Bi-aromatic compounds bound by a heteroethynylene radical...

Details Bi-aromatic compounds bound by a heteroethynylene radical... Bi-aromatic compounds bound by a heteroethynylene radical...

1999-04-08

2001-03-13

Aulakh, C. S. (Department: 1612)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Ester doai

C560S010000, C560S011000, C560S055000, C560S056000, C560S100000, C562S427000, C562S466000, C564S161000, C514S569000, C514S617000

Reexamination Certificate

active

06201019

ABSTRACT:

The invention relates, as novel and useful industrial products, to bi-aromatic compounds whose aromatic rings are linked via a divalent heteroethynylene radical. The invention also relates to the use of these novel compounds in pharmaceutical compositions intended for use in human or veterinary medicine, or alternatively in cosmetic compositions.
The compounds according to the invention have pronounced activity in the fields of cell differentiation and proliferation and find applications more particularly in the topical and systemic treatment of dermatological complaints associated with a keratinization disorder, dermatological (or other) complaints with an inflammatory and/or immunoallergic component, and dermal or epidermal proliferations, whether they are benign or malignant. These compounds can also be used in the treatment of connective tissue degenerative diseases, for combating ageing of the skin, whether this is light-induced or chronological ageing, and for treating cicatrization disorders. They moreover find an application in the opthalmological field, in particular in the treatment of corneopathy.
The compounds according to the invention can also be used in cosmetic compositions for body and hair hygiene.
Bi-aromatic compounds whose aromatic rings are linked via a divalent propynylene have already been described in EP-661,258 as active substances in pharmaceutical or cosmetic compositions.
The compounds according to EP-661,258 correspond to the following general formula:
in which:
Ar is a divalent aromatic radical optionally substituted with a radical R
5
or a heteroaromatic radical optionally substituted with a radical R
6
when the hetero atom is nitrogen,
R
1
represents H, —CH
3
, —CH
2
OR
6
, —OR
6
, —COR
7
or —S(O)
t
R
9
, t being 0, 1 or 2.
R
2
and R
3
represent H, C
1
-C
20
alkyl, —OR
6
or —SR
6
,
or R
2
and R
3
taken together, form a 5- or 6-membered ring optionally substituted with methyl groups and/or optionally interrupted by an oxygen or sulphur atom,
R
4
and R
5
represent H, a halogen, lower alkyl or —OR
6
,
R
6
represents H, lower alkyl or —COR
9
,
R
7
represents H, lower alkyl,
 or —OR
8
,
R
8
represents H, linear or branched C
1
-C
20
alkyl, alkenyl, mono- or polyhydroxyalkyl, optionally substituted aryl or aralky, or a sugar or amino acid or peptide residue,
R
9
represents lower alkyl,
R and R′ represent H, lower alkyl, mono- or polyhydroxyalkyl, optionally substituted aryl or a sugar, amino acid or peptide residue or R and R′, taken together, form a heterocycle, and
X represents a divalent radical which, from right to left or vice-versa, has the formula:
in which:
R
10
represents H, lower alkyl or —OR
6
,
R
11
represents —OR
6
,
or R
10
and R
11
, taken together, form an oxo (═O) radical,
and the salts of the said compounds of the above formula when R
1
represents a carboxylic acid function, and the optical and geometrical isomers of these said compounds.
The compounds according to the present invention differ from those of EP-661,258 essentially in that the radical X or divalent propynylene radical has been replaced with a divalent heteroethynylene radical.
The reason for this is that it has been found, surprisingly and unexpectedly, that this structural change makes it possible to significantly increase the pharmaceutical and cosmetic properties thereof and also to decrease certain side effects thereof.
A subject of the present invention is thus novel compounds which can be represented by the following general formula:
in which:
Ar represents a radical chosen from the formulae (a) to (c) below:
Z being O or S, or N—R
6
,
R
1
represents a halogen atom, —CH
3
, —CH
2
—OR
7
, —OR
7
, —COR
8
or a polyether radical,
R
2
and R
3
, which may be identical or different, represent H, linear or branched C
1
-C
20
alkyl, C
3
-C
12
cycloalkyl, —OR
7
or —SR
7
, at least one from among R
2
and R
3
being linear or branched C
1
-C
20
alkyl or C
3
-C
10
cycloalkyl, or
R
2
and R
3
, taken together, form a 5- or 6-membered ring, optionally substituted with at least one methyl and/or optionally interrupted by a hetero atom chosen from O and S,
R
4
and R
5
represent H, a halogen atom, linear or branched C
1
-C
20
alkyl, —OR
7
or a polyether radical,
R
6
represents H, linear or branched C
1
-C
10
alkyl or —OCOR
9
,
R
7
represents H, linear or branched C
1
-C
10
alkyl or —COR
9
,
R
8
represents H, linear or branched C
1
-C
10
, alkyl, —OR
10
or
R
9
represents linear or branched C
1
-C
10
alkyl,
R
10
represents H, linear or branched C
1
-C
20
alkyl, mono- or polyhydroxyalkyl, allyl, optionally substituted aryl or aralkyl, or a sugar residue,
r′ and r″, which may be identical or different, represent H, C
1
-C
10
alkyl, mono- or polyhydroxyalkyl, optionally substituted aryl, an amino acid or peptide residue, or, taken together with the nitrogen atom, form a heterocycle,
X represents a divalent radical which, from right to left or vice-versa, has the formula:
in which:
Y represents O, S(O)
n
or Se(O)
n′
,
n and n′ being 0, 1 or 2,
with the proviso that when n=2 and Ar is a radical of formula (a) above, in which R
1
=—CH
3
and R
5
=H, then at least one of the radicals R
2
or R
3
is other than —CH
3
,
and the salts of the compounds of formula (I) when R
1
represents a carboxylic acid function, as well as the optical isomers of the said compounds of formula (I).
When the compounds according to the invention are in the form of a salt, this is preferably a salt of an alkali metal or alkaline-earth metal, or alternatively of zinc or of an organic amine.
According to the present invention, the term “C
1
-C
10
alkyl” preferably refers to the methyl, ethyl, isopropyl, butyl, tert-butyl, hexyl, 2-ethylhexyl and octyl radicals.
The term “linear or branched C
1
-C
20
alkyl” refers in particular to the methyl, ethyl, propyl, 2-ethylhexyl, octyl, dodecyl, hexadecyl and octadecyl radicals.
The term “C
3
-C
12
cycloalkyl radical” refers to a mono- or polycyclic radical, in particular the cyclopropyl, cyclopentyl, cyclohexyl, 1-methylcyclohexyl and 1-adamantyl radicals.
The term “polyether radical” refers to a radical containing from 2 to 5 carbon atoms interrupted by at least two oxygen atoms, such as the methoxymethoxy, methoxyethoxy and methoxyethoxymethoxy radicals.
The term “monohydroxyalkyl” refers to a radical preferably containing 2 or 3 carbon atoms, in particular a 2-hydroxyethyl, 2-hydroxypropyl or 3-hydroxypropyl radical.
The term “polyhydroxyalkyl” refers to a radical preferably containing 3 to 6 carbon atoms and from 2 to 5 hydroxyl groups, such as the 2,3-dihydroxypropyl, 2,3,4-trihydroxybutyl and 2,3,4,5-tetrahydroxypentyl radicals or the pentaerythritol residue.
The term “aryl” preferably refers to a phenyl radical optionally substituted with at least one halogen atom, a hydroxyl or a nitro function.
The term “aralkyl” preferably refers to a benzyl or phenethyl radical optionally substituted with at least one halogen atom, a hydroxyl or a nitro function.
The term “sugar residue” refers to a residue derived in particular from glucose, from galactose or from mannose, or alternatively from glucuronic acid.
The term “amino acid residue” refers in particular to a residue derived from lysine, from glycine or from aspartic acid, and the term “peptide residue” refers more particularly to a dipeptide or tripeptide residue resulting from the combination of amino acids.
The term “heterocycle” preferably refers to a piperidino, morpholino, pyrrolidino or piperazino radical, optionally substituted in position 4 with a C
1
-C
6
lower alkyl or a mono- or polyhydroxyalkyl as defined above.
When R
1
, R
4
and/or R
5
represents a halogen atom, this is preferably a fluorine, chlorine or bromine atom.
According to a first preferred embodiment, the compounds according to the invention correspond to the following general formula:
in which:
Ar′ represents a radical of formula:
R
1
, R
4
, R
5
and X being as defined above for formula (I),
R
11
, R
12
, R
13

Affiliated with

Also associated with

Rating

Bi-aromatic compounds bound by a heteroethynylene radical... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Bi-aromatic compounds bound by a heteroethynylene radical..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Bi-aromatic compounds bound by a heteroethynylene radical... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2440684