meant a phenyl radical optionally substituted by at least one halogen atom, an optionally protected hydroxyl in the form of an ether or acetate function, a nitro function or an amino function optionally substituted by an alkyl or acetyl group. By "optionally substituted aralkyl radical" is meant a benzyl radical or a phenethyl radical optionally substituted by at least one halogen atom, an optionally protected hydroxyl radical in the form of an ether or acetate function, a nitro function, or an amino function optionally substituted by a alkyl or acetyl group. By a lower acyl radical, is meant a radical having from 1 to 4 carbon atoms, and preferably an acetyl or propionyl radical. By "amino acid residue" is meant a moiety derived, for example, from one of the 20 amino acids of L or D configuration constituting mammalian proteins.

The term "heterocycle" is preferably understood to mean a piperidino, morpholino, pyrrolidino or piperazino radical, optionally substituted in the 4-position with an alkyl radical of Ci-Cβ or with a mono- or polyhydroxyalkyl radical as defined above. By "polyether radical" is meant a radical having from 1 to 6 carbon atoms and from 1 to 3 oxygen or sulfur atoms, such as the methoxymethyl ether, methoxyethoxymethyl ether or methylthiomethyl ether radicals. By halogen atom, a fluorine, chlorine or bromine atom is preferably understood. According to the present invention, the compounds of formula (I) which are more particularly preferred are those for which at least one and preferably all the conditions given below are respected: Ri represents a radical COR6-Ar represents a radical of formula (a) or (b) - R2 or R3 represent an adamantyl radical or R2 and R3 taken together form with the adjacent aromatic ring a saturated 5- or 6- link cycle optionally substituted by methyl groups and / or optionally interrupted by an oxygen or sulfur atom.

Among the compounds of formula (I) above falling within the scope of the present invention, the following may be mentioned in particular: 4- (3, 5, 5, 8, 8-pentamethyl-5,6,7,8-tetrahydro) -naphthalen-2-yl-slanyl) -ethylbenzoate, 4- (3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylseryl) -benzoic acid 6- ( 3, 5, 5, 8, 8 -pentamethi 1-5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanyl) -ethyl nicotinate, 6- (3, 5, 5, 8, 8-pentamet il -5, 6, 7, 8-tet rahydro-naphthalen-2-ylsallanyl) -nicotinic acid, 6- (5, 5, 8, 8-tetramethyl-3-propoxy-5, 6, 7, 8-tetrahydro-naphthalene- 2-ylsalanyl) -nicotinate of ethyl, 6- (5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -nicotinic acid, 3- (4-tert-butyl-phenyl-islanyl) -benzoic acid, 6- (4-tert-butyl-phenyl-islanyl) -nicotinic acid, 4- (4-tert-butyl-phenylislanyl) -benzoic acid, 4- (4, 4-dimethyl-thiochroman-8-ylslanyl) -benzoic acid, 3- (4,4-dimethyl-t-chlorenan-8-yl-slanyl) -benzoic acid, 6- (4,4-dimethyl-thiochroman-8-yl-silyl) -nicotinic, acid 4- (5,5,8, 8-tet ramet il-5, 6,7,8-tetrahydro-naphthalen-2-ylsenyl) -benzoic acid, 3- (5,5,8,8- tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -benzoic acid, 6- (5,5,8,8-tet ramet il-5,6,7,8-tetrahydro-naphthalene- 2) -ylselanyl) -nicotinic acid, 4- [5-adamantan-l-yl-4- (2-methoxy-ethoxymethoxy) -2-methyl-phenyl-islanyl] -benzoic acid, 3- [5-adamantan-l-yl-4] - (2-methoxy-ethoxymethoxy) -2-methyl-phenyl-islanyl] -benzoic acid, 6- (methoxy-ethoxy-methoxy-5, 5,8,8-tetramethyl-5-6,8-tetrahydro-naphthalene-2 - ilselanyl) -nicotinic acid, 3- (4-methoxyethoxymethoxy-5, 5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylsallanyl) -benzoic acid, 4- (4-methoxyethoxymethoxy) 5, 5,8, 8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylsallanyl) -3-methoxy-benzoic acid, 3- (4-methoxyethoxymethoxy-5,5,8, 8-tetram) et il-5, 6,7,8-tetrahydro-naphthalen-2-yl-slanyl) -methoxy-benzoic acid, 6- (4-methoxymethoxy-5, 5, 8, 8-tetramet-il-5, 6, 7, 8- tetrahydro-naphthalen-2-ylslanyl) -nicotinic acid, 6- (3-methoxyethoxymethoxy-5, 5, 8, 8-tet ramet il-5, 6,7,8-tetrahydro-naphthalen-2-yl slanyl) - nicotinic, 2- (3-methoxyethoxymethoxy-5,5,8, 8-tet ramet il-5, 6,7,8-tetrahydro-naphthalen-2-ylsanyl) -nicotinic acid, 4 - (3-methoxyethoxymethoxy-5) , 5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylselanyl) -benzoic acid, 3- (3-methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6, 7,8-tetrahydro-naphthalen-2-yl-slanyl) -benzoic acid, 6- (3,5-di-tert-butyl-2-methoxymethoxy-phenyl-islanyl) -nicotinic acid, 2- (3,5-di-tert-butyl) acid -2-methoxymethoxy-phenyl-islanyl) nicotinic, 4- (3,5-di-tert-butyl-2-methoxymethoxy-phenyl-islanyl) -benzoic acid, 3- (3,5-di-tert-butyl-2-methoxymethoxy-) acid phenyl-islanyl) -benzoic acid, 6- [4-adamine-l-yl-3-benzyloxy-phenyl-selanyl] -nicotinic acid, 6- (3, 5-d) i-tert-butyl-2-benzyloxyphenyl selanyl) • nicotinic acid, 3-methoxy-4- (4-benzyloxy-5,6,7,8-tetrahydro-5,5,8,8 tetramethylnapht-alen-2 acid) -yl selanyl) -benzoic acid, 4- (4-benzyloxy-5,6,7,8-tet-5,9,8,8-tetramet-ilnaphthalen-2-ylslanyl) -benzoic acid, 6- (4- benzyloxy-5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramet-lnaphthalen-2-ylslanyl) -nicotinic acid, 3-methoxy-4- (3-benzyloxy-5,6,7,8) -tetrahydro-5,5,8,8-tetramethylnaphthalen-2-ylslanyl) -benzoic acid, 6- (3-benzyloxy-5,6,7,8-tetrahydro-5, 5, 8, 8-tetramethylnaphthalene- 2-ylsenyl) -nicotinic acid, 4- (3-hexyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramet-ilnaphthalen-2-ylslanyl) -3-methoxy-benzoic acid, 6- (3-Hexyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-ylslanyl) -nicotinic acid, 4- (5-adamantan-1-yl-4-benzyloxy) - 2-methyl-phenyl-selanyl) -benzoic acid, 6- [3- (5-hydroxy-pentyloxy) -5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-silanyl ] - nicotinic, 4 - (5, 5, 8, 8 -tetrameti 1-5, 6, 7, 8-tetrahydro-naphthalen-2-yl slanyl) -ethylbenzoate, 4- (3-methoxyethoxymethoxy-5, 5,8,8 -tet ramet il-5, 6,7,8-tetrahydro-naphthalen-2-ylslanyl) -ethylbenzoate, 4- (3-hydroxy-5, 5, 8, 8-tet ramet il-5, 6, 7, 8 -tetrahydro-naphthalen-2-ylslanyl) -ethylbenzoate, 4- (3-hydroxy-5, 5, 8, 8-tetramethyl-5, 6, 7, 8-tetrahydro-naphthalen-2-ylseryl) -benzoic acid 6- (3-methoxyethoxymethoxy-5, 5, 8, 8-tetramethyl-5,6,7,8-tet rahydro-naphthalen-2-ylslanyl) - ethyl nicotinate, 6- (3-hydroxy-5, 5 , 8, 8-tetramethyl-5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanyl) -ethyl nicotinate, 6- (3-hydroxy-5, 5, 8, 8-tet ramet il-5, 6, 7, 8-tet rahydro-naphthalen-2-ylsallan) -nicotinic, 6- [3- (3-ethoxycarbonyl-propoxy) -5, 5, 8, 8-tet ramet i 1- 5, 6, 7, 8 -tetrahydro-naphthalen-2-ylseryl] -ethyl nicotinate, 6- [3- (3-carboxy-propoxy) -5,5,8, 8-tet-ramethyl-5,6,7,8-tetrahydro- naphthalen-2-ylslanyl] -nicotinic acid, 4- [3- (3-ethoxy rbonyl-propoxy) -5, 5, 8, 8-tet ramet i 1- 5, 6, 7, 8-tetrahydro-naphthalen-2-yl-silyl] -benzoic acid, 4- [3- (3-carboxy-propoxy) -5,5,8, 8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ylslanyl] -benzoic acid, 4- [3- (7- methoxycarbonyl-heptyloxy) -5, 5, 8, 8-tet ramet il-5, 6, 7, 8-tetrahydro-naphthalen-2-yl-silyl] -ethylbenzoate, 4- [3- (7-carboxy-heptyloxy ) -5, 5, 8, 8-tetramethyl-5, 6, 7, 8-tetrahydro-naphthalen-2-ylsallanyl] -benzoic acid, 6- [3- (7-methoxycarbonyl-heptyloxy) -5, 5, 8, 8-tetramet i 1- 5, 6, 7, 8 -tetrahydro-naphthalen-2-yl slanyl] -ethyl nicotinate, 6- [3- (7-carboxy-heptyloxy) -5, 5, 8, 8- tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylselanyl] -nicotinic acid, 6- [3- (2-acetoxy-ethoxy) -5,5,8,8-tetramethyl-5,6,7, 8- tetrahydro-naphthalen-2-ylslanyl] -nicnicinate, 6- [3- (2-hydroxy-ethoxy) -5,5,8,8-tet-ramethyl-5,6,7,8-tetrahydro- naphthalen-2-ylsenyl) -nicotinic acid, 4- [3- (2-acetoxy-ethoxy) -5,5,8,8-tet ramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-slanyl] - ethyl benzoate, 4- [3- (2-hydroxy-ethoxy) -5,5,8, 8-tetramethyl acid il-5, 6,7,8-tetrahydro-naphthalen-2-ylslanyl] -benzoic acid, 6- (3-adamantan-l-yl-4-methoxy-phenyl-islanyl) -nicotinic acid, [6- (3,5, 5,8, 8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -pyridin-3-yl] methanol, N-ethyl-6- (3, 5, 5, 8, 8- pentamethyl-5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanyl) -nicotinamide, Morpholin-4-yl- [6- (3, 5, 5, 8, 8-pentamethyl-5, 6,7,8 -tetrahydro-naphthalen-2-ylslanyl) -pyridin-3-yl] -methanone, N- (4-hydroxy-phenyl) -6- (3,5,5,8,8-pentamethyl-5,6,7, 8- tetrahydro-naphthalen-2-ylslanyl) -nicotinamide, 6- (3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -pyridine-3-carbaldehyde . Another object of the present invention is the processes for preparing the compounds of formula (I), in particular, according to the reaction scheme given in FIG. 1. The derivatives of formula (I) can be obtained (FIG. 1) by a sequence of reactions comprising, the action of a lithiated base such as tBuLi on the product (2) in a solvent such as THF, followed by the addition of selenium and the formation of the dimer by oxidation in basic medium (EtOH, NaOH) . The product (3) obtained is subjected to the action of sodium borohydride in a solvent such as ethanol, then it is coupled with an iodoaryl in the presence of a nickel catalyst.

When Ri represents the COOH radical, the compounds are prepared by protecting Ri by an alkyl-type protecting group. Saponification of the ester function in the presence of a base, such as sodium or lithium hydroxide in an alcohol solvent or in THF, leads to the corresponding acids. When Ri represents an alcohol radical, the compounds can be obtained from the acid by reduction in the presence of hydride such as boron hydride. The alcohol can be esterified according to the classical methods. When Rx represents an aldehyde radical, the compounds can be obtained by oxidation of the corresponding alcohols by the action of manganese oxide or pyridinium dichromate. When Ri represents an amide radical, the compounds can be obtained by transformation of the acid into acid chloride, then by reaction with a suitable amine. These compounds bind to the RXRs receptors, possessing some agonist activity, the others an antagonistic activity. The binding and trans-activating properties as an agonist for RXRs receptors can be determined by methods known in the art, such as for example: LEVIN et al., Nature 1992, 355, 359-61; ALLEÑBY et al., Proc. Nati Acad. Sci., 1993, 90, 30-4. The agonist activity of RXRs can also be determined by the assay as described in French patent application no. 95-07301 filed on June 19, 1995 by the applicant firm. This test comprises the following steps: (i) a sufficient amount of a compound which is an active ligand of at least one receptor of the nuclear steroidiene / t-hydrioyenne superfamily receptor is applied topically on a part of the skin of a mammal; of a specific ligand of the RXRs receptors and being able to heterodimerize with the RXRs such as an agonist molecule of the RARs, (ii) is administered systemically or topically on this same part of the skin of the mammal before, during, or after the step (i) a molecule capable of presenting an agonist activity of the RXRs, (iii) the response is evaluated on the part of the skin thus treated of the mammal. Thus the response to a topical application on the ear of a mammal of an agonist molecule of the RARs corresponding to an increase in thickness of this ear can be increased by the systemic or topical administration of an agonist molecule of the RXRs receptors. The RXRa antagonist activity can be evaluated in the transactivation assay by dose determination (IC50) which inhibits in 50% the transactivating activity of a selective agonist RXRa: the acid 6- [l- (3,5,5,8, 8 -pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-yl) cyclopropyl] nicotinic acid (CD 3127) according to the following protocol: Hela cells are co-transfected with an expression vector encoding RXRa (p565-RXRa ) and a messenger plasmid containing the 1/2 CRBP II response element cloned upstream of the heterologous thymidine kinase promoter and the messenger gene of chloramphenicol acetyl transferase (CAT). Eighteen hours after co-transfection, the cells are treated with a fixed concentration of CD 3127 and cross-concentrations of the molecule to be evaluated. After twenty-four hours of treatment, the dosage of the CAT activity is carried out by ELISA. The fixed concentration of CD3127 used is 10"8 and corresponds to its EC50.

The subject of the present invention is also, as a medicament, the compounds of formula (I) as defined above. The compounds according to the invention are particularly well suited in the following fields of treatment: 1) for treating dermatological conditions linked to a keratinization disorder which is based on differentiation and on proliferation mainly for treating vulgar, comedonic, polymorphic acnes , rosacea, nodulocystic acnes, conglobata, senile acnes, secondary acnes, such as solar, medication or professional acne. 2) to treat other types of keratinization disorders, mainly ichthyosis, ichthyosiform states, Darrier's disease, palmoplantar keratoderma, leukoplakias and leukoplasiform states, cutaneous or mucous lichen (buccal), 3) to treat other dermatological conditions linked to a keratinization disorder with an inflammatory and / or immuno-allergic component and mainly all forms of psoriasis whether cutaneous, mucosal or ungular, and even psoriatic rheumatism, or even cutaneous atopy, such as eczema or respiratory atopy or even gingival hypertrophy; the compounds can also be used in certain inflammatory conditions that do not present the keratinization disorder, 4) to treat all dermal or epidermal proliferations, whether benign or malignant, whether of viral origin or of non-viral origin, such as common warts , flat warts and verruciform epidermodysplasia, oral or florid papillomatosis and proliferations that can be induced by ultra-violets, mainly in the case of basal and spinocellular epithelioma, 5) to treat other dermatological disorders such as globular dermatosis and collagen diseases, 6) to treat certain ophthalmological problems, mainly corneopathies, 7) to prepare or combat skin aging, either photo-inductive or chronological, or to reduce pigmentation and actinic keratosis, or all the pathologies associated with chronological or actinic aging, 8) to prevent or cure the stigmata of epidermal and / or dermal atrophy induced by local or systemic corticosteroids, or any other form of cutaneous atrophy, 9) to prevent or treat scarring disorders, to prevent or to repair striae or even to promote healing, 10) to combat disorders of sebaceous function such as acne hyperseborrhea or simple seborrhea, 11) in the treatment or prevention of cancerous or precancerous conditions, more particularly, promyelocytic leukemias , 12) in the treatment of inflammatory conditions such as arthritis, 13) in the treatment of any condition of viral origin at cutaneous or general level, 14) in the prevention or treatment of alopecia, 15) in the treatment of conditions dermatological or general immunological component, 16) in the treatment of cardiovascular system conditions such as arteriosclerosis, l to hypertension, non-insulin-dependent diabetes as well as obesity, 17) in the treatment of skin disorders due to exposure to U.V.

In the therapeutic fields mentioned above, the compounds according to the invention can be advantageously used in combination with other compounds of retinoid-like activity, with vitamins D or their derivatives, with corticosteroids, with free radical anti-, a-hydroxy or -Ice acids or their derivatives, or even also with ion channel blockers. Vitamins D or their derivatives are, for example, derivatives of vitamin D2 or D3 and, in particular, 1,25-dihydroxyvitamin D3. By free radicals, for example, α-tocopherol, Super Oxide Dismutase, Ubiquinol or certain metal chelators are understood. By a-hydroxy or α-keto acids or their derivatives, it is understood, for example, lactic, malic, citric, glycolic, mandelic, tartaric, glyceric or ascorbic acids, salicylic acid derivatives or their salts, amides or esters. Finally, by ion channel blockers, it is understood, for example, Minoxidil (2,4-diamino-6-piperidino-pir imidina-3-oxide) and its derivatives. The present invention also relates to medicinal compositions containing at least one compound of formula (I) as defined above, one of its optical or geometric isomers or one of its salts.

The present invention thus has the object of a new medicament composition intended primarily for the treatment of conditions mentioned above and which is characterized in that it comprises, in a pharmaceutically acceptable carrier and compatible with the mode of administration accepted for the latter, the minus a compound of formula (I), one of its optical or geometric isomers or one of its salts. The administration of the compounds according to the invention can be carried out enterally, parenterally, topically or ocularly. Enterally, medicines can be presented in the form of tablets, capsules, dragees, syrups, suspensions, solutions, powders, granules, emulsions, microspheres or nanospheres or lipid or polymeric vesicles that allow the controlled release. Parenterally, the compositions may be in the form of solutions or suspensions for perfusion or injection. The compounds according to the invention are generally administered in a daily dose of approximately 0.01 mg / kg to 100 mg / kg in body weight, and this in a ratio of 1 to 3 doses.

Topically, the pharmaceutical compositions based on compounds according to the invention are intended more particularly for the treatment of the skin and mucous membranes and can then be presented in the form of ointments, creams, milks, powder ointments, soaked tampons, of solutions, gels, sprays, lotions or suspensions. They can also be present in the form of microspheres or nanospheres or lipid or polymeric vesicles or polymeric patches and hydrogels allowing a controlled release. These topical compositions can be presented, on the other hand, either in anhydrous form, or in aqueous form, according to clinical indication. By eye, they are mainly eye drops. These compositions for topical or ocular use contain at least one compound of formula (I) as defined above, or one of its optical or geometric isomers or even one of its salts, in a concentration preferably comprised between 0.001% and 5% by weight. weight with respect to the total weight of the composition. The compounds of formula (I) according to the invention also find an application in the cosmetic field, in particular in body and capillary hygiene and, in particular, for the treatment of acne-prone skin, for the growth of hair, anti-aging fall, to fight against the oily aspect of the skin and hair, in the protection against the harmful aspects of the sun or in the treatment of physiologically dry skin, to prevent and / or fight against photo-inductive or chronological aging. In the cosmetic field, the compounds according to the invention can be advantageously used, on the other hand, in combination with other compounds of retinoid-like activity, with vitamins D or their derivatives, with corticosteroids, with free radicals, α-hydroxy or α-keto acids or their derivatives, or even with ion channel blockers, all of these different products being as defined below. The present invention therefore also relates to a cosmetic composition which is characterized in that it comprises, on a cosmetically acceptable support suitable for topical application, at least one compound of formula (I) as defined above or one of its optical or geometric isomers or one of its salts, this cosmetic composition can be presented in the form of a cream, a milk, a lotion, a gel, microspheres or nanospheres or lipid or polymeric vesicles, a soap or a shampoo. The concentration of the compound of formula (I) in the cosmetic compositions according to the invention is advantageously between 0.001% and 3% by weight with respect to the composition as a whole. The medicinal and cosmetic compositions according to the invention may also contain inert or even pharmacodynamically or cosmetically active additives or combinations of these additives, and in particular: wetting agents; depigmenting agents such as hydroquinone, acelaic acid, caffeic acid, or kojic acid; emollients; moisturizing agents such as glycerol, PEG 400, tiamura folinone, and its derivatives or even urea; anti-seborrhoeic or anti-acne agents, such as S-carboxymethylcysteine, S-benzyl-cis-teamin, its salts or derivatives thereof, or benzoyl peroxide; antibiotics such as erythromycin and its esters, neomycin, clindamycin and their esters, tetracyclines; antifungal agents such as ketoconazole or polymethylene-4,5-isothiazolidones-3; agents that promote the growth of hair, such as inoxidil (2,4-diamino-6-piperidino-pyrimidine-3-oxide) and its derivatives, Diazoxide (7-chloro-3-methyl, 1, 2, 4 - benzothiadiazine 1,1-dioxide) and Phenytoin (5,5-diphenyl-imidazolidine 2,4-dione); Anti-inflammatory agents are not teroidienes; carotenoids and, mainly, ß-carotene; anti-psoriatic agents such as anthralin and its derivatives; and finally the eicosa-5, 8, 11, 14 -tetrainoic and eicosa-5, 8, 11-trinoic acids, their esters and amides. The compositions according to the invention may also contain flavor improving agents, preservatives such as parahydroxybenzoic acid esters, stabilizing agents, moisture regulating agents, pH regulating agents, osmotic pressure modifying agents, emulsifying agents, UV filters. -A and UV-B, antioxidants, such as a-tocopherol, butyl-hydroxyanisole or butylhydroxy toluene. A number of examples of obtaining active compounds of formula (I) according to the invention, as well as various specific formulations based on such compounds, will now be given by way of illustration and without limitation.

A. EXAMPLES OF COMPOUNDS EXAMPLE 1: 4- (3, 5, 5, 8, 8-Pentame-il-5, 6,7, 8-tetrahydro-naphthalen-2-yl-selanyl) -ethylbenzoate (a) , 6, 7, 8-tetrahydro-3, 5, 5, 8, 8-pentamethylnaphthalene-2-diselenide 1.7 M ter-butylitol in pentane (37.4 mm, 22 ml) was added to a solution of 2-bromo-5 , 6, 7, 8-tetrahydro-3,5,5,8,8-pentamethylnaphthalene (4.4 g, 15.8 mmol) in THF (100 ml) at -78 ° C in 10 minutes. The mixture was stirred at 0 ° C for 30 minutes. Selenium (1.33 g, 16.8 mmol) was added twice. The mixture was stirred at 0 ° C for 15 minutes, then at room temperature for 30 minutes. A solution of 1 N HCl (40 ml) was added, then the reaction mixture was treated with ethyl ether. The organic phase was washed twice in water, dried over anhydrous magnesium sulfate and concentrated in a rotary evaporator under vacuum at 40 ° C. 10 ml of ethanol and 50 mg of soda were added to the obtained oil. The mixture was stirred vigorously for a few minutes in the air (csp all precipitate), then it was concentrated on the rotary evaporator under vacuum at 40 ° C. The solid obtained was filtered on silica (elution with heptane), then crystallized from a mixture of ethanol / (ether.

Solid yellow. M 3.26 g. Performance: 74%. Tf. 126 ° C NMR XH (CDC13): 1.14 (6H, s), 1.23 (6H, s), 1.61 (4H, s), 2.35 (3H, s), 7.05 (1H, Ar, s), 7.55 (1H Ar , s). (b) ethyl 4- (3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -benzoate A solution of 5, 6, 7, 8-tetrahydro -3, 5, 5, 8, 8-pentamethylnaphthalene-2-diselenide (500 g, 0.89 mmol) and sodium borohydride (68 mg, 1.8 mmol) in 5 ml of ethanol was stirred 1 hour at room temperature. Ethyl iodobenzoate (440 mg, 1.6 mmol) and Bi s (bipyridine) nickel 2 bromide (10 mg, 0.016 mmol) were added (Organometallics 1985, 4, 657-661). The solution was heated for 5 minutes at reflux. At room temperature, it was diluted with ethyl ether. The organic phase was washed with water, dried over anhydrous magnesium sulfate, then concentrated. The residue was purified by rapid discharge (eluent: heptane, then ethyl ether). White solid. M 495 mg. Yield: 72%. Tf: 104 ° C NMR ñ (CDCl 3): 1.22 (6H, s), 1.29 (6H, s), 1.33-1.39 (3H, t), 1.67 (4H, s), 2.32 (3H, s), 4.29- 4.38 (2H, q), 7.21-7.26 (3H, 'c), 7.51 (1H, s), 7.84-7.87 (2H, d).

EXAMPLE 2: 4- (3, 5, 5, 8, 8-Pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -benzoic acid. Sodium (450 mg, 11.25 mmol) was added to the solution of 4- (3, 5, 5, 8, 8-Pentamet-il-5, 6, 7, 8-tet rahydro-naphthalen-2-ylslanyl) -benzoate. ethyl (450 mg, 1.04 mmol) in a mixture of 10 ml of THF, 1 ml of methanol and 1 ml of water. The reaction medium was heated at reflux for 12 hours. It was then poured into a mixture of ethyl ether / water, acidified to pH 1 by a concentrated hydrochloric acid solution and extracted into ethyl ether. After decanting, the organic phase was washed twice with water, dried over anhydrous magnesium sulfate and concentrated in a rotary evaporator under vacuum at 40 ° C. White powder M 371 mg. Yield: 88%. Tf: 249 ° C. XH NMR (CDC13): 1.21 (6H, s), 1.29 (6H, s), 1.67 (4H, s), 2.32 (3H, s), 7.21-7.24 (2H, d, J = 6.9 Hz), 7.38 ( 1H, s), 7.48 (1H, s), 7.85-7.88 (2H, d; J = 8.35 Hz).

EXAMPLE 3: 6- (3, 5, 5, 8, 8-Pentame-il-5, 6,7, 8-tetrahydro-naphthalen-2-yl-silyl) -nicnicinate ester In a manner analogous to example 1 (b), reaction of 750 mg (1.33 mmol) of diselenide in 15 ml of ethanol with 102 mg (2.7 mmol) of sodium borohydride, 665 mg (2.4 mmol) of ethyl 6-iodonicotinate and 15 mg (0.024 mmol) of Bis (bipyridine) ) nickel 2 bromide, 779 mg (75%) of the expected derivative was obtained in the form of a white solid. Tf: 117 ° C. XH NMR (CDC13): 1.25 (6H, s), 1.31 (6H, s), 1.34-1.40 (3H, t), 1.69 (4H, s), 2.37 (3H, s), 4.32-4.40 (2H, q ), 6.83-6.87 (1H, d, J = 8.3 Hz), 7.28 (1H, s), 7.65 (1H, s), 7.91-7.96 (1H, dd, J = 6.10 Hz, J '= 2, 21 Hz), 8.99-9.00 (1H, d, J = 2.14 Hz).

EXAMPLE 4: Acid 6- (3, 5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -nicotinic acid Analogously to example 2, by reaction of 750 mg (1.74 mmol) of 6- (3 , 5, 5, 8, 8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -nicnicinate with 700 mg (17.5 mmol) of soda in a THF / methanol / water mixture, they obtained 625 mg (89%) of white cotton. Tf: 258 ° C. XH NMR (DMSO): 1.05 (6H, s), 1.11 (6H, s), 1.48 (4H, s), 2.14 (3H, s), 6.79-6.83 (1H, d, J = 8.3 Hz), 7.24 ( 1H, s), 7.45 (1H, s), 7.83-7.88 (1H, dd, J = 6.03 Hz, J '= 2.3 Hz), 8.69-8.70 (1H, d, J = 2.2 Hz), 13.12 (1H, s).

EXAMPLE 5: 6- (5, 5, 8, 8-Tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -nicotinate of ethyl (a) 1,2,4,4 -tetrameti 1-7 -propoxy- 1, 2, 3, 4-tetrahydro-naphthalen-6-diselenide. Analogously to example 1 (a), by reaction of 6 g (18.5 mmol) of 6-bromo-l, 1, 4, 4-tet ramet il-7-propoxy-1, 2, 3, 4-tet rahydronaphthalene With 1.7 M tert-Butyllithium in pentane and Selenium in 20 ml of THF, 3.2 g of the expected selenium derivative was obtained in the form of a yellow solid. Tf: 92-98 ° C. XH NMR (CDC13): 1.05-1.10 (6H, m), 1.25 (9H, m), 1.55-1.66 (4H, m), 1.86 (2H, sext), 3.98 (2H, t), 6.67 (1H, s) ), 7.42 (1H, s). (b) 6- (5,5,8, 8-Tetramethyl-3-propoxy-5, 6, 7, 8-tetrahydro-naphthalen-2-yl-silyl) -nicnicinate, ethyl In analogy to example 1 (b), by reaction of 850 mg (1.31 mmol) of diselenide in 85 ml of ethanol with 120 mg (2.62 mmol) of sodium borohydride, 581 mg, (2.1 mmol) of ethyl 6-iodonicotinate and 20 mg (0.032 mmol) of Bis (bipyridine) nickel 2 bromide, 610 mg (61%) of the expected compound were obtained as white crystals. Tf: 110-12 ° C. XH NMR (CDC13): 0.81-0.87 (3H, t), 1.24 (6H, s), 1.31 (6H, s), 1.35-1.41 (3H, t), 1.57-1.65 (2H, m), 1.69 (4H, s), 3.87-3.92 (2H, t), 4.32-4.41 (2H, q), 6.66 (1H, s), 7.00-7.03 (1H, d, J = 8.3 Hz), 7.59 (1H, s), 7. 91-7.95 (1H, dd, J = 6.2 Hz, J '= 2.1 Hz), 8.98-8.99 (1H, d, J = 1.7 Hz).

EXAMPLE 6: 6- (5, 5, 8, 8-Tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -nicotonic acid Analogously to Example 2, by reaction of 485 mg (1.02 mmol) of 6- (5, 5, 8, 8-tet ramethyl-3-propoxy-5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanyl) -nicotinate of ethyl with 385 mg (9.6 mmol) of soda in ethanol (20 ml) gave 444 mg (97%) of white solid. Tf: 220 ° C.

EXAMPLE 7: 3- (4-tert-Butyl-phenyl-selenyl) -benzoic acid A mixture of 4-tert-butyl-phenyl-diselenide (0.3 mmol) of 480 mg borohydride polymer supported on amberlyst IRA 400 resin at 2.5 mmol / g (Aldrich), bis (bipyridine) nickel II dibromide (5 mg) (Organometallics 1985, 4, 657-661) and Ethyl 3-iodobenzoate (0.4 mmol) was heated 12 hours at 67 ° C. The mixture was filtered and the solution was concentrated. The solid obtained was purified on SPE cartridge loaded with silica gel. The fractions containing the expected product were combined and concentrated in vacuo. The ester was saponified in a mixture of 2.5 ml of THF, 2.5 ml of ethyl alcohol and 0.5 ml of an aqueous solution of soda at 33%. The reaction medium was acidified to an HCl solution, an ethyl ether was extracted, dried over magnesium sulfate and concentrated to give the expected product. 1H NMR / CDC13: 1.32 (s, 9H), 7.32 to 7.38 (m, 3H); 7.46 (d, 2H); 7.61 (d, 1 H); 7.95 (d, 1H); 8.19 (d; 1H) EXAMPLE 8: 6- (4-tert-Butyl-phenyl-selenyl) -nicotinic acid The product was obtained analogously to Example 7, from 4-tert-butyl-phenyl-diselenide and ethyl 6-iodo-nicotinate. 1 H NMR / CDC13: 1.36 (s, 9H); 7.02 (d, 1H); 7.45 (d, 2H); 7.65 (d, 2 H); 7.96 (d, 1 H); 9.05 (d, 1H).

EXAMPLE 9: 4- (4-tert-Butyl-phenyl-selenyl) -benzoic acid The product was obtained analogously to Example 7, from 4-tert-butyl-phenyl-diselenide and ethyl 4-iodo-benzoate. NMR ^ / CDCls: 1.34 (ds, 9H); 7.35 (d, 2H); 7.39 (d, 2H), 7.54 (d, 2H); 7.92 (d, 2H).

EXAMPLE 10: 4- (4,4-Dimethyl-thiochroman-8-ylsenalyl) -benzoic acid (a) 2-bromo-1- (3-methylbut-2-enylthio) benzene. In a three-necked flask, 19. 30 g (102.0 mmoles) of 2-bromotophenol, 160 ml of DMF and 15.50 g (112.0 mmoles) of potassium carbonate. 13 ml (112.0 mmoles) of 1-bromo-3-met il-2-butene were added dropwise and stirred at room temperature for two hours. The reaction medium was poured into water, extracted with ethyl acetate, the organic phase was decanted, washed with water, dried over magnesium sulfate, evaporated. 26.00 g (99%) of the expected compound was collected in the form of an orange oil. XH NMR (CDC13) d 1.65 (s, 3H), 1.73 (s, 3H), 3.56 (d, 2H), J = 7.7 Hz), 5.32 (td, 1H, J = 7.7 / 1.4 Hz), 6.96 to 7.06 (m, 1H), 7.22 to 7.26 (m, 2H), 7.52 (d, 1H, J = 7.7 Hz). (b) 4,4-dimethyl-8-bromotiochroman In a three-necked flask, 26.00 g (102.0 mmol) of 2-bromo-1- (3-methyl-butyl-2-enylthio) benzene, 180 ml. toluene and 23.20 g (122.0 mmoles) of paratoluene sulfonic acid. They were heated to reflux for four hours and the reaction medium was evaporated to dryness. It was recovered by an aqueous solution of sodium hydrogen carbonate, extracted with ethyl acetate, the organic phase was decanted, dried over magnesium sulfate, evaporated. The obtained residue was purified by chromatography on a column of silica, eluted with heptane. 20.00 g (76%) of the expected compound was collected in the form of an orange oil. XH NMR (CDC13) d 1.33 (s, 6H), 1.94 (t, 2H, J = 6.0 Hz), 3.04 (t, 2H, J = 6.1 Hz), 6.89 (t, 1H, J = 7.9 Hz), 7.34 (d, 2H, J = 7.9 Hz). (c) 4, 4 -Dimethyl-thiochroman-8 -dielenide A crystal of iodine, magnesium (208 mg, 8.56 mmol) and a few drops of a solution of 4,4-dimethyl-8-bromothiochroman (2 g, 7.78 mmol ) in the ethyl ether (15 ml) were heated until the beginning of the organomagnesium. The rest of the solution was then added dropwise. The reaction medium was heated 2 hours, then selenium (6.15 mg, 7.78 mmol) was added at room temperature. Stirring was continued for 30 minutes, then a solution of IN HCl was added. The reaction mixture was treated with ethyl ether. The organic phase was washed twice in water, dried over anhydrous magnesium sulfate and concentrated in a vacuum evaporator at 40 ° C. Ethanol and sodium hydroxide were added to the oil obtained. The mixture was stirred vigorously for a few minutes, then concentrated in the evaporator under vacuum at 40 ° C. The product was purified on a silica column (dichloromethane 20-heptane 80). White solid. Mass 300 mg. Yield: 15%. XH NMR (CDC13): 1.33 (6H, s), 196 (2H, m), 3.09 (2H, m), 6.93 (1H, Ar, t, J = 7.8 Hz), 7.26 (1H Ar, dd, J = 7.8 Hz, J = 1.3 Hz), 7.47 (1H Ar dd, J = 7.8 Hz, J = 1.3 Hz). (d) 4- (4,4-Dimethyl-thiochroman-8-ylsenalyl) -benzoic acid The product was obtained in a manner analogous to Example 7, from 4,4-dimethyl-il-t-chromo-8-diselenide and from Ethyl 4-iodobenzoate. 1H NMR / CDC13: 1.36 (s, 6H), 1.95 (m, 2H), 2.99 (m, 2H), 6.99 (t, 1H), 7.31 to 7.46 (m, 4H), 7.91 (d, 2H).

EXAMPLE 11: 3- (4,4-Dimethyl-thiochroman-8-ylsenalyl) -benzoic acid The product was obtained analogously to Example 7, from 4,4-dimethyl-thiochroman-8-diselenide and from 3 -Iodo-benzoate of ethyl. 1H NMR / CDC13: 1.35 (s, 6H), 1.95 (m, 2H), 3.02 (m, 2H), 6.94 (t, 1H), 7.18 (dd, 1H), 7.33 to 7.39 (m, 2H), 7.61 (dd, 1H), 8.08 (dd, 1H), 8.16 (d, 1H).

EXAMPLE 12 6- (4,4-Nit-ethylthio-thiochroman-8-ylsenalyl) -nicotinic acid The product was obtained in a manner analogous to Example 7, starting with 4,4-dimethyl-thiochroman-8-diselenide and 6-dimethyl. -nodo ethyl nicotine. NMR ^ / CDCls: 1.37 (s, 6H); 1.95 (m, 2H), 2.97 (m, 2H), 6.90 (d, 1H), 7.04 (t, 1H); 7.48 to 7.57 (m, 2H), 7.96 (dd, 1H), 9.03 (d, 1H).

EXAMPLE 13 4- (5, 5, 8, 8-Tetramethyl-5, 6, 7, 8-tetrahydronaphthalen-2-ylselenalyl) -benzoic acid (a) 5,6,7,8-tetrahydro-5,5,8 , 8-tet ramet ilnaphthalene-2-diselenide. A solution of 1.7 M ter-but-illithium in pentane (37.4 mmol, 22 ml) was added to a solution of 2-bromo-5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramet ilnaphthalene (4.22). g, 15.8 mmol) in THF (100 ml) at -78 ° C in 10 minutes. The mixture was stirred at 0 ° C for 30 minutes. Selenium (1.33 g, 16.8 mmol) was added twice. The mixture was stirred at 0 ° C for 15 minutes, then at room temperature for 30 minutes. A solution of IN HCl (40 ml) was added, then the reaction mixture was treated with ethyl ether. The organic phase was washed twice with water, dried over anhydrous magnesium sulfate and concentrated on the rotary evaporator under vacuum at 40 ° C. 10 ml of ethanol and 50 mg of soda were added to the obtained oil. The mixture was stirred vigorously for a few minutes in air (csp all precipitate), then concentrated in the rotary evaporator in vacuo at 40 ° C. The solid obtained was filtered on silica (elution with heptane), then crystallized from an ethanol / ether mixture. Solid orange Mass: 2.9 g. Performance: 69%. 1NMR (CDC13): 1.21 (6H, s), 1.25 (6H, s), 1.65 (4H, s), 7.20 (1H Ar, d, J = 8.25 Hz), 7.38 (1H Ar, dd, J = 1.9 Hz, J = 8.25 Hz), 7.51 (1H Ar, d, J = 1.9 Hz). (b) 4- (5, 5, 8, 8-tetramethyl-5, 6, 7, 8-tetrahydro-naphthalen-2-ylsenalyl) -benzoic acid The product was obtained in a manner analogous to Example 7, starting from , 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramet-ilnaphthalene-2-diselenide and ethyl 4-iodo-benzoate. NMR ^ / CDCl ^ 1.26 (s, 6H), 1.30 (s, 6H), 1.70 (s, 4H), 7.27 to 7.37 (m, 4H), 7.54 (d, 1H), 7.91 (d, 2H).

EXAMPLE 14: 3- (5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalene-2-ylenesalyl) -benzoic acid The product was obtained in a manner analogous to Example 7, starting from 5, 6, 7 , 8-tetrahydro-5, 5, 8, 8-tetramethylnaphthalene-2-diselenide and ethyl 4-iodo-benzoate. 1H NMR / CDC13: 1.25 (s, 6H), 1.27 (s, 6H), 1.68 (s, 4H), 7.24 to 7.26 (m, 2H), 7.34 (t, 1H), 7.48 (s, 1H), 7.60 (dd, 1H), 7.94 (d, 1H), 8.19 (d, 1H).

EXAMPLE 15: 6- (5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ylsenalyl) -nicotonic acid The product was obtained in a manner analogous to Example 7, starting from 5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethylnaphthalene-2-diselenide and ethyl 6-iodo-nicotinate. 1H NMR / CDC13: 1.29 (s, 6H), 1.32 (s, 6H), 1.72 (s, 4H), 7.03 (s, 1H), 7.36 (d, 1H), 7.45 (dd, 1H), 7.65 (d , 1H), 7.99 (dd, 1H), 9.07 (d, 1H).

EXAMPLE 16: 4- [5-Adamantan-l-yl-4- (2-methoxyethoxymethoxy) -2-methyl-phenyl-selenyl) -benzoic acid a) 5-Adamantan-1-yl-4- (2-methoxy) ethoxymethoxy) -2-methyl-phenyl-disillenide. A small part of a solution of 2- (adamantan-1-yl) -4-bromo-5-methy1-1-methoxyethoxymethoxy phenyl (17 g, 41.5 mmol) in the THF (160 ml) was poured onto a mixture of magnesium (1.51 g) and an iodine crystal, warming slightly. When the reaction medium was discolored, the remainder of the solution was added to maintain a slight reflux. After the end of the addition, the solution was refluxed for 1 hour. After returning to room temperature, 3.6 g of selenium was added. The reaction medium was stirred 3 hours at room temperature, then a solution of 1 N hydrochloric acid (105 ml) and ethyl ether was added to the reaction medium. The organic phase was washed with water, dried over magnesium sulfate and concentrated on the rotary evaporator. Then sodium hydroxide (131 mg) and ethanol (27 ml) were added. The suspension was stirred in the air at room temperature for 12 hours. The product was purified by filtration on silica eluted with dichloromethane. 12 g (71%) of a yellow solid were obtained. Tf: 101 ° C. 1 H NMR / CDC13: 1.73 (s, 6H); 2.00 (s, 9H); 2.30 (s, 3H); 3.40 (s, 3H); 3.59 (m, 2H); 3.83 (m, 2H); 5.29 (s, 2H); 6.95 (s, 1H); 7.48 (s, 1H). b) 4- [5-Adamantan-l-yl-4- (2-methoxyethoxymethoxy) -2-methyl-phenyl-selenanyl) -benzoic acid. The product was obtained in a manner analogous to Example 7, starting from 5-Adamantan-l-yl-4- (2-methoxy-ethoxymethoxy) -2-methyl-il-phenyl-disenylidene and ethyl 4-iodo-benzoate. NMR ^ / CDCls: 1.75 (s, 6H); 2.07 (s, 9H); 2.34 (s, 3H); 3.42 (s, 3H); 3.62 (m, 2H), 3.89 (m, 2H); 5.35 (s, 2H), 7.14 (s, 1H), 7.19 (d, 2H), 7.50 (s, 1H), 7.87 (d, 2H).

EXAMPLE 17: 3- (5-Adamantan-l-yl-4- (2-methoxy-oxy-oxoxy) -2-methyl-phenyl-selenalyl] -benzoic acid The product was obtained in a manner analogous to Example 7, starting from Adamantan-l-yl-4- (2-methoxy-ethoxymethoxy) -2-methyl-yl-phenylenedylidene and ethyl 3-iodo-benzoate 1 H-NMR / CDC13: 1.75 (s, 6H); 2.06 (s, 9H ), 2.34 (s, 3H), 3. 41 (s, 3H), 3.62 (m, 2H), 3.87 (m, 2H), 5.34 (s, 2H), 7.10 (s, 1H), 7.28 (t, 1H), 7.38 (dd, 1H), 7.47 (s, 1H), 7.87 (dd, 1H), 8.02 (d, 1H).

EXAMPLE 18: 6- (4-Methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -nicotinic acid a) 4-methoxyethoxymethoxy-5,6,7 , 8-tetrahydro-5, 5,8,8-tetramethylnaphthalene-2-diselenide Analogously to example 1 (a), from 2-bromo-5, 5,8, 8-tet ramethi 1-4-methoxyethoxymethoxy -5, 6,7,8-tet rahydro-naphthalene, the expected compound was obtained in the form of an orange oil. b) 6- (4-Methoxyethoxymethoxy-5, 5, 8, 8-tet ramethyl-5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanyl) -nicotinic acid. The product was obtained analogously to Example 7, starting from 4-methoxyethoxymethoxy-5,6,7,8-tetrahydro-5, 5, 8, 8-tet ramet i-lnaphthalene-2-diselenide and 6-iodine Ethyl nicotinate. 1H NMR / CDC13: 1-27 (s, 6H), 1.42 (s, 6H), 1.67 (m, 4H), 3.36 (s, 3H), 3.56 (m, 2H), 3.82 (m, 2H), 5.29 (s, 2H), 7.11 (d, 1H), 7.31 (d, 1H), 7.35 (d, 1H), 8.00 (dd, 1H), 9.06 (d, 1H).

EXAMPLE 19: 3- (4-Hexymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylsenyl) -benzoic acid The product was obtained analogously to example 7, from 4-methoxyethoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2-diselenide and ethyl 3-iodobenzoate. 1 H NMR / CDC13: 1-26 (s, 6H); 1.38 (s, 6H); 1.62 (m, 4H), 3.36 (s, 3H), 3.53 (m, 2H), 3.78 (m, 2H), 5.22 (s, 2H), 7. 12 (d, 1H), 7.15 (d, 1H), 7.35 (t, 1H); 7.65 (dd, 1H), 7.96 (dd, 1H); 8.20 (d, 1H).

EXAMPLE 20: 4- (4-Methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ylslanyl) -3-methoxy-benzoic acid The product was obtained analogously to the example 7, from 4-methoxyethoxymethoxy-5,6,7,8-tetrahydro-5, 5, 8, 8-tetramet-ilnaphthalene-2-diolide and ethyl 4-iodo-3-methoxybenzoate. 1 H NMR / CDC13: 1-26 (s, 6H); 1.42 (s, 6H); 1.66 (m, 4H), 3.35 (s, 3H), 3.54 (m, 2H), 3.81 (m, 2H), 3.98 (s, 3H), 5., 27 (s, 2H), 6.94 (d, 1H) ), 7.25 (d, 1H), 7.30 (d, 1H), 7.48 to 7.53 (m, 2H).

EXAMPLE 21: 3- (4-Methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ylseryl) -4-methoxy-benzoic acid The product was obtained analogously to the example 7, from 4-methoxyethoxymethoxy-5,6,7,8-tetrahydro-5, 5, 8, 8-tet ramethylnaphthalene-2-diselenide and ethyl 3-iodo-4-methoxybenzoate. 1 H NMR / CDC13: 1-25 (s, 6H); 1.40 (s, 6H); 1.65 (m, 4H), 3.34 (s, 3H), 3.53 (m, 2H), 3.80 (m, 2H), 3.97 (s, 3H), 5.26 (s, 2H), 6.88 (d, 1H), 7.21 (d, 1H), 7.24 (d, 1H), 7.82 (d, 1H), 7.94 (dd, 1H).

EXAMPLE 22: 6- (4-Methoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ylslanyl) -nicotinic acid a) 4-methoxymethoxy-5, 6, 7, 8 -tetrahydro-5, 5, 8, 8-tetra-methylnaphthalene-2-diselenide Analogously to example l (a), from 2-bromo-5, 5,8, 8-tet ramet i 1-4- Methoxymethoxy-5,6,7,8-tetrahydro-naphthalene, the expected compound was obtained in the form of an orange oil. b) 6- (4-Methoxymethoxy-5, 5, 8, 8-tet ramet il-5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanyl) -nicotinic acid The product was obtained analogously to Example 7 , from 4-methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2 -diselenide and ethyl 6-iodo-nicotinate. 1H NMR / CDC13: 1-27 (s, 6H), 1.43 (s, 6H), 1.67 (m, 4H), 3.49 (s, 3H), 5.20 (s, 2H), 7.11 (d, 1H), 7.24 (d, 1H), 7.35 (d, 1H), 8.01 (dd, 1H), 9.07 (d, 1H).

EXAMPLE 23: 6- (3-Methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ylslanyl) -nicotinic acid a) 3-methoxyethoxymethoxy-5,6,7,8 -tetrahydro-5,5,8,8-tetramet-ilnaphthalene-2-diselenide Analogously to example 1 (a), from 2-bromo-5, 5, 8, 8-tet ramet il-3-methoxyethoxymethoxy- 5,6,7,8-tetrahydro-naphthalene, the expected compound was obtained in the form of an orange oil. b) 6- (3-Methoxyethoxymethoxy-5, 5, 8, 8-tet ramethyl-5, 6, 7, 8-tetrahydronaphthalen-2-ylselanyl) -nicotinic acid The product was obtained in a manner analogous to Example 7, starting from of 3-methoxyethoxymethoxy-5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tet ramet ilnaphthalene-2-diselenide and of ethyl 6-iodo-nicotinate. 1 H NMR / CDC13: 1.25 (s, 6H); 1.31 (s, 6H), 1.69 (s, 4H), 3. 36 (s, 3H), 3.51 (m, 2H), 3.74 (m, 2H), 5.22 (s, 2H), 7.04 (d, 1H), 7.23 (s, 1H), 7.61 (s, 1H), 7.97 (dd, 1H), 9.05 (d, 1H).

EXAMPLE 24: 2- (3-Methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,7,7,8-tetrahydronaphthalen-2-ylslanyl) -nicotinic acid The product was obtained in a manner analogous to Example 7, starting from of 3-methoxyethoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2-diselenide and ethyl 2-iodo-nicotenoate. NMR ^ / CDCl;,: 1.25 (s, 6H); 1.31 (s, 6H); 1.68 (s, 4H); 3. 37 (s, 3H), 3.52 (m, 2H); 3.74 (m, 2H), 5.17 (s, 2H), 7.10 (dd, 1H), 7.22 (s, 1H), 7.54 (s, 1H), 8.29 (dd, 1H), 8.44 (dd, 1H).

EXAMPLE 25: 4- (3-Methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,7,7,8-tetrahydronaphthalen-2-ylslanyl) -benzoic acid The product was obtained analogously to Example 7, starting from of 3-methoxyethoxymethoxy-5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethylnaphthalene-2-diselenide and ethyl 4-iodo-benzoate. 1H NMR / CDC13: 1.19 (s, 6H), 1.29 (s, 6H), 1.63 (s, 4H), 3. 36 (s, 3H), 3.50 (m, 2H), 3.71 (m, 2H), 5.22 (s, 2H), 7.16 (s, 1H), 7.36 (s, 1H), 7.41 (d, 2H), 7.93 (d, 2H).

EXAMPLE 26: 3- (3-Methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-naphthalen-2-ylslanyl) -benzoic acid. The product was obtained in a manner analogous to Example 7, starting from 3-methoxyethoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2 -diselenide and from 3-iodo-benzoate of ethyl. NMR ^ / CDCls: 1.12 (s, 6H); 1.27 (s, 6H), 1.63 (m, 4H), 3.37 (s, 3H), 3.52 (m, 2H), 3.77 (s, 2H), 5.26 (s, 2H), 7.12 (s, 1H), 7.13 (s, 1H), 7.38 (t, 1H), 7.69 (dd, 1H), 7.99 (dd, 2H), 8.25 (d, 1H).

EXAMPLE 27: 6- (3,5-Di-tert-butyl-2-methoxymethoxy-phenyl-islanyl) -nicotinic acid a) 2-bromo-4,6-di-tert-butyl-1-methoxymethoxyphenyl. A mixture of 2-bromo-4,6-di-tert-but-yl-phenol (4.4 mmol), cesium carbonate (2.95 g) and methoxymethyl chloride (4.8 mmol) in DMF (18 ml) were stirred at room temperature for 24 hours. The reaction medium was extracted by ethyl ether. The organic phase was washed with water, dried over magnesium sulfate and concentrated on the rotary evaporator. The product was purified by filtration on silica. b) 4,6-di-tert-butyl-l-methoxymethoxyphen-2-yl-diselenide. Analogously to example 10 (c), from 10 g of the product obtained above, 1.1 g of magnesium and 2.63 g of selenium, 7.6 g (76%) of the expected product were obtained in the form of a yellow solid. NMR ^ / CDCl;): 1.18 (s, 9H); 1.42 (s, 9H); 3.68 (s, 3H), 5.08 (s, 2 H); 7.23 (d, 1H); 7.54 (d, 1H). c) 6- (3,5-Di-tert-butyl-2-methoxymethoxy-phenyl-selanyl) -nicotinic acid The product was obtained analogously to Example 7, starting from 4,6-di-ter-but il-1-methoxy-methoxyphen-2-yl diselenide and ethyl 6-iodo-nicotone. NMR ^ / CDCls: 1.30 (s, 9H); 1.45 (s, 9H); 3.51 (s, 3H); . 17 (s, 2H); 6.94 (d, 1H); 7.50 (d, 1H); 7.56 (d, 1H); 7. 98 (dd, 1H); 9.05 (d, 1H).

EXAMPLE 28: 2- (3,5-Di-tert-Butyl-2-methoxymethoxy-phenyl-islanyl) -nicotinic acid. The product was obtained in a manner analogous to Example 7, starting from 4,6-di-tert-butyl-1-methoxy-methoxy-2-yl-diselenide and 2-iodo-nicot-ethyl-ethyl. 1 H NMR / CDC13: 1.30 (s, 9H); 1.46 (s, 9H); 3.51 (s, 3H); 5.16 (s, 2H); 7.12 (dd, 1H); 7.44 (s, 1H), 8.30 (dd, 1H), 8.46 (dd, 1H).

EXAMPLE 29: 4- (3,5-Di-tert-butyl-2-methoxymethoxy-phenylislanyl) -benzoic acid The product was obtained in a manner analogous to Example 7, starting with 4,6-di-tert-butyl- 1-methoxy-methoxyphen-2-yl diselenide and ethyl 4-iodo-benzoate. 1 H NMR / CDC13: 1.25 (s, 9H); 1.44 (s, 9H); 3.55 (s, 3H); 5.15 (s, 2H); 7.33 to 7.41 (m, 3H); 7.92 (d, 2H).

EXAMPLE 30: 3- (3,5-Di-tert-butyl-2-methoxymethoxy-phenyl-islanyl) -benzoic acid The product was obtained in a manner analogous to Example 7, starting with 4,6-di-tert-butyl- 1-methoxy-methoxyphen-2-yl diselenide and ethyl 3-iodo-benzoate. NMR ^ / CDCls: 1.20 (s, 9H); 1.44 (s, 9H); 3.60 (s, 3H), 5.17 (s, 2H); 7.15 (d, 1H), 7.32 to 7.36 (m, 2H), 7.56 (dd, 1H), 7.96 (dd, 1H), 8.18 (d, 1H).

EXAMPLE 31: 6- [4-Adamantan-l-yl-3-benzyloxy-phenyl-selenalyl] -nicotinic acid a) 2- (adamantan-1-yl) -5-bromo-l- (2-methoxyethoxymethoxy) -phenyl was added 60% sodium hydride (2.5 g) per fractions to a solution of 2- (adamantan-1-yl) -5-bromo-1-phenol (20.9 g) in a mixture of THF and DMF (5/5). Stirring was continued 30 minutes at T.A. after the end of the addition, then methoxyethoxymethyl chloride (8.92 g) was added. The reaction medium was stirred 4 hours at T.A. then it was treated with water and ethyl ether. The organic phase was washed with water, dried over magnesium sulfate and concentrated. After filtration on silica, 17 g (64%) of expected product were obtained in the form of a white solid. Mp = 88 ° C. b) 4-Adamantan-l-yl-3- (2-methoxy-ethoxymethoxy) -phenyl-diselenide. Analogously to example 1 (a), from 13.04 g of 2- (adamantan-1-yl) -5-bromo-l-methoxyethoxy-methoxyphenyl, 9.9 g (76%) of expected product were obtained in the form of a yellow oil NMR ^ / CDCls: 1.55 (s, 6H); 2.05 (d, 9H); 3.38 (s, 3H); 3.57 (m, 2H); 3.82 (m, 2H); 5.27 (s, 2H), 7.11 (d, 1H); 7.22 (dd, 1H); 7.38 (d, 1H). c) 4 -Adamantan-l-i 1-3-hydroxy-phenyldiselenide. A mixture of product obtained previously (200 mg) of concentrated sulfuric acid (1.4 ml) of methanol (20 ml) and THF (20 ml) was stirred 12 hours at room temperature. The reaction medium was extracted with ethyl acetate. The organic phase was washed twice with water, dried over magnesium sulfate and concentrated on a rotary evaporator in vacuo. The expected product was purified by flash chromatography to give an orange powder. d) 4 -Adamantan-l-il-3-benzyloxy-pheni ldi selenide. A mixture of product previously obtained (4.4 mmol), of cesium carbonate (2.95 g) and of benzyl chloride (1.3 ml) in the DMF (18 ml) was stirred at room temperature for 24 hours. The reaction medium was extracted by ethyl ether. The organic phase was washed with water, dried over magnesium sulfate and concentrated on the rotary evaporator. The product was purified by filtration on silica (heptane, after dichloromethane). The expected compound was obtained in the form of a yellow powder. e) 6- [4-Adamantan-l-yl-3-benzyloxy-phenyl-selenalyl] -nicotinic acid The product was obtained in a manner analogous to Example 7, starting from 4-Adamantan-l-yl-3-benzyloxy-phenyldiselenide and of ethyl 6-iodo-nicotone. 1 H NMR / CDC13, acetone D6: 1.74 (s, 6H); 2.06 (s, 3H); 2.17 (s, 6H); 5.12 (s, 2H); 6.97 (d, 1H), 7.26 to 7.48 (m, 8H), 7.95 (dd, 1H), 9.04 (d, 1H).

EXAMPLE 32: 6- (3,5-Di-tert-butyl-2-benzyloxy-phenyl-islanyl) -nicotinic acid a) 3,5-Di-tert-butyl-2-benzyloxy-phenyldiselenide The operating mode was identical to that followed for Example 31 (c) and 31 (d), applied to the product of example 27 (b). b) 6- (3,5-Di-tert-butyl-2-benzyloxy-phenyl-islanyl) -nicotinic acid The product was obtained analogously to Example 7, starting from 3,5-di-tert-but-il-2. -benzyloxy-phenyldiselenide and ethyl 6-iodo-nicotinate. NMR ^ / CDCls, acetone D6: 1.33 (s, 9H); 1.44 (s, 9H); 5.13 (s, 2H); 7.00 (d, 1H); 7.24 to 7.32 (m, 5H), 7.51 (d, 1H), 7.60 (d, 1H), 7.98 (dd, 1H), 9.01 (d, 1H).

EXAMPLE 33: 3-Methoxy-4- (4-benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-ylseryl) -benzoic acid a) 4-hydroxy-5,6 , 7,8-tetrahydro-5,5,8, 8 -tet ramethyl 1 -naphthalene-2-diselenide The product of example 22 (a), 4-methoxymethoxy-5,6,7,8-tetrahydro-5, 5 , 8, 8-tetramet-ilnaphthalene-2-disdenide (12.4 g), treated analogously to example 15 (b), 11 g (100%) of the expected compound were obtained as a yellow solid. Tf = 200 ° C. 1 H NMR / CDC13: 1-22 (s, 6H); 1.42 (s, 6H); 1.63 (m, 4H); 5.25 (s, 1H); 6.75 (d, 1H); 7.11 (d, 1H). b) 4-benzyloxy-5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-naphthalene-2-diselenide A mixture of the product obtained above (2.5 g, 4.4 mmol), of cesium carbonate (2.95 g) and of benzyl chloride (1.3 ml) in the DMF (18 ml) was stirred at room temperature for 24 hours. The reaction medium was extracted by ethyl ether. The organic phase was washed with water, dried over magnesium sulfate and concentrated on the rotary evaporator. The product was purified by filtration on silica (heptane, then dichloromethane). 2.1 g (63%) of the expected compound were obtained in the form of a yellow powder. NMR ^ CDCls: 1.21 (s, 6H); 1.34 (s, 6H); 1.59 (m, 4H); 4.96 (s, 2H); 7.02 (d, 1H); 7.21 (d, 1H); 7.29 to 7.41 (m, 5H). c) 3-Methoxy-4- (4-benzyloxy-5,6,7,8-tet-5,5,8,8-tetramethylnaphthalen-2-ylsiloyl) -benzoic acid The product was obtained analogously to the example 7, from 4-benzyloxy-5, 6, 7, 8-tet rahydro-5, 5, 8, 8-tet ramet ilnaft aleno-2-diselenide and ethyl 4-iodo-3-methoxybenzoate. 1H-NMR / CDC13: 1-27 (s, 6H), 1.43 (s, 6H), 1.66 (m, 4H), 3.98 (s, 3H), 5.04 (s, 2H), 6.88 (d, 1H), 7.01 (d, 1H), 7.29 (s, 1H), 7.33 to 7.52 (m, 7H).

EXAMPLE 34: 4- (4-Benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-talen-2-yl-silyl) -benzoic acid The product was obtained analogously to Example 7 , from 4-benzyloxy-5,6,7,8-tetrahydro-5, 5, 8, 8-tetramethylnaphthalene-2-diselenide and ethyl 4-iodo-benzoate. 1H NMR / CDC13: 1.26 (s, 6H), 1.41 (s, 6H), 1.65 (m, 4H), 5.02 (s, 2H), 6.92 (d, 1H), 7.22 (d, 1H), 7.31 to 7.41 (m, 7H), 7.90 (d, 2H).

EXAMPLE 35: 6- (4-Benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-ylslanyl) -nicotinic acid The product was obtained in a manner analogous to Example 7, starting from of 4-benzyloxy-5,6,7,8-tetrahydro-5, 5, 8, 8-tet ramethylnaphthalene-2-diselenide and ethyl 6-iodo-nicotinate. 1H NMR / CDC13: 1.28 (s, 6H), 1.43 (s, 6H), 1.67 (m, 4H), 5.07 (s, 2H), 7.00 (d, 1H), 7.04 (d, 1H), 7.32 to 7.44 (m, 6H), 7.96 (dd, 1H), 9.06 (d, 1H).

EXAMPLE 36: 3-Methoxy-4- (3-benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-naphthalen-2-yl-slanyl) -benzoic acid a) 3-hydroxy-5, 6,7,8-tetrahydro-5,5,8,8-tetramet-il-naphthalene-2-diselenide The product of example 23 (a), 3-methoxyethoxy-methoxy-5,6,7,8-tetrahydro-5 , 5, 8, 8 -tetramethylnanephthalene-2-diselenide was treated analogously to Example 31 (c), the expected compound was obtained in the form of a yellow solid (100%). b) 3-benzyloxy-5,6,7,8-tetrahydro-5, 5, 8, 8-tet ramethyl-naphthalene-2-diselenide The product obtained above was treated analogously to example 33 (b) c) 3-methoxy-4- (3-benzyloxy-5,6,7,8-tet rahydro-5,5,8,8-tet ramet ilnaphthalen-2-ylslanyl) -benzoic acid The product was obtained analogously to Example 7, from 3-benzyloxy-5, 6, 7, 8-tet rahydro-5, 5, 8, 8-tet ramethylnaphthalene-2-diselenide and ethyl 4-iodo-methoxybenzoate. NMR XH / CDC13: 1.22 (s, 6H), 1.25 (s, 6H), 1.67 (s, 4H), 3.97 (s, 3H), 5.07 (s, 2H), 6.89 (d, 1H), 6.90 (s) , 1H), 7.22 to 7.25 (m, 5H), 7.50 to 7.53 (m, 3H).

EXAMPLE 37: 6- (3-Benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetra-methylnaphthalen-2-yl-phenyl) -nicotinic acid The product was obtained in a manner analogous to Example 7, from 3-benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2-diselenide and ethyl 6-iodo-nicotinate. NMR ^ / acetone D6, CDC13: 1.25 (s, 6H), 1.27 (s, 6H), 1.68 (s, 4H), 5.08 (s, 2H), 6.94 (s, 1H), 7.04 (d, 1H), 7.31 (s, 3H), 7.62 (s, 1H), 7.94 (dd, 1H), 9.04 (d, 1H).

EXAMPLE 38: 4- (3-Hexyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetra-methylnaphthalen-2-ylslanyl) -3-methoxy-benzoic acid a) 3-hexyloxy-5 , 6, 7, 8-tet rahydro-5, 5, 8, 8-tetramet-il-naphthalene-2-diselenide Sodium hydride at 60% (225 mg, 5.63 mmol) was added per fractions to a solution of 4-hydroxy -5, 6.7, 8-tetrahydro-5,5,8, 8-tetramethylnaphthalene-2-diselenide (1.2 g, 2.56 mmole) in 15 ml of THF and 15 ml of THF. Stirring was continued 30 minutes at T.A. after the end of the addition, then iodohexane (1 ml, 6.8 mmol) was added. The reaction medium was stirred for 4 hours at T.A., then treated with water and ethyl ether. The organic phase was washed with water, dried over magnesium sulfate and concentrated. After purification by chromatography on silica (heptane 95, CH2C12 5), the product was obtained as a yellow oil. 1 H NMR / CDC13: 0.90 (m, 9H) '; 1.30 to 1.48 (m, 12H); 1.59 (m, 4H); 1.77 (m, 2H); 3.85 (t, 2H), 6.92 (d, 1H); 7.17 (d, 1H). b) 4- (3-Hexyloxy-5,6,7,8-tetrahydro-5, 5, 8, 8-tet ramet ilnaphthalen-2-ylsalylan) -3-methoxy-benzoic acid The product was obtained in a manner analogous to Example 7, from 3-hexyloxy-5,6,7,8-tet rahydro-5, 5, 8, 8-tetramethylnaphthalene-2-diselenide and ethyl 4-iodo-3-methoxybenzoate. 1H NMR / CDC13: 0.89 (t, 3H), 1.27 (s, 6H), 1.30 to 1.37 (m, 4H), 1.42 (s, 6H), 1.48 (m, 2H), 1.63 (m, 4H), 1.82 (m, 2H), 3.90 (t, 2H), 3.98 (s, 3H), 6.91 (d, 1H), 6.93 (s, 1H), 7.24 (s, 1H), 7.49 to 7.55 (m, 2H).

EXAMPLE 39: 6- (3-Hexyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetra-methylnaphthalen-2-ylslanyl) -nicotinic acid The product was obtained analogously to Example 7, from 3-hexyloxy-5, 6, 7, 8-tet rahydro-5, 5, 8, 8-tetramethylnaphthalene-2-diselenide and of ethyl 6-iodo-nicotinate. 1H NMR / CDC13: 0.89 (t, 3H), 1.27 (s, 6H), 1.30 to 1.37 (m, 4H), 1.42 (s, 6H), 1.48 (m, 2H), 1.63 (m, 4H), 1.84 (m, 2H), 3.92 (t, 2H), 6.97 (d, 1H), 7.08 (d, 1H), 7.29 (d, 1H), 8.00 (dd, 1H), 9.08 (d, 1H).

EXAMPLE 40: 4- (5-Adamantan-l-yl-4-benzyloxy-2-methyl-phenyl-selenyl) -benzoic acid a) 5 -Adamantan-l -yl-4-benzyloxy-2-methyl-phenyl di selenide . The operating mode was identical to that followed by example 31 (c) and 31 (d), applying to the product of Example 16 (a). b) 4- (5-Adamantan-1-yl-4-benzyloxy-2-methyl-phenyl-selenyl) -benzoic acid The product was obtained analogously to Example 7, starting from 5-Adamantan-1-yl-4 -benzyloxy-2-methyl-phenyl-diselenide and ethyl 4-iodobenzoate. 1 H NMR / acetone D6, CDC13: 1.70 (s, 6H); 2.02 (s, 3H), 2.11 (s, 6H), 2.41 (s, 3H), 5.16 (s, 2H), 6.85 (dd, 1H), 6.98 (s, 1H), 7.35 to 7.58 (m, 6H) 7.97 (dd, 2H), 9.05 (d, 1H).

EASEM 41: 6- [3- [5-tert-Butyl-dimethyl-silanyloxy) -pentyloxymethyl] -5,6,7,8-tetrahydro-5, 5,8,8-tetramethylnaphthalen-2-yl-silanyl] nicotinate of ethyl. a) 5- (3-Bromo-5, 5, 8, 8-tetramet-il-5,6,7,8-tetrahydro-naphthalen-2-yloxy) -pentyl acetate. A solution of 3-bromo-5, 5, 8, 8-tet ramet il-5, 6, 7, 8-tetrahydronaphthalen-2-ol (10 g, 0.35 mol), of 5-bromopentyl acetate (8.15 g) ), and of potassium carbonate (33.6 g) in the methyl ethyl ketone (200 ml), was heated to reflux for 2 hours. The reaction medium was treated with water and ethyl acetate. After decanting, the organic phase was washed twice with water, dried over magnesium sulfate and concentrated on a rotary evaporator under vacuum at 40 ° C. The product was purified by flash chromatography on a silica column. Yellow oil Yield: 93%. b) [5- (3-Bromo-5, 5, 8, 8-tetramet-il-5, 6, 7, 8-tet-rahydro-naphthalen-2-yloxy) -pentyloxy] -tert-butyl-dimethyl-silane The acetate obtained above was saponified, then the resulting hydroxyl group was protected according to the following operating mode: tert-butyldimethylsilane chloride (2.64 g) was added to a mixture of 5- (3-Bromo-5, 5, 8, 8-tet ramet il-5, 6, 7, 8-naphthalen-2-yloxy) -pentan-1-ol (4.3 g, 11.7 mmol) and 80% sodium hydride (422 mg) in THF (20 ml). The mixture was stirred at room temperature 2 hours. The solution was poured into a mixture of water and ethyl acetate. The organic phase was washed twice with water, dried over magnesium sulfate, and concentrated on a rotary evaporator under vacuum at 40 ° C. The product was purified by flash chromatography on a silica column. Yellow oil Performance: 64%. c) 3- [5- (tert-Butyl-dimethyl-silanyloxy) -pentyloxy] -5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalene-2-diselenide. The expected product was obtained from the bromine obtained above, in a similar manner to example la. Yellow oil Yield: 10%. d) 6- [3- [5- (tert-butyl-dimethyl-silanyloxy) -pentyloxy] -5,6,7,8-tetrahydro-5, 5, 8, 8-tetramethylnaphthalen-2-ylslanyl] ethyl nicotinate Analogously to example 1 (b), by reaction of 257 mg (0.27 mmol) of the diselenide previously obtained in 25 ml of ethanol with 119 mg of sodium borohydride, 120 mg (0.43 mmol) of ethyl 6- andodonicotone and 4 mg of bis dibromide (bipyridine) nickel (II), 152 mg (56%) of the expected derivative was obtained in the form of a yellow oil. 1N-NMR (CDC13): 0.00 (6H, s), 0.85 (9H, s), 1.22 (6H, s), 1.30 (6H, s), 1.33 to 1.50 (6H, m), 1.60 to 1.67 (7H, m), 3.48 (2H, t), 3.92 (2H, t), 4.35 (2H, q), 6.84 (1H, s), 6.99 (1H, d), 7.57 (1H, s), 7.91 ( 1H, dd), 8.97 (1H, d).

EXAMPLE 42: 6- [3- [5- (tert-Butyl-di-ethyl-silanyloxy) -pentyloxy] -5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl-silyl] acid nicotinic Analogously to example 2, by reaction of 312 mg (0.49 mmol) of 6- [3- [5- (tert-butyl-dimethyl-silanyloxy) -pentyloxy] -5,6,7,8-tetrahydro- 5, 5, 8, 8-tetra-methylnaphthalen-2-ylslanyl] ethyl nicotinate with 213 mg (5.3 mmol) of soda in a THF / ethanol mixture (5 ml / 5 ml) yielded 210 mg (71%) of yellow powder. Tf: 161 ° C.

EXAMPLE 43: 6- [3- (5-Hydroxypentyloxy) -5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-naphthalen-2-ylslanyl] nicotinic acid.

A mixture of the product from the previous example (210 mg, 0.35 mmol), from a 1M solution in the THF of tetra-n-butylammonium fluoride (380 μL) in the THF (5 ml) was stirred at room temperature 3 hours. 380 μl of the tetra-n-butyl ammonium fluoride solution were added to the reaction medium. Agitation was continued 3.5 hours, then even added 380 μl of TBAF and the addition was continued for an additional 1.20 hours. The reaction medium was treated with a solution of IN HCl and ethyl acetate. After decanting, the organic phase was washed with water, dried over anhydrous magnesium sulfate and concentrated.

The product was purified by crystallization from a mixture of heptane, ethyl ether. Mass: 194 mg, white powder. Mp: 190-192 ° C.

EXAMPLE 44: 4- (5, 5, 8, 8, -tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -ethylbenzoate. (a) 5, 6, 7, 8-tet rahydro-5, 5, 8, 8-tet ramet ilnaphthalene-2-diselenide. A solution of ter-butyllithium, 1.7 M in the pentane (37.4 mmol, 22 ml) was added to a solution of 2-bromo-5,6,7,8-tet rahydro-5, 5, 8, 8-tetra- methylnaphthalene (4.22 g, 15.8 mmol) in THF (100 ml) at -78 ° C in 10 minutes. The mixture was stirred at 0 ° C for 30 minutes. Selenium (1.33 g, 16.8 mmol) was added twice. The mixture was stirred at 0 ° C for 15 minutes, then at room temperature for 30 minutes. An INN HCl solution (40 ml) was added, then the reaction mixture was treated with ethyl ether. The organic phase was washed twice with water, dried over anhydrous magnesium sulfate and concentrated on the rotary evaporator under vacuum at 40 ° C. 10 ml of ethanol and 50 mg of soda were added to the obtained oil. The mixture was stirred vigorously for a few minutes in the air (csp all precipitate), then concentrated in the rotary evaporator under vacuum at 40 ° C. The solid obtained was filtered on silica (elution with heptane) then crystallized from a mixture of ethane / ether. Solid orange Mass: 2.9 g. Performance: 69%. XH NMR (CDC13): 1.21 (6H, s), 1.25 (6H, s), 1.65 (4H, s), 7.20 (1H Ar, d, J = 8.25 Hz), 7.38 (1H Ar, dd, J = 1.9 Hz, J = 8.25 Hz), 7.51 (1H Ar, d, J = 1.9 Hz). b) ethyl 4- (5, 5, 8, 8 -Tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -benzoate Analogously to example 1 (b), by reaction of 213 mg (0.4 mmol) of diselenide previously obtained in 20 ml of ethanol with 73 mg of sodium borohydride (1.92 mmol), 177 mg (0.64 mmol) of ethyl 4-iodobenzoate and 37 mg of tetrakis triphenylphosphine palladium. After purification by flash chromatography (heptane 70-CH2Cl2 30), 151 mg of the expected derivative was obtained as a yellow solid. Tf = 73 ° C. XH NMR (CDC13): 1.26 (6H, s), 1.29 (6H, s), 1.37 (t, 3H), 1.70 (4H, s), 4.34 (q, 2H), 7.15 to 7.25 (m, 3H), 7.32 (1H, d), 7.44 (1H, d), 7.89 (1H, d).

EXAMPLE 45: 4- (3-Methoxyethoxymethoxy-5, 5,8, 8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-silyl) -benzoic acid ethyl ester Analogously to example 1 (b), by reaction of 3.35 g (4.5 mmol) of 3-methoxyethoxymethoxy-5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tet ramethylnaphthalene-2 -diselenide in 100 ml of ethanol with 501 mg of sodium borohydride (13.5 mmoles), 2.5 g (9 mmoles) of ethyl 4-iodobenzoate and 90 mg of Bis (bipyridine) nickel II dibromide. After purification by flash chromatography (heptane 85, AcOEt 15), 2.58 g of the expected derivative was obtained in the form of a yellow oil (83%).

EXAMPLE 46: 4- (3-hydroxy-5, 5,8, 8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -benzoic acid ethyl ester. A mixture of ethyl 4 - (3-methoxyethoxymethoxy-5, 5, 8, 8-tetramethyl-5, 6, 7, 8-tetrahydro-naphthalen-2-ylsenyl) -benzoate (2.3 g, 4.4 mmol) of sulfuric acid Concentrate (475 μl) of methanol (40 ml) and THF (20 ml) was stirred 48 hours at room temperature. The reaction medium was extracted with ethyl ether. The organic phase was washed twice with water, dried over magnesium sulfate and concentrated on a rotary evaporator in vacuo. The product was purified by crystallization in heptane. 2.06 g (97%) of the expected compound were obtained in the form of an orange powder. Tf = 113 ° C.

EXAMPLE 47: 4- (3-Hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -benzoic acid. Analogously to example 2, by reaction of 400 mg (0.92 mmol) of 4 - (3-Hydroxy-5, 5, 8, 8-tet ramet i 1-5, 6.7, 8-tetrahydro-naphthalene-2 ethyl-ethyl-benzoate with 336 mg (8.4 mmol) of soda in a THF / ethanol mixture (20 ml / 20 ml), 214 mg (58%) of pink powder was obtained. Tf: 217 ° C.

EXAMPLE 48: 6- (3-Methoxyethoxymethoxy-5, 5,8, 8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-silyl) -nicnicinate, ethyl In analogy to example 1 (b), by reaction of 3.35 g (4.45 mmol) of 3-methoxyethoxymethoxy-5,6,7,8-tetrahydro-5, 5, 8, 8 -tetramethylnaphthalene-2 -diselenide in 100 ml of ethanol with 501 mg of sodium borohydride ( 13.5 mmoles), 2.5 g (9 mmoles) of ethyl 4-iodobenzoate and 90 mg of Bis (bipyridine) nickel II dibromide. After purification by flash chromatography (heptane 85, AcOEt 15), 2.09 g of the expected derivative was obtained in the form of a yellow oil (45%). 1H-NMR / CDC13: 1.25 (s, 6H), 1.31 (s, 6H), 1.38 (t, 3H), 1.69 (m, 4H), 3.36 (s, 3H), 3.50 (m, 3H), 3.73 (m , 2H), 4.37 (q, 2H), 5.22 (s, 2H), 7.01 (d, 1H), 7.22 (s, 1H), 7.60 (s, 1H), 7.94 (dd, 1H), 8.99 (d, 1 HOUR).

EXAMPLE 49: 6- (3-Hydroxy-5, 5,8, 8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-silyl) -ethyl nicotinate A mixture of 6- (3-methoxyethoxymethoxy) 5, 5, 8, 8-tetramethyl-5, 6, 7, 8 -tetrahydro-naphthalen-2-ylslanyl) -nicnicinate (2.6 g, 5 mmol) of concentrated sulfuric acid (535 μl) of ethanol (75 ml) ) and THF (25 ml) was stirred 3 days at room temperature. The reaction medium was extracted with ethyl ether. The organic phase was washed twice with water, dried over magnesium sulfate and concentrated on a rotary evaporator in vacuo. The solid obtained was washed with ethyl ether. 2.01 g (93%) of the expected compound were obtained in the form of an orange powder Tf = 138 ° C.

EXAMPLE 50: 6- (3-Hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylselanyl) -nicotinic acid Analogously to example 2, by reaction of 400 mg (0.92 mmol) of ethyl 6- (3-Hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -nicotinate with 357 mg (8.9 mmol) of soda in a THF / ethanol mixture (20 ml / 20 ml), 60 mg (16%) of yellow powder was obtained. Tf: 250 ° C.

EXAMPLE 51: 6- [3- (3-ethoxy-carbonyl-propoxy) -5,5,8, 8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-silyl] -nicnicinate-ethyl ester. In a three-necked flask, 432 mg (102.0 mmol) of 6- (3-hydroxy-5, 5, 8, 8-tetramethyl-5, 6, 7, 8-tet rahydro-naphthalen-2-ylslanyl) -nicnicinate, 276 mg (2 mg) mmoles) of potassium carbonate and 390 mg (2 mmoles) of ethyl 4-bromobutanoate. The mixture was heated at 80 ° C for 12 hours. The reaction medium was poured into water, extracted with ethyl ether, the organic phase was decanted, washed with water, dried over magnesium sulfate, evaporated. After purification by flash chromatography (heptane 9, AcOEt 1), 467 mg (85%) of the expected compound was collected in the form of an orange oil. NMR-H / CDCls: 1.20 to 1.31 (m, 15H), 1.38 (t, 3H), 1.69 (s, 4H), 1.96 (m, 2H), 2.38 (t, 2H), 2.85 (t, 2H) , 4.12 (q, 2H), 4.36 (q, 2H), 6.88 (d, 1H), 7.02 (s, 1H), 7.48 (s, 1H), 8.26 (dd, 2H), 8.83 (d, 1H).

EXAMPLE 52: 6- [3- (3-Carboxy-propoxy) -5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl] -nicotinic acid. Analogously to example 2, by reaction of 340 mg (0.62 mmoles) of 6- [3- (3-ethoxy-carbonyl-propoxy) -5,5,8,8-tetramethyl-5,6,7,8- ethyl tetrahydronaphthalen-2-ylslanyl] -nicotinate with 250 mg (62.2 mmoles) of soda in ethanol (10 ml), 211 mg (69%) of white powder were obtained. Tf: 177 ° C.

EXAMPLE 53: 4- [3- (3-ethoxycarbonyl-propoxy) -5,5,8, 8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-slanyl) -ethylbenzoate Analogously to Example 51, by reaction of 300 mg (0.86 mmol) of 4- (3-hydroxy-5, 5, 8, 8-tetramet-il-5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanyl] -benzoate of Ethyl with 336 mg (1.72 mmol) of ethyl 4-bromobutanoate and 238 mg of potassium carbonate in the ECM (10 ml) gave 364 mg (78%) of a yellow oil.1H NMR / CDC13: 1.16 a 1.32 (m, 15H), 1.38 (t, 3H), 1.66 (m, 4H), 1.98 (m, 2H), 2.30 (t, 2H), 3.98 (t, 2H), 4.08 (q, 2H), 4.35 (9, 2H), 6.78 (s, 1H), 7.28 (s, 1H), 7.41 (dd, 2H), 7.87 (dd, 2H).

EXAMPLE 54: 4- [3- (3-Carboxy-propoxy) -5,5,8,8-temethyl-5,6,7,8-tetrahydronaphthalen-2-ylslanyl] -benzoic acid. Analogously to example 2, by reaction of 250 mg (0.46 mmol) of ethyl 4 - [3- (3-carboxy-propoxy) -5,5,8, 8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl] -benzoate with 183 mg (4.6 mmol) of soda in a THF / ethanol mixture (5/5 ml), 172 mg (76%) of white powder was obtained. Tf: 230 ° C.

EXAMPLE 55: 4- [3- (7-methoxycarbonyl-heptyloxy) -5,5,8, 8-teramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl] -benzoic acid ethyl ester. Analogously to example 51, by reaction of 370 mg (0.86 mmol) of 4- (3-hydroxy-5, 5, 8, 8-tet ramethyl-5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanil ] -benzoate of ethyl with 408 mg (1.72 mmol) of methyl 8-bromooctanoate and 238 mg of potassium carbonate in the MEC (10 ml), 502 mg (99%) of a yellow oil was obtained. CDC13: 1.16 (s, 6H), 1.26 to 1.29 (m, 12H9, 1.38 (t, 3H), 1.56 to 1.68 (m, 8H), 2.28 (t, 2H), 3.36 (s, 3H), 3.92 (t , 2H), 4.36 (q, 2H), 6.78 (s, 1H), 7.27 (s, 1H), 7.41 (dd, 2H), 7.88 (dd, 2H).

EXAMPLE 56: 4- [3- (7-Carboxy-heptyloxy) -5,5,8,8-tetramethyl-5,6,7,8-etrahydronaphthalen-2-ylslanyl] -benzoic acid. Analogously to example 2, by reaction of 410 mg (0.7 mmoles) of 4 - [3- (7-methoxycarbonyl-heptyloxy) -5,5,8, 8-tetramethyl-5,6,7,8-tetrahydronaphthalene- Ethyl 2-ylslanyl] -benzoate with 280 mg (7 mmol) of sodium hydroxide in a THF / ethanol mixture (5/5 ml) gave 326 mg (85%) of white powder. Tf: 183.

EXAMPLE 57: 6- [3- (7-Methoxycarbonyl-heptyloxy) -5,5,8, 8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-silyl] -nicnicinate from ethyl. Analogously to example 51, by reaction of 460 mg (1.06 mmol) of 6- (3-hydroxy-5, 5, 8, 8-tetramet-il-5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanil -nicot ethyl ester with 515 mg (2.17 mmoles) of methyl 8-bromo-octanoate and 295 mg of potassium carbonate in the MEC (10 ml), 487 mg (78%) of a yellow oil was obtained.

EXAMPLE 58: 6- [3- (7-Carboxy-heptyloxy) -5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaph-alan-2-ylslanyl] -nicotinic acid. Analogously to example 2, by reaction of 390 mg (0.66 mmol) of 6- [3- (7-methoxycarbonyl-heptyloxy) -5,5,8, 8-tetramethyl-5, 6,7, 8- ethyl tetrahydro-naphthalen-2-ylslanyl] -nicotinate with 265 mg (6.6 mmoles) of soda in a THF / ethanol mixture (5/1 ml), 277 mg (77%) of white powder were obtained. Tf: 186 ° C.

EXAMPLE 59: 6- (3- (2-Acetoxy-ethoxy) -5,5,8, 8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-silyl) -nicnicinate from ethyl. ^^ i = ^ a) (2-bromoetyl) acetate. Acetic anhydride (11.35 ml, 0.12 mol) was added dropwise in a solution of 2-bromoethanol (12.5 g, 0.1 mol), DMAP (1.22 g) in 125 ml of dichloromethane. The mixture was stirred at room temperature for 12 hours, treated in water and in dichloromethane. The organic phase was washed with water, dried over magnesium sulfate and concentrated on the rotary evaporator and purified by distillation. Yellowish liquid (94%). b) 6- (3- (2-acetoxy-ethoxy) -5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-silyl) -nicniconate ethane In a manner analogous to the example 51, by reaction of 477 mg (1.10 mmol) of 6- (3-hydroxy-5, 5, 8, 8-tetramet-il-5, 6,7, 8-tetrahydro-naphthalen-2-yl selanyl] -nicotinate from ethyl acetate with 396 mg (2.2 mmol) of 2-bromoethyl acetate) and 304 mg of potassium carbonate in the ECM (10 ml) gave 545 mg (96%) of a yellow oil. 1H-NMR / CDC13: 1.24 (s, 6H), 1.32 (s, 6H), 1.38 (t, 3H), 1.69 (s, 4H), 1.99 (s, 3H), 3.00 (t, 3H), 4.24 (t , 2H), 4.38 (q, 2H), 6.89 (d, 1H), 7.03 (s, 1H), 7.54 (s, 1H), 8.27 (dd, 1H), 8.83 (d, 1H).

EXAMPLE 60: 6- (3- (2-Hydroxy-ethoxy) -5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -nicotinic acid Analogously to the example 2, by reaction of 419 mg (0.81 mmol) of 6- [3- (2-acetoxy-ethoxy) -5,5,8,8-tetramet-il-5,6,7,8-tetrahydro-naphthalene-2 ilselanyl] -nicniconate with 320 mg (8 mmol) of soda in a THF / ethanol mixture (4/4 ml), 273 mg (75%) of white powder was obtained. Tf: 170 °.

EXAMPLE 61 4-83- (2-Acetoxy-ethoxy) -5,5,8, ethyl 8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanil-benzoate Analogously to example 51, by reaction of 400 mg (0.93 mmol) of ethyl 4- (3-hydroxy-5, 5, 8, 8-tet ramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl] -benzoic acid with 334 mg (2.2 mmol) of (2-bromoethyl) acetate and 257 mg of potassium carbonate in the MEC (10 ml) gave 333 mg (69%) of a yellow oil. RMN ^ / CDCls: 1.16 (s) , 6H), 1.29 (s, 6H), 1.38 (t, 3H), 1.59 (s, 4H), 1.99 (s, 3H), 4.16 (m, 2H), 4.29 to 4.40 (m, 4H), 6.82 ( s, 1H), 7.28 (s, 1H), 7.43 (d, 1H), 7.89 (d, 1H).

EXAMPLE 62: 4- (3- (2-Hydroxy-ethoxy) -5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -benzoic acid. Analogously to example 2, by reaction of 322 mg (0.62 mmol) of 4 - [3- (2-acetoxy-ethoxy) -5, 5, 8, 8-tetramethi 1-5, 6, 7, 8-tetrahydro Ethyl-naphthalen-2-ylslanyl] -benzoate with 250 mg (6.2 mmol) of sodium hydroxide in a THF / ethanol mixture (3/3 ml) gave 226 mg (81%) of white powder. Tf: 197 °.

EXAMPLE 63: 4- (3- (2-Chloro-ethoxy) -5,5,8, 8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -benzoic acid ethyl ester. Analogously to example 51, by reaction of 431 mg (1 mmol) of 4 - (3-hydroxy-5, 5, 8, 8-tetramet-il-5, 6, 7, 8-tetrahydro-naphthalen-2-yl-silyl) ] ethylbenzoate with 222 mg (1.5 mmol) of l-bromo-2-chloroetyl and 278 mg of potassium carbonate in the ECM (20 ml), 200 mg (40%) of a yellow oil was obtained.

EXAMPLE 64: 4- [3- (2-iodo-ethoxy) -5,5,8, 8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl] -benzoic acid ethyl ester. A mixture of 200 mg (0.4 mmol) of 4- [3- (2-chloroethoxy) -5,5,8, 8-tetramethyl-5,6,7,8-tet rahydro-naphthalene- .a% * • & *. Ethyl 2-ylslanyl] -benzoate with 607 mg (4 mmol) of sodium iodide in the ECM (4 ml), was heated to reflux for 12 hours. The reaction medium was treated with water and with ethyl ether. The organic phase was washed with water, dried over magnesium sulfate and concentrated on the rotary evaporator. The obtained oil was again put into reaction under the same conditions. 159 mg (68%) of a yellow solid were obtained, Mp = 87 ° C.

EXAMPLE 65 6- (3-Adamantan-l-yl-4-methoxy-enyl-islanyl) -nicotinic acid The product was obtained analogously to Example 7, starting from 3-Adamantan-l-yl-4-methoxy-phenyl-diselenide and ethyl 6-iodonicotinate. NMR XH / THF D8: 1.79 (s, 6H), 2.04 (s, 3H), 2.13 (s, 6H), 3.89 (s, 3H), 6.93 (d, 1H), 7.02 (d, 1H), 7.52 a 7. 55 (m, 2H), 7.91 (dd, 1H), 8.9 (d, 1H).

EXAMPLE 66: [6- (3, 5, 5, 8, 8-Pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -pyridin-3-yl] -methanol In a flask and under a stream of nitrogen, 3 g (7 mmol) of 6- (3, 5, 5, 8, 8-Pentamet-il-5,6,7,8-tetrahydro-naphthalen-2-yl-silyl) -ethyl nicotinate, 800 were introduced mg (20 mmoles) of double lithium aluminum iodide and 90 ml of THF. It was heated at reflux for two hours, the reaction medium was cooled, the excess hydride was hydrolyzed and the salt was filtered. After evaporation of the filtrate, the obtained residue was recrystallized from heptane. 1.36 g (50%) of [6- (3, 5, 5, 8, 8-Pentamet-il-5, 6, 7, 8-tetrahydro-naphthalen-2-yl-slanyl) -pyridin-3-yl] was collected. methanol of melting point 110-1 ° C.

EXAMPLE 67: N-Ethyl-6- (3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylselanyl) -nicotinamide (a) Chloride of 6- (3, 5, 5, 8, 8-pentamet-il-5, 6, 7, 8-tetra-hydro-naphthalen-2-ylslanyl) -nicotinoyl. Into a flask, 2 g (5 mmoles) of 6- (3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-ylslanyl) -nicotinic acid, 20 ml of toluene were introduced , 100 μl of DMF and 450 μl of thionyl chloride. It was heated to reflux for one hour, the reaction medium was evaporated. 100% expected acid chloride was collected which will be used as in the continuation of the synthesis. (b) N-Ethyl-6- (3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylselanyl) -nicotinamide By reaction of 2.1 g (5 mmol) of the The above acid chloride with 1 ml of ethylamine (70% in water) in 20 ml of THF gave 2.02 g (95%) of the expected amide of melting point 218-20 ° C.

EXAMPLE 68 Morpholin-4-yl- [6- (3, 5, 5, 8, 8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-ylslanyl) -pyridin-3-yl] -methanone By reaction of 2.1 g (5 mmol) of the preceding acid chloride with 1 ml of morpholine in 20 ml of THF gave 2.17 g (93%) of the expected amide of melting point 147-8 ° C.

EXAMPLE 69: N- (4-Hydroxy-phenyl) -6- (3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-ylsillanyl) -nicotinamimda by reaction of 2.1 g ( 5 mmoles) of the above acid chloride with 540 mg (5 mmoles) of 4-amino-phenyl in 40 ml of THF in the presence of 830 μl of triethylamine, 2.35 g (96%) of the expected amide melting point were obtained 223-25 ° C.

EXAMPLE 70 6- (3, 5, 5, 8, 8-Pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -pyridine-3-carbaldehyde By reaction of 890 mg (2.3 mmol) of [ 6- (3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -pyridin-3-yl] -methanol with 1.12 g (3 mmoles) of pyridinium dichromate in 90 ml of dichloromethane, 600 mg (68%) of 6- (3, 5, 5, 8, 8-Pentamet-il-5, 6, 7, 8-tetrahydro-naphthalene-2 were obtained after filtration on silica. ilselanil) -pyridine-3-carbaldehyde of melting point 150-2 ° C.

B. EXAMPLES OF FORMULATION 1) ORAL VIA (a) The following composition was prepared in the form of a tablet of 0.8 g Compound of example 3 0.005 g Pregelatinized starch 0.265 g Microcrystalline cellulose 0.300 g Lactose 0.200 g Magnesium stearate 0.030 g For the treatment of acne, were administered to an adult of 1 to 3 tablets per day for 3 to 6 months depending on the severity of the case treated. (b) A drinkable suspension was prepared, destined to be conditioned in 5 ml ampoules Compound of example 12 0.050 g Glycerin 0.500 g Sorbitol at 70% 0.500 g Sodium saccharinate 0.010 g Methyl parahydroxybenzoate 0.040 g Aroma c.s. Purified water c. s. p. 5 ml For the treatment of acne, one adult will receive 1 ampoule per day for 3 months depending on the severity of the case treated. (c) The following formulation intended to be packaged in capsules was prepared: Compound of example 5 0.025 g Corn starch 0.060 g Lactose c.s.p. 0.300 g The capsules used were constituted by gelatin, titanium oxide and a preservative. In the treatment of psoriasis, an adult individual will be administered 1 capsule per day for 10 days. 2) TOPICAL (a) The following non-ionic Water-in-Aceite cream was prepared: Compound of example 23 0.100 g Mixture of lanolin alcohols emulsifiers, waxes and refined oils, sold by the BDF Company under the name " Eucérine anhidre "39,900 g Methyl parahydroxybenzene 0.075 g Propyl parahydroxybenzoate 0.075 g Sterile demineralized water c.s.p. 100,000 g This cream will be applied on psoriatic skin 1 to 2 times a day for 30 days. (b) A gel was prepared by making the following formulation: Compound of Example 39 0.050 g Erythromycin base 4000 g Butylhydroxytoluene 0.050 g Hydroxypropylcellulose sold by the Hercules Company under the name of "KLUCEL HF" 2,000 g Ethanol (at 95 °) c.s.p. 100, 000 g This gel will be applied on a skin attacked by dermatosis or acne skin 1 to 3 times a day for 6 to 12 weeks depending on the severity of the case treated. (c) An antisborreic lotion was prepared by mixing the following ingredients: Compound of example 46 O. 030 g Propylene glycol 5,000 g Butylhydroxytoluene 0.100 g Ethanol (at 95 ° C) q.s. 100, 000 g This lotion will be applied twice a day on a seborrheic scalp and a significant improvement is observed in a period comprised between 2 and 6 weeks. (d) A cosmetic composition was prepared against the harmful effects of the sun by mixing the following ingredients: Compound of example 59 1,000 g Bencilideno canfor 4.000 g Triglycerides of fatty acids 31,000 g Glycerol monostearate 6,000 g Stearic acid 2,000 g Cetyl alcohol 1,200 g Lanolin 4000 g Preservatives 0.300 g Propylene glycol 2,000 g Triethanolamine 0.500 g Perfume 0.400 g Demineralized water c.s.p. 100,000 g This composition will be applied on a daily basis, it allows to fight against photo-induced aging. (e) The following non-ionic Water Oil cream was prepared: Compound of Example 16 0.500 g Vitamin D3 0.020 g Cetyl alcohol 4000 g Glycerol monostearate 2,500 g PEG stearate 50 2,500 g Manteca de Carite 9.200 g Propylene glycol 2,000 g Methyl parahydroxybenzoate 0.075 g Propyl parahydroxybenzoate 0.075 g Sterile demineralized water c.s.p. 100,000 g This cream will be applied on psoriatic skin 1 to 2 times a day for 30 days. (f) A topical gel was prepared by mixing the following ingredients: Compound of example 4 0.050 g Ethanol 43,000 g a-tocopherol 0.050 g Carboxy vinyl polymer sold under the name "Carbopol 941 'by the company" Goodrich "0.500 g Triethanolamine in aqueous solution at 20% by weight 3,800 g Water 9,300 g Propylene glycol csp 100,000 g This gel will be applied in the treatment of acne 1 to 3 times a day for 6 to 12 weeks depending on the severity of the case treated. prepared a hair anti-hair loss lotion and for the hair growth proceeding to the mixture of the following ingredients: Compound of example 31 0.05 Compound sold under the name "Minoxidil" 1.00 g Propylene glycol 20.00 g Ethanol 34.92 g Polyethylene glycol (molecular mass = 400 ) 4 0 0 0 g Butylhydroxyanisole 0 .0 1 g Butylhydroxytoluene 0.02 g Water csp 1 0 0 0 0 g This lotion will be applied twice a day for 3 months on a leather elludo who has suffered a significant hair loss. (h) An anti-acne cream was prepared by mixing the following ingredients: Compound of example 7 0.050 g Retinoic acid 0.010 g Mixture of glycerol and polyethylene glycol stearates (75 moles) sold under the name "Gelot 64" by the "GATTEFOSSE" company 15,000 g Polyoxyethylenated core oil with 6 moles of ethylene oxide sold under the name "Labrafil M2130 CS" by the company "GATTEFOSSE" 8,000 g Perhydroescalene 10,000 g Preservatives cs Polyethylene glycol (molecular mass = 400) 8,000 g Salt Ethylenediamine tetraacetic acid disodium 100,000 g This cream will be applied to skin attacked with dermatosis or acne skin 1 to 3 times a day for 6 to 12 weeks. (i) An oil-in-water cream was prepared by making the following formulation: Compound of example 43 0.020 g Betamethasone 17-valerate 0.050 g S-carboxymethyl cysteine 3,000 g Polyoxyethylene stearate (40 moles of ethylene oxide) sold under the name "Myrj 52" by the company "ATLAS" 4.000 g Polyoxyethylenated sorbitan monolaurate with 20 moles of ethylene oxide sold under the name "Tween 20" by the company "ATLAS" 1,800 g Mixture of glycerol mono and distearate sold under the name "Géléol" by the company "GATTEFOSSE" 4.200 g Propylene glycol 10,000 g Butylhydroxyanisole 0.010 g Butylhydroxytoluene 0.020 g Ceto-stearic alcohol 6,200 g Preservatives q.s.

Perhydroescaleno 18,000 g Caprylic-capric triglyceride mixture sold under the name "Miglyol 812" by the company "DYNAMIT NOBEL" 4.000 g Triethanolamine (99% by weight) 2,500 g Water c.s.p. 100,000 g This cream will be applied twice a day on a skin attacked by dermatoses for 30 days. (j) The following oil-in-water type cream was prepared: Lactic acid 5,000 g Compound of example 1 0.020 g Polyoxyethylene stearate (40 moles of ethylene oxide) sold under the name "Myrj 52" by the company " ATLAS "4,000 g Sorbitan monolaurate, polyoxyethylenated with 20 moles of ethylene oxide sold under the name of Tween 20" by the company "ATLAS" 1,800 g Mixture of glycerol mono and distearate sold under the name of "Geleol" by the company "GATTEFOSSE" 4,200 g Propylene glycol 10,000 g Butyl hydroxyanisole 0.010 g Butyl hydroxytoluene 0.020 g Cetostearyl alcohol 6,200 g Preservatives cs Perhydroescalene 18,000 g »..ijffri? I .., Caprylic triglyceride mixture Sold under the name" Migliol 812"by the company" DYNAMIT NOBEL "4.000 g Water 100.000 g This cream will be applied once a day, helps to fight against aging either photo-induced or chronological. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (20)

CLAIMS Having described the invention as above, the content of the following claims is claimed as property:

1. Compounds, characterized in that they correspond to the following general formula (I): (i) wherein: Ri represents: (i) the radical -CH3 (ii) the radical -CH2-0-R5 (iii) the radical -COR6 having R5 and R6 the meanings given below, - Ar represents a radical chosen from the radicals of formulas (a) - (e) below: (a) (b) (c) (d) (e) having R the meaning given below, - R 2 and R 3 identical or different independently represent a radical selected from: (v) a hydrogen atom, (vi) a radical chosen from the radicals tert-butyl, 1-met-il-cyclohexyl or 1- adamantyl, (vii) a radical -ORs, Rs having the meaning given below, (viii) a polyether radical, it being understood that at least one of the radicals R2 or R3 represents a radical (ii), - R2 and R3 taken together can form a cycle with the adjacent aromatic cycle saturated with 5 or 6 links optionally substituted by methyl groups and / or optionally interrupted by an oxygen or sulfur atom, R 4 represents a hydrogen atom, a halogen atom, a lower alkyl radical, an ORg radical, a polyether radical, or a radical CORio, Rg and Rio having the meanings given below, Rs represents a hydrogen atom, a lower alkyl radical, or a radical CORn having Rn the meaning given below, - R6 represents a radical selected from: (iv) a hydrogen atom (v) a lower alkyl radical (vi) a radical 0Ri2 having Ri2 the meaning given below, N R " having R 'and R "the meanings given below, R represents a hydrogen atom, a halogen atom, a lower alkyl radical, a nitro radical, a 0R? 3 radical, a polyether radical or a radical of the following formula: having R? 3, R? , R15 the meanings given below, Rg represents a hydrogen atom, a lower alkyl radical, an optionally substituted aryl radical, an optionally substituted aralkyl radical, a monohydroxyalkyl or polyhydroxyalkyl radical, or a lower acyl radical, Rg represents a hydrogen atom , a lower alkyl radical, an optionally substituted aryl radical, an optionally substituted aralkyl radical, a monohydroxyalkyl or polyhydroxyalkyl radical, a lower acyl radical, a radical - (CH2) n-COOR? 6 or a radical - (CH2) nX, having n, R and X the meanings given below, Rio and Rn identical or different represent a lower alkyl radical, Ri2 represents a hydrogen atom, a lower alkyl radical, an optionally substituted aryl or aralkyl radical, a monohydroxyalkyl radical or a polyhydroxyalkyl radical , - R 'and R "identical or different represent a hydrogen atom, a lower alkyl radical r, an optionally substituted aryl radical, or an amino acid residue, or even R 'and R "taken together can form a heterocycle with the nitrogen atom, - R 3 represents a hydrogen atom, or a lower alkyl radical, R 4 and R 15 identical or different represent a hydrogen atom, or a lower alkyl radical, R 6 represents a hydrogen atom, or a lower alkyl radical, n represents an integer comprised between 1 and 12 included, X represents an atom of halogen.

2. Compounds according to claim 1, characterized in that they occur in the form of salts of an alkali metal or alkaline earth metal, zinc, an organic amine or a mineral or organic acid.

3. Compounds according to claim 1 or 2, characterized in that the lower alkyl radicals are chosen from the methyl, ethyl, isopropyl, butyl, or tert-iobutyl radicals.

4. Compounds according to any of the preceding claims, characterized in that the monohydroxyalkyl radicals correspond to radicals having 2 or 3 carbon atoms, mainly a 2-hydroxyethyl, 2-hydroxy-propyl or 3-hydroxypropyl radical, the radical being protected monohydroxyalkyl in the form of acetyl or tert-butyldimethylsilyl.

5. Compounds according to any of the preceding claims, characterized in that the polyhydroxyalkyl radicals are chosen from the 2, 3-dihydroxypropyl, 2, 3, 4-trihydroxy-butyl, 2, 3, 4, 5-tetrahydroxypentyl radicals or the rest of the pentaerythritol , the hydroxyl groups being protected in the form of acetyl or of tert-butyldimethylsilyls.

6. Compounds according to any of the preceding claims, characterized in that the aryl radicals correspond to a phenyl radical, optionally substituted by at least one halogen, a hydroxyl, or a nitro function.

7. Compounds according to any of the preceding claims, characterized in that the aralkyl radicals are protected between the benzyl or phenethyl radical optionally substituted by at least one halogen, a hydroxyl, a nitro function.

8. Compounds according to any of the preceding claims, characterized in that the lower acyl radicals are chosen from the acetyl radical or the propionyl radical.

9. Compounds according to any of the preceding claims, characterized in that the polyether radicals are chosen from the methoxymethylether, methoxyethoxymethylether or methylthiomethyl ether radicals.

10. Compounds according to any of the preceding claims, characterized in that the amino acid residues are chosen from the group consisting of the residues that are derived from lysine, glycine or aspartic acid.

11. Compounds according to any of the preceding claims, characterized in that the heterocyclic radicals are chosen from the group consisting of the piperidino, morpholino, pyrrolidino, or piperazino radicals, optionally substituted in the 4-position by an alkyl radical in C6-C6 or by a mono - or polyhydroxyalkyl.

12. Compounds according to claim 1, characterized in that they are taken, alone or in mixtures, in the group consisting of: 4- (3, 5, 5, 8, 8 -pentamethyl- 5, 6, 7, 8-tetrahydro-naphthalene -2- ilselanyl) -ethylbenzoate, 4- (3,5,5,8,8-pentamethyl-5,6,7,8-tet-rahydro-naphthalen-2-yl selanyl) -benzoic acid 6- ( 3, 5, 5, 8, 8-pentamethyl-5, 6, 7, 8-tetrahydro-naphthalen-2-yl slanyl) -ethyl nicotinate, 6- (3, 5, 5, 8, 8-pentamet- 5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanyl) -nicotinic acid, 6- (5, 5, 8, 8-tetramethyl-3-propoxy-5, 6, 7, 8-tetrahydro-naphthalene-2-) ilselanyl) -nicniconate, 6- (5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-yl-silyl) -nicotinic acid, 3- (5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-yl-silyl) -nicotinic acid -ter-butyl-phenyl-islanyl) -benzoic acid, 6- (4-tert-butyl-phenyl-selanyl) -nicotinic acid, 4- (4-tert-butyl-phenyl-islanyl) -benzoic acid, 4- (4, 4 -dimet) acid i 1-t iochroman-8-ylslanyl) -benzoic acid, 3- (4, 4-dimethyl-thiochroman-8-ylslanilic acid) ) -benzoic acid, 6- (4, 4-dimet i 1-thiochroman-8-ylslanyl) -nicotinic acid, 4- (5,5,8, 8-tet ramethyl-5,6,7,8-tetrahydro-) acid Naphthalene-2-yl selanyl) -benzoic acid, 3- (5,5,8,8-tet-ramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-slanyl) -benzoic acid, 6- (5, 5,8,8-tetramet-il-5,6,7,8-tetrahydro-naphthalen-2-yl selanyl) -nicotinic acid 4- [5-adamantan-l-yl-4- (2-methoxy-ethoxymethoxy) -2- met-phenyl-islanyl] -benzoic acid, 3- [5-adamantan-l-1,4- (2-methoxy-ethoxymethoxy) -2-methyl-yl-phenyl-islanyl] -benzoic acid, 6- (4-methoxy-ethoxy-methoxy) -5, 5,8, 8-tetramethi-1-5, 6,7,8-tetrahydro-naphthalen-2-yl-slanyl) -nicotinic acid, 3- (4-methoxyethoxymethoxy-5, 5, 8, 8-tet ramethyl- 5, 6, 7, 8- tetrahydro-naphthalen-2-ylslanyl) -benzoic acid, 4- (4-methoxyethoxymethoxy-5, 5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalene- 2-ylslanyl) -3-methoxy-benzoic acid, 3- (4-methoxyethoxymethoxy-5, 5,8,8-tetramethi-l, 6,7,8-tetrahydro-naphthalen-2-yl-silyl) -4-methoxy -benzoic acid, 6- ( 4-methoxymethoxy-5, 5,8,8-tetramet-il-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -nicotinic acid, 6- (3-methoxyethoxymethoxy-5, 5,8, 8-tetramethyl-5,7,7,8-tetrahydro-naphthalen-2-yl-phenyl) -nicotinic acid, 2- (3-methoxyethoxymethoxy-5, 5, 8, 8-tetramet-il-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -nicotinic acid, 4 - (3-methoxyethoxymethoxy-5, 5,8, 8-tet ramet il-5, 6, 7,8-tetrahydro-naphthalen-2-ylsallanyl) -benzoic acid, 3- (3-methoxyethoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalene-2-ylselanyl) -benzoic acid, 6- (3,5-di-tert-but-i-1-2-methoxymethoxy-phenyl-selanyl) - - nicotinic acid, 2- (3,5-di-tert-butyl-2-methoxymethoxy-phenyl-seryl) acid ) - nicotinic, 4- (3,5-di-tert-butyl-2-methoxymethoxy-phenyl-islanyl) -benzoic acid, 3- (3,5-di-tert-but-1-2-methoxymethoxy-phenyl-selanyl) acid ) - benzoic acid, 6- [4-adammantan-l-yl-3-benzyloxy-phenyl-islanyl] -nicotinic acid, 6- (3,5-di-tert-butyl-2-benzyloxy-phenyl-islanyl) -nicotinic acid, -methoxy-4- (4-benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-ylslanyl) -benzo ico, 4- (4-benzyloxy-5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramet-ilnaphthalen-2-ylsanyl) -benzoic acid, 6- (4-benzyloxy-5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethylnaphthalen-2-ylslanyl) -nicotinic acid, 3-methoxy-4- (3-benzyloxy-5, 6, 7, 8-tet rahydro-5, 5, 8, 8- tetramethylnaphthalen-2-ylslanyl) -benzoic acid, 6- (3-benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl-slanyl) - nicotinic, 4- (3-hexyloxy-5,6,7,8-tetrahydro-5, 5, 8, 8-tetramethylnaphthalen-2-ylseryl) -3-methoxy-benzoic acid, 6- (3-hexyloxy) -5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramet ilnaftalen-2 -i 1 sel anil) -nicotinic acid, 4- (5-adamantan-1-yl-4-benzyloxy -2 - met-phenyl-selanyl) -benzoic acid, 6- [3- (5-hydroxy-pentyloxy) -5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-silyl] - nicotinic, 4- (5, 5, 8, 8-tetramet and 1-5, 6,7,8-tetrahydro-naphthalen-2-yl slanyl) -ethylbenzoate, 4- (3-methoxyethoxymethoxy-5, 5, 8, 8 -tetramethyl-5, 6,7,8-tetra ethyl hydro-naphthalen-2-ylslanyl) -benzoate, 4- (3-hydroxy-5, 5, 8, 8-tet ramet il-5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanyl) -benzoate ethyl, 4- (3-hydroxy-5, 5, 8", 8-tet ramethyl-5, 6, 7, 8-tet rahydro-naphthalen-2-yl selanyl) -benzoic acid, 6- (3-methoxyethoxymethoxy) -5, 5, 8, 8-tet ramet il-5, 6,7,8-tetrahydro-naphthalen-2-ylslanyl) -nicotinate ethyl, 6- (3-hydroxy-5, 5, 8, 8-tetramet il-5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanyl) -nicnicinate, ethyl 6- (3-hydroxy-5,5,8, 8-tet ramet il-5, 6,7,8 -tetrahydro-naphthalen-2-yl selanyl) -nicotinic acid, 6- [3- (3-ethoxycarbonyl-propoxy) -5, 5, 8, 8-tetramet-i-5, 6, 7, 8 -tetrahydro-naphthalene- 2-ylsenyl] - ethyl nicotinate, 6- [3- (3-carboxy-propoxy) -5,5,8, 8-tetramethi, 1-5,6,7,8-tetrahydro-naphthalen-2-yl-silyl] -nicotinic acid, 4- [3- (3-ethoxycarbonyl-propoxy) -5,5,8,8-tet-ramethyl-5,6,7,8-tetrahydro-naphthalen-2-ylseryl] -benzoic acid ethyl ester; - [3- (3-carboxy-propoxy) -5, 5, 8, 8-tet ramet i l-5, 6,7,8-tetrahydronaphthalen-2-ylslanyl] -benzoic acid, 4- [3- (7-methoxycarbonyl-heptyloxy) -5, 5, 8, 8-tet ramet i 1- 5, 6, 7 Ethyl 8-tetrahydro-naphthalen-2-ylslanyl] -benzoate, 4- [3- (7-carboxy-heptyloxy) -5,5,8,8-tetramet-i-5, 6, 7, 8- tetrahydro-naphthalen-2-ylsallanyl] -benzoic acid, 6- [3- (7-methoxycarbonyl-heptyloxy) -5, 5, 8, 8-tetramet-il-5, 6, 7, 8-tetrahydro-naphthalene-2-ylselanil ] - ethyl nicotinate, 6- [3- (7-carboxy-heptyloxy) -5,5,8,8-tetramethyl-5-6,8-tetrahydro-naphthalen-2-yl-slanyl] -nicotinic acid, 6- [3- (2-Acetoxy-ethoxy) -5,5,8,8-tetramethyl-5,6,7,8-tet -hydro-naphthalen-2-yl-silyl] -nicnicinate, 6- [3] - (2-hydroxy-ethoxy) -5, 5, 8, 8-tetramethyl-5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanyl) -nicotinic acid, 4- [3- (2-acetoxy-ethoxy) -5, 5, 8, 8 -ethyl ramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-silyl] -benzoic acid ethyl ester 4- [3- (2-hydroxy-ethoxy) -5,5 , 8,8-tetramethyl-5, 6, 7, 8-tetrahydro-naphthalen-2-yl-slanyl] -b enzoic, 6- (3-adamantan-l-yl-4-methoxy-phenyl-islanyl) -nicotinic acid, [6- (3, 5, 5, 8, 8-pentamethyl-5, 6, 7, 8-tetrahydro-naphthalen-2-ylslanyl) -pyridin-3-yl] methanol, N-ethyl-6- (3 , 5, 5, 8, 8-pentamethyl-5, 6, 7, 8-tetrahydro-naphthalen-2-yl selanyl) -nicotinamide, Morpholin-4-yl- [6- (3,5,5,8, 8 -pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -pyridin-3-yl] -methanone, N- (4-hydroxy-phenyl) -6- (3, 5, 5, 8, 8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-ylslanyl) -nicotinamide, 6- (3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalene- 2- ilselanil) -pyridine-3-carbaldehyde.

13. Compounds according to claim 1, characterized in that one or at least one, and preferably all, of the following characteristics are present: Ri represents a radical CORß-Ar represents a radical of formula (a) or (b) R 2 or R 3 represent an adamantyl radical or R 2 and R 3 taken together form with the adjacent aromatic ring a saturated 5- or 6-membered chain optionally substituted by methyl groups and / or optionally interrupted by an oxygen or sulfur atom.

14. Compounds according to any of the preceding claims for use as a medicament. , -ife,.

15. Compounds according to claim 14, for use as a medicament for the treatment of dermatological affections linked to a keratinization disorder which is based on differentiation and on proliferation mainly for treating vulgar, comedonic, polymorphic, rosaceous acnes, acnés noduloguís ticos, conglobata, senile acnes, secondary acnes, such as solar acne, medicated or professional; to treat other types of keratinization problems, mainly ichthyosis, ictios iformes, Darrier's disease, palmoplantar keratoderma, leukoplakias and leukoplasiform states, cutaneous lichen or mucous (buccal); to treat other dermatological conditions linked to a problem of keratinization with an inflammatory and / or immuno-allergic component and mainly all forms of psoriasis whether cutaneous, mucosal or ungular, and even psoriatic rheumatism, or even cutaneous atopy, such such as eczema or respiratory atopy or even gingival hypertrophy; the compounds can also be used in certain inflammatory conditions that do not present the problem of keratinization; to treat all dermal or epidermal proliferations, whether benign or malignant, whether of viral origin or of non-viral origin, such as common warts, flat warts and verrucous epidermodysplasia, oral or florid papilloma tosis and proliferations that can to be induced by ultra-violets mainly in the case of basal and spinocellular epithelioma; to treat other dermatological disorders such as globular dermatoses and collagen diseases; to treat certain ophthalmological problems, mainly corneopathies; to prepare or fight against the aging of the skin, either photo-inductive or chronological, or to reduce the pigmentations and actinic keratosis, or all the pathologies associated with chronological or actinic aging; to prevent or cure the stigmata of epidermal and / or dermal atrophy induced by local or systemic corticosteroids, or any other form of cutaneous atrophy; to prevent or treat the problems of healing, to prevent or repair stretch marks or even to promote healing; to fight against problems of sebaceous function such as hyper seborrhea of acne or simple seborrhea; for the treatment or prevention of cancerous or precancerous conditions, more particularly, promyelocytic leukemias; for the treatment of inflammatory conditions such as arthritis, for the treatment of any viral condition at cutaneous or general level; for the prevention or treatment of alopecia; for the treatment of dermatological or general conditions of immunological component; for the treatment of cardiovascular system conditions such as arteriosclerosis, hypertension, non-insulin dependent diabetes as well as obesity; for the treatment of skin disorders due to exposure to U.V.

16. Pharmaceutical composition, characterized in that it comprises, in a pharmaceutically acceptable carrier, at least one of the compounds as defined in any of claims 1 to 13.

17. Composition according to claim 16, characterized in that the concentration in compound (s) according to any of claims 1 to 13 is comprised between 0.001% and 5% by weight with respect to the composition as a whole.

18. Cosmetic composition, characterized in that it comprises, in a cosmetically acceptable support, at least one of the compounds as defined in any of claims 1 to 13.

19. Composition according to claim 18, characterized in that the concentration in compound (s) according to any of claims 1 to 13 is comprised between 0.001% and 3% by weight with respect to the composition as a whole.

20. Use of a cosmetic composition as defined in any of claims 18 or 19 for body or hair hygiene. COMPOUNDS DIARILSELENUROS AND ITS USE IN HUMAN OR VETERINARY MEDICINE AS WELL AS IN COSMETOLOGY SUMMARY OF THE INVENTION The invention relates to new compounds dia1 and selenides which have as general formula (I): (I) as well as to the use of the latter in pharmaceutical compositions intended for use in human or veterinary medicine (mainly dermatological, rheumatic, respiratory, cardiovascular and ophthalmological conditions), or even in cosmetic compositions.