EP2794578A1

EP2794578A1 - Novel anti-aging and depigmenting cosmetic compositions

Info

Publication number: EP2794578A1
Application number: EP12810398.3A
Authority: EP
Inventors: Natacha Frison; Benoit Folleas; Jean-Louis Brayer; Florence WAFFLART
Original assignee: Diverchim SA
Current assignee: Diverchim SA
Priority date: 2011-12-22
Filing date: 2012-12-18
Publication date: 2014-10-29
Also published as: CA2859894A1; US20150004110A1; CN104203927A; BR112014015389A8; CN104203927B; KR20140113984A; JP2015502391A; WO2013093320A1; BR112014015389A2; FR2984730A1

Abstract

The invention relates to the use of 1-aryl-2-aryloxyethane compounds with formula I, wherein n and m are equal to 0 or 1, provided that n+m=1, R1 and R2 particularly representing hydrogen atoms, R3 and R4 particularly representing hydrogen or halogen atoms or hydroxy or alkoxy groups, and R5 particularly representing hydrogen atoms or hydroxy, alkyl, alkoxy, amino or nitro groups, in cosmetic compositions intended for anti-aging and/or depigmenting and/or anti-inflammatory and/or healing care products.

Description

New anti-aging and depigmenting cosmetic compositions

The invention relates to new anti-aging and depigmenting cosmetic compositions. They contain 1-aryl-2-aryloxyethanes representing a family of compounds with interesting biological properties.

In 1989, Moinet et al. Described the synthesis of a family of new 1-aryl-2-aryloxyethanes (Lipha, FR26531 19) with diuretic, antihypertensive, platelet anti-aggregating and anti-lipoxygenase properties. In particular, 2- [2- (4-fluoro-phenoxy) -ethyl] -phenol is a diuretic and anti-hypertensive agent in its sulphated form (RP Garay, JP Labaune, D. Mesangeau, C. Nazaret, T. Imbert, G. Moinet, J. Pharm Exp Therapeutics, 1990, 255, 415-422).

Other compounds such as pyrocatecholecarboxylic acid derivatives (Hoffmann Laroche, EP0310126) for the treatment of cardiovascular and bronchopulmonary diseases, and such as heterocycle-containing derivatives (Pfizer, US5248685), for the treatment of asthma , have also been described in the 90s.

In 2006, Bayer describes the use of certain derivatives for their antiparasitic properties (WO 19876).

Certain 1-alyl-2-ylyloxyethanes are reaction intermediates in the preparation of phenoxypropanoamines, antagonist compounds of the βι and β-forms of adrenaline (SN Louis, TL Nero, D. Iakovidis, Colagrande FM, GP Jackman, WJ Louis Eur J Med Che u, 1999, 919-937).

It thus appears that these compounds and their numerous sub-families, possess interesting biological properties on the one hand, not studied so far in the topical field on the other hand. An object of the invention is to use 1-alkyl-2-alkyloxyethanes or their derivatives in cosmetic compositions.

Another object of the invention is to use 1-alkyl-2-alkyloxyethanes or their derivatives in cosmetic compositions intended for anti-aging and / or depigmenting care.

Another object of the invention is to provide a process for the preparation of new l-aiyl-2- aryloxyéthanes.

According to a general aspect, the subject of the invention is the use of the compounds of formula I

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

■ R ¹ and R ² , identical or different, represent

° of ^hydrogen atoms,

° of ^halogen atoms selected from fluorine, chlorine, bromine or ^iodine,

° linear or branched alkyl groups comprising from 1 to 10 carbon atoms, especially methyl groups, ethyl, isopropyl, optionally substituted by one or more halogens chosen (s) from fluorine, chlorine, bromine or ^iodine, by a -CF ₃ group, with a hydroxy,

° -OH groups,

° linear or branched alkoxy groups comprising from 1 to 10 carbon atoms, including methoxy, ethoxy, optionally substituted with one or more halogens chosen (s) from fluorine, chlorine, bromine or ^iodine, in particular the trifluoromethoxy group -OCF,

° phenoxy -OPH groups,

° aryloxy groups -OAr, in which Ar represents an aromatic group having 6 to 12 carbon atoms optionally substituted by one or more ^atoms selected halogen (s) from fluorine, chlorine, bromine, or optionally substituted by one or more -OH groups in free or protected form, and in particular protected in the form of

group -OMes, group -OTHP of formula of group derived from ethylene

glycol of formula in which O varies from 1 to 12,

R ^a represents a hydrogen, a linear or branched alkyl group having from 1 to 6 carbon atoms,

R ^c represents a linear or branched alkyl group of 1 to 10 carbon atoms,

a group derived from propylene glycol of formula,

in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

of a group derived from an osidic compound which may be a- or β-furanose or a- or β-pyranose, of siloxy group of formula -OSi (R ^a ) ₃ in which R ^a has the meanings indicated above, of group -OSitBdPh of formula

or group -OSitBdM of formula,

Benzyloxy groups -OCH ₂ Ph,

Alkenyl groups comprising from 2 to 10 carbon atoms, linear or branched and having at least one C = C double bond,

Acyloxy groups comprising from 2 to 10 carbon atoms, derivatives of carboxylic acids,

° -OTHP groups of formula above,

° -OMes groups,

Groups derived from ethylene in which

O varies from 1 to 12, R ^a represents a hydrogen or a linear or branched alkyl group having from 1 to 6 carbon atoms,

R ^c represents a linear or branched alkyl group of 1 to 10 carbon atoms,

Groups derived from propylene glycol of formula,

in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

O -OH groups optionally coupled to osidic compounds that can be a- or β-furanose or a- or β-pyranose,

Siloxy groups of formula -OSi (R ^a b in which R ^a has the meanings indicated above,

° groups -OSitBdPh of formula

° -OSitBdM groups of formula,

said R ¹ and R ¹ possibly forming a ring having 3 carbon atoms, ring having the following formula

in which

R ^a, R ^b, R ^a and R ^b, identical or different, represent

° of ^hydrogen atoms,

° of halogen ^atoms selected from fluorine, chlorine, bromine or ^iodine, ° linear or branched alkyl groups comprising from 1 to 10 carbon atoms, especially methyl groups, ethyl, isopropyl, optionally substituted by one or more halogens chosen (s) from fluorine, chlorine, bromine or ^iodine, by a -CF ₃ group, with a hydroxy,

with the proviso that R / is a hydroxy group,

■ R; and R ^"1, identical or different, represent

° of ^hydrogen atoms,

° of halogen ^atoms selected from fluorine, chlorine, bromine,

Linear, branched or cyclic alkyl groups comprising from 1 to 10 carbon atoms, especially methyl, ethyl or isopropyl groups, optionally substituted by one or more halogens chosen from fluorine, chlorine, bromine or the like ^; iodine, with a -CF ₃ group, with a hydroxy,

Hydroxyl groups -OH,

Linear or branched alkoxy groups comprising from 1 to 10 carbon atoms, especially methoxy, ethoxy, isopropoxy or tert-butoxy groups, optionally substituted by one or more halogens chosen from fluorine, chlorine, bromine or ^iodine, and in particular the trifluoromethoxy group -OCF,

Benzyloxy groups,

An alkenyloxy group comprising from 2 to 10 carbon atoms, linear or branched and having at least one C = C double bond,

An alkynyloxy group comprising from 2 to 10 carbon atoms, linear or branched, and comprising at least one C-= = C triple bond;

-OTHP groups of formula

substituted -OTHP groups of the following formula

in which

x is equal to 0 or 1, y varies from 0 to 4,

R ^b is hydrogen or acetyl -C (O) -CH, Groups derived from ethylene glycol of formula in which

O varies from 1 to 12,

R ^a represents a linear or branched alkyl group having from 1 to 6 carbon atoms, R ^c represents a linear or branched alkyl group of 1 to 10 carbon atoms,

Groups derived from propylene glycol of formula

in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

O -OH groups optionally coupled to an osidic compound which may be an α- or β-furanose or an α- or β-pyranose,

A siloxy group of formula -OSi (R ^a ) ₃ in which R ^a has the meanings indicated above,

Formula -OSitBdPh

° -OSitBdM of formula,

■ R ³ represents

a ^hydrogen atom,

a ^halogen atom selected from fluorine, chlorine, bromine, a linear, branched or cyclic containing from 1 to 10 carbon atoms, including methyl, ethyl, isopropyl, optionally substituted by one or more halogens chosen (s) from fluorine, chlorine, bromine or ^iodine, a group -CF _3, hydroxy,

An alkenyl group comprising from 2 to 6 carbon atoms, linear or branched, and comprising at least one C = C double bond,

An alkynyl group comprising from 2 to 6 carbon atoms, linear or branched and having at least one C-= = C triple bond _;

A phenyl group optionally substituted with a halogen atom, a -CF group, a linear or branched alkyl group comprising from 1 to 10 carbon atoms, a linear or branched alkoxy group comprising from 1 to 10 carbon atoms,

A hydroxyl group -OH,

A linear or branched alkoxy group comprising from 1 to 10 carbon atoms, especially methoxy, ethoxy, isopropoxy or tert-butoxy groups, optionally substituted by one or more halogens chosen from fluorine, chlorine, bromine or ^iodine, and in particular the trifluoromethoxy group -OCF,

a benzyloxy group,

a phenoxy group,

a thiophenyl group,

an acyloxy group comprising from 2 to 10 linear carbon atoms,

A group -OTHP of formula

substituted for the following formula

in which

x is equal to 0 or 1, y varies from 0 to 4,

R ^b is hydrogen or acetyl -C (O) -CH,

A group -OS0 R ⁰ in which R ^c is an alkyl group comprising 1 to 6 carbon atoms, in particular methyl or ethyl, or an aromatic group containing from 6 to 18 carbon atoms, optionally substituted by one or more halogen atoms, hydroxy or alkoxy group, nitro group,

An -OSO M group in which M represents an Na ion or a group derived from ethylene glycol of formula

in which

O varies from 1 to 12,

A group derived from propylene glycol of formula

in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

An -OH group optionally coupled to an osidic compound that may be an α- or β-furanose or an α- or β-pyranose,

Formula -OSitBdPh

° -OSitBdM of formula, ° -COOH,

° -CN,

° -NH,

° -NH, X

- -NR ^d R,

° -NHR ^d R ⁺ , X

° -NHCOR,

° -NHCOOR ^g ,

° -N0 ₂ ,

R ^d . R ^e represents linear or branched alkyl groups having from 1 to 4 carbon atoms, optionally substituted with one or more halogen atoms, or carbon chains interrupted by oxygen or sulfur atoms, benzyl groups optionally substituted by a halogen atom, a hydroxy group, an alkoxy group having from 1 to 8 carbon atoms,

R ¹ represents a linear or branched alkyl group containing from 1 to 4 carbon atoms, a phthalimido group (in this case NH is replaced by N), a benzyl group optionally substituted by a halogen atom, a hydroxyl group, a alkoxy group and in particular substituted with the methoxy group in the para position,

R ^g represents a linear or branched alkyl group comprising from 1 to 4 carbon atoms, optionally substituted by one or more halogen atoms, or a carbon chain interrupted by oxygen or sulfur atoms, a phenyl group, a group benzyl optionally substituted by a halogen atom, a hydroxy group, an alkoxy group and in particular substituted with the methoxy group in the para position,

X ^" representing a halide ion,

A group derived from piperazine, in particular

provided that R ¹ and R ^"1 do not simultaneously represent -OH groups or groups having a phenyl bonded oxygen atom, said compounds of formula I being used in racemic form or a single enantiomer for the preparation of cosmetic compositions having anti-aging and / or depigmenting and / or healing and / or anti-inflammatory properties.

In a particular aspect, said compounds of formula I are used in racemic form or ^a single enantiomer for the preparation of cosmetic compositions for anti-aging and / or depigmenting.

The compounds of formula I belong to a family of compounds called "1-aryl-2-aryloxyethanes".

1

/ S. OAr

2

"Aryl" refers to an aromatic group having 6 carbon atoms, optionally substituted with the groups R "and R ^{" 1} , and attached to the ethane chain by the carbon 1.

These groups may both be equal to the hydrogen atom: in this case, the aryl group is a phenyl group, -Cc Hs.

• If the groups R "and R ^{" 1} are not both equal to the hydrogen atom, then the aryl group in position 1 of the above formula is monosubstituted.

If the groups R "and R ^{" 1} are both different from the hydrogen atom, then the aryl group at the 1-position of the above formula is disubstituted.

R "and R ^{" 1} have the meanings indicated above and in particular represent H, -OH, -OCH, -F, -Br, -OC (O) CH.

By the proviso "... R" and R ^"1 do not simultaneously represent -OH groups or groups having a phenyl-bonded oxygen atom, the aryl group derived from benzene-1,2-diol is excluded. in particular, it is possible to exclude pyrocatechol and its derivatives in which the -OH group would be in another form, including a protected form such as the ester form.

"Aryloxy" refers to an aryl group attached to carbon 2 of the ethane chain by an ^oxygen atom. It is optionally monosubstituted by a group R ^* represented in the general formula I and having the meanings designated above.

• R ^* may be equal to the hydrogen atom. In this case, the aryloxy group is a phenoxy group, -OCc Hs.

• R ^* may be different from the hydrogen atom. In this case, R ^* is in particular equal to -OH, -F, a nitrogen group, -CH, -O-CH, -O-CH ₂ -PI1.

R ¹ and R ² have the meanings indicated above and in particular represent hydrogen atoms or -OH.

In the general formula, "n" and "m" are equal to 0 or 1. Their sum is always equal to 1.

If n = 0 then m = 1: the compound is 1-aryl-2-aryloxyethane.

• If n = l then m = 0: the compound is a ketone.

In the term "1-aryl-2-aryloxyethanes or their derivatives", the term "derivatives" corresponds to the case where n = 1 and m = 0: the compound is a ketone.

"Cosmetic compositions" means mixtures containing at least one active compound intended for the care of the body and in particular of the skin.

"Anti-aging properties" refers to all the properties of the cosmetic compositions by which it is possible to combat aging of the skin, in particular by dermic strengthening and by the improvement of epidermal differentiation.

"Anti-inflammatory properties" refers to the set of properties of the cosmetic compositions by which the secretion of molecules related to inflammation of the skin, such as the secretion of protaglandin PGE _{2, can be} controlled.

"Depigmenting properties" refers to the set of properties of cosmetic compositions by which the melanogenesis or bio-synthesis of melanocytes can be reduced or inhibited. "Healing properties" refers to the set of properties of cosmetic compositions by which the proliferation and migration of fibroblasts and / or keratinocytes on a wound can be increased.

A particular aspect of the invention relates to the use of the compounds of Fonmile II

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ , R, R "and R ^{" 1} have the meanings indicated above,

■ -NR ^'a R ^{"b *} is a group having a nitrogen atom attached to the ring, possibly in its salt form, this group being selected from

° -NH,

- -NR ^d R,

° -NHCOR,

° -NHCOOR ^g ,

° -N0,

A group derived from piperazine, in particular

R ^d R ^e representing straight or branched alkyl groups having 1 to 4 carbon atoms, optionally substituted by one or more halogen atoms, or chains carbon atoms interrupted by oxygen or sulfur atoms, benzyl groups optionally substituted with a halogen atom, a hydroxy group or an alkoxy group containing from 1 to 8 carbon atoms,

R ^g represents a linear or branched alkyl group comprising from 1 to 4 carbon atoms, optionally substituted by one or more halogen atoms, or a carbon chain interrupted by oxygen or sulfur atoms, a phenyl group, a group benzyl optionally substituted by a halogen atom, a hydroxy group, an alkoxy group and in particular substituted by the methoxy group in the para position.

In particular, compounds belonging to the family of 1-aryl-2-aryloxyethanes and having a nitrogen-substituted group of the aryloxy group, have been prepared.

"Group comprising a nitrogen atom attached to the ring" denotes a nitro, primary, secondary or tertiary amine function or their salts, an amide or carbamate function.

This nitrogen group can occupy the ortho, meta or para positions.

Another particular aspect of the invention relates to the use of compounds of formula

III

in which

■ R ^"1 and R ³ have the meanings indicated above,

■ R ^la, R ^lb, R ^a and R ^b, identical or different, represent

° of ^hydrogen atoms,

° of halogen ^atoms selected from fluorine, chlorine, bromine or ^iodine, ° linear or branched alkyl groups comprising from 1 to 10 carbon atoms, especially methyl groups, ethyl, isopropyl, optionally substituted by one or more halogens chosen (s) from fluorine, chlorine, bromine or ^iodine, by a -CF ₃ group, by a hydroxy

In the formula shown below, the carbon 1 of the ethane chain bears a cyclopropyl group. This cyclopropyl group may itself be substituted by ^the groups R, R ^b, R ^a and R ^b, identical or different, whose meanings are given above. R ^a, R ^b, R ^a and R ^b include four ^hydrogen atoms.

1

/ -V. OAr

k -

These cyclopropyls have a -OH on the aromatic group at the α-position of carbon carrying the cyclopropyl group.

This cyclopropyl group may itself be substituted by ^the groups R, R ^b, R ^a and R ^b, identical or different, whose meanings are given above. R ^a, R ^b, R ^a and R ^b include four ^hydrogen atoms.

IV

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ , R, R ^"1 and R ^* have the meanings given above.

Compounds IV are distinguished by a hydroxy group specifically ortho to phenyl.

According to an advantageous embodiment of the invention, the compounds of formula IVA are used

wherein R ³ has the meaning as above.

The compounds IVA are distinguished by a phenyl group specifically ortho to phenyl in which the groups R ¹ , R ² and R ^"1 are three hydrogen atoms, R ³ may occupy the ortho, meta or para positions.

Another particular aspect of the invention relates to the use of the compounds of formula I

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ , R ² , R ¹ and R ³ have the meanings indicated above,

provided that R "and R ^{" 1} are both different from -OH or any form in which - OH is protected.

We exclude catechol derived compounds, already described.

in which

R ¹ , R ² , R ¹ and R ³ have the meanings indicated above,

We exclude ketones carrying a group derived from catechol. R ^"1 and R ^* may occupy the ortho, meta or para positions.

VI

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

■ R ¹ , R ² , R "and R ^~ have the meanings indicated above,

■ R ^c is a halogen atom chosen from fluorine, chlorine or bromine.

The compounds of formula VI have a halogen attached to the -OAr group described in the following general formula:

1

, OAr

Ar '

R ^"1 and R can occupy ortho, meta or para positions.

According to an advantageous embodiment of the invention, compounds of formula VII are used

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

■ R ¹ , R ² , R "and R ^~ have the meanings designated above.

Among the compounds having a halogen attached to the group -OAr of the

formula compounds of formula VII are distinguished by a fluorine atom in para position. R ^"1 may occupy the ortho, meta or para positions.

Another particular aspect of the invention relates to the use of the compounds of

VIII

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

■ R ¹ , R ² , R "and R ^~ have the meanings indicated above,

■ -OR ^d is a group chosen from

OH,

Benzyloxy groups,

^D phenoxy groups,

° -OTHP groups of formula

P substituted with the following formula

in which

x is equal to 0 or 1, y varies from 0 to 4,

R ^b is hydrogen or acetyl -C (O) -CH,

^D -OSC ^ R ^{0 groups} in which R ^c is an alkyl group comprising from 1 to 6 carbon atoms, in particular methyl or ethyl, or an aromatic group containing from 6 to 18 carbon atoms, optionally substituted with one or more atoms halogen, hydroxy or alkoxy group, nitro,

^D -OSO ₃ M groups in which M represents an Na ⁺ ion or

Groups derived from ethylene in which

O varies from 1 to 12,

Groups derived from propylene glycol of formula

in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

O -OH groups optionally coupled to an osidic compound which may be a- or β-furanose or a- or β-pyranose.

The compounds of formula VIII have an oxygen attached to the -OAr group described in the following general formula:

1

/ S. OAr

Ar "^

2

This oxygenated group has the meanings indicated above. It represents in particular a hydroxy group, -OCH, -O-CH Ph.

IX wherein R \ R ^"1 and R ^' have the meanings given above.

^According to the general formula I, n = l and m = 0, the carbon 1 of the formula

a carbonyl group: the compounds of formula III are 1-alkyl-2-alkyloxy ketones.

According to an advantageous embodiment of the invention, compounds of formula IXA are used.

wherein R ^"1 and R ³ have the meanings given above.

These ketones contain an OH in the ortho position on the aromatic group at carbonyl. R ^"1 may occupy the positions meta, para or the other ortho position of the cycle; R ³ may occupy the ortho, meta or para positions of the cycle.

According to one particular aspect of the invention, compounds of formula X are used

wherein R ¹ , R, R ", R ^{" 1} and R ³ have the meanings given above.

Carbon 1 of the formula is a methylene group here: the compounds of formula X are 1-alkyl-2-alkyloxyethanes, optionally substituted with the groups R ¹ and R ² , the meaning of which is previously indicated, R ¹ and R ² being in particular equal to carbon atoms, ^hydrogen, ketones thus being excluded here. R ^"1 and R ^* may occupy the ortho, meta or para positions.

According to an advantageous embodiment of the invention, compounds of formula XA are used.

wherein R ¹ , R ¹ and R ³ have the meanings given above.

These compounds, which do not belong to the ketone family, comprise an OH in the ortho position.

1

, OAr

Ar '

on the group -Ar located in a carbon 1 of the formula

R ^"1 may occupy the positions meta, para or the other ortho position of the cycle; R ³ may occupy the ortho, meta or para positions of the cycle.

According to another particular aspect of the invention, compounds of formula XI are used

wherein ^R, R \ R ^"1 and R ^'have the meanings described above.

The compounds XI are alcohols obtained from the ketones of formula IX

The R "group particularly represents a ^hydrogen atom, an alkyl group, an alkoxy group, a halogen chosen from fluorine, chlorine, bromine or ^iodine, and is especially a ^hydrogen atom. According to an advantageous embodiment of the invention, compounds of formula XI A are used.

wherein R \ R ^"1 and R ^' have the meanings given above.

These alcohols contain a -OH in the ortho position on the -Ar group located in a carbon 1 of the

1

OAr

Ar ^ -

formula ²

According to one particular aspect of the invention, XIIA, XIIB and XIIC fonmile compounds are used.

wherein

R ¹ , R ² , R 1 and R ^' have the meanings indicated above,

N is 0 or 1, m is 0 or 1, provided that n + m = 1. The compounds of formula XIIA, XIIB and XIIC belong to the family of 1-aryl-2-aryloxyethanes in which the aryl group in position 1 on the ethane chain of the formula

next is monosubstituted.

^■ In the compounds of formula XIIA, the R "group occupies the ortho position on the ring.

^■ In the compounds of formula XIIB, the group R ^"1 occupies the meta position on the ring.

^■ In the compounds of formula XIIC, R ^"1 group is in the para position on the ring. According to another particular aspect of the invention, compounds of formula I wherein

R ¹ , R, R ¹ and R ^' have the meanings given above, with the proviso that R "and R ^{" 1} are both different from H,

N is 0 or 1, m is 0 or 1, provided that n + m = 1.

These compounds belong to the family of 1-aryl-2-aryloxyethanes in which the group

1

, OAr

Ar "

aryl in position 1 on the ethane chain of the formula is disubstituted by the groups R "and R ^{" 1} , the meanings of which are defined above.

R "is in the ortho position on the cycle, R ^{" 1} may occupy the meta, para or second ortho position of the cycle. R "and R ^{" 1} are different from the hydrogen atom.

According to another particular aspect of the invention, compounds of formulas XIIIA, XIIIB and XIIIC are used.

XIIIA

XIIIB XIIIC

in which

R ¹ , R ² , R ¹ and R ³ have the meanings indicated above,

N is 0 or 1, m is 0 or 1, provided that n + m = 1.

The compounds of formulas XIIIA, XIIIB and XIIIC belong to the family of 1-aryl-2-aryloxyethanes in which the -OAr group in position 2 on the ethane chain of the formula is substituted by the group R ³ whose meanings are defined above.

R ³ represents in particular a ^hydrogen atom, a ^halogen atom selected from fluorine, chlorine, bromine or ^iodine, -OH, an alkoxy group, an alkyl group optionally substituted by halogen, a nitrogen-containing group and is in particular a ^hydrogen atom, a fluorine or bromine atom, -OH, -OCH _3, -0-CH -C ₆ H _5, -CH, -N0, -NH, -NH-C (0 ) -CH ₃ .

R ³ can occupy all the positions on the cycle:

^■ In the compounds of formula XIIIA, the R ³ group occupies the ortho position,

^■ In the compounds of formula XIIIB, the R ³ group occupies the meta position,

^■ In the compounds of formula XIIIC, the R ³ group is in the para position.

According to one particular aspect of the invention, compounds of formulas XIID, XIIE and XIIF are used.

in which R \ R ^"1 and R ³ have the meanings given above.

In the compounds of formulas XIID, XIIE and XIIF, the group R ³ is attached to the para position. The position of the group carried by the other aromatic ring, R "or R ^{" 1} , is variable, all positions being possible.

^■ In the compounds of formula XIId, the R "group occupies the ortho position,

^■ In the compounds of XIITH formula, the group R ^"1 occupies the meta position,

^■ In the compounds of formula thirteenth, the group R ^"1 is in the para position.

The invention relates to the use of compounds of the following formulas:

Compound 9 Compound 10

compound 11 compound 12

compound 13 compound 14

compound 17 compound 18

compound 19 compound 20

compound 21 composed 22

compound 23 compound 24

Compound 25 Compound 26

compound 27 compound 28 compound 29

compound 31 composed 32

compound 33 compound 34

compound 35 compound 36

compound 47 composed 48

Compound 49 Compound 50

compound 51 composed 52

compound 53 compound 54

compound 57 compound 58

compound 59 compound 60

compound 61 composed 62

compound 63 compound 64

compound 65 compound 66 compound 68

compound 71 compound 72

compound 73 composed 74

compound 75 composed 76

compound 77 composed 78

Compound 79 Compound 80

Compound 81 Compound 82

compound 83 composed 84

Compound 85 Compound 86 Compound 87

compound 90

compound 91 composed 92

compound 93 compound 94

compound 95 composed 96

compound 98

compound 99 compound 100

compound 101 compound 102

compound 103 compound 104

compound 105 compound 106

107 compound 108

compound 109 composed 110

compound 111 compound 112

113 compound 114

compound 115 composed 116

compound 117 compound 118

compound 119 compound 120

compound 129 compound 130

The invention also relates to the use of the compounds of the following formulas

Compound 137 The compounds listed above are used as active ingredients for the preparation of cosmetic compositions having anti-aging and / or depigmenting and / or cicatrizing and / or anti-inflammatory properties.

The invention relates to the use of the compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 1 10, 1 1 1, 1 12, 1 13, 1 14, 1 15, 1 16, 1 17, 1 18, 1 19, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, or 130 mentioned above for the preparation of cosmetic compositions having anti-aging and / or depigmenting properties and / or cicatrizing and / or anti-inflammatory.

The ^invention also relates to the use of compounds 131, 132, 133, 134, 135, 136, or 137 described above for the preparation of cosmetic compositions having anti-aging properties and / or depigmenting and / or healing and / or anti -inflammatory. According to a particular aspect of the invention, one or more compounds of formula I are used for the preparation of cosmetic compositions in which the anti-aging properties belong to the group consisting of the reinforcement of the half, the proliferation of dermal fibroblasts, the production of collagen, ^inhibition of gene ^expression "matrix metallopeptidase" MMP9 and protein "heat shock protein beta-1" 1 HSPB.

The "metallopeptidase 9 matrix" (MMP-9) is an enzyme encoded by the MMP-9 gene. It is involved in the degradation of extracellular proteins. It is involved in the remodeling of the extracellular matrix and, in particular, in the degradation of type IV and type V collagens.

"Extracellular matrix" refers to the set of extracellular macromolecules of the connective tissue.

The "heat shock protein beta-1 HSPB1" protein plays a role in the regulation of cellular development, in the inhibition of apoptosis and, in particular, in cell differentiation.

According to another particular aspect of the invention, one or more compounds of formula I for the preparation of cosmetic compositions in which the anti-inflammatory properties belong to the group consisting of inhibition of leukocyte elastase ^or secretion inhibition of prostaglandins E2.

Elastases are a subfamily of the serine protease responsible for the degradation of ^elastin. Among the many natural substrates for this enzyme, there is, in addition to ^elastin, the cartilage proteoglycan, fibronectin, and collagen types I, II, III and IV. On the skin, ^inhibition of ^elastase helps to fight against the effects of photo-induced aging or not and to limit ^the appearance of wrinkles and stretch marks.

Prostaglandins E2 (PGE2) play a role in inflammatory processes.

According to another particular aspect of the invention, one or more compounds of formula I for the preparation of cosmetic compositions in which the healing properties belong to the group consisting of proliferation and migration of keratinocytes to the recovery ^of a wound.

The migration and proliferation phases of cells are major phases of healing that occur after the inflammation phase. They are necessary for the recolonization of the wound. An increase in cell migration and proliferation allows improved healing.

The evaluation of the healing effect is thus evaluated:

by studying the proliferation and / or migration of fibroblasts,

by studying the proliferation and / or migration of keratinocytes.

In the study on proliferation and / or migration of fibroblasts, the biological model consists of normal human dermal fibroblasts (NHDF) whose culture conditions are 37 ° C and 5% CO in DMEM.

There is provided a control (in NHDF medium ^of DMEM test 0% FCS) (n = 6)) and uses a reference (FCS, fetal calf serum at 10% (n = 2)). For the compounds tested, n = 2.

Incubation is allowed 72 hours.

The assay involves inoculating normal human fibroblasts into 96-well plates suitable for migration studies. In these plates, the supports are pretreated with a solution of collagen and a cache is placed at the center of each well, preventing ^the adhesion of the cells in this zone and thereby forming an artificial wound. After labeling the cells with calcein, the caches are removed and then the cells are treated with the compounds or reference. The cell migration is microscopically followed for 72 hours with snapshots at 0 h, 24h, 48 h and 72 h. The results, expressed as a percentage of recovery, are compared to the untreated control.

In the study concerning the proliferation and / or migration of keratinocytes, the biological model consists of normal human epidermal keratinocytes (NHEK) whose culture conditions are 37 ° C and 5% CO in a medium of keratinocytes-SFM. EP-EGF (keratinocyte culture medium - serum free medium (SFM) without pituitary extract (EP) and without Epidermal Growth Factor (EGF), control (n = 6), reference: EGF (Epidermal Growth Factor) at 10 ng / ml (n = 2), compounds tested (n = 2).

Incubate for 72 hours.

The assay involves inoculating normal human keratinocytes into 96-well plates suitable for migration studies. In these plates, the supports are pretreated with a solution of collagen and a cache is placed at the center of each well, preventing ^the adhesion of the cells in this zone and thereby forming an artificial wound. After labeling the cells at calcein, the caches are removed and then the cells are treated with the compounds or reference. The cell migration is microscopically followed for 72 hours with snapshots at 0 h, 24h, 48 h and 72 h.

The results, expressed as a percentage of recovery, are compared to the untreated control.

According to another particular aspect of the invention, one or more compounds of formula I for the preparation of cosmetic compositions in which the depigmenting properties belong to the group consisting of ^the anti-tyrosinase ^activity and melanogenesis anti activity.

The "anti-melanogenesis activity" makes it possible to reduce the production of melanin, the main pigment responsible for the color of the skin.

The tyrosine involved in the manufacture of melanin, the "anti-tyrosinase activity" allows an inhibition of the production of melanin and, consequently, a depigmenting action. The depigmenting effect was evaluated on a NDP-MSH-stimulated B-type melanocyte line, (natural melanogenesis stimulating hormone, Melanocyte Stimulate Hormone, [Nie, DPhe] -a-MSH). The synthesis of melanin has been evaluated.

The study was carried out for compounds in solution in DMSO. The effects of the following 3 compounds at concentrations of 30 μιτιοΙΧ ¹ (30 μΜ) and 100 μιτιοΙΧ ¹ (100 μΜ) were compared:

Compound of formula I, and in particular IVA1 (compound 1)

• 4- (2,4-dihydrophenyl) butane or aicinol [18979-61 -8], already known for its depigmenting effects,

1 - (2,4-dihydroxyphenyl) -3- (2,4-dimethoxy-3-methylphenyl) propane [869743-37-3].

The results obtained showed that the compounds of formula I had a net inhibitory effect. On the other hand, the comparative study of the effects of the compounds of formula I with the effects of the two other compounds mentioned above, shows that the compounds of formula I are more effective with respect to depigmentation than the other two compounds.

The invention relates to cosmetic compositions containing as active substance one or more compounds of formula I

in which

■ R ¹ and R ² , identical or different, represent

° of ^hydrogen atoms,

° of ^atoms selected halogen (s) from fluorine, chlorine, bromine or ^iodine,

° -OH groups,

° phenoxy -OPH groups,

° aryloxy groups -OAr, in which Ar represents an aromatic group having 6 to 12 carbon atoms optionally substituted by one or more ^atoms selected halogen (s) from fluorine, chlorine, bromine, or optionally substituted by one or more -OH groups in free or protected form, and in particular protected form

of group -OMes, of group -OTHP of formula e group derived from ethylene

formula glycol in which

O varies from 1 to 12,

R ^a represents a hydrogen or a linear or branched alkyl group having from 1 to 6 carbon atoms, R ^c represents a linear or branched alkyl group of 1 to 10 carbon atoms,

a group derived from propylene glycol of formula, in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

group -OSitBDM of formula,

Benzyloxy groups -OCH ₂ Ph,

° -OTHP groups of formula above,

° -OMes groups,

Groups derived from ethylene glycol of formula

in which

O varies from 1 to 12,

R ^a represents a hydrogen or a linear or branched alkyl group having from 1 to 6 atoms of carbon,

R ^c represents a linear or branched alkyl group of 1 to 10 carbon atoms,

Groups derived from propylene glycol of formula, in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

° groups -OSitBdPh of formula

° -OSitBdM groups of formula,

in which

R ^a, R ^b, R ^a and R ^b, identical or different, represent

° of ^hydrogen atoms,

with the proviso that R / is hydroxy -OH,

■ R; and R ^"1, identical or different, represent

° of ^hydrogen atoms,

° of halogen ^atoms selected from fluorine, chlorine, bromine, ° linear alkyl groups, branched or cyclic containing from 1 to 10 carbon atoms, especially methyl groups, ethyl, isopropyl, optionally substituted by one or more selected halogen (s) from fluorine, chlorine, bromine or ^iodine, with a -CF ₃ group, by a hydroxy,

Hydroxyl groups -OH,

Linear or branched alkoxy groups comprising from 1 to 10 carbon atoms, especially methoxy, ethoxy, isopropoxy or tert-butoxy groups, optionally substituted by one or more halogens chosen from fluorine, chlorine, bromine or ^iodine, and in particular the trifluoromethoxy group -OCF _3,

Benzyloxy groups,

An alkynyloxy group comprising from 2 to 10 carbon atoms, linear or branched, and comprising at least one C triple = C triple bond,

° -OTHP groups of formula

Stated with the following formula

in which

x is equal to 0 or 1, y varies from 0 to 4, R ¹ is hydrogen or acetyl -C (O) -CH,

Groups derived from ethylene glycol of formula

in which

O varies from 1 to 12,

Groups derived from propylene glycol of formula in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

Formula -OSitBdPh

° -OSitBdM of

■ R ³ represents

° an ^hydrogen atom,

° a ^halogen atom selected from fluorine, chlorine, bromine,

A linear, branched or cyclic alkyl group comprising from 1 to 10 carbon atoms, including methyl, ethyl, isopropyl, optionally substituted by one or more halogens chosen (s) from fluorine, chlorine, bromine or ^iodine, a group -CF _3, hydroxy,

^D an alkenyl group comprising 2 to 6 carbon atoms, linear or branched and having at least one double bond C = C,

A phenyl group optionally substituted with a halogen atom, a -CF ₃ group, a linear or branched alkyl group comprising from 1 to 10 carbon atoms, a linear or branched alkoxy group comprising from 1 to 10 carbon atoms,

A hydroxyl group -OH,

A linear or branched alkoxy group comprising from 1 to 10 carbon atoms, especially methoxy, ethoxy, isopropoxy or tert-butoxy groups, optionally substituted by one or more halogens chosen from fluorine, chlorine, bromine or ^iodine, and in particular the trifluoromethoxy group -OCF _3,

A benzyloxy group,

A phenyloxy group,

A thiophenyl group,

An acyloxy group comprising from 2 to 10 carbon atoms, linear or branched,

A group -OTHP of formula

A substituted -OTHP group of the following formula

in which

x is equal to 0 or 1, y varies from 0 to 4,

R ^b is hydrogen or acetyl -C (O) -CH,

^A group -OS0 R ⁰ in which R ^c is an alkyl group having 1 to 6 carbon atoms, in particular methyl or ethyl, or an aromatic group containing from 6 to 18 carbon atoms, optionally substituted by one or more halogen atoms, hydroxy or alkoxy group, nitro group,

^D -OSO M group wherein M is an Na ion or, ° a group derived from ethylene glycol of the formula

in which

O varies from 1 to 12,

A group derived from propylene glycol of formula

in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

Formula -OSitBdPh

° -OSitBdM of formula,

° -COOH,

° -CN,

° -NH,

° -NH, X

- -NR ^d R,

° -NHR ^d R ⁺ , X

° -NHCOR,

° -NHCOOR ^g ,

° -N0 ₂ ,

X ^" representing a halide ion,

A group derived from piperazine, in particular

with the proviso that R / and R ^"1 do not simultaneously represent -OH groups or groups having a phenyl-bonded oxygen atom,

said active substance being in association with a cosmetically acceptable vehicle.

In a particular aspect, the ^invention relates to a cosmetic composition containing as active substance one or more compounds of formula I

in which :

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

■ R ¹ and R ² have the meanings mentioned above

■ R "and R ^{" 1} , identical or different, represent:

- of the ^hydrogen atoms,

hydroxyl groups,

And R ³ represents:

- a linear, branched or cyclic containing from 2 to 10 carbon atoms, especially ethyl, isopropyl, optionally substituted by one or more halogens chosen (s) from fluorine, chlorine, bromine or ^iodine, by a -CF ₃ group, with a hydroxy,

an alkynyl group comprising from 2 to 6 carbon atoms, linear or branched, and comprising at least one C-= = C triple bond. said active substance being in association with a cosmetically acceptable vehicle.

Because of their cosmetic properties, the compounds according to the invention find use in therapeutics as depigmenting agents of the skin, anti-aging agents, cicatrizants, anti-inflammatories.

For these purposes, they will be used in the form of cosmetic compositions containing as active ingredient at least one of the compounds of general formulas I in combination or in admixture with an inert, non-toxic, cosmetically acceptable excipient or carrier.

Suitable excipients for such administrations are oils, water and alcohol as well as surfactants, additives such as preservatives, antioxidants, dyes, perfumes.

The invention relates to cosmetic compositions consisting of a mixture comprising at least one compound of formula I as active principle in combination with one or more compounds having anti-aging and / or depigmenting and / or healing and / or anti-inflammatory properties. , particularly in combination with fatty acids such as ^linoleic acid ^or azelaic acid, and / or with antioxidants such as vitamin C and / or derivatives tocopherol, and / or with peeling aids such as retinoic ^acid or ^glycolic acid,

said composition having anti-aging and / or depigmenting and / or cicatrizing and / or anti-inflammatory properties.

The cosmetic compositions may contain a mixture of compound of formula I associated, in varying proportions, with one or more other compounds already known for their anti-aging and / or depigmenting and / or healing and / or anti-inflammatory and / or antioxidant.

The cosmetic compositions may thus possibly contain another agent known for its depigmenting properties such as:

· Linoleic acid, a deficiency of which causes a dry skin,

Azelaic acid, a tyrosinase inhibitor, having a depigmenting effect on melasma, chloasma, post-inflammatory hyperpigmentations,

• retinoic acid which inhibits tyrosinase and also causes desquamation moderate

or an antioxidant such as vitamin C or a tocopherol derivative.

According to one particular aspect of the invention, the cosmetic compositions have a content of compounds of formula I of 0.001% to 10% by weight.

The dosage may vary depending on the form. If a mixture of compounds I is used, the proportions of compounds of formula I of this mixture may vary, so that the overall percentage by weight is from 0.001% to 10%.

According to a particular aspect of the invention, the cosmetic compositions are in the form of cream, ointment, gel, ointment, lotion, patch, oil, serum, milk, spray, balm, emulsion, microemulsion.

The cosmetic compositions will be presented under one of the cosmetic forms suitable for dermal administration. In this respect, mention may be made of creams, ointments, gels, oils, seines, milks, sprays, emulsions and encapsulations.

According to one particular aspect of the invention, the cosmetic compositions contain as active substance one or more compounds of formula II

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ , R, R "and R ^{" 1} have the meanings indicated above,

° -NH,

- -NR ^d R,

° -NHCOR,

° -NHCOOR ^g ,

° -N0, A group derived from piperazine, in particular

R ^d R ^e representing straight or branched alkyl groups having 1 to 4 carbon atoms, optionally substituted by one or more halogen atoms, or carbon chains interrupted by oxygen or sulfur atoms, benzyl groups optionally substituted with a halogen atom, a hydroxy group, an alkoxy group having from 1 to 8 carbon atoms,

in combination with a cosmetically acceptable vehicle.

These are compounds containing a nitrogen group, in particular nitro, amino, amido, carried by the

-OAr group of the following general formula

According to a particular aspect of the invention, the cosmetic compositions contain at least as active substance one or more compounds of formula

in which

■ R ^"1 and R ³ have the meanings indicated above,

■ R ^la, R ^lb, R ^a and R ^b, identical or different, represent

° of ^hydrogen atoms,

° of halogen ^atoms selected from fluorine, chlorine, bromine or ^iodine,

in combination with a cosmetically acceptable vehicle.

These compounds are characterized in that they contain a cyclopropyl.

According to one particular aspect of the invention, the cosmetic compositions contain as active substance one or more compounds of formula IV

in which

R ¹ , R ² , R ^"1 and R ^' have the meanings indicated above,

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

in combination with a cosmetically acceptable vehicle.

According to a particular aspect of the invention, the cosmetic compositions contain as active substance one or more compounds of formula IVA

in which

R ³ has the meaning indicated above,

in combination with a cosmetically acceptable vehicle.

According to a particular aspect of the invention, the cosmetic compositions contain as active substance one or more compounds of formula V

in which

R \ R ^"1 and R ³ have the meanings given above,

with the proviso that R "and R ^{" 1} are both different from -OH or any form in which - OH is protected,

in combination with a cosmetically acceptable vehicle. According to a particular aspect of the invention, the cosmetic compositions contain as active substance one or more of the compounds of formulas 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1, 1, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 1, 10, 1, 1 , 1 12, 1 13, 1 14, 1 15, 1 16, 1 17, 1 18, 1 19, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, or 130 mentioned above, in combination with a cosmetically acceptable vehicle.

According to a particular aspect of the invention, the cosmetic compositions contain as active substance one or more of the compounds of formulas 131, 132, 133, 134, 135, 136 or 137 mentioned above, in association with a cosmetically acceptable vehicle.

According to a particular aspect of the invention, the cosmetic compositions contain a mixture comprising one or more compounds belonging to the list of compounds 1, 2, 3, 4, 5 , 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 1 10, 1 1 1, 1 12, 1 13, 1 14, 1 15, 1 16, 1 17, 1 18, 1 19, 120, 121, 122, 123, 124 , 125, 126, 127, 128, 129, or 130 previously mentioned as active ingredient, in combination with one or more compounds having anti-aging and / or depigmenting and / or healing and / or anti-inflammatory properties, particularly in combination with fatty acids such as ^linoleic acid ^or azelaic acid, and / or with antioxidants such as vitamin C and / or tocopherol derivatives, and / or with peeling aids such as ^retinoic acid ^or glycolic acid,

According to one particular aspect of the invention, the cosmetic compositions contain a mixture comprising one or more compounds belonging to the list of compounds 131, 132, 133, 134, 135, 136, or 137 mentioned previously as active principle, in combination with one or more compounds having anti-aging properties and / or depigmenting and / or healing and / or anti-inflammatory drugs, particularly in combination with fatty acids such as ^linoleic acid ^or azelaic acid, and / or antioxidants such as vitamin C and / or tocopherol derivatives, and / or with peeling aids such as ^retinoic acid ^or glycolic acid,

The ^invention also relates to compounds of formula I

in which :

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

■ R ¹ and R ² have the meanings mentioned above ■ R "and R ^-1 , identical or different, represent:

- of the ^hydrogen atoms,

hydroxyl groups,

And R ³ represents:

an alkynyl group comprising from 2 to 6 carbon atoms, linear or branched, and comprising at least one C triple = C triple bond.

The ^invention also relates to a compound of formula X

in which

N is 0, and m is 1,

R ¹ and R have the meanings mentioned above,

■ R "and R ^{" 1} , identical or different, represent:

- of the ^hydrogen atoms,

hydroxyl groups,

■ and R5 represents:

an alkynyl group comprising from 2 to 6 carbon atoms, linear or branched and having at least one triple bond C

The invention relates to compounds of formula II

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

■ R "and R ^{" 1} have the meanings indicated above,

° -NH,

- -NR ^d R,

° -NHCOR,

° -NHCOOR ^g ,

° -N0,

A group derived from piperazine, in particular

compounds having a nitrogen group, in particular nitro, amino, amido, carried by the

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ and R ² have the meanings indicated above,

■ R 'and R ^~ have the meanings described above, with ^the exception of ^atoms hydrogen,

-NR ^a R ^{* b} represents a group comprising a nitrogen atom attached to the ring, optionally in its salt form, this group being chosen from

° -NH,

- -NR ^d R,

° -NHCOR,

° -NHCOOR ^g ,

° -N0,

A group derived from piperazine, in particular

1

/ S. OAr

Ar "^

-OAr group of the following general formula

According to another particular aspect, ^the invention relates to compounds of formula II

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ and R ² have the meanings indicated above,

R 'represents a hydroxyl group and R ^"1 has the meanings indicated above,

° -NH,

- -NR ^d R,

° -NHCOR,

° -NHCOOR ^g ,

° -N0,

A group derived from piperazine, in particular

R ^g represents a linear or branched alkyl group having from 1 to 4 carbon atoms, optionally substituted by one or more halogen atoms, or a chain carbonated interrupted by oxygen or sulfur atoms, a phenyl group, a benzyl group optionally substituted by a halogen atom, a hydroxy group, an alkoxy group and in particular substituted by the methoxy group in the para position.

1

.OAr

^ \ ^

Ar '

-OAr group of the following general formula

The invention relates to the compounds of formula

in which

■ R ^"1 and R ³ have the meanings indicated above,

■ R ^la, R ^lb, R ^a and R ^b, identical or different, represent

° of ^hydrogen atoms,

° of halogen ^atoms selected from fluorine, chlorine, bromine or ^iodine,

° linear or branched alkyl groups comprising from 1 to 10 carbon atoms, especially methyl groups, ethyl, isopropyl, optionally substituted by one or more halogens chosen (s) from fluorine, chlorine, bromine or ^iodine, by a -CF ₃ group, by a hydroxy

These compounds are characterized in that they contain a cyclopropyl.

The invention relates to formula compounds

3, 7, 8, 9, 10, 11, 12, 13, 14, 18, 19, 20, 21, 22, 27, 28, 29, 30, 32, 33, 34, 35, 36, 37, 38 , 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 64, 65 ,,,,, , 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 1, 10, 11, 12, 13 , 1 14, 1 15, 1 16, 1 17, 1 18, 120, 121, 122, 124, 125, 126, 127, 128, 129, or 130 mentioned above. The invention also relates to the compounds of formulas 131, 132, 133, 134, 135, 136 or 137 mentioned above.

According to a particular aspect, the invention relates more particularly to compounds of formula:

compound 35 compound 39

composed 43

compound 51 compound 130

The invention relates to a process for the preparation of Fonmile XA compounds

in which

R ¹ , R ² , R ^"1 and R ³ have the meanings indicated above,

► comprising a reaction step of a pheno alcohol XIV, with mesyl chloride

to obtain the protected compound XV

R ¹ , R ² , R ^"1 having the meanings indicated above,

Comprising a step of reaction of the compound XV of formula above with a derivative of

ph XVI

R ³ having the meanings indicated above,

to obtain the protected compound XVII,

R ¹ , R ² , R ^"1 and R ³ having the meanings indicated above,

Comprising a step of deprotection of the phenolic function of the compound XVII formula above

to obtain the compound of formula

R ¹ , R ² , R ^"1 and R ³ having the meanings indicated above,

and in particular R ¹ and R ² are both hydrogen atoms.

This method is applicable to prepare compounds having a -OH group ortho on the

1

, OAr

Ar '

-Ar group of the following general formula

The synthesis, comprising 3 steps, is represented in the following diagram

In the first step, the phenolic alcohol XIV reacts with the mesyl chionire to give the dimesylated compound. This step is a way to protect the phenolic -OH on the one hand and to activate the -OH carried by the ethane chain on the other hand. The first step thus provides the dimesyl compound XV which, in the second step, undergoes a substitution by reaction with the phenol XVI to give the compound XVII, belonging to the family of 1-alkyl-2-alkyloxyethanes. Basic hydrolysis is the last step and liberates the phenolic -OH compound XA.

The invention also relates to a process for the preparation of compounds of formula V

in which

R ¹ , R ² , R ¹ and R ³ have the meanings indicated above,

provided that R "and R ^{" 1} are both different from -OH or any form in which - OH is protected, comprising a Mitsunobu-type reaction carried out on an allyl alcohol of formula

and a phenol XVI of formula

to obtain the compounds of formula V,

R ¹ , R ² , R ¹ and R ^* have the meanings indicated above,

and in particular R ¹ and R ² are both hydrogen atoms.

In contrast to the process previously described, this process is applicable to prepare compounds which do not have an ortho -OH group on the -Ar group of the following general formula

The synthesis, consisting in making a Mitsunobu reaction, is represented in the following diagram:

X \ I XMII Y

Compound XVIII reacts with phenol XVI in the presence of triphenylphosphine then diethyl azodicarboxylate to give a compound of the 1-aryl-2-aryloxyethane family, R "being different from -OH or any protected form of -OH.

The invention also relates to a process for the preparation of the compounds of formula III

■ R ^"1 and R ³ having the meanings indicated above,

R ^a , R ^lb , R ^a and R ^b , identical or different, representing

° of ^hydrogen atoms,

° of halogen ^atoms selected from fluorine, chlorine, bromine or ^iodine,

► Process comprising a Mitsunobu type reaction step on an alcohol of formula

XIX

R ^"1, R ^a, R ^b, R ^a and R ^b have the meanings designated above,

to get the compound XX

R ³ having the meanings indicated above,

A process comprising a deprotection reaction of the phenolic -OH of the compound XX represented above,

to obtain compound III

R ^a, R ^b, R ^a, R ^b, R and R ⁵ having the ion designated significat above,

and in particular ^the R, R ^b, R ^a and R ^b being four hydrogen atoms.

In this process, the Mitsunobu reaction is carried out on the cyclopropane alcohol XIX and is followed by a deprotection of the phenolic -OH, as shown in the following scheme:

When R ^la = R ^lb = R ^a = R ^b = R ^"1 = H then compound XIX is commercial.

When R ^a = R ^lb = R ^a = R ^b = H and R ^"1 and R ³ have the meanings designated above, the derivatives can be obtained by fomiation cyclopropyl through techniques known rhomme ^art (Cy C and al, Eur J. Med Chem 1991 26 (2) p 125-128, Kirmse W et al, Chem.

Ber. 1986 1 19 (2) 3694-3703; Qiao J et al, Bioorg. Med. Chem. Lett 2009 19 (2) p 462-468): for example dibromoethane in basic condition (Muthusamy S et al, Tet Lett 2005 46 (4) p

635-368).

Deprotection conditions appeal to the knowledge of ^man of ^art and resort to conventional techniques such as ^the use of boron tribromide.

The invention also relates to a process for the preparation of compounds of formula IIA

in which R ¹ , R ² and R ^"1 have the meanings indicated above,

► comprising a reaction step of a pheno alcohol XIV, with mesyl chloride

to obtain the protected compound XV

XV

R ¹ , R and R ^"1 having the meanings indicated above,

Comprising a step of reaction of the compound XV of formula above with a derivative of XVIA

to obtain the protein compound

R ¹ , R ² and R ^"1 having the meanings indicated above,

Comprising a step of deprotection of the phenolic function of compound XVIIA of formula above

to obtain the compound of formula

R ¹ , R ² and R ^"1 having the meanings indicated above

and in particular R ¹ and R ² being two hydrogen atoms.

The invention also relates to a process for the preparation of compounds of formula IIB

IIB R ¹ , R and R ^"1 having the meanings indicated above,

including a reduction of the cost

IIA

by reduction under pressure of hydrogen in the presence of a catalyst

to obtain the compound IIB shown above.

The invention relates to a process for preparing the compounds of Fonmile IIC

in which

R ¹ , R ² , R ^"1 and R _f have the meanings indicated above,

► comprising a reaction step of a pheno alcohol XIV, with mesyl chloride

to obtain the protected compound

R ¹ , R ² , R ^"1 having the meanings indicated above,

ph XVIA

to obtain the protected compound XVII A,

R ¹ , R ² , R ^"1 and R _f having the meanings indicated above,

to get the compound of fo

IIC

R ¹ , R ² , R ^"1 and R _t having the meanings indicated above,

and in particular R ¹ and R ² are both hydrogen atoms. This route makes it possible to obtain compounds bearing an amide function.

^The acetamide of the formula XVIA with R _f = -CH ₃ is commercial. The molecules of formula XVIA can be obtained by direct amidation of raminophénol by a derivative anhydride or ^acid chloride, as described by David Rely in Helv. Chim. Acta 1939, 22 p89, Palm et al., J. Med. Chem. 1998, 41 (27), 5382-5392, Deng W et al., Bioorg. Med. Chem. Lett. 2006, 16 (2), 469-472.

The invention relates to a process for the preparation of compounds of formula I

in which N, m, R ¹ , R ² , R ^"1 and R ^* have the meanings given above,

R "is a -OH group coupled to a saccharide compound which may be an α- or β-furanose or an α- or β-pyranose,

A process comprising a coupling reaction between compound IV of formula

and a sugar which may be a- or β-furanose or a- or β-pyranose, the -OH being protected, in particular in the form of acetates, and the anomeric position being previously activated in the form of bromine or trichoroacetimidate,

to give a sugar derivative of formula I shown above.

It is ^a question ^of a Koenigs-Κηοΐ type of change. The phenol function of the compound of general formula I reacts with a saccharide unit which may be an α- or β-furanose or a- or β-pyranose, protected and previously activated in the form of a brominated derivative, which may be commercial, or in the form of trichloroacetimidate derivative. The preparation of these is described in the literature (Thisbe Lindhorts, Essentials of Carbohydrate Chemistry and Biochemistry, WILEY-VCH 2000). This coupling is followed or not by ^a deprotection of acetates, for example, in basic medium.

EXAMPLES

Meaning of the abbreviations used:

TEA: triethylamine

DMSO: dimethylsulfoxide

NDP-MSH: [Nie, DPhe] -a-MSH

DMEM: Dulbecco / Vogt Modified Eagle's minimal essential medium. Eagle's essential minimum medium, (cell culture medium developed by Harry Eagle, it is used to maintain the cells of a tissue culture). The techniques ^of analysis are:

Nuclear magnetic resonance:

NMR spectra were made at 300 MHz (Briicker spectrometer) for the proton. The chemical shifts are expressed in ppm, the residual chloroform being taken as internal reference (singlet at 7.28ppm), or the residual dimethylsulfoxide being taken as internal reference (bulk at 2.50ppm). The multiplicity of signals is symbolized by the following letters: s singlet, d doublet, dd doublet of doublet, t triplet, q quadruplet and m multiplet. Chromatography: LCMS

^The LC / MS analysis corresponds to a coupling of ^the HPLC analysis and ^the mass spectrometry analysis. It is performed on a Alliance Waters 2695-ZQ2000 aircraft.

HPLC (Waters 2690)

Detector: DAD detector (Waters, ref .: 2996, λ = 190nm to 800nm):

Detector: Corona ™ (ESA):

Mass Sensor (Waters, part number ZQ2000): 100 - 1500 Dalton; Negative and positive ion

HPLC oven temperature: 40 ° C

Flow rate: 1 mL / min

The methods used for HPLC are given below. For the analytical results, the method and the retention time are specified. XTerra method

Column: XTerra ® MS C 18: 4.6 mm x 150 mm, 5μιτι (Waters, ref 186000490)

Eluent A: Water (HCOOH-0.02%); Eluent B = CH CN) with gradient ^elution

Condition ^of elution gradient

Mi HCO; H to MeCN Curve

not. 0.2

90 10

4 75 25 8

5 65 35 6

11 5 95 7

14 5 95 7

17 90 10 6

20 90 10 6 XBridge method

Column: XBridge TM C 18: 4.6 mm x 150 mm, 5μιτι (Waters, 1860031 16)

Eluent A: Water (HCOOH-0.02%); Eluent B = CH CN) with gradient ^elution

Condition ^of elution gradient

Min HCO _: H has 0.2 "MeCN Curve

90 10

-1 75 25 S

5 65 5 6

5 95 7

1 -1 5 95 7

1 7 90 10 6

20 90 10 6

Example 1: General Procedure for the Preparation of Compounds of Formula XA

XA

R ¹ , R, R ^"1 and R ³ having the meanings indicated above,

by a multi-step synthesis represented in the following diagram:

• stage 1: protection / activation In a three-necked 250mL dry, under a flow ^of nitrogen and magnetic stirring the diol XIV (1 equiv) was diluted in dichloromethane (5 volumes) and then TEA (2.2 equivalents) is added. The reaction medium is cooled to 5 ° C. ^Using ^a dropping funnel, methanesulfonyl chloride (2.2 equivalents) diluted in dichloromethane (5 volumes) was added while controlling the temperature. The reaction medium is then stirred at room temperature for one night. The reaction medium is poured into an ice-water / HCI mixture. After three extractions with dichloromethane, the organic phases are washed with saturated NaCl solution. After drying over MgSO 4 and filtration on sinter, the filtrate is concentrated in vacuo. The residue is purified by trituration in pentane. The products obtained are oils or solids according to the natures of R ¹ , R ² and R ^"1 .

• stage 2: substitution

In a three-necked flask of OOmL, dry, under a flow ^of nitrogen and magnetic stirring the dimesylate compound XV (1 equivalent) is dissolved in ^acetonitrile (10 volumes). A phenol of formula XVI (1.2 equivalent) is added as well as CO (1.2 equivalent). The reaction medium is refluxed for 4 hours. At room temperature, the reaction medium is filtered to remove the salts and the filtrate is concentrated in vacuo. The residue is taken up in dichloromethane and aqueous NaHCO 3 solution. After three extractions with dichloromethane, the organic phases are washed with a saturated solution of NaCl. After drying over MgSO 4, the organic phase is filtered and concentrated in vacuo. The products obtained are monomésylates of formula XII, oils or solids according to the natures of R ¹ , R ² , R ^"1 and R \ purified in particular by chromatography on silica or by trituration in isopropyl ether / pentane mixtures of variable composition.

• stage 3: deprotection

In a three-necked 50 mL equipped ^with a condenser, with magnetic stirring, the monomesylate of formula XII (1 equivalent) is dissolved in ^ethanol (12 volumes). A sodium hydroxide solution 2 mol.L ¹ (2 equivalents) was added and ^the whole is heated with stirring at reflux for 4h. At room temperature, the reaction medium is concentrated in vacuo. The residue is taken up in ^water and the solution is acidified. It is extracted with dichloromethane and the organic phases are washed with a saturated solution of NaCl. After drying over MgSO 4, the organic phase is filtered and concentrated in vacuo. The compounds XA, oils or solids, purified in particular by chromatography on silica gel, are obtained. Example 2 Preparation of compound 1 of formula

It is repaired by the multi-step synthesis shown in the following diagram:

Compound 1

· Stage 1: protection / activation

Stage 1 is carried out according to the procedure described in Example 1 from compound XIVA. After filtration and drying under vacuum, compound XVA is isolated. It is a white solid obtained with 92% yield. He is engaged in the next stage. · Stage 2: substitution

Stage 2 is carried out according to the procedure described in Example 1 using 4-fluorophenol. The residue is purified on silica gel column eluted with a gradient heptane - ^ethyl acetate. The monomatesate XIIA is obtained. It is a yellow oil, obtained with 55-65% yield. He is engaged in the next stage.

• stage 3: deprotection

Stage 3 is carried out according to the procedure described in Example 1. The residue was purified on silica gel column eluted with a gradient heptane - ^ethyl acetate. Compound 1 is a colorless oil obtained with 60-70% yield.

1 H NMR (300 MHz, CDCl 3): δ (ppm) 3.14 (t, 2H, CH ₂ -C ₆ H ₅ ); 4.24 (t, 2H, CH-O); 6.81 (s, 1H, -OH); 6.85-7.22 (m, 8Η, aromatic H).

HPLC: XTerra t _r = 12.25min

Mass ES ^" : [MH] ^" = 231.2. Example 3: general procedure for the preparation of compounds V;

Mitsunobu reaction for molecules without free phenol function

The synthesis is represented in the following diagram:

XVIII Y

R ¹ , R, R ¹ and R ^* having the meanings indicated above.

General Procedure: In a three-necked 25 ml, under ^nitrogen flux and magnetic stirring the alcohol compound XVIII (1 equivalent) was diluted in tetrahydrofuran (16 volumes) and a phenol derivative (1 equivalent) and triphenylphosphine (1.3 equivalent ) are added. The reaction medium is stirred at room temperature. Then, the diethyl azodicarboxylate (1.3 equivalent) is added dropwise. The reaction medium is stirred at room temperature overnight. The reaction medium is concentrated. The residue is taken up in ^distilled water and ^the ethyl ^acetate. After three extractions ^of ethyl ^acetate, the organic phases are washed with saturated NaCl solution. After drying over MgSO 4 and sintering, the filtrate is concentrated in vacuo. The residue is purified by chromatography on silica gel eluted with a gradient heptane / ^ethyl acetate.

Example 4: Mitsunobu reaction for molecules without free phenol function

The phenol derivative may be in particular 4-fluorophenol.

The synthesis with 4-fluorophenol is represented in the following scheme:

XVIII

Procedure: in the case where R ^"1 is a methyl in para

In a three-necked 25 ml, under ^nitrogen flux and magnetic stirring the compound XVIII (1 equivalent) was diluted in tetrahydrofuran (15 volumes) and then the 4-fluorophenol (1 equivalent) and triphenylphosphine (1.3 equivalent) are added. The reaction medium is stirred at ambient temperature. Then, the diethyl azodicarboxylate (1.3 equivalent) is added dropwise. The reaction medium is stirred at room temperature overnight. The reaction medium is concentrated. The residue is taken up in ^distilled water and ^the ethyl ^acetate. After three extractions ^of ethyl ^acetate, the organic phases are washed with saturated NaCl solution. After drying over MgSO 4 and filtration on ice, the filtrate is concentrated in vacuo. The residue is purified by chromatography on silica gel eluted with a gradient heptane / ^ethyl acetate. The fraction containing the desired product is concentrated: a colorless oil is obtained with 54% yield.

1 H NMR (300 MHz, CDCl 3): δ (ppm): 2.34 (s, 3H, -CH ₃ ); 3.09 (t, 2H, CH-C ₆ H ₅ ); 4.15 (t, 2H, CH 2 -O); 6.85-7.29 (m, 8H, aromatic H).

HPLC: XTerra t _r = 13.56min

Mass ES ⁺ : [M + Na] ⁺ = 253.3.

Example 5: general procedure for the preparation of compounds IIB;

reduction reaction for molecules with a free amino function

The synthesis is represented in the following diagram:

R ¹ , R, R "and R ^{" 1} having the meanings indicated above.

General procedure for ^the step of the nitro function of reduction: in a flask equipped with ^a three-way cock, the compound IIA (1 equivalent) was diluted ⁱⁿ ethyl ^acetate (20 volumes) and then the reaction medium is purged with alternating vacuum / ^nitrogen atmosphere. Palladium catalyst on charcoal 10% was added and the reaction medium is purged by alternation ^of a ^nitrogen atmosphere ^and ^hydrogen atmosphere. The reaction mixture was stirred at room temperature under atmospheric pressure of ^hydrogen for 7 h. After filtration over a cake of celite, the filtrate is concentrated under vacuum and the residue is purified by chromatography on silica or by crystallization.

Example 6: Reduction reaction for molecules with free amino function

The derivative XVIII may especially be 2-hydroxyphenylethanol.

The synthesis is in this case: This reduction step is carried out according to the procedure described in ^Example 5 from the compound 19, which is itself obtained according to the general procedure described in ^Example 1.

Compound 21 is obtained, after crystallization from dichloromethane, in the form ^of a beige solid in 60% yield.

1 H NMR (300MHZ, DMSO-d6):? (Ppm) 2.90 (t, 2H, CH -C ₆ H _5); 3.96 (t, 2H, CH-O); 4.58 (bs, 2H, -NH 2): 6.46-7.14 (m, 8H, aromatic H); 9.42 (bs, 1H, -OH).

HPLC: XTerra t _r = 7.63min

Mass ES ⁺ : [M + H] ⁺ = 230.3. EXAMPLE 7 Coupling Reaction of an Osidic Derivative on a Phenol Function

The general synthesis is represented on the following diagram:

R ¹ , R, R ^"1 and R ^* have the meanings designated above.

^■ Step 1: Coupling of the saccharide derivative activated in the form of trichloroacetimidate In a three-necked flask of 50mL, under ^nitrogen flux and magnetic stirring the phenol derivative of formula V (1 equivalent) is dissolved in dichloromethane (7 vol), then the activated osidic derivative in the form of trichloroacetimidate (1.3 equivalent) is introduced, previously solubilized in 8 volumes of dichloromethane. At 0 ° C, in the presence of molecular sieve beads, a solution of BF ₂ (2 equivalents) is added. At room temperature, the reaction medium is stirred for 2 hours. It is then poured on a saturated solution of NaHCCh. After extraction with dichloromethane, the organic phases are washed with a saturated solution of NaCl. After drying over MgSO 4 and sintering, the filtrate is concentrated in vacuo. The residue is purified by chromatography on silica gel eluted with a heptane / dichloromethane gradient. The fraction containing the desired product is concentrated.

^■ Step 2: Deprotection of the hydroxyl of the saccharide unit

In a 20 ml flask, under an inert atmosphere, the above derivative (1 equivalent) is solubilized in methanol (10 volumes). At room temperature, a solution of 1M sodium methanolate is added and the reaction mixture is stirred for 2.5 hours. After adding acidic resin, the medium is filtered and concentrated under vacuum. The residue obtained is purified by chromatography or by trituration in carefully chosen solvents.

Example 8 Preparation of compound 29

The general s nthesis is shown in the following diagram

compound 1 compound 30 compound 29

Step 1: coupling of the activated osidic derivative

This stage 1 is carried out according to the procedure described in ^Example 7 starting from the compound 1.

After purification by silica gel chromatography, compound 30 is isolated. ^It is a white solid obtained with 85% yield.

1 H NMR (300MHZ, DMSO-d6):? (Ppm) 2.05 (s, 12H, -CO-CH: 3.08 (t, 2H, CH -C ₆ H _5); 3.90

(m, 1H, anomeric H); 4.02-4.33 (m, 4H, H glucose); 5.10-5.23 (m, 2H, H glucose); 5.35 (t,

2H, CH 2 -O); 6.80-7.29 (m, 8H, aromatic H).

HPLC: XBridge t _r = 13.16min

ES mass ^" : [M + H ₂ O-H] = 580.2.

Step 2: deprotection

Stage 2 is carried out according to the procedure described in ^Example 7 starting from the compound 30.

After purification by trituration in a pentane / isopropyl ether mixture, the compound 29 is isolated. ^It is a white solid obtained with 80% yield.

1 H NMR (300MHZ, DMSO-d6): δ (ppm) 3.04 (m, 2H); 3.12 (m, 1H); 3.28 (t, 2H, CH -C ₆ H _5);

3.46 (m, 1H); 3.83 (m, 1H,); 4.16 (t, 2H, CH-O); 4.59 (m, 1H, -OH); 4.83 (d, 1H); 5.04-5.32

(m, 3H, -OH); 6.93-7.25 (m, 8Η, aromatic H).

HPLC: XBridge t _r = 10.10min

Mass ES ^" : [MH] ^" = 393.4. Example 9: General Procedure for the Preparation of Compounds 35, 39, 43, 47, 51 and 130

compound 51 compound 130

A multi-state synthesis represented in the following scheme is performed

XVA

• stage 1: protection / activation

In a three-necked 250mL dry, under a flow ^of nitrogen and magnetic stirring the compound 2- (2-hydroxy-ethyl) -phenol (1 equivalent) was diluted in dichloromethane (5 volumes) and then TEA (2.2 equivalents) is added. The reaction medium is cooled to 5 ° C. ^Using ^a dropping funnel, methanesulfonyl chloride (2.2 equivalents) diluted in dichloromethane (5 volumes) was added while controlling the temperature. The reaction medium is then stirred at room temperature overnight. The reaction medium is poured into an ice-water / HCI mixture. After three extractions with dichloromethane, the organic phases are washed with saturated NaCl solution. After drying over MgSO 4 and sintering, the filtrate is concentrated in vacuo. The residue is purified by trituration in pentane. The products obtained are oils or solids according to the natures of R. • stage 2: substitution

In a three-necked flask of OOmL, dry, under a flow ^of nitrogen and magnetic stirring the XVA compound (1 equivalent) is dissolved in ^acetonitrile (10 volumes).

Phenols derivatives (1.2 equivalents) are added as well as CO (1.2 equivalents).

Said phenol derivatives are the following:

HO. ,

1. p _0ur obtaining ^the compound 35

to ^obtain the compound 39 to ^obtain compound 43

to ^obtain compound 51

to ^obtain compound 130

The reaction medium is refluxed for 4 hours. At the end of the reaction, the reaction mixture is hydrolysed by 25 volumes of ^distilled water. After two extractions with dichloromethane, the organic phases are washed with saturated NH 4 Cl solution, dried over MgSO 4, filtered and concentrated in vacuo.

The residue obtained is purified by chromatography on silica gel eluted with a heptane / chloroform or heptane / isopropyl ether or heptane / isopropanol gradient, depending on the polarity of the compounds.

The colorless liquids, obtained with 20-60% yield, are each engaged in the next stage of deprotection. • stage 3: deprotection

In a three-necked 50 mL equipped ^with a condenser, with magnetic stirring, the monomesylate

formula (1 equivalent) is dissolved in ^ethanol (12 volumes). A sodium hydroxide solution 2 mol.L ¹ (2 equivalents) was added and ^the whole is heated with stirring at reflux for 4h.

After the reaction is complete after 20 hours, the ethanol solvent is removed under vacuum and the residue is taken up in a mixture of distilled water and dichloromethane. After repeated extraction, the organic phases are dried over MgSO 4, filtered and concentrated in vacuo.

The residue is purified by chromatography on silica gel eluted with a gradient heptane / ^ethyl acetate.

The reaction yield is 45-70%.

The compounds obtained are characterized in the following manner:

Compound 35: colorless oil

Ή NMR (300 MHz, CDCl):? (Ppm) 1.22 (t, 3H, _CH}) 2.60 (q, 2H, CH -CH); 3.13 (t, 2H, CH-Ph); 4.26 (t, 2H, CH-O); 6.84-6.96 (m, 4H, aromatic H); 7.10-7.21 (m, 4H, aromatic H)

HPLC: XBridge t _r = 13.2min

ES ⁺ mass: [M + H] ⁺ = 243.1

Compound 39: colorless oil

Ή NMR (300 MHz, CDCl):? (Ppm) 1.22 (s, 6H, _CH}); 2.87 (heptuplet, 1H, CH-); 3.13 (t, 2H, CH-Ph); 4.26 (t, 2H, CH-O); 6.85-6.95 (m, 4H, aromatic H); 7.13-7.21 (m, 4H, aromatic H)

HPLC: XBridge t _r = 13.5min

Mass ES ⁺ : [M + H] ⁺ = 255.2 Compound 43: colorless oil

¹H NMR (300 MHz, CDCl)): δ (ppm) 0.66 (t, 3H, -CH ₂ -CH <): 1.26 (s, 6H, -C-CH; 1.62 (m, 2H, -C-CH 2 -): 3.13 (t, 2H, CH ₂ -P) 4.27 (t, 2H, CH ₂ -0) 6.85-7.26 (m, 8H, aromatic H) HPLC: XBridge t _r = 13.9min

Mass ES ^" : [MH] ^" = 283.2

Compound 47: colorless oil

Ή NMR (300MHz, CDCl):? (Ppm) 1.30 (t, 9H, -C _{_(CH})}):} 3.13 (t, 2H, CH ₂ -P); 4.27 (t, 2H, CH 2 -O); 6.86-7.33 (m, 8H, aromatic H)

HPLC: XBridge t _r = 13.7min

Mass ES ^" : [MH] ^" = 269.2

Compound 51: colorless oil

NMR Ή (300 MHz, CDCl 3): δ (ppm) 0.46-1.67 (m, 19H, - (CH ₂ h-CH ₎ ); 3.13 (t, 2H, CH ₂ -Ph); 4.27 (t, 2H, CH ₂ 0) 6.84-6.96 (m, 4H, aromatic H) 7.13-7.24 (m, 4H, aromatic H) HPLC: XBridge t _r = 12.6min

Mass ES ^" : [MH] ^" = 339.3

Compound 130: colorless oil

NMR Ή (300MHz, CDCh): δ (ppm) 0.93 (t, 3H, -CH ₂ -CH <): 1.60 (m, 2H, -CH ₂ -CH); 2.54 (t,

2H, -CH ₂ -CH ₂ -); 3.14 (t, 2H, CH ₂ -Ph); 4.26 (t, 2H, CH ₂ -0); 6.84-6.97 (m, 4H, aromatic H); 7.08-7.22 (m, 4H, aromatic H)

HPLC: XBridge t _r = 13.5min

ES mass ^" : [MH] ^" = 255.2

Example 10: Summary Table of the Molecules Obtained in Examples 1 to 9

No. molecule Appearance Ή NMR (CDCh or DMSO-de)

Oil 3.14 (t, 2H, CH ₂ -Ph); 4.24 (t, 2H, CH ₂ -O); 6.81 (s, 1H, -

Compound 1

colorless OH); 6.85-7.22 (m, 8Η, aromatic H)

2.33 (s, 3Η, -CH; 3.13 (t, 2Η, CH ₂ -Ph); 4.26 (t, 2Η,

Oil

Compound 2 CH2-0); 6.81 -7.22 (m, 8Η, aromatic H)

colorless 3.14 (t, 2H, CH 2 -P); 4.24 (t, 2H, CH ₂ -O); 6.54 (s, 1H, -OH); 6.79-6.85 (m, 2Η, aromatic H); 6.88-6.94 (m,

Compound 3 Yellow Oil

2Η, aromatic H); 7.09-7.26 (m, 2Η, aromatic H); 7.36-7.42 (m, 2Η, aromatic H)

3.15 (t, 2Η, CH-Ph); 4.29 (t, 2Η, CH-O); 6.70-7.03 (m,

Compound 4 Yellow Oil 5Η, aromatic H); 7.15-7.26 (m, 2Η, aromatic H);

7.28-7.33 (m, 2Η, aromatic H)

3.17 (t, 2Η, CH-Ph); 4.18 (t, 2Η, CH-O); 6.87-6.94 (m,

Oil

Compound 5 2Η, aromatic H); 6.98-7.08 (m, 2Η, aromatic H);

colorless

7.31 -7.41 (m, 5 Η, aromatic H)

Oil 3.18 (t, 2Η, CH-Ph); 4.20 (t, 2Η, CH-O); 6.82-7.18 (m,

Compound 6 colorless 6Η, aromatic H); 7.22-7.37 (m, 2Η, aromatic H)

3.26 (t, 2Η, CH-Ph); 4.20 (t, 2Η, CH-O); 6.83-6.90

(m, 2Η, aromatic H); 6.95-7.03 (m, 2Η,

Oil

Aromatic H); 7.12 (m, 1 Η, aromatic H);

Compound 7 colorless

7.23-7.37 (m, 2Η, aromatic H); 7.60 (m, 1 Η, aromatic)

3.08 (t, 2Η, CH-Ph); 4.15 (t, 2Η, CH-O); 6.81 -6.88 (m,

Compound 8 White solid 2Η, aromatic H); 6.95-7.07 (m, 4Η, aromatic H);

7.24-7.29 (m, 2Η, aromatic H)

3.05 (t, 2Η, CH-Ph); 3.90 (s, 6Η, -OCH, 4.13

Beige solid

Compound 9 (t, 2Η, CH 2 -O); 6.76-7.02 (m, 7Η, aromatic H)

3.30 (t, 2Η, CH-Ph); 4.17 (t, 2Η, CH-O); 6.81 -6.88 (m,

2Η oil, aromatic H); 6.94-7.02 (m, 2Η, aromatic H);

Colorless compound 7.34-7.37 (m, 1H, aromatic H); 7.39-7.55 (m, 2Η, aromatic H); 7.67 (m, 1 Η, aromatic H)

2.32 (s, 3Η, -CH; 3.09 (t, 2Η, CH-Ph); 4.14 (t, 2Η, CH-O); 6.84-6.89 (m, 2Η, aromatic H); 6.90-7.10 (m, 2Η); ,

Oil

Aromatic H); 7.1 1 -7.14 (m, 3Η, aromatic H); 7.23-

Compound 1 1 colorless

7.29 (m, 1 Η, aromatic H) 2.41 (s, 3H, -CH: 3.17 (t, 2H, CH-Ph); 4.17 (t, 2H, CH -

Oil

Compound 12 0); 6.86-6.93 (m, 2H, aromatic H); 6.99-7.07 (m, 2H, colorless

Aromatic H); 7.21 -7.31 (m, 4Η, aromatic H)

2.33 (s, 3Η, -CH: 3.09 (t, 2Η, CH-Ph); 4.15 (t, 2Η, CH -

Oil

Compound 13 O); 6.83-6.90 (m, 2Η, aromatic H); 6.96-7.04 (m, 2Η, colorless

Aromatic H); 7.16-7.27 (m, 4Η, aromatic H)

3.1 1 (t, 2Η, CH-Ph); 3.80 (s, 3Η, -OCH: 3.87 (s, 3Η,

Compound 14 Yellow oil -OCH; 4.12 (t, 2Η, CH-O); 6.82-6.95 (m, 6Η, aromatic H); 7.23-7.29 (m, 2Η, aromatic H)

3.03 (t, 2Η, CH-Ph); 3.77 (s, 3Η, -OCH: 4.08 (t, 2Η,

Compound 15 Golden Oil CH-0); 6.77-6.87 (m, 5Η, aromatic H); 7.12-7.26 (m,

4Η, aromatic H)

3.10 (t, 2Η, CH-Ph); 3.84 (s, 3Η, -OCH, 4.13 (t, 2Η,

Oil

Compound 16 CH-O); 6.82-7.02 (m, 6Η, aromatic H); 7.23-7.28 (m, colorless

2Η, aromatic H)

3.12 (t, 2Η, CH-Ph); 4.22 (t, 2Η, CH-O); 6.75-6.96 (m,

Compound 17 Golden oil

6Η, aromatic H); 7.13-7.21 (m, 2Η, aromatic H)

1.80 (m, 1 Η, cyclopropyl); 2.10 (m, 1 Η, cyclopropyl); 2.70

Oil

Compound 18 (m, 2Η, cyclopropyl); 3.86 (s, 3Η, -O-CH); 4.02 (s, 2Η, colorless

-CH-O); 6.62-7.40 (m, 8Η, aromatic H)

3.02 (t, 2Η, CH-Ph); 4.27 (t, 2Η, CH-O); 6.71 -7.19 (m,

Compound 19

White solid 4Η, aromatic H); 7.18 (d, 2Η, aromatic H); 8.19

(m, 2Η, aromatic H); 9.54 (s, 1 Η, -OH)

2.94 (t, 2Η, CH-Ph); 4.05 (t, 2Η, CH-O); 5.02 (s, 2Η,

Compound

White solid CH ₂ benzyl); 6.71 -7.16 (m, 8Η, aromatic H); 20

7.29-7.38 (m, 5Η, aromatic H); 9.50 (s, 1 Η, -OH)

2.90 (t, 2Η, CH-Ph); 3.96 (t, 2Η, CH-O); 4.59 (s, 2Η, NH); 6.45-6.51 (d, 2Η, aromatic H); 6.62-6.69 (d,

Compound 21 Beige solid 2Η, aromatic H); 6.72-7.15 (m, 4Η, aromatic H);

9.42 (s, 1 Η, -OH) 1.99 (s, 3H, N-COCH: 2.28 (s, 3H, O-COCH: 2.91 (t,

2H, CH ₂ -Ph); 3.96 (t, 2H, CH ₂ -0); 4.08 (s, 2H, NH ₂ );

Compound 22 Cream solid 6.82-6.85 (d, 2H, aromatic H); 7.08-7.43 (m, 4H, aromatic H); 7.44-7.47 (d, 2H, aromatic H); 9.78 (s, I H, -OH)

5.28 (s, 2Η, CH-Ph); 6.82-7.08 (m, 6Η, aromatic H);

Compound 23 White solid 7.55 (dd, 1 Η, aromatic H); 7.78 (d, 1 Η, aromatic H);

1 1.08 (s, 1 Η, -OH)

4.06-4.17 (m, 2Η, CH-Ph); 5.28 (m, 1 Η, CH-OH); 6.82-7.20

Yellow oil

Compound 24 (m, 8H, aromatic H); 8.40 (s, 1H, -OH)

3.12 (t, 2Η, CH-Ph); 4.22 (t, 2Η, CH-O); 5.10 (s, 2Η,

Compound 25 Solid white

Benzyl CH2); 6.87-7.47 (m, 13Η, aromatic H)

3.1 1 (t, 2Η, CH-Ph); 4.25 (t, 2Η, CH ₂ -0); 5.49 (s, 1 Η, -

Compound 26 Yellow solid

OH) ; 6.80-7.25 (m, 8Η, aromatic H)

Oil 3.13 (t, 2Η, CH 2 -PIl); 4.14 (t, 2Η, CH ₂ -0); 5.00 (s, 1 Η, -

Compound 27

colorless OH); 6.75-7.28 (m, 8Η, aromatic H)

3.14 (t, 2Η, CH 2 -PI 1); 4.16 (t, 2Η, CH ₂ -0); 5.00 (s, 2Η,

Compound 28 White solid

Benzyl CH2); 6.83-7.47 (m, 13Η, aromatic H)

3.04 (m, 2Η); 3.12 (m, 1 Η); 3.28 (t, 2Η, CH 2 -C ₆ H ₅ ); 3.46 (m, 1H); 3.83 (m, 1H,); 4.16 (t, 2H, CH ₂ -0); 4.59 (m,

Compound 29 White solid

1 Η, -ΟΗ); 4.83 (d, 1 Η); 5.04-5.32 (m, 3Η, -OH); 6.93-7.25 (m, 8Η, aromatic H).

2.05 (s, 12Η, -CO-CH; 3.08 (t, 2Η, CH 2 -C ₆ H ₅ ); 3.90 (m, 1H, anomeric H); 4.02-4.33 (m, 4H, H glucose);

Compound 30 White solid

5.23 (m, 2H, H glucose); 5.35 (t, 2H, CH ₂ -0); 6.80-7.29 (m, 8Η, aromatic H).

3.13 (t, 2Η, CH 2 -PIl); 4.24 (t, 2Η, CH ₂ -0); 6.85-7.28 (m,

Compound 31 Yellow oil

8Η, aromatic H)

5.32 (s, 2Η, CH 2 -PI 1); 6.82-7.26 (m, 6Η, aromatic H);

Yellow solid

Compound 32 7.55 (dd, 1 Η, aromatic H); 7.75 (d, 1Η, aromatic H) clear 1.22 (t, 3H, CH; 2.60 (q, 2H, CH ₂ -CH); 3.13 (t, 2H,

Oil

Compound 35 CH2-P); 4.26 (t, 2H, CH 2 -O); 6.84-6.96 (m, 4H, colorless H)

aromatics); 7.10-7.21 (m, 4H, aromatic H)

1.22 (t, 3Η, CH: 1.61 (q, 2Η, CH ₂ ): 5.31 (s, 2Η, CH ₂ -ph); 6.85-7.16 (m, 6Η, aromatic H); 7.55 (m, 1Η, H);

Compound 36 Beige solid

aromatic); 7.80 (m, 1 Η, aromatic H); 1 1.85 (s, 1 Η, - OH)

1.22 (s, 6Η, CH; 2.87 (heptuplet, 1 Η, CH-); 3.13 (t, 2Η,

Oil

Compound 39 CH2-PI1); 4.26 (t, 2Η, CH 2 -O); 6.85-6.95 (m, 4Η, colorless H)

aromatics); 7.13-7.21 (m, 4Η, aromatic H)

1.23 (s, 6Η, CH; 2.88 (heptuplet, 1 Η, CH- (CH)); 5.30 (s, 2H, CH 2 -PI); 6.94 (m, 5Η, aromatic H); 7.20 (m,

Compound 40 Yellow solid

1 Η, aromatic H); 7.56 (m, 1 Η, aromatic H); 7.82 (m, 1 Η, aromatic H)

0.66 (t, 3Η, -CH-CH; 1.26 (s, 6Η, -C-CH; 1.62 (m,

Oil

Compound 43 2Η, -C-CH 2 -); 3.13 (t, 2Η, CH 2 -PIl); 4.27 (t, 2Η, CH 2 -O);

colorless

6.85-7.26 (m, 8Η, aromatic H)

0.70 (t, 3Η, CH-CH; 1.30 (s, 6Η, CH; 1.62 (q, 2Η, CH 2 -CH) 5.31 (s, 2H, CH 2 -PI); 6.94 (m, 5Η, H);

Compound 44 Beige aromatic solid); 7.26 (m, 1 Η, aromatic H); 7.55 (m, 1 Η,

Aromatic H); 7.82 (m, 1 Η, aromatic H); 1 1.87 (s, 1 Η, -OH)

Oil 1.30 (t, 9Η, -C- (CH ₃ b); 3.13 (t, 2Η, CH 2 -PI); 4.27 (t, 2Η,

Compound 47

colorless CH2-O); 6.86-7.33 (m, 8Η, aromatic H)

0.46-1.67 (m, 19Η, - (CH ₂ k-CH ₎ ); 3.13 (t, 2Η, CH 2 -PIl);

Oil

Compound 51 4.27 (t, 2Η, CH 2 -O); 6.84-6.96 (m, 4Η, aromatic H);

colorless

7.13-7.24 (m, 4Η, aromatic H)

1.41 (t, 3Η, CH; 4.00 (q, 2Η, CH ₂ ); 5.30 (s, 2Η, CH ₂ -Ph); 6.80-7.07 (m, 6Η, aromatic H); 7.54 (m, 1Η, H);

Compound 56 Beige solid

aromatic); 7.79 (m, 1 Η, aromatic H); 1 1.87 (s, 1 Η, - OH) 1.41 (t, 3H, -CH-CH; 4.07 (dd, 2H, -CH (OH) -

Compound 57 White solid CH ₂ ): 4.17 (m, 2H, -CH ₂ -CH); 5.27 (d, 1H, -CH (OH) -);

6.83-7.25 (m, 8H, aromatic H)

3.91 (s, 3H, -O-CH: 5.41 (s, 2H, -CO-CH 2 -): 6.86-7.07

Compound 124 White solid (m, 6H, aromatic H); 7.52-7.82 (m, 2H, aromatic H)

Compound 125 Brown Oil 3.93 (s, 3H, -O-CH: 4.20 (m, 2H, -CH (OH) -CH ₂ -) 5.23

(dd, 1H, -CH (OH) -); 6.84-7.21 (m, 8H, aromatic H)

1.22 (d, 3H, -CH3 Rhamnose); 2.07 (s, 6H, -CO-CH: 2.21 (s, 3H, -CO-CH: 3.15 (t, 2H, CH 2 -C ₆ H ₅ ); 4.00 (m,

Compound 127 White solid

1H, anomeric H); 4.22 (m, 2H, CH 2 -O); 5.15-5.50 (m, 4H, H Rhamnose); 6.83-7.30 (m, 8Η, aromatic H).

1.28 (d, 3Η, -CH 3 Rhamnose); 3.07 (m, 2Η, CH-C ₆ H ₅ ); 4.14 (m, 2H, CH 2 -O); 3.51 -4.19 (m, 4H, H Rhamnose);

Compound 128 White solid

5.56 (s, 1H, H Rhamnose); 6.82-7.28 (m, 8H, aromatic H).

3.79 (s, 3H, -OCH: 5.29 (s, 2H, CH 2 -PIl); 6.80-7.07 (m,

Compound 129 Beige solid 6H, aromatic H); 7.54 (m, 1H, aromatic H); 7.79

(m, 1H, aromatic H); 1 1.86 (s, 1 Η, -OH)

0.85 (t, 3Η, CH, 1.49 (q, 2Η, CH 2 -CH), 2.44 (t, 2H, -CH-CH), 3.04 (t, 2H, CH 2 -PI), 4.16 (t, 2Η, CH 2 O) 6.70-7.12 (m, 8Η, aromatic H)

Oil

Compound 130 0.93 (t, 3Η, -CH-CH; 1.60 (m, 2Η, -CH 2 -CH); 2.54 (t, colorless

2H, -CH 2 -CH -); 3.14 (t, 2H, CH 2 -PI 1); 4.26 (t, 2Η, CH ₂ -O); 6.84-6.97 (m, 4Η, aromatic H); 7.08-7.22 (m, 4Η, aromatic H)

2.62 (m, 3Η, -CH; 5.31 (s, 2Η, -CO-CH 2 -); 6.85-7.16

Compound 133 Beige solid (m, 6Η, aromatic H); 7.52-7.82 (m, 2Η, aromatic H)

3.79 (s, 3Η, -O-CH; 4.12 (m, 2Η, -CH (OH) -CH ₂ -); 5.27

Compound 134 Brown oil (dd, 1 Η, -CH (OH) -); 6.84-7.27 (m, 8H, aromatic H) 5.04 (s, 2H, -CH 2-Ph); 5.19 (s, 2H, -CO-CH ₂ -): 6.55 (m,

2H, aromatic H); 6.84 (m, 2H, aromatic H); 7.15

Compound 135 Beige solid

(m, 2H, aromatic H); 7.40 (m, 5H, aromatic H); 7.56 (m, 1H, aromatic H); 8.03 (m, 1 Η, aromatic H)

3.83-4.17 (m, 2Η, -CH ₂ -O-); 5.03 (s, 2Η, -CH ₂ -Ph) 5.38

Compound 136 Beige solid (m, 1 Η, -CH (OH) -); 6.84 (m, 2H, aromatic H); 6.70- 7.50 (m, 13H, aromatic H)

3.12 (t, 2Η, CH-Ph); 3.80 (s, 3Η, -OCH: 4.24 (t, 2Η,

Compound 137 Beige solid CH ₂ -O); 6.80-6.97 (m, 6Η, aromatic H); 7.13-7.22 (m,

2Η, aromatic H)

Table 1

BIOLOGICAL TESTS ■ Results on skin plasty maintained in survival:

1. Preparation of explants

From ^an abdominoplasty ^a woman aged 53, 45 skin explants were prepared. The explants were monitored in BEM (BIO-EC ^' s Explants Medium) at 37 ° C in a humid atmosphere, enriched with 5% CO ₂

. Application of products

The solutions are prepared in DMSO from pure products in order ^to arrive at final concentrations of 2, 20 and 100 \\.% By ^the incorporation ^of an identical volume of 10 μΐ in each well and for each treatment. The treatment was carried out in the monitoring medium on days 0, 1, 2, 5 and 7.

3. Levies

At D0, the 3 explants of lot T0 were removed and each explant was cut in half. One part was fixed in buffered formalin for ^observation of general morphology. ^The other was frozen and stored at -80 ° C.

On D5 and D9, 3 explants from each batch were collected and treated in the same way.

. Histological treatment

After 48 hours of fixation in buffered formalin, the samples were taken dehydrated and impregnated in paraffin ^using ^a Leica dehydration PLC 1020. They were lumped by the procedure H MO-153 ^using ^a station ^potting Leica EG 160. 1 cuts 5 μιτι were performed according to the MO-H- procedure 173 ^using ^a microtome such Minot, Leica RM 2125 and mounted on Superfrost glass slides histological ^8.

5. Microscopic observations

Microscopic observations were made by light microscopy and fluorescence, ^using ^a Leica Orthoplan-type microscope, ^the objective x 25. The shots were performed with a sorting camera CCD Sony DXC 390P and stored at using ^the ^archiving software of Leica IM 1000 data.

The ^observation of general morphology was performed on paraffin sections after staining with Masson's trichrome, Goldner variant according to the procedure MO-H- 157.

6. Staining and immunostaining

Immunolabelling will be performed on sections with adequate anti-body. The cores may be stained with propidium ^iodide.

Example 11: Histological Expertise of General Morphology

Compound 1, of formula and the reference compound, (+) - dehydroisoandiOSterone (DHEA Acros ref 154980100) were tested at a concentration of 2 μg / ml in DMSO, on abdominal plastids. After 9 days of follow-up, compound 1 showed a very marked epidermal and dermal restructuring activity: the epidermal structure is clearly acanthosic (thicker) with a good morphology, and the papillary dermis is much denser. While the reference product, (+) - dehydroisoandiOsterone, does not alter the epidermal structure nor the papillary dermis at the concentration of 2 μg / ml.

Example 12: Stains and Immunolabelling

A thorough study by staining and immunomarking of the sections of previous plastids treated with compound 1 shows a clear overexpression of collagen I in the half papillary

very slight densification of collagen III in the papillary dermis

a clear over-expression of collagen IV along the epidermal junction a moderate overexpression of collagen VII along the dermo-epidermal junction.

Effects of Compound 1 on the Expression of Markers by Keratinocytes

The ^expression of specific markers was assessed by RT-qPCR (quantitative reverse transcription polymerase chain reaction) on the messenger RNA extracted from monolayers of each treatment. The transcriptomic profile contains 64 genes selected for their importance in the differentiation of keratinocytes. PCR reactions (polymerase chain reactions) were performed by quantitative PCR with the system "Light Cycler" (Roche Molecular System Inc.) and according to the procedures recommended by the supplier. Example 13 Analysis of the Differential Expression -PCR Arrays

Normal human epidermal keratinocytes were incubated in the presence of compound 1 or ^a reference to calcium chlonire. The ^expression of specific markers was assessed by RT-qPCR on the messenger RNA extracted from monolayers of each treatment.

Under the experimental conditions of this study, compound 1 tested at Ι ΟμΜ presented a similar effect but less calcium chlonire to 1.5 mM by stimulating the ^expression of markers involved in lipid synthesis, anti-microbial defense, ^innate immunity and cell-cell interactions. In addition, parallel thereto, an inhibition of gene ^expression "matrix metallopeptidase" MMP9 involved in the degradation of the extracellular matrix and HSPB stress protein 1, "heat shock protein beta-1", was also observed.

Compound 1 therefore has a pro-differentiating effect.

Example 14: Investigation of Effects of Compound 1 on Epidermal Differentiation

Transglutaminase, TG, and filaggrin are two protein markers of epidermal differentiation involved in ^the aiTaiigement keratin filaments and the formation of ^the envelope of the horny layer. ^The immuno in situ labeling of TGK and filaggrin in normal human epidermal keratinocytes cultured in the presence of calcium chlonire or compound 1 showed the concentration-dependent stimulation of ^protein expression of filaggrin and TGK by compound 1. Example 15: Search for anti-inflammatory effects of compound 1

The effects of compound 1 were evaluated on two lanes ^of ignition, the way of "chemokines" and the way of "prostaglandins" by measuring the release of ^{interleukin-8} (IL-8) and prostaglandin E2 (PGE2) by a human keratinocyte line NCTC-2544 stimulated by phorbol myristate acetate (PMA).

Compound 1 has a clear anti-inflammatory effect by inhibiting concentration-dependent manner the release of PGE2 without changing the release ^of IL-8.

Example 16: Investigation of Effects of Compound 1 on Dermal Strengthening

The effects of this compound were evaluated on normal human dermal fibroblasts in monolayer by measuring the neosynthesis of glycosaminoglycans designated by sulfated GAGs (incorporation of [° S] -sulfate). Compound 1 stimulated the neosynthesis of sulfated GAGs in a non-concentration dependent manner. This could explain ^the dermal strengthening effect already observed in ex vivo skin explants.

■ Evaluation of the depigmenting effect on NDP-MSH-stimulated B16 melanocyte line

Example 17: Evaluation ^of anti-melanogenesis activity

The anti-melanogenesis activity of the compounds in solution in DMSO was evaluated by measuring melanin synthesis in a B16 melanocyte model stimulated with a stable derivative of Γα-MSH (natural melanogenesis stimulating hormone): NDP MSH.

Culture and treatments

The melanocytes were seeded in a 96-well plate and cultured for 24 hours (37 ° C., 5% CO 2, DMEM 1 g / L glucose without red phenol supplemented with glucose at 3 g / l, L-glutamine at 2 mM, penicillin 50 U / mL, 50 μg / mL Streptimycin, 10% FBS (FCS). After incubation, the culture medium was then replaced with culture medium supplemented or not (non-stimulated control) with a stable derivative of Γα-MSH and containing or not (controls) the test compounds or the reference (kojic acid to 25, 100, 400, 800 ng / mL). Each experiment was performed in n = 3, with ^the exception of the witnesses made n = 6, and the cells were incubated for 72 hours. Cell-free wells received in parallel the same amounts of medium supplemented or not with NDP-MSH and containing or not the Compounds under ^test or reference to quantify background noise associated with the presence of the compounds.

Determination of melanin

At the end of ^incubation of 72 hours, the total melanin (intra- and extra-cellular) was quantified by measuring the ^absorbance at 405nm of each sample (direct reading culture plates) against melanin standard solutions (concentrations melanin tested from 0.78 to 100 ng / mL).

The background noise, measured in wells without cells, was cut to the measured values to take into account ^the effect related to melanin production without regard to possible interference due to the presence of the compounds. The results were expressed in percentage of melanin relative to the control and ^that as the percentage ^of inhibition.

Evaluation of cell viability - MTT reduction test

At the end of treatment, cells were incubated with MTT (tetrazolium salt) whose transformation into blue formazan crystals is proportional to ^the activity of succinate dehydrogenase (mitochondrial enzyme). After dissociation of the cells, the formazan was solubilized in DMSO medium and the optical density (OD), representative of the number of living cells and their metabolic reactivity, was measured with a 540nm microplate reader (VERSAmax, Molecular Devices).

The results obtained are summarized in the following table:

Name and concentrations tested Standardized Data Viability (MTT)

(μΜ) Inhibition (%)% stimulated control

Witness

10 ^"7 M 0 100

stimulated

Witness No

- 100 100

stimulated

25 ng / mL 24 85

Kojic acid 100 ng / mL 78 76

400 ng / mL 90 76 10 0 83

Compound 1

30 93 86

100 1 12 ΊΊ

Compound 2 30 100 108

Compound 3 30 1 10 96

Compound 4 30 95 97

Compound 5 30 49 103

Compound 8

100 50 93

Compound 10

100 27 91

Compound 11

100 44 109

Compound 14

100 100 80

Compound 16

100 52 83

Compound 18

100 105 75

Compound 19 30 82 91

3 83 106

Compound 20 10 108 84

30 1 15 59

Compound 22

100 61 86 Compound 24

100 84 78

Compound 25 30 46 93

Compound 27 30 95 77

Compound 30 30 13 88

Compound 31 3 20 91

10 70 104

30 109 88

Compound 35 3 54 105

10 92 97

30 112 88

Compound 39 3 70 119

10 111 101

30 119 86

Compound 40 10 5 102

30 58 90

Compound 43 3 88 116

10 119 90

30 120 9

Compound 44 10 24 89

30 117 80

Compound 47 3 75 116

10 111 89

30 116 18

Compound 51 3 104 107

10 116 47

30,115 0

Compound 57 30 47 97

Compound 125 30 13 90

Compound 127 30 29 90 Compound 130 3 72 98

10 1 10 89

30 1 16 81

Table 2

Example 18: Evaluation of the Depigmenting Effect by Comparison with 2 Reference Molecules

The operating conditions are the same as those of Example 12.

The following three molecules have been compared in their effects:

- compound 1

4- (2,4-dihydroxyphenyl) butane [18979-61 -8], or rucinol, ref 1

1- (2,4-dihydroxyphenyl) -3- (2,4-dimethoxy-3-methylphenyl) propane [869743-37-3], patent Unigen Pharmaceuticals US2005 / 267047, ref 2

The table below summarizes the results obtained:

Table 3 Compound 1 therefore has a net inhibitory effect at the two concentrations tested and is slightly more effective than the two reference products used.

EXAMPLE 19 Activity of Compound 1 on PPAR Receptors (Peroxysome Proliferator Activated Receptor)

Tests ^affinity

The ^affinity of compound 1 for PPAR receptors (a and γ) was tested in vitro assays Binding assays (tests performed by the company Cerep).

It is ^a question ^of a binding competition assay in nuclear receptor, between radiolabeled ligand and the test molecule (here the compound 1).

The principle of the technique consists in measuring the displacement of the radioactive ligand bound to the receptor by the molecule to be tested.

^■ Materials and Methods

The specific binding of ligand is defined by the difference between total binding and nonspecific binding determined in the presence ^of an excess of unlabeled ligand.

The results are expressed in:

percentage of specific control binding ((measured specific binding / control specific binding) x 100))

- percentage ^of inhibition of specific control binding ((100 - (measured specific binding / control specific binding))

obtained in the presence of compound 1.

The values ^of ICso (concentration at which the maximum control specific binding is inhibited by 50%), and Hill coefficient (nH) were determined by non linear regression analysis of the competition curves with an average value using the replicated ^adjusting ^the Hill equation (Y = D + [(A - D) / (l + (C / _C50) ^nH)]).

in which,

- Y = the specific binding

- D = the specific minimum link

- A = the specific maximum binding

- C = the concentration of the compound

- C50 ⁼ IC50 - nH = the steering coefficient of the line

This analysis was done using software developed by Cerep (Hill Software) and validated by comparison with the data generated by the software SigmaPlot <R> 4.0 for Windows (<R> 1997 by SPSS Inc).

The ^inhibition constant (i) was calculated using the ^equation of Cheng-Prusoff [i = IC ₅ o / (l + (L / _D)], wherein

- L = the radioligand concentration in the test

- o = ^affinity of the radioligand for the receptor. The o was determined by a Scatchard analysis:

Table 4

^■ Results

Table 5 At various concentrations of compounds, and whether with PPARalpha or PPARgamma receptor, the percent ^inhibition is close to zero. There ^'therefore has no ^activity of compound 1 against PPAR receptors.

The 49% value indicates a mild to moderate effect. Tests ^activity

^The agonist or antagonist activity of the compound 1 of the PPAR receptors has been tested by fluorescence techniques.

^■ Materials and Methods

The results are expressed:

as a percentage of response specific agonist control (measured specific response / control specific agonist response) x 100) and

in percentage ^inhibition of the specific agonist response control (100 - ((measured specific response) / specific agonist response control) x 100)) obtained in the presence of compound 1.

The ^values ECSO (concentration at which the maximum specific response was 50%) and the values ^of ICso (concentration at which the specific maximum control agonist response is inhibited by 50%) are determined by non-linear regression analysis of concentration-response curves with a replicate mean value using ^the adjustment of ^the Hill equation (Y = D + [(a - D) / (l + (C / _C50) ^nH)]

in which,

- Y = the specific answer

- D = the minimum specific answer

- A = the maximum specific response

- C = the concentration of the compound

- nH = the steering coefficient of the line

This analysis was done using software developed by Cerep (Hill Software) and validated by comparison with the data generated by the software SigmaPlot <R> 4.0 for Windows (<R> 1997 by SPSS Inc). For antagonists, the apparent dissociation constants (KB) were calculated using ^the Cheng-Prusoff equation modified 1 + (A / EC ₅₀ A)), in which

- A = the concentration of Γ agonist of reference in the test

- ECS _Î A = the value ^of Γ ECSO of reference agonist.

^■ results of ^the agonist activity

Table 7

The percentage of response is low (- 1 to 4), the compound 1 n ^is not therefore an agonist. ^■ results ^antagonist activity

Table 8

The percentage ^of inhibition is low (-5 to 4), the compound 1 n ^is not therefore an antagonist. These various tests therefore show that compound 1 ^is not a PPAR activator.

Claims

1. Use of Compounds of General Formula I

I

in which

■ n and m are equal to 0 or 1, their sum always being equal to 1,

■ R ¹ and R ² , identical or different, represent

° of ^hydrogen atoms,

° of ^halogen atoms selected from fluorine, chlorine, bromine or ^iodine,

° -OH groups,

° phenoxy -OPH groups,

° aryloxy groups -OAr, in which Ar represents an aromatic group having 6 to 12 carbon atoms optionally substituted by one or more ^atoms selected halogen (s) from fluorine, chlorine, bromine, or optionally substituted by one or more -OH groups in free form or in protected form in the form of

group -OMes, group -OTHP of formula of group derived from ethylene formula glycol in which

O varies from 1 to 12,

R ^a represents a hydrogen or a linear or branched alkyl group having from 1 to 6 carbon atoms,

R ^c represents a linear or branched alkyl group of 1 to 10 carbon atoms,

a group derived from propylene glycol of formula,

in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

or group -OSitBdM of formula,

Benzyloxy groups -OCH ₂ PIl,

° -OTHP groups of formula above,

° -OMes groups,

Groups derived from ethylene glycol of formula

in which

O varies from 1 to 12,

R ^c represents a linear or branched alkyl group of 1 to 10 carbon atoms,

Groups derived from propylene glycol of formula, in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

Siloxy groups of formula -OSi (R ^a ) ₃ in which R ^a has the meanings indicated above,

° groups -OSitBdPh of formula

° -OSitBdM groups of formula,

said R ¹ and R ¹ possibly forming a ring having 3 carbon atoms, ring having the following formula in which

R ^a, R ^b, R ^a and R ^b, identical or different, represent

° of ^hydrogen atoms,

° of halogen ^atoms selected from fluorine, chlorine, bromine or ^iodine,

with the proviso that R "is in this case a hydroxy -OH group,

■ R'and R ^"1 identical or different, represent

° of ^hydrogen atoms,

Hydroxyl groups -OH,

Benzyloxy groups,

° -OTHP groups of formula

-OTHP groups substituted with the following formula

in which

x is equal to 0 or 1, y varies from 0 to 4,

R ^b is hydrogen or acetyl -C (O) -CH,

Groups derived from ethylene in which

O varies from 1 to 12,

Groups derived from propylene glycol of formula in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

Formula -OSitBdPh

° -OSitBdM of formula,

■ R represents

° an ^hydrogen atom,

° a ^halogen atom selected from fluorine, chlorine, bromine,

A linear, branched or cyclic alkyl group comprising from 1 to 10 carbon atoms, in particular a methyl, ethyl or isopropyl group, optionally substituted by one or more halogens chosen from fluorine, chlorine, bromine or the like ^; iodine, with a -CF ₃ group, with a hydroxy,

A hydroxyl group -OH,

a benzyloxy group,

a phenoxy group,

a thiophenyl group,

an acyloxy group comprising from 2 to 10 linear carbon atoms,

A group -OTHP of formula

A substituted -OTHP group of the following formula

in which

x is equal to 0 or 1, y varies from 0 to 4,

R ^b is hydrogen or acetyl -C (O) -CH,

A group -OSC ^ R ⁰ in which R ^c is an alkyl group comprising from 1 to 6 carbon atoms, in particular methyl or ethyl, or an aromatic group containing from 6 to 18 carbon atoms, optionally substituted with one or more atoms halogen, hydroxy or alkoxy group, nitro,

An -OSO M group in which M represents an Na ⁺ or ⁺ ion,

A group derived from ethylene or a col of formula in which

O varies from 1 to 12,

A group derived from propylene glycol of formula

in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

Formula -OSitBdPh -OSitBdM of

° -COOH,

° -CN,

° -NH,

° -NH, X

- -NR ^d R,

° -NHR ^d R ⁺ , X

° -NHCOR,

° -NHCOOR ^g ,

° -N0,

X ^" representing a halide ion,

A group derived from piperazine, in particular

said compounds of formula I being used in racemic form or a single enantiomer for the preparation of cosmetic compositions having anti-aging and / or depigmenting properties.

2. Use according to claim 1, compounds of formula II

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ , R, R "and R ^~ have the meanings given in claim 1,

° -NH,

- -NR ^d R,

° -NHCOR,

° -NHCOOR ^g ,

° -N0,

A group derived from piperazine, in particular

3. Use according to claim 1, compounds of formula III

in which

R ^"1 and R ³ have the meanings given in claim 1, R ^a, R ^b, R ^a and R '\ identical or different, represent

° of ^hydrogen atoms,

° of halogen ^atoms selected from fluorine, chlorine, bromine or ^iodine,

° linear or branched alkyl groups comprising from 1 to 10 carbon atoms, especially methyl groups, ethyl, isopropyl, optionally substituted by one or more halogens chosen (s) from fluorine, chlorine, bromine or ^iodine, by a -CF ₃ group, with a hydroxy.

4. Use according to one of claims 1 to 3, compounds of Fonmile IV

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ , R, R ^"1 and R ³ have the meanings given in claim 1,

- or compounds of fo IVA

in which R ³ has the meaning given in claim 1,

- or fonmil compounds

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ , R ² , R ¹ and R ³ have the meanings given in claim 1,

with the proviso that R "and R ^{" 1} are both different from -OH or any form in which OH is protected, or compounds of formula V

V

in which

R ¹ , R ² , R ¹ and R ³ have the meanings given in claim 1, provided that R "and R ^{" 1} are both different from -OH or any form in which

OH is protected,

- or compounds of formulas

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ , R ² , R "and R ^~ have the meanings given in claim 1,

■ R ^c is a halogen atom selected from fluorine, chlorine or bromine,

- or compounds of formulas

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ , R ² , R "and R ^~ have the meanings given in claim 1,

or compounds of formula VIII

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ , R ² , R "and R ^~ have the meanings given in claim 1,

■ -OR ^d is a group chosen from

OH,

Benzyloxy groups,

^D phenoxy groups,

° -OTHP groups of formula

Substituted -OTHP groups of the following formula

in which

x is equal to 0 or 1, y varies from 0 to 4,

R ^b is hydrogen or acetyl -C (O) -CH,

^D ₃ -OSO ₃ M groups in which M represents a Na ⁺ or ⁺ ion, ° groups derived from ethylene glycol of formula

in which O varies from 1 to 12,

Groups derived from propylene glycol of formula

in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

O -OH groups optionally coupled to an osidic compound which may be an α- or β-furanose or a- or β-pyranose, or compounds of formula

in which R \ R ^"1 and R ^* have the meanings indicated in the claim

- or compounds of formula

in which R ¹ , R, R ", R ^{" 1} and R ³ have the meanings given in claim 1, or compounds of formula XA

in which

R ¹ , R ² , R ^"1 and R ³ have the meanings given in claim 1, - or compounds of formula XI

wherein R \ R ^"1 and R ^* have the meanings referred to in claim 1, - or compounds of formula XIIA, XIIB and XIIC

wherein

R ¹ , R ² , R ¹ and R ^* have the meanings given in claim 1,

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

- or compounds of XIIIA, XIIIB and XIIIC fonmiles

XIIIC in which

R ¹ , R ² , R ", R ^{" 1} and R ³ have the meanings indicated in the specification

N is 0 or 1, m is 0 or 1, provided that n + m = 1. - or compounds of formulas XIID, XIIE and XIIF

in which R \ R ^"1 and R ^* have the meanings given in claim 1.

5. Use according to one of claims 1 to 4, compounds of formulas 1 to 137.

6. Use according to ^any one of claims 1 to 5, one or more compounds of formula I for the preparation of cosmetic compositions in which the anti-aging properties belong to the group consisting of strengthening the dermis, the dermal fibroblast proliferation , collagen production, ^inhibition of gene ^expression "matrix metallopeptidase" MMP9 and protein "heat shock protein beta-1" HSPB 1

- or for the preparation of cosmetic compositions in which the depigmenting properties belong to the group formed by ^{anti-tyrosinase} activity and ^activity anti melanogenesis.

7. Cosmetic composition containing as active substance one or more compounds of

formula

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

■ R ¹ and R ² , identical or different, represent

° of ^hydrogen atoms,

° of ^atoms selected halogen (s) from fluorine, chlorine, bromine or ^iodine,

° -OH groups,

° linear or branched alkoxy groups comprising from 1 to 10 carbon atoms, including methoxy, ethoxy, optionally substituted with one or more halogens chosen (s) from fluorine, chlorine, bromine or ^iodine, in particular the trifluoromethoxy group -OCF, ° phenoxy -OPH groups,

of group -OMes, of group -OTHP of formula e group derived from ethylene

formula glycol in which

O varies from 1 to 12,

R ^c represents a linear or branched alkyl group of 1 to 10 carbon atoms,

a group derived from propylene glycol of formula,

in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

group -OSitBDM of formula,

Benzyloxy groups -OCH ₂ PIl, Alkenyl groups comprising from 2 to 10 carbon atoms, linear or branched and having at least one C = C double bond,

° -OTHP groups foimule above,

° -OMes groups,

Groups derived from ethylene glycol of formula

in which

O varies from 1 to 12,

R ^c represents a linear or branched alkyl group of 1 to 10 carbon atoms,

Groups derived from propylene glycol of formula,

in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

° groups -OSitBdPh of formula

° -OSitBdM groups of formula,

said R ¹ and R ² possibly forming a ring having 3 carbon atoms, the ring having the following formula

in which

R ^a, R ^b, R ^a and R ^b, identical or different, represent

° of ^hydrogen atoms,

° of halogen ^atoms selected from fluorine, chlorine, bromine or ^iodine,

with the proviso that R "is hydroxy -OH,

■ R'and R ^"1 identical or different, represent

° of ^hydrogen atoms,

Hydroxyl groups -OH,

Benzyloxy groups,

An alkynyloxy group comprising from 2 to 10 carbon atoms, linear or branched and having at least one triple bond _;

° -OTHP groups of formula

substituted -OTHP groups of the following formula

in which

x is equal to 0 or 1, y varies from 0 to 4,

R ^b is hydrogen or acetyl -C (O) -CH,

Groups derived from ethylene glycol of formula

in which

O varies from 1 to 12,

Groups derived from propylene glycol of formula

in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above,

A siloxy group of formula -OSi (R ^a ) ₃ in which R ^a has the meanings given above,

Formula -OSitBdPh

° -OSitBdM of formula,

■ R ^* represents

° an ^hydrogen atom,

° a ^halogen atom selected from fluorine, chlorine, bromine,

An alkynyl group comprising from 2 to 6 carbon atoms, linear or branched, and comprising at least one C triple = C triple bond,

A hydroxyl group -OH,

A benzyloxy group,

A phenyloxy group,

A thiophenyl group,

An acyloxy group comprising from 2 to 10 carbon atoms, linear or branched

A group -OTHP of formula

a substituted -OTHP group of the following formula

in which

x is equal to 0 or 1, y varies from 0 to 4,

R ^b is hydrogen or acetyl -C (O) -CH,

^A group -OSC ^ R ⁰ in which R ^c is an alkyl group having 1 to 6 carbon atoms, in particular methyl or ethyl, or an aromatic group comprising 6 to 18 carbon atoms, optionally substituted by one or more atoms halogen, hydroxy or alkoxy group, nitro,

^D -OSO M group wherein M is Na ⁺ ion or ⁺

A group derived from ethylene glycol of formula

in which

O varies from 1 to 12,

A group derived from propylene glycol of formula

in which

O 'varies from 1 to 5,

R ^a and R ^c have the meanings indicated above, An -OH group optionally coupled to an osidic compound that may be an α- or β-furanose or an α- or β-pyranose,

Formula -OSitBdPh

-OSitBdM of fo

° -COOH,

° -CN,

° -NH,

° -NH, X

- -NR ^d R,

° -NHR ^d R ⁺ , X

° -NHCOR,

° -NHCOOR ^g ,

° -N0,

X ^" representing a halide ion,

A group derived from piperazine, in particular

8. Cosmetic composition containing as active substance one or more compounds of formula I

in which :

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ and R ² have the meanings mentioned in claim 1,

■ R "and R ^{" 1} , identical or different, represent:

- of the ^hydrogen atoms,

hydroxyl groups,

And R ³ represents:

a linear, branched or cyclic alkyl group comprising from 2 to 10 carbon atoms, in particular an ethyl or isopropyl group, optionally substituted by one or more halogens chosen (s) from fluorine, chlorine, bromine or ^iodine, a group -CF _3, hydroxy,

an alkynyl group comprising from 2 to 6 carbon atoms, linear or branched, and comprising at least one C-= = C triple bond.

9. Cosmetic composition according to claim 7 or 8, consisting of a mixture comprising at least one compound of formula I as active ingredient in combination with one or more compounds having anti-aging and / or depigmenting properties, in particular in combination with fatty acids such as ^linoleic acid ^or azelaic acid, and / or with antioxidants such as vitamin C and / or derivatives tocopherol, and / or with peeling aids such as ^retinoic acid or ^glycolic acid,

said composition having anti-aging and / or depigmenting properties.

10. Cosmetic composition according to one of claims 7 or 9, containing as a substance

activates one or more compounds of formula II

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

■ R ¹ , R, R "and R ^~ have the meanings indicated in the specification

° -NH,

- -NR ^d R,

° -NHCOR,

° -NHCOOR ^g ,

° -N0,

A group derived from piperazine, in particular

in combination with a cosmetically acceptable vehicle,

or one or more compounds of formula III

in which

R ^"1 and R ³ have the meanings given in claim 1, ■ R ^la, R ^lb, R ^a and R ^b, identical or different, represent

° of ^hydrogen atoms,

° of halogen ^atoms selected from fluorine, chlorine, bromine or ^iodine,

in combination with a cosmetically acceptable vehicle, or one or more

in which

R ¹ , R ² , R ^"1 and R ^' have the meanings indicated in the specification

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

in combination with a cosmetically acceptable vehicle,

or one or more compounds of formula IVA

in which

R ³ has the meaning indicated in claim 1,

in combination with a cosmetically acceptable vehicle,

in which R ¹ and R ¹ have the meanings given in claim 1,

in combination with a cosmetically acceptable vehicle.

11. Cosmetic composition according to one of claims 7, 9 or 10, containing as active substance, one or more of compounds 1 to 137 in combination with a cosmetically acceptable vehicle.

12. Compound of formula I

in which :

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ and R ² have the meanings mentioned in claim 1,

■ R "and R ^{" 1} , identical or different, represent:

- of the ^hydrogen atoms,

hydroxyl groups,

And R ³ represents:

13. Compound of formula X

in which

N is 0, and m is 1,

R ¹ and R have the meanings mentioned in claim 1,

■ R "and R ^{" 1} , identical or different, represent:

- of the ^hydrogen atoms,

hydroxyl groups,

And R ³ represents:

14. Compounds of formula II

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ and R have the meanings mentioned in claim 1,

■ R "and R ^~ have the meanings given in claim 1, with ^the exception of ^atoms hydrogen, -NR ^a R ^{* b} represents a group comprising a nitrogen atom attached to the ring, optionally in its salt form, this group being chosen from

° -NH,

- -NR ^d R,

° -NHCOR,

° -NHCOOR ^g ,

° -N0,

A group derived from piperazine, in particular

R ^g represents a linear or branched alkyl group comprising from 1 to 4 carbon atoms, optionally substituted by one or more halogen atoms, or a carbon chain interrupted by oxygen or sulfur atoms, a phenyl group, a group benzyl optionally substituted by a halogen atom, a hydroxy group, an alkoxy group and in particular substituted by the methoxy group in the para position. These are compounds containing a nitrogen group, in particular nitro, amino, amido, carried by the

1

, OAr

Ar '

-OAr group of the following general formula

15. Compounds of formula II

in which

N is 0 or 1, m is 0 or 1, provided that n + m = 1,

R ¹ and R have the meanings mentioned in claim 1,

R "represents a hydroxyl group and R ^{" 1} has the meanings mentioned in claim 1,

° -NH,

- -NR ^d R,

° -NHCOR,

° -NHCOOR ^g ,

° -N0,

A group derived from piperazine, in particular

-OAr group of the following general formula

16. Compounds of formula III

in which

R ^"1 and R ³ have the meanings given in claim 1,

■ R ^la, R ^lb, R ^a and R ^b, identical or different, represent

° of ^hydrogen atoms,

° of halogen ^atoms selected from fluorine, chlorine, bromine or ^iodine,

17. Formula compounds

compound 14 compound 18

composed 32

compound 33 compound 34

compound 35 compound 36

compound 37 composed 38

compound 39 compound 40

compound 41 composed 42

composed 43 composed 44

compound 45 compound 46

compound 48

Compound 49 Compound 50

compound 51 composed 52

compound 53 compound 54

compound 55 compound 56

compound 60

compound 64

compound 67 compound 68

compound 69 compound 70

compound 72

compound 73 composed 74

compound 75 composed 76

compound 77 composed 78

Compound 79 Compound 80

Compound 81 Compound 82

compound 83 composed 84

compound 85 compound 86

87 compound 88

compound 89

compound 91 composed 92

compound 93 compound 94

compound 101 composed 101

compound 103 compound 104

compound 105 compound 106

107 compound 108

compound 109 compound 1 10

compound 1 1 1 compound 1 12

compound 1 13 compound 1 14

compound 120

compound 125 compound 1

127 compound 128

compound 129 compound 130

Compound 131 Compound 132

compound 133 compound 134

135 compound 136

compound 137

18. Formula compound

compound 51 compound 1