Cosmetic composition containing a neuropeptide Y receptor...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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Reexamination Certificate

active

06313128

ABSTRACT:

The present invention relates to a cosmetic composition containing a neuropeptide Y receptor antagonist. Neuropeptide Y, referred to hereinbelow as “NPY” for short, is a neuromediator which is involved in a certain number of physiological processes and for which an involvement in regulating lipolysis has been demonstrated (P. Valet and M. J. Clin. Invest. 1990, 85, 291-295). NPY receptor antagonists, hereinafter referred to as “NPY antagonists”, have been described as medicines, but their efficacy in the treatment of any disease has not been proven to date.
It has now been found that NPY antagonists can be used for the preparation of cosmetic compositions.
More particularly, it has been found that cosmetic compositions containing an NPY-antagonist component can be used as lypolysis/lypogenesis regulators in the skin without, however, interferring with the skin's natural functions.
It has also been found that cosmetic compositions containing an NPY-antagonist component and an &agr;2-antagonist component are particularly advantageous.
Thus, according to one of its aspects, the present invention relates to a cosmetic composition containing at least one NPY-antagonist component mixed with a cosmetic excipient. The NPY antagonist contained in the cosmetic composition may be a non-peptide compound, a peptide, a cell or tissue extract of animal or plant origin or a product obtained by fermentation of a microorganism, for example a bacterium or a fungus.
NPY antagonists which are advantageous in the cosmetic compositions of the present invention are those of groups A, B and C below.
A. Synthetic products selected from groups (I) to (VIII) below are advantageous NPY-antagonist components.
I. Compounds of formula (I)
in which
Ar
1
represents naphthyl, phenyl, quinolyl or isoquinolyl, optionally substituted with Cl, F, (C
1
-C
4
)alkyl, (C
1
-C
4
)alkoxy, hydroxyl or (C
1
-C
4
)dialkylamino;
Ar
2
represents phenyl or thienyl, optionally substituted with Cl, F, (C
1
-C
4
)alkyl, (C
1
-C
4
)alkoxy or hydroxyl;
R
1
, R
2
and R′
2
represent, independently of each other, hydrogen, (C
1
-C
4
)alkyl or alternatively R
1
represents nothing and N is attached to Ar
2
and, optionally, R
2
and R′
2
form a double bond,
or alternatively R
1
or R
2
is attached to Ar
2
and represents (C
1
-C
3
)alkylene;
R
3
and R
4
, which are identical or different, represent hydrogen, (C
1
-C
4
)alkyl or form, with the nitrogen atom to which they are attached, a saturated C
5
-C
7
heterocycle selected from pyrrolidine, piperidine and hexahydroazepine;
Z
1
represents (C
1
-C
12
)alkylene interrupted or substituted optionally with (C
5
-C
7
)cycloalkyl or phenyl;
Q
1
represents methyl, amino, (C
1
-C
4
)alkoxycarbonylamino, (C
1
-C
4
)alkylamino, di(C
1
-C
4
)alkylamino, pyrrolidinyl, piperidino, morpholino, piperazinyl, (C
1
-C
4
)alkyl-4-piperazinyl, amidino, (C
1
-C
4
)alkylamidino, guanidino, (C
1
-C
4
)alkylguanidino, pyridyl, imidazolyl, pyrimidinyl, indolyl, hydroxyl, (C
1
-C
4
)alkoxy, (C
2
-C
8
)alkoxycarbonyl, N-[amino(C
1
-C
4
)alkyl]-N-[(C
1
-C
4
)alkyl]amino, carbamoyl or phenyl optionally substituted with Cl, F, (C
1
-C
4
)alkyl, (C
1
-C
4
)alkoxy or hydroxyl;
Q
2
represents hydrogen or (C
1
-C
4
)alkyl;
Q
3
represents hydrogen or (C
1
-C
4
)alkyl or Q
1
and Q
3
are linked to form a heterocycle and together represent (C
2
-C
3
)alkylene whereas Z
1
represents nothing, in the form of pure enantiomers or mixtures thereof in any proportions, as well as the addition salts thereof with acids;
which can be prepared according to EP 614,911.
II—Raloxifen analogues, in particular
a) Compounds of formula (II)
in which:
A° is —O—, —S(O)
m
—, —N(R°
6
)—, —(CH
2
)
2
— or —C═C—;

6
is hydrogen or a (C
1
-C
6
)alkyl, and m is 0, 1 or 2;
X° is a bond or a (C
1
-C
6
)alkenylene;

2
is a group of formula
in which

4
and R°
5
are, independently, a (C
1
-C
6
)alkyl or constitute, with the nitrogen atom to which they are attached, a heterocyclic group selected from hexamethyleneiminyl, piperazino, heptamethyleneiminyl, 4-methylpiperidyl, imidazolinyl, piperidyl, pyrrolidinyl or morpholinyl;
R° is a hydroxyl, a halogen, a hydrogen, a (C
3
-C
8
)cycloalkyl, a (C
2
-C
7
)alkanoyloxy, a (C
1
-C
6
)alkoxy or a phenyl, the said phenyl optionally being substituted with one, two or three substituents selected from groups consisting of (C
1
-C
4
)alkyl, (C
1
-C
4
)alkoxy, nitro, chloro, fluoro, trifluoromethyl, —OSO
2
—(C
3
-C
10
)alkyl or ——C(O)—NH—R°
3
;
R
1
is hydroxyl, halogen, hydrogen, (C
3
-C
8
)cycloalkyl, (C
2
-C
7
)alkanoyloxy, (C
1
-C
6
)alkoxy or phenyl, it being possible for the said phenyl optionally to be substituted with one, two or three substituents selected from the group consisting of (C
1
-C
4
)alkyl, (C
1
-C
4
)alkoxy, nitro, chloro, fluoro, trifluoromethyl, —OSO
2
—(C
1
-C
10
)alkyl or —O—C(O)—NH—R°
3
;
in which each R°
3
represents, independently, (C
1
-C
6
)alkyl, (C
3
-C
8
)cycloalkyl, unsubstituted or substituted phenyl in which the substitutent is halogen, (C
1
-C
6
)alkyl or (C
1
-C
6
)alkoxy;
with the limitation that when X° is a bond and A° is —S—, then R° and R°
1
are not both selected from the group consisting of hydroxyl, methoxy and (C
2
-C
7
)alkanoyloxy; as well as the salts or solvates thereof, which can be prepared according to WO 96/12489, in particular a compound selected from:
3-(4-methoxyphenyl)-4-[4-(2-pyrrolidin-1-ylethoxy)benzoyl]-1,2-dihydronaphthalene,
3-phenyl-4-[4-(2-pyrrolidin-1-ylethoxy)benzoyl]-7-methoxy-1,2-dihydronaphthalene,
3-(4-methoxyphenyl)-4-[4-[2-(piperid-1-yl)ethoxy]benzoyl]-1,2-dihydronaphthalene,
3-(4-hydroxyphenyl)-4-[4-[2-(pyrrolidin-1-yl)ethoxy]benzoyl]-1,2-dihydronaphthalene,
3-(4-methoxyphenyl)-4-[4-[2-(hexamethyleneimin-1-yl)ethoxy]benzoyl]-1,2-dihydronaphthalene,
3-(4-methoxyphenyl)-4-[4-[2-(piperid-1-yl)ethoxy]benzoyl]-1,2-dihydronaphthalene,
3-(4-methoxyphenyl)-4-[4-[2-(piperid-1-yl)ethoxy]benzoyl-7-methoxy-1,2-dihydronaphthalene,
3-(4-methoxyphenyl)-4-[4-[2-(N-methyl-1-pyrrolidinium)ethoxy]benzoyl]-1,2-dihydronaphthalene,
3-(4-methoxyphenyl)-4-[4-[2-dimethylaminoethoxy)benzoyl]-1,2-dihydronaphthalene,
3-(4-methoxyphenyl)-4-(4-diethylaminoethoxybenzoyl)-1,2-dihydronaphthalene,
3-(4-methoxyphenyl)-4-(4-diisopropylaminoethoxybenzoyl) -1,2-dihydronaphthalene,
2-(4-hydroxyphenyl)-3-[4-[2-(hexamethyleneimin-1-yl)ethoxy]benzoyl]-6-hydroxybenzofuran,
2-(4-hydroxyphenyl)-3-[4-[2-(piperid-1-yl)ethoxy]benzoyl]-6-hydroxybenzofuran,
2-(4-hydroxyphenyl)-3-[4-[2-pyrrolidin-1-yl)ethoxy]-benzoyl]-6-hydroxybenzofuran,
2-(4-hydroxyphenyl)-3-[4-[2-(N,N-diethylamino)ethoxyl -benzoyl]-6-hydroxybenzofuran,
2-(4-hydroxyphenyl)-3-[4-[2-(N,N-diisopropylamino)ethoxy]benzoyl]-6-hydroxybenzofuran,
2-(4-hydroxyphenyl)-3-[4-[2-(N,N-dimethylamino)ethoxy]benzoyl]-6-hydroxybenzofuran,
1-ethyl-2-(4-methoxyphenyl)-3-[4-[2-(piperid-1-yl)ethoxy]benzoyl]-6-hydroxyindole,
2-(4-methoxyphenyl)-3-[4-[2-(hexamethyleneimin-1-yl)ethoxylbenzoyl]-6-methoxybenzofuran,
2-(4-methoxyphenyl)-3-[4-[2-(piperid-1-yl)ethoxy]benzoyl]-6-methoxybenzofuran,
2-(4-methoxyphenyl)-3-[4-[2-(pyrrolidin-1-yl]ethoxy]benzoyl3-6-methoxybenzofuran,
2-(4-methoxyphenyl)-3-[4-[2-(N,N-diethylamino)ethoxy]benzoyl]-6-methoxybenzofuran,
2-(4-methoxyphenyl)-3-[4-[2-(N,N-diisopropylamino)ethoxy]benzoyl]-6-methoxybenzofuran,
2-(4-methoxyphenyl)-3-[4-[2-(N,N-dimethylamino)ethoxy]benzoyl]-6-methoxybenzofuran,
1-ethyl-2-(4-methoxyphenyl)-3-[4-[2-(piperid-1-yl)ethoxy]benzoyl]-6-methoxyindole,
2-(4-methoxyphenyl)-3-[4-[3-(hexamethyleneimin-1-yl)propoxy]benzoyl]benzo[b]thiophene,
2-(4-methoxyphenyl)-3-[4-[2-(hexamethyl

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