WO2006079568A2

WO2006079568A2 - Use of 3-sulfanylpropanamide derivatives for stimulating hair and eyelash growth and/or for stopping the loss and/or limiting the depigmentation thereof

Info

Publication number: WO2006079568A2
Application number: PCT/EP2006/001545
Authority: WO
Inventors: Philippe Breton; Christophe Boulle
Original assignee: L'oreal
Priority date: 2005-01-31
Filing date: 2006-01-23
Publication date: 2006-08-03
Also published as: WO2006079568A3; EP1853352A2; JP2008528539A

Abstract

The invention relates to the use of an effective amount of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof : (I) in which: a) R1 and R2 independently represent: a hydrogen atom; an optionally substituted C1-C2O alkyl radical; an optionally substituted, saturated or unsaturated hydrocarbon-based ring; b) R3 represents: a hydrogen atom; an optionally substituted C1-C20 alkyl radical; an optionally substituted saturated hydrocarbon-based ring; in a cosmetic composition for caring for and/or making up keratin fibres, especially human keratin fibres, to induce and/or stimulate their growth, to stop their loss and/or to increase their density. The invention also relates to novel 3-sulfanylpropanamide compounds and to compositions containing them, which are intended to increase their density of keratin fibres and/or to improve their appearance and/or to reduce their canities. The invention also relates to a cosmetic treatment process which is intended to stimulate the growth of keratin fibres and/or to stop their loss and/or to stimulate their pigmentation and/or to limit their depigmentation and/or bleaching.

Description

Use of 3-sulfanylpropanamide derivatives for stimulating hair and eyelash growth and/or for stopping the loss and/or limiting the depigmentation thereof

FIELD OF THE INVENTION The invention relates to the use of a

3-sulfanylpropanamide compound in a composition for promoting and/or inducing and/or stimulating the pigmentation of keratin fibres and also for limiting their depigmentation and/or bleaching. The invention also relates to novel

3-sulfanylpropanamide compounds and to compositions containing them intended to be used for increasing the density and/or improving the appearance of the said keratin fibres and/or for reducing canities thereof . The invention also relates to a cosmetic treatment process for stimulating the growth of keratin fibres and/or for stopping their loss and/or for stimulating their pigmentation and/or for limiting their depigmentation and/or bleaching . The human keratin fibres to which the invention applies are especially head hair, the eyebrows, the eyelashes , beard hairs , moustache hairs and pubic hairs . More especially, the invention applies to human head hair and/or eyelashes . The invention also applies to human nails .

BACKGROUND OF THE IMVENTION Hair growth and hair renewal are mainly 01545

determined by the activity of the hair follicles and of their matrix environment . Their activity is cyclical and comprises essentially three phases, namely the anagenic phase, the catagenic phase and the telogenic phase .

The anagenic phase (active phase or growth phase) , which lasts several years and during which the hair gets longer, is followed by a very short and transient catagenic phase that lasts a few weeks . During this phase, the hair undergoes a change, the follicle becomes atrophied and its dermal implantation appears higher and higher .

The terminal phase or telogenic phase, which lasts a few months, corresponds to a resting phase of the follicle and the hair ends up by falling out . At the end of this rest period, a new follicle is regenerated in situ and another cycle begins .

The head of hair is thus under permanent renewal, and, out of the approximately 150 000 hairs that make up a head of hair, about 10% are at rest and will be replaced within a few months .

The natural loss or falling-out of the hair may be estimated, on average, as being a few hundred hairs per day for a normal physiological state . This process of permanent physical renewal undergoes a natural change during ageing, the hairs become finer and their cycles shorter . In addition, various causes may result in a substantial, temporary or permanent loss of hair . This may be loss and impairment of hair at the terminal stage of pregnancy (post-partum) , during states of dietary malnutrition or imbalance, during physiological stress, or during states of asthenia or of hormonal dysfunction, as may be the case during or at the terminal stage of the menopause . It may also be a case of loss or impairment of the hair related to seasonal phenomena .

It may also be a matter of alopecia, which is essentially due to a disturbance in hair renewal, resulting, in a first stage, in acceleration of the frequency of the cycles to the detriment of the quality of the hair, and then of their quantity. The successive growth cycles result in hairs that are finer and finer and shorter and shorter, gradually transforming into an unpigmented down, thus resulting in a progressive impoverishment of the head of hair. Certain areas are preferentially affected, especially the temporal or frontal lobes in men, and a diffuse alopecia of the crown of the head in women .

The term alopecia also covers a whole family of afflictions of hair follicles whose final consequence is the permanent, partial or general loss of the hair . This is more particularly a matter of androgenic alopecia . In a large number of cases , early loss of hair occurs in genetically predisposed individuals ; this is then a matter of androchronogenetic alopecia. This form of alopecia especially affects men . In certain dermatoses of the scalp with an inflammatory component, for instance psoriasis or seborrhoeic dermatitis, hair loss may be greatly accentuated or may result in highly disrupted follicular cycles . The cosmetics and pharmaceutical industries have for many years been investigating compositions for eliminating or reducing alopecia, and especially for inducing or stimulating hair growth or reducing its loss . In this perspective, a large number of compositions comprising very diverse active agents have already been proposed, for instance 2, 4-diamino- 6-piperidinopyrimidine 3-oxide, or "minoxidil",, described in patents US 4 139 619 and US 4 596 812 , or the numerous derivatives thereof such as those described in patent applications EP 0 353 123, EP 0 356 271 , EP 0 408 442, EP 0 522 964 , EP 0 420 707 , EP 0 459 890 and EP 0 519 819.

Clinical studies have shown that PGF2-α analogues have the property of inducing the growth of body hairs and eyelashes in man and animals (Murray A . and Johnstone M. D . , 1997 , Am . J. Opht . , 124 ( 4 ) , 544- 547) . In man, tests performed on the scalp have shown that a prostaglandin E2 analogue (viprostol) has the property of increasing the hair density (Roenigk H . H. , 1988, Clinic Dermatol . , 6 (4) , 119-121) . Moreover, patent WO 98/33497 describes pharmaceutical compositions containing prostaglandins or prostaglandin derivatives, for combating hair loss in man . Prostaglandins of the type A2, F2α and E2 are mentioned as being preferred . However, prostaglandins are molecules with a very short biological half-life, which act in an autocrine or paracrine manner, this reflecting the local and labile nature of the metabolism of prostaglandins (Narumiya S . et al . , 1999, Physiol . Rev. , 79 (4 ) , 1193-1226) .

It is thus seen to be important, in order to maintain and/or increase the hair density in man, to preserve the endogenous reserves of PGF2-α and similarly of PGE2 in various compartments of the hair follicle or its immediate cutaneous environment .

One solution that gives good results is the use of lipoxygenase-inhibiting compounds and/or cyclooxygenase-inducing compounds to promote hair growth; one theory is that the use of such compounds directs the metabolism of fatty acids- towards the endogenous synthesis of prostaglandins in preference to other routes . However, to further improve these results , it would be desirable to be able to prolong the activity of the prostaglandins involved in growing the hair and keeping it alive . It is moreover well known that the programmes of differentiation of the keratinocytes of the epidermis and of the hair follicle are clearly different . Thus , it is known that the keratins of the hair shaft represent a family (Langbein et al . , 2001, J. Biol . Chem. 276 : 35123-35132 ) that is different from the one expressed in the epidermis, that differentiation markers such as the keratins K_x and Ki₀ are not expressed in the hair follicle and in particular in the outer sheath (Lenoir et al . , 1988 , Dev. Biol . 130 : 610-620 ) , that trichohyalin (O' Guin et al . , 1992, J. Invest . Dermatol . 98 : 24-32) and keratin Kβirs (Porter et al . , 2001, Br . J . Dermatol . 145 : 558- 568) are expressed in the hair follicle, in particular in the inner sheath, but not in the epidermis, and that type-1 cyclooxygenase, although expressed in the epidermis, is not expressed in the keratinocytes of the hair follicle but in the dermal papilla (Michelet . et al . , 1997 , J. Invest . Dermatol . 108 : 205-209) .

The Applicant has now demonstrated that an enzyme specifically involved in the degradation of these prostaglandins is present in the dermal papilla of the hair, which is a compartment that is a decisive factor in the life of the hair . Specifically, the Applicant has now proven the presence of type-1 15-hydroxyprostaglandin dehydrogenase (abbreviated to 15-PGDH) at this level . The Applicant has also shown that the inhibition of type-1 15-PGDH has a beneficial effect on hair growth (see WO 03/090699) .

Type-1 15-PGDH is a key enzyme in the deactivation of prostaglandins, in particular of PGF2-α and PGE2, which are important mediators of hair growth and survival . It corresponds to the classification EC 1.1.1.141 and is NAD⁺-dependent . This enzyme catalyses an oxidation reaction on carbon 15 of the hydroxyl into ketone . It has been isolated from pig kidney; its inhibition with a thyroid hormone, triiodothyronine, at doses very much higher than the physiological doses, has especially been observed . Type-2 15-PGDH is itself NADP-dependent .

However, it has never been proposed to use a type-1 15-PGDH inhibitor to maintain and/or increase the density of human keratin fibres and especially the hair density and/or to reduce the heterogeneity of the diameters of the keratin fibres and especially of the hair in man . The expression "increase the density of human keratin fibres , and especially the hair density" means increasing the number of keratin fibres, and especially of hairs per cm² of skin or of scalp .

Consequently, one subj ect of the present invention is the use of at least one particular 15-hydroxyprostaglandin dehydrogenase inhibitor in a composition or for the preparation of a composition for promoting the growth of human keratin fibres such as head hair and/or other bodily hairs .

Moreover, there is also a need for novel products for caring for and/or treating human keratin fibres , but also for human skin, which promotes their pigmentation and/or limits their depigmentation and which makes it possible in particular to prevent and/or reduce the canities of human keratin fibres such as head hair, the eyelashes and/or certain other bodily hairs .

The colour of human hair and skin depends on various factors and especially on the seasons of the year, race, sex and age . It is mainly determined by the concentration of melanin produced by the melanocytes . These melanocytes are specialized cells that synthesize melanin via particular organelles, the melanosomes . Melanin synthesis (or melanogenesis) is complex and schematically involves the following main steps :

Tyrosine >Dopa >Dopaquinone >Dopachrome >Melanin

Tyrosinase (monophenol dihydroxyl phenylalanine : oxygen oxidoreductase EC 1.14.18.1) participates in this sequence of reactions by especially catalysing the reaction for conversion of 45

tyrosine into dopa (dihydroxyphenylalanine) and the reaction for conversion of dopa into dopaquinone .

The upper part of the hair follicle appears as a tubular invagination of the epidermis , which is buried just down to the deep layers of the dermis . The lower part, or hair bulb, itself comprises an invagination in which is found the dermal papilla . Around the dermal papilla, in the lower part of the bulb, is an area populated with cells with a high degree of proliferation (matrix cells) . These cells are the precursors of the keratinized cells that will constitute the hair . The cells that result from the proliferation of these precursors migrate vertically in the bulb and become gradually keratinized in the upper part of the bulb; this assembly of keratinized cells will form the hair stem. Pigmentation of the hair and of other bodily hairs requires the presence of melanocytes in the bulb of the hair follicle . These melanocytes are in an active state, i . e . they synthesize melanins (or melanin pigments) . These pigments are transferred to the keratinocytes intended to form the hair stem, which will give rise to the growth of a pigmented head hair or other bodily hair. This structure is known as a "follicular pigmentation unit" .

It is known that, in the maj ority of populations , a brown skin coloration and maintenance of a constant coloration of head hair are important aspirations .

It is accepted that the appearance of grey or white bodily hairs and/or head hairs, or canities, is associated with a decrease in melanin in the hair stem. This phenomenon occurs naturally during the life of an individual . However, people are seeking to have a more youthful appearance and, with an aesthetic aim, they are often tempted to combat this phenomenon, especially when it occurs at a relatively early age .

Many solutions have thus been proposed in the field of artificial coloration by providing exogenous dyes intended to give the hair a coloration as close as possible to that which it has naturally . Another approach consists in stimulating the natural pigmentation pathway.

Among the proposed solutions, mention may be made of compositions containing a phosphodiesterase inhibitor (WO 95/17161) , DNA fragments (WO 95/01773) , diacylglycerol (WO 94/04122) , prostaglandins

(WO 95/11003) or pyrimidine 3-oxide derivatives (EP 829 260 ) .

The Applicant has now found, unexpectedly, that it is possible to stimulate the synthesis of melanin by the melanocytes by specifically inhibiting the degradation of the prostaglandins synthesized by these melanocytes or those present in its environment . Accordingly, one subject of the present invention is also the use of at least one particular 15-hydroxyprostaglandin dehydrogenase inhibitor in a composition or for the preparation of a composition for promoting the pigmentation of the skin or the integuments , in particular human keratin fibres such as head hair and/or other bodily hairs .

The involvement of certain prostaglandins in the pigmentation of bodily hairs or the skin in man or animals is described in the document Wand M . , 1997 ,

Arch . Ophtalmol . , 115; Abdel Malek et al . , 1987, cancer Res . , 47. However, since prostaglandins are molecules with a very short biological half-life and as a result of the local and labile nature of their metabolism (Narumiya S . et al . ) , it appears important to be able to prolong the activity of the prostaglandins involved in the pigmentation of human skin, bodily hairs and/or head hair .

Moreover, the Applicant has shown that 15-hydroxyprostaglandin dehydrogenase is also expressed in the melanocyte of head hairs, which had never been demonstrated hitherto (see WO 04/073 594) . In addition, the Applicant has demonstrated the presence of 15-PGDH in the dermal papilla and the melanocyte of head hairs, and has proposed using a 15-PGDH inhibitor to promote the pigmentation of human skin, bodily hairs and/or head hair . It is now possible to locally regulate the level of prostaglandins and especially that present in the melanocyte, in particular of head hair, by acting on the degradation catalysed both by the 15-PGDH of the melanocyte and of the fibroblast of the dermal papilla . The Applicant has also shown that the melanocytes of head hairs express prostaglandin H synthase 1 (PGHS-I or COX-I, E . C : 1.14.99.1) . This demonstrates for the first time that the melanocytes of head hair have an autonomous metabolism of prostaglandins .

In document WO 04/073 594, it was furthermore shown that it is possible to specifically inhibit the 15-PGDH present in the dermal papilla and/or in the melanocyte of head hair . Such an inhibition thus makes it possible to stop the deactivation of the prostaglandins in the environment of the melanocyte of head hair . The prostaglandins can thus continue via the autocrine or paracrine route to stimulate the melanocytes . Specifically, the application of such inhibitors stimulates the production of melanin by the melanocytes .

DESCRIPTION OF THE INVENTION

> The present invention thus relates to a composition for caring for and/or treating the skin and/or keratin fibres, especially human skin and/or keratin fibres such as the hair, containing at least one particular 15-hydroxyprostaglandin dehydrogenase inhibitor especially of type 1 and a physiologically acceptable medium .

According to the invention, the term ^λλ15-PGDH inhibitor" means any substance, simple or complex compound, of natural or synthetic origin, capable of inhibiting or of reducing the activity of the enzyme 15-PGDH, and/or capable of inhibiting, reducing or slowing down the reaction catalysed by this enzyme . The 15-PGDH inhibitors according to the invention are preferably type-1 15-PGDH inhibitors .

Advantageously, the inhibitor is a specific NAD-dependent type-1 15-PGDH inhibitor .

Also, surprisingly, the Applicant has found that certain salified or non-salified, solvated or non- solvated 3-sulfanylpropanamide derivatives are inhibitors of 15-hydroxyprostaglandin dehydrogenase, in particular of type 1. It has moreover been found that these compounds have favourable activity on increasing the density of human keratin fibres and/or on limiting the canities thereof .

The present invention relates to the use, especially the cosmetic use, of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof :

(D in which : a) Ri and Ra independently represent : 1) a hydrogen atom, 2) a Ci-C₂O alkyl radical optionally substituted with at least one substituent Ai,

3) a saturated hydrocarbon-based ring C¹ optionally substituted with at least one substituent A₁;

4 ) an unsaturated hydrocarbon-based ring C² optionally substituted with at least one substituent A₂; b) R₃ represents :

1) a hydrogen atom,

2) a Ci-C₂O alkyl radical optionally substituted with at least one substituent A₃,

3) a saturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A₄; c) Ai represents :

1) a fluorine atom, 2) a group CF₃, CN, OR, SR, NRR' , SO₂NRR' , NRSO₂R' ,

SO₂R, 3 ) a group having the following formula :

with :

- W = O, NH, S , - X = O, NH , C₁-C₆ N-alkyl , - Y = C₁-C₄ alkyl , C₁-C₅ alkoxy, NH₂,

C₁-C₆ NH-alkyl, C₁-C₅ N-dialkyl,

4 ) a saturated hydrocarbon-based ring C⁴ optionally substituted with at least one substituent A₄,

5) a heterocycle Hy₁ chosen from pyrrole, furan, dihydrofuran, tetrahydrofuran, thiophene, thiazole, oxazole, oxazolidine, isoxazole, isoxazolidine, oxadiazole, pyridine, pyran, dihydropyran, tetrahydropyran, pyrimidine, piperazine, pyridazine, pyrazine, morpholine, quinoline, isoquinoline, 2-thiohydantoin,

2-OXO-2, 3-dihydro-l, 3-thiazole and pyridone, this heterocycle possibly being substituted with at least one substituent A₄,

6) an unsaturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A₄ and optionally fused to a hydrocarbon-based or heterocyclic ring C⁶; d) Α₂ represents :

1 ) a fluorine atom, 2 ) a group of formula CF₃, CN, OR, SR, NRR' , COR, EP2006/001545

16

COOR, CONRR' , NRCOR' , NRCONR' R", SO₂NRR' , NRSO₂R' , SO₂R, 3) a C₁-C20 alkyl group optionally substituted with at least one substituent A₄ ; e) A₃ represents :

1) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' ,

3) a group of formula (II)

with W, X and Y having the same meaning as above,

5) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄ or a heterocycle Hy₂ optionally substituted with at least one substituent A₄ and containing at least one hetero atom chosen from N, 0 and S and a combination thereof; f) A₄ represents :

1) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' ,

3) a C₁-C₂₀ alkyl group, or

4) a ring C⁶ optionally fused to another ring C⁷, these rings optionally containing at least one hetero atom to form a heterocycle Hy₂; g) R, R' and R", which may be identical or different, represent :

1) a hydrogen atom,

2) a saturated Ci-Cβ alkyl group optionally substituted with at least one substituent A₄, or

3) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄,

4 )' a heterocycle Hy2 comprising at least one hetero atom chosen from N, S and O or a combination thereof and possibly being substituted with at least one substituent A₄.

A subject of the invention is also the use, especially the cosmetic use, of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof, as defined above, as an agent for promoting and/or inducing and/or stimulating the pigmentation of the skin and/or keratin fibres, especially human skin and/or keratin fibres, and/or as an agent for preventing and/or limiting the depigmentation and/or bleaching of the skin and/or keratin fibres , especially human skin and/or keratin fibres , and, especially as an agent for preventing and/or limiting the canities of human keratin fibres . A subject of the invention is also the cosmetic use of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof in a care and/or makeup composition for keratin fibres, especially human keratin fibres, to induce and/or stimulate their growth, to stop their loss and/or to increase their density. A subject of the invention is also the cosmetic use of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof in a care and/or makeup composition for the skin and/or keratin fibres, especially human skin and/or keratin fibres, to induce and/or stimulate the pigmentation of the said skin and/or the said fibres and/or to limit their depigmentation and/or bleaching.

A subject of the invention is also the use of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof for the manufacture of a care or treatment composition for keratin fibres, especially human keratin fibres, which is intended to induce and/or stimulate the growth of the said fibres and/or to stop their loss and/or to increase their density.

A subject of the invention is also the use of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof for the manufacture of a care or treatment composition for the skin and/or keratin fibres, especially human skin and/or keratin fibres, which is intended to induce and/or stimulate the pigmentation of the skin and/or the said keratin fibres and/or to limit the depigmentation and/or bleaching of the skin and/or keratin fibres, and which is especially intended to prevent and/or limit the bleaching or canities of human keratin fibres .

A subject of the invention is also the cosmetic use of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof in a care and/or makeup composition for keratin fibres, especially human keratin fibres, as an agent for reducing their loss and/or for increasing their density and/or for limiting their bleaching . This composition also makes it possible to keep the keratin fibres in good condition and/or to improve their appearance .

The invention also applies to the keratin fibres of mammals of the animal species (for example dog, horse or cat) .

The human keratin fibres to which the invention applies are especially head hair, the eyebrows, the eyelashes, beard hairs, moustache hairs and pubic hairs, and also the nails . More especially, the invention applies to human head hair and/or eyelashes . Thus , the invention also relates to the cosmetic use of at least one 3~sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof, in a cosmetic composition for human haircare to reduce the loss of the hair and/or to increase its density and/or to treat androchronogenetic alopecia and/or to reduce its depigmentation and/or bleaching. A subject of the invention is also the use of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof for the preparation of a human hair composition, which is intended to induce and/or stimulate the growth of the hair and/or to stop its loss and/or to increase its density and/or to treat androgenic alopecia and/or to induce and/or stimulate its pigmentation and/or to limit its depigmentation and/or bleaching .

The invention also relates to the cosmetic use of at least one 3-sulfanylpropanamide compound of formula (I ) or a salt and/or solvate thereof, in a cosmetic composition for human haircare to treat alopecia of natural origin and in particular androgenic alopecia, and also to the use of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof for the preparation of a human haircare composition for treating alopecia of natural origin and in particular androgenic alopecia . Thus, this composition makes it possible to keep the hair in good condition and/or to combat the natural loss of the hair and more especially that of men .

A subject of the invention is also the cosmetic use of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof, in a cosmetic composition for caring for and/or making up human eyelashes, to induce and/or stimulate the growth of the eyelashes and/or to increase their density and/or to limit their bleaching, and also to the use of at least one

3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof, for the preparation of a composition for caring for and/or treating human eyelashes , which is intended to induce and/or stimulate the growth of the eyelashes and/or to increase their density and/or to induce and/or stimulate their pigmentation and/or to limit their depigmentation and/or bleaching. This composition thus makes it possible to keep the eyelashes in good condition and/or to improve their condition and/or appearance .

A subj ect of the invention is also the use of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof, as an inhibitor of 15-hydroxyprostaglandin dehydrogenase, especially of type 1. A subject of the invention is also the use of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof, for the manufacture of a composition for treating disorders associated with the activity of type-1 15-hydroxyprostaglandin dehydrogenase in particular in man .

A subject of the present invention is also a cosmetic process for treating human keratin fibres (especially the hair or the eyelashes) and/or the skin, in particular that from which the said fibres emerge, for instance the scalp and the eyelids, characterized in that it consists in applying to the said keratin fibres and/or the said skin a cosmetic composition comprising at least one compound of formula (I) or a salt and/or solvate thereof, leaving this composition in contact with the said keratin fibres and/or the said skin, and optionally rinsing the said fibres and/or the said skin .

This treatment process does indeed have the characteristics of a cosmetic process insofar as it makes it possible to improve the aesthetic appearance of human keratin fibres and especially the hair and the eyelashes and also the aesthetic appearance of the skin by giving them greater vigour and/or an improved appearance . In addition, it may be used daily for several months, without medical prescription.

More especially, one subject of the present invention is a cosmetic process for caring for human hair and/or the scalp, to improve their condition and/or their appearance, characterized in that it consists in applying to the hair and/or to the scalp a cosmetic composition comprising an effective amount of at least one compound of formula (I) or a salt and/or solvate thereof, leaving the composition in contact with the hair and/or the scalp, and optionally rinsing the hair and/or the scalp . A subject of the invention is also a cosmetic process for caring for human skin, in order to improve its condition and/or its appearance, characterized in that it consists in applying to the said skin a cosmetic composition comprising an effective amount of at least one compound of formula (I) or a salt and/or solvate thereof, leaving the composition in contact with the said skin, and optionally rinsing it off .

A subject of the invention is also a cosmetic process for caring for and/or making up human eyelashes, to improve their condition and/or their appearance, characterized in that it consists in applying to the eyelashes and/or the eyelids a mascara composition comprising at least one compound of formula (I) or a salt and/or solvate thereof, and then leaving the composition in contact with the eyelashes and/or the eyelids . This mascara composition may be applied alone or as a base coat for a standard pigmented mascara and may be removed like a standard pigmented mascara . A subject of the invention is also the cosmetic use of a 3-sulfanylpropanamide compound of formula ( I ) or a salt and/or solvate thereof, as an agent for preserving the amount and/or the activity of the prostaglandins, especially in the hair follicles .

A subj ect of the invention is also the use of at least one 3-sulfanylpropanamide compound of formula (I ) or a salt and/or solvate thereof, for the manufacture of a composition for preserving the amount and/or the activity of the prostaglandins especially in the hair follicles .

Among the compounds of formula (I) , a certain number of compounds are novel and constitute another subj ect of the invention .

These are the 3-sulfanylpropanamide compounds that satisfy at least one of the formulae (III) , (IV) , (V) , (VII) and (VIII) below or one of the corresponding salts and/or solvates thereof :

in which Q represents : a) a phenyl radical substituted with at least one radical Z ; or b) an aromatic heterocycle chosen from pyrimidine, quinoline, isoquinoline, pyrrole, furan or thiophene, optionally substituted with at least one radical Z, with Z representing : fluorine , - the groups CF₃, CN, OR, SR, NRR' , SO₂NRR' , NRSO₂R' , SO₂R, SiRR' R", with R, R' and R" having the same meaning as above, - a group of formula (II) :

with W, X and Y having the same meaning as above; a C₁-C₁₀ alkyl group optionally substituted with at least one substituent A₄, with A₄ having the same meaning as above; and which T represents : a) a saturated alkyl radical chosen from methyl, ethyl , n-butyl, isobutyl and tert-butyl; or b) a saturated C₄-C₆ hydrocarbon-based ring:

A subject of the invention is also a care and/or mascara composition for the hair or the eyelashes, containing a cosmetically acceptable medium for topical application and a 3-sulfanylpropanamide compound that satisfies at least one of the formulae (III) , (IV) , (V) , (VII ) and (VIII) below, or a salt and/or solvate thereof as defined above .

A subject of the invention is also a care and/or makeup composition for keratin fibres, comprising, in a physiologically acceptable medium, in particular a cosmetic medium, at least one 3-sulfanylpropanamide compound that satisfies at least one of the formulae (III) , ( IV) , (V) , (VII) and (VIII) below or a salt and/or solvate thereof and at least one additional active agent that promotes the regrowth of human keratin fibres and/or that limits their loss , chosen from aminexil, FP receptor agonists, prostaglandins and derivatives thereof, and vasodilators, and more especially chosen from aminexil, minoxidil, latanoprost, (5E) -7- { (IR, 2R, 3R, 5S) -3 , 5-di- hydroxy-2- [ (3R) -3-hydroxy-5-phenylpentyl] cyclopentyl} - hept-5-enoic acid, butaprost, travoprost, diethyl 2, 4-pyridinedicarboxylate and 6-0- [ ( 9Z , 12Z) octadeca- 9, 12-dienoyl] hexapyranose, and mixtures thereof . DETAILED DESCRIPTION OF THE EMBODIMENTS OF THE

INVENTION The term "15-hydroxyprostaglandin dehydrogenase inhibitor" means a compound of formula (I) capable of inhibiting or reducing the activity of the enzyme 15-PGDH, especially of type 1 and in particular human 15-PGDH, and/or capable of inhibiting, reducing or slowing down the reaction catalysed by this enzyme .

According to one advantageous embodiment of the invention, the compound of formula (I) is a specific inhibitor of 15-PGDH, in particular of type 1 ; the term "specific inhibitor" means an active agent that has little or no inhibitory effect on prostaglandin synthesis, in particular on the synthesis of PGF2-α or PGE2. According to one particular embodiment of the invention, the inhibitor of 15-PGDH especially of type 1 has little or no inhibitory effect on prostaglandin synthase (abbreviated to PGF synthase or PGFS) .

Specifically, the Applicant has found that PGF synthase is also expressed in the dermal papilla . Maintenance of an effective amount of prostaglandins at the site of action thus results from a complex biological equilibrium between the synthesis and the degradation of these molecules . The exogenous supply of compounds that inhibit catabolism will thus be less effective if this activity is combined with an inhibition of the synthesis of these prostaglandins .

Advantageously, the compounds of formula (I) , in salified or non-salified, solvated or non-solvated form, have inhibitory activity on 15-PGDH that is higher than the inhibitory activity on PGF synthase, and are thus selective inhibitors . In particular, the ratio between the inhibitory activities on PGF synthase and on 15-PGDH, respectively, for a given concentration, determined especially by the concentrations that inhibit 50% of the enzymatic activity of PGF synthase ( IC₅₀fc) relative to the concentration that inhibits 50% of the enzymatic activity of 15-PGDH ( IC₅₀dh) is at least greater than 1 and especially at least 3 : 1.

In the text hereinbelow, and unless otherwise mentioned, the use of the term "compound of formula ( I ) " should be understood as meaning either the compound of formula ( I) or a salt or solvate and in particular a hydrate thereof, or a solvated salt (in particular a hydrated salt) thereof .

According to the invention, the compounds of formula ( I ) are in isolated form, i . e . non-polymeric form .

According to the invention, the term "salts of a compound of formula ( I ) " means the organic or mineral salts of a compound of formula ( I ) . As mineral salts that may be used according to the invention, mention may be made of the sodium or potassium salts and also the ammonium, zinc (Zn²⁺) , calcium (Ca²⁺) , copper (Cu²⁺) , iron (Fe²⁺ and Fe³⁺) , strontium (Sr²⁺) , magnesium (Mg²⁺) and manganese (Mn²⁺) salts; hydroxides, hydrohalides (for example hydrochlorides ) , carbonates , hydrogen carbonates, sulfates, hydrogen phosphates , phosphates .

The organic salts that may be used according to the invention are, for example, the triethanolamine, monoethanolamine, diethanolamine, hexadecylamine, N, N,N' ,N' -tetrakis (2-hydroxypropyl) ethylenediamine, tris-hydroxymethylaminomethane, hydroxide, hydrohalide, carbonate, hydrogen carbonate, citrate, lactate, glycolate, gluconate, acetate, propionate, fumarate, oxalate, tartrate, sulfate, phosphate and hydrogen phosphate salts . As possible solvates of the compounds of formula (I) , mention may be made of the hydrates, alcoholates and hydroalcoholates .

According to the invention, the term "at least one" means one or more (2, 3 or more) . In particular, the composition may contain one or more compounds of formula (I) . This or these compound (s ) may be cis or trans or Z or E isomers or a mixture of cis/trans or Z/E isomers . They may also be in tautomeric form. This or these compound (s) may be enantiomers and/or diastereoisomers or a mixture of these isomers , in particular a racemic mixture .

For the purposes of the invention, the term "hydrocarbon-based" means a group of hydrogen and carbon atoms .

For the purposes of the invention, the term "alkyl radical" means a hydrocarbon-based radical that may be linear or branched and saturated or unsaturated. In particular, the alkyl radical contains from 1 to 20 and preferably from 1 to 10 carbon atoms . As examples of alkyl radicals that may be used in the invention, mention may be made of methyl, ethyl, isopropyl, n-butyl, tert-butyl, n-hexyl, 2-ethylhexyl, ethylene and propylene radicals .

According to the invention, the rings C¹ to C⁷ and Hy_∑ of formula (I) contain from 3 to 7 atoms, for example 4, 5 or 6 atoms, and may be saturated or unsaturated, unless otherwise mentioned. In addition, the heterocycles may contain from 1 to 4 hetero atoms, which may be identical or different, chosen from N, S and O and a combination thereof . These rings may moreover be fused to another ring of identical or different chemical nature, to form fused rings . In addition, these rings may be substituted with one or more identical or different substituents, in particular A_∑ or A₄. These rings may be linked via any atom thereof capable of forming a covalent bond with a carbon atom. As saturated hydrocarbon-based rings that may be used in the invention, mention may be made of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl radicals . Unsaturated hydrocarbon-based rings that may be mentioned include cyclohexenyl and phenyl rings . As fused hydrocarbon-based rings that may be used, mention may be made of aryl radicals, for instance the naphthyl ring . Unsaturated hydrocarbon- based rings that are preferred are aryl rings, for instance phenyl or naphthyl rings .

As heterocycles that may be used in the invention, in particular for the heterocycle Hy2, mention may be made of the following monoheterocycles : azetidine, pyrrole, dihydropyrrole, pyrrolidine, furan, dihydrofuran, tetrahydrofuran, thiophene, dihydrothiophene, tetrahydrothiophene, imidazole, dihydroimidazole, imidazolidine, dihydrothiazole, thiazole, dihydrothiazole, thiazolidine, pyrazole, dihydropyrazole, pyrazolidine, oxazole, dihydrooxazole, oxazolidine, isoxazole, dihydroisoxazole, isoxazolidine, isothiazole, dihydroisothiazole, isothiazolidine, triazole, dihydrotriazole, triazolidine, oxadiazole, dihydrooxadiazole, oxadiazolidine, thiadiazole, dihydrothiadiazole, thiadiazolidine, tetrazole, pyridine, dihydropyridine, tetrahydropyridine, piperidine, pyran, dihydropyran, tetrahydropyran, pyrimidine, dihydropyrimidine, tetrahydropyrimidine, piperazine, pyridazine, pyrazine, triazine, morpholine, azepine, diazepine . Preferably, FIy₂ represents a pyrrole, furan, dihydrofuran, EP2006/001545

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tetrahydrofuran, thiophene, thiazole, oxazole, oxazolidine, isoxazole, isoxazolidine, oxadiazole, pyridine, pyran, dihydropyran, tetrahydropyran, pyrimidine, piperazine, pyridazine, pyrazine, morpholine, quinoline, isoquinoline, 2-thiohydantoin, 2-OXO-2 , 3-dihydro-l, 3-thiazole or pyridone ring.

This monoheterocycle Hy₂ may also be fused to a saturated or unsaturated hydrocarbon-based or heterocyclic ring C⁷ of 4 to 7 atoms and better still of 5 to 6 atoms, which may be identical to or different from the heterocycle Hy₂. When this fused ring C⁷ is a heterocycle, it may contain from 1 to 4 identical or different hetero atoms chosen from O, N and S and a combination thereof . As fused heterocycles that may be used in the invention, mention may be made of purine and pteridine rings . As heterocycles fused to a hydrocarbon-based ring that may be used in the invention, mention may be made of benzofuran, benzothiophene, benzothiazole, indole, benzimidazole, quinoline, isoquinoline and quinazoline radicals .

Advantageously, one from among R₁ and R₂ represents hydrogen .

In particular, the 3-sulfanylpropanamide derivatives have the formula (Ia) below, or a corresponding salt and/or solvate thereof :

in which R₁ and R3 have the same definitions as above .

Preferably, Ri represents a linear or, branched, saturated or unsaturated Ci to Ci₀ alkyl radical or a saturated or unsaturated hydrocarbon-based ring, this radical or this ring being substituted with an unsaturated hydrocarbon-based or heterocyclic ring C⁵, this ring C⁵ itself being optionally substituted with one or more substituents Ai, which may be identical or different, chosen in particular from: linear or branched, saturated or unsaturated Ci to Cio alkyl radicals, preferably saturated C_x-C₆ alkyl radicals and more preferentially methyl and ethyl radicals; - Ci-Cβ alkoxy radicals , preferentially methoxy; aryl rings such as phenyl and naphthyl .

Preferably, the (hetero) ring C⁵ represents furan or phenyl . Advantageously, this ring C⁵ represents a phenyl radical, optionally substituted with a trifluoromethyl group .

According to one embodiment of the invention, R³ represents a linear or branched, saturated or unsaturated Ci to Ci₀ alkyl radical or a saturated or unsaturated hydrocarbon-based ring. More preferentially, R3 is chosen from methyl, tert-butyl, cyclopentyl and cyclohexyl .

As examples of 3-sulfanylpropanamide compounds of formula (I) and more particularly of formula (Ia) that may be used in the invention, mention may be made of the following compounds : 3- (tert-butylsulfanyl) -N- [ (5-methyl-2-furyl) methyl] - propanamide,

N-cyclobutyl-3- (methylsulfanyl) propanamide, 3- (methylsulfanyl) -N- (1-phenylethyl) propanamide, N-benzyl-3- (methylsulfanyl) propanamide, 3~ (methylsulfanyl) -N- [2^'- (trifluoromethyl) phenyl] - propanamide,

N- (4-methoxybenzyl) -3- (methylsulfanyl) propanamide, N- (2-furylmethyl) -3- (methylsulfanyl) propanamide; and in particular : N- [ (5-methyl-2-furyl) methyl] -3- (methylsulfanyl) propanamide .

According to another aspect of the invention, the invention relates to novel compounds corresponding to formula (I) and satisfying one of the formulae (III) , (IV) , (V) , (VII) and (VIII) below or a corresponding salt and/or solvate thereof:

in which Q represents : a) a phenyl radical substituted with at least one radical Z ; or b) an aromatic heterocycle chosen from pyrimidine, quinoline, isoquinoline, pyrrole, furan and thiophene, optionally substituted with at least one radical Z, with Z representing: fluorine,

- the groups CF₃, CN, OR, SR, NRR' , SO₂NRR' , NRSO₂R' , SO₂R, SiRR' R", with R and R' having the same meaning as above, - a group of formula (II ) :

with :

- W = O , NH, S - X = O, NH, C₁-C₆ N-alkyl - Y = C₁-C₄ alkyl, Ci-C₅ alkoxy, NH₂, C₁-C₆ NH-alkyl, Ci-C₆ N-dialkyl

- a C₁-C₁₀ alkyl group optionally substituted with at least one substituent A₄; and in which T represents : a) a saturated alkyl radical chosen from methyl, ethyl, n-butyl, isobutyl and tert-butyl; or b) a saturated C₄-C₆ hydrocarbon-based ring; 45

36

As examples of compounds that may be used in the invention, mention may be made of the following compounds : Compound 1 : N- [ (5-methyl-2-furyl) methyl] -

3- (methylsulfanyl) propanamide

Compound 2 : N- (2-furylmethyl) -3- (methylsulfanyl) - propanamide

Compound 3 : N- (4-methoxybenzyl) -3- (methylsulfanyl) propanamide

Compound 4 : N-hexyl-3- (methylsulfanyl ) propanamide

Compound 5 : 3- (methylsulfanyl) -N- [2- (trifluoromethyl) phenyl] propanamide

Compound 6 : N-benzyl-3- (methylsulfanyl) propanamide

Compound 7 : 3- (methylsulfanyl ) -N- (1-phenylethyl ) - propanamide

Compound 8 : N-cyclobutyl-3- (methylsulfanyl) propanamide

Compound 9 : 3- (tert-butylsulfanyl) -N- [ (5-methyl-

2-furyl) methyl] propanamide

Compound 10 : 3- (tert-butylsulfanyl) -N- (2-furylmethyl) - propanamide

Compound 11 : 3- (cyclopentylsulfanyl) -N- [ (5-methyl- 2-furyl)methyl] propanamide

Compound 12 : 3- (cyclopentylsulfanyl) -N- (2-furylmethyl) propanamxde

Compound 13 : 3- (tert-butylsulfanyl) -N- [2- (trifluoromethyl) phenyl] propanamide

Compound 14 : 3- [ (3 , 3, 4 , 4 , 5 , 5 , 6, 6, 7 , 7 , 8 , 8 , 9, 9, 10 , 10 , 10- heptadecafluorodecyl) sulfanyl] -N- { 4- [ ( Z) - (4, 7 , 7- trimethyl-3-oxobicyclo [2.2.1] hept-2-ylidene) methyl] - benzyl}propanamide

Compound 15: N- [3- (2H-1, 2, 3-benzotriazol-2-yl) - 2-hydroxy-5- (1, 1, 3, 3-tetramethylbutyl) benzyl] - 3-[ (3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 9, 9, 10, 10,10- heptadecaf luorodecyl) sulfanyl ]propanamide

Compound 16: 3- [ (3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 8- tridecafluorooctyl) sulfanyl] -N- { 4- [ (Z) - (4, 7 , 7- trimethyl-3-oxobicyclo [2.2.1] hept-2- ylidene) methyl ] benzyl }propanamide

As examples of novel compounds according to the invention that satisfy one of the formulae (III) , (IV) , (V) , (VII) and (VIII) , mention may be made of compounds 1, 2, 3, 4, 5_f 7 and 8.

The salified or non-salified and/or solvated or non-solvated compounds of formula (I) may be manufactured according to the reaction scheme indicated below:

One equivalent of product (a) is mixed with 1.1 equivalents of amine (b) as solution in a dichloromethane/aqueous sodium hydroxide two-phase mixture . The reaction is performed for 4 hours at room temperature . The reaction medium is then left to settle . The dichloromethane phase is separated out and then dried over magnesium sulfate . The solvent is then evaporated off to give the desired compound in crystalline form. The acid chlorides (a) are either commercial P2006/001545

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or are prepared in two steps on the basxs of the following publications : Step 1

for example :

Synthesis of Some Novel α, β-Ethylenic SuIfones, Reddy M. V. R. , Vijayalakshmi S . , Reddy D. B . , Reddy P . V. R. , Phosphorus, Sulfur Silicon Relat . Elem. 60 (1991) 3-4 , 209-214 ; or alternatively :

Selective Preparation of β-Monoesters of Mercaptosuccinic Acid with Acid or Base Labile Sulfur Protecting Groups and Esters, Gustavson L . M. , Jones D . S . , Nelson J. S . , Srimvasan, A. , Synth . Commun . 21 (1991) 2, 249-263 ; or alternatively:

A Novel and Convenient Synthesis of E, E, - Bis (styryl) sulfones and E, E-I, 4-Diaryl-l, 3-butadienes, Reddy M. V. R. , Manjubhashini A. B . , Reddy S . , Reddy P . V. R. , Reddy D . B . , Synth . Commun . 21 (1991) 15-16, 1589-1596.

Step 2 :

for example :

Simpleand Convenient Procedure for the Preparation of Acid Chlorides of Penicillins, Mata E . G. , Boschettx C . E . , Mascaretti 0. A. , Org. Prep . Proced. Int . 27 (1995) 2, 229-232.

To the Applicant' s knowledge, no prior art document describes or suggests that the 3-sulfanyl- propanamide compounds of formula (I) or salts and/or solvates thereof have the property of inducing and/or stimulating the growth of human keratin fibres and in particular human hair and eyelashes , and/or of stopping their loss and/or of stimulating the pigmentation of the skin and/or keratin fibres and/or of limiting their pigmentation and/or bleaching, or that these compounds may be used topically to increase the density of human keratin fibres and/or to limit their bleaching and more especially to increase the density and/or bleaching of the hair and the eyelashes . The effective amount of a compound of formula

(I) (salified or non-salified, and solvated or non- solvated) corresponds to the amount of compound required to obtain the desired result (i . e . to increase the density of keratin fibres and especially the hair and the eyelashes or to promote their growth or reduce their bleaching) . A person skilled in the art is thus capable of evaluating this effective amount, which depends on the nature of the compound used, the person on whom it is applied and the time of this application . In the text hereinbelow, and unless otherwise mentioned, the amounts of the various ingredients in the composition are given as weight percentages relative to the total weight of the composition .

To give an order of magnitude, according to the invention, the compound of formula (I) (salified or non-salified, and solvated or non-solvated) or a mixture of compounds of formula (I) (salified or non- salified, and solvated or non-solvated) may be used in an amount ranging from 10^~3% to 10% of the total weight of the composition, preferably in an amount representing from 10^"3% to 5% and better still from ICT² to 2% of the total weight of the composition, for example from 0.5% to 2% .

The composition of the invention may be for cosmetic or pharmaceutical use . The composition of the invention is preferably for cosmetic use . In addition, the composition must contain a non-toxic, physiologically acceptable medium that can be applied to human skin, including the scalp and the eyelids and to keratin fibres . For the purposes of the invention, the term "cosmetic" means a composition of pleasant appearance, odour and feel .

The compound of formula (I) (salified or non- salified, and solvated or non-solvated) may be used in a composition that should be ingested, injected or applied to the skin or to keratin fibres (to any area of skin or fibres to be treated) .

According to the invention, the compound of formula (I) or a mixture of compounds of formula (I) may be used orally in an amount of from 0.1 to 300 mg per day, for example from 5 to 10 mg/day. A preferred composition of the invention is a composition for cosmetic use and in particular for topical application to the skin and keratin fibres , and more especially to the scalp, the hair and the eyelashes .

This composition may be in any known presentation form that is suitable for the mode of use . For topical application to the skin or keratin fibres, the composition may be in the form of an aqueous , alcoholic or aqueous-alcoholic solution or suspension, or an oily suspension or solution, an emulsion or dispersion of more or less fluid consistency and especially of liquid or semi-liquid consistency, obtained by dispersion of a fatty phase in an aqueous phase (O/W) or conversely (W/O) , a solid (O/W) or (W/O) emulsion or dispersion, a more or less fluid or solid aqueous, aqueous-alcoholic or oily gel, ' a free or compacted powder to be used in unmodified form or to be incorporated into a physiologically acceptable medium, or alternatively microcapsules, microparticles or vesicular dispersions of ionic and/or nonionic type . A composition in the form of a foam or alternatively in the form of a spray or aerosol, then comprising a pressurized propellant, may also be envisaged .

It may also be in the form of a lotion, serum, milk, O/W or W/O cream, gel, unguent, ointment, powder, balm, patch, impregnated pad, cake or foam. In particular, the composition for application to the scalp or the hair may be in the form of a haircare lotion, for example for daily or twice- weekly application, a shampoo or a hair conditioner, in particular for twice-weekly or weekly application, a liquid or solid scalp cleansing soap for daily application, a hairstyle shaping product (lacquer, hair setting product or styling gel) , a treatment mask, a foaming gel or cream for cleansing the hair . It may also be in the form of a hair dye or mascara to be applied with a brush or a comb .

Moreover, for application to the eyelashes or body hairs , the composition to which the invention applies may be in the form of a pigmented or unpigmented mascara, to be applied with a brush to the eyelashes or alternatively to beard or moustache hair . For a composition for use by injection, the composition may be in the form of an aqueous lotion or an oily suspension . For oral use, the composition may be in the form of capsules, granules, drinkable syrups or tablets .

According to one particular embodiment, the composition according to the invention is in the form of a hair cream or hair lotion, a shampoo, a conditioner for the hair or a mascara for the hair or for the eyelashes .

The amounts of the various constituents of the physiological medium of the composition according to the invention are those generally used in the fields under consideration . In addition, these compositions are prepared according to the usual methods .

When the composition is an emulsion, the proportion of the fatty phase may range from 2% to 80% by weight and preferably from 5% to 50% by weight relative to the total weight of the composition . The aqueous phase is adjusted as a function of the content of fatty phase and of compound (s) (I) and also of that of the optional additional ingredients , to obtain 100% by weight . In practice, the aqueous phase represents from 5% to 99.9% by weight .

The fatty phase may contain fatty or oily compounds that are liquid at room temperature (25 "C) and atmospheric pressure (760 mm Hg) , which are generally known as oils . These oils may be mutually compatible or incompatible and may form a macroscopically homogeneous liquid fatty phase or a two-phase or three-phase system. In addition to the oils, the fatty phase may contain waxes , gums, lipophilic polymers or "pasty" or viscous products containing solid parts and liquid parts .

The aqueous phase contains water and optionally an ingredient that is miscible in all proportions with water, for instance Ci to C₈ lower alcohols such as ethanol or isopropanol, polyols, for 6 001545

48

instance propylene glycol, glycerol or sorbitol, or alternatively acetone or ether .

For a composition in emulsion form, the composition may contain one or more emulsifiers optionally combined with one or more co-emulsifiers used to obtain a composition in emulsion form, these emulsifiers and co-emulsifiers being those generally used in cosmetics and pharmaceuticals . Their nature also depends on the sense of the emulsion. In practice, the emulsifier and, where appropriate, the co- emulsifier are present in the composition in a proportion ranging from 0.1% to 30% by weight, preferably from 0.5% to 20% by weight and better still from 1% to 8% by weight . The emulsion may also contain microcapsules or microparticles, and vesicular dispersions and especially lipid vesicles and especially liposomes .

When the composition is in the form of an oily solution or gel, the fatty phase may represent more than 90% of the total weight of the composition . Advantageously, for a hair application, the composition of the invention is an aqueous, alcoholic or aqueous-alcoholic solution or suspension and better still a water/ethanol solution or suspension . The alcoholic fraction may represent from 5% to 99.9% and better still from 8% to 80% .

For a mascara application, the composition of the invention is especially in the form of a wax-in- water or wax-in-oil dispersion, a gelled oil or an aqueous gel, which may be pigmented or unpigmented. The composition of the invention may also comprise other additional ingredients usually used in the fields under consideration, chosen from solvents , aqueous-phase or oily-phase solvents, thickeners or gelling agents, dyes that are soluble in the medium of the composition, solid particles such as fillers or pigments, antioxidants, sequestrants , preserving agents , fragrances, electrolytes, neutralizers , film- forming polymers, UV blockers, for instance sunscreens, cosmetic and pharmaceutical active agents with a beneficial effect on the skin or keratin fibres, other than the compounds of formula (I ) , and mixtures thereof . These additives may be present in the composition in the amounts generally used in cosmetics and dermatology, and especially in a proportion of from 0.01% to 50% and better still from 0.1% to 20%, for example from 0.1% to 10% , relative to the total weight of the composition . Depending on their nature, these additives may be introduced into the fatty phase, into the aqueous phase and/or into the lipid vesicles and especially liposomes . Needless to say, a person skilled in the art will take care to select the optional additional ingredients and/or the amount thereof such that the advantageous properties of the composition according to the invention, i . e . the inhibition of 15-PGDH and in particular the increase in the density of keratin fibres and/or the reduction in their bleaching, are not, or are not substantially, adversely affected by the envisaged addition .

As solvents that may be used in the invention, mention may be made of C2 to Cs lower alcohols, for instance ethanol, isopropanol, propylene glycol and certain light cosmetic oils, for instance C₆ to C₁6 alkanes .

As oils that may be used in the invention, mention may be made of oils of mineral origin (liquid petroleum jelly or hydrogenated isoparaffin) , oils of plant origin (liquid fraction of shea butter, sunflower oil, apricot oil, fatty alcohol or fatty acid) , oils of animal origin (perhydrosqualene) , synthetic oils (fatty acid ester, purcellin oil) , silicone oils (linear or cyclic polydimethylsiloxane, phenyl trimethicone) and fluoro oils (perfluoropolyethers) . Waxes that may be mentioned include silicone waxes , beeswax, rice wax, candelilla wax, carnauba wax, paraffin wax and polyethylene wax .

As emulsifiers that may be used in the invention, examples that may be mentioned include glyceryl stearate, glyceryl laurate, sorbitol stearate, sorbitol oleate, alkyl dimethicone copolyols (with alkyl > 8) and mixtures thereof for a W/0 emulsion . Polyethylene glycol monostearate or monolaurate, polyoxyethylenated sorbitol stearate or oleate, and dimethicone copolyols , and mixtures thereof, may also be used for an 0/W emulsion .

As hydrophilic gelling agents that may be used in the invention, mention may be made of carboxyvinyl polymers (carbomer) , acrylic copolymers such as acrylate/alkylacrylate copolymers, polyacrylamides, polysaccharides such as hydroxypropylcellulose, natural gums and clays , and, as lipophilic gelling agents that may be used, mention may be made of modified clays , for instance Bentones, metal salts of fatty acids , for instance aluminium stearates , hydrophobic-treated silica and ethylcellulose, and mixtures thereof .

As cosmetic or pharmaceutical active agent other than the compound of formula (I) , which may be used in the invention, mention may be made of hydrophilic active agents chosen from proteins or protein hydrolysates, amino acids , polyols, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins , plant extracts (those from Iridacea plants or from soybean) and hydroxy acids such as fruit acids or salicylic acid; and lipophilic active agents such as retinol (vitamin A) and its derivatives, especially an ester (retinyl palmitate) , tocopherol (vitamin E) and 006/001545

52

its derivatives, especially an ester (tocopheryl acetate) , essential fatty acids , ceramides , essential oils , salicylic acid derivatives , for instance 5-n-octanoylsalicylic acid, hydroxy acid esters , and phospholipids, for instance lecithin, and mixtures thereof .

According to one particular embodiment of the invention, the compound of formula (I) may be combined with at least one additional active compound that promotes the regrowth and/or limits the loss of keratin fibres (hair or eyelashes) . These additional compounds are chosen especially from the lipoxygenase inhibitors as described in EP 0 648 488, the bradykinin inhibitors described especially in EP 0 845 700, prostaglandins and derivatives thereof, especially those described in WO 98/33497, WO 95/11003, JP 97-100 091 and JP 96-134 242, prostaglandin receptor agonists or antagonists, the non-prostanoic prostaglandin analogues as described in EP 1 175 891, EP 1 175 890 , WO 01/74307 , WO 01/74313, WO 01/74314, WO 01/74315 or WO 01/72268, and mixtures thereof.

As other additional active compounds that promote the growth of keratin fibres and/or limit their loss, which may be present in the composition according to the invention, mention may be made of vasodilators , antiandrogens, cyclosporins and analogues thereof, antimicrobial and antifungal agents, anti-inflammatory 6 001545

53

agents , and retinoids, alone or in a mixture .

The vasodilators that may be used are especially potassium-channel agonists, including minoxidil, and also the compounds described in patents US 3 382 247, 5 756 092, 5 772 990, 5 760 043, 5 466 694, 5 438 058 and 4 973 474, cromakalim, nicorandil and diaxozide, alone or in combination .

The antiandrogens that may be used especially include steroidal and non-steroidal 5α-reductase inhibitors, for instance finasteride and the compounds described in US 5 516 779, cyprosterone acetate, azelaic acid and the salts and derivatives thereof, and the compounds described in US 5 480 913, flutamide, oxendolone, spironolactone, diethylstilbestrol and the compounds described in patents US 5 411 981 , 5 565 467 and 4 910 226.

The antimicrobial or antifungal compounds may be chosen from selenium derivatives , octopirox, triclocarban, triclosan, zinc pyrithione, itraconazole, asiatic acid, hinokitiol, mipirocine, tetracyclines, especially erythromycin and the compounds described in EP 0 680 745 , clinycin hydrochloride, benzoyl peroxide or benzyl peroxide, minocycline and compounds belonging to the imidazole class, such as econazole, ketoconazole or miconazole or salts thereof, nicotinic acid esters, especially including tocopheryl nicotinate, benzyl nicotinate and C₁-C₆ alkyl nicotinates , for instance methyl nicotinate or hexyl nicotinate ..

The anti-inflammatory agents may be chosen from steroidal anti-inflammatory agents, for instance glucocorticoids , corticosteroids (for example : hydrocortisone) and non-steroidal anti-inflammatory agents, for instance glycyrrhetinic acid and α-bisabolol, benzydamine, salicylic acid and the compounds described in EP 0 770 399, WO 94/06434 and FR 2 268 523. The retinoids may be chosen from isotretinoin, acitretin, tazarotene, retinal and adapalene .

As other active compounds for promoting the growth and/or limiting the loss of hair that may be used in combination with the compound of formula (I) , which may or may not be salified and may or may not be solvated, mention may be made of aminexil, diethyl 2, 4- pyridinedicarboxylate, 6-0- [ ( 9Z, 12Z) octadeca- 9, 12-dienoyl] hexapyranose, benzalkonium chloride, benzethonium chloride, phenol, oestradiol, chlorpheniramine maleate, chlorophylline derivatives , cholesterol, cysteine, methionine, menthol, peppermint oil , calcium pantothenate, panthenol, resorcinol, protein kinase C activators , glycosidase inhibitors , glycosaminoglycanase inhibitors, pyroglutamic acid esters, hexosaccharide or acylhexosaccharide acids, substituted arylethylenes, N-acylamino acids, flavonoids, ascomycin derivatives and analogues, histamine antagonists, saponins , proteoglycanase inhibitors, oestrogen agonists and antagonists, pseudoterines , cytokines , growth factor promoters , IL-I or IL-6 inhibitors, IL-IO promoters, TNF inhibitors , benzophenones, hydantoin, retinoic acid; vitamins , for instance vitamin D, vitamin B12 analogues and pantothenol; triterpenes, for instance ursolic acid and the compounds described in US 5 529 769, US 5 468 888 and US 5 631 282/ antipruriginous agents, for instance thenaldine, trimeprazine or cyproheptadine; antiparasitic agents, in particular metronidazole, crotamiton or pyrethroids ; calcium antagonists, for instance cinnarizine, diltiazem, nimodipine, verapamil, alverine and nifedipine; hormones such as oestriol or its analogues , thyroxine and its salts, and progesterone; FP receptor (type-F prostaglandin receptor) agonists such as latanoprost, (5E) -7- { (IR, 2R, 3R, 5S) -3, 5-dihydroxy-2- [ (3R) -3-hydroxy-5- phenylpentyl] cyclopentyl }hept-5-enoic acid, (5E) -7- { ( 1R, 2R, 3R, 5S) -3, 5-dihydroxy-2- [ (3R) -3-hydroxy-5- phenylpentyl] cyclopentyl }hept-5-enoic acid, bimatoprost, travoprost or unoprostone, salts or esters thereof; mixtures thereof . Advantageously, the composition according to the invention comprises at least one 15-PGDH inhibitor as defined above and at least one prostaglandin or prostaglandin derivative, for instance the prostaglandins of series 2 especially including PGF2-α and PGE2 in salt or ester form (for example the isopropyl esters) , derivatives thereof, for instance 16, 16-dimethyl PGE2, 17-phenyl PGE2 , 16, 16-dimethyl PGF2-α, 17-phenyl PGF2~α, prostaglandins of series 1, for instance 11-deoxyprostaglandin El, 1-deoxy- prostaglandin El in salt or ester form, analogues thereof, especially latanoprost, fluprostenol, bimatoprost, cloprostenol , viprostol, butaprost, misoprostol, unoprostone, and the salts or esters thereof .

The composition advantageously contains at least one non-prostanoic EP2 and/or EP4 receptor agonist as described especially in EP 1 175 892.

It may also be envisaged for the composition comprising at least the compound of formula (I) , salified or non-salified, solvated or non-solvated, to be encapsulated in particular in liposomal form, as described especially in document WO 94/22468. Thus , the compound encapsulated may be delivered selectively to the hair follicle .

The composition according to the invention may be applied to the areas of the skin to be treated and in particular to the alopecic areas of the scalp and the hair of an individual, or only to the white hairs , and optionally left in contact for several hours and optionally rinsed off .

The composition containing an effective amount of a compound of formula (I) , salified or non- salified, solvated or non-solvated, may, for example, be applied in the evening, kept in contact throughout the night and optionally shampooed out in the morning . These applications may be repeated daily for one or more months according to the individual .

Advantageously, in the process according to the invention, between 5 μL and 500 μL of a solution or composition as defined above, comprising from 0.001% to 5% of 15-PGDH inhibitor, are applied to the areas of the scalp and/or the hair to be cared for or treated.

Exemplary embodiments of the invention, which shall not limit its scope in any way, will now be given by way of illustration .

EXAMPLES

Example 1 : Synthesis of N- [ (5-methγl-2-furyl)methyl] -3- (methylsulfanyl)propanamide (compound 1) : Synthetic scheme:

Procedure :

To a solution, cooled on an ice bath, of 3-methylthiopropionyl chloride (27.1 mL, 235 mM) in 500 mL of methylene chloride is added dropwise under nitrogen over 15 minutes a solution of 5-methyl- furfurylamine (28 mL, 250 mM) in anhydrous pyridine (21 mL, 260 mM) . The reaction medium is stirred for 24 hours . The reaction medium is then washed with aqueous IN hydrochloric acid solution (3 times 100 mL) and then with aqueous IN sodium hydroxide solution, and then with water (3 times 100 mL) . The organic phase is dried over sodium sulfate and the solvent is then evaporated off under vacuum. The product is washed with hot water . On cooling, the product solidifies . The solid obtained is finely divided and then stirred in

200 mL of water for 2 hours . The solid is then filtered off and dried to give 41.94 g (yield = 84%) of a white powder .

Structural analyses : Nuclear magnetic resonance: The spectra obtained are in accordance with the proposed structure :

¹H NMR (DMSO-d6) : 2.04 (s , 3H) ; 2.22 (d, 3H) ; 2.39 (t, 2H) ; 2.65 (t, 2H) ; 4.19 (d, 2H) ; 5.97 (dd, IH) ; 6.09 (d, IH) ; 8.27 (t, IH) . Mass spectrometry: Analysis by ESI+ and ESI- makes it possible to confirm the molecular mass of the expected product C₁₀H₁₅NO₂S, M=213. (Detection of [M+H] ⁺, [M+Na] ⁺, [M+H+CH₃OH] ⁺, [2M+Na] ⁺, [M-H] ^' and of the fragment [M+H-C₄H₉H₉NOS] ⁺) . Examples 2 , 9 , 10 , 11 and 12 :

Compounds 2, 9 , 10 , 11 and 12 may be synthesized via a synthetic method similar to that for compound 1.

E xample 2: Structural analyses:

Nuclear magnetic resonance: The spectra obtained are in accordance with the proposed structure : ¹H NMR (DMSO-d6) : 2.04 (s , 3H) ; 2.40 (t, 2H) ; 2.66 (t, 2H) ; 4.25 (d, 2H) ; 6.24 (m, IH) ; 6.38 (dd, IH) ; 7.56 (dd, IH) ; 8.27 (t, IH) .

Mass spectrometry: Analysis by ESI+ and ESI- makes it possible to confirm the molecular mass of the expected product C₉H₁₃NO₂S, M=I99. (Detection of [M+H] ⁺, [M+Na] ⁺, [ MH-NaCH₃OH] ⁺, [2M+H] ⁺ [2M+Na] ⁺, [M-H] - and [M+CH₃COO] -) . Example 3 : Synthesis of N- (4-methoxybenzyl) -3- (methylsulfanyl)propanamide (compound 3) : Reaction scheme :

Procedure:

3-Methylthiopropionyl chloride ( I g, 7.25 mM) is added with stirring at room temperature to 4-methoxybenzylamine (2393-23-9) (8 mM, 1.1 g) dissolved in a dichloromethane (20 mL) /sodium hydroxide ( 0.8 M, 10 mL) mixture . The reaction is monitored for 1 hour and the mixture is then allowed to settle and the organic phase is washed with saturated aqueous sodium chloride solution . The organic phase is dried over sodium sulfate, filtered and concentrated under reduced pressure to give a crude oil (1.91 g) . This oil is purified by chromatography on a column of silica gel, eluting with a 99/1 dichloromethane/methanol mixture to give compound 3 in the form of a white powder (yield = 80%) . Analysis :

Elemental analysis:

Calculated: C 60.2 ; H 7.2 ; N 5.9; O 13.4 ; S 13.4 Found: C 60.15; H 7.17 ; N 5.81; O 13.30 ; S 13.22 Nuclear magnetic resonance: The spectra obtained are in accordance with the proposed structure :

¹H NMR (DMSO-d6) : 2.05 (s, 3H) ; 2.41 (t, 2H) ; 2.67 (t, 2H) ; 3.72 (s, 3H) ; 4.2 (d, 2H) ; 6.87 (d, 2H) ; 7.18 (d, 2H) ; 8.28 (t, IH) . Example 4 : Synthesis of N-hexyl-3- (methylsulfanyl) - propanamide (compound 4) : Reaction scheme:

Procedure : 3-Methylthiopropionyl chloride (21 itiL,

182 mM) is added with stirring at room temperature to a solution of hexylamine (26.5 mL, 200 mM) and triethyl- amine (28.1 mL, 200 mM) in dichloromethane . The reaction medium is stirred for two hours . The reaction mixture is then washed with hydrochloric acid ( IN) and then washed with saturated aqueous sodium chloride solution . The organic phase is dried over sodium sulfate, filtered and concentrated under reduced pressure to give a colourless oil . This oil is distilled to give a colourless liquid that crystallizes under cold conditions (30.00 g; yield = 81%) . Structural analyses :

Nuclear magnetic resonance: The spectra obtained are in accordance with the proposed structure : ¹H NMR (DMSO-d6) : 0.86 (t, 3H) ; 1.25 (m, 6H) ; 1.38 (m, 2H) / 2.04 (s, 3H) ; 2.33 (t, 2H) ; 2.63 (t, 2H) ; 3.02 (m, 2H) ; 7.8 (t, IH) .

Mass spectrometry: The quasimolecular ions [M+H] ⁺, [M+Na] ⁺, [M+Na+CH₃OH] ⁺, [2M+H] ⁺, [2M+Na] ⁺, [M-H] - and also the fragment ion [C5H11NO+H] + (detected at m/z, ESP+=102 ) of the expected molecule C₁₀H₂iNOS are mainly detected.

Example 5 : Synthesis of 3~ (methylsulfanyl) -N- [2- (trifluoromethyl)phenyl]propanamide (compound 5) :

Reaction scheme :

Procedure :

To a solution, cooled on an ice bath, of 3-methylthiopropionyl chloride (26 inL, 225 mM) in 500 mL of methylene chloride is added dropwise under nitrogen over 15 minutes a solution of 2- (trifluoro- methyl ) aniline (31 mL₇ 248 mM) in anhydrous triethylamine (35 mL, 284 mM) . The reaction medium is stirred for 16 hours . The reaction medium is then washed with aqueous IN hydrochloric acid solution (3 times 100 mL) and then with aqueous IN sodium hydroxide solution, and then with water (3 times

100 mL) . The organic phase is dried over sodium sulfate and the solvent is then evaporated off under vacuum. The product obtained is distilled under vacuum to give an oil that solidifies under cold conditions to give 39.20 g of a beige-coloured solid (yield = 66%) . Structural analyses :

Nuclear Magnetic Resonance: The spectra obtained are in accordance with the proposed structure : ¹H NMR (DMSO-d6) : 2.1 (s, 3H) ; 2.64 (m, 2H) ; 2.73 (d, IH) ; 2.75 (dd, IH) ; 7.44 (d, IH) ; 7.48 (m, IH) ; 7.67 (m, IH) ; 7.72 (d, IH) ; 9.58 (s, IH) . Mass spectrometry: The quasimolecular ions [M+H] ⁺, [M+Na] ⁺, [M+Na+CH₃OH] ⁺, [2M+Na] ⁺, [M-H] ^" of the expected molecule C11H12F3NOS are mainly detected . Examples 6, 7 , 8 and 13 :

Compounds 6, 1 , 8 and 13 may be synthesized via a synthetic method similar to that for compound 5. Example 7: Structural analyses: Nuclear Magnetic Resonance: The spectra obtained are in accordance with the proposed structure :

¹H NMR (CDCl₃) : 2.08 (s , 3H) ; 2.45 (t, 2H) ; 2.76 (t, 2H) ; 4.42 (d, IH) ; 5.91 (se, IH) ; 7.28 (m, 5H) . Mass spectrometry: Analysis by ESI+ and ESI- makes it possible to confirm the molecular mass of the expected product Ci₂H₁₇NOS, M=223. (Detection of [M+H] ⁺, [M+Na] ⁺, [2M+H] ⁺, [2M+Na] ⁺, [M-H] ^" . Example 8: Structural analyses:

Nuclear Magnetic Resonance: The spectra obtained are in accordance with the proposed structure :

¹H NMR (DMS0-d6) : 1.6 (m, 2H) ; 1.83 (m, 2H) ; 2.03 (s,

3H) ; 2.12 (m, 2H) ; 2.3 (t, 2H) ; 2.61 (t, 2H) ; 4.16 (m, IH) ; 8.11 (d, IH) .

Mass spectrometry: Analysis by ESI+ and ESI- makes it possible to confirm the molecular mass of the expected product C₈Hi₅NOS, M=173. (Detection of [M+H] ⁺, [M+Na] ⁺) .

Examples 14 and 15 : The synthesis of compounds 14 and 15 is that described in patent application EP 652 210.

Example 16 :

Compound 16 may be synthesized via a synthetic method similar to that for compound 14. EXAMPLE 17 : Demonstration of the 15-PGDH-specific inhibitory properties of the compounds of formula (I) .

1 °) Test on 15-PGDH

The enzyme 15-PGDH is obtained as described in patent application FR 02/05067 filed in the name of L' Oreal , as a suspension in a medium adjusted to a concentration of 0.3 mg/mL and then blocked at -80⁰C .

For the purposes of the test, this suspension is thawed and stored in ice .

In parallel, a 100 mM, pH 7.4 Tris buffer containing 0.1 mM of dithiothreitol (D5545 , Sigma- Aldrich, L' isle D' Abeau Chesne, BP 701 , 38297 , Saint Quentin Fallavier) , 1.5 mM of β-NAD (N6522, Sigma- Aldrich, L' isle D' Abeau Chesne, BP 701 , 38297, Saint Quentin Fallavier) , and 50 μM of prostaglandin E₂ (P4172 , Sigma-Aldrich, L' isle D'Abeau Chesne, BP 701, 38297, Saint Quentin Fallavier) is prepared. 0.965 ml of this buffer (brought to 37 °C beforehand) is introduced into the cuvette of a spectrophotometer (Perkin-Elmer, Lambda 2) thermostatically maintained at 37⁰C, the measuring wavelength of which is set at 340 ran. 0.035 mL of enzymatic suspension at 37⁰C is introduced into the cuvette concomitantly with the recording (corresponding to an increase in the optical density at 340 nm) . The maximum reaction rate is recorded.

The test values (containing the compounds (I) ) are compared with the control value (without compound (I) ) ; the results indicated represent the concentration at which the compound of formula (I ) reduces the enzymatic activity of 15-PGDH by 50%, namely IC₅₀dh - 2) Test on PGF synthase

The enzyme PGFS is obtained as described in document FR-A-02/05067, at a concentration of 0.5 mg/mL, as a suspension in a suitable medium, and blocked at -80⁰C . For the purposes of the test, this suspension is thawed and stored in ice .

In parallel, a 100 mM, pH 6.5 Tris buffer containing 20 μM of 9 , 10-phenanthrenequinone* (P2896, Sigma-Aldrich, L' isle D' Abeau Chesne, BP 701, 38297 , Saint Quentin Fallavier) and 100 μM of β-NADPH (N1S30 , Sigma-Aldrich, L' isle D' Abeau Chesne, BP 701, 38297 , Saint Quentin Fallavier) is prepared in a brown flask (protected from light) .

*A stock solution with a titre of 1 mM is prepared in absolute ethanol and brought to 40 °C; the flask is placed in an ultrasound cuvette to facilitate the dissolution of the product . 0.950 mL of this buffer (brought to 37 ^αC beforehand) is introduced into the cuvette of a spectrophotometer (Perkin-Elmer, Lambda 2) thermostatically maintained at 37⁰C, the measuring wavelength of which is set at 340 nrα. 0.05 mL of enzymatic suspension at 37⁰C is introduced into the cuvette concomitantly with the recording (corresponding to a reduction in the optical density at 340 nm) . The maximum reaction rate is recorded.

The test values (containing compound (I) ) are compared with the control value (without compound (I) ) ; the results indicated represent the concentration at which the compound of formula ( I) reduces the enzymatic activity of PGFS by 50%, namely IC_50fS .

The results are given in the table below ;

Furthermore, compound 5 inhibits 15-PGDH to a proportion of 21% at 100 μM.

From this table, it is seen that compounds 1 to 8 are indeed 15-PGDH inhibitors . Furthermore, they inhibit 15-PGDH more efficiently and more selectively than PGFS : the IC_50dh is lower than the IC_5Of3.

The compositions below are obtained via the usual techniques commonly used in the cosmetic or pharmaceutical field.

In each of the formulation examples, a fluid is obtained that may be used as an application once or twice a day to the scalp, to reduce hair loss and/or to promote hair growth . EXAMPLE 18 : Hair lotion

- Compound of Example 1 1.00 g

- Propylene glycol 30.00 g - Ethyl alcohol 40.00 g

- Water qs 100.00 g

This lotion is applied to the scalp, once or twice a day, at a rate of 1 mL per application . This lotion makes it possible to reduce hair loss and to promote hair regrowth; it also makes it possible to repigment the hair and thus to hide the white and/or grey hairs . EXAMPLE 19 : Hair lotion

- Compound 1 1.00 g - Propylene glycol 30.00 g

- Ethyl alcohol 40.00 g

- Water qs 100.00 g

This lotion is applied to the scalp, once or twice a day, at a rate of 1 mL per application, by gently massaging the scalp to make the active agent penetrate in . The head of hair is then dried in the open air . This lotion makes it possible to reduce hair loss and to promote regrowth of the hair, and also to repigment grey and/or white hairs . ESg&MBLΞ 20 : Was/water mascara

- Beeswax 6.00% - Paraffin wax 13.00%

- Hydrogenated j ojoba oil 2 %

- Water-soluble film-forming polymer 3 %

- Triethanolamine stearate 8 %

- Compound 1 1 % - Black pigment 5 %

- Preserving agent qs

- Water qs 100 %

This mascara is applied to the eyelashes like a standard mascara with a mascara brush . It promotes the regrowth and the repigmentation of the eyelashes . EXAMPLE 21 : Hair lotion

- Compound of Example 1 1.00 g

- Latanoprost 0.10 g

- Propylene glycol 30.00 g - Ethyl alcohol 40.00 g

- Water qs 100.00 g

This lotion is applied to the scalp, once or twice a day, at. a rate of 1 mL per application, by gently massaging the scalp to make the active agents penetrate in . The head of hair is then dried in the open air . This lotion makes it possible to reduce hair loss and to promote regrowth of the hair while at the same time repigmenting it .

Claims

1. Use of an effective amount of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof :

<« in which : a) Ri and R₂ independently represent:

1) a hydrogen atom,

2) a Ci-C₂O alkyl radical optionally substituted with at least one substituent A₁,

4) an unsaturated hydrocarbon-based ring C² optionally substituted with at least one substituent A₂; b) R3 represents :

1) a hydrogen atom,

2) a C1-C₂₀ alkyl radical optionally substituted with at least one substituent A3, 3) a saturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A₄; c) Ai represents :

1 ) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' , SO₂NRR' , NRSO₂R' , SO₂R, 3) a group having the following formula :

with:

- W = O, NH, S, - X = O, NH, C₁-C₆ N-alkyl,

- Y = C_x-C₄ alkyl, Ci-C₆ alkoxy, NH₂,

Ci-C₆ NH-alkyl, C₁-C₆ N-dialkyl,

4) a saturated hydrocarbon-based ring C⁴ optionally substituted with at least one substituent A₄, 5) a heterocycle Hy₁ chosen from pyrrole, furan, dihydrofuran, tetrahydrofuran, thiophene, thiazole, oxazole, oxazolidine, isoxazole, isoxazolidine, oxadiazole, pyridine, pyran, dihydropyran, tetrahydropyran, pyrimidine, piperazine, pyridazine, pyrazine, morpholine, quinoline, isoquinoline, 2-thiohydantoin, 2-OXO-2, 3-dihydro-l, 3-thiazole and pyridone, this heterocycle possibly being substituted with at least one substituent A₄, 6) an unsaturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A₄ and optionally fused to a hydrocarbon-based or heterocyclic ring C⁶; d) A₂ represents : 1) a fluorine atom, 2) a group of formula CF₃, CN, OR, SR, NRR' , COR, COOR, CONRR' , NRCOR' , NRCONR' R", SO₂NRR' , NRSO₂R' , SO₂R,

3) a C1-C20 alkyl group optionally substituted with at least one substituent A₄; e) A₃ represents :

1) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' ,

3) a group of formula (II)

with W, X and Y having the same meaning as above,

4) a saturated hydrocarbon-based ring C⁴ optionally substituted with at least one substituent A₄, 5) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄ or a heterocycle Hy₂ optionally substituted with at least one substituent A₄ and containing at least one hetero atom chosen from N, 0 and S and a combination thereof; f) A₄ represents :

1) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' ,

3) a Ci-C_2O alkyl group, or 4) a ring C⁶ optionally fused to another ring C⁷, these rings optionally containing at least one hetero atom to form a heterocycle Hy₂; g) R, R' and R", which may be identical or different, represent : 1) a hydrogen atom, 2) a saturated C₁-C₆ alkyl group optionally substituted with at least one substituent A₄, or 3) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄, 4) a heterocycle Hy₂ comprising at least one hetero atom chosen from N, S and O or a combination thereof and possibly being substituted with at least one substituent A₄, as an agent for inducing and/or stimulating the growth of keratin fibres, especially human keratin fibres , and/or for stopping their loss and/or increasing their density.

2. Cosmetic use of at least one 3-sulfanyl- propanamide compound of formula (I) or a salt and/or solvate thereof :

(D in which : a) R₁ and Ra independently represent :

1) a hydrogen atom, 2) a Ci-C₂₀ alkyl radical optionally substituted with at least one substituent Ai,

3) a saturated hydrocarbon-based ring C¹ optionally substituted with at least one substituent Ai;

4) an unsaturated hydrocarbon-based ring C² optionally substituted with at least one substituent A2; b) R₃ represents :

1) a hydrogen atom,

2) a C₁-C20 alkyl radical optionally substituted with at least one substituent A₃,

3 ) a saturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A₄; c) Ai represents :

1) a fluorine atom, 2) a group CF₃, CN, OR, SR, NRR' , SO₂NRR' , NRSO₂R' , SO₂R,

3) a group having the following formula :

(IJ) with: - W = O, NH, S,

- X = O, NH, C_x-C₆ N-alkyl, - Y = Ci-C₄ alkyl, Ci-C₆ alkoxy, NH₂, Ci-C₆ NH-alkyl, C_x-C₆ N-dialkyl,

4) a saturated hydrocarbon-based ring C⁴ optionally substituted with at least one substituent A₄,

5) a heterocycle Hy₁ chosen from pyrrole, furan, T/EP2006/001545

74

dihydrofuran, tetrahydrofuran, thiophene, thiazole, oxazole, oxazolidine, isoxazole, isoxazolidine, oxadiazole, pyridine, pyran, dihydropyran, tetrahydropyran, pyrimidine, piperazine, pyridazine, pyrazine, morpholine, quinoline, isoquinoline, 2-thiohydantoin, 2-OXO-2, 3-dihydro-l, 3-thiazole and pyridone, this heterocycle possibly being substituted with at least one substituent A₄, 6) an unsaturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A₄ and optionally fused to a hydrocarbon-based or heterocyclic ring C⁶; d) Α₂ represents : 1 ) a fluorine atom,

2 ) a group of formula CF₃, CN, OR, SR, NRR' , COR, COOR, CONRR' , NRCOR' , NRCONR' R", SO₂NRR' , NRSO₂R' , SO₂R,

3) a C_X-C₂₀ alkyl group optionally substituted with at least one substituent A₄; e) A₃ represents :

1) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' ,

3) a group of formula (II)

with W, X and Y having the same meaning as above,

5) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄ or a heterocycle Hy₂ optionally substituted with at least one substituent A₄ and containing at least one hetero atom chosen from N, O and S and a combination thereof; f) A₄ represents :

1) a fluorine atom,

2 ) a group CF₃, CN, OR, SR, NRR' ,

3) a C1-C20 alkyl group, or

4 ) a ring C⁶ optionally fused to another ring C⁷, these rings optionally containing at least one hetero atom to form a heterocycle Hy₂; g) R, R' and R", which may be identical or different, represent : 1) a hydrogen atom, 2 ) a saturated Ci-C₆ alkyl group optionally substituted with at least one substituent A₄, or 3 ) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄, 4) a heterocycle Hy₂ comprising at least one hetero atom chosen from N, S and 0 or a combination thereof and possibly being substituted with at least one substituent A₄ , in a cosmetic care and/or makeup composition for keratin fibres, especially human keratin fibres, to induce and/or stimulate their growth, to stop their loss and/or to increase their density.

3. Use of at least one 3-sulfanyl- propanamide compound of formula ( I) or a salt and/or solvate thereof :

(D in which : a) Ri and R₂ independently represent :

1) a hydrogen atom,

2) a C_x-C2o alkyl radical optionally substituted with at least one substituent A₁, 3) a saturated hydrocarbon-based ring C¹ optionally substituted with at least one substituent A₁; 4) an unsaturated hydrocarbon-based ring C² optionally substituted with at least one substituent A₂; b) R₃ represents :

1 ) a hydrogen atom,

2) a C₁-C₂O alkyl radical optionally substituted with at least one substituent A₃,

3 ) a saturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A₄ ; c) Ai represents :

1) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' , SO₂NRR' , NRSO₂R' , SO₂R, 3) a group having the following formula:

with:

- W = O, NH, S, - X = O, NH, C_x-C₆ N-alkyl, - Y = C_x-C₄ alkyl, C₁-C₆ alkoxy, NH₂,

Ci-C₆ NH-alkyl, C_x-C₆ N-dialkyl,

5) a heterocycle Hy_x chosen from pyrrole, furan, dihydrofuran, tetrahydrofuran, thiophene, thiazole, oxazole, oxazolidine, isoxazole, isoxazolidine, oxadiazole, pyridine, pyran, dihydropyran, tetrahydropyran, pyrimidine, piperazine, pyridazine, pyrazine, morpholine, quinoline, isoquinoline, 2-thiohydantoin,

2-OXO-2 , 3-dihydro-l, 3-thiazole and pyridone, this heterocycle possibly being substituted with at least one substituent A₄ ,

6 ) an unsaturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A₄ and optionally fused to a hydrocarbon-based or heterocyclic ring C⁶; d) Jkz represents :

1) a fluorine atom,

2 ) a group of formula CF₃, CN, OR, SR, NRR' , COR, COOR, CONRR' , NRCOR' , NRCONR' R" , SO₂NRR' ,

NRSO₂R' , SO₂R,

3) a Ci-C₂Q alkyl group optionally substituted with at least one substituent A₄; e) A₃ represents : 1 ) a fluorine atom,

2 ) a group CF₃, CN, OR, SR, NRR' ,

3 ) a group of formula ( II)

with W, X and Y having the same meaning as above,

5) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄ or a heterocycle Hy₂ optionally substituted with at least one substituent A₄ and containing at least one hetero atom chosen from N, 0 and S and a combination thereof; f) Αή, represents : 1 ) a fluorine atom,

2 ) a group CF₃, CN , OR, SR, NRR' , 3) a C₁-C₂O alkyl group, or

4 ) a ring C⁶ optionally fused to another ring C⁷, these rings optionally containing at least one hetero atom to form a heterocycle Hy₂; g) R, R' and R", which may be identical or different, represent :

1) a hydrogen atom,

2) a saturated Ci-Cg alkyl group optionally substituted with at least one substituent A₄, or 3) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄, 4) a heterocycle Hy₂ comprising at least one hetero atom chosen from N, S and O or a combination thereof and possibly being substituted with at least one substituent A₄, for the manufacture of a care and/or treatment composition for keratin fibres, especially human keratin fibres, which is intended to induce and/or stimulate their growth and/or to stop their loss and/or to increase their density .

4. Use of an effective amount of at least one 3-sulfanylpropanamide compound of formula (I) or a salt and/or solvate thereof :

(1) in which: a) Ri and R₂ independently represent :

1) a hydrogen atom,

2) a C1-C20 alkyl radical optionally substituted with at least one substituent Ai,

4) an unsaturated hydrocarbon-based ring C² optionally substituted with at least one substituent A₂; b) R₃ represents :

1) a hydrogen atom,

2) a C1-C20 alkyl radical optionally substituted with at least one substituent A₃, 3) a saturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A₄, c) Ai represents :

1) a fluorine atom,

2 ) a group CF₃, CN, OR, SR, NRR' , SO₂NRR' , NRSO₂R' , SO₂R,

3) a group having the following formula:

(U) with:

- W = 0, NH, S,

- X = 0, NH, C_x-C₅ N-alkyl,

- Y = Ci -C₄ alkyl, C_x-C₆ alkoxy, NH₂, C₁-C₅ NH-alkyl, Ci-C₆ N-dialkyl,

5) a heterocycle Hyi chosen from pyrrole, furan, dihydrofuran, tetrahydrofuran, thiophene, thiazole, oxazole, oxazolidine, isoxazole, isoxazolidine, oxadiazole, pyridine, pyran, dihydropyran, tetrahydropyran, pyrimidine, piperazine, pyridazine, pyrazine, morpholine, quinoline, isoquinoline, 2-thiohydantoin,

2-OXO-2, 3-dihydro-l, 3-thiazole and pyridone, this heterocycle possibly being substituted with at least one substituent A₄;

6) an unsaturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A₄ and optionally fused to a hydrocarbon-based or heterocyclic ring C⁶; d) A₂ represents :

1) a fluorine atom, 2 ) a group of formula CF₃, CN, OR, SR, NRR' , COR, COOR, CONRR' , NRCOR' , NRCONR' R", SO₂NRR' , NRSO₂R' , SO₂R, 3) a C1-C20 alkyl group optionally substituted with at least one substituent A₄; e) A₃ represents :

1 ) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' , 3 ) a group of formula ( I I )

with W, X and Y having the same meaning as above; 4) a saturated hydrocarbon-based ring C⁴ optionally substituted with at least one substituent A₄, 5) a unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄ or a heterocycle Hy₂ optionally substituted with at least one substituent A₄ and containing at least one hetero atom chosen from W, 0 and S and a combination thereof; f) A₄ represents :

1) a fluorine atom, 2) a group CF₃, CN, OR, SR, NRR' ,

3) a C1-C20 alkyl group, or

1) a hydrogen atom,

2) a saturated Ci-Cg alkyl group optionally substituted with at least one substituent A₄, or 3) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄,

4) a heterocycle Hy2 comprising at least one hetero atom chosen from N, S and O or a combination thereof and possibly being substituted with at least one substituent A₄, as an agent for inducing and/or stimulating the pigmentation of the skin and/or keratin fibres , especially human skin and/or keratin fibres , and/or for limiting their depigmentation and/or bleaching . 5. Cosmetic use of at least one 3-sulfanyl- propanamide compound of formula (I) or a salt and/or solvate thereof :

(I) in which : a) Ri and R₂ independently represent :

1) a hydrogen atom,

2) a Ci-C₂O alkyl radical optionally substituted with at least one substituent Ai,

3) a saturated hydrocarbon-based ring C¹ optionally substituted with at least one substituent A_x;

4 ) an unsaturated hydrocarbon-based ring C² optionally substituted with at least one substituent A₂; b) R3 represents : 1 ) a hydrogen atom, 2) a Ci-C₂O alkyl radical optionally substituted with at least one substituent A₃,

3) a saturated hydrocarbon-based ring C³ optionally- substituted with at least one substituent A₄; c) Ai represents :

1) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' , SO₂NRR' , NRSO₂R' , SO₂R,

3) a group having the following formula :

with :

- W = O, NH, S, - X = O, NH, C₁-C₅ N-alkyl, - Y = Ci-C₄ alkyl, C_x-C₆ alkoxy, NH₂, Ci-C₅ NH-alkyl, C_x-C₅ N-dialkyl,

5) a heterocycle Hy₁ chosen from pyrrole, furan, dihydrofuran, tetrahydrofuran, thiophene, thiazole, oxazole, oxazolidine, isoxazole, isoxazolidine, oxadiazole, pyridine, pyran, dihydropyran, tetrahydropyran, pyrimidine, piperazine, pyridazine, pyrazine, morpholine, quinoline, isoquinoline, 2-thiohydantoin, 2-OXO-2, 3-dihydro-l, 3-thiazole and pyridone, this heterocycle possibly being substituted with at least one substituent A₄; 6) an unsaturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A4 and optionally fused to a hydrocarbon-based or heterocyclic ring C⁶; d) A₂ represents :

1) a fluorine atom,

2) a group of formula CF₃, CN, OR, SR, NRR' , COR, COOR, CONRR' , NRCOR' , NRCONR' R", SO₂NRR' , NRSO₂R' , SO₂R,

3) a Ci-C₂O alkyl group optionally substituted with at least one substituent A₄; e) A₃ represents :

1) a fluorine atom, 2 ) a group CF₃, CN, OR, SR, NRR' ,

3) a group of formula (II)

with W, X and Y having the same meaning as above, 4 ) a saturated hydrocarbon-based ring C⁴ optionally substituted with at least one substituent A₄, 5) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄ or a heterocycle Hy₂ optionally substituted with at least one substituent A₄ and containing at least one hetero atom chosen from N, O and S and a combination thereof; f) Jk₄ represents :

1) a fluorine atom,.

2) a group CF₃, CN, OR, SR, NRR' , 3) a C1-C20 alkyl group, or

4 ) a ring C⁶ optionally fused to another ring C⁷, these rings optionally containing at least one hetero atom to form a heterocycle Hy₂; g) R, R^? and R", which may be identical or different, represent :

1) a hydrogen atom,

2) a saturated Ci-Cδ alkyl group optionally substituted with at least one substituent A₄, or

3 ) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄,

4) a heterocycle Hy2 comprising at least one hetero atom chosen from N, S and O or a combination thereof and possibly being substituted with at least one substituent A₄, in a cosmetic care and/or makeup composition for the skin and/or keratin fibres, especially human skin and/or keratin fibres , to induce and/or stimulate the pigmentation of the said skin and/or the said keratin fibres and/or for limiting their depigmentation and/or bleaching .

6. Use of at least one 3-sulfanyl- propanamide compound of formula (I) or a salt and/or solvate thereof :

(I) in which : a) Ri and R₂ independently represent :

1) a hydrogen atom,

2) a C₁-C20 alkyl radical optionally substituted with at least one substituent Ai,

3 ) a saturated hydrocarbon-based ring C¹ optionally substituted with at least one substituent Ai;

4 ) an unsaturated hydrocarbon-based ring C² optionally substituted with at least one substituent A₂; b) R₃ represents : 1) a hydrogen atom,

1 ) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' , SO₂NRR' , NRSO₂R' , SO₂R,

3) a group having the following formula :

with:

- W = O, NH, S, - X = O, NH, Ci-C₆ N-alkyl, - Y = Ci-C₄ alkyl, C_x-C₆ alkoxy, NH₂,

Ci-C₆ NH-alkyl, C_x-C₆ N-dialkyl,

2-OXO-2, 3-dihydro-l , 3-thiazole and pyridone, this heterocycle possibly being substituted with at least one substituent A₄ ,

1 ) a fluorine atom, 2 ) a group of formula CF₃, CN, OR, SR, NRR' , COR, COOR, CONRR' , NRCOR' , NRCONR' R" , SO₂NRR' , NRSO₂R' , SO₂R,

3) a C₁-C20 alkyl group optionally substituted with at least one substituent A₄; e) A₃ represents : 1) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' ,

3) a group of formula (II)

with W, X and Y having the same meaning as above,

5) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄ or a heterocycle Hy₂ optionally substituted with at least one substituent A₄ and containing at least one hetero atom chosen from N, 0 and S and a combination thereof; f) A₄ represents : 1 ) a fluorine atom,

2 ) a group CF₃, CN, OR, SR, NRR' ,

3) a C_x-C₂O alkyl group, or

4 ) a ring C^δ optionally fused to another ring C⁷, these rings optionally containing at least one hetero atom to form a heterocycle Hy₂; g) R, R' and R" , which may be identical or different, represent :

1 ) a hydrogen atom,

2 ) a saturated Ci-Cs alkyl group optionally substituted with at least one substituent A₄, or 3 ) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄, 4 ) a heterocycle Hy2 comprising at least one hetero atom chosen from N, S and O or a combination thereof and possibly being substituted with at least one substituent A₄, for the manufacture of a composition for caring for and/or treating the skin and/or keratin fibres, especially human skin and/or keratin fibres, which is intended to induce and/or stimulate the pigmentation of the said skin and/or the said fibres and/or to limit their depigmentation and/or bleaching .

7. Use of at least one 3-sulfanyl- propanamide compound of formula ( I) or a salt and/or solvate thereof :

(I) in which : a) Ri and R₂ independently represent :

1 ) a hydrogen atom, 2 ) a C₁-C₂₀ alkyl radical optionally substituted with at least one substituent Ai,

1 ) a hydrogen atom,

3) a group having the following formula :

(il) with : - W = O, NH, S,

- X = O, NH, Ci-C₅ N-alkyl, - Y = Ci-C₄ alkyl, C_x-C₆ alkoxy, NH₂, Ci-C₆ NH-alkyl, C_x-C₆ N-dialkyl,

5) a heterocycle Hy_x chosen from pyrrole, furan, dihydrofuran, tetrahydrofuran, thiophene, thiazole, oxazole, oxazolidine, isoxazole, isoxazolidine, oxadiazole, pyridine, pyran, dihydropyran, tetrahydropyran, pyrimidine, piperazine, pyridazine, pyrazine, morpholine, quinoline, isoquinoline, 2-thiohydantoin, 2-OXO-2, 3-dihydro-l, 3-thiazole and pyridone, this heterocycle possibly being substituted with at least one substituent A₄, 6) an unsaturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A₄ and optionally fused to a hydrocarbon-based or heterocyclic ring C⁶; d) A₂ represents : 1) a fluorine atom,

3) a Ci-C₂₀ alkyl group optionally substituted with at least one substituent A₄ ; e) A₃ represents :

1) a fluorine atom,

2 ) a group CF₃, CN, OR, SR, NRR' ,

3 ) a group of formula (II)

with W, X and Y having the same meaning as above,

4) a saturated hydrocarbon-based ring C⁴ optionally substituted with at least one substituent A₄ ,

1) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' ,

3) a C_x-C₂O alkyl group, or

4 ) a ring C⁶ optionally fused to another ring C⁷, these rings optionally containing at least one hetero atom to form a heterocycle Hy₂; g) R, R' and R", which may be identical or different, represent : 1 ) a hydrogen atom, 2) a saturated Ci-Cε alkyl group optionally substituted with at least one substituent A₄ , or 3) an unsaturated hydrocarbon-based ring C⁵ optionally substituted with at least one substituent A₄ , 4 ) a heterocycle Hy₂ comprising at least one hetero atom chosen from N, S and 0 or a combination thereof and possibly being substituted with at least one substituent A₄, as an agent for inhibiting 15-hydroxyprostaglandin dehydrogenase, especially of type 1.

8. Use of at least one 3-sulfanyl- propanamide compound of formula ( I) or a salt and/or solvate thereof :

(D in which : a) Ri and R₂ independently represent : 1) a hydrogen atom,

2 ) a C1-C20 alkyl radical optionally substituted with at least one substituent Ai,

3) a saturated hydrocarbon-based ring C¹ optionally substituted with at least one substituent Ai; 4 ) an unsaturated hydrocarbon-based ring C² optionally substituted with at least one substituent A₂; b) R₃ represents :

1) a hydrogen atom, 2) a Ci-C_2O alkyl radical optionally substituted with at least one substituent A₃,

3) a saturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A₄ ; c) Ai represents : 1 ) a fluorine atom, 2) a group CF₃, CN, OR, SR, NRR' , SO₂NRR' , NRSO₂R' , SO₂R,

3) a group having the following formula :

with:

- W = O, NH, S,

- X = O, NH, C₁-C₆ N-alkyl,

- Y = C₁-C₄ alkyl, C₁-C₆ alkoxy, NH₂,

C₁-C₆ NH-alkyl, C₁-C₆ N-dialkyl, 4) a saturated hydrocarbon-based ring C⁴ optionally substituted with at least one substituent A₄,

5) a heterocycle Hy₁ chosen from pyrrole, furan, dihydrofuran, tetrahydrofuran, thiophene, thiazole, oxazole, oxazolidine, isoxazole, isoxazolidine, oxadiazole, pyridine, pyran, dihydropyran, tetrahydropyran, pyrimidine, piperazine, pyridazine, pyrazine, morpholine, quinoline, isoquinoline, 2-thiohydantoin, 2-OXO-2 , 3-dihydro-l, 3-thiazole and pyridone, this heterocycle possibly being substituted with at least one substituent A₄,

6) an unsaturated hydrocarbon-based ring C³ optionally substituted with at least one substituent A₄ and optionally fused to a hydrocarbon-based or heterocyclic ring C⁶; d) A₂ represents : 1) a fluorine atom,

2) a group of formula CF₃, CN, OR, SR, NRR' , COR, COOR, CONRR' , NRCOR' , NRCONR' R", SO₂NRR' , NRSO₂R' , SO₂R, 3) a Ci-C₂O alkyl group optionally substituted with at least one substituent A₄; e) A₃ represents :

1) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' , 3) a group of formula (II)

with W, X and Y having the same meaning as above,

1) a fluorine atom,

2 ) a group CF₃, CN, OR, SR, NRR' , 3 ) a C_X-C₂₀ alkyl group, or

4 ) a ring C⁶ optionally fused to another ring C⁷, these rings optionally containing at least one hetero atom to form a heterocycle Hy₂; g) R, R' and R", which may be identical or different, represent : 1) a hydrogen atom,

2 ) a saturated C₁-Cg alkyl group optionally substituted with at least one substituent A₄ , or

4) a heterocycle Hy₂ comprising at least one hetero atom chosen from N, S and O or a combination thereof and possibly being substituted with at least one substituent A₄, for the manufacture of a composition for caring for and/or treating human skin and/or keratin fibres , which is intended to treat disorders associated with type-1 15-hydroxyprostaglandin dehydrogenase .

9. Use according to one of the preceding claims , characterized in that the human keratin fibres are head hair, the eyebrows , the eyelashes, beard hair, moustache hair and pubic hair, and the nails .

10. Cosmetic use of at least one 3-sulfanyl- propanamide compound of formula (I) or a salt and/or solvate thereof, as defined in Claim 1, in a cosmetic composition for caring for human hair to reduce hair loss and/or to increase its density and/or to treat andro-chrono-genetic alopecia and/or to treat alopecia of natural origin and/or to reduce the depigmentation and/or bleaching of the hair .

11. Use of at least one 3-sulfanyl- propanamide compound of formula (I) or a salt and/or solvate thereof, as defined in Claim 1, for the preparation of a human hair care composition which is intended to induce and/or stimulate hair growth and/or to stop its loss and/or to increase its density and/or to treat androgenic alopecia and/or to treat alopecia of natural origin and/or to induce and/or stimulate the pigmentation of the hair and/or to limit its depigmentation and/or bleaching .

12. Cosmetic use of at least one 3-sulfanyl- propanamide compound of formula (I) or a salt and/or solvate thereof, as defined in Claim 1 , in a cosmetic composition for caring for and/or making up human eyelashes, to induce and/or stimulate the growth of the eyelashes and/or to increase their density and/or to reduce their bleaching .

13. Use of at least one 3-sulfanyl- propanamide compound of formula (I) or a salt and/or solvate thereof, as defined in Claim 1, for the preparation of a composition for caring for and/or treating human eyelashes , which is intended to induce and/or stimulate the growth of the eyelashes and/or to increase their density and/or to induce and/or stimulate their pigmentation and/or to limit their depigmentation and/or bleaching.

14. Use according to one of the preceding claims, characterized in that the heterocycle Hy₂ represents one of the following heterocycles : azetidine, pyrrole, dihydropyrrole, pyrrolidine, furan, dihydrofuran, tetrahydrofuran, thiophene, dihydrothiophene, tetrahydrothiophene, imidazole, dihydroimidazole, imidazolidine, dihydrothiazole, thiazole, dihydrothiazole, thiazolidine, pyrazole, dihydropyrazole, pyrazolidine, oxazole, dihydrooxazole, oxazolidine, isoxazole, dihydroisoxazole, isoxazolidine, isothiazole, dihydroisothiazole, isothiazolidine, triazole, dihydrotriazole, triazolidine, oxadiazole, dihydrooxadiazole, oxadiazolidine, thiadiazole, dihydrothiadiazole, thiadiazolidine, tetrazole, pyridine, dihydropyridine, tetrahydropyridine, piperidine, pyran, dihydropyran, tetrahydropyran, pyrimidine, dihydropyrimidine, tetrahydropyrimidine, piperazine, pyridazine, pyrazine, triazine, morpholine, azepine, diazepine .

15. Use according to one of the preceding claims, characterized in that Hy₂ represents one of the following compounds : pyrrole, furan, dihydrofuran, tetrahydrofuran, thiophene, thiazole, oxazole, oxazolidine, isoxazole , isoxazolidine, oxadiazole, pyridine, pyran, dihydropyran, tetrahydropyran, pyrimidine, piperazine, pyridazine, pyrazine, morpholine, quinoline, isoquinoline, 2-thiohydantoin, 2-OXO-2, 3-dihydro-l, 3-thiazole or pyridone .

16. Use according to one of the preceding claims, characterized in that one from among R₁ and R₂ represents hydrogen .

17. Use according to one of the preceding claims, characterized in that Ri represents a linear or branched, saturated or unsaturated Ci to Ci₀ alkyl radical or a saturated or unsaturated hydrocarbon-based ring, this radical or this ring being substituted with an unsaturated hydrocarbon-based or heterocyclic ring C⁵, this ring C⁵ itself being optionally substituted with one or more substituents A₁.

18. Use according to one of the preceding claims , characterized in that Ai is chosen from:

- linear or branched, saturated or unsaturated Ci-Cio alkyl radicals;

- C₁-Cg alkoxy radicals ; - aryl rings .

19. Use according to one of the preceding claims , characterized in that A₁ is chosen from methyl, ethyl and methoxy radicals and phenyl and naphthyl rings .

20. Use according to one of the preceding claims, characterized in that R3 represents a linear or branched, saturated or unsaturated Ci to C₁₀ alkyl radical or a saturated or unsaturated hydrocarbon-based ring .

21. Use according to one of the preceding claims, characterized in that R₃ is chosen from methyl, tert-butyl, cyclopentyl and cyclohexyl radicals .

22. Use according to one of the preceding claims, characterized in that the compound is in hydrate form.

23. Use according to one of the preceding claims, characterized in that the compound has the formula ( Ia) below, or a corresponding salt and/or solvate thereof :

in which R₁ and R3 have the same definitions as above .

24. Use according to one of the preceding claims , characterized in that the compound has one of the formulae (III) , (IV) , (V) , (VII) and (VIII) below:

in which Q represents : a) a phenyl radical substituted with at least one radical Z; or b) an aromatic heterocycle chosen from pyrimidine, quinoline, isoquinoline, pyrrole, furan or thiophene, optionally substituted with at least one radical Z , 6 001545

102

with Z representing : fluorine,

- the groups CF₃, CN, OR, SR, NRR' , SO₂NRR' , NRSO₂R' , SO₂R, SiRR' R", with R and R' having the same meaning as above,

- a group of formula (II) :

with W, X and Y having the same meaning as above, a Ci-Cio alkyl group optionally substituted with at least one substituent A₄; and in which T represents : a) a saturated alkyl radical chosen from methyl , ethyl , n-butyl, isobutyl and tert-butyl; or b) a saturated C₄-C₆ hydrocarbon-based ring:

45

103

25. Use according to one of the preceding claims, characterized in that the salt of the compound of formula (I) is chosen from the sodium and potassium salts, the ammonium salts, the zinc (Zn²⁺) , calcium (Ca²⁺) , copper (Cu²⁺) , iron (Fe²⁺ and Fe³⁺) , strontium (Sr²⁺) , magnesium (Mg²⁺) and manganese (Mn²⁺) salts, and the triethanolamine, monoethanolamine, diethanolamine, hexadecylamine, N, N, N' ,N' -tetrakis (2-hydroxypropyl) - ethylenediamine, tris-hydroxymethylaminomethane, hydroxide, hydrohalide, carbonate, hydrogen carbonate, citrate, lactate, glycolate, gluconate, acetate, propionate, fumarate, oxalate, tartrate, sulfate, phosphate and hydrogen phosphate salts .

26. Use according to one of the preceding claims, characterized in that the compound of formula

(I ) satisfies one of the following formulae : Compound 1 : N- [ (5-methyl-2-furyl)methyl] -3- (methyl- sulfanyl) propanamide

Compound 2 : N- (2-furylmethyl) -3- (methylsulfanyl) - propanamide

Compound 3 : N- (4-methoxybenzyl) -3- (methylsulfanyl) - propanamide

Compound 4 : N-hexyl-3- (methyl sulfanyl) propanamide

Compound 5 : 3- (methylsulfanyl ) -N- [2- (trif luoromethyl ) phenyl ] propanamide

Compound 6 : N-benzyl-3- (methylsulfanyl) propanamide

Compound 7 : 3- (methylsulfanyl) -N- (1-phenylethyl) - propanamide

Compound 8 : N-cyclobutyl-3 - (methylsulfanyl) propanamide

27. use according to one of the preceding claims , characterized in that the compound of formula (I) or a mixture of compounds of formula ( I) is used in a concentration ranging from 10^"3% to 5% relative to the total weight of the composition .

28. Use according to one of the preceding claims, characterized in that the composition is a composition for topical application .

29. Composition for caring for and/or making up the skin and/or keratin fibres, for topical application, containing a physiologically acceptable medium and an effective amount of at least one 3-sulfanylpropanamide compound corresponding to one of the formulae (III) , (IV) , (V) , (VII) and (VIII) below or a salt and/or solvate thereof :

in which Q represents : a) a phenyl radical substituted with at least one radical Z ; or b) an aromatic heterocycle chosen from pyrimidine, quinoline, isoquinoline, pyrrole, furan or thiophene, optionally substituted with at least one radical Z, with Z representing : fluorine,

- the groups CF₃, CN, OR, SR, NRR' , SO₂NRR', NRSO₂R', SO₂R, SiRR' R", a group of formula (II) :

with :

- W = O, NH, S,

- X = O, NH, Ci-C₆ N-alkyl,

- Y = C_x-C₄ alkyl, C_x-C₆ alkoxy, NH₂, C₁-C₆ NH-alkyl, C_x-C₆ N-dialkyl,

- a C₁-C_xQ alkyl group optionally substituted with at least one substituent A₄;

R, R' and R", which may be identical or different, represent : 1) a hydrogen atom,

2) a saturated C_x-C₆ alkyl group optionally substituted with at least one substituent A₄, or

3 ) an unsaturated hydrocarbon-based ring C₅ optionally substituted with at least one substituent A₄,

4 ) a heterocycle Hy₂ comprising at least one hetero atom chosen from N, S and 0 or a combination thereof and possibly being substituted with at least one substituent A₄, in which A₄ represents : 1 ) a fluorine atom, 2 ) a group CF₃, CN, OR, SR, NRR'

3) a Ci-C_2O alkyl group, or

4) a ring C⁶ optionally fused to another ring C⁷, these rings optionally containing at least one hetero atom to form a heterocycle Hy₂, in which T represents : a) a saturated alkyl radical chosen from methyl , ethyl, n-butyl, isobutyl and tert-butyl; or b) a saturated C4-C6 hydrocarbon-based ring;

30. Composition according to Claim 29, characterized in that the salt of the compound of formula ( I) is chosen from the sodium and potassium salts, the ammonium salts , the zinc (Zn²⁺, calcium (Ca²⁺) , copper (Cu²⁺) , iron (Fe²⁺ and Fe³⁺) , strontium (Sr²⁺) , magnesium (Mg²⁺) and manganese (Mn²⁺) salts, and 5 the triethanolamine, diethanolamine, monoethanolamine, hexadecylamine, N, N, N' ,N' -tetrakis (2-hydroxypropyl) - ethylenediamine, tris-hydroxymethylaminomethane, hydroxide, hydrohalide, carbonate, hydrogen carbonate, citrate, lactate, glycolate, gluconate, acetate, 0 propionate, fumarate, oxalate, tartrate, sulfate, phosphate and hydrogen phosphate salts .

31. Composition according to either of

Claims 29 and 30, characterized in that the compound of formula (I) satisfies one of the following formulae : 5 Compound 1 : N- [ (5-methyl-2-furyl) methyl] -3- (methyl- sulfanyl) propanamide

Compound 2 : N- ( 2-furylmethyl ) -3- (methylsulfanyl ) - propanamide

Compound 3 : N- ( 4 -methoxybenzyl ) -3- (methylsulfanyl ) - propanamide

Compound 4 : N-hexyl-3- (methylsulfanyl) propanamide

Compound 5 : 3- (methylsulfanyl) -N- [2- (trifluoromethyl) phenyl] propanamide

Compound 6 : N-benzyl-3- (methylsulfanyl) propanamide

Compound 7 : 3- (methylsulfanyl) -N- (1-phenylethyl) - propanamide

Compound 3 : N-cyclobutyl-3^~ (methylsulfanyl) propanamide

32. Composition according to one of Claims 29 to 31 , characterized in that the compound of formula ( I ) or a mixture of compounds of formula (I) is used in a concentration ranging from 10^"3% to 5% relative to the total weight of the composition .

33. Composition according to one of

Claims 29 to 32, characterized in that it is in the form of a hair cream or hair lotion, a shampoo, a hair conditioner, a hair mascara or an eyelash mascara.

34. Composition according to one of Claims 29 to 33 , characterized in that it contains other ingredients chosen from solvents, aqueous-phase or oily-phase thickeners or gelling agents , dyestuffs that are soluble in the medium of the composition, fillers , pigments, antioxidants, sequestrants , preserving agents, fragrances, electrolytes, neutralizers , film-forming polymers , UV blockers, cosmetic or pharmaceutical active agents other than the compounds of formula (I) , and mixtures thereof.

35. Composition according to one of Claims 29 to 34 , characterized in that it also contains at least one active agent chosen from proteins, protein hydrolysates, amino acids , polyols , urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts , hydroxy acids , retinol, tocopherol, retinol or tocopherol derivatives, essential fatty acids, ceramides , essential oils , salicylic acid derivatives , for instance, 5-n-octanoylsalicylic acid, hydroxy acid esters and phospholipids, and mixtures thereof .

36. Composition according to one of Claims 29 to 35, characterized in that it contains at least one additional active agent that promotes the regrowth and/or limits the loss of keratin fibres .

37. Composition according to Claim 36, characterized in that the additional active agent is chosen from aminexil, diethyl 2, 4-pyridine- dicarboxylate, 6-0- [ ( 9Z, 12Z) -octadeca-9, 12-dienoyl] - hexapyranose, lipoxygenase inhibitors, bradykinin inhibitors, prostaglandins and derivatives thereof, prostaglandin receptor agonists or antagonists, non- prostanoic prostaglandin analogues, vasodilators, anti- androgens, cyclosporins and analogues thereof, antimicrobial agents , antiinflammatory agents, retinoids, benzalkonium chloride, benzethonium chloride, phenol, oestradiol, chlorpheniramine maleate, chlorophylline derivatives, cholesterol, cysteine, methionine, menthol, peppermint oil, calcium pantothenate, panthenol, resorcinol, protein kinase C activators , glycosidase inhibitors, glycosamino- glycanase inhibitors, pyroglutamic acid esters, hexosaccharidic or acylhexosaccharic acids, substituted arylethylenes, N-acylamino acids, flavonoids, ascomycin derivatives and analogues , histamine antagonists, saponins, proteoglycanase inhibitors, oestrogen 6 001545

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agonists and antagonists, pseudoterines, cytokines and growth factor promoters , IL-I or IL-6 inhibitors, IL-IO promoters, TNF inhibitors , vitamins, benzophenones, hydantoin, retinoic acid, anti-pruriginous agents, antiparasitic agents, antifungal agents, calcium antagonists, hormones , triterpenes, antiandrogens, steroidal or non-steroidal 5-α-reductase inhibitors, potassium canal agonists and FP receptor agonists, and mixtures thereof .

38. Composition according to one of

Claims 29 to 37 , characterized in that it contains at least one additional active compound that promotes regrowth and/or limits the loss of keratin fibres, chosen from aminexil, FP receptor agonists, prostaglandins and derivatives thereof, and vasodilators .

39. Composition according to one of

Claims 29 to 38, characterized in that the additional active compound is chosen from aminexil, minoxidil, latanoprost, (5E) -7- { ( IR, 2R, 3R, 5S) -3 , 5-dihydroxy~2- [ (3R) -3-hydroxy-5-phenylpentyl] cyclopentyl}-hept-5- enoic acid, butaprost, travoprost, diethyl 2, 4- pyridinedicarboxylate and 6-0- [ ( 9Z, 12Z) -octadeca-9, 12- dienoyl] hexapyranose .

40. Cosmetic process for treating human keratin fibres and/or the skin, in particular that from which the said fibres emerge, characterized in that it consists in applying to the said fibres and/or the said skin a cosmetic composition comprising at least one compound of formula (I) or a salt and/or solvate thereof as defined in Claims 1 to 28, leaving the composition in contact with the said keratin fibres and/or the said skin, and optionally rinsing the said fibres and/or the said skin .

41. Cosmetic process for caring for and/or making up human eyelashes, in order to improve their condition and/or their appearance, characterized in that it consists in applying to the eyelashes and/or the eyelids a mascara composition comprising at least one compound of formula (I) or a salt and/or solvate thereof as defined in Claims 1 to 28 and leaving the composition in contact with the eyelashes and/or the eyelids .

42. Cosmetic process for caring for human hair and/or the scalp, in order to improve their condition and/or their appearance, characterized in that it consists in applying to the hair and/or the scalp a cosmetic composition comprising an effective amount of at least one compound of formula (I) or a salt and/or solvate thereof as defined in Claims 1 to 28 , leaving the composition in contact with the hair and/or the scalp, and optionally rinsing the hair and/or the scalp .

43. Cosmetic process for treating human EP2006/001545

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skin, in order to improve its condition and/or its appearance, characterized in that it consists in applying to the said skin a cosmetic composition comprising an effective amount of at least one compound of formula (I) or a salt and/or solvate thereof as defined in Claims 1 to 28 , leaving the composition in contact with the said skin, and optionally rinsing it off .

44. 3-Sulfanylpropanamide compound, characterized in that it satisfies one of the formulae (III) , (IV) , (V) , (VII) and (VIII) below, or a corresponding salt and/or solvate thereof:

in which Q represents : a) a phenyl radical substituted with at least one radical Z; or b) an aromatic heterocycle chosen from pyrimidine, quinoline, isoquinoline, pyrrole, furan or thiophene, optionally substituted with at least one radical Z, with Z representing :

- fluorine,

- the groups CF₃, CN, OR, SR, NRR' , SO₂NRR' , NRSO₂R' , SO₂R, SiRR' R", a group of formula (II) :

with :

- W = O, NH, S, - X = O, NH, C₁-C₆ N-alkyl, - Y = Ci-C₄ alkyl, C_x-C₆ alkoxy, NH₂,

Ci-C₆ NH-alkyl, C_x-C₆ N-dialkyl , a C_x-C₁O alkyl group optionally substituted with at least one substituent A₄;

R_Λ R' and R", which may be identical or different, represent :

1 ) a hydrogen atom,

3) an unsaturated hydrocarbon-based ring C₅ optionally substituted with at least one substituent A₄,

4 ) a heterocycle Hy₂ comprising at least one heteroatom chosen from N, S and O or a combination thereof and possibly being substituted with at least one substituent A₄ , in which A₄ represents :

1) a fluorine atom,

2) a group CF₃, CN, OR, SR, NRR' ,

3 ) a C₁-C₂₀ alkyl group, or 4 ) a ring C⁶ optionally fused to another ring C⁷, these rings optionally containing at least one hetero atom to form a heterocycle Hy₂, in which T represents : a) a saturated alkyl radical chosen from methyl, ethyl, n-butyl, isobutyl and tert-butyl; or b) a saturated C₄-Cg hydrocarbon-based ring;

45. Compound according to Claim 44, characterized in that xt satisfies one of the following formulae : Compound 1 : N- [ (5-methyl-2-furyl) methyl] -3- (methyl- sulfanyl) propanamide

Compound 2 : N- ( 2-fυrylmethyl ) -3- (methylsulfanyl ) - propanamide

Compound 3 : N- (4-methoxybenzyl) -3- (methylsulfanyl) propanamide

Compound 4 : N-hexyl-3- (methylsulfanyl) propanamide

Compound 5 : 3- (methylsulfanyl) -N- [2- (trifluoromethyl) phenyl] propanamide

Compound 7 : 3- (methylsulfanyl) -N- (1-phenylethyl) - propanamide

Compound 8 : N-cyclobutyl-3- (methylsulfanyl) propanamide