Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
  • A61K8/42—Amides
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
  • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
  • A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
  • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
  • A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
  • A61Q1/02—Preparations containing skin colorants, e.g. pigments
  • A61Q1/10—Preparations containing skin colorants, e.g. pigments for eyes, e.g. eyeliner, mascara
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q7/00—Preparations for affecting hair growth

Definitions

• 2-oxy-acetamide compound its uses and compositions for stimulating or inducing the growth of keratin fibers and / or curbing their fall FIELD OF THE INVENTION
• the subject of the invention is a composition for caring for or making up keratin fibers, containing an effective amount of a 2-oxy-acetamide compound, intended to increase the density of these fibers and / or improve their appearance. More specifically, the invention relates to a composition for caring for or making up hair or eyelashes, intended to induce and / or stimulate their growth and / or slow down their fall. It also relates to new 2-oxy-acetamide compounds and to a cosmetic treatment process intended to stimulate the growth of keratin fibers and in particular of the hair and / or to curb their fall.
• the human keratin fibers to which the invention applies are in particular hair, eyebrows, eyelashes, beard hair, mustache hair and pubic hair. More specifically, the invention applies to human hair and / or eyelashes.
• the invention relates to a composition for caring for and / or making up hair or eyelashes, for topical application, containing a 2-oxy-acetamide compound, intended to increase their density and / or their appearance.
• Hair growth and hair renewal are mainly determined by the activity of the hair follicles and their matrix environment. Their activity is cyclical and essentially comprises three phases, namely the anagen phase, the catagen phase and the telogen phase.
• the anagen phase active or growth phase
• the catagen phase active or growth phase
• the anagen phase active or growth phase
• transient catagen phase which lasts a few weeks. During this phase, the hair undergoes an evolution, the follicle atrophies and its dermal implantation appears higher and higher.
• the terminal phase or telogen phase which lasts a few months, corresponds to a resting phase of the follicle and the hair ends up falling out. At the end of this rest period, a new follicle is regenerated on site, and another cycle begins again. The hair is therefore constantly renewed and of the approximately 150,000 hairs in hair, approximately 10% are at rest and will be replaced in a few months.
• Natural hair loss or loss can be estimated, on average, a few hundred hairs per day for a normal physiological state. This permanent physical renewal process undergoes a natural evolution during aging, the hair becomes thinner and their cycles shorter.
• different causes can cause significant, temporary or permanent loss of hair. It can be hair loss and alteration during pregnancy (post partum), during states of undernutrition or food imbalances, during physiological stress or even during states of asthenia or hormonal dysfunction as may be the case during or after menopause. It can also be a question of hair loss or alterations in relation to seasonal phenomena. It can also be an alopecia, which is essentially due to a disturbance of the capillary renewal leading initially to the acceleration of the frequency of the cycles to the detriment of the quality of the hair, then of their quantity. Successive growth cycles result in increasingly thinner and shorter hair, gradually transforming into an unpigmented down.
• alopecia also covers a whole family of damage to the hair follicle, the final consequence of which is the permanent, partial or general loss of hair. It is more particularly about androgenic alopecia. In a significant number of cases, early hair loss occurs in genetically predisposed subjects, it is then andro-chrono-genetic alopecia; this form of alopecia especially concerns men.
• hair loss can be strongly accentuated or lead to cycles of the follicles which are highly disturbed.
• compositions which make it possible to suppress or reduce alopecia, and in particular to induce or stimulate hair growth or to reduce hair loss.
• compositions comprising very diverse active agents, such as, for example, 2,4-diamino 6-piperidinopyrimidine 3-oxide or "minoxidil” described in US Patents 4,139,619 and US 4,596 812 or its numerous derivatives such as those described in documents EP 0353123, EP 0356271, EP 0408442, EP 0522964, EP 0420707, EP 0459890, EP 0519819.
• active agents such as, for example, 2,4-diamino 6-piperidinopyrimidine 3-oxide or "minoxidil” described in US Patents 4,139,619 and US 4,596 812 or its numerous derivatives such as those described in documents EP 0353123, EP 0356271, EP 0408442, EP 0522964, EP 0420707, EP 0459890, EP 0519819.
• prostaglandins are molecules with a very short biological half-life time and acting 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 therefore appears to be important, in order to maintain and / or increase the capillary density in humans, to preserve the endogenous reserves of PGF2- ⁇ as of PGE2 in the various compartments of the hair follicle or of its close cutaneous environment.
• the differentiation programs of the keratinocytes of the epidermis and of the hair follicle are clearly different.
• the keratins of the hair shaft represent a family (Langbein et al., 2001, J. Biol. Chem. 276: 35123-35132) distinct from that expressed in the epidermis, as the differentiation markers such that keratins K and K 10 are not expressed in the hair follicle and in particular in the external sheath (Lenoir et al., 1988, Dev. Biol. 130: 610-620), than trichohyaline (O'Guin et al ., 1992, J. Invest. Dermatol.
• keratin K ⁇ irs are expressed in the hair follicle in particular in the internal sheath but not in the epidermis, and that type 1 cyclo-oxygenase, if it is 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 determining compartment for the life of the hair. Indeed, the applicant has now proven the presence of 15-hydroxy prostaglandin dehydrogenase (15-PGDH for short) type 1 at this level. He also showed that inhibition of 15-PGDH type 1 has a beneficial effect on hair growth.
• 15-PGDH 15-hydroxy prostaglandin dehydrogenase
• the present invention relates to a hair care or treatment composition containing at least one particular inhibitor of 15-hydroxy prostaglandin dehydrogenase type 1 and a physiologically acceptable medium.
• 15-PGDH type 1 is a key enzyme in the deactivation of prostaglandins, in particular PGF2- ⁇ , and PGE2, which are important mediators of hair growth and survival. It meets the EC 1.1.1.141 classification and is NAD + dependent. She was isolated from pork kidney; in particular, its inhibition by a thyroid hormone, tri-iodo thyronine, has been observed at doses much higher than physiological doses. 15-PGDH type 2 is NADP dependent. However, it has never been proposed to use a 15-PGDH type 1 inhibitor to maintain and / or increase the density of human keratin fibers and in particular human hair and / or to reduce the heterogeneity of the diameters of the fibers. keratin and especially hair in humans.
• the present invention therefore relates to a composition for caring for and / or making up keratin fibers, in particular hair or mascara for topical application containing in a physiologically acceptable medium an effective amount of at least one 2-oxy-acetamide compound of formula (I) or one of its salts and / or its solvates:
• R and R 2 are independently chosen from: 1) hydrogen, with Ri different from R 2 , 2) a CC 20 alkyl radical optionally substituted with at least one substituent AL 3) a C 1 hydrocarbon ring of 3 to 7 atoms optionally attached to at least one C 2 ring of 4 to 7 atoms, the C 2 ring optionally containing at least one heteroatom to form a Hy 2 heterocycle, these C 1 and C 2 rings optionally comprising a carbonyl or thiocarbonyl function and / or being substituted by at least one substituent A 2 , 4) a heterocycle Hy !
• a 2 is chosen from: 1) a halogen, 2) one of the groups CF 3 , CN, OF, SR 4 , NF ⁇ R' ⁇ OCOR 4 , COR 4> CSP, COOR 4 , SO 2 R 4 , SiR 4 R 'R " 4 , NO 2 , OCF 3 , where FI ,, R' 4 and R" 4 independently represent a hydrogen or a C 1 -C alkyl radical 20 optionally substituted by a phenyl radical, 3) a CC alkyl radical 20 optionally substituted by an OR group 5 , 4) a C ring of 4 to 7 atoms optionally containing at least one hetero
• the invention also relates to the in particular cosmetic use of at least one 2-oxy-acetamide compound of formula (I) or of one of its salts and / or of its solvates, as defined above, as agent for induce and / or stimulate the growth of keratin fibers in particular human and / or slow down their fall and / or increase their density.
• It also relates to the cosmetic use of at least one 2-oxy-acetamide compound of formula (I) or of a salt and / or its solvates in a care or treatment composition for keratin fibers, in particular human fibers. to reduce their fall and / or increase their density.
• This composition also makes it possible to maintain the keratin fibers in good condition and / or to improve their appearance.
• Another subject of the invention is the use of at least one 2-oxy-acetamide compound of formula (I) or one of its salts and / or its solvates for the manufacture of a care or treatment composition for keratin fibers, especially human fibers, intended to induce and / or stimulate the growth of said fibers and / or slow down their fall and / or increase their density.
• the invention also applies to keratin fibers of mammals of the animal species (dog, horse or cat for example).
• the human keratin fibers to which the invention applies are in particular hair, eyebrows, eyelashes, beard hair, mustache hair and pubic hair. More specifically, the invention applies to human hair and / or eyelashes.
• the invention also relates to the cosmetic use of at least one 2-oxy-acetamide compound of formula (I) or of one of its salts and / or of its solvates, in a cosmetic care composition.
• human capillary to reduce hair loss and / or increase their density and / or treat alopecia, andro-chrono-genetic.
• It also relates to the use of at least one 2-oxy-acetamide compound of formula (I) or of one of its salts and / or of its solvates for the preparation of a hair composition for humans, intended inducing and / or stimulating hair growth and / or slowing hair loss and / or increasing their density and / or treating androgenic alopecia.
• the invention also relates to the cosmetic use of at least one 2-oxy-acetamide compound of formula (I) or of one of its salts and / or of its solvates, in a cosmetic composition for hair care.
• human to treat alopecia of natural origin and in particular androgenic as well as the use of at least one 2-oxy-acetamide compound of formula (I) or one of its salts and / or its solvates for the preparation of a hair care composition for human beings, intended for treating alopecia of natural origin and in particular androgenic.
• this composition makes it possible to maintain the hair in good condition and / or fight against natural hair loss and more particularly that of men.
• Another subject of the invention is the cosmetic use of at least one 2-oxy-acetamide compound of formula (I) or one of its salts and / or its solvates, in a cosmetic care composition and / or for making up human eyelashes, to induce and / or stimulate the growth of eyelashes and / or increase their density, as well as the use of at least one 2-oxy-acetamide compound of formula (I) or of a its salts and / or its solvates, for the preparation of a composition for caring for or treating human eyelashes, intended to induce and / or stimulate the growth of eyelashes and / or increase their density.
• This composition thus makes it possible to maintain the eyelashes in good condition and / or to improve their condition and / or their appearance.
• Another subject of the invention is the use of at least one 2-oxy-acetamide compound of formula (I) or one of its salts and / or its solvates as an inhibitor of the 15-hydroxy prostaglandin dehydrogenase type 1 including human skin. It also relates to the use of at least one 2-oxy-acetamide compound of formula (I) or of one of its salts and / or of its solvates for the manufacture of a composition intended for treating related disorders the presence of 15-hydroxy prostaglandin dehydrogenase type 1, in particular in humans.
• the present invention also relates to a process for the cosmetic treatment of human keratin fibers (hair or eyelashes in particular) and / or of the skin from which said fibers emerge, including the scalp and the eyelids, characterized in that it consists in applying to said keratin fibers and / or said skin, a cosmetic composition comprising at least one compound of formula (I) or one of its salts and / or its solvates, to leave it in contact with the keratin fibers and / or the skin from which said fibers emerge, and optionally rinsing said fibers and / or said skin.
• a cosmetic composition comprising at least one compound of formula (I) or one of its salts and / or its solvates
• This treatment process has the characteristics of a cosmetic process insofar as it makes it possible to improve the aesthetics of human keratin fibers and in particular of the hair and eyelashes by giving them greater vigor and an improved appearance. In addition, it can be used daily for several months, without medical prescription.
• the subject of the present invention is a process for the cosmetic care of human hair and / or scalp, with a view to improving 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 one of its salts and / or its solvates, to leave the latter in contact with the hair and / or the scalp, and possibly to rinse the hair and / or the scalp.
• a cosmetic composition comprising an effective amount of at least one compound of formula (I) or one of its salts and / or its solvates, to leave the latter in contact with the hair and / or the scalp, and possibly to rinse the hair and / or the scalp.
• the subject of the invention is also a method of cosmetic care and / or of making up human eyelashes, with a view to improving 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 one of its salts and / or its solvates and to leave it in contact with the eyelashes and / or the eyelids.
• This mascara composition can be applied alone or as an undercoat of a conventional pigmented mascara and can be removed as a conventional pigmented mascara.
• a further subject of the invention is a hair or eyelash care and / or mascara composition containing a cosmetically acceptable medium and for topical application and a compound of formula (I) or one of its salts and / or its solvates.
• the subject of the invention is also a composition for caring for and / or making up keratin fibers, comprising in a physiologically acceptable medium, in particular a cosmetic medium, at least one compound of formula (I) or one of its salts and / or of its solvates and at least one additional active agent promoting the regrowth of human keratin fibers and / or limiting their fall chosen from aminexil, agonists of the FP receptor, prostaglandins and their derivatives, and vasodilators and more especially chosen from aminexil, minoxidil, latanoprost, acid (5E) -7 - ⁇ (1 R, 2R, 3R, 5S) -3.5- dihydroxy-2 - [(3R) -3-hydroxy-5-phenyl pentyl ] cyclopentyl ⁇ hept-5-enoique, butaprost and travoprost.
• a physiologically acceptable medium in particular a cosmetic medium
• Another subject of the invention is the cosmetic use of a 2-oxy-acetamide compound of formula (I) or of one of its salts and / or of its solvates, as an agent for preserving the quantity and / or the prostaglandin activity in the hair follicle.
• Another subject of the invention is the use of at least one 2-oxy-acetamide compound of formula (I) or one of its salts and / or its solvates for the manufacture of a composition intended to preserve the amount and / or activity of prostaglandins in the hair follicle.
• the subject of the invention is also new 2-oxy-acetamide compounds satisfying at least one of the formulas (II), (III), (IV) and (V) below or one of the salts and / or corresponding solvates: Formula (Ih
• R 7 and R 8 independently represent: 1) hydrogen, 2) halogen such as F or Cl, 3) one of the groups CF 3 , CN, OF ⁇ , SR 4 , NHRe, NReR'e, OCOR 4 , COR 4 , CSR 4 , COOR 4l SO 2 R 4 , SiR 4 R ' 4 R " 4 , OCF 3 , O ⁇ R 4 , R' 4 and R" 4 independently represent a hydrogen or a linear or branched alkyl radical, in particular saturated , in C ⁇ -C 2Q optionally substituted by a phenyl radical and where R 6 and R ' 6 represent an alkyl radical in CC 20 optionally substituted by a phenyl radical, 4) an alkyl radical in C r C 20 optionally substituted by an OR group 5 where R 5 represents a hydrogen or a linear or branched alkyl radical, in particular saturated, in C ⁇ -C 20 , 5) a C 11 ring saturated or not with 4
• X and Y independently represent a hydrogen or A 2 as defined above (confers formula (I)) or can form a C 13 ring, saturated or not, saturated with 4 to 7 atoms, this C 13 ring optionally comprising at least one heteroatom, being optionally substituted by at least one substituent A 2 and optionally joined to another C 14 ring, saturated or not; provided that when Z represents the dibenzofuran heterocycle, X and Y independently represent: 1) hydrogen, 2) halogen such as F and Cl, 3) one of the groups CF 3 , CN, OR 9 , SR 4 , NF ⁇ R ', ”, OCOR 4 , COR 4 , CSR 4 , COOR 4 , SO 2 R, SiR 4 R'R" 4 , NO 2 , OCF 3 , where F, R ' 4 and R " 4 independently represent hydrogen or a CC 2 o alkyl radical, linear or branched, in particular saturated, and optionally substituted by a pheny
• X and Y independently represent: 1) hydrogen, in this case X different from Y, 2) fluorine, 3) one of the groups OR 10 , SR 4 , NR 4 R ' 4 , OCOR 4 , COR 4 , CSR 4 , COOR 6 , SiR 4 R ' 4 R “ 4 , OCF 3 , where R 4 , R' 4 and R" 4 independently represent a hydrogen or an alkyl radical in CrC 20, linear or branched, in particular saturated, and optionally substituted by a phenyl radical, where R 6 represents a C ⁇ -C 20 alkyl radical, linear or branched, in particular saturated, and optionally substituted by a phenyl radical and where Rio represents a hydrogen or a benzyl radical or a C 3 alkyl radical - C 20 , linear or branched, in particular saturated, and optionally substituted by a phenyl radical, 4) a C 2 -C 20 alkyl radical, linear or branched, in
• R 3 has the same definition as given above for formula (I)).
• the compounds of formula (II), (III), (IV) and (V) are inhibitors of 15-PGDH type 1 and better selective inhibitors.
• 15-hydroxy prostaglandin dehydrogenase inhibitor is meant a compound of formula (I) capable of inhibiting or decreasing the activity of the 15-PGDH type 1 enzyme, in particular human, and / or capable of inhibit, decrease or slow down the reaction catalyzed by this enzyme.
• the compound of formula (I) is a specific inhibitor of 15-PGDH; by specific inhibitor is meant an active which is little or no inhibitor of the synthesis of prostaglandins, in particular of the synthesis of PGF2- ⁇ or of PGE2.
• the 15-PGDH inhibitor is little or no inhibitor of prostaglandin synthesis, in particular of the synthesis of PGF2- ⁇ or of PGE2.
• the 15-PGDH type 1 inhibitor is little or no inhibitor of prostaglandin synthase (denoted PGF synthase or PGFS).
• PGF synthase is also expressed in the dermal papilla. Maintaining an effective amount of prostaglandins at the site of action therefore results from a complex biological balance between the synthesis and the degradation of these molecules. The exogenous supply of compounds inhibiting catabolism will therefore be less effective if this activity is combined with an inhibition of the synthesis of these prostaglandins.
• These compounds are called selective 15-PGDH inhibitors over PGF synthase.
• the ratio between the inhibitory activities of PGF synthase and 15-PGDH respectively for a given concentration, determined in particular by the inhibitory concentration of 50% of the enzymatic activity of PGF synthase (IC 50fS ) relative to the inhibitory concentration of 50% of the enzymatic activity of 15-PGDH (IC 50 d). is at least greater than 1, and in particular at least 3: 1, advantageously greater than or equal to 5: 1.
• compound of formula (I) must be understood to mean both the compound of formula (I) and one of its salts, of its solvates, in particular particular hydrates or one of its solvated salts (hydrated in particular).
• compound salts of formula (I) is meant according to the invention, the organic or inorganic salts of a compound of formula (I).
• inorganic salts which can be used according to the invention, mention may be made of the sodium or potassium salts as well as the ammonium, zinc (Zn 2+ ), calcium (Ca 2+ ), copper (Cu 2+ ) salts, iron (Fe 2+ and Fe 3+ ), strontium (Sr 2 * ), magnesium (Mg 2+ ) and manganese (Mn 2+ ); hydroxides, halohydrates (hydrochlorides for example), carbonates, hydrogen carbonates, sulfates, hydrogen phosphates, phosphates.
• organic salts which can be used according to the invention are, for example, the salts of tri-ethanolamine, mono-ethanolamine, ethanolamine, hexadecylamine and N, N, N ', N'-tetrakis- (hydroxy-propyl-2) ethylene diamine as well as those organic acids such as citrates, lactates, glycolates, gluconates, acetates, propionates, fumarates, oxalates and tartrates.
• organic acids such as citrates, lactates, glycolates, gluconates, acetates, propionates, fumarates, oxalates and tartrates.
• solvates of the compounds of formula (I) mention may be made of hydrates, alcoholates or hydroalcoholates.
• the compounds of formula (I) are in isolated form, that is to say non-polymeric.
• At least one means one or more (2, 3 or more).
• the composition may contain one or more compounds of formula (I).
• This or these compounds may be cis or trans or Z or E isomers or a mixture of cis / trans or Z / E isomers. They can also be in tautomeric form.
• This or these compounds may be enantiomers and / or diastereoisomers or a mixture of these isomers, in particular a racemic mixture.
• hydrocarbon is meant within the meaning of the invention a group of hydrogen and carbon atoms.
• alkyl radical is meant within the meaning of the invention a hydrocarbon radical which can be linear or branched and saturated or unsaturated.
• the alkyl radical contains from 1 to 20 carbon atoms, preferably from 1 to 10.
• alkyl radical which can be used in the invention, mention may be made of methyl, ethyl, isopropyl, n-butyl, fer- butyl, n-hexyl, ethyl-2-hexyl, ethylene, propylene.
• halogen atom which can be used in the invention, mention may be made of chlorine, fluorine or bromine atoms, and better still chlorine and fluorine atoms.
• the rings C 1 to C 4 , C 6 to C 14 as well as the heterocycles Hy 1 ( Hy 2 , and Hy to Hyu can be saturated or unsaturated. They contain in particular from 5 to 6 atoms.
• the C 9 ring can have up to 15 atoms and represent, for example, a crown ether having 5 -CH 2 CH 2 O- units.
• C 1 , C 3 , C 7 , C 9 , C rings 11 , C 13 , Hy 1 ( Hy 3 , Hy 5 , Hy 7 , Hy 9 , Hyu can be combined with one or more other cycles of identical or different chemical nature.
• saturated hydrocarbon rings which can be used in the invention, mention may be made of the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl radical.
• unsaturated hydrocarbon rings mention may be made of the cyclohexenyl or phenyl radical.
• combined hydrocarbon rings which can be used in the invention, mention may be made of the naphthyl, azulenyl radical.
• Ri and / or R 2 and / or R 3 may represent a hydrocarbon ring as defined above but also a heterocycle comprising from 1 to 4 heteroatoms chosen from N, O, S and their associations.
• these hydrocarbon or heterocyclic rings optionally include a carbonyl or thiocarbonyl function.
• R 1 and / or R 2 represent a heterocycle Hyi chosen in particular from: azetidine, pyrrole, dihydropyrrole, pyrrolidine, furan, dihydrofuran, tetrahydrofuran, thiophene, dihydrothiophene, tetrahydrothiophene, imidazole, dihydroimidazole , dihydrothiazole, thiazolidine, dihydropyrazole, pyrrazolidine, oxazole, dihydrooxazole, oxazolidine, isoxazole, dihydroisoxazole, isoxazolidine, isothiazole, dihydroisothiazole, isothiazolidine, triazole, dihydrotriazole, triadolid dihydradiazole, triazolidine, diadiazide, , tetrahydropyridine, piperidine, pyran, dihydro
• Hy ! represents a ⁇ -butyrolactone, a piperidine, a 1,3-benzodioxole optionally substituted by a linear or branched alkyl radical, in particular saturated with C 1 -C 4 .
• Ri represents hydrogen and R 2 represents one of the following groups: - a saturated C 10 or linear C 10 alkyl radical, such as a methyl, ethyl, butyl, propyl, pentyl, hexyl radical, optionally substituted by one or two substituents AL - a saturated hydrocarbon ring of 3 to 6 carbon atoms, - a heterocycle Hyi saturated or not with 5, 6 or 7 atoms, comprising from 1 to 2 heteroatoms chosen from O, N and S and optionally a carbonyl function and / or from one to four substituents A ' 2 , - a phenyl ring optionally substituted by one or two substituents A " 2 chosen from a halogen (fluorine or chlorine in particular), NO 2 , OCF 3 , CF 3 , OR 4 , OCH 2 R 4 , COOR 4 , an alkyl radical in C C ⁇ 0 in particular saturated (such as ethyl, propyl,
• the substituents Ai or A 2 carried by the same ring or the same alkyl radical can be identical or different. In addition, they can be identical or different for Ri, R 2 and R 3 .
• the radicals R 4 ,, R ', R “and R'” 4 may be identical or different for the same group, the same radical or from a substituent A ⁇ to a substituent A 2 .
• Ai represents a hydrocarbon ring or a heterocycle comprising 1 to 2 heteroatoms chosen from O and N, this hydrocarbon or heterocyclic ring having 5 or 6 atoms and optionally a carbonyl function and / or a substituent A 3 ; or a group chosen from SiR 4 R ' 4 R " 4.
• R, R' 4 , R " 4 and R '" 4 represent a hydrogen, a phenyl radical or an alkyl radical in CC 10 such as a methyl, ethyl, ter-butyl, n-butyl, n-butyl, n-propyl, isopropyl or pentyl radical.
• a ′ 2 represents a linear or branched alkyl radical, in particular saturated with C C ⁇ 0 such as methyl.
• a 3 represents a linear or branched alkyl radical in particular saturated with CC 10 such as methyl, CF 3 , a halogen atom such as F, OH or OCH 3
• R 3 represents a heterocycle Hy 5 chosen from: azetidine, dihydropyrrole, pyrrolidine, dihydrofuran, tetrahydrofuran, dihydrothiophene, tetrahydrothiophene, imidazole, dihydroimidazole, imidazolidine, thiazole, dihydrothiazole, thiazole oxazole, dihydro-oxazole, oxazolidine, isoxazole, dihydro-isoxazole, isoxazolidine, isothiazole, dihydro-isothiazole, isothiazolidine, triazole, dihydrotriazole, triazolidine, oxadiazole, dihydro-oxadiazole, tyradidiazide, thiadiazolidine, thiadiazolidine piperidine, pyran, dihydropyran, tetrahydropyran, pyrimidine
• R 3 represents one of the following groups: - a saturated or unsaturated hydrocarbon ring, optionally substituted by one or more substituents A '" 2 chosen from a phenyl radical, COOR 4 , OR, COR 4 , CN, a heterocycle with 5 or 6 saturated or unsaturated atoms comprising from 1 to 2 heteroatoms chosen from O, S and N as pyrrole or imidazole, a halogen (fluorine or chlorine), a phenyl radical optionally substituted by CN, a linear or branched C ⁇ - alkyl radical C 10 in particular saturated as ethyl, methyl, isopropyl, isobutyl, ter-butyl, with R 4 representing a hydrogen or a linear or branched alkyl radical in CrC 10 in particular saturated as methyl or ethyl, - a phenyl ring joined to one or two rings C 4 hydrocarbon or heterocyclic, saturated or unsaturated, of 5 to
• Hy 2l Hy, Hy 6 , Hy 7 , Hy 8 , Hy 9 , Hy 10 and Hyu which can be used in the invention, mention may be made independently of the azetidine, pyrrole, dihydropyrrole, pyrrolidine, furan, dihydrofuran, tetrahydrofuran rings.
• thiophene dihydrothiophene, tetrahydrothiophene, imidazole, dihydro-imidazole, imidazolidine, thiazole, dihydrothiazole, thiazolidine, pyrazole, dihydropyrazole, pyrazolidine, oxazole, dihydro-oxazole, isazazine isole, isoxazole isiazole, isoxazole , triazole, dihydrotriazole, triazolidine, oxadiazole, dihydro-oxadiazole, oxadiazolidine, thiadiazole, dihydrothiadiazole, thiadiazolidine, tetrazole, pyridine, dihydropyridine, tetrahydropyridine, piperidine, pyran, dihydropyran, tetrahydropyran, pyrimidine, dihydropyrimidine, tetrahydropyrimidine, pipe
• pyrrole pyrrolidine
• imidazole furan, thiophene, oxazole, thiazole, isoxazole, isothiazole, oxadiazole, pyrazole, tetrazole, pyridine, pyrimidine, triazole, pyrazine, pyridazine, piperidine, piperazine, morpholine or even ether rings.
• crown 15-C-5 for Hy 9 .
• the 2-oxy-acetamide compounds satisfy the following formula (1a) or one of its salts and / or one of its solvates:
• ⁇ ) Ru is chosen from: 1) a linear or branched C C ⁇ o alkyl radical, in particular saturated and optionally substituted with at least one substituent A 4 , 2) a C 15 hydrocarbon ring, saturated or not, of 5 to 6 atoms optionally substituted with at least one A 5 substituent;
• R 2 is chosen from: 1) a linear or branched CC 10 alkyl radical, in particular saturated and optionally substituted with at least one substituent A 4 , 2) a saturated or unsaturated C 16 hydrocarbon ring of 5 to 6 atoms optionally attached to at least one saturated or unsaturated C 17 ring of 5 to 6 atoms optionally containing at least one heteroatom to form a Hy 17 heterocycle, these C 16 and C 17 rings optionally comprising a carbonyl function and / or being substituted by at least one substituent A 5 ;
• a 4 is chosen from: 1) a C 18 ring, saturated or not, of 5 to 6 atoms optionally containing at least one hetero
• R 15 , R '15 and R" 15 independently represent a hydrogen or a linear or branched alkyl radical in particular saturated with CC 10 optionally substituted by a phenyl radical, 3) a linear or branched alkyl radical in particular saturated with CrC 10 optionally substituted by a group OR ⁇ 4 , 4) a C 19 ring saturated or not with 5 to 6 atoms optionally containing at least one heteroatom to form a heterocycle Hy 19 and / or possibly comprising a carbonyl function;
• R 14 is chosen from: 1) hydrogen, 2) a linear or branched alkyl radical, in particular saturated with CrC;
• Hy ⁇ 7 , Hy ⁇ 8 , and Hy 19 independently represent a heterocycle of 5 to 6 atoms which may contain from 1 to 4 heteroatoms chosen from N, O, S and their associations and / or contain a carbonyl function.
• the 2-oxy-acetamide compounds satisfy one of the following formulas (II) to (V) or one of the corresponding salts and / or solvates:
• R7 and R8 independently represent: 1) hydrogen, 2) halogen F or Cl, 3) one of the groups CF 3 , CN, OFl ,, SR 4 , NHR 6 , NR 6 R ' 6 , OCOR 4 , COR 4 , CSR 4 , COOR 4 , SO 2 R 4 , SiR 4 R ' 4 R “ 4 , OCF 3 , where R 4 , R' 4 and R" 4 represent independently hydrogen or a d-do alkyl radical optionally substituted by a phenyl radical and where Re and R ' 6 represent a C ⁇ -C 20 alkyl radical optionally substituted by a phenyl radical, 4) a C ⁇ -C 20 alkyl radical optionally substituted by an OR 5 group where R5> represents a hydrogen or a dC 20 alkyl radical, 5) a C 11 ring of 4 to 7 atoms optionally containing at least one heteroatom to form a Hyu heterocycle and
• X and Y independently represent a hydrogen or A 2 as defined above for formula (I) or can form a C 13 ring joined from 4 to 7 atoms and better still from 5 to 6 atoms, optionally comprising at least one heteroatom chosen from N, O, S and their associations, and being optionally substituted by one or more substituent A 2 , and optionally attached to another C 14 ring; provided that: - when Z represents the dibenzofuran heterocycle, X and Y independently represent: 1) hydrogen, 2) halogen (Fou Cl), 3) one of the groups CF 3 , CN, OR 9 , SR 4 , NR 4 R ' 4 , OCOR 4 , COR 4 , CSR 4 , COOR 4 , SO 2 R 4 , SiR 4 R' 4 R " 4 , NO 2 , OCF 3 , where R, R ' 4 and R" 4 independently represent a hydrogen or a CC 2 o alkyl radical optionally substituted by a pheny
• X and Y independently represent: 0 1) hydrogen, in this case X is different from Y 2) fluorine, 3) one of the groups OR 10 , SR 4 , NR 4 R ' 4 , OCOR 4 , COR 4 , CSR 4 , COORe, SiR 4 R 'R " 4 , OCF 3 , where R 4 , R' 4 and R" independently represent a hydrogen or an alkyl radical in dC 20 optionally substituted with a phenyl radical, where R ⁇ represents an alkyl radical in dC 20 optionally substituted by a phenyl radical and where R 10 represents a hydrogen or a benzyl radical or a C 3 -C 20 alkyl radical optionally substituted by a phenyl radical, 4) a C 2 -C 20 alkyl radical optionally substituted by an OR 5 , 5) group X and Y can also form a C 13 ring with 5 links (or atoms), saturated or not and optionally containing
• R 3 has the same meaning as given for formula (I).
• cycles C 11 and C 12 have the same meaning as above.
• the effective quantity of a compound of formula (I) corresponds to the quantity necessary to obtain the desired result (namely to increase the density of keratin fibers and in particular of hair and eyelashes or to promote their shoot). Those skilled in the art are therefore able to assess this effective amount which depends on the nature of the compound used, the person to whom it is applied, and the time of this application.
• the amounts of the various ingredients of the composition are given as a percentage by weight relative to the total weight of the composition.
• the compound of formula (I) (salified or not, solvated or not) or a mixture of compounds of formula (I) and / or their salts can be used in an amount representing from 10 "3 % to 10% of the total weight of the composition and preferably in an amount representing from 10 3 to 5% and better still from 10 " 2 % to 2% of the total weight of the composition, for example 0.5 at 2%.
• the composition of the invention can be for cosmetic or pharmaceutical use.
• the composition of the invention is for cosmetic use.
• the composition must contain a physiologically acceptable medium which is non-toxic and capable of being applied to the skin, including the scalp and the eyelids, and to the keratin fibers of human beings.
• cosmetic is meant within the meaning of the invention a composition of pleasant appearance, odor and feel.
• the compound of formula (I), salified or not, solvated or not, can be used in a composition which must be ingested, injected or applied to the skin or to the keratin fibers (on any skin area or fibers to be treated).
• the compound of formula (I) or a mixture of compounds of formula (I) can be used orally in an amount of 0.1 to 300 mg per day, in particular from 5 to 10 mg / d.
• a preferred composition of the invention is a composition for cosmetic use and in particular for topical application to the skin and keratin fibers, and more especially to the scalp, hair and eyelashes.
• composition can be in any known dosage form adapted to the mode of use.
• the composition may be in the form of an aqueous, alcoholic or hydroalcoholic solution or suspension or of an oily suspension or solution, of an emulsion or dispersion of more or less consistency. less fluid and in particular liquid or semi-liquid, obtained by dispersion of a fatty phase in an aqueous phase (O / W) or vice versa (W / O), of a solid emulsion or dispersion (O / W) or (E / H), a more or less fluid or solid aqueous, hydro-alcoholic or oily gel, a free or compacted powder to be used as it is or to be incorporated in a physiologically acceptable medium, or alternatively microcapsules or microparticles, Ionic and / or nonionic type vesicular dispersions.
• compositions in the form of a foam or else in the form of a spray or aerosol then comprising a propellant under pressure it is also possible to envisage a composition in the form of a foam or else in the form of a spray or aerosol then comprising a propellant under pressure.
• It can thus be in the form of a lotion, serum, milk, O / W or W / O cream, gel, ointment, ointment, powder, balm, patch, soaked tampon, bread, mousse.
• the composition for application to the scalp or the hair may be in the form of a hair care lotion, for example of daily or bi-weekly application, of a shampoo or of a hair conditioner, in particular bi-weekly or weekly application, a liquid or solid soap for cleaning the scalp of daily application, a product for shaping the hairstyle (hairspray, product for styling, styling gel ), a treating mask, a foaming cream or gel for cleaning the hair. It can also be in the form of a hair dye or mascara to be applied by brush or comb.
• composition to which the invention applies can be in the form of a mascara, pigmented or not, to be applied by brush to the eyelashes or even to the hairs. beard or mustache.
• the composition may be in the form of an aqueous lotion or an oily suspension.
• the composition may be in the form of capsules, granules, drinkable syrups or tablets.
• the composition according to the invention is in the form of a hair cream or lotion, hair shampoo or conditioner, hair mascara or for eyelashes.
• the amounts of the various constituents of the composition according to the invention are those generally used in the fields under consideration.
• these compositions are prepared according to the usual methods.
• the proportion of the fatty phase can 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) as well as that of any additional ingredients, to obtain 100% by weight. In practice, the aqueous phase represents from 5% to 99.9% by weight.
• the fatty phase can contain fatty or oily compounds, liquid at room temperature (25 ° C) and atmospheric pressure (760 mm Hg), generally called oils. These oils may or may not be compatible with each other and form a macroscopically homogeneous liquid fatty phase or a two- or three-phase system.
• the fatty phase can, in addition to oils, contain waxes, gums, lipophilic polymers, "pasty” or viscous products containing solid parts and liquid parts.
• the aqueous phase contains water and optionally an ingredient miscible in any proportion with water, such as lower alcohols, C 1 to C 8 such as ethanol, isopropanol, polyols such as propylene glycol, glycerol, sorbitol or acetone or ether.
• water such as lower alcohols, C 1 to C 8 such as ethanol, isopropanol, polyols such as propylene glycol, glycerol, sorbitol or acetone or ether.
• the emulsifiers and coemulsifiers used to obtain a composition in the form of an emulsion are generally used in the cosmetic and pharmaceutical fields. Their nature is, moreover, a function of the direction of the emulsion.
• the emulsifier and optionally the coemulsifier 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% .
• the emulsion can, in addition, contain lipid vesicles and in particular liposomes.
• the fatty phase can represent more than 90% of the total weight of the composition.
• the composition is an aqueous, alcoholic or hydro-alcoholic solution or suspension and better still a water / ethanol solution or suspension.
• the alcohol fraction can represent from 5% to 99.9% and better still from 8% to 80%.
• the composition of the invention is in particular in the form of a wax-in-water or wax-in-oil dispersion, a gelled oil, an aqueous gel, pigmented or not.
• composition of the invention may also comprise other additional ingredients usually used in the fields concerned, chosen from solvents, thickeners or gelling agents of aqueous phase or of oily phase, coloring matters soluble in the medium of the composition, solid particles such as fillers or pigments, antioxidants, preservatives, perfumes, electrolytes, neutralizers, film-forming polymers, UV blocking agents such as sunscreens, cosmetic and pharmaceutical active agents with beneficial action for the skin or keratin fibers, other than the compounds of formula (I), their mixtures.
• additives can be present in the composition according to the quantities generally used in the cosmetic and dermatological field and in particular at a rate of 0.01 to 50% of the total weight of the composition and better still from 0.1 to 20% and for example of 0 , 1 to 10%.
• additives depending on their nature, can be introduced into the fatty phase, into the aqueous phase and / or into the lipid vesicles and in particular liposomes.
• the person skilled in the art will take care to choose any additional ingredients and / or their amount in such a way that the advantageous properties of the composition according to the invention, namely the inhibition of type-15-PGDH and in particular the 'increase in the density of keratin fibers, are not or substantially not, altered by the planned addition.
• solvents which can be used in the invention mention may be made of lower C 2 to C 8 alcohols such as ethanol, isopropanol, propylene glycol and certain light cosmetic oils such as C 6 to C 6 alkanes.
• oils which can be used in the invention mention may be made of oils of mineral origin (petrolatum oil, hydrogenated isoparaffin), oils of vegetable origin (liquid fraction of shea butter, sunflower oil, apricot oil, alcohol or fatty acid), oils of animal origin (perhydrosqualene), synthetic oils (fatty acid ester, Purcellin oil), silicone oils (linear or cyclic polydimethylsiloxane, phenyltrimethicone) and fluorinated oils (perfluoropolyethers).
• oils of mineral origin petrolatum oil, hydrogenated isoparaffin
• oils of vegetable origin liquid fraction of shea butter, sunflower oil, apricot oil, alcohol or fatty acid
• oils of animal origin perhydrosqualene
• synthetic oils fatty acid ester, Purcellin oil
• silicone oils linear or cyclic polydimethylsiloxane, phenyltrimethicone
• fluorinated oils perfluoropolyethers.
• waxes mention may be made
• emulsifiers which can be used in the invention, mention may, for example, be made of glycerol stearate or laurate, sorbitol stearates or oleates, alkyl dimethiconecopolyol (with alkyl> 8) and their mixtures for a W / O emulsion.
• Polyethylene glycol monostearate or monolaurate, polyoxyethylenated sorbitol stearate or oleate, dimethiconecopolyols and their mixtures can also be used for an O / W emulsion.
• hydrophilic gelling agents which can be used in the invention, mention may be made of carboxyvinyl polymers (carbomers), acrylic copolymers such as acrylate / alkyl acrylate copolymers, polyacrylamides, polysaccharides such as hydroxypropylcellulose, natural gums and clays, and, as lipophilic gelling agents, mention may be made of modified clays such as Bentones, metal salts of fatty acids such as aluminum stearates, hydrophobic treated silica, ethylcellulose, their mixtures.
• hydrophilic active agents such as proteins or protein hydrolysates, amino acids, polyols, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts (those of Iridaceae or soybeans) and hydroxy acids such as fruit acids or salicylic acid; and lipophilic active agents, such as retinol (vitamin A) and its derivatives, in particular esters (retinol palmitate), tocopherol (vitamin E) and its derivatives, in particular esters (tocopherol acetate), essential fatty acids, ceramides, oils essential, salicylic acid derivatives such as 5-octanoyl salicylic acid, hydroxy acid esters, phospholipids such as lecithin, mixtures thereof.
• hydrophilic active agents such as proteins or protein hydrolysates, amino acids, polyols, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts (those of Iridaceae or soybeans)
• additional compounds are in particular chosen from lipoxygenase inhibitors as described in EP 648488, bradykinin inhibitors described in particular in EP 845700, prostaglandins and their derivatives in particular those described in WO 98/33497, WO 95/11003, JP 97- 100091, JP 96-134242, prostaglandin receptor agonists or antagonists, non-prostanoic analogs prostaglandins as described in EP 1175891 and EP1175890, WO 01/74307, WO 01/74313, WO 01/74314, WO 01/74315 or WO 01/72268, their mixtures.
• vasodilators As other additional active compounds promoting the growth of keratin fibers and / or limiting their fall (in particular the hair or the eyelashes) which may be present in the composition according to the invention, mention may be made of vasodilators, antiandrogens, cyclosporins and their analogs, antimicrobials and antifungals, anti-inflammatories, retinoids, alone or in a mixture.
• the vasodilators which can be used are in particular the potassium channel agonists including minoxidil, as well as the compounds described in US Pat. diaxozide, alone or in combination.
• the antiandrogens which can be used in particular include the steroidal or nonsteroidal inhibitors of 5 ⁇ -reductase, such as finasteride and the compounds described in US 5 516779, cyprosterone acetate, azelaic acid, its salts and its derivatives and the compounds described in US 5,480,913, flutamide, oxendolone, spironolactone, diethylstilbestrol and the compounds described in US patents 5,411,981, 5,565,467 and 4,910,226.
• 5 ⁇ -reductase such as finasteride and the compounds described in US 5 516779, cyprosterone acetate, azelaic acid, its salts and its derivatives and the compounds described in US 5,480,913, flutamide, oxendolone, spironolactone, diethylstilbestrol and the compounds described in US patents 5,411,981, 5,565,467 and 4,910,226.
• the antimicrobial or antifungal compounds can be chosen from selenium derivatives, octopirox, triclocarban, triclosan, pyrithione zinc, itraconazole, asian acid, hinokitiol, mipirocin, tetracyclines, in particular the erythromycin and the compounds described in EP 0680745, clinycin hydrochloride, benzoyl or benzyl peroxide, minocycline and the compounds belonging to the imidazole class such as econazole, ketoconazole or miconazole or their salts, esters nicotinic acid, including in particular tocopherol nicotinate, benzyl nicotinate and C ⁇ C g alkyl nicotinates such as methyl or hexyl nicotinates.
• the anti-inflammatory drugs can be chosen from steroidal anti-inflammatory drugs such as glucocorticoids, corticosteroids (for example: hydrocortisone) and non-steroidal anti-inflammatory drugs such as glycyrrhetinic acid and ⁇ -bisabolol, benzydamine, salicylic acid and the compounds described in EP 0770399, WO 94/06434 and FR 2 268523.
• steroidal anti-inflammatory drugs such as glucocorticoids, corticosteroids (for example: hydrocortisone) and non-steroidal anti-inflammatory drugs such as glycyrrhetinic acid and ⁇ -bisabolol, benzydamine, salicylic acid and the compounds described in EP 0770399, WO 94/06434 and FR 2 268523.
• the retinoids can be chosen from isotretinoin, acitretin, tazarotene, retinal and adapalene.
• aminexil 6-0 - [(9Z, 12Z) -octadeca-9,12-dienoyl] hexapyranose, benzalkonium chloride, benzethonium chloride, phenol, estradiol, chlorpheniramine maleate, chlorophyllin derivatives , cholesterol, cysteine, methionine, menthol, peppermint oil, calcium panthotenate, panthenol, resorcinol, protein kinase C activators, glycosidase inhibitors, glycosaminoglycanase inhibitors, pyroglutamic acid esters, hexosaccharide or acyl-hexosaccharic acids, substituted
• the composition according to the invention comprises at least one 15-PGDH inhibitor as defined above and at least one prostaglandin or a prostaglandin derivative such as, for example, prostaglandins of series 2, in particular PGF2- ⁇ and PGE2 in the form saline or ester (eg isopropyl esters), their derivatives such as 16.16 dimethyl PGE2, 17 phenyl PGE2, 16.16 dimethyl PGF2- ⁇ , 17 phenyl PGF2- ⁇ prostaglandins of series 1 such as deoxy 11 prostaglandin E1, the 1 deoxy prostaglandin E1 in saline or ester form, their analogs in particular latanoprost, acid (5E) -7 - ⁇ (1R, 2R, 3R, 5S) -3.5- dihydroxy-2 - [( 3R) -3-hydroxy-5-phenylpentyl] cyclopentyl ⁇ hept-5-enoique, viprostol, bimatoprost, clopro
• the composition contains at least one non-prostanoic agonist of the EP2 and / or EP4 receptors, in particular as described in EP 1175892.
• composition comprising at least the compound of formula (I), salified or not, solvated or not, is in liposome form, as especially described in document WO 94/22468.
• the compound encapsulated in the liposomes can be delivered selectively to the hair follicle.
• composition according to the invention can be applied to the alopecic areas of the scalp and to the hair of an individual, and optionally left in contact for several hours and optionally rinsed.
• the 2-oxy-acetamide compounds satisfy one of the following three formulas:
• the compounds to which the invention applies are compounds 2, 3, 5, 6, 8, 9, 10, 12, 13, 18, 19, 21, 23, 24, 28, 32, 34, 35 and in particular to the new compounds 2, 3, 5, 6, 8, 9, 10, 12, 13, 18, 19, 21, and to the compounds 23 and 24.
• the compounds to which the invention applies are the new compounds 2, 3, 12, 13 and 21 as well as compounds 23 and 24.
• the reaction mixture is concentrated to the maximum and then diluted with 100 mL of dichloromethane.
• the organic phase is washed with water (2 times 50 mL) and then with a saturated sodium chloride solution.
• the organic phase is dried over sodium sulfate, filtered and then concentrated to the maximum.
• the crude is taken up in the minimum amount of ethyl ether and stirred for 30 minutes.
• the solid is removed and the filtrate purified on silica gel (eluent: dichloromethane). After distilling off the solvent and drying under vacuum in the presence of phosphorus pentoxide, a beige solid (0.36 g, with a yield (Yield) of 24%) is obtained.
• the reaction mixture is concentrated to the maximum and then diluted with 100 ml of dichloromethane.
• the organic phase is washed with water (2 times 50 mL) and then with a saturated sodium chloride solution.
• the organic phase is dried over sodium sulfate, filtered and then concentrated to the maximum.
• the crude is taken up in the minimum amount of ethyl ether and stirred for 30 minutes.
• Mass spectrometry The quasi-molecular ions (MH) + , (MNa) + of the expected molecule C 7 H 8 CINO 2 are mainly detected.
• a suspension of 28 mg of potassium carbonate in 1 ml of acetone is introduced into a reaction tube fitted with a magnetic bar.
• a solution of 6.4 mg of 8-hydroxy quinoline (CAS: 148-24-3; Fluka reference: F55080) in 0.5 mL of acetone and a solution of 7.9 mg of 2-chloro-2 ', 6'-aceto-xylidide (CAS: 1131-01-7) in 0.5 mL of acetone are then added.
• the medium is diluted with 1 ml of acetone, the
• 35 tube is closed and heated at reflux for 24 hours.
• the reaction medium is cooled to room temperature, filtered through a frit, the solid is rinsed with 2.5 ml of acetone.
• the filtrate is concentrated under vacuum, taken up in 330 ⁇ L of a 9/1 dichloromethane / methanol mixture and added to a suspension of 80 mg of PL-TBD resin (resin 1, 3,4,6,7,8- hexahydro-2H -pyrimido [1, 2-a] pyrimidine charged at 2.7 mmol / g) in 1.5 ml of
• compound 4 is obtained in the form of white crystals (11.2 mg) with a yield of 82% by reaction between 1- (4-hydroxy-phenyl) -ethanone (4-hydroxyacetophenone CAS: 99-93-4) and ethyl 4 (2-chloroacetamido) -benzoate (4- (2- Chloro-acetylamino) -benzoic acid ethyl ester CAS: 26226-72-2).
• EXAMPLE 27 Demonstration of the specific inhibitory properties of 15-PGDH of the compounds of formula (I).
• Test on 15-PGDH type 1 The enzyme 15-PGDH is obtained as described in application FR 02/05067 filed in the name of L'Oréal, in suspension in a medium suitable for a concentration of 0.3 mg / mL then blocked at - 80 ° C. For the purposes of the test, this suspension is thawed and stored in ice.
• a 100 mM Tris buffer, pH 7.4, is prepared, containing 0.1 mM of dithiothreitol (D5545, Sigma-AIdrich, L'isie D'Abeau Chesne, BP 701, 38297, Saint Quentin Fallavier), 1, 5 mM of ⁇ -NAD (N6522, Sigma-AIdrich, L'isie D'Abeau Chesne, BP 701, 38297, Saint Quentin Fallavier), 50 ⁇ M of Prostaglandin E 2 (P4172, Sigma- AIdrich, L'isie D'Abeau Chesne, BP 701, 38297, Saint Quentin Fallavier).
• test values (containing the compounds of formula (I)) are compared to the control value (without compound (I)); the results indicated represent either the percentage inhibition of the enzymatic activity of 15-PGDH for a given concentration of compound of formula (I), or the concentration at which the compound of formula (I) reduces the activity by 50% 15-PGDH enzyme, i.e. IC 50dh -
• the PGFS enzyme is obtained as described in document FR-A-02/05067, at a concentration of 0.5 mg / ml, in suspension in an appropriate medium, and blocked at -80 ° C. For the purposes of the test, this suspension is thawed and stored in ice.
• BP 701, 38297, Saint Quentin Fallavier 100 ⁇ M of ⁇ - NADPH (N1630, Sigma-AIdrich, L'isie D'Abeau Chesne, BP 701, 38297, Saint Quentin Fallavier).
• a stock solution titrating 1 mM is prepared in absolute ethanol, brought to 40 ° C; the bottle is placed in an ultrasonic tank to facilitate the solubilization of the product.
• test values (containing the compound (I)) are compared to the control value (without compound (I)); the results indicated represent either the percentage inhibition of the PGFS enzymatic activity for a given concentration of compound of formula (I), or the concentration at which the compound of formula (I) reduces by 50% the enzymatic activity of PGFS, namely IC 50fS .
• compounds 1 to 20, 27 to 35 do not inhibit the PGFS enzyme at 100 ⁇ M.
• compositions are obtained by the usual techniques commonly used in the cosmetic or pharmaceutical field.
• EXAMPLE 28 Compound hair lotion 23 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 the rate of 1 ml per application, massaging the scalp lightly to make the active ingredient penetrate. The hair is then dried in the open air. This lotion reduces hair loss and promotes regrowth. It also improves the appearance of hair.
• EXAMPLE 29 Hair lotion - Compound 21 1, 00 - Propylene glycol 30.00 - Ethyl alcohol 40.00 - Water qs 100.00 This lotion is applied to the scalp, once or twice a day, at the rate of 1 ml per application, gently massaging the scalp to penetrate the active ingredient. The hair is then dried in the open air. This lotion reduces hair loss and promotes regrowth. It also improves the appearance of hair.
• This mascara is applied to the eyelashes like a classic mascara with a mascara brush.
• This lotion is applied to the scalp, once or twice a day, at the rate of 1 ml per application, by gently massaging the scalp to penetrate the active ingredient. The hair is then dried in the open air. This lotion reduces hair loss and promotes regrowth. It also improves the appearance of hair.
• This lotion is applied to the scalp, once or twice a day, at the rate of 1 ml per application, by gently massaging the scalp to penetrate the active ingredient. The hair is then dried in the open air. This lotion reduces hair loss and promotes regrowth. It also improves the appearance of hair.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Epidemiology (AREA)
• Birds (AREA)
• Organic Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Medicinal Chemistry (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Chemical & Material Sciences (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Engineering & Computer Science (AREA)
• Dermatology (AREA)
• Hematology (AREA)
• Diabetes (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Quinoline Compounds (AREA)
• Furan Compounds (AREA)
• Cosmetics (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Applications Claiming Priority (3)

Publications (1)

Family

ID=34972478

Family Applications (1)

Country Status (3)

Families Citing this family (5)

Family Cites Families (3)

• 2005
  • 2005-04-18 EP EP05757128A patent/EP1763382A1/fr not_active Withdrawn
  • 2005-04-18 JP JP2007508932A patent/JP2007533708A/ja not_active Withdrawn
  • 2005-04-18 WO PCT/FR2005/000926 patent/WO2005107687A1/fr not_active Application Discontinuation

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events