The invention relates, as novel and useful industrial products, to a novel class of compounds which are modulators of the Peroxisome Proliferator- Activated Receptor (PPAR) type receptors. It also relates to their method of preparation and to their use in pharmaceutical compositions for use in human or veterinary medicine, or alternatively in cosmetic compositions.

The activity of the PPAR-type receptors has been the subject of numerous studies. There may be mentioned, as a guide, the publication entitled "Differential Expression of Peroxisome Proliferator-Activated Receptor Subtypes During the Differentiation of Human Keratinocytes", Michel Rivier et al., J. Invest.

Dermatol 111, 1998, p. 1116-1121, in which a large number of bibliographic references relating to PPAR-type receptors is listed. There may also be mentioned, as a guide, the dossier entitled"The PPARs : From orphan receptors to Drug Discovery", Timothy M. Willson, Peter J. Brown, Daniel D. Sternbach, and Brad R. Henke, J. Med. Chem., 2000, Vol. 43, p. 527-550.

The PPAR receptors activate transcription by binding to elements of DNA sequences, called peroxisome proliferator response elements (PPRE), in the form of a heterodimer with the retinoid X receptors (called RXRs).

Three human PPAR subtypes have been identified and described : PPARa, PPARy and PPAR (or NUC1).

PPARa is mainly expressed in the liver while PPAR8 is ubiquitous.

It is described in Patent Application W098/32444 that PPARa selective compounds play a role in the barrier function and the differentiation of the stratum corneum.

PPARy is the most widely studied of the three subtypes. All the

references suggest a critical role of the PPARy receptors in the regulation of differentiation of adipocytes, where it is highly expressed. It also plays a key role in systemic lipid homeostasis.

It has in particular been described in Patent Application WO 96/33724 that PPARy-selective compounds, such as prostaglandin-J2 or-D2, are potential active agents for treating obesity and diabetes.

One of the aims of the present invention is to provide a novel class of PPAR-modulating compounds.

Thus, the present invention relates to compounds corresponding to the following general formula (I) : (I) -Ar1 represents an optionally substituted radical of formula :

- Z represents the substituent : it being understood that Z is at the para position with respect to X on the ring An ; R1 and Y having the meanings given below, - Ar2 represents an optionally substituted radical of formula :

- R1 represents a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, a heteroaryl radical, an aralkyl radical, a polyether radical, a monohydroxyalkyl radical or a polyhydroxyalkyl radical ; - R2 represents a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, a heteroaryl radical, an aralkyl radical, a polyether radical, a monohydroxyalkyl radical or a polyhydroxyalkyl radical ; - R3 represents a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, a heteroaryl radical, an aralkyl radical, a polyether radical, a monohydroxyalkyl radical, a polyhydroxyalkyl radical, a radical COR5 or CSR5 ; R5 having the meanings given below, - Y represents an oxygen or sulphur atom, or the radical N-R4 ; R4 having the meanings given below, - R4 represents a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, a heteroaryl radical, a polyether radical, an aralkyl radical or forms, with R1 and the nitrogen atom of Y, a heterocycle or a heteroaryl ; - R5 represents an aryl radical, a heteroaryl radical, an aralkyl radical, an alkyl radical having from 1 to 12 carbon atoms, a polyether radical, an alkoxy radical, a monohydroxyalkyl radical, a polyhydroxyalkyl radical, a radical R6-N-R7 or a radical O-R8 ; R6, R7 and R8 having the meanings given below,

- R6 and R7 may be identical or different and represent a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, a monohydroxyalkyl radical, a polyhydroxyalkyl radical, a polyether radical, an aryl radical, a heteroaryl radical, an aralkyl radical or alternatively, taken together, form a heterocycle ; - R8 represents a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, a monohydroxyalkyl radical, a polyhydroxyalkyl radical, a polyether radical, an aryl radical, a heteroaryl radical or an aralkyl radical ; - X represents an S atom, a radical S=O, a radical O=S=O, an Se atom, an O atom, a radical N-R9, a radical C=O, a radical HO-C-R11 or a radical R10-C- R11 ; R9, R10 and R11 having the meanings given below, - R9 represents a hydrogen atom, a radical-COR12, an alkyl radical having from 1 to 12 carbon atoms, a polyether radical, an aryl radical or an aralkyl radical ; R12 having the meanings given below, - R10 and R11, which are identical or different, represent a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, a heteroaryl radical, an aralkyl radical, a monohydroxyalkyl radical, a polyhydroxyalkyl radical, a polyether radical, an alkoxy radical, or R10 and R11, taken together, can form a ring optionally interrupted by heteroatoms and preferably the rings are dithianyl, dioxanyl, dithiolanyl, dioxolanyl or cyclopropanyl radicals ; - A represents an S, O or Se atom or a radical N-R13 ; R13 having the meanings given below, - R12 represents an alkyl radical having from 1 to 12 carbon atoms ; - R13 represents a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, a heteroaryl radical, a polyether radical or an aralkyl

radical ; and when R2 represents a hydrogen atom, R5 is different from an aryl radical and R3 is different from a hydrogen atom, and the optical and geometric isomers of the said compounds of formula (I) and their salts.

In particular, when the compounds according to the invention are provided in the form of salts, they are salts of an alkali or alkaline-earth metal, zinc salts, or salts of an organic amine.

According to the present invention, the expression hydroxyl radical is understood to mean the-OH radical.

According to the present invention, the expression alkyl radical having from 1 to 12 carbon atoms is understood to mean a hydrogenated or fluorinated, linear or cyclic, optionally branched, radical containing 1 to 12 carbon atoms which may be interrupted by one or more heteroatoms, and preferably the alkyl radicals having from 1 to 12 carbon atoms are methyl, ethyl, isopropyl, butyl, tert-butyl, hexyl, octyl, decyl or cyclohexyl radicals.

The expression monohydroxyalkyl radical is understood to mean a radical having 1 to 6 carbon atoms, and preferably having from 2 to 3 carbon atoms, in particular a 2-hydroxyethyl, 2-hydroxypropyl or 3-hydroxypropyl radical.

The expression polyhydroxyalkyl radical is understood to mean a radical containing from 3 to 6 carbon atoms and from 2 to 5 hydroxyl groups, such as 2, 3-dihydroxypropyl, 2, 3, 4-trihydroxybutyl or 2, 3, 4, 5-tetrahydroxypentyl radicals, or the pentaerythritol residue.

The expression polyether radical is understood to mean a polyether radical having from 1 to 6 carbon atoms interrupted by at least one oxygen atom such as methoxymethoxy, ethoxymethoxy or methoxyethoxymethoxy radicals.

The expression alkoxy radical having from 1 to 7 carbon atoms is

understood to mean a radical containing from one to seven carbon atoms such as the methoxy, ethoxy, isopropyloxy, tert-butoxy, hexyloxy, benzyloxy or phenoxy radicals, which may be optionally substituted with an alkyl radical having from 1 to 12 carbon atoms.

The expression aryl radical is understood to mean a phenyl, biphenyl, cinnamyl or naphthyl radical which may be mono-or disubstituted with a halogen atom, a radical CF3, an alkyl radical having from 1 to 12 carbon atoms, an alkoxy radical having from 1 to 7 carbon atoms, a nitro functional group, a polyether radical, an aryl radical, a benzoyl radical, an alkyl ester group, a carboxylic acid, a hydroxyl radical optionally protected by an acetyl or benzoyl group or an amino functional group optionally protected by an acetyl or benzoyl group or optionally substituted with at least one alkyl having from 1 to 12 carbon atoms.

The expression aralkyl radical is understood to mean a benzyl, phenethyl or naphthalen-2-ylmethyl radical which may be mono-or disubstituted with a halogen atom, a radical CF3, an alkyl radical having from 1 to 12 carbon atoms, an alkoxy radical having from 1 to 7 carbon atoms, a nitro functional group, a polyether radical, an aryl radical, a benzoyl radical, an alkyl ester group, a carboxylic acid, a hydroxyl radical optionally protected by an acetyl or benzoyl group or an amino functional group optionally protected by an acetyl or benzoyl group or optionally substituted with at least one alkyl having from 1 to 12 carbon atoms.

The expression heteroaryl radical is preferably understood to mean an aryl radical interrupted by one or more heteroatoms, such as the pyridyl, furyl, thienyl, isoxazolyl, oxadiazolyl, oxazolyl, isothiazolyl, quinazolinyl, benzothiadiazolyl, benzimidazole, indolyl or benzofuran radical, optionally substituted with at least one halogen, an alkyl having from 1 to 12 carbon atoms,

an alkoxy having from 1 to 7 carbon atoms, an aryl radical, a nitro functional group, a polyether radical, a heteroaryl radical, a benzoyl radical, an alkyl ester group, a carboxylic acid, a hydroxyl optionally protected by an acetyl or benzoyl group or an amino functional group optionally protected by an acetyl or benzoyl group or optionally substituted with at least one alkyl having from 1 to 12 carbon atoms.

The expression heterocycle is preferably understood to mean the morpholino, piperidino, piperazino, 2-oxopiperidin-1-yl and 2-oxopyrrolidin-1-yl radicals optionally substituted with at least one alkyl group having from 1 to 12 carbon atoms, an alkoxy having from 1 to 7 carbon atoms, an aryl radical, a nitro functional group, a polyether radical, a heteroaryl radical, a benzoyl radical, an alkyl ester group, a carboxylic acid, a hydroxyl optionally protected by an acetyl or benzoyl group or an amino functional group optionally protected by an acetyl or benzoyl group or optionally substituted with at least one alkyl having from 1 to 12 carbon atoms.

Among the compounds of formula (I) above falling within the scope of the present invention, the following compounds may be mentioned in particular (alone or as a mixture) : 1 b. Ethyl [4- (3-aminophenylsulphanyl) phenyl] acetate 2. Ethyl [4- (4-aminophenylsulphanyl) phenyl] acetate 3a. Ethyl {4- [3- (3-phenylpropylamino) phenylsulphanyl] phenyl} acetate 3b. {4-[3-(3-Phenylpropylamino)phenylsulphanyl]phenyl}acetic acid 4a. Ethyl (4- {3- [bis (3-phenylpropyl) amino] phenylsulphanyl}phenyl) acetate 4b. (4- {3- [Bis (3-phenylpropyl) amino] phenylsuphanyl}phenyl)acetic acid 5a. Ethyl [4- (3-Phenethylamino) phenylsulphanylphenyl] acetate 5b. [4- (3-Phenethylamino) phenylsulphanylphenyl] acetic acid 6a. Ethyl [4- (3-Diphenethylaminophenylsulphanyl) phenyl] acetate

6b. [4- (3-Diphenethylaminophenylsulphanyl) phenyl] acetic acid 7a. Ethyl [4- (3-heptylaminophenylsulphanyl) phenyl] acetate 7b. [4- (3-Heptylaminophenylsulphanyl) phenyl] acetic acid 8a. Ethyl [4- (3-diheptylaminophenylsulphanyl) phenyl] acetate 8b. [4- (3-Diheptylaminophenylsulphanyl) phenyl] acetic acid 9a. Ethyl [4- (3-butylaminophenylsulphanyl) phenyl] acetate 9b. [4- (3-Butylaminophenylsulphanyl) phenyl] acetic acid 10a. Ethyl [4- (3-dibutylaminophenylsulphanyl) phenyl] acetate 10b. [4- (3-Dibutylaminophenylsulphanyl) phenyl] acetic acid 11a. Ethyl {4-[4-(3-phenylpropylamino)phenylsulphanyl]phenyl} acetate 11 b. {4- [4- (3-Phenylpropylamino) phenyisulphanyl] phenyl} acetic acid 12a. Ethyl (4- {4- [bis (3-phenylpropyl) amino] phenylsulphanyl} phenyl) acetate 12b. (4-{4-[Bis (3-phenylpropyl) amino] phenylsulphanyl} phenyl) acetic acid 13a. Ethyl [4- (4-phenethylaminophenylsulphanyl) phenyl] acetate 13b. [4-(4-Phenethylaminophenylsulphanyl)phenyl] acetic acid 14a. Ethyl [4- (4-diphenethylaminophenylsulphanyl) phenyl] acetate 14b. [4-(4-Diphenethylaminophenylsulphanyl)phenyl] acetic acid 15a. Ethyl [4- (4-heptylaminophenylsulphanyl) phenyl] acetate 15b. [4-(4-Heptylaminophenylsulphanyl)phenyl] acetic acid 16a. Ethyl [4- (4-diheptylaminophenylsulphanyl) phenyl] acetate 16b. [4-(4-Diheptylaminophenylsulphanyl)phenyl] acetic acid 17a. Ethyl [4- (4-dibutylaminophenylsulphanyl) phenyl] acetate 17b. [4- (4-Dibutylaminophenylsulphanyl) phenyl] acetic acid 18a. Ethyl (4- {3- [3-benzyl-1- (3-phenylpropyl) ureido] phenylsulphanyl}- phenyl) acetate 18b. (4- {3- [3-Benzyl-1- (3-phenylpropyl) ureido] phenylsulphanyl} phenyl) acetic acid

19a. Ethyl (4- {3- [3-phenyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetate 19b. (4- {3- [3-Phenyl-1- (3-phenylpropyl) ureido] phenylsulphanyl} phenyl) acetic acid 20a. Ethyl (4- {3- [3- (2, 3-dichlorophenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetate 20b. (4- {3- [3- (2, 3-Dichlorophenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetic acid 21a. Ethyl (4- {3- [3-heptyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetate 21b. (4- {3- [3-Heptyl-1- (3-phenylpropyl) ureido] phenylsulphanyl}phenyl) acetic acid 22a. Ethyl (4- {3- [3-phenethyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetate 22b. (4- {3- [3-Phenethyl-1- (3-phenylpropyl) ureido] phenylsulphanyl} phenyl) acetic acid 23a. Ethyl (4- {3- [1- (3-phenylpropyl)-3- (4-trifluoro- methylphenyl) ureido] phenylsulphanyl} phenyl) acetate 23b. (4- {3- [1- (3-Phenylpropyl)-3- (4-trifluoro- methylphenyl)ureido]phenylsulphanyl}phenyl)acetic acid 24a. Ethyl (4- {3- [3- (4-methoxyphenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetate 24b. (4- {3- [3- (4-Methoxyphenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetic acid 25a. Ethyl (4- {3- [3-adamantan-1-yl-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetate 25b. (4-{3-[3-Adamantan-1-yl-1-(3-phenylpropyl) ureido]-

phenylsulphanyl} phenyl) acetic acid 26a. Ethyl (4- {3- [3- (2-phenoxyphenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetate 26b. (4- {3- [3- (2-Phenoxyphenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetic acid 27a. Ethyl (4- {3- [3-allyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetate 27b. (4- {3- [3-Allyl-1- (3-phenylpropyl) ureido] phenylsulphanyl} phenyl) acetic acid 28a. Ethyl (4- {3- [3-cyclohexyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetate 28b. (4- {3- [3-Cyclohexyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetic acid 29a. Ethyl (4- {3- [3- (2-nitrophenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetate 29b. (4- {3- [3- (2-Nitrophenyl)-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetic acid 30a. Ethyl (4- {3- [3-hexyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetate 30b. (4- {3- [3-Hexyl-1- (3-phenylpropyl) ureido] phenylsulphanyl}phenyl) acetic acid 31a. Ethyl (4- {3- [3-naphthalen-2-yl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetate 31 b. (4- {3- [3-Naphthalen-2-yl-1- (3-phenylpropyl) ureido]- phenylsulphanyl}phenyl)acetic acid 32a. Ethyl (4- {3- [3- (2-ethoxyphenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetate 32b. (4- {3- [3- (2-Ethoxyphenyl)-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetic acid

33a. Ethyl (4- {3- [3- (4-butoxyphenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetate 33b. (4- {3- [3- (4-Butoxyphenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetic acid 34a. Ethyl (4- {3- [3-pentyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetate 34b. (4- {3- [3-Pentyl-1- (3-phenylpropyl) ureido] phenylsulphanyl}phenyl) acetic acid 35a. Ethyl (4- {3- [3-butyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetate 35b. (4- {3- [3-Butyl-1- (3-phenylpropyl) ureido] phenylsulphanyl}phenyl) acetic acid 36a. Ethyl (4- {3- [3- (4-dimethylaminophenyl)-1- (3- phenylpropyl) ureido] phenylsulphanyl} phenyl) acetate 36b. (4- {3- [3- (4-Dimethylaminophenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetic acid 37a. Ethyl {4- [3- (3-benzyl-1-phenethylureido) phenylsulphanyl] phenyl} acetate 37b. {4-[3-(3-Benzyl-1-phenethylureido)phenylsulphanyl]phenyl} acetic acid 38a. Ethyl {4-[3-(1-phenethyl-3-phenylureido)phenylsulphanyl]phenyl} acetate 38b. {4-[3-(1-Phenethyl-3-phenylureido)phenylsulphanyl]phenyl}ace tic acid 39a. Ethyl (4- {3- [3- (2, 3-dichlorophenyl)-1-phenethylureido]- phenylsulphanyl} phenyl) acetate 39b. (4-{3-[3-(2,3-Dichlorophenyl)-1-phenethylureido]- phenylsulphanyl} phenyl) acetic acid 40a. Ethyl {4-[3-(3-heptyl-1-phenethylureido)phenylsulphanyl]phenyl} acetate 40b. {4-[3-(3-Heptyl-1-phenethylureido)phenylsulphanyl]phenyl} acetic acid 41a. Ethyl {4-[3-(1,3-diphenethylureido)phenylsulphanyl]phenyl} acetate 41b. {4-[3-(1,3-Diphenethylureido)phenylsulphanyl]phenyl} acetic acid

42a. Ethyl (4- {3- [1-phenethyl-3- (4-trifluoromethyl- phenyl) ureido] phenylsulphanyl} phenyl) acetate 42b. (4-{3-[1-Phenethyl-3-(4-trifluoromethylphenyl)- ureido] phenylsulphanyl} phenyl) acetic acid 43a. Ethyl (4- {3- [3- (4-methoxyphenyl)-1-phenethyl- ureido] phenylsulphanyl} phenyl) acetate 43b. (4- {3- [3- (4-Methoxyphenyl)-1-phenethylureido]- phenylsulphanyl} phenyl) acetic acid 44a. Ethyl {4-[3-(3-adamantan-1-yl-1-phenethylureido)- phenylsulphanyl] phenyl} acetate 44b. {4-[3-(3-Adamantan-1-yl-1-phenethylureido)phenylsulphanyl]ph enyl} acetic acid 45a. Ethyl (4- {3- [1-phenethyl-3- (2-phenoxyphenyl)- ureido] phenylsulphanyl} phenyl) acetate 45b. (4-{3-[1-Phenethyl-3-(2-phenoxyphenyl) ureido]- phenylsulphanyl} phenyl) acetic acid 46a. Ethyl {4- [3- (3-allyl-1-phenethylureido) phenylsulphanyl] phenyl} acetate 46b. {4- [3- (3-Allyl-1-phenethylureido) phenylsulphanyl] phenyl} acetic acid 47a. Ethyl {4-[3-(3-cyclohexyl-1-phenethylureido)- phenylsulphanyl] phenyl} acetate 47b. {4-[3-(3-Cyclohexyl-1-phenethylureido)phenylsulphanyl]phenyl } acetic acid 48a. Ethyl (4- {3- [3- (2-nitrophenyl)-1-phenethylureido]- phenylsulphanyl} phenyl) acetate 48b. (4- {3- [3- (2-Nitrophenyl)-1-phenethylureido] phenylsulphanyl} phenyl) acetic acid 49a. Ethyl {4-[3-(3-hexyl-1-phenethylureido)phenylsulphanyl]phenyl} acetate 49b. {4-[3-(3-Hexyl-1-phenethylureido)phenylsulphanyl]phenyl} acetic acid

50a. Ethyl {4- [3- (3-naphthalen-2-yl-l-phenethylureido)- phenylsulphanyl] phenyl} acetate 50b. {4-[3-(3-Naphthalen-2-yl-1-phenethylureido)pheneylsulphanyl] phenyl} acetic acid 51a. Ethyl (4- {3- [3- (2-ethoxyphenyl)-1-phenethyl- ureido] phenylsulphanyl} phenyl) acetate 51 b. (4- {3- [3- (2-Ethoxyphenyl)-1-phenethylureido]- phenylsulphanyl} phenyl) acetic acid 52a. Ethyl (4- {3- [3- (4-butoxyphenyl)-1-phenethyl- ureido] phenylsulphanyl} phenyl) acetate 52b. (4-{3-[3-(4-Butoxyphenyl)-1-phenethylureido]- phenylsulphanyl} phenyl) acetic acid 53a. Ethyl {4-[3-(3-pentyl-1-phenethylureido)phenylsulphanyl]phenyl} acetate 53b. {4-[3-(3-Pentyl-1-phenethylureido)phenylsulphanyl]phenyl}ace tic acid 54a. Ethyl {4- [3- (3-butyl-1-phenethylureido) phenylsulphanyl] phenyl} acetate 54b. {4-[3-(3-Butyl-1-phenethylureido)phenylsulphanyl]phenyl} acetic acid 55a. Ethyl (4- {3- [3- (4-dimethylaminophenyl)-1- phenethylureido] phenylsulphanyl} phenyl) acetate 55b. (4- {3- [3- (4-Dimethylaminophenyl)-1-phenethyl- ureido] phenylsulphanyl} phenyl) acetic acid 56a. Ethyl {4-[3-(3-benzyl-1-heptylureido)phenylsulphanyl]phenyl} acetate 56b. {4-[3-(3-Benzyl-1-heptylureido)phenylsulphanyl]phenyl} acetic acid 57a. Ethyl {4- [3- (1-heptyl-3-phenylureido) phenylsulphanyl] phenyl} acetate 57b. {4-[3-(1-Heptyl-3-phenylureido)phenylsulphanyl]phenyl}acetic acid 58a. Ethyl {4-[3-(1,3-diheptylureido)phenylsulphanyl]phenyl} acetate 58b. {4-[3-(1,3-Diheptylureido)phenylsulphanyl]phenyl} acetic acid 59a. Ethyl {4-[3-(1-heptyl-3-phenethylureido)phenylsulphanyl]phenyl}ace tate

59b. {4-[3-(1-Heptyl-3-phenethylureido)phenylsulphanyl]phenyl}ace tic acid 60a. Ethyl (4-{3-[1-heptyl-3-(4-trifluoromethylphenyl)- ureido] phenylsulphanyl} phenyl) acetate 60b. (4- {3- [1-Heptyl-3- (4-trifluoromethylphenyl)- ureido] phenylsulphanyl} phenyl) acetic acid 61a. Ethyl (4- {3- [1-heptyl-3- (4-methoxyphenyl) ureido]- phenylsulphanyl} phenyl) acetate 61 b. (4- {3- [1-Heptyl-3- (4-methoxyphenyl) ureido] phenylsulphanyl} phenyl) acetic acid 62a. Ethyl {4- [3- (3-adamantan-1-yl-l-heptylureido)- phenylsulphanyl] phenyl} acetate 62b. {4-[3-(3-Adamantan-1-yl-1-heptylureido)phenylsulphanyl]pheny l}acetic acid 63a. Ethyl (4- {3- [1-heptyl-3- (2-phenoxyphenyl) ureido]- phenylsulphanyl} phenyl) acetate 63b. (4- {3- [1-Heptyl-3- (2-phenoxyphenyl) ureido] phenylsulphanyl}phenyl) acetic acid 64a. Ethyl {4-[3-(3-allyl-1-heptylureido)phenylsulphanyl]phenyl} acetate 64b. {4-[3-(3-Allyl-1-heptylureido)phenylsulphanyl]phenyl} acetic acid 65a. Ethyl {4-[3-(3-cyclohexyl-1-heptylureido)phenylsulphanyl]phenyl} acetate 65b. {4-[3-(3-Cyclohexyl-1-heptylureido)phenylsulphanyl]phenyl} acetic acid 66a. Ethyl (4- {3- [1-heptyl-3- (2-nitrophenyl) ureido]- phenylsulphanyl} phenyl) acetate 66b. (4-{3-[1-Heptyl-3-(2-nitrophenyl) ureido] phenylsulphanyl} phenyl) acetic acid 67a. Ethyl {4- [3- (l-heptyl-3-hexylureido) phenylsulphanyl] phenyl} acetate 67b. {4-[3-(1-Heptyl-3-hexylureido)phenylsulphanyl]phenyl}acetic acid 68a. Ethyl {4- [3- (l-heptyl-3-naphthalen-2-ylureido)- phenylsulphanyl] phenyl} acetate

68b. {4-[3-(1-Heptyl-3-naphthalen-2-ylureido)phenylsulphanyl]phen yl}acetic acid 69a. Ethyl (4- {3- [3- (2-ethoxyphenyl)-1-heptylureido]- phenylsulphanyl} phenyl) acetate 69b. (4- {3- [3- (2-Ethoxyphenyl)-l-heptylureido] phenylsulphanyl} phenyl) acetic acid 70a. Ethyl (4- {3- [3- (4-butoxyphenyl)-1-heptylureido]- phenylsulphanyl} phenyl) acetate 70b. (4- {3- [3- (4-Butoxyphenyl)-1-heptylureido] phenylsulphanyl} phenyl) acetic acid 71a. Ethyl {4-[3-(1-heptyl-3-pentylureido)phenylsulphanyl]phenyl} acetate 71b. {4-[3-(1-Heptyl-3-pentylureido)phenylsulphanyl]phenyl} acetic acid 72a. Ethyl {4- [3- (3-butyl-1-heptylureido) phenylsulphanyl] phenyl} acetate 72b. {4-[3-(3-Butyl-1-heptylureido)phenylsulphanyl]phenyl} acetic acid 73a. Ethyl (4- {3- [3- (4-dimethylaminophenyl)-1-heptyl- ureido] phenylsulphanyl} phenyl) acetate 73b. (4- {3- [3- (4-Dimethylaminophenyl)-1-heptylureido]- phenylsulphanyl} phenyl) acetic acid 74a. Ethyl {4-[3-(3-benzyl-1-butylureido)phenylsulphanyl]phenyl} acetate 74b. {4-[3-(3-Benzyl-1-butylureido)phenylsulphanyl]phenyl} acetic acid 75a. Ethyl {4-[3-(1-butyl-3-phenylureido)phenylsulphanyl]phenyl} acetate 75b. {4-[3-(1-Butyl-3-phenylureido)phenylsulphanyl]phenyl}acetic acid 76a. Ethyl (4- {3- [1-butyl-3- (2, 3-dichlorophenyl)- ureido] phenylsulphanyl} phenyl) acetate 76b. (4-{3-[1-Butyl-3-(2,3-dichlorophenyl) ureido] phenylsulphanyl} phenyl) acetic acid 77a. Ethyl {4-[3-(1-butyl-3-heptylureido)phenylsulphanyl]phenyl} acetate 77b. {4-[3-(1-Butyl-3-heptylureido)phenylsulphanyl]phenyl}acetic acid

78a. Ethyl {4-[3-(1-butyl-3-phenethylureido)phenylsulphanyl]phenyl} acetate 78b. {4-[3-(1-Butyl-3-phenethylureido)phenylsulphanyl]phenyl}acet ic acid 79a. Ethyl (4- {3- [1-butyl-3- (4-trifluoromethylphenyl)- ureido] phenylsulphanyl} phenyl) acetate 79b. (4- {3- [1-Butyl-3- (4-trifluoromethylphenyl) ureido]- phenylsulphanyl} phenyl) acetic acid 80a. Ethyl (4- {3- [1-butyl-3- (4-methoxyphenyl) ureido]- phenylsulphanyl} phenyl) acetate 80b. (4- {3- [1-Butyl-3- (4-methoxyphenyl) ureido] phenylsulphanyl} phenyl) acetic acid 81a. Ethyl {4- [3- (3-adamantan-1-yl-1-butylureido)- phenylsulphanyl] phenyl} acetate 81 b. {4-[3-(3-Adamantan-1-yl-1-butylureido)phenylsulphanyl]phenyl } acetic acid 82a. Ethyl (4- {3- [1-butyl-3- (2-phenoxyphenyl) ureido]- phenylsulphanyl} phenyl) acetate 82b. (4- {3- [1-Butyl-3- (2-phenoxyphenyl) ureido] phenylsulphanyl} phenyl) acetic acid 83a. Ethyl {4- [3- (3-allyl-1-butylureido) phenylsulphanyl] phenyl} acetate 83b. {4-[3-(3-Allyl-1-butylureido)phenylsulphanyl]phenyl} acetic acid 84a. Ethyl {4-[3-(1-butyl-3-cyclohexylureido)phenylsulphanyl]phenyl} acetate 84b. {4-[3-(1-Butyl-3-cyclohexylureido)phenylsulphanyl]phenyl}ace tic acid 85a. Ethyl (4- {3- [1-butyl-3- (2-nitrophenyl) ureido] phenylsulphanyl} phenyl) acetate 85b. (4- {3- [1-Butyl-3- (2-nitrophenyl) ureido] phenylsulphanyl} phenyl) acetic acid 86a. Ethyl {4-[3-(1-butyl-3-hexylureido)phenylsulphanyl]phenyl} acetate 86b. {4-[3-(1-Butyl-3-hexylureido)phenylsulphanyl]phenyl}acetic acid 87a. Ethyl {4-[3-(1-butyl-3-naphthalen-2-ylureido)- phenylsulphanyl] phenyl} acetate

87b. {4- [3- (1-Butyl-3-naphthalen-2-ylureido) phenylsulphanyl] phenyl} acetic acid 88a. Ethyl (4- {3- [1-butyl-3- (2-ethoxyphenyl) ureido]- phenylsulphanyl} phenyl) acetate 88b. (4- {3- [1-Butyl-3- (2-ethoxyphenyl) ureido] phenylsulphanyl} phenyl) acetic acid 89a. Ethyl (4- {3- [3- (4-butoxyphenyl)-1-butylureido]- phenylsulphanyl} phenyl) acetate 89b. (4- {3- [3- (4-Butoxyphenyl)-l-butylureido] phenylsulphanyl} phenyl) acetic acid 90a. Ethyl 14- [3- (I-butyl-3-pentylureido) phenylsulphanyl] phenyl) acetate 90b. {4-[3-(1-Butyl-3-pentylureido)phenylsulphanyl]phenyl}acetic acid 91a. Ethyl {4-[3-(1,3-dibutylureido)phenylsulphanyl]phenyl} acetate 91b. {4-[3-(1,3-Dibutylureido)phenylsulphanyl]phenyl} acetic acid 92a. Ethyl (4- {4- [3-benzyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetate 92b. (4- {4- [3-Benzyl-1- (3-phenylpropyl) ureido] phenylsulphanyl} phenyl) acetic acid 93a. Ethyl (4- {4- [3-heptyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl}phenyl) acetate 93b. (4-{4-[3-Heptyl-1-(3-phenylpropyl) ureido] phenylsulphanyl} phenyl) acetic acid 94a. Ethyl (4- {4- [3-phenethyl-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetate 94b. (4-{4-[3-Phenethyl-1-(3-phenylpropyl)ureido]phenylsulphanyl} phenyl) acetic acid 95a. Ethyl (4- {4- [1- (3-phenylpropyl)-3- (4-tri- fluoromethylphenyl) ureido] phenylsulphanyl} phenyl) acetate 95b. (4- {4- [1- (3-Phenylpropyl)-3- (4-tri- fluoromethylphenyl) ureido] phenylsulphanyl} phenyl) acetic acid

96a. Ethyl (4- {4- [3- (2-phenoxyphenyl)-1- (3-phenyl- propyl) ureido] phenylsulphanyl}phenyl) acetate 96b. (4- {4- [3- (2-Phenoxyphenyl)-1- (3-phenyl- propyl) ureido] phenylsulphanyl} phenyl) acetic acid 97a. Ethyl (4- {4- [3-allyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetate 97b. (4- {4- [3-Allyl-1- (3-phenylpropyl) ureido] phenylsulphanyl} phenyl) acetic acid 98a. Ethyl (4- {4- [3-cyclohexyl-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetate 98b. (4- {4- [3-Cyclohexyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetic acid 99a. Ethyl (4- {4- [3- (2-nitrophenyl)-1- (3-phenyl- propyl) ureido] phenylsulphanyl} phenyl) acetate 99b. (4- {4- [3- (2-Nitrophenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetic acid 100a. Ethyl (4- {4- [3-hexyl-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetate 100b. (4- {4- [3-Hexyl-1- (3-phenylpropyl) ureido] phenylsulphanyl} phenyl) acetic acid 101a. Ethyl (4- {4- [3-naphthalen-2-yl-1- (3-phenyl- propyl) ureido] phenylsulphanyl} phenyl) acetate 101b. (4- {4- [3-Naphthalen-2-yl-1- (3-phenyl- propyl) ureido] phenylsulphanyl} phenyl) acetic acid 102a. Ethyl (4- {4- [3- (2-ethoxyphenyl)-1- (3-phenyl- propyl) ureido] phenylsulphanyl} phenyl) acetate 102b. (4- {4- [3- (2-Ethoxyphenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetic acid

103a. Ethyl (4- {4- [3- (4-butoxyphenyl)-1- (3-phenyl- propyl) ureido] phenylsulphanyl} phenyl) acetate 103b. (4- {4- [3- (4-Butoxyphenyl)-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetic acid 104a. Ethyl (4- {4- [3-pentyl-1- (3-phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetate 104b. (4- {4- [3-Pentyl-1- (3-phenylpropyl) ureido] phenylsulphanyl} phenyl) acetic acid 105a. Ethyl (4- {4- [3-butyl-1- (3-phenylpropyl) ureido]- phenylsulphanyl} phenyl) acetate 105b. (4- {4- [3-Butyl-1- (3-phenylpropyl) ureido] phenylsulphanyl} phenyl) acetic acid 106a. Ethyl {4- [4- (3-benzyl-1-phenethylureido) phenylsulphanyl] phenyl} acetate 106b. {4-[4-(3-Benzyl-1-phenethylureido)phenylsulphanyl]phenyl} acetic acid 107a. Ethyl {4-[4-(1-phenethyl-3-phenylureido)phenylsulphanyl]phenyl} acetate 107b. {4-[4-(1-Phenethyl-3-phenylureido)phenylsulphanyl]phenyl}ace tic acid 108a. Ethyl (4- {4- [3- (2, 3-dichlorophenyl)-1-phenethyl- ureido] phenylsulphanyl}phenyl) acetate 108b. (4- {4- [3- (2, 3-Dichlorophenyl)-1-phenethylureido]- phenylsulphanyl} phenyl) acetic acid 109a. Ethyl {4- [4- (3-heptyl-1-phenethylureido) phenylsulphanyl] phenyl} acetate 109b. {4-[4-(3-Heptyl-1-phenethylureido)phenylsulphanyl]phenyl} acetic acid 110a. Ethyl {4-[4-(1,3-diphenethylureido)phenylsulphanyl]phenyl} acetate 110b. {4-[4-(1,3-Diphenethylureido)phenylsulphanyl]phenyl} acetic acid 111 a. Ethyl (4- {4- [l-phenethyl-3- (4-trifluoro- methylphenyl) ureido] phenylsulphanyl} phenyl) acetate 111 b. (4-{4-[1-Phenethyl-3-(4-trifluoromethyl-

phenyl) ureido] phenylsulphanyl} phenyl) acetic acid 112a. Ethyl (4- {4- [3- (4-methoxyphenyl)-1-phenethyl- ureido] phenylsulphanyl} phenyl) acetate 112b. (4- {4- [3- (4-Methoxyphenyl)-1-phenethylureido]- phenylsulphanyl} phenyl) acetic acid 113a. Ethyl {4-[4-(3-adamantan-1-yl-1-phenethyl-1 ureido) phenylsulphanyl] phenyl} acetate 113b. {4-[4-(3-Adamantan-1-yl-1-phenethylureido)- phenylsulphanyl] phenyl} acetic acid 114a. Ethyl (4- {4- [1-phenethyl-3- (2-phenoxyphenyl)- ureido] phenylsulphanyl} phenyl) acetate 114b. (4- {4- [1-Phenethyl-3- (2-phenoxyphenyl) ureido]- phenylsulphanyl} phenyl) acetic acid 115a. Ethyl {4-[4-(3-allyl-1-phenethylureido)phenylsulphanyl]phenyl} acetate 115b. {4-[4-(3-Allyl-1-phenethylureido)phenylsulphanyl]phenyl} acetic acid 116a. Ethyl {4- [4- (3-cyclohexyl-1-phenethylureido)- phenylsulphanyl] phenyl} acetate 116b. {4- [4- (3-Cyclohexyl-1-phenethylureido) phenylsulphanyl] phenyl) acetic acid 117a. Ethyl (4- {4- [3- (2-nitrophenyl)-1-phenethyl- ureido] phenylsulphanyl} phenyl) acetate 117b. (4-{4-[3-(2-Nitrophenyl)-1-phenethylureido]phenylsulphanyl}p henyl) acetic acid 118a. Ethyl {4-[4-(3-hexyl-1-phenethylureido)phenylsulphanyl]phenyl} acetate 118b. {4-[4-(3-Hexyl-1-phenethylureido)phenylsulphanyl]phenyl} acetic acid 119a. Ethyl {4- [4- (3-naphthalen-2-yl-1-phenethyl- ureido) phenylsulphanyl] phenyl} acetate

119b. {4- [4- (3-Naphthalen-2-yl-1-phenethylureido)- phenylsulphanyl] phenyl} acetic acid 120a. Ethyl (4- {4- [3- (2-ethoxyphenyl)-1-phenethyl- ureido] phenylsulphanyl}phenyl) acetate 120b. (4- {4- [3- (2-Ethoxyphenyl)-1-phenethylureido]- phenylsulphanyl} phenyl) acetic acid 121a. Ethyl (4-{4-[3-(4-butoxyphenyl)-1-phenethyl- ureido] phenylsulphanyl}phenyl) acetate 121 b. (4- {4- [3- (4-Butoxyphenyl)-1-phenethylureido]- phenylsulphanyl} phenyl) acetic acid 122a. Ethyl {4-[4-(3-pentyl-1-phenethylureido)phenylsulphanyl]phenyl} acetate 122b. {4-[4-(3-Pentyl-1-phenethylureido)phenylsulphanyl]phenyl} acetic acid 123a. Ethyl {4-[4-(3-butyl-1-phenethylureido)phenylsulphanyl]phenyl} acetate 123b. {4-[4-(3-Butyl-1-phenethylureido)phenylsulphanyl]phenyl} acetic acid 124a. Ethyl {4- [4- (3-benzyl-1-heptylureido) phenylsulphanyl] phenyl} acetate 124b. {4-[4-(3-Benzyl-1-heptylureido)phenylsulphanyl]phenyl} acetic acid 125a. Ethyl {4-[4-(1-heptyl-3-phenylureido)phenylsulphanyl]phenyl} acetate 125b. {4-[4-(1-Heptyl-3-phenylureido)phenylsulphanyl]phenyl}acetic acid 126a. Ethyl (4- {4- [3- (2, 3-dichlorophenyl)-1-heptyl- ureido] phenylsulphanyl} phenyl) acetate 126b. (4- {4- [3- (2, 3-Dichlorophenyl)-1-heptylureido]- phenylsulphanyl} phenyl) acetic acid 127a. Ethyl {4- [4- (1, 3-diheptylureido) phenylsulphanyl] phenyl} acetate 127b. {4-[4-(1,3-Diheptylureido)phenylsulphanyl]phenyl} acetic acid 128a. Ethyl {4- [4- (1-heptyl-3-phenethylureido) phenylsulphanyl] phenyl} acetate 128b. {4-[4-(1-Heptyl-3-phenethylureido)phenylsulphanyl]phenyl}ace tic acid 129a. Ethyl (4- {4- [1-heptyl-3- (4-trifluoro-

methylphenyl) ureido] phenylsulphanyl} phenyl) acetate 129b. (4- {4- [1-Heptyl-3- (4-trifluoromethyl- phenyl) ureido] phenylsulphanyl} phenyl) acetic acid 130a. Ethyl (4- {4- [1-heptyl-3- (4-methoxyphenyl) ureido]- phenylsulphanyl} phenyl) acetate 130b. (4- {4- [1-Heptyl-3- (4-methoxyphenyl) ureido] phenylsulphanyl} phenyl) acetic acid 131 a. Ethyl {4- [4- (3-adamantan-1-yl-1-heptylureido)- phenylsulphanyl] phenyl} acetate 131b. {4-[4-(3-Adamantan-1-yl-1-heptylureido)phenylsulphanyl]pheny l} acetic acid 132a. Ethyl (4-14- [l-heptyl-3- (2-phenoxyphenyl)- ureido] phenylsulphanyl}phenyl) acetate 132b. (4- {4- [1-Heptyl-3- (2-phenoxyphenyl) ureido] phenylsulphanyl} phenyl) acetic acid 133a. Ethyl {4-[4-(3-allyl-1-heptylureido)phenylsulphanyl]phenyl} acetate 133b. {4- [4- (3-Allyl-1-heptylureido) phenylsulphanyl] phenyl} acetic acid 134a. Ethyl {4-[4-(3-cyclohexyl-1-heptylureido)phenylsulphanyl]phenyl}ac etate 134b. {4-[4-(3-Cyclohexyl-1-heptylureido)phenylsulphanyl]phenyl} acetic acid 135a. Ethyl (4- {4- [1-heptyl-3- (2-nitrophenyl) ureido]- phenylsulphanyl} phenyl) acetate 135b. (4-{4-[1-Heptyl-3-(2-nitrophenyl) ureido] phenylsulphanyl}phenyl) acetic acid 136a. Ethyl {4-[4-(1-heptyl-3-hexylureido)phenylsulphanyl]phenyl} acetate 136b. {4-[4-(1-Heptyl-3-hexylureido)phenylsulphanyl]phenyl}acetic acid 137a. Ethyl {4-[4-(1-heptyl-3-naphtalen-2-ylureido)- phenylsulphanyl] phenyl} acetate

137b. {4- [4- (l-Heptyl-3-naphthalen-2-ylureido) phenylsulphanyl] phenyl} acetic acid 138a. Ethyl (4- {4- [3- (2-ethoxyphenyl)-1-heptylureido]- phenylsulphanyl} phenyl) acetate 138b. (4- {4- [3- (2-Ethoxyphenyl)-l-heptylureido] phenylsulphanyl} phenyl) acetic acid 139a. Ethyl (4- {4- [3- (4-butoxyphenyl)-1-heptylureido]- phenylsulphanyl} phenyl) acetate 139b. (4- {4- [3- (4-Butoxyphenyl)-l-heptylureido] phenylsulphanyl} phenyl) acetic acid 140a. Ethyl {4-[4-(1-heptyl-3-pentylureido)phenylsulphanyl]phenyl} acetate 140b. {4-[4-(1-Heptyl-3-pentylureido)phenylsulphanyl]phenyl}acetic acid 141a. Ethyl {4-[4-(3-butyl-1-heptylureido)phenylsulphanyl]phenyl} acetate 141 b. {4-[4-(3-Butyl-1-heptylureido)phenylsulphanyl]phenyl} acetic acid.

A general description of the preparation of the compounds of general formula of the appended Figure 1 is given below.

The reaction scheme described in Figure 1 is a general scheme allowing the production of the compounds according to the invention.

The compounds of general formula (I) may be obtained (Figure 1) by coupling a thiol, an alcohol, an amine or a seleniated derivate (depend on X value) with an aromatic iodinated compound, using a metal catalyst such as nickel or palladium derivatives, in the presence of a hydride donor such as sodium borohydride and if necessary a base. Concerning diaryl amine compounds, the copper or palladium catalyzed amination (Tetrahedron 58, (2002) 2041-2075) of the nitro aniline compound with aryl halogenide may be used, followed by the reduction of the nitro to the corresponding amino group. Concerning the preparation of diaryl ether coupling of the corresponding alkoxide catalyzed by

palladium may be used. Concerning the preparation of diaryl ketone compounds, palladium catalysed conversion of halogenoaryl derivatives compound to the corresponding organotin derivatives followed by a palladium catalysed coupling with acyl chloride derivative may afford the target product. The ketone might be protected in order to avoid problem during reductive amination. The next step is a reductive amination of the preceding amine and of an aldehyde, which may be carried out with isolation of the intermediate imine or otherwise, followed by reduction of the latter by the action of a reducing agent such as NaBH3CN. The alkylated amine obtained can then be subjected to the action of an isocyanate or an isothiocyanate in a solvent such as dichloromethane to give the corresponding urea or thiourea. It can also be further alkylated by reductive amination reaction in the presence of an aldehyde under the same conditions as above. The amide may also be formed by the action of an acid in the presence of a coupling agent such as 0- (7-azabenzotriazol-1-yl)-N, N, N', N'-tetramethyluronium hexafluorophosphate (HATU) in the presence of a base such as DIEA or an acyl halide and a base. The derivatives obtained are then saponified by the action, for example, of a base such as NaOH to give the corresponding acids. The sulphate compounds (X : S) oxydated by the action of metachloroperbenzoic acid (MCPBA) in the presence of dichloromethane.

The compounds according to the invention have PPAR-type receptor modulating properties. This activity on the PPARa, and Y receptors is measured in a transactivation test and quantified by the dissociation constant Kdapp (apparent), as described in Example 142.

The preferred compounds of the present invention have a dissociation constant of less than or equal to 1 000 nM, and advantageously of less than or equal to 500 nM.

The subject of the present invention is also, as a medicament, the compounds of formula (I) as described above.

The subject of the present invention is the use of the compounds of formula (I) for manufacturing a composition intended for regulating and/or restoring the metabolism of skin lipids.

The compounds according to the invention are particularly suitable in the fields of the following treatments : 1) for treating dermatological conditions linked to a keratinization disorder related to cell differentiation and proliferation, in particular to treat acne vulgaris, comedo- type acne, polymorphic acne, acne rosacea, nodulocystic acne, acne conglobata, senile acne, secondary acne such as solar acne, acne medicamentosa or occupational acne ; 2) for treating other types of keratinization disorders, in particular ichthyosis, ichthyosiform states, Darrier's disease, keratosis palmais et plantais, leukoplasia and leukoplasiform states, cutaneous or mucosal (buccal) lichen ; 3) for treating other dermatological conditions with an inflammatory immunoallergic component, with or without cell proliferation disorder, and in particular all the forms of psoriasis, whether cutaneous, mucosal or ungual, and even psoriatic rheumatism, or cutaneous atopy, such as eczema or respiratory atopy or gingival hypertrophy ; 4) for treating any dermal or epidermal proliferations whether benign or malignant, whether of viral origin or not, such as verruca vulgaris, verruca plana and epidermodysplasia verruciformis, oral or florid papillomatoses, T lymphom, and proliferations which may be induced by ultraviolet radiation, in particular in the case of baso-and spinocellular epitheliomas, and any precancerous skin lesions such as keratoacanthomas ; 5) for treating other dermatological disorders such as immune dermatoses such

as lupus erythematosus, bullous immune diseases and collagen diseases, such as scleroderma ; 6) in the treatment of dermatological or general conditions with an immunological component ; 7) in the treatment of skin disorders due to exposure to UV radiation and for repairing or combating skin ageing, whether photoinduced or chronological or for reducing actinic keratoses and pigmentations, or any pathologies associated with chronological or actinic ageing, such as xerosis ; 8) for combating sebaceous function disorders such as acne hyperseborrhoea, simple seborrhoea, or seborrhoeic dermatitis ; 9) for preventing or treating cicatrization disorders, or for preventing or repairing stretch marks ; 10) in the treatment of pigmentation disorders, such as hyperpigmentation, melasma, hypopigmentation or vitiligo ; 11) in the treatment of lipid metabolism conditions, such as obesity, hyperlipidaemia, non-insulin-dependent diabetes or X syndrome ; 12) in the treatment of inflammatory conditions such as arthritis ; 13) in the treatment or prevention of cancerous or precancerous states ; 14) in the prevention or treatment of alopecia of different origins, in particular alopecia due to chemotherapy or to radiation ; 15) in the treatment of immune system disorders, such as asthma, diabetes mellitus type 1, multiple sclerosis, or other selective dysfunctions of the immune system ; and 16) in the treatment of conditions of the cardiovascular system such as arteriosclerosis or hypertension.

The subject of the present invention is also a pharmaceutical composition comprising, in a physiologically acceptable medium, at least one

compound of formula (I) as defined above.

The administration of the composition according to the invention may be carried out enterally, parenterally, topically or ocularly. Preferably, the pharmaceutical composition is packaged in a form suitable for application by the topical route.

By the enteral route, the composition may be provided in the form of tablets, gelatin capsules, sugar-coated tablets, syrups, suspensions, solutions, powders, granules, emulsions, suspensions of lipid or polymeric microspheres or nanospheres or vesicles allowing controlled release. By the parenteral route, the composition may be provided in the form of solutions or suspensions for perfusion or injection.

The compounds according to the invention are generally administered at a daily dose of about 0. 001 mg/kg to 100 mg/kg of body weight, in 1 to 3 doses.

The compounds are used by the systemic route at a concentration generally of between 0. 001% and 10% by weight, preferably between 0. 01 % and 1 % by weight, relative to the weight of the composition.

By the topical route, the pharmaceutical composition according to the invention is more particularly intended for the treatment of the skin and the mucous membranes and may be provided in the form of salves, creams, milks, ointments, powders, impregnated pads, syndets, solutions, gels, sprays, mousses, suspensions, lotions, sticks, shampoos or washing bases. It may also be provided in the form of suspensions of lipid or polymeric microspheres or nanospheres or vesicles or of polymeric patches and of hydrogels allowing controlled release. This composition for the topical route may be provided in anhydrous form, in aqueous form or in the form of an emulsion.

The compounds are used by the topical route at a concentration

which is generally between 0. 001% and 10% by weight, preferably between 0. 01 % and 1 % by weight, relative to the total weight of the composition.

The compounds of formula (I) according to the invention also find application in the cosmetics field, in particular in body and hair care, and more particularly for regulating and/or restoring skin lipid metabolism.

The subject of the invention is therefore also the cosmetic use of a composition comprising, in a physiologically acceptable carrier, at least one of the compounds of formula (I) for body or hair care.

The cosmetic composition according to the invention containing, in a cosmetically acceptable carrier, at least one compound of formula (I) or one of its optical or geometric isomers or one of its salts, may be provided in particular in the form of a cream, a milk, a lotion, a gel, suspensions of lipid or polymeric microspheres or nanospheres or vesicles, impregnated pads, solutions, sprays, mousses, sticks, soaps, shampoos or washing bases.

The concentration of compound of formula (I) in the cosmetic composition is preferably between 0. 001% and 3% by weight, relative to the total weight of the composition.

The pharmaceutical and cosmetic compositions as described above may in addition contain inert additives, or even pharmacodynamically active additives as regards the pharmaceutical compositions, or combinations of these additives, and in particular : - wetting agents ; - flavour enhancers ; - preservatives such as esters of parahydroxybenzoic acid ; - stabilizers ; - moisture regulators ; - pH regulators ;

- osmotic pressure modifiers ; - emulsifiers ; - UV-A and UV-B screening agents ; - antioxidants, such as a-tocopherol, butylated hydroxyanisole or butylated hydroxytoluene, Super Oxide Dismutase, Ubiquinol or certain metal chelators ; - depigmenting agents such as hydroquinone, azelaic acid, caffeic acid or kojic acid ; - emollients ; - moisturizing agents such as glycerol, PEG 400, thiamorpholinone, and its derivatives, or urea ; - antiseborrhoeic or anti-acne agents, such as S-carboxymethylcysteine, S- benzylcysteamine, their salts or their derivatives, or benzoyl peroxide ; - antibiotics such as erythromycin and its esters, neomycin, clindamycin and its esters, tetracyclines ; - antifungal agents such as ketoconazole or 4, 5-polymethylene-3-isothiazolidones ; - agents promoting hair regrowth, such as Minoxidil (2, 4-diamino-6- piperidinopyrimidine 3-oxide) and its derivatives, Diazoxide (7-chloro-3-methyl- 1, 2, 4-benzothiadiazine 1, 1-dioxide) and Phenytoin (5, 4-diphenylimidazolidine 2, 4- dione) ; - nonsteroidal anti-inflammatory agents ; - carotenoids and, in particular, P-carotene ; - antipsoriatic agents such as anthralin and its derivatives ; - 5, 8, 11, 14-eicosatetraynoic and 5, 8, 11-eicosatriynoic acids, their esters and amides ; - retinoids, that is to say ligands for the RAR or RXR receptors, which may be natural or synthetic ; - corticosteroids or oestrogens ;

- a-hydroxy acids and o-keto acids or their derivatives, such as lactic, malic, citric, glycolic, mandelic, tartaric, glyceric and ascorbic acids, and their salts, amides or esters, or a-hydroxy acids or their derivatives, such as salicylic acid and its salts, amides or esters ; - ion channel, such as potassium channel, blockers ; - or alternatively, more particularly for pharmaceutical compositions, in combination with medicaments known to interfere with the immune system (for example cyclosporine, FK 506, glucocorticoids, monoclonal antibodies, cytokines or growth factors, and the like).

Of course, persons skilled in the art will be careful to choose the possible compound (s) to be added to these compositions such that the advantageous properties intrinsically attached to the present invention are not or not substantially impaired by the addition envisaged.

Several examples of production of active compounds of formula (I) according to the invention, results of biological activity thereof and various concrete formulations based on such compounds, will now be given by way of illustration and without being limiting in any manner.

EXAMPLES The products were analysed by HPLC/Mass. Column : 2. 1X5 mm, 3, High purity C18 Hypersil.

Mobile phase : A (CH3CN/0. 1 v/v HC02H) ; B (H20/0. 1 v/v HCO2H), Waters Alliance 2790 LC Mobile Phase Solvents A% 35. 0 Solvent A B% 65. 0 Solvent B Flow rate (ml/min) 0. 450 Analytical time (min) 5. 00

Column temperature (°C) 60 Maximum column temperature (°C) 10 Waters Alliance 2790 LC Rapid Equilibration System time (min) 0. 30 Re-equilibration time (min) 0. 50 The gradient contains 3 entries which are : Time A% B% Flow rate Curve 0. 00 5. 0 65. 0 0. 450 1 3. 00 95. 0 5. 0 0. 450 6 5. 00 95. 0 5. 0 0. 450 6 EXAMPLE 1 : Ethyl 4-(3-aminophenvlsulphanvlOphenyllacetate a) Ethyl 4-iodophenylacetate 1. 25 ml (0. 023 mol) of concentrated sulphuric acid are added dropwise to a mixture of 6. 14 g (0. 023 mol) of 4-iodophenylacetic acid in 50 ml of ethanol. The reaction medium is then heated under reflux for 7 h, and then concentrated in a rotary evaporator under vacuum. Water is added to the residue obtained. The solution is neutralized by adding sodium bicarbonate. The desired product is extracted by adding ethyl ether. The organic phase is washed with water, dried over magnesium sulphate and concentrated in a rotary evaporator.

The product is purified by filtration on a silica column, eluted with a dichloromethane 8/heptane 2 mixture. After evaporation of the solvents, 6. 2 g (96%) of the expected compound are recovered in the form of a colourless oil. b) Ethyl [4-(3-aminophenvisulphanvl) phenvl] acetate A solution of 3-aminothiophenol (2 g, 0. 016 mol) in 30 ml of THF is added over a mixture of borohydride polymer supported Amberlitee IRA400 resin (2. 5 mmol/g) (Aldrich : 32864-2) (16. 2 g, 0. 04 mol), bis (bipyridine) nickel (II)

bromide (150 mg) (Organometallics 1985, 4, 657-661) and ethyl 4-iodophenylacetate (3g, 0. 011 mol) in ethanol (120ml). The mixture is stirred under reflux for 3 h and 12 h at room temperature. The reaction medium is filtered and the filtrate concentrated in a rotary evaporator under vacuum. The product is purified by chromatography on a silica column (dichloromethane 5/ heptane 5). After evaporation of the solvents, the expected compound 2. 2 g (70%), is isolated in the form of a yellow oil.

'H NMR (CDCI3, 400 MHz) : 1. 28 (3H, t), 3. 61 (2H, s), 4. 18 (2H, q), 6. 57 (1H, Ar, d), 6. 66 (1H, Ar, s), 6. 75 (1H, Ar, d), 7. 09 (1H, Ar, t), 7. 23 (2H, Ar, d), 7. 335 (2H, Ar, d).

EXAMPLE 2 : Ethvl f4- (4-aminoahenylsulahanvl) phenvllacetate In a manner similar to Example 1 (b), by reacting ethyl 4-iodophenylacetate (2. 5 g, 0. 01 mol), 30 mi of THF, borohydride polymer supported Amberlitee IRA400 resin (2. 5 mmol/g) (Aldrich : 32864-2) (13. 5 g), bis (bipyridine) nickel (II) bromide (125 mg) (Organometallics 1985, 4, 657-661) and 4, 4'-dithiodianiline (1. 7 g, 0. 013 mol), 1. 1 g (42%) of the expected derivative is obtained in the form of a yellow oil.

'H NMR (CDCI3, 400 MHz) : 1. 26 (3H, t), 3. 55 (2H, s), 4. 15 (2H, q), 6. 67 (2H, Ar, d), 7. 10 (2H, Ar, d), 7. 15 (2H, Ar, d), 7. 32 (2H, Ar, d).

EXAMPLE 3 : {4-[3-(3-Phenylpropylamino)phenylsulphanyl]phenyl}acetic acid a) Ethyl 4- [3- (3-phenylpropvlamino) phenLrlsulphanyl] phenyl} acetate A solution of 3-phenylpropionaldehyde (257 mg, 1. 91 mmol) and acetic acid (1 ml) is added to a solution of ethyl [4- (3-aminophenyisulphanyl) phenyl] acetate (Example 1 (b)) (550 mg, 1. 91 mmol)

in 15 ml of DMF. DMF 241 mg and sodium cyanoborohydride (3. 83 mmol) are added and the mixture is stirred for 12 h at room temperature. After extracting with ethyl ether, the organic phase is washed with water, dried over magnesium sulphate and concentrated in a rotary evaporator under vacuum. The product is purified by chromatography on a silica column (dichloromethane 7/ heptane 3). After evaporation of the solvents, 601 mg (77%) of the expected derivative and 100 mg (10%) of ethyl (4- {3- [bis (3-phenylpropyl) amino] phenylsulphanyl} phenyl) acetate are obtained.

'H NMR (CDCI3, 400 MHz) : 1. 29 (3H, t), 1. 91 to 1. 99 (2H, m), 2. 74 (2H, t), 3. 13 (2H, t), 3. 63 (2H, s), 3. 69 (1H, NH, s), 4. 20 (2H, q), 6. 5 (1H, Ar, d), 6. 61 (1H, Ar, s), 6. 71 (1H, Ar, d), 7. 11 (1 H, Ar, t), 7. 21 to 7. 26 (5H, Ar, m), 7. 33 (4H, Ar, t). b) f4- [3- (3-Phenylpropylamino) phenylsulphanyl] phenyl'acetic acid In a manner similar to Example 1 (c), the product is obtained by reacting ethyl {4-[3-(3-phenylpropylamino)phenylsulphanyl]phenyl} acetate (Example 3 (a)) (50 mg), sodium hydroxide (80 mg), water (500 VLI) and ethanol (500 µl) in THF (3 ml).

EXAMPLE 4 : (4-{3-[Bis(3-phenylpropyl)amino]phenyl- sulphanvlTphenvl) acetic acid In a manner similar to Example 1 (c), the product is obtained by reacting ethyl (4- {3- [bis (3-phenylpropyl) amino] phenylsulphanyl} phenyl) acetate obtained in (Example 3 (a)) (50 mg), sodium hydroxide (80 mg), water (500 vol) and ethanol (500 pI) in THF (3 ml).

EXAMPLE 5 : r4- (3-Phenylethylamino) phenvisulphanylphenvllacetic acid a) Ethyl [4- (3-phenylethylamino) phenylsulphanylphenyl] lacetate In a manner similar to Example 3 (a), by reacting

3-phenylacetaldehyde (230 mg, 1. 91 mmol), acetic acid (1 ml), ethyl [4- (3-aminophenylsulphanyl) phenyl] acetate (Example 1 (b)) (550 mg, 1. 91 mmol) in 15 ml of DMF and 241 mg of sodium cyanoborohydride (3. 83 mmol), 643 mg (86%) of the expected derivative are obtained in the form of a colourless oil and 26 mg (10%) of ethyl [4- (3-diphenethylaminophenylsulphanyl) phenyl] acetate. b) [4-(3-Phenethylamino)phenylsulphanylphenyl]acetic acid In a manner similar to Example 1 (c), the product is obtained by reacting ethyl [4- (3-phenethylamino) phenylsulphanylphenyl] acetate (Example 5 (a)) (50 mg), sodium hydroxide (80 mg), water (500 pilz and ethanol (500 gl) in THF (3 ml).

EXAMPLE 6 : r4- (3-Diphenethylaminophenylsulphanvl) phenvllacetic acid In a manner similar to Example 1 (c), the product is obtained by reacting ethyl [4- (3-diphenethylaminophenylsulphanyl) phenyl] acetate obtained in Example 5 (a) (50 mg), sodium hydroxide (80 mg), water (500 jut) and ethanol (500 pl) in THF (3 ml).

EXAMPLE 7 : [4- (3-Heatylaminophenvisulphanvl) phenyllacetic acid a) Ethyl [4- (3-heptylaminophenylsulphanyl) phenvl] acetate In a manner similar to Example 3 (a), by reacting heptaldehyde (219 mg, 1. 91 mmol), acetic acid (1 ml), ethyl [4- (3-aminophenylsulphanyl) phenyl] acetate (Example 1 (b)) (550 mg, 1. 91 mmol) in 15 ml of DMF and 241 mg of sodium cyanoborohydride (2. 71 mmol), 330 mg (45%) of the expected derivative are obtained in the form of a colourless oil and 64 mg (7%) of ethyl [4- (3-diheptylaminophenylsulphanyl) phenyl] acetate.

'H NMR (CDCI3, 400 MHz) : 0. 93 (3H, t), 1. 28 (3H, t), 1. 32 to 1. 41 (8H, m), 1. 57 to 1. 64 (2H, m), 3. 07 (2H, t), 3. 06 (2H, t), 3. 60 (2H, s), 4. 18 (2H, q), 6. 49 (1H, Ar, d),

6. 61 (1H, Ar, s), 6. 68 (1H, Ar, d), 7. 11 (1H, Ar, t), 7. 23 (2H, Ar, d), 7. 32 (2H, Ar, d). b) [4-(3-Heptylaminophenylsulphanyl)phenyl]acetic acid In a manner similar to Example 1 (c), the product is obtained by reacting ethyl [4- (3-heptylaminophenyisulphanyl) phenyl] acetate (Example 7 (a)) (50 mg), sodium hydroxide (80 mg), water (500 µl) and ethanol (500 µl) in THF (3 ml).

EXAMPLE 8 : [4-(3-Diheptylaminophenylsulphanyl)phenyl]acetic acid In a manner similar to Example 1 (c), the product is obtained by reacting ethyl [4- (3-diheptylaminophenylsulphanyl) phenyl] acetate obtained in Example 7 (a) (50 mg), sodium hydroxide (80 mg), water (500 µl) and ethanol (500 Ll) in THF (3 ml).

EXAMPLE 9 : [4-(3-Butylaminophenylsulphanyl)phenyl]acetic acid a) Ethyl [4- 3-butylaminophenylsulphanyl)phenyl]acetate In a manner similar to Example 3 (a), by reacting butyraldehyde (138 mg, 1. 91 mmol), acetic acid (1 ml), ethyl [4- (3-aminophenyisulphanyl) phenyl] acetate (Example 1 (b)) (550 mg, 1. 91 mmol) in 15 ml of DMF and 241 mg of sodium cyanoborohydride (2. 71 mmol), 140 mg (21%) of the expected derivative are obtained in the form of a colourless oil and 464 mg (61%) of ethyl [4-(3-dibutylaminophenylsulphanyl)phenyl] acetate.

'H NMR (CDCl3, 400 MHz) : 0. 97 (3H, t), 1. 28 (3H, t), 1. 39 to 1. 45 (2H, m), 1. 57 to 1. 61 (2H, m), 3. 08 (2H, t), 3. 62 (2H, s), 3. 67 (1H, NH, s), 4. 12 (2H, q), 6. 51 (1H, Ar, d), 6. 61 (1H, Ar, s), 6. 69 (1H, Ar, d), 7. 11 (1H, Ar, t), 7. 23 (2H, Ar, d), 7. 33 (2H, Ar, d). b [4- (3-Butylaminophenylsulphanyl) phenyllacetic acid In a manner similar to Example 1 (c), the product is obtained by

reacting ethyl [4- (3-butylaminophenylsulphanyl) phenyl] acetate (Example 9 (a)) (50 mg), sodium hydroxide (80 mg), water (500 pal) and ethanol (500 µl) in THF (3 ml).

EXAMPLE 10 : r4- (3-Dibutylaminophenvisulphanvl) phenyllacetic acid In a manner similar to Example 1 (c), the product is obtained by reacting ethyl [4- (3-dibutylaminophenylsulphanyl) phenyl] acetate obtained in Example 9 (a) (50 mg, 0. 174 mmol), sodium hydroxide (80 mg), water (500 µl) and ethanol (500 µl) in THF (3 ml).

EXAMPLE 11 : {4-[4-(3-Phenylpropylamino)phenylsulphanyl]phenyl}acetic acid a) Ethyl {4-[4-(3-phenylpropylamino)phenylsulphanyl]phenyl}acetate In a manner similar to Example 3 (a), by reacting 3-phenylpropionaldehyde (128 mg, 0. 96 mmol), acetic acid (1 ml), ethyl [4-(4-aminophenylsulphanyl)phenyl] acetate (Example 2 (a)) (275 mg, 0. 96 mmol) in 15 ml of DMF 120 mg and sodium cyanoborohydride (1. 91 mmol), 307 mg (79%) of the expected derivative and 55 mg (11%) of ethyl (4-f4- [bis (3-phenylpropyl) amino] phenylsulphanyl} phenyl) acetate are obtained.

'H NMR (CDCl3, 400 MHz) : 1. 27 (3H, t), 1. 96 to 2. 03 (2H, m), 2. 77 (2H, t), 3. 19 (2H, t), 3. 56 (2H, s), 3. 86 (1H, NH, s), 4. 16 (2H, q), 6. 58 (1H, Ar, d), 7. 09 (2H, Ar, d), 7. 15 (2H, Ar, d), 7. 23 to 7. 26 (3H, Ar, m), 7. 32 to 7. 36 (4H, Ar, m). b). {4- [4- (3-Phenylpropylamino) phenylsulphanyphenyl} acetic acid In a manner similar to Example 1 (c), the product is obtained by reacting ethyl {4-[4-(3-phenylpropylamino)phenylsulphanyl]phenyl} acetate (Example 11 (a)) (50 mg), sodium hydroxide (80 mg), water (500 ti) and ethanol (500 FI) in THF (3 ml).

EXAMPLE 12 : (4-f4-rBis (3-phenylaroavl) aminolphenvl- sulphanyl}phenyl)acetic acid In a manner similar to Example 1 (c), the product is obtained by reacting ethyl (4- {4- [bis (3-phenylpropyl) amino] phenylsulphanyl}phenyl) acetate obtained in Example 11 (a) (50 mg), sodium hydroxide (80 mg), water (500 µl) and ethanol (500, ul) in THF (3 ml).

EXAMPLE 13 : [4-(4-Phenethylaminophenylsulphanyl)phenyl]acetic acid a) Ethyl [4-(4-phenethvlaminophenylsulphanyl)phenyllacetate In a manner similar to Example 3 (a), by reacting phenylacetaldehyde (115 mg, 0. 96mol), acetic acid (1 ml), ethyl [4- (4-aminophenylsulphanyl) phenyl] acetate (Example 2 (a)) (275 mg, 0. 96 mmol) in 15 ml of DMF and 241 mg of sodium cyanoborohydride (3. 83 mmol), 311 mg (83%) of the expected derivative are obtained in the form of a colourless oil and 17 mg (4%) of ethyl [4- (4-diphenethylaminophenylsulphanyl) phenyl] acetate.

1H NMR (CDCI3, 400 MHz) : 1. 29 (3H, t), 2. 97 (2H, t), 3. 45 (2H, t), 3. 58 (2H, s), 3. 95 (1H, NH, s), 4. 18 (2H, q), 6. 32 (2H, Ar, d), 7. 12 (2H, Ar, d), 7. 18 (2H, Ar, d), 7. 27 to 7. 30 (3H, Ar, m), 7. 36 to 7. 40 (4H, Ar, m). b) [4-(4-Phenethylaminophenylsulphanyl)phenyl]acetic acid In a manner similar to Example 1 (c), the product is obtained by reacting ethyl [4- (4-phenethylaminophenylsulphanyl) phenyl] acetate (Example 13 (a)) (50 mg), sodium hydroxide (80 mg), water (500 PLI) and ethanol (500 µl) in THF (3 ml).

EXAMPLE 14 : r4-f4-Diahenethytaminophenvisulphanvl) phenyllacetic acid In a manner similar to Example 1 (c), the product is obtained by

reacting ethyl [4- (4-diphenethylaminophenylsulphanyl) phenyl] acetate obtained in Example 13 (a) (50 mg), sodium hydroxide (80 mg), water (500 µl) and ethanol (500 pI) in THF (3 ml).

EXAMPLE 15 : r4- (4-Heptylaminophenylsulphanvl) nhenyllacetic acid a) Ethyl [4- (4-heptylaminophenylsulphanyl) phenyl] acetate In a manner similar to Example 3 (a), by reacting heptaldehyde (109 mg, 0. 96 mmol), acetic acid (1 ml), ethyl [4- (4-aminophenylsulphanyl) phenyl] acetate (Example 2 (a)) (275 mg, 0. 96 mmol) in 15 ml of DMF and 241 mg of sodium cyanoborohydride (2. 71 mmol), 250 mg (68%) of the expected derivative are obtained in the form of a colourless oil and 43 mg (9%) of ethyl [4- (4-diheptylaminophenylsulphanyl) phenyl] acetate.

'H NMR (CDCI3, 400 MHz) : 0. 92 (3H, t), 1. 28 (3H, t), 1. 30 to 1. 43 (8H, m), 1. 63 to 1. 67 (2H, m), 3. 14 (2H, t), 3. 55 (2H, s), 3. 86 (1H, NH, s), 4. 15 (2H, q), 6. 60 (2H, Ar, d), 7. 08 (2H, Ar, d), 7. 15 (2H, Ar, d), 7. 35 (2H, Ar, d). b) [4-(4-Heptylaminophenylsulphanyl)phenyl]acetic acid In a manner similar to Example 1 (c), the product is obtained by reacting ethyl [4- (4-heptylaminophenyisulphanyl) phenyl] acetate (Example 15 (a)) (50 mg), sodium hydroxide (80 mg), water (500 pI) and ethanol (500 ; J) in THF (3 ml).

EXAMPLE 16 : [4-(4-Diheptylaminophenylsulphanyl)phenyl]acetic acid In a manner similar to Example 1 (c), the product is obtained by reacting ethyl [4- (4-diheptylaminophenylsulphanyl) phenyl] acetate obtained in Example 15 (a) (50 mg), sodium hydroxide (80 mg), water (500 gi) and ethanol (500 lli) in THF (3 ml).

EXAMPLE 17 : r4- (4-Dibutylaminophenvisulahanvl) phenvllacetic acid a) Ethyl [4-(4-dibutylaminophenylsulphanyl)phenyl]acetate In a manner similar to Example 3 (a), by reacting butyraldehyde (69 mg, 0. 96 mmol), acetic acid (1 ml), ethyl [4- (4-aminophenylsulphanyl) phenyl] acetate (Example 2 (a)) (275 mg, 0. 96 mmol) in 15 ml of DMF and 241 mg of sodium cyanoborohydride (2. 71 mmol), 313 mg (82%) of ethyl [4- (4-dibutylaminophenylsulphanyl) phenyl] acetate are obtained. b) r4-Dibutylaminophenylsulphanyl phenyllacetic acid In a manner similar to Example 1 (c), the product is obtained by reacting ethyl [4- (4-dibutylaminophenylsulphanyl) phenyl] acetate (Example 17 (a)) (50 mg), sodium hydroxide (80 mg), water (500 VLI) and ethanol (500 µl) in THF (3 ml).

Table 1 : Results of analysis of the products of Examples 1b to 17b EXAMPLE Quantity Molar HPLC ES Mass (mg) mass (% total Spectrometry surface area) (M+H") 1 b 1. 4 259. 33 100 259 2b 1. 7 259. 33 72. 96 259 3b 178. 6 377. 51 89. 68 378 4b 49. 3 495. 68 82. 13 496 5b 157. 6 363. 48 75. 62 363 6b 13. 4 467. 63 73. 84 468 7b 20. 4 357. 52 93. 81 358 8b 29. 9 455. 70 98. 15 456 9b 4. 1 315. 43 72. 45 315 10b 93. 3 371. 54 94. 21 372 11 b 19. 2 377. 51 95. 56 378 12b 34. 1 495. 68 82. 98 496 13b 21. 4 363. 48 89. 16 363 14b 6. 7 467. 63 87. 55 468 15b 3. 6 357. 52 89. 2 358

16b26. 1455. 70 95. 67 456 17b125. 437154 92. 31372 EXAMPLES 18 TO 141 : SYNTHESIS OF EXAMPLES 18 to 141 Examples 18 to 141 were obtained by parallel chemistry. The reactions of a starting amine and a starting isocyanate are performed in several reactors simultaneously according to the operating protocol described below.

A. Formation of urea for the [4-(aminophenylsulphanyl)phenyl] acetic acid derivatives Operating protocol : The starting amine (see Table 3) is introduced into each 5 ml reactor. 2 ml of dichloromethane are added. Next, 0. 062 mmol of isocyanate (see Table 4) are added. The reactors are stirred for 7 h at room temperature. 0. 062 mmol of isocyanates are added if the starting amine has not completely disappeared (TLC monitoring). In this case, the stirring is continued for 12 h at room temperature.

The reaction media are concentrated to dryness for 2 h at 40°C in a centrifugal evaporator under vacuum. The products are purified by filtration on silica cartridges (6 ml), 1 : DCM, 2 : DCM 80/AcOEt 20, and then concentrated to dryness, 2 h at 40°C in a centrifugal evaporator.

Table 2 : Starting amines Example Name Molar Number Quantity No. mass of mol per (mmol) reactor 3a Ethyl {4-[3-(3-phenyl-#405. 56 0. 031123 12. 6 propylamino) phenyl- sulphanyl[phenyl acetate 5a Ethyl [4- (3-phenethyl- 391. 53 0. 031123 12. 2 amino) phenylsulphanyl- henyl acetate 7a Ethyl [4- (3-heptyl- 385. 57 0. 031123 12. 0 aminophenylsulphanyl)- phenyl] acetate 9a Ethyl [4-(3-butyl-#343. 49 0. 018923 6. 5 aminophenylsulphanyl)- henyl]acetate 11a #Ethyl {4-[4-(3-phenyl-#405. 56 0. 031123 12. 6 propylamino)phenyl- sulphanyl]phenyl acetate 13a Ethyl [4-(4-phenethyl-#391. 53 0. 031123 12. 2 aminophenylsulphanyl)- phen I acetate 15a Ethyl [4-(4-heptyl-#385. 57 0. 031123 12. 0 aminophenylsulphanyl)- henyl acetate Table 3: Starting isocyanates CHEMISTRY Structure MW n (mmol) Mol m (mg) V 2 eq equivalent (miroL) BENZYL ISOCYANATE 133. 15 0. 0622 2 8. 3 8 .. N ,..... _ :.,, : ; $ PHENYL ISOCYANATE $ 119. 12 0. 0622 2 7. 4 7 zizi zu 11 0 2, 3-DICHLOROPHENYL ISOCYANATE 188. 01 0. 0622 11. 7 ou Cl Ci Cl HEPTYL ISOCYANATE 141. 21 0. 0622 8. 8 10 A N PHENETHYL ISOCYANATE 147. 18 0. 0622 2 9. 2 9 % NS ISOCYANATE F 187. 12 0. 0622 2 11. 6 ISOCYANATS I,, 0 0 4-METHOXYPHENYL ISOCYANATE N 149. 15 0. 0622 2 9. 3 0 0 k 1-ADAMANTYLISOCYANATE 177. 25 0. 0622 2 11. 0 Nez H ,.."H H 2-PHENOXYPHENYL ISOCYANATE 211. 22 0. 0622 2 13. 1 11 ! H 0 O ? i ! fT ALLYL ISOCYANATE 83. 09 0. 0622 2 5. 2 6 f,, 0 CYCLOHEXYL ISOCYANATE N 125. 17 0. 0622 2 7. 8 8 1 0 k 2-NITROPHENYL ISOCYANATE O-164. 12 0. 0622 2 10. 2 */ N N 0 u HEXYL ISOCYANATE 0. 0622 J 2 j 7. 9) 9 2-NAPHTHYL ISOCYANATE N 169. 18 0. 0622 2 10. 5 T O f 2-ETHOXYPHENYL ISOCYANATE 163. 18 0. 0622 2 10. 2 9 y w....-. n O -0/ 4-BUTOXYPHENYL ISOCYANATE N 191. 23 0. 0622 2 11. 9 11 j PENTYL ISOCYANATE N 113. 16 0. 0622 2 7. 0 8 \ N-BUTYL ISOCYANATE N 99. 13 0. 0622 2 6. 2 7 0 0 4-(DIMETHYLAMINO) PHENYL/162. 1 9 0. 0622 2 10. 1 ISOCYANATE zu 0 B. Saponification W aapon} orl to ; ; ,'-'-'Co2 Et , 'CO2H 0 N'I I THF, 4A 0 N-k l R1"E<OH R1" ior H20

Each of the esters obtained above is solubilized in 2 ml of THF.

100 pLI of ethanol are then introduced. 100 pl of a sodium hydroxide solution at 35% is then added. The mixture is stirred at room temperature for 48 h. The progress of the reaction is monitored by thin-layer chromatography (DCM 80/AcOEt 20). After extracting with ether, acidifying with a 1N hydrochloric acid solution, the organic phase is washed twice with water, dried over magnesium sulphate and concentrated to dryness in a centrifugal evaporator under vacuum.

The products are purified by filtration on silica cartridges (6 ml) if necessary, and then concentrated to dryness for 2 h at 40°C in a centrifugal evaporator under vacuum. The final products are analysed by mass-coupled HPLC.

Table 4: Analysis of the products of Examples 18b to 141b Exam Amine Isocyanate Final product Quantity MW HPLC ES pie (mg) (% total MAS surface S area) (M+H , 18b Ethyl {4- [3- (3-phenylpropyl- benzyl isocyanate (4- {3- [3-Benzyl-1- (3-phenylpropyl)- 15. 6 510. 66 81. 3 511 amino) phenylsulphanyl] phe ureido] phenylsulphanyl} phenyl] acetic nyl} acetate acid 19b Ethyl {4- [3- (3-phenylpropyl- phenyl isocyanate (4- {3- [3-Phenyl-1- (3- 22. 6 496. 63 89. 21 497 amino) phenylsulphanyl] phe phenylpropyl) ureido] phenylsulphanyl}- n I acetate hen I acetic acid 20b Ethyl {4- [3- (3-phenylpropyl- 2, 3-dichlorophenyl (4-f3- [3- (2, 3-Dichlorophenyl)-l- (3- 15. 7 565. 52 60. 51 566 amino) phenylsulphanyl] phe isocyanate phenylpropyl)- nyl} acetate ureido] phenylsulphanyl} phenyl) acetic acid 21 b Ethyl {4-13- (3-phenylpropyl- heptyl isocyanate (4- {3- [3-Heptyl-1- (3- 19. 4 518. 72 85. 44 519 amino) phenylsulphanyl] phe phenylpropyl) ureido] phenylsulphanyl}- nyl} acetate phenyl) acetic acid 22b Ethyl {4- [3- (3-phenylpropyl- phenethyl (4- {3- [3-Phenethyl-1- (3- 15. 1 524. 68 79. 28 525 amino) phenylsulphanyl] phe isocyanate phenylpropyl) ureido]- nyl} acetate phenylsulphanyl} phenyl) acetic acid 23b Ethyl {4- [3- (3-phenylpropyl- 4- (trifluoromethyl)- (4- {3- [1- (3-Phenylpropyl)-3- (4- 4. 9 564. 63 75. 5 565 amino) phenylsulphanyl] phe phenyl isocyanate trifluor- nyl} acetate methylphenyl) ureido] phenylsulphanyl} phenyl) acetic acid 24b Ethyl {4- [3- (3-phenylpropyl- 4-methoxyphenyl (4- {3-p- (4-Methoxyphenyl)-l- (3- 19. 0 526. 65 93. 51 527 amino) phenylsulphanyl] phe isocyanate phenylpropyl)- nyl} acetate ureido] phenylsulphanyl} phenyl) acetic acid 25b Ethyl {4- [3- (3-phenylpropyl- 1-adamantyl (4- {3- [Adamantan-1-yl-1- (3- 11. 8 554. 75 35. 5 555 amino) phenylsulphanyl] phe isocyanate phenylpropyl) ureido]- nyl} acetate phenylsul hanyl} phenyl) acetic acid 26b Ethyl {4- [3- (3-phenylpropyl- 2-phenoxyphenyl (4- {3- [3- (2-Phenoxyphenyl)-l- (3- 19. 4 588. 73 87. 33 589 amino) phenylsulphanyl] phe isocyanate phenylpropyl)- nyl} acetate ureido] phenylsulphanyl} phenyl) acetic acid 27b Ethyl {4- [3- (3-phenylpropyl- allyl isocyanate (4- {3- [3-Allyl-1- (3- 15. 7 460. 60 89. 29 461 amino) phenylsulphanyl] phe phenoxypropyl) ureido] phenyl- nyl} acetate sulphanyl} phenyl) acetic acid 28b Ethyl {4- [3- (3-phenylpropyl- cyclohexyl (4- {3- [3-Cyclohexyl-1- (3- 14. 8 502. 68 57. 7 503 amino) phenylsulphanyl] phe isocyanate phenylpropyl) ureido]- nyl} acetate phenylsulphanyl} phenyl) acetic acid 29b Ethyl {4- [3- (3-phenylpropyl- 2-nitrophenyl (4- {3- [3- (2-Nitrophenyl)-l- (3- 17. 7 541. 63 92 542 amino) phenylsulphanyl] phe isocyanate phenylpropyl) ureido]- nyl} acetate phenylsulphanyl} phenyl) acetic acid 30b Ethyl f4- [3- (3-phenylpropyl- hexyl isocyanate (4- {3- [3-Hexyl-1- (3- 21. 1 504. 69 86. 67 505 amino) phenylsulphanyl] phe phenylpropyl) ureido] phenyl- nyl} acetate sulphanyl phenyl) acetic acid 31 b Ethyl {4- [3- (3-phenylpropyl- 2-naphthyl (4- {3- [3-Naphthalen-2-yl-1- (3- 19. 5 546. 69 79. 59 547 amino) phenylsulphanyl] phe isocyanate phenylpropyl) ureido]- nyl} acetate phenylsul hanyl} phenyl) acetic acid 32b Ethyl {4- [3- (3-phenylpropyl- 2-ethoxyphenyl (4- {3- [3- (2-Ethoxyphenyl)-l- (3- 20. 0 540. 68 87. 68 541 amino) phenylsulphanyl] phe isocyanate phenylpropyl) ureido]- nyl} acetate phenylsulphanyl} phenyl) acetic acid 33b Ethyl {4- [3- (3-phenylpropyl- 4-butoxyphenyl (4- {3- [3- (4-Butoxyphenyl)-1- (3- 5. 8 568. 74 80. 69 569 ( amino) phenylsulphanyl] phe isocyanate phenylpropyl)-prep) nyl} acetate ureido] phenylsulphanyl} phenyl) acetic acid 34b Ethyi {4- [3- (3-pheny) propy)- penty ! isocyanate (4- {3- [3-Pentyl-1- (3- 17. 1 490. 67 96. 36 491 amino) phenylsulphanyl] phe phenylpropyl) ureido] phenyl- nyl} acetate sulphanyl} phenyl) acetic acid 35b Ethyl f4- [3- (3-phenylpropyl- n-butyl isocyanate (4- {3- [3-Butyl-l- (3- 33. 4 476. 64 82. 58 477 amino) phenylsulphanyl] phe phenylpropyl) ureido] phenylsulphanyl}- nyl} acetate phenyl) acetic acid 36b Ethyl {4- [3- (3-phenylpropyl- 4- (4- {3- [3- (4-Dimethylaminophenyl)-1- 16. 8 539. 70 60. 24 540 amino) phenylsulphanyl] phe (dimethylamino) ph (3-phenylpropyl)- nyl} acetate enyl isocyanate ureido] phenyisulphanyl) phenyl) acetic acid 37b Ethyl [4- (3- benzyl isocyanate {4- [3- (3-Benzyl-l-phenethylureido)-24. 4 496. 63 97. 31 497 phenethylamino) phenylsulp phenylsulphanyl] phenyl} acetic acid hanylphenyl] acetate 38b Ethyl [4- (3- phenyl isocyanate {4- [3- (l-Phenethyl-3-phenylureido)-14. 0 482. 60 74. 12 483 phenethylamino) phenylsulp phenylsulphanyl] phenyl} acetic acid hanylphenyI acetate 39b Ethyl [4- (3- 2, 3-dichlorophenyl (4- {3- [3- (2, 3-Dichlorophenyl)-1- 16. 6 551. 49 79 551 phenethylamino) phenylsulp isocyanate phenethylureido]- hanylphenyl] acetate phenylsulphanyl} phenyl) acetic acid 40b Ethyl 14- (3- heptyl isocyanate {4- [3- (3-Heptyl-l- 16. 9 504. 69 58. 09 505 phenethylamino) phenylsulp phenethylureido) phenyl- hanylphenyl] acetate sul hanvildhenyi} acetic acid 41b Ethyl [4- (3- phenethyl {4- [3- (1, 3- 16. 9 510. 66 79. 84 511 phenethylamino) phenylsulp isocyanate Diphenethylureido) phenylsulphanyl]- hanylphenyl] acetate phenyl} acetic acid 42b Ethyl [4- (3- 4- (4- {3- [1-phenethyl-3- (4- 16. 0 550. 60 45. 29 551 phenethylamino) phenylsulp (trifluoromethyl) ph trifluoromethylphenyl)- hanylphenyl] acetate enyl isocyanate ureido] phenylsulphanyl} phenyl) acetic acid 43b Ethyl 14- (3- 4-methoxyphenyl (4- {3- [3- (4-Methoxyphenyl)-l-19. 0 512. 63 82. 71 513 phenethylamino) phenylsulp isocyanate phenethylureido]- hanylphenyl] acetate phenylsulphanyl} phenyl) acetic acid 44b Ethyl [4- (3- 1-adamantyl {4- [3- (3-Adamantan-1-yl-1- 14. 9 540. 73 52. 66 541 phenethylamino) phenylsulp isocyanate phenethylureido) phenyl- hanylphe yllacetate sulphan Ilphenyllacetic acid 45b Ethyl [4- (3- 2-phenoxyphenyl (4- {3- [1-Phenethyl-3- (2- 2. 9 574. 70 95. 43 575 ( phenethylamino) phenylsulp isocyanate phenoxyphenyl) ureido]- prep) hanylphenyl] acetate phenylsulphanyIphenyl) acetic acid 46b Ethyl [4- (3- allyl isocyanate {4- [3- (3-Allyi-1-16. 0 446. 57 59. 31 447 phenethylamino) phenylsulp phenethylureido) phenylsulphanyl]- hanylphenyI acetate phenyI acetic acid 47b Ethyl [4- (3- cyclohexyl {4- [3- (3-Cyclohexyl-l- 17. 6 488. 65 53. 61 489 phenethylamino) phenylsulp isocyanate phenethylureido) phenyl- hanylphenyl] acetate sulphanyl] phenyl} acetic acid 48b Ethyl [4- (3- 2-nitrophenyl (4- {3- [3- (2-Nitrophenyl)-1- 17. 2 527. 60 84 528 phenethylamino) phenylsulp isocyanate phenethylureido] phenyl- hanylphenyl] acetate sulphan Iphenyl) acetic acid 49b Ethyl [4- (3- hexyl isocyanate {4- [3- (3-Hexyl-1- 16. 3 490. 67 76. 67 491 phenethylamino) phenylsulp phenethylureido) phenylsulphanyl]- hanylphenyI acetate phenyI acetic acid 50b Ethyl [4- (3- 2-naphthyl {4- [3- (3-Naphthalen-2-yl-1- 19. 9 532. 66 72. 65 533 phenethylamino) phenylsulp isocyanate phenethylureido) phenyl- hanylphe yl] acetate sulphan I] phenyl} acetic acid 51b Ethyl [4- (3- 2-ethoxyphenyl (4-13- [3- (2-Ethoxyphenyl)-l-16. 3 526. 65 78. 93 527 phenethylamino) phenylsulp isocyanate phenethylureido]- hanylphenyl] acetate phenylsulphanyl} phenyl) acetic acid 52b Ethyl [4- (3- 4-butoxyphenyl (4- {3- [3- (4-Butoxyphenyl)-1- 19. 2 554. 71 60. 45 555 phenethylamino) phenylsulp isocyanate phenethylureido]- hanylphenyf acetate phenylsulphanyl} phenyl acetic acid 53b Ethyl [4- (3- pentyl isocyanate 14- [3- (3-Pentyl-1-6. 3 476. 64 84. 42 477 ( phenethylamino) phenylsulp phenethylureido) phenyl-prep) hanylphenylI acetate sulphan Iphenyl} acetic acid 54b Ethyl [4-(3-n-butyl isocyanate {4- [3- (3-Buty)-1-13. 2 462. 62 60. 75 463 phenethylamino) phenylsulp phethylureido) phenylsulphanyl]- hanylphenyl] acetate phenyl acetic acid 55b Ethyl [4- (4-{3-[3-(4-Dimethylaminophenyl)-1-9. 3 525. 67 18. 09 526 phenethylamino) phenylsulp (dimethylamino) ph phenethyl- hanylphenyl] acetate enyl isocynate ureido] phenylsulphanyl} phenyl) acetic acid 56b Ethyl [4- (3- benzyl isocyanate {4- [3- (3-Benzyl-l- 3. 5 490. 67 87. 45 491 ( heptylaminophenylsulphanyl heptylureido) phenylsulphanyl]- prep) ) phenyl] acetate acetic acid 57b Ethyl [4- (3- phenyl isocyanate {4- [3- (1-Heptyl-3- 3. 7 476. 64 92. 06 477 ( heptylaminophenylsulphanyl phenylureido) phenylsulphanyl]- prep) ) phenyl] acetate phenyl} acetic acid 58b Ethyl [4- (3- heptyl isocyanate {4- [3- (1, 3- 15. 6 498. 73 81. 78 499 heptylaminophenylsulphanyl Diheptylureido) phenylsulphanyl]- ) phenyl] acetate phenyl} acetic acid 59b Ethyl [4- (3- phenethyl {4- [3- (1-Heptyl-3- 4. 9 504. 69 92. 39 505 ( heptylaminophenylsulphanyl isocyanate phenethylureido) phenyl- prep) ) phenyl] acetate sulphanyl] phenyl} acetic acid 60b Ethyl [4- (3- 4- (4- {3- [1-Heptyl-3- (4- 3. 6 544. 64 79. 05 545 ( heptylaminophenylsulphanyl (trifluoromethyl) ph trifluoromethylphenyl)-prep) ) phenyl] acetate enyl isocyanate ureido] phenylsulphanyl} phenyl) acetic acid 61 b Ethyl [4- (3- 4-methoxyphenyl (4- {3- [1-Heptyl-3- (4- 2. 7 506. 66 86. 14 507 ( heptylaminophenylsulphanyl isocyanate methoxyphenyl) ureido]- prep) ) phenyl] acetate phenylsulphanyl} phenyl) acetic acid 62b Ethyl [4- (3- 1-adamantyl {4- [3- (3-Adamantan-1-yl-l-11. 2 534. 76 35 535 heptylaminophenylsulphanyl isocyanate heptylureido)- hen l acetate hen Isul han 1 hen I acetic acid 63b Ethyl [4- (3- 2-phenoxyphenyl (4- {3- [l-Heptyl-3- (2- 8. 7 568. 74 88. 55 569 heptylaminophenylsulphanyl isocyanate phenoxyphenyl) ureido]- ) phenyl] acetate phenylsulphanyl} phenyl) acetic acid 64b Ethyl [4- (3- allyl isocyanate {4- [3- (3-Allyl-1- 3. 7 440. 61 85. 5 441 heptylaminophenylsulphanyl heptylureido) phenylsulphanyl]- ) phenyl] acetate phenyl} acetic acid 65b Ethyl 14- (3- cyclohexyl {4- [3- (3-Cyclohexyl-I-17. 1 482. 69 82. 19 483 heptylaminophenylsulphanyl isocyanate heptylureido) phenyl- ) phenyl] acetate sulphanyl] phenyl} acetic acid 66b Ethyl [4- (3- 2-nitrophenyl (4- {3- [1-Heptyl-3- (2- 10. 8 521. 64 91 522 heptylaminophenylsulphanyl isocyanate nitrophenyl) ureido]- ) phenyllacetate hanyllphenyl) acetic acid 67b Ethyl [4- (3- hexyl isocyanate {4- [3- (1-Heptyl-3-hexylureido) phenyl- 16. 6 484. 70 83. 45 485 heptylaminophenylsulphanyl sulphanyl] phenyl} acetic acid ) phenyl] acetate 68b Ethyl 14- (3- 2-naphthyl {4- [3- (l-Heptyl-3-naphthalen-2-yi-14. 4 526. 70 74. 3 527 heptylaminophenylsulphanyl isocyanate ureido) phenylsulphanyl] phenyl} acetic ) phenyl] acetate acid 69b Ethyl [4- (3- 2-ethoxypheny ! (4- {3- [3- (2-Ethoxypheny))-1- 18. 6 520. 69 88. 51 521 heptylaminophenylsulphanyl isocyanate heptylureido]- ) phenyl] acetate phenylsulphanyl} phenyl) acetic acid 70b Ethyl [4- (3- 4-butoxyphenyl (4- {3- [3- (4-Butoxyphenyl)-1- 25. 5 548. 75 56. 02 549 heptylaminophenylsulphanyl isocyanate heptylureido]- ) phenyl] acetate phenylsulphanyl} phenyl) acetic acid 71 b Ethyl [4- (3- pentyl isocyanate {4- [3- (l-Heptyl-3- 16. 2 470. 68 89. 45 471 heptylaminophenylsulphanyl pentylureido) phenylsulphanyl]- phenyl] acetate phenyl} acetic acid 72b Ethyl 14- (3- n-butyl isocyanate {4- [3- (3-Butyl-l- 11. 4 456. 65 91. 58 457 heptylaminophenylsulphanyl heptylureido) phenylsulphanyl]- ) phenyl] acetate phenyl} acetic acid 73b Ethyl [4- (3- 4- (4- {3-j3- (4-Dimethylaminophenyl)-1- 12. 5 519. 71 47. 52 520 heptylaminophenylsulphanyl (dimethylamino) ph heptylureido]- ) phenyl] acetate enyl isocyanate phenylsulphanyl} phenyl) acetic acid 74b Ethyl [4- (3- benzyi isocyanate {4- [3- (3-Benzy)-1-8. 3448. 58 80. 03 449 butylaminophenylsulphanyl) butylureido) phenylsulphanyl]- phenyllacetate phenyl) cetic acid 75b Ethyl [4- (3- phenyl isocyanate {4- [3- (l-Butyl-3-5. 5 434. 56 81. 38 435 butylaminophenylsulphanyl) phenylureido) phenylsulphanyl]- phenyl] acetate etic acid 76b Ethyl [4- (3- 2, 3-dichlorophenyl (4- {3- [1-Butyl-3- (2, 3- 2. 6 503. 45 82. 37 503 butylaminophenylsulphanyl) isocyanate dichlorophenyl) ureido]- phenyl] acetate phenylsulphanyl} phenyl) acetic acid 77b Ethyl [4- (3- heptyl isocyanate {4- [3- (l-Butyl-3- 8. 5 456. 65 75. 56 457 butylaminophenylsulphanyl) heptylureido) phenylsulphanyl]- phenyllacetate hen I acetic acid 78b Ethyl [4- (3- phenethyl {4- [3- (1-Butyl-3- 8. 3 462. 61 79. 07 463 butylaminophenylsulphanyl) isocyanate phenethylureido) phenyfsulphanyl]- phenyl] acetate etic acid 79b Ethyl [4- (3- 4- (4- {3- [l-Butyl-3- (4- 6. 2 502. 55 58. 9 503 butylaminophenylsulphanyl) (trifluoromethyl) ph trifluoromethylphenyl) ureido]- phenyl] acetate enyl isocyanate phenylsulphanyl} phenyl) acetic acid 80b Ethyl [4- (3- 4-methoxyphenyl (4- {3- [1-Butyl-3- (4- 6. 8 464. 58 76. 76 465 butylaminophenylsulphanyl) isocyanate methoxyphenyl) ureido]- phenyl] acetate phenylsulphanyl} phenyl) acetic acid 81 b Ethyl [4- (3- 1-adamantyl 14- [3- (3-Adamantan-I-yi-I-6. 8 492. 68 16. 8 493 butylaminophenylsulphanyl) isocyanate butylureido) phenyl- phenyllacetate sul han i phenyllacetic acid 82b Ethyl [4- (3- 2-phenoxyphenyl (4- {3- [1-Butyl-3- (2- 8. 4 526. 65 84. 34 527 butylaminophenylsulphanyl) isocyanate phenoxyphenyl) ureido]- phenyllacetate hen lsul hanyl) phenyl) acetic acid 83b Ethyl [4- (3- allyl isocyanate {4- [3- (3-Allyl-1- 8. 0 398. 52 77. 42 399 butylaminophenylsulphanyl) butylureido) phenylsulphanyl]- phenyl] acetate phenyl} acetic acid 84b Ethyl 14- (3- cyclohexyl {4- [3- (l-Butyl-3-7. 2 440. 61 65. 3 441 butylaminophenylsulphanyl) isocyanate cyclohexylureido) phenyl- hen I acetate sul han_I hen I acetic acid P Yd P Y. P Y 85b Ethyl [4- (3- 2-nitrophenyl (4- {3- [1-Butyl-3- (2-nitrophenyl) ureido]- 7. 7 479. 55 91 480 butylaminophenylsulphanyl) isocyanate phenylsulphanyl} phenyl) acetic acid phenyl] acetate 86b Ethyl [4- (3- hexyl isocyanate {4- [3- (l-Butyl-3-hexylureido) phenyl- 7. 3 442. 62 85. 74 443 butylaminophenylsulphanyl) sulphanyl] phenyl} acetic acid phenyllacetate 87b Ethyl [4- (3- 2-naphthyl {4- [3- (l-Butyl-3-naphthalen-2-yl-7. 7 484. 62 75. 14 485 butylaminophenylsulphanyl) isocyanate ureido) phenylsulphanyl] phenyl} acetic phenyl] acetate acid 88b Ethyl [4- (3- 2-ethoxyphenyl (4- {3- [1-Butyl-3- (2- 7. 8 478. 61 84. 83 479 butylaminophenylsulphanyl) isocyanate ethoxyphenyl) ureido] phenyl- phenyl] acetate sulphanyl} phenyl) acetic acid 89b Ethyl [4- (3- 4-butoxyphenyl (4- {3- [3- (4-Butoxyphenyl)-1- 2. 4 506. 66 79. 69 507 butylaminophenylsulphanyl) isocyanate butylureido] phenyl- phenyl] acetate phenyl) acetic acid 90b Ethyl 14- (3- pentyl isocyanate {4- [3- (l-Butyl-3-7. 9 428. 59 74. 5 429 butylaminophenylsulphanyl) pentylureido) phenylsulphanyl]- phenyl] acetate phenyl} acetic acid 91 b Ethyl [4- (3- n-butyl isocyanate {4- [3- (1, 3- 3. 1 414. 57 74. 38 415 butylaminophenylsulphanyl) Dibutylureido) phenylsulphanyl] phenyl) phenyl] acetate acetic acid 92b Ethyl {4- [4- (3- benzyl isocyanate (4- {4- [3-Benzyl-1- (3- 15. 1 510. 66 92. 08 511 phenylpropylamino) phenyls phenylpropyl) ureido] phenyl- ulphanyIphenyI acetate sulphanyl phenyl) acetic acid 93b Ethyl {4- [4- (3- heptyl isocyanate (4- {4- [3-Heptyl-1- (3- 3. 4 518. 72 70. 96 519 phenylpropylamino) phenyls phenylpropyl) ureido] phenyl- ulphanyl] phenyl} acetate sulphanyl} phenyl) acetic acid 94b Ethyl {4- [4- (3- phenethyl (4- {4- [3-Phenethyl-I- (3- 14. 7 524. 68 82. 71 525 phenylpropylamino) phenyls isocyanate phenylpropyl) ureido]- ulphanyl] phenyl} acetate phenylsulphanyl} phenyl) àcetic acid 95b Ethyl {4- [4- (3- 4- (4- {4- [1- (3-Phenylpropyl)-3- (4-tri- 7. 1 564. 63 22. 07 565 phenylpropylamino) phenyls (trifluoromethyl) ph fluoromethylphenyl) ureido] phenylsulp ulphanyl] phenyl} acetate enyl isocyanate hanyl} phenyl) acetic acid 96b Ethyl {4- [4- (3- 2-phenoxyphenyl (4- {4- [3- (2-Phenoxyphenyl)-l- (3- 19. 3 588. 73 76. 89 589 phenylpropylamino) phenyls isocyanate phenyl- ulphanyl] phenyl} acetate propyl) ureido] phenylsulphanyl} phenyl) acetic acid 97b Ethyl {4- [4- (3- allyl isocyanate (4- {4- [3-Allyi-1- (3- 11. 5 460. 60 88. 2 461 phenylpropylamino) phenyls phenylpropyl) ureido] phenyl- ulphanyIphenyl} acetate sulphanyIphenyl) acetic acid 98b Ethyl {4- [4- (3- cyclohexyl (4- {4- [3-Cyclohexyl-1- (3- 11. 8 502. 68 45. 57 503 phenylpropylamino) phenyls isocyanate phenylpropyl) ureido]- ulphanyllphenyl) acetate phenylsul hanyllphenyl) acetic acid 99b Ethyl {4- [4- (3- 2-nitrophenyl (4-f4- [3- (2-Nitrophenyl)-l- (3- 30. 1 541. 63 77 542 phenylpropylamino) phenyls isocyanate phenylpropyl)- ulphanyl] phenyl} acetate ureido] phenylsulphanyl} phenyl) acetic acid 100b MY 824. 074. 5 hexyl isocyanate (4- {4- [3-Hexyl-1- (3- 12. 9 504. 69 79. 2 505 phenylpropyl) ureido] phenyl- sulphanyl} phenyl) acetic acid 101 b Ethyl {4- [4- (3- 2-naphthyl (4- {4- [3-Naphthalen-2-yl-1- (3-phenyl- 14. 8 546. 69 54. 03 547 phenylpropylamino) phenyls isocyanate propyl) ureido] phenylsulphanyl} phenyl) ulphanyl] phenyl} acetate acetic acid 102b Ethyl {4- [4- (3- 2-ethoxyphenyl (4-14- [3- (2-Ethoxyphenyl)-l- (3- 34. 3 540. 68 70. 75 541 phenylpropylamino) phenyls isocyanate phenylpropyl)- ulphanyl] phenyl} acetate ureido] phenylsulphanyl} phenyl) acetic acid 103b MY 824. 074. 5 4-butoxyphenyl (4- {4- [3- (4-Butoxyphenyl)-1- (3- 17. 1 568. 74 36. 13 569 isocyanate phenylpropyl)- ureido] phenylsulphanyl} phenyl) acetic acid 104b Ethyl {4- [4- (3- pentyl isocyanate (4- {4- [3-Pentyl-1- (3- 14. 1 490. 67 73. 12 491 phenylpropylamino) phenyls phenylpropyl) ureido]- ulphanyl] phenyl} acetate phenylsulphanyl} phenyl) acetic acid 105b Ethyl {4- [4- (3- n-butyl isocyanate (4- {4- [3-Butyl-1- (3- 11. 9 476. 64 94. 96 477 phenylpropylamino) phenyls phenylpropyl) ureido]- ulphanyl] phenyl} acetate phenylsulphanyl} phenyl) acetic acid 106b Ethyl [4- (4- benzyl isocyanate {4- [4- (3-Benzyl-l-12. 8 496. 63 92. 47 497 phenethylaminophenylsulph phenethylureido) phenyl- anyl) phenyl] acetate sulphanyl] phenyl} acetic acid 107b Ethyl [4- (4- phenyl isocyanate {4- [4- (1-Phenethyl-3- 11. 7 482. 60 75. 58 483 phenethylaminophenylsulph phenylureido) phenyl- anyl) phenyl] acetate sulphanyl] phenyl} acetic acid 108b Ethyl [4- (4- 2, 3-dichlorophenyl (4- {4- [3- (2, 3-Dichlorophenyl)-1- 17. 1 551. 49 24. 78 551 phenethylaminophenylsulph isocyanate phenethylureido]- anyl) phenyl] acetate phenylsulphanyl} phenyl) acetic acid 109b Ethyl [4- (4- heptyl isocyanate {4- [4- (3-Heptyl-l- 20. 5 504. 69 82. 55 505 phenethylaminophenylsulph phenethylureido) phenyl- anyl) phenyl] acetate sulphanyl] phenyl} acetic acid 110b Ethy) [4- (4- phenethy) {4- [4- (1, 3- 12. 4 510. 66 83. 74 511 phenethylaminophenylsulph isocyanate Diphenethylureido) phenylsulphanyl]- anyl) phenyl] acetate phenyl} acetic acid 111 b Ethyl [4- (4- 4- (4- {4- [1-Phenethyl-3- (4- 24. 4 550. 60 20. 11 551 phenethylaminophenylsulph (trifluoromethyl) ph trifluoromethyl- anyl) phenyl] acetate enyl isocyanate phenyl) ureido] phenylsulphanyl} phenyl ) acetic acid 112b Ethyl [4- (4- 4-methoxyphenyl (4- {4- (3-Methoxyphenyl)-1- 13. 5 512. 63 96. 49 513 phenethylaminophenylsulph isocyanate phenethylureido]- anyl) phenyl] acetate phenylsulphanyl} phenyl) acetic acid 113b Ethyl [4- (4- 1-adamantyl {4- [4- (3-Adamantan-1-yl-1- 12. 2 540. 73 50. 4 541 phenethylaminophenylsulph isocyanate phenethylureido)- anyl) phenyl] acetate phenylsulphanyl] phenyl} acetic acid 114b Ethyl [4- (4- 2-phenoxyphenyl (4- {4- [1-Phenethyl-3- (2- 13. 2 574. 70 86. 26 575 phenethylaminophenylsulph isocyanate phenoxyphenyl) ureido]- anyl) phenyl] acetate phenylsulphanyl} phenyl) acetic acid 115b Ethyl [4- (4- ailyl isocyanate {4- [4- (3-Allyi-1-8. 3 446. 57 83. 01 447 phenethylaminophenylsulph phenethylureido) phenyl- anyl) phenyl] acetate sulphanyl] phenyl} acetic acid 116b Ethyl [4- (4- cyclohexyl {4- [4- (3-Cyclohexyl-1-9. 3 488. 65 77. 7 489 phenethylaminophenylsulph isocyanate phenethylureido)- anyl) phenyl] acetate phenylsulphanylphenyl} acetic acid 117b Ethyl [4- (4- 2-nitrophenyl (4- {4- [3- (2-Nitrophenyl)-1- 11. 9 527. 60 88 528 phenethylaminophenylsulph isocyanate phenethylureido]- _ ç anyl) phenyl] acetate phenyisulphanyXp e yyl) acetic acid _ 118b Ethyl [4- (4- hexyl isocyanate {4- [4- (3-Hexyl-I-10. 9 490. 67 71. 58 491 phenethylaminophenylsulph phenethylureido) phenyl- an I hen I acetate sul han I hen 1 acetic acid 119b Ethyl 14- (4- 2-naphthyl {4- [4- (3-Naphthalen-2-yl-l-7. 9 532. 66 60. 52 533 phenethylaminophenylsulph isocyanate phenethylureido)- anyl) phenyl] acetate phenylsulphanyl] phenyl} acetic acid 120b Ethyl [4- (4- 2-ethoxyphenyl (4- {4- [3- (2-Ethoxyphenyl)-1- 16. 2 526. 65 82. 87 527 phenethylaminophenylsulph isocyanate phenethylureido]- anyl) phenyl] acetate phenylsulphanyl} phenyl) acetic acid 121 b Ethyl [4- (4- 4-butoxyphenyl (4- {4- [3- (4-Butoxyphenyl)-1- 20. 6 554. 71 38. 53 555 phenethylaminophenylsulph isocyanate phenethylureido]- anylßphenyl] acetate phenylsulphanyl} phenyl) acetic acid 122b Ethyl 14- (4- pentyl isocyanate {4- [4- (3-Pentyl-1- 3. 8 476. 64 81 477 phenethylaminophenylsulph phenethylureido) phenyl- anyl) phenyl] acetate sulphanyl] phenyl} acetic acid 123b Ethyl [4- (4- n-butyl isocyanate {4- [4- (3-Butyl-1-10. 9 462. 61 79. 59 463 phenethylaminophenylsulph phenethylureido) phenylsulphanyl]- _ an_I hen I _ace_tat_e __ _ _ _ hen I acetic acid _ _ _ _ _ _ 124b Ethyl [4- (4- benzyl isocyanate 14- [4- (3-Benzyl-l-28. 1 1490. 67 85. 96 491 heptylaminophenylsulphanyl heptylureido) phenylsulphanyl]- ) phenyllacetate hen I cetic acid 125b Ethyl [4- (4- phenyl isocyanate f4- [4- (1-heptyl-3- 15. 0 476. 64 96. 78 477 heptylaminophenylsulphanyl phenylureido) phenylsulphanyl]- ) phenyl] acetate phenyl} acetic acid 126b Ethyl [4- (4- 2, 3-dichlorophenyl (4- {4- [3- (2, 3-Dichlorophenyl)-1- 16. 9 545. 53 43 546 heptylaminophenylsulphanyl isocyanate heptylureido]- ) phenyl] acetate phenylsulphanyl} phenyl) acetic acid 127b Ethyl [4- (4- heptyl isocyanate {4- [4- (1, 3- 22. 3 498. 73 85. 48 499 heptylaminophenylsulphanyl Diheptylureido) phenylsulphanyl] pheny ) I acetate I acetic acid 128b Ethyl 14- (4- phenethyl {4- [4- (l-Heptyl-3-18. 6 504. 69 98. 29 505 heptylaminopheny4sulphanyl isocyanate phenethylureido) phenyl- ) phenyl] acetate sul han I phenyl} acetic acid 129b Ethyl [4- (4- 4- (4- {4- [1-Heptyl-3- (4-trifluoromethyl- 3. 8 544. 64 75. 16 545 ( heptylaminophenylsulphanyl (trifluoromethyl) ph phenyl) ureido] phenylsulphanyl} phenyl prep) ) phenyl] acetate enyl isocyanate) acetic acid 130b Ethyl [4- (4- 4-methoxyphenyl (4- {4- [l-Heptyl-3- (4- 18. 6 506. 66 92. 79 507 heptylaminophenylsulphanyl isocyanate methoxyphenyl) ureido] phenyl- ) phenyl] acetate sulphanyl} phenyl) acetic acid 131 b Ethyl [4- (4- 1-adamantyl {4- [4- (3-Adamantan-1-yl-1- 10. 3 534. 76 50. 19 535 heptylaminophenylsulphanyl isocyanate heptylureido)- ) phenyl] acetate hen Isul hanyl] phenyl} acetic acid 132b Ethyl [4- (4- 2-phenoxyphenyl (4- {4- [1-Heptyl-3- (2- 5. 1 568. 74 92. 79 569 heptylaminophenylsulphanyl isocyanate phenoxyphenyl) ureido]- ) phenyl] acetate phenylsulphanyl} phenyl) acetic acid 133b Ethyl 14- (4- allyl isocyanate {4- [4- (3-Allyl-l- 10. 0 440. 61 86. 18 441 heptylaminophenylsulphanyl heptylureido) phenylsulphanyl]- ) phenyl] acetate phenyl} acetic acid 134b Ethyl [4- (4- cyclohexyl {4- [4- (3-Cyclohexyl-1- 26. 6 482. 69 83. 74 483 heptylaminophenylsulphanyl isocyanate heptylureido) phenyl- ) phenyl] acetate sulphanyl] phenyl} acetic acid 135b Ethyl [4- (4- 2-nitrophenyl (4- {4- [1-Heptyl-3- (2- 12. 4 521. 64 92 522 heptylaminophenylsulphanyl isocyanate nitrophenyl) ureido] phenyl- ) phenyllacetate sulphanyllphenyl) acetic acid 136b Ethyl [4- (4- hexyl isocyanate {4- [4- (l-Heptyl-3-13. 9 484. 70 94. 84 485 heptylaminophenylsulphanyl hexylureido) phenylsulphanyl]- ) phenyl] acetate phenyl} acetic acid 137b Ethyl [4- (4- 2-naphthyl {4- [4- (1-Heptyl-3-naphthalen-2-yl- 15. 2 526. 70 77. 28 527 heptylaminophehylsulphanyl isocyanate ureido) phenylsulphanyl] phenyl} acetic ) phenyl] acetate acid 138b Ethyl [4- (4- 2-ethoxyphenyl (4- {4- [3- (2-Ethoxyphenyl)-1- 20. 8 520. 69 83. 86 521 heptylaminophenylsulphanyl isocyanate heptylureido]- ) phenyl] acetate phenylsulphanyl} phenyl) acetic acid 139b Ethyl [4- (4- 4-butoxyphenyl (4- {4- [3- (4-Butoxyphenyl)-1- 28. 8 548. 75 31. 13 549 heptylaminophenylsulphanyl isocyanate heptylureido] phenyl- ) phenyl] acetate sulphanyl} phenyl) acetic acid 140b Ethyl [4- (4- pentyl isocyanate {4- [4- (l-Heptyl-3-13. 3 470. 68 76. 93 471 heptylaminophenylsulphanyl pentylureido) phenylsulphanyl]- ) phenyl] acetate phenyl} acetic acid 141b Ethyl [4- (4- n-butyl isocyanate {4- [4- (3-Butyl-l- 8. 2 456. 65 73. 31 457 heptylaminophenylsulphanyl heptylureido) phenylsulphanyl]- ) phenyllacetate hen I ac tic acid

Compounds 18a to 141a are the esters corresponding to the acids 18b to 141b obtained before the saponification step.

EXAMPLE 142-CROSS CURVE PPAR TRANSACTIVATION TEST The activation of receptors with an agonist (activator) in HeLN cells leads to the expression of a reporter gene, luciferase, which, in the presence of a substrate, generates light. The modulation of the receptors is measured as quantity of luminescence produced after incubating the cells in the presence of a reference agonist. The ligands will displace the agonist from its site. The measurement of the activity is performed by quantification of the light produced. This measurement makes it possible to determine the modulator activity of the compounds according to the invention by determining the constant which represents the affinity of the molecule for the receptor. Since this value can fluctuate according to the basal activity and the expression of the receptor, it is called apparent Kd (KdApp in nM).

To determine this constant,"cross curves"for the product to be tested against a reference agonist are produced in a 96-well plate : 10 concentrations of the test product plus a concentration 0 are placed in a line, and 7 concentrations of the agonist plus one concentration 0 are placed in a column. This represents 88 measurement points for 1 product and 1 receptor. The 8 remaining wells are used for repeatability controls.

In each well, the cells are in contact with a concentration of the product to be tested and a concentration of the reference agonist, 2- (4- {2- [3- (2, 4-difluorophenyl)-1-heptylureido] ethyl} phenylsulphanyl)- 2-methylpropionic acid for PPARa, {2-methyl-4- [4-methyl- 2- (4-trifluoromethylphenyl) thiazol-5-ylmethylsulphanyl] phenoxy} acetic acid for PPAR and 5- {4- [2- (methylpyridin-2-ylamino) ethoxy] benzyl} thiazolidine-2, 4-dione

for PPARy. Measurements are also carried out for the controls total agonist with the same products.

The HeLN cell lines used are stable transfectants containing the plasmids ERE-ßGlob-Luc-SV-Neo (reporter gene) and PPAR (a, 6, y) Gal-hPPAR.

These cells are inoculated into 96-well plates in an amount of 10 000 cells per well in 100 pi of DMEM medium free of phenol red and supplemented with 10% lipid- free calf serum. The plates are then incubated at 37°C, 7% C02 for 16 hours.

The various dilutions of the test products and of the reference ligand are added in an amount of 5 lli per well. The plates are then incubated for 18 hours at 37°C, 7% C02. The culture medium is removed by turning over and 100 gel of a 1 : 1 PBS/Luciferin mixture are added to each well. After 5 minutes, the plates are read by the luminescence reader.

These cross curves make it possible to determine the AC50 values (concentrations at which 50% activation is observed) for the reference ligand at various concentrations of test product. These AC50 values are used to calculate the Schild regression by plotting a straight line corresponding to the Schild equation ("quantitation in receptor pharmacology"Terry P. Kenakin, Receptors and Channels, 2001, 7, 371-385) which leads to Kd app values being obtained (in nM).

Transactivation results: Compounds PPAR alpha PPAR delta PPAR gamma Kd app (nM) Kd app (in nM) Kd app (in nM) Reference 1 2- (4- {2- [3- (2, 4-Difluorophenyl)- 200 n. a. n. a. 1-heptylureido] ethyl} phenylsulphanyl)-2-methyl propionic acid Reference 2 : {2-Methyl-4- [4-methyl-2- (4-tri- n. a. 10 n. a. fluoromethylphenyl) thiazol-5-ylmethylsulphanyl] phenoxy} acetic acid Reference 3 : 5- {4- [2- (Methylpyridin-2-ylamino)- n. a. n. a. 30 ethoxy] benzyl} thiazolidine-2, 4-dione Example 30b 8 000 120 2 000 Example 116b 250 120 500 n.a. means not active

EXAMPLE 143-COMPOSITIONS Various concrete formulations based on the compounds according to the invention have been illustrated in this example.

A-ORAL ROUTE (a) 0. 2 g tablet - Compound of Example 2a 0. 001 g - Starch 0. 114 g - Bicalcium phosphate 0. 020 g - Silica 0. 020 g - Lactose 0. 030 g - Talc 0. 010 g - Magnesium stearate 0. 005 g (b) Oral suspension in 5 ml vials - Compound of Example 7b 0. 001 g - Glycerine 0. 500 g - Sorbitol at 70% 0. 500 g - Sodium saccharinate 0. 010 g - Methyl para-hydroxybenzoate 0. 040 g - Flavouring qs - Purified water qs 5 ml (c) 0. 8 g tablet - Compound of Example 45b 0. 500 g - Pregelatinized starch 0. 100 g - Microcrystalline cellulose 0. 115 g - Lactose 0. 075 g - Magnesium stearate 0. 010 g

(d) Oral suspension in 10 ml vials - Compound of Example 115a 0. 200 g - Glycerine 1. 000 g <BR> <BR> <BR> <BR> <BR> - Sorbitol at 70% 1. 000 g - Sodium saccharinate 0. 010 g - Methyl para-hydroxybenzoate 0. 080 g - Flavouring qs - Purified water qs 10 ml B-TOPICAL ROUTE (a) Salve - Compound of Example 76b 0. 020 g -Isopropyl myristate 81. 700 g - Fluid liquid paraffin 9. 100 g - Silica ("Aerosil 200"sold by DEGUSSA) 9. 180 g (b) Salve - Compound of Example 95a 0. 300 g - Petroleum jelly qs 100 g (c) Nonionic water-in-oil cream - Compound of Example 46a 0. 100 g - Mixture of emulsifying lanolin alcohols, waxes and oils ("anhydrous eucerin"sold by BDF) 39. 900 g - Methyl para-hydroxybenzoate 0. 075 g - Propyl para-hydroxybenzoate 0. 075 g - Sterile demineralized water qs 100 g

(d) Lotion - Compound of Example 57a 0. 100 g - Polyethylene glycol (PEG 400) 69. 900 g - Ethanol at 95% 30. 000 g (e) Hydrophobic salve - Compound of Example 21b 0. 300 g - Isopropyl myristate 36. 400 g - Silicone oil ("Rhodorsil 47 V 300"sold by RHONE-POULENC) 36. 400 g -Beeswax 13. 600 g - Silicone oil ("Abil 300, 000 cst"sold by GOLDSCHMIDT) qs 100 g (f) Nonionic oil-in-water cream - Compound of Example 19a 1. 000 g - Cetyl alcohol 4. 000 g - Glyceryl monostearate 2. 500 g - PEG 50 stearate 2. 500 g - Shea butter 9. 200 g - Propylene glycol 2. 000 g - Methyl para-hydroxybenzoate 0. 075 g - Propyl para-hydroxybenzoate 0. 075 g - Sterile demineralized water qs 100 g