U.S. patent application number 11/446129 was filed with the patent office on 2006-10-05 for tricyclic quinoxaline and quinoline derivatives as uv filters.
Invention is credited to Hans Neunhoeffer, Frank Pflucker, Volker Scholz, Michael Schwarz.
Application Number | 20060222607 11/446129 |
Document ID | / |
Family ID | 7677094 |
Filed Date | 2006-10-05 |
United States Patent
Application |
20060222607 |
Kind Code |
A1 |
Pflucker; Frank ; et
al. |
October 5, 2006 |
Tricyclic quinoxaline and quinoline derivatives as UV filters
Abstract
The invention relates to the use of quinoxaline derivatives of
formula I, represented by formulas Ia and Ib, as photostable UV
filters, in particular in cosmetic and pharmaceutical preparations
for protecting the human epidermis or human hair against UV
radiation, above all in the 280-400 nm range. ##STR1##
Inventors: |
Pflucker; Frank; (Darmstadt,
DE) ; Schwarz; Michael; (Weiterstadt, DE) ;
Scholz; Volker; (Darmstadt, DE) ; Neunhoeffer;
Hans; (Muhltal, DE) |
Correspondence
Address: |
MILLEN, WHITE, ZELANO & BRANIGAN, P.C.
2200 CLARENDON BLVD.
SUITE 1400
ARLINGTON
VA
22201
US
|
Family ID: |
7677094 |
Appl. No.: |
11/446129 |
Filed: |
June 5, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10471101 |
Sep 8, 2003 |
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PCT/EP02/01402 |
Feb 11, 2002 |
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11446129 |
Jun 5, 2006 |
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Current U.S.
Class: |
424/59 ; 524/90;
544/345 |
Current CPC
Class: |
A61K 8/4946 20130101;
A61P 17/16 20180101; A61K 2800/52 20130101; A61Q 17/04 20130101;
C07D 487/04 20130101; A61P 17/06 20180101; A61K 8/494 20130101 |
Class at
Publication: |
424/059 ;
524/090; 544/345 |
International
Class: |
A61K 8/49 20060101
A61K008/49; C07D 487/02 20060101 C07D487/02; C08K 5/34 20060101
C08K005/34 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 9, 2001 |
DE |
101 11 728.0 |
Claims
1-14. (canceled)
15. A quinoxaline compound of formula VIII ##STR45## wherein R,
R.sup.1 and R.sup.2 are each, independently of one another, H,
alkyl, alkoxy, alkenyl or alkynyl, each having up to 20 carbon
atoms, cycloalkyl, cycloalkoxy, cycloalkenyl or bicyclic systems,
each having up to 10 carbon atoms, where, in all of these groups,
one or more hydrogen atoms may also be substituted by Sub.sup.1
and/or one or two CH.sub.2 groups may be replaced by C.dbd.O, and
the cyclic systems may contain 1 to 3 heteroatoms, Hal, OH,
NO.sub.2,
--(CR.sup.5R.sup.6).sub.n--NR.sup.5R.sup.6--(CR.sup.5R.sup.6).sub.n--N.db-
d.CR.sup.5R.sup.6,
--(CR.sup.5R.sup.6).sub.n--CR.sup.5.dbd.NR.sup.5,
--(CR.sup.5R.sup.6).sub.n--NHCOR.sup.5,
--(CR.sup.5R.sup.6).sub.n--NHCOOR.sup.5, --SR.sup.5,
--SO.sub.2--R.sup.5, NR.sup.5--SO--R.sup.6, --SO--R.sup.5,
water-solubilising substituents, carboxylate, sulfonate or ammonium
radicals, COR.sup.5, COOR.sup.5, CON.sup.5R.sup.6, CN,
O.dbd.S(--R.sup.5).dbd.O, O.dbd.S(--OR.sup.5).dbd.O,
O.dbd.S(--NR.sup.5R.sup.6).dbd.O, R.sup.5OP(--OR.sup.6).dbd.O, OAr,
--(CR.sup.5R.sup.6).sub.n--Ar, --Si(alkyl).sub.3,
--Si(alkyl).sub.2H, -Het, --NHHet, --OHet or
--(CR.sup.5R.sup.6).sub.n-Het, R.sup.1 and R.sup.2 together, with
carbon atoms to which they are bonded, may jointly form an
unsaturated, partially or fully saturated 4-, 5-, 6- or 7-membered
ring, which optionally contains one or more heteroatoms, may be
further fused and/or may also be monosubstituted or
polysubstituted, R.sup.4 is H or a branched or unbranched
C1-20-alkyl radical, in which optionally one or more H atoms may be
replaced by Sub, Sub is Hal, hydroxyl, cyano, amino, nitro,
C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-alkoxy, COR.sup.5,
COOR.sup.5, OAr, OHet, --(CR.sup.5R.sup.6).sub.n--Ar or
--(CR.sup.5R.sup.6).sub.n--Het,
--(CR.sup.5R.sup.6).sub.n--NR.sup.5R.sup.6, CONR.sup.5R.sup.6, CN,
O.dbd.S(--R.sup.5).dbd.O, O.dbd.S(--OR.sup.5).dbd.O,
O.dbd.S(--NR.sup.5R.sup.6).dbd.O or R.sup.5OP(--OR.sup.6).dbd.O,
Sub.sup.1 is Hal, hydroxyl, cyano, amino, nitro,
C.sub.1-C.sub.4-alkylamino, C.sub.1-C.sub.4-dialkylamino,
C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-alkoxy, COOH or COO-alkyl,
Hal is fluorine, chlorine, bromine or iodine, n is 0, 1, 2, 3 or 4,
m is 1, 2 or 3, R.sup.5 and R.sup.6 are each, independently of one
another, H, alkyl, alkenyl, alkynyl, each having up to 20 carbon
atoms, cycloalkyl, cycloalkenyl, bicyclic systems, each having up
to 10 carbon atoms, where these radicals may be up to
trisubstituted by Sub.sup.1 and/or one or two CH.sub.2 groups may
be replaced by C.dbd.O, and the cyclic systems may also contain 1
to 3 heteroatoms, --(CR'R'').sub.n--Ar or --(CR'R'').sub.n--Het, or
the radicals R.sup.5 and R.sup.6 may also, with one another, in
each case together with carbon atoms to which they are bonded,
jointly form an unsaturated, partially or fully saturated 4-, 5-,
6- or 7-membered ring, which optionally contains one or more
heteroatoms, may also be monosubstituted or polysubstituted and/or
may be further fused, R' and R'' are each, independently of one
another, H or C.sub.1-C.sub.4-alkyl, in which one or two CH.sub.2
groups may also be replaced by C.dbd.O, Ar is an unsubstituted or
monosubstituted or polysubstituted aromatic ring or fused ring
systems having 6 to 18 carbon atoms, in which one or two CH groups
may also be replaced by C.dbd.O, and Het is an unsubstituted or
monosubstituted or polysubstituted heteroaromatic ring having 5 to
7 ring members or a fused ring system, where the heteroatoms
present are one or more N, S and/or O atoms, and in which one or
two CH groups in the .alpha.- or .beta.-position to the heteroatoms
may also be replaced by C.dbd.O.
16. A compound according to claim 15, wherein R.sup.4 is H, methyl,
ethyl or ethyl or ethylhexyl.
17. A compound according to claim 15, wherein R is a branched or
unbranched C.sub.1-20-alkyl radical, in which, optionally one or
more H atoms are replaced by Sub.
18. A compound according to claim 17, wherein Sub is methyl, ethyl,
isopropyl or tertiary-butyl.
19. A compound according to claim 15, which is
1-(2-ethylhexyl)-2-phenylimidazo[3,4-b]quinoxaline.
20. A compound according to claim 15, wherein the phenyl ring of
formula VII is substituted in accordance with one of the patterns
shown below TABLE-US-00017 R m Position ##STR46## CH.sub.3 1-3 o/
m/ p; m/ m/ p; o/p; m/ m C.sub.2H.sub.5 1-3 '' C.sub.3H.sub.7 1-3
'' .sup.nC.sub.4H.sub.9 1-3 '' .sup.tC.sub.4H.sub.9 1-3 ''
.sup.iC.sub.4H.sub.9 1-3 '' C.sub.5H.sub.11 1-3 '' C.sub.18H.sub.37
1-3 '' (2'-Etyl)-hexyl- 1-3 '' OCH.sub.3 1-3 o/ m/ p; m/ m/ p; o/p;
m/ m OC.sub.2H.sub.5 1-3 '' OC.sub.3H.sub.7 1-3 '' OC.sub.4H.sub.9
1-3 '' OC.sub.5H.sub.11 1-3 '' OC.sub.18H.sub.37 1-3 '' OCOCH.sub.3
1-2 o; m; p; o/p OCOC.sub.2H.sub.5 1-2 '' OCOC.sub.3H.sub.7 1-2 ''
OCOC.sub.4H.sub.9 1-2 '' OCOC.sub.5H.sub.11 1-2 ''
OCOC.sub.18H.sub.37 1-2 '' OH 1-3 o/ m/ p; m/ m/ p; o/p; m/ m F 1-2
o; p; o/p Cl 1-2 o; p; o/p CF.sub.3 1 o; m; p NO.sub.2 1-3 m/; m/
m; o/ o/ p NHCOR.sup.5 1 P NHCOOR.sup.5 1 P COR.sup.5 1-2 o; p; o/p
COOR.sup.5 1-2 o; p; o/p CONR.sup.5R.sup.6 1-2 o; p; o/p CN 1 P
O.dbd.S(OR.sup.5).dbd.O 1 P O.dbd.S(R.sup.5).dbd.O 1 P
O.dbd.S(NR.sup.5R.sup.6).dbd.O 1 P R.sup.5OP(--OR.sup.6).dbd.O 1
P
21. A compound according to claim 15, wherein R is CH.sub.3;
C.sub.2H.sub.5; C.sub.3H.sub.7; .sup.nC.sub.4H.sub.9;
.sup.1C.sub.4H.sub.9; .sup.iC.sub.4H.sub.9; C.sub.5H.sub.11;
C.sub.18H.sub.37; (2'-Etyl)-hexyl-; OCH.sub.3; OC.sub.2H.sub.5;
OC.sub.3H.sub.7; OC.sub.4H.sub.9; OC.sub.5H.sub.11;
OC.sub.18H.sub.37; OCOCH.sub.3; OCOC.sub.2H.sub.5;
OCOC.sub.3H.sub.7; OCOC.sub.4H.sub.9; OCOC.sub.5H.sub.11;
OCOC.sub.18H.sub.37; OH; F; Cl; CF.sub.3; NO.sub.2; NHCOR.sup.5;
NHCOOR.sub.5; COR.sub.5; COOR.sub.5; CONR.sup.5R.sup.6; CN;
O.dbd.S(OR.sup.5).dbd.O; O.dbd.S(R.sup.5).dbd.O;
O.dbd.S(NR.sub.5R.sup.6).dbd.O; or R.sup.5OP(--OR.sup.6).dbd.O.
22. A cosmetic or pharmaceutical composition comprising a compound
of claim 15 and a pharmaceutically or cosmetically acceptable
excipient.
23. A cosmetic or pharmaceutical composition comprising an
effective amount of a compound of claim 15 alone or together with a
UV-absorbent compound suitable for protection of the human
epidermis or human hair against UV light in the range of 280 to 400
nm together with one or more pharmaceutically or cosmetically
acceptable excipients.
24. A cosmetic or pharmaceutical composition comprising a compound
of claim 20 and a pharmaceutically or cosmetically acceptable
excipient.
25. A cosmetic or pharmaceutical composition comprising an
effective amount of a compound of claim 20 alone or together with a
UV-absorbent compound suitable for protection of the human
epidermis or human hair against UV light in the range of 280 to 400
nm together with one or more pharmaceutically or cosmetically
acceptable excipients.
26. A process for the preparing a compound of formula VII according
to claim 15 comprising reacting 2,3-dichloroquinoxaline, which is
substituted by R.sup.1 and R.sup.2 corresponding to the target
compound of formula VII, to form a compound of formula VII.
27. A process according to claim 26, wherein one of the chlorine
atoms of the 2,3-dichloroquinoxaline is replaced by an amino
function and the other chlorine atom is replaced by
--NH--R.sup.4.
28. A process according to claim 27 further comprising reacting the
obtained quinoxaline with a suitably substituted benzaldehyde
compound to obtain a compound of formula VII.
29. A method for protecting skin and/or hair of a human from
ultraviolet radiation comprising applying onto said skin and/or
hair an effective amount of a compound of formula VIII according to
claim 15.
30. A method according to claim 29, wherein R.sup.4 is H, methyl,
ethyl or ethyl or ethylhexyl, R is a branched or unbranched
C.sub.1-20-alkyl radical, in which, optionally one or more H atoms
are replaced by methyl, ethyl, isopropyl or tertiary-butyl.
31. A method according to claim 29, wherein R.sup.4 is H, methyl,
ethyl or ethyl or ethylhexyl, R is a branched or unbranched
C.sub.1-20-alkyl radical, in which, two or three H atoms are
replaced by methyl, ethyl, isopropyl or tertiary-butyl.
32. A method for protecting skin and/or hair of a human from
ultraviolet radiation comprising applying onto said skin and/or
hair an effective amount of a compound of formula VIII according to
claim 20.
33. A compound according to claim 15, wherein m is 2 or 3, and R is
alkyl, alkoxy, alkenyl or alkynyl, each having up to 20 carbon
atoms, cycloalkyl, cycloalkoxy, cycloalkenyl or bicyclic systems,
each having up to 10 carbon atoms, where, in all of these groups,
one or more hydrogen atoms may also be substituted by Sub.sup.1
and/or one or two CH.sub.2 groups may be replaced by C.dbd.O, and
the cyclic systems may contain 1 to 3 heteroatoms, Hal, OH,
NO.sub.2, --(CR.sup.5R.sup.6).sub.n--NR.sup.5R.sup.6,
--(CR.sup.5R.sup.6).sub.n--N.dbd.CR.sup.5R.sup.6,
--(CR.sup.5R.sup.6)--CR.sup.5.dbd.NR.sup.5,
--(CR.sup.5R.sup.6).sub.n--NHCOR.sup.5,
--(CR.sup.5R.sup.6).sub.n--NHCOOR.sup.5, --SR.sup.5,
--SO.sub.2--R.sup.5, NR.sup.5--SO--R.sup.6, --SO--R.sup.5,
water-solubilising substituents, carboxylate, sulfonate or ammonium
radicals, COR.sup.5, COOR.sup.5, CON.sup.5R.sup.6, CN,
O.dbd.S(--R.sup.5).dbd.O, O.dbd.S(--OR.sup.5).dbd.O,
O.dbd.S(--NR.sup.5R.sup.6).dbd.O, R.sup.5OP(--OR.sup.6).dbd.O, OAr,
--(CR.sup.5R.sup.6).sub.n--Ar, --Si(alkyl).sub.3,
--Si(alkyl).sub.2H, -Het, --NHHet, --OHet or
--(CR.sup.5R.sup.6)n-Het.
34. A compound according to claim 21, wherein m is 2 or 3.
Description
[0001] The invention relates to the use of quinoxaline derivatives
as photostable UV filters in cosmetic and pharmaceutical
preparations for protection of the human epidermis or human hair
against UV radiation, especially in the range 280-400 m.
[0002] The light-protection agents employed in cosmetic and
pharmaceutical preparations have the job of preventing or at least
reducing the effects of harmful influences of sunlight on the human
skin. In addition, however, these light-protection agents also
serve to protect further ingredients against destruction or
degradation by UV radiation. In hair-cosmetic preparations, the aim
is to prevent damage to the keratin fibres by UV rays.
[0003] As is known, the skin reacts sensitively to solar radiation,
which can cause normal sunburn or erythema, but also various
degrees of burning.
[0004] However, solar radiation also has other adverse effects: it
causes the skin to lose its elasticity and causes the formation of
wrinkles and thus results in premature ageing. Dermatosis is
sometimes also observed, and in the extreme case skin cancer can
arise.
[0005] Owing to this knowledge, changes have also occurred in sun
protection.
[0006] Whereas the main aim a few years ago was erythema-preventing
UV-B protection, protection against UV-A radiation is now included
in sun-protection preparations.
[0007] UV-A radiation is essentially the trigger for pigmentation
of the skin.
[0008] It is also desirable to protect hair against photochemical
damage in order to prevent changes in colour shade, bleaching or
damage of a mechanical nature.
[0009] As is known, the most dangerous part of solar radiation is
formed by ultraviolet rays having a wavelength of less than 400 m.
It is also known that the presence of the ozone layer in the
earth's atmosphere, which absorbs part of solar radiation, means
that the lower limit for the ultraviolet rays which reach the
earth's surface is about 280 m. All this knowledge therefore makes
the development of efficient filter substances for the UV-A and
also for the UV-B region appear necessary.
[0010] There is a growing demand for light-protection agents for
cosmetic and pharmaceutical preparations which can serve, in
particular, as UV-A filters and whose absorption maxima should
therefore be in the range from about 320 to 400 m. There is
furthermore also a demand for broad-band protection, i.e. UV-A and
UV-B protection, in the range 280-400 m.
[0011] In order to achieve the desired effect using the smallest
possible amount, light-protection agents of this type should
additionally have highly specific absorbance. In addition,
light-protection agents for cosmetic preparations have to meet a
multiplicity of further demands, for example good solubility in
cosmetic oils or in water, high stability of the emulsions prepared
therewith, toxicological acceptability and low inherent odour and
low inherent colour.
[0012] A further requirement that light-protection agents have to
satisfy is adequate photostability. However, this is often only
guaranteed to an inadequate extent with the UV-A and UV-B absorbing
light-protection agents available hitherto.
[0013] Although the prior art contains various approaches for
improving the photostability of good light-protection filters, such
as, for example, of dibenzoylmethanes, by combination with various
UV-B filters (FR 2 440 933), or also for stabilising the UV filters
by addition of certain substances (EP 0514491), adequate solutions
are still, however, not available therewith.
[0014] Furthermore, DE-A 197 46 656 and EP 0 852 137 propose
substance classes, such as 4,4-diarylbutadienes or compounds
containing an R.sup.4--NH--CR.sup.3.dbd.CR.sup.1R.sup.2 structure,
as novel light-protection filters, but these do not adequately meet
the demand for suitable compounds for the UV-A and UV-B
regions.
[0015] The object was therefore to find a novel structural class as
light-protection agents for cosmetic and pharmaceutical purposes
which absorb in the UV-A and/or UV-B region, are photostable, have
low inherent colour, i.e. a sharp band structure, have high
absorbance and are soluble in oil or water, depending on the
substituent.
[0016] It has been found in the earlier application DE 10013318.5
that quinoxaline derivatives containing a wide variety of radicals
have excellent UV-B and/or UV-A properties and meet the
above-described requirements to a high extent.
[0017] It has now been found that specific derivatives of the
formula I are particularly suitable for achieving this object.
[0018] A first subject-matter of the present invention is therefore
the use of compounds of the formula I, reproduced as formulae Ia
and Ib, ##STR2## in which X is an N atom or a C--R.sup.3 group A is
a group selected from the formula II or III ##STR3## where [0019]
X.sup.1, X.sup.2, X.sup.3 and X.sup.4 are each, independently of
one another, .dbd.N--, --NR.sup.4--, --CR.sup.5R.sup.6--,
--C(.dbd.O)-- or a .dbd.CR-- group, with the proviso that, in the
formula II, from one to 3 of the X.sup.1--X.sup.4 groups are
selected from .dbd.N-- and --NR.sup.4-- and that, in the formula
III, one or two of the X.sup.1--X.sup.3 groups are selected from
.dbd.N-- and --NR.sup.4--, [0020] R, R.sup.1, R.sup.2 and R.sup.3
are each, independently of one another, H, alkyl, alkoxy, alkenyl
or alkynyl, each having up to 20 carbon atoms, cycloalkyl,
cycloalkoxy, cycloalkenyl or bicyclic systems, each having up to 10
carbon atoms, where, in all of these groups, one or more hydrogen
atoms may also be substituted by Sub.sup.1 and/or one or two
CH.sub.2 groups may be replaced by C.dbd.O, and the cyclic systems
may contain from 1 to 3 heteroatoms, such as S, N and/or 0, Hal,
OH, NO.sub.2, --(CR.sup.5R.sup.6).sub.n--NR.sup.5R.sup.6,
--(CR.sup.5R.sup.6).sub.n--N.dbd.CR.sup.5R.sup.6,
--(CR.sup.5R.sup.6).sub.n--CR.sup.5.dbd.NR,
--(CR.sup.5R.sup.6).sub.n--NHCOR.sup.5,
--(CR.sup.5R.sup.6).sub.n--NHCOOR.sup.5, --SR.sup.5,
--SO.sub.2--R.sup.5, NR.sup.5--SO--R.sup.6, --SO--R.sup.5,
water-solubilising substituents selected from the group consisting
of carboxylate, sulfonate or ammonium radicals, COR.sup.5,
COOR.sup.5, CON.sup.5R.sup.6, CN, O.dbd.S(--R.sup.5).dbd.O,
O.dbd.S(--OR.sup.5).dbd.O, O.dbd.S(--NR.sup.5R.sup.6).dbd.O,
R.sup.5OP(--OR.sup.5).dbd.O, OAr, --(CR.sup.5R.sup.6).sub.n--Ar,
--Si(alkyl).sub.3, --Si(alkyl).sub.2H, -Het, --NHHet, --OHet or
--(CR.sup.5R.sup.6).sub.n-Het, [0021] R.sup.1 and R.sup.2 together,
also with carbon atoms to which they are bonded, may jointly form
an unsaturated, partially or fully saturated 4-, 5-, 6- or
7-membered ring, which may optionally contain heteroatoms, such as
S, N and/or O, may be further fused and/or may also be
monosubstituted or polysubstituted, [0022] Sub.sup.1 is Hal,
hydroxyl, cyano, amino, nitro, C.sub.1-C.sub.4-alkylamino,
C.sub.1-C.sub.4-dialkylamino, C.sub.0-C.sub.4-alkyl or
C.sub.1-C.sub.4-alkoxy, COOH or COO-alkyl, Hal is fluorine,
chlorine, bromine or iodine, [0023] n is 0, 1, 2, 3 or 4, [0024]
R.sup.5 and R.sup.6 are each, independently of one another, H,
alkyl, alkenyl, alkynyl, each having up to 20 carbon atoms,
cycloalkyl, cycloalkenyl, bicyclic systems, each having up to 10
carbon atoms, where these radicals may be up to trisubstituted by
Sub.sup.1 and/or one or two CH.sub.2 groups may be replaced by
C.dbd.O, and the cyclic systems may also contain from 1 to 3
heteroatoms, such as S, N and/or O, [0025] --(CR'R'').sub.n--Ar or
--(CR'R'').sub.n-Het, [0026] the radicals R.sup.5 and R.sup.6 may
also, with one another, in each case together with carbon atoms to
which they are bonded, jointly form an unsaturated, partially or
fully saturated 4-, 5-, 6- or 7-membered ring, which may optionally
contain heteroatoms, such as S, N and/or O, may also be
monosubstituted or polysubstituted and/or may be further fused,
[0027] R' and R'' are each, independently of one another, H or
C.sub.1-C.sub.4-alkyl, in which one or two CH.sub.2 groups may also
be replaced by C.dbd.O, [0028] Ar is an unsubstituted or
monosubstituted or polysubstituted aromatic ring or fused ring
systems having from 6 to 18 carbon atoms, in which one or two CH
groups may also be replaced by C.dbd.O, [0029] Het is an
unsubstituted or monosubstituted or polysubstituted heteroaromatic
ring having from 5 to 7 ring members or a fused ring system, where
the heteroatoms present are one or more N, S and/or O atoms, and in
which one or two CH groups in the .alpha.- or .beta.-position to
the heteroatoms may also be replaced by C.dbd.O, [0030] R.sup.4 is
H, alkyl, alkoxy, alkenyl, alkynyl, each having up to 20 carbon
atoms, cycloalkyl, cycloalkoxy, cycloalkenyl, bicyclic systems,
each having up to 10 carbon atoms, where these radicals may be up
to trisubstituted by Sub.sup.2 and/or one or two CH.sub.2 groups
may be replaced by C.dbd.O, and where the cyclic systems may also
contain from 1 to 3 heteroatoms, such as S, N and/or O, [0031]
Sub.sup.2 is Hal, hydroxyl, cyano, amino, nitro,
C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-alkoxy, COR.sup.5,
COOR.sup.5, OAr, OHet, --(CR.sup.5R.sup.6).sub.n--Ar or
--(CR.sup.5R.sup.6).sub.n--Het,
--(CR.sup.5R.sup.6).sub.n--NR.sup.5R.sup.6, CONR.sup.5R.sup.6, CN,
O.dbd.S(--R.sup.5).dbd.O, O.dbd.S(--OR.sup.5).dbd.O,
O.dbd.S(--NR.sup.5R.sup.6).dbd.O or R.sup.5OP(--OR.sup.6).dbd.O, as
photostable UV filters.
[0032] The compounds of the formula I according to the invention
are also referred to below as quinoxaline derivatives, although
compounds which, in the strict chemical sense, are not quinoxaline
derivatives are also covered thereby.
[0033] The compounds of the formula I can be prepared substantially
analogously to the literature. Preparation processes are described,
for example, in D. Ames, M. Brohi; J. Chem. Soc perkin. Trans. 1
(1980) 1384-1389. For a detailed disclosure of the preparation of
compounds of the formula I according to the invention, reference is
also made, in particular, to the example part of this application
(Examples A-G).
[0034] The compounds of the formula I exhibit excellent
UV-absorbent properties both in the UV-A region and, in the
presence of an additional chromophoric group, in the UV-B region,
thus providing broad-band protection. The solubility of the
substances in water or in cosmetic oils can likewise easily be
induced through the choice of suitable substituents. Lipophilic
radical, i.e. radicals which increase the oil solubility of the
compounds of the formula I are, for example, aliphatic or
cycloaliphatic radicals, in particular alkyl radicals having up to
20 carbon atoms, alkoxy, mono- and dialkylamino, alkoxycarbonyl,
mono- and dialkylaminocarbonyl, mono- and dialkylaminosulfonyl
radicals, furthermore also cyano, nitro, bromine, chlorine, iodine
or fluorine substituents.
[0035] Hydrophilic radicals, i.e. radicals which facilitate the
water solubility of the compounds of the formula I are, for
example, carboxyl and sulfoxy radicals and in particular salts
thereof with any desired physiologically tolerated cations, such as
the alkali metal salts or the trialkylammonium salts.
[0036] The alkyl radicals in the radicals R and R.sup.1 to R.sup.6
have up to 20 carbon atoms and may be in unbranched or branched
form and accordingly are preferably methyl, ethyl, n-propyl,
i-propyl, butyl, sec-butyl, i-butyl, tert-butyl, pentyl,
1-methylbutyl, 2-methylbutyl, 3-methylbutyl, hexyl, 1-methylpentyl,
2-methylpentyl, heptyl, octyl, nonyl, decyl, undecyl or dodecyl,
furthermore also 2,2-dimethylpropyl, 1-ethylpropyl, 3-methylpentyl,
4-methylpentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl,
1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl,
2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl,
1-ethylbutyl, 2-ethylbutyl, 1-ethylhexyl, 2-ethylhexyl, tridecyl,
tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl
or eicosyl.
[0037] Preferred alkenyl radicals which may be mentioned are
branched and unbranched alkenyl chains, preferably having up to 10
carbon atoms: vinyl, propenyl, isopropenyl, 1-butenyl, 2-butenyl,
1-pentenyl, 2-pentenyl, 2-methyl-1-butenyl, 2-methyl-2-butenyl,
3-methyl-1-butenyl, 1-hexenyl, 2-hexenyl, 1-heptenyl, 2-heptenyl,
octenyl, nonenyl or decenyl.
[0038] Suitable alkynyl radicals are preferably branched or
unbranched alkynyl chains having up to 10 carbon atoms, such as,
for example, ethynyl, propynyl, butynyl, i-butynyl, pentynyl,
hexynyl, heptynyl or octynyl.
[0039] Cycloalkyl radicals which may be mentioned are preferably
branched or unbranched C.sub.3-C.sub.10-cycloalkyl chains, such as
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,
cyclooctyl, 1-methylcyclopropyl, 1,2-dimethylcyclopentyl,
1-methyl-2-ethylcyclopropyl, cyclononyl or cyclodecyl.
[0040] Suitable alkoxy radicals are branched or unbranched alkoxy
chains having up to 20 carbon atoms, preferably having up to 12
carbon atoms, particularly preferably having from 1 to 8 carbon
atoms, such as, for example, methoxy, ethoxy, propoxy, i-propoxy,
butoxy, 1-methylpropoxy, 2-methylpropoxy, pentoxy,
1,1-dimethylpropoxy, 1-methylbutoxy, 3-methylbutoxy,
2-methylbutoxy, hexoxy, heptoxy or octoxy.
[0041] Cycloalkyl radicals which may be mentioned for R and R.sup.1
to R.sup.6 are preferably branched or unbranched cycloalkyl chains
having 3-10 carbon atoms, such as cyclopropyl, cyclobutyl,
cyclopentyl, cyclohexyl, cycloheptyl, 1-methylcyclopropyl,
1-ethylcyclopropyl, 1-propylcyclopropyl, 1,2-dimethyl-cyclopropyl,
1-methylcyclohexyl, 1,3-dimethylcyclohexyl, cyclooctyl, cyclononyl
or cyclodecyl.
[0042] Cycloalkenyl radicals which may be mentioned are preferably
branched or unbranched C.sub.3-C.sub.10-cycloalkenyl chains having
one or more double bonds, such as cyclopropenyl, cyclobutenyl,
cyclopentenyl, cyclopentadienyl, cyclohexenyl, 1,3-cyclohexadienyl,
1,4-cyclohexadienyl, cycloheptenyl, cycloheptatrienyl,
cyclooctenyl, cyclononenyl or cyclodecenyl.
[0043] Bicycloalkyl or bicycloalkenyl radicals which may be
mentioned are saturated or unsaturated bicyclic ring systems,
preferably having up to 10 carbon atoms, preferably bicyclic
terpenes, such as pinane, pinene, bornane or camphor derivatives,
decalin or adamantane.
[0044] These cyclic systems may also contain from 1 to 3
heteroatoms, such as sulfur, nitrogen or oxygen. Examples thereof
which may be mentioned are ring systems, such as piperidine,
pyrrolidine, pyrazine or pyridazine, pyrimidine, morpholine,
tetrahydrofuran, dihydrofuran, thiolane, piperazine, thiazolidine
or oxazolidine groups.
[0045] In the radicals above and below which may be substituted by
Sub.sup.1, Sub.sup.1 is preferably halogen, such as fluorine,
chlorine, bromine or iodine, preferably fluorine or chlorine,
furthermore preferably C.sub.1-C.sub.4-alkylamino or
C.sub.1-C.sub.4-dialkylamino, C.sub.1-C.sub.4-alkyl or
C.sub.1-C.sub.4-alkoxy, or alternatively hydroxyl or amino.
[0046] In the radicals above and below which may be substituted by
Sub.sup.2, Sub.sup.2 is preferably halogen, such as fluorine,
chlorine, bromine or iodine, preferably fluorine or chlorine,
furthermore preferably C.sub.1-C.sub.4-alkylamino or
C.sub.1-C.sub.4-dialkylamino, C.sub.1-C.sub.4-alkyl or
C.sub.1-C.sub.4-alkoxy, or alternatively hydroxyl or amino, further
preference also being given to the meaning COR.sup.5,
--(CR.sup.5R.sup.6).sub.n--Ar, --(CR.sup.5R.sup.6).sub.n-Het, OAr,
OHet, COOR.sup.5 or R.sup.5OP(--OR.sup.6).dbd.O.
[0047] Suitable mono- or dialkylamino radicals are preferably
methylamino, dimethylamino, ethylamino, methylethylamino,
diethylamino, propylamino, methylpropylamino, dipropylamino,
ethylpropylamino, butylamino, dibutylamino, methylbutylamino or
isopropylamino, furthermore also 1,1-dimethylpropylamino,
pentylamino, hexylamino, 1-methyl-1-ethylpropylamino, heptylamino
or octylamino.
[0048] In the compounds and formulae above and below, Ar is an
unsubstituted or monosubstituted or polysubstituted aromatic ring
or a fused ring system having from 6 to 18 carbon atoms, preferably
having from 6 to 10 carbon atoms, in which, in addition, one or two
CH groups may be replaced by C.dbd.O. Particularly preferred groups
which may be mentioned are unsubstituted or substituted phenyl or
naphthyl.
[0049] Het in the definitions above and below is an unsubstituted
or monosubstituted or polysubstituted heteroaromatic ring having
from 5 to 7 ring members or a fused ring system, preferably having
up to 14 ring atoms, in which one or more N, S and/or O atoms are
present as heteroatoms and in which, in addition, one or two CH
groups may be replaced by C.dbd.O. Unless defined otherwise, the
heterocyclic rings preferably have 1-13 carbon atoms and 1-6
heteroatoms, in particular 3-9 carbon atoms and 14 heteroatoms. For
example, heteroaromatic radicals such as 2- or 3-thienyl, 2- or
3-furyl, 2-, 3- or 4-pyridyl, pyrimidyl, pyrazolyl, pyrazolonyl,
imidazolyl, triazinyl, pyrazinyl, thiazolyl, indolyl, quinolyl,
quinoxalinyl or isoquinolyl are suitable.
[0050] The Ar and Het groups described above are preferably
unsubstituted or monosubstituted, disubstituted or trisubstituted,
possible substituents in principle being all substituents so long
as they do not have a toxic effect on the compounds as a whole. The
substituents defined as Sub.sup.2 are preferably suitable and
accordingly preference is given- to the following substituents:
halogen, in particular F or Cl, hydroxyl, amino, cyano,
C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-alkoxy, COR.sup.5,
COOR.sup.5, OAr, OHet, --(CR.sup.5R.sup.6).sub.n--Ar or
--(CR.sup.5R.sup.6).sub.n-Het,
--(CR.sup.5R.sup.6).sub.n--NR.sup.5R.sup.6 CONR.sup.5R.sup.6, CN,
O.dbd.S(--R.sup.5).dbd.O, O.dbd.S(--OR.sup.5).dbd.O,
O.dbd.S(--NR.sup.5R.sup.6).dbd.O or R.sup.5OP(--OR.sup.6)--O.
[0051] It is furthermore also possible for a CH group in the ring
system to be replaced by C.dbd.N--, i.e. the substituent is then
.dbd.N--R*, in which R* is the same as R.sup.5 or is --NH--Ar.
[0052] The following substituents are furthermore very particularly
preferred: fluorine, chlorine, --COOH, alkoxy having up to 8 carbon
atoms, --COO-alkyl having up to 8 carbon atoms, --CO-phenyl,
--CO-aryl, --CO-Het, -quinoxalinyl or --CO--NH--R.sup.5.
[0053] This list has a purely illustrative character and is in no
way intended to be limiting.
[0054] In the above definitions, the groups Ar, Het, R.sup.5 and/or
R.sup.6 may likewise in turn carry substituents as described above
or below for these groups.
[0055] The quinoxaline derivative is particularly preferably
selected from one of the formulae IV, V, VI and VII ##STR4## in
which R, R.sup.1, R.sup.2 and R.sup.4 are as defined above,
R.sup.1' and R.sup.2', independently of one another and of R.sup.1
or R.sup.2, are likewise as defined above for R.sup.1, and
R.sup.4', independently of R.sup.4, is likewise as defined above
for R.sup.4, where R.sup.1, R.sup.2, R.sup.1', R.sup.2', R.sup.4'
and R.sup.4 are preferably H, and R is preferably H, methyl,
.sup.tbutyl or a phenyl ring, which may be monosubstituted or
polysubstituted by groups which are as defined above for
R.sup.1.
[0056] Use is preferably made of a quinoxaline derivative selected
from the compounds of the formula VIII ##STR5## where R, R.sup.1
and R.sup.2 are as defined above, R.sup.4 is H or a branched or
unbranched C1-20-alkyl radical, in which, if desired, one or more H
atoms may be replaced by Sub, Sub and R.sup.4 are preferably H,
methyl, ethyl or ethyl or ethylhexyl, and
[0057] R is preferably a branched or unbranched C1-20-alkyl
radical, in which, if desired, one or more H atoms may be replaced
by Sub. Particular preference is given to compounds in which R is
methyl, ethyl, isopropyl or tertiary-butyl.
[0058] Preference is furthermore given to
1-(2-ethylhexyl)-2-phenylimidazo[3,4-b]quinoxaline.
[0059] It is particularly preferred for the phenyl ring to be
substituted in accordance with one of the patterns shown in Table
1. TABLE-US-00001 TABLE I R m Position ##STR6## CH.sub.3 1-3 o/
m/p; m/ m/ p; o/p; m/m C.sub.2H.sub.5 1-3 '' C.sub.3H.sub.7 1-3 ''
.sup.nC.sub.4H.sub.9 1-3 '' .sup.tC.sub.4H.sub.9 1-3 ''
.sup.iC.sub.4H.sub.9 1-3 '' C.sub.5H.sub.11 1-3 '' C.sub.18H.sub.37
1-3 '' (2'-Etyl)-hexyl- 1-3 '' OCH.sub.3 1-3 o/m/p; m/m/p; o/p; m/m
OC.sub.2H.sub.5 1-3 '' OC.sub.3H.sub.7 1-3 '' OC.sub.4H.sub.9 1-3
'' OC.sub.5H.sub.11 1-3 '' OC.sub.18H.sub.37 1-3 '' OCOCH.sub.3 1-2
o; m; p; o/p OCOC.sub.2H.sub.5 1-2 '' OCOC.sub.3H.sub.7 1-2 ''
OCOC.sub.4H.sub.9 1-2 '' OCOC.sub.5H.sub.11 1-2 ''
OCOC.sub.18H.sub.37 1-2 '' OH 1-3 o/ m/ p; m/ m/ p; o/p; m/ m F 1-2
o; p; o/p Cl 1-2 o; p; o/p CF.sub.3 1 o; m; p NO.sub.2 1-3 m/; m/
m; o/ o/ p NHCOR.sup.5 1 p NHCOOR.sup.5 1 p COR.sup.5 1-2 o; p; o/p
COOR.sup.5 1-2 o; p; o/p CONR.sup.5R.sup.6 1-2 o; p; o/p CN 1 p
O.dbd.S(OR.sup.5).dbd.O 1 p O.dbd.S(R.sup.5).dbd.O 1 p
O.dbd.S(NR.sup.5R.sup.6).dbd.O 1 p R.sup.5OP(--OR.sup.6).dbd.O 1
p
[0060] The quinoxaline derivatives according to the invention are
outstandingly suitable as UV filter substances. As already
mentioned, the quinoxalines can be designed synthetically in such a
way that the presence of an additional chromophoric group gives
rise to UV-absorbent properties both in the UV-A and in the UV-B
region. Broad-band protection can thus be achieved. Furthermore,
the solubility of the substances in water or cosmetic oils can be
influenced through the choice of substituents.
[0061] Some UV-A and UV-B filter substances with which the
quinoxalines according to the invention can preferably be combined
chemically are listed below (Table 2). This selection is in no way
intended to be limiting. The combination can take place through
conventional chemical reactions. TABLE-US-00002 TABLE 2 Combined UV
filter Example 4-Aminobenzoic acid see formula VIII
Dimethoxyphenylglyoxalic acid 2,2',4,4'-Tetrahydroxybenzophenone
3,3,5-Trimethylcyclohexyl salicylate see formula IX
2,2'-Dihydroxy-4-methoxybenzophenone 5-Methyl-2-(1 -methylethyl)
2-aminobenzoate 3-Imidazol-4-ylacrylic acid and ethyl ester
4-Isopropylbenzyl salicylate
1-(4'-Isopropylphenyl)-3-phenylpropane-1,3-dione
3-Benzylidenebornan-2-one (3-benzylidenecamphor)
3-(4'-Methyl)benzylidenebornan-2-one see formula X
3(4'-Trimethylammonium)benzylidenebornan-2-one methylsulfate
1-(4'-tert-Butylphenyl)-3-(4-methoxyphenyl)propane- see formula Xl
1,3-dione (e.g. Eusolex .RTM. 9020)
3-(4'Sulfo)benzylidenebornan-2-one and salts
2-Hydroxy-4-methoxybenzophenone-5-sulfonic acid / Na salt
2-Ethylhexyl salicylate 2-Hydroxy-4-methoxy-4'-methylbenzophenone
2-Hydroxy-4-methoxybenzophenone 2-Isoamyl 4-methoxycinnamate
2-Ethylhexyl 4-methoxycinnamate 1-Glyceryl 4-aminobenzoate ##STR7##
Formula VIII ##STR8## Formula IX ##STR9## Formula X ##STR10##
Formula Xl
[0062] It is therefore particularly preferred in accordance with
the invention for at least one of the radicals selected from R and
R.sup.1 to R.sup.6 to correspond to a UV filter from Table 2 bonded
via a suitable functional group (preferably an ester, ether, amine,
imine, imide or amide function).
[0063] The invention also relates to the novel compounds of the
formula IV ##STR11## in which R.sup.1, R.sup.2 and R.sup.4 are as
defined in claim 1, and R is .sup.t-butyl or a phenyl ring, which
may be monosubstituted or polysubstituted by groups which are as
defined for R.sup.1 in claim 1, or one of the radicals selected
from R and R.sup.1, R.sup.2 and R.sup.4 corresponds to a UV filter
from Table 2 bonded via a suitable functional group, preferably an
ester, ether, amine, imine, imide or amide function, which are also
particularly preferably used.
[0064] Particular preference is given here to quinoxaline
derivatives of the formula VIII ##STR12## where R, R.sup.1 and
R.sup.2 are as defined above, R.sup.4 is H or a branched or
unbranched C1-20-alkyl radical, in which, if desired, one or more H
atoms may be replaced by Sub, Sub is as defined above, and R.sup.4
is preferably H, methyl, ethyl or ethyl or ethylhexyl, and R is
preferably a branched or unbranched C1-20-alkyl radical, in which,
if desired, one or more H atoms may be replaced by Sub. Particular
preference is given to compounds of the formula III in which R is
methyl, ethyl, isopropyl or tertiary-butyl. Particular preference
is furthermore given to
1-(2-ethylhexyl)-2-phenylimidazo[3,4-b]quinoxaline.
[0065] The quinoxaline derivatives of the formula IV according to
the invention can be prepared starting from
2,3-dichloroquinoxalines which are substituted by R.sup.1 and
R.sup.2 corresponding to the target-compound. A process of this
type is therefore a further subject-matter of the present
invention.
[0066] In a preferred variant, a chlorine atom in the
2,3-dichloroquinoxaline is replaced, in a first reaction step, by
an amino function. In a further reaction step, the second chlorine
atom is preferably replaced by --NH--R.sup.4.
[0067] In another, likewise preferred process variant, a chlorine
atom in the 2,3-dichloroquinoxaline is replaced by --NH--R.sup.4 in
a first reaction step, and the second chlorine atom is replaced by
an amino function in a second reaction step.
[0068] Ring closure to give the imidazoquinoxaline according to the
invention is then preferably carried out in both cases by reaction
with a suitably substituted benzaldehyde derivative.
[0069] The choice of suitable reaction conditions for these
reactions presents the person skilled in the art with no
difficulties at all. Suitable conditions are indicated in Example H
for an illustrative example (preparation of
1-(2-ethylhexyl)-2-phenylimidazo[3,4-b]quinoxaline).
[0070] If desired, the quinoxaline derivatives can also be combined
with any desired UV filter substances, which results in an
improvement in the protective performance (SPF boost) through
synergistic effects. Some UV-A and UV-B filter substances with
which the quinoxalines according to the invention can preferably be
combined are listed below. This selection is in no way intended to
be limiting. The combination can, besides by direct chemical
reaction (as shown above in Table 2), of course also take place
through physical combination with UV filters. In principle, all UV
filters are suitable for a combination. Particular preference is
given to UV filters whose physiological acceptability has already
been demonstrated. Substances are known from the specialist
literature both for UV-A and UV-B filters, for example
benzylidenecamphor derivatives, such as
[0071] 3-(4'-methylbenzylidene)-dl-camphor (for example
Eusolex.RTM. 6300), [0072] 3-benzylidenecamphor (for example
Mexoryl.RTM. SD), [0073] polymers of N-{(2 and
4)-[(2-oxoborn-3-ylidene)methyl]benzyl}acrylamide (for example
Mexoryl.RTM. SW), [0074]
N,N,N-trimethyl-4-(2-oxoborn-3-ylidenemethyl)anilinium
methylsulfate (for example Mexoryl.RTM. SK) or [0075]
.alpha.-(2-oxoborn-3-ylidene)toluene-4-sulfonic acid (for example
Mexoryl.RTM. SL), benzoyl- or dibenzoylmethanes, such as [0076]
-1'-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione (for
example Eusolex.RTM.9020) or [0077] -4-isopropyldibenzoylmethane
(for example Eusolex.RTM. 8020), [0078] benzophenones, such as
[0079] 2-hydroxy-4-methoxybenzophenone (for example Eusolex.RTM.
4360) or [0080] 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and
its sodium salt (for example Uvinul.RTM. MS-40), [0081]
methoxycinnamic acid esters, such as [0082] octyl methoxycinnamate
(for example Eusolex.RTM. 2292), [0083] isopentyl
4-methoxycinnamate, for example as a mixture of the isomers (for
example Neo Heliopan.RTM. E 1000), [0084] salicylate derivatives,
such as [0085] 2-ethylhexyl salicylate (for example Eusolex.RTM.
OS), [0086] 4-isopropylbenzyl salicylate (for example Megasol.RTM.)
or [0087] 3,3,5-trimethylcyclohexyl salicylate (for example
Eusolex.RTM. HMS), [0088] 4-aminobenzoic acid and derivatives, such
as [0089] 4-aminobenzoic acid, [0090] 2-ethylhexyl
4-(dimethylamino)benzoate (for example Eusolex.RTM. 6007), [0091]
ethoxylated ethyl 4-aminobenzoate (for example Uvinul.RTM. P25),
and further substances, such as [0092] 2-ethylhexyl
2-cyano-3,3-diphenylacrylate (for example Eusolex.RTM. OCR), [0093]
2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium and
triethanolamine salts (for example Eusolex.RTM. 232), [0094]
3,3'-(1,4-phenylenedimethylene)bis(7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-
-ylmethanesulfonic acid and its salts (for example Mexoryl.RTM. SX)
and [0095]
2,4,6-trianilino-(p-carbo-2'-ethylhexyl-1'-oxy)-1,3,5-triazine (for
example Uvinul.RTM. T 150).
[0096] The compounds mentioned in the list should only be regarded
as examples. It is of course also possible to use other UV
filters.
[0097] These organic UV filters are generally incorporated into
cosmetic preparations in an amount of from 0.5 to 10 percent by
weight, preferably 1-8%.
[0098] Further suitable organic UV filters are, for example, [0099]
2-(2H-benzotriazol-2-yl)-4-methyl-6-(2-methyl-3-(1,3,3,3-tetramethyl-1-(t-
rimethylsilyloxy)disiloxanyl)propyl)phenol (for example
Silatrizole.RTM.), [0100] 2-ethylhexyl
4,4'-[(6-[4-((1,1-dimethylethyl)aminocarbonyl)phenylamino]-1,3,5-triazine-
-2,4-diyl)diimino]bis(benzoate) (for example UV-Asorb.RTM. HEB),
[0101]
.alpha.-(trimethylsilyl)-co-[trimethylsilyl)oxy]poly[oxy(dimethyl
[and approximately 6% of
methyl[2-[p-[2,2-bis(ethoxycarbonyl]vinyl]phenoxy]-1-methyleneethyl]
and approximately 1.5% of
methyl[3-[p-[2,2-bis(ethoxycarbonyl)vinyl)phenoxy)propenyl) and
from 0.1 to 0.4% of (methylhydrogen]silylene]] (n.apprxeq.60) (CAS
No. 207 574-74-1) [0102]
2,2'-methylenebis(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)ph-
enol) (CAS No. 103 59745-1) [0103]
2,2'-(1,4-phenylene)bis)-1H-benzimidazole-4,6-disulfonic acid,
monosodium salt) (CAS No. 180 898-37-7) and [0104]
2,2'-(1,4-phenylene)bis)-1H-benzimidazole-5,5'-monosulfonic acid,
monosodium salt [0105]
2,4-bis{[4-(2-ethylhexyloxy)-2-hydroxylphenyl}-6-(4-methoxyphenyl)-1,3,5--
triazine (CAS No. 103 597-45-, 187 393-00-6).
[0106] These organic UV filters are generally incorporated into
cosmetic preparations in an amount of from 0.5 to 20 percent by
weight, preferably 1-15%. They are usually present in formulations
according to the invention in weight ratios of from 15:1 to 1:15,
preferably from 10:1 to 1:10 and particularly preferably from 5:1
to 1:5 to the quinoxaline derivatives of the formula 1.
[0107] Preferred compounds having UV-filtering properties are
3-(4'-methylbenzylidene)dl-camphor,
1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione,
4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octyl
methoxycinnamate, octyl methoxycinnamate, 3,3,5-trimethylcyclohexyl
salicylate, 2-ethylhexyl 4-(dimethylamino)benzoate, 2-ethylhexyl
2-cyano-3,3-diphenylacrylate, 2-phenylbenzimidazole-5-sulfonic acid
and its potassium, sodium and triethanolamine salts.
[0108] Conceivable inorganic UV filters are, for example, those
from the group consisting of titanium dioxides, such as, for
example, coated titanium dioxide (for example Eusolex.RTM. T-2000,
Eusolex.RTM. T-AQUA), zinc oxides (for example Sachtotec.RTM.),
iron oxides and also cerium oxides. Titanium oxide and zinc oxide
are preferably in the form of micronised inorganic pigments. These
inorganic UV filters are generally incorporated into cosmetic
preparations in an amount of from 0.5 to 20 percent by weight,
preferably 2-10%. They are usually present in formulations
according to the invention in weight ratios of from 25:1 to 1:25,
preferably from 10:1 to 1:10 and particularly preferably from 5:1
to 1:5 to the quinoxaline derivatives of the formula I.
[0109] The use according to the invention of the quinoxaline
derivatives has a further, interesting and advantageous aspect. The
combination with other UV filters often results in
photostabilisation of these UV fillers by the quinoxaline
derivative.
[0110] It is known that some UV filters which have advantageous
light-protection filter properties per se have the great
disadvantage of a certain instability to UV radiation.
[0111] For example, the dibenzoylmethane derivatives, such as
Eusolex 9020 (4-tbutyl-4'-methoxydibenzoylmethanes), are substances
which are exposed to photochemical decomposition. The photochemical
decomposition of this class of compounds follows a Norrish type I
acyl cleavage. The reaction products formed in the process are no
longer available as light-protection filter substances. Although
some proposed solutions have already been indicated in the prior
art, there nevertheless continues to be a demand for simple and
effective ways of effectively countering this photolytic
decomposition.
[0112] The quinoxaline derivatives described here are outstandingly
suitable for this purpose, in particular combination with Eusolex
9020 results in considerably improved photostabilisation of the
substance.
[0113] In preferred embodiments of the invention, both the
compounds of the formula I according to the invention and the
conventional UV filters mentioned above can be encapsulated in
capsules. It is particularly preferred to encapsulate UV filters
which are either not stable on storage in the formulation or tend
to penetrate the skin on application. The encapsulation here can be
carried out by conventional methods known from the literature.
Suitable capsule materials are organic and inorganic polymers. It
is particularly preferred to include the UV filters, and in
particular also the quinoxaline derivatives of the formula I
according to the invention, in oxide capsules, preferably silica
capsules, which are preferably produced in a sol-gel process, as
described in the international application WO 00/09652.
[0114] In accordance with the invention, the UV light-protection
filters described here can in each case be used alone or naturally
also in combination, which is preferred, in sunscreens. They can be
combined with UV-B/A chromophores, for example all filters approved
and known worldwide, for improving the protective performance (SPF
boost) through synergistic effects. They can preferably be employed
in combination both with inorganic and with organic UV-A and UV-B
filters or mixtures thereof.
[0115] Through combination of one or more compounds of the formula
I with further UV filters, the protective action against harmful
effects of UV radiation can be optimised.
[0116] It is furthermore possible and advantageous to combine the
preparations according to the invention with antioxidants. A
combination of this type then exhibits both a protective action as
antioxidant and also against burns due to UV radiation. A
protective action against oxidative stress or against the action of
free radicals can thus also be achieved.
[0117] The invention therefore also relates to the use of a
compound of the formula I according to claim 1 in combination with
antioxidants in cosmetic or pharmaceutical preparations.
[0118] The present invention therefore also relates to cosmetic and
pharmaceutical preparations which comprise one or more of the
compounds of the formula I, optionally in combination with further
light-protection agents or antioxidants.
[0119] The invention also relates to a method for protecting the
skin and natural or sensitised hair against solar radiation, in
which an effective amount of at least one compound of the formula I
in a cosmetic preparation is applied to the skin or the hair.
"Sensitised hair" is taken to mean hair which has been subjected,
for example, to permanent-wave treatment, a dyeing process or a
bleaching process.
[0120] The filters according to the invention for protection
against UV-A and UV-B radiation can in each case be incorporated
into cosmetic preparations in concentrations of from 0.1 to 20% by
weight, preferably from 1 to 15% by weight. In this way, it is
possible to prepare preparations in which up to 100% of the
light-protection filters employed are the UV filters described
here. These are substances which are dissolved, dispersed or
emulsified in a simple manner in water and oils, depending on the
substituents on the skeleton.
[0121] The preparations according to the invention may in addition
comprise further conventional skin-protecting or skincare active
ingredients. These may in principle be any active ingredients known
to the person skilled in the art.
[0122] Particularly preferred active ingredients are
pyrlmidinecarboxylic acids and/or aryl oximes, as well as
coumaranone derivatives.
[0123] Pyrimidinecarboxylic acids occur in halophilic
microorganisms and play a role in osmoregulation of these organisms
(E. A. Galinski et al., Eur. J. Biochem., 149 (1985) pages
135-139). Of the pyrimidinecarboxylic acids, particular mention
should be made here of ectoin
((S)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and
hydroxyectoin
((S,S)-1,4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylic
acid and their derivatives. These compounds stabilise enzymes and
other biomolecules in aqueous solutions and organic solvents.
Furthermore, they stabilise, in particular, enzymes against
denaturing conditions, such as salts, extreme pH values,
surfactants, urea, guanidinium chloride and other compounds.
[0124] Ectoin and ectoin derivatives, such as hydroxyectoin, can
advantageously be used in medicaments. In particular, hydroxyectoin
can be employed for the preparation of a medicament for the
treatment of skin diseases. Other areas of application of
hydroxyectoin and other ectoin derivatives are typically in areas
in which, for example, trehalose is used as additive. Thus, ectoin
derivatives, such as hydroxyectoin, can be used as protectant in
dried yeast and bacteria cells. Pharmaceutical products, such as
nonglycosylated, pharmaceutical active peptides and proteins, for
example t-PA, can also be protected with ectoin or its
derivatives.
[0125] Of the cosmetic applications, particular mention should be
made of the use of ectoin and ectoin derivatives for the care of
aged, dry or irritated skin. Thus, European Patent Application
EP-A-0 671 161 describes, in particular, that ectoin and
hydroxyectoin are employed in cosmetic preparations, such as
powders, soaps, surfactant-containing cleansing products,
lipsticks, rouge, makeups, care creams and sunscreen
preparations.
[0126] Preference is given here to the use of a
pyrimidinecarboxylic acid of the following formula, ##STR13## in
which R.sup.1 is a radical H or C1-8-alkyl, R.sup.2 is a radical H
or C1-4-alkyl, and R.sup.3, R.sup.4, R.sup.5 and R.sup.5 are each,
independently of one another, a radical from the group consisting
of H, OH, NH.sub.2 and C1-4-alkyl. Preference is given to the use
of pyrimidinecarboxylic acids in which R.sup.2 is a methyl or ethyl
group, and R.sup.1 or R.sup.5 and R.sup.6 are H. Particular
preference is given to the use of the pyrimidinecarboxylic acids
ectoin ((S)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic
acid) and hydroxyectoin ((S,
S)-1,4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylic
acid). The preparations according to the invention preferably
comprise pyrimidinecarboxylic acids of this type in amounts of up
to 15% by weight.
[0127] Of the aryl oximes, preference is given to the use of
2-hydroxy-5-methyllaurophenone oxime, which is also known as HMLO,
LPO or F5. Its suitability for use in cosmetic compositions is
disclosed, for example, in DE-A-41 16 123. Preparations which
comprise 2-hydroxy-5-methyllaurophenone oxime are accordingly
suitable for the treatment of skin diseases which are accompanied
by inflammation. It is known that preparations of this type can be
used, for example, for the therapy of psoriasis, various forms of
eczema, irritative and toxic dermatitis, UV dermatitis and further
allergic and/or inflammatory diseases of the skin and integumentary
appendages. Preparations according to the invention which, in
addition to the compound of the formula I, additionally comprise an
aryl oxime, preferably 2-hydroxy-5-methyllaurophenone oxime,
exhibit surprising antiinflammatory suitability. The preparations
here preferably comprise from 0.01 to 10% by weight of the aryl
oxime, it being particularly preferred for the preparation to
comprise from 0.05 to 5% by weight of aryl oxime.
[0128] Coumaranone derivatives which may advantageously be present
in the preparations according to the invention are compounds of the
formula ##STR14## in which --X-- is a single bond, --CH.sub.2--,
.dbd.CH--, --C(O)--, .dbd.C(OR.sup.5)--, --C(NR.sup.5)--,
--CH(NR.sup.5R.sup.6)-- or --CH(OR.sup.5)--, and R.sup.1, R.sup.2,
R.sup.5, R.sup.4, R.sup.5, and R.sup.6 may be identical or
different and are, independently of one another, [0129] H [0130]
straight-chain or branched C.sub.1- to C.sub.1-2-alkyl and/or
alkylcarbonyl groups, [0131] straight-chain or branched C.sub.3- to
C.sub.1-2-alkenyl and/or -alkenylcarbonyl groups, [0132]
straight-chain or branched C.sub.1- to C.sub.1-2-hydroxyalkyl
groups, in which the hydroxyl group may be bonded to a primary or
secondary carbon atom of the chain, and furthermore the alkyl chain
may also be interrupted by oxygen, [0133] C.sub.3- to
C.sub.10-cycloalkyl and/or cycloalkylcarbonyl groups and C.sub.3-
to C.sub.12-cycloalkenyl and/or cycloalkenylcarbonyl groups, in
which each of the rings may also be bridged by --(CH.sub.2).sub.n--
groups, where n=from 1 to 3, [0134] aryl and/or arylcarbonyl
groups, [0135] heteroaryl and/or heteroarylcarbonyl groups, where
these groups may be substituted by alkyl, hydroxyl, alkoxy, amino,
mono- and dialkylamino, sulfonic acid, carboxyl and/or halogen
groups, [0136] mono- and/or oligoglycosyl radicals, ##STR15##
##STR16## in which Me is a proton or an alkali metal ion, in
particular a sodium or potassium ion.
[0137] The radicals can thus be bonded to the parent structure as
ethers or as esters. Compounds of this type are described in the
German patent application DE 10003785.2. Compositions which
comprise coumaranone derivatives of this type have a particularly
gentle action on the skin, which these compounds exhibit an
antioxidant and free-radical-scavenging action.
[0138] The parent structure
4,6,3',4'-tetrahydroxybenzyl-3-coumaranone has very good
properties. This compound conforms to the above formula, in which
X.dbd.--CH.sub.2--, and
R.sup.1.dbd.R.sup.2.dbd.R.sup.3.dbd.R.sup.4.dbd.H. The solubility
of this compound in water can be improved by selecting, for
example, the radicals R.sup.1, R.sup.2, R.sup.3 and R.sup.4 as
sulfate or phosphate groups. A mixture of mono-, di- and
trisulfate, which is referred to below as "sulfated coumaranone,",
is particularly suitable. Particular emphasis should be placed on
the trisulfate (X.ident.CH.sub.2--;
R.sup.1.dbd.R.sup.3.dbd.R.sup.4.dbd.SO.sub.3Me, R.sup.2.dbd.H),
which is represented by the following formula. ##STR17##
[0139] All compounds or components which can be used in the
preparations are either known and commercially available or can be
synthesised by known processes.
[0140] The cosmetic and pharmaceutical preparations comprising
light-protectibn agents are generally based on a vehicle which
comprises at least one oil phase. However, preparations on a purely
aqueous basis are also possible in the case of the use of compounds
having hydrophilic substituents. Accordingly, oils, oil-in-water
and water-in-oil emulsions, creams and pastes, lip protection
compositions or fat-free gels are possible.
[0141] Sunscreen preparations of this type can thus be in liquid,
pasty or solid form, for example as water-in-oil creams,
oil-in-water creams and lotions, W/O/W systems or O/W/O systems,
aerosol foam creams, gels, oils, fat sticks, powders, sprays or
alcoholic/aqueous lotions. They can furthermore also be formulated
as micronised systems or as PIT (phase inversion temperature)
emulsions.
[0142] Conventional oil components in cosmetics are, for example,
paraffin oil, glyceryl stearate, isopropyl myristate, diisopropyl
adipate, acetylstearyl 2-ethylhexanoate, hydrogenated
polyisobutene, Vaseline, caprylic acid/capric acid triglycerides,
microcrystalline wax, lanolin, mineral oils, mineral waxes, esters
of fatty acids with alcohols having a low carbon number, for
example with isbpropanol, propylene glycol or glycerol, alkyl
benzoates, silicone oils, such as dimethylpolysiloxanes,
diethylpolysiloxanes, diphenylpolysiloxanes, and stearic acid.
[0143] The preparations may comprise cosmetic adjuvants which are
usually used in preparations of this type, such as, for example,
thickeners, softeners, moisturisers, surface-active agents,
emulsifiers, preservatives, antifoams, perfumes, fats and waxes,
lanolin, propellants, stabilisers, antioxidants, bactericides, dyes
and/or pigments which colour the composition itself or the skin,
and other ingredients usually used in cosmetics.
[0144] Suitable emulsifiers are preferably known W/O and in
addition also O/W emulsifiers, such as, for example, polyglycerol
esters, sorbitan esters or partially esterified glycerides. Typical
examples of fats are glycerides; waxes which should be mentioned
are, inter alia, beeswax, carnauba wax, paraffin wax or microwaxes,
optionally in combination with hydrophilic waxes. Stabilisers which
can be employed are metal salts of fatty acids, such as, for
example: magnesium stearate, aluminium stearate and/or zinc
stearate. Suitable thickeners are, for example, crosslinked
polyacrylic acids and derivatives thereof, polysaccharides, in
particular xanthan gum, guar-guar, agar-agar, alginates and
tyloses, carboxymethylcellulose and hydroxyethylcellulose,
furthermore fatty alcohols, monoglycerides and fatty acids,
polyacrylates, polyvinyl alcohol and polyvinylpyrrolidone. It is
furthermore also possible to add plant extracts, protein
hydrolysates and vitamin complexes.
[0145] Antioxidants which can be used are, for example, amino
acids, imidazoles, peptides, carotenoids, .alpha.-hydroxyacids,
unsaturated fatty acids, vitamin A, C and/or E, and suitable
derivatives of these substances.
[0146] There are many proven substances known from the specialist
literature which can be used as antioxidants, for example amino
acids (for example glycine, histidine, tyrosine, tryptophan) and
derivatives thereof, imidazoles (for example urocanic acid) and
derivatives thereof, peptides, such as D,L-carnosine, D-carnosine,
L-carnosine and derivatives thereof (for example anserine),
carotenoids, carotenes (for example .alpha.-carotene,
.beta.-carotene, lycopene) and derivatives thereof, chlorogenic
acid and derivatives thereof, lipoic acid and derivatives thereof
(for example dihydrolipoic acid), aurothioglucose, propylthiouracil
and other thiols (for example thioredoxin, glutathione, cysteine,
cystine, cystamine and the glycosyl, N-acetyl, methyl, ethyl,
propyl, amyl, butyl and lauryl, palmitoyl, oleyl, .gamma.-linoleyl,
cholesteryl and glyceryl esters thereof), and salts thereof,
dilauryl thiodipropionate, distearyl thiodipropionate,
thiodipropionic acid and derivatives thereof (esters, ethers,
peptides, lipids, nucleotides, nucleosides and salts), and
sulfoximine compounds (for example buthionine sulfoximines,
homocysteine sulfoximine, buthionine sulfones, penta-, hexa- and
heptathionine sulfoximine) in very low tolerated doses (for example
pmol to .mu.mol/kg), and also (metal) chelating agents, (for
example .alpha.-hydroxy fatty acids, palmitic acid, phytic acid,
lactoferrin), .alpha.-hydroxy acids (for example citric acid,
lactic acid, malic acid), humic acid, bile acid, bile extracts,
bilirubin, biliverdin, EDTA, EGTA and derivatives thereof,
unsaturated fatty acids and derivatives thereof, vitamin C and
derivatives (for example ascorbyl palmitate, magnesium ascorbyl
phosphate, ascorbyl acetate), tocopherols and derivatives (for
example vitamin E acetate), vitamin A and derivatives (for example
vitamin A palmitate), and coniferyl benzoate of benzoin resin,
rutinic acid and derivatives thereof, .alpha.-glycosyl rutin,
ferulic acid, furfurylideneglucitol, carnosine,
butylhydroxytoluene, butylhydroxyanisole, nordohydroguaiaretic
acid, trihydroxybutyrophenone, quercetin, uric acid and derivatives
thereof, mannose and derivatives thereof, zinc and derivatives
thereof (for example ZnO, ZnSO4), selenium and derivatives thereof
(for example selenomethionine), stilbenes and derivatives thereof
(for example stilbene oxide, transstilbene oxide).
[0147] Mixtures of antioxidants are likewise suitable for use in
the cosmetic preparations according to the invention. Known and
commercial mixtures are, for example, mixtures comprising, as
active ingredients, lecithin, L-(+)-ascorbyl palmitate and citric
acid (for example Oxynex.RTM. AP), natural tocopherols,
L-(+)ascorbyl palmitate, L-(+)-ascorbic acid and citric acid (for
example (for example Oxynex.RTM. K LIQUID), tocopherol extracts
from natural sources, L-(+)-ascorbyl palmitate, L-(+)-ascorbic acid
and citric acid (for example Oxynex.RTM. L LIQUID),
DL-.alpha.-tocopherol, L-(+)-ascorbyl palmitate, citric acid and
lecithin (for example Oxynex.RTM. LM) or butylhydroxytoluene (BHT),
L-(+)-ascorbyl palmitate and citric acid (for example Oxynex.RTM.
2004).
[0148] The quinoxaline derivatives of the formula I are usually
present in the formulations according to the invention in weight
ratios to the antioxidants of from 10,000:1 to 1:5, preferably from
500:1 to 1:2 and particularly preferably from 50:1 to 1:1.
[0149] The preparations according to the invention may comprise
vitamins as further ingredients. The cosmetic preparations
according to the invention preferably comprise vitamins and vitamin
derivatives selected from vitamin A, vitamin A propionate, vitamin
A palmitate, vitamin A acetate, retinol, vitamin B, thiamine
chloride hydrochloride (vitamin B.sub.1), riboflavin (vitamin
B.sub.2), nicotinamide, vitamin C (ascorbic acid), vitamin D,
ergocalciferol (vitamin D.sub.2), vitamin E, DL-.alpha.-tocopherol,
tocopherol E acetate, tocopherol hydrogensuccinate, vitamin
K.sub.1, esculin (vitamin P active ingredient), thiamine (vitamin
B.sub.1), nicotinic acid (niacin), pyridoxine, pyridoxal,
pyridoxamine, (vitamin B.sub.6), panthothenic acid, biotin, folic
acid and cobalamine (vitamin B.sub.12), particularly preferably
vitamin A palmitate, vitamin C, DL-.alpha.-tocopherol, tocopherol E
acetate, nicotinic acid, panthothenic acid and biotin.
[0150] The aqueous phase of the preparations according to the
invention optionally advantageously comprise alcohols, diols or
polyols having a low carbon number, and ethers thereof, preferably
ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol,
ethylene glycol monoethyl or monobutyl ether, or analogous
products, furthermore alcohols such as ethanol, isopropanol,
1,2-propanediol and, in particular, one or more thickeners, such
as, for example, silicon dioxide, aluminium silicates,
polysaccharides or derivatives thereof, for example hyaluronic
acid, xanthan gum or hydroxypropylmethylcellulose, or a
polyacrylate from the group consisting of the so-called
Carbopols.
[0151] Conventional film formers are, for example, hydrocolloids,
such as chitosan, microcrystalline chitosan or quaternary chitosan,
polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymers,
polymers from the acrylic acid series, quaternary cellulose
derivatives and similar compounds. Examples of suitable
preservatives are formaldehyde solutions, p-hydroxybenzoate or
sorbic acid. Suitable pearlescent agents are, for example,
glycoldistearic acid esters, such as ethylene glycol distearate,
but also fatty acids and fatty acid monoglycol esters. Dyes which
can be used are the substances which are suitable and approved for
cosmetic purposes, as compiled, for example, in the publication
"Kosmetische Farbemittel" [Cosmetic Colorants] by the Dye
Commission of the German Research Society, published in Verlag
Chemie, Weinheim, 1984. These dyes are usually employed in
concentrations of from 0.001 to 0.1% by weight, based on the
mixture as a whole.
[0152] If desired, the sunscreens according to the invention may
also comprise one or more chemical substances having self-tanning
properties.
[0153] Chemical substances having self-tanning properties which can
be employed are all natural and synthetic substances known to the
person skilled in the art which are suitable for the preparation of
cosmetic preparations. These may be either vegetable extracts or
synthetic self-tanning agents, such as, for example,
dihydroxyacetone or .alpha.-ketols.
[0154] If the composition according to the invention is intended to
protect natural or sensitised hair against sunlight, it can be in
the form of a rinse-out shampoo, lotion, gel or emulsion, the
preparation in question being applied before or after shampooing,
before or after colouring or bleaching or before or after permanent
waving; or the composition is in the form of a lotion or gel for
styling and treatment, in the form of a lotion or gel for brushing
or blow-waving, in the form of a hair lacquer, hair spray, aerosol
foam cream, permanent waving composition, dye or bleach for the
hair. In addition to the light-protection filters according to the
invention (VIS and/or IR filters) or the combination of
light-protection filters according to the invention, this
composition may also comprise various adjuvants used in this type
of composition, such as surfactants, thickeners, polymers,
softeners, preservatives, foam stabilisers, electrolytes, organic
solvents, silicone derivatives, oils, waxes, anti-grease agents,
dyes and/or pigments which colour the composition itself or the
hair, or other ingredients usually used for hair care.
[0155] Further typically cosmetic use forms are also lipsticks,
lip-care sticks, mascara, eyeliner, eyeshadow, rouge, powder,
emulsion and wax make-up, and sunscreen, pre-sun and after-sun
preparations.
[0156] The light-protection filters according to the invention can
be incorporated directly into cosmetic preparations without further
preparatory measures.
[0157] These substances furthermore offer the great advantage of
exhibiting no toxic or allergic reactions with the skin.
[0158] The light-protection preparations can advantageously
comprise in accordance with the invention, as already described
above, further UV filter substances, where the total amount of the
filter substances is, for example, from 0.1% by weight to 30% by
weight, preferably from 0.5 to 10% by weight, in particular from 1
to 6% by weight, based on the total weight of the preparations.
[0159] The preparations according to the invention can furthermore
also be used as pharmaceutical compositions for preventative
treatment of inflammation and allergies of the skin and also in
certain cases for the prevention of certain types of cancer. The
pharmaceutical composition according to the invention can be
administered orally or topically. For oral administration, the
pharmaceutical preparation is in the form of, inter alia,
pastilles, gelatine capsules, coated tablets, as a syrup, solution,
emulsion or suspension. Topical application is carried out, for
example, as an ointment, cream, gel, spray, solution or lotion.
[0160] The cosmetic and pharmaceutical preparations according to
the invention can be prepared with the aid of methods which are
well known to the person skilled in the art.
[0161] The properties of compounds of the formula I should likewise
be regarded as positive for use in foods, as food supplements, as
dietary agent or as functional food. The further explanations given
for foods logically also apply to food supplements and functional
foods.
[0162] The foods which can be enriched in accordance with the
present invention with one or more of the compounds according to
the invention include all materials which are suitable for
consumption by animals or consumption by humans, for example
vitamins and provitamins thereof, fats, minerals or amino acids.
(The foods may be solid, but also liquid, i.e. in the form of a
beverage). Foods which can be enriched with one or more compounds
of the formula I in accordance with the present invention are, for
example, also foods which originate from a single natural source,
such as, for example, sugar, unsweetened juice, squash or puree of
a single plant species, such as, for example, unsweetened apple
juice (for example also a mixture of different types of apple
juice), grapefruit juice, orange juice, apple compote, apricot
squash, tomato juice, tomato sauce, tomato puree, etc. Further
examples of foods which can be enriched with one or more compounds
of the formula I in accordance with the present invention are corn
or cereals from a single plant species and materials produced from
plant species of this type, such as, for example, cereal syrup, rye
flour, wheat flour or oatbran. Mixtures of foods of this type are
also suitable for being enriched in accordance with the present
invention with one or more of the compounds according to the
invention, for example multivitamin preparations, mineral mixtures
or sweetened juice. As further examples of foods, mention may be
made of food preparations, for example prepared cereals, biscuits,
mixed drinks, foods prepared especially for children, such as
yoghurt, diet foods, low-calorie foods or animal feeds.
[0163] The foods which can be enriched in accordance with the
present invention with one or more compounds of the formula I thus
include all edible combinations of carbohydrates, lipids, proteins,
inorganic elements, trace elements, vitamins, water or active
metabolites of plants and animals.
[0164] The foods which can be enriched in accordance with the
present invention with one or more compounds of the formula I are
preferably administered orally, for example in the form of meals,
pills, tablets, capsules, powders, syrup, solutions or
suspensions.
[0165] These enriched foods according to the invention can be
prepared using techniques which are well known to the person
skilled in the art.
[0166] Even without further comments, it is assumed that a person
skilled in the art will be able to utilise the above description in
its broadest scope. The preferred embodiments should therefore
merely be regarded as descriptive disclosure which is absolutely
not limiting in any way.
[0167] The following examples are intended to illustrate the
present invention without limiting it. All amount data, proportions
and percentages are, unless stated otherwise, based on the weight
and the total amount or the total weight of the preparations.
[0168] The complete disclosure content of all applications and
publications mentioned above and below are incorporated into this
application by way of reference.
PREPARATION EXAMPLES
Example A
Synthesis of 1H-pyrazolo[3,4-b]quinoxalines (A and B
[0169] ##STR18##
[0170] Preparation: 320 mg of 2-carbonyl-3-chloroquinoxaline (1.55
mmol) and hydrazine hydrate (194 mg, 3.88 mmol) are heated at the
boil for 72 hours in THF.
[0171] The solvent is removed by distillation, and water (50 ml)
and saturated sodium hydrogencarbonate solution (10 ml) are added
to the residue. The mixture is extracted with chloroform
(3.times.100 ml), and the combined organic phases are dried over
magnesium sulfate. The solvent is removed by distillation, and
recrystallisation of the residue from cyclohexane/tert-butyl methyl
ether gives 3-methyl-1H-pyrazoloquinoxaline and
3-phenyl-1H-pyrazoloquinoxaline in a yield of 80% and 97%
respectively. TABLE-US-00003 Characterisation of
3-methyl-1H-pyrazolo[3,4-b]quinoxaline (A) Melting point:
225.degree. C. 300MHz .sup.1H-NMR(CDCl.sub.3): .delta. = 13.55 (s
br., 1H, --NH, exchangeable with D.sub.2O) 8.19-7.71 (m, 4H,
hetaryl arom.) 2.66 (s, 3H, CH.sub.3) 75MHz
.sup.13C-NMR(CDCl.sub.3): .delta. = 143.76 (quat. C) 142.20 (quat.
C) 140.94 (quat. C) 139.79 (quat. C) 135.59 (quat. C) 130.46 (tert.
C) 129.80 (tert. C) 128.16 (tert. C) 128.24 (tert. C) 11.43
(--CH.sub.3) MS(70eV):m/e(%) = 185(13)[M.sup.++1],
184(100)[M.sup.+], 183(12), 143(40), 116(20), 102(10), 90(10)
C.sub.10H.sub.8N.sub.4(184.20g/mol): Calc. [%] C 65.21 H 4.38 N
30.42 Found [%] C 64.92 H 4.36 N 30.23 Characterisation of
3-phenyl-1H-pyrazolo[3,4-b]quinoxaline (B) Melting point:
251.degree. C. 300MHz .sup.1H-NMR(CDCl.sub.3): .delta. = 14.35 (s
br., 1H, NH, exchangeable with D.sub.2O) 8.63-7.35 (m, 4H, hetaryl,
5H, phenyl) 8.31-8.63 (m.sub.c, 4H, hetaryl arom.) 7.35-7.89
(m.sub.c, 5H, arom.) 75MHz .sup.13C-NMR(CDCl.sub.3): .delta. =
144.27 (quat. C) 141.61 (quat. C) 140.88 (quat. C) 140.50 (quat. C)
134.62 (quat. C) 133.64 (quat. C) 131.00 (quat. C) 130.11 (quat. C)
128.83 (3 .times. tert. C) 128.40 (tert. C) 128.01 (tert. C) 126.24
(2 .times. tert. C) MS(70eV):m/e(%) = 247(18)[M++1], 246(100)[M+],
245(15), 219(17), 143(18), 116(17), 89(10), 58(10)
C.sub.15H.sub.10N.sub.4(246.27g/mol): Calc. [%] C 73.16 H 4.09 N
22.75 Found [%] C 73.22 H 4.18 N 22.58
Example B
Synthesis of N-arylprrolo[2,3-b]quinoxalines
[0172] ##STR19##
[0173] Preparation: 1.05 mmol of the aromatic amine are added to a
solution of 1.00 mmol of the 2-alkynyl-chloroquinoxaline in a polar
solvent (anhydrous) (R.sup.1.dbd.H or Ph; Si(iPr).sub.3: THF), and
the mixture is refluxed for 2-12 hours. The solid which
precipitates during the reaction or due to evaporation of the
solution is filtered off and purified by recrystallisation from
ethanol/ethyl acetate or by column chromatography on silica gel
using cyclohexane/ethyl acetate (1:1). The pyrroloquinoxalines are
obtained in yields of 53-88%. TABLE-US-00004 Characterisation of
N-[4(t-butoxycarbonyl)phenyl]-2-phenyl[2,3-b]pyrroloquinoxaline (A)
IR(KBr): Wavenumber[cm.sup.-1] = 3132 (.nu.(N--R), NR.sub.2) 3065
(.nu.(C--H), Ph) 2973 (.nu.(C--H), t-butyl) 1710 (.nu.(C.dbd.O),
CO.sub.2R) 1617 (.nu.(C.dbd.C), Ph) 1499 (.nu.(C.dbd.C), Ph) 1341
((skeleton), Ph) 1308 ((skeleton), Ph) 792 (.gamma.(C--H), Ph) 762
(.gamma.(C--H), Ph) 300MHz .sup.1H-NMR(CDCl.sub.3): .delta. =
8.17-8.20 (m, 1H, hetaryl arom.) 8.03-8.08 (m, 1H, hetaryl arom.)
7.99-8.02 (m, 2H, arom.) 7.73-7.78 (m, 2H, hetaryl arom.) 7.54-7.57
(m, 2H, arom.) 7.43-7.49 (m, 5H, arom.) 7.30 (s, 1H, hetaryl arom.)
1.58 (s, 9H, C.sub.4H.sub.9) 75MHz .sup.13C-NMR(CDCl.sub.3):
.delta. = 166.64 (C.sub.quat, CO.sub.2R) 150.89 (C.sub.quat, arom.)
143.71 (C.sub.quat, arom.) 142.65 (C.sub.quat, arom.) 140.80
(C.sub.quat, arom.) 139.59 (C.sub.quat, arom.) 138.50 (C.sub.quat,
arom.) 130.11 (C--H, arom.) 129.83 (C--H, arom.) 129.58 (C--H,
arom.) 129.01 (C--H, arom.) 128.68 (C--H, arom.) 128.44 (C--H,
arom.) 128.07 (C--H, arom.) 127.98 (C--H, arom.) 127.24 (C--H,
arom.) 102.06 (C-3, pyrrole) 51.43 (C(CH.sub.3).sub.3) 27.67
(C(CH.sub.3).sub.3) MS(70eV):m/e(%) = 422(16)[M.sup.++1],
421(58)[M.sup.+], 406(2), 360(100), 349(9), 321(37), 295(2),
218(1), 191(2), 174(4), 137(2), 128(3), 120(5), 102(4), 91(2),
76(4) Characterisation of
N-[4-(acetyl)phenyl]-2-(triisopropyl)silylpyrrolo[2,3-
b]-quinoxaline (B) IR(KBr): Wavenumber[cm.sup.-1] = 3183
(.nu.(N--R), NR2) 3046 (.nu.(C--H), Ph) 1697 (.nu.(C.dbd.O), COCH3)
1643 (.nu.(C.dbd.C), Ph) 1597 (.nu.(C.dbd.C), Ph) 1583
(.nu.(C.dbd.C), Ph) 1347 ((skeleton), Ph) 1282 ((skeleton), Ph) 841
(.gamma.(Si--C), SiR3) 755 (.gamma.(C--H), Ph) 300MHz
.sup.1H-NMR(CDCl3): .delta. = 8.32 (m, 1H, hetaryl arom.) 8.05-8.08
(m, 1H, hetaryl arom.) 7.98-8.01 (m, 2H, arom.) 7.71-7.77 (m, 2H,
hetaryl arom.) 7.56-7.59 (m, 2H, arom.) 7.25 (s, 1H, hetaryl arom.)
2.14 (s, 3H, CH3) 1.35 (sep, 3H, CH) 1.13 (s, 9H, CH3) 1.09 (d, 9H,
CH3) MS(70eV):m/e(%) = 443(3)[M+], 373(2), 344(1), 303(43),
301(100), 286(1), 261(63), 259(25), 245(7), 231(68), 217(7),
195(11), 181(8), 153(7), 122(19), 103(43), 93(13), 79(6) HRMS(high
Calc. for: 443, 2447 resolution mass) Found for: 443, 2446 (El)
(C.sub.27H.sub.33N.sub.3OSi)[M.sup.+] Characterisation of
4-[N-(pyrrolo[2,3-b]quinoxaline)]benzoic acid (C) IR(KBr):
Wavenumber[cm.sup.-1] = 3133 (.nu.(N--R), NR.sub.2) 3056
(.nu.(C--H), Ph) 1710 (.gamma.(C.dbd.O)) 1611 (.gamma.(C.dbd.C),
Ph) 1493 (.gamma.(C.dbd.C), Ph) 1414 ((skeleton), Ph) 1348
((skeleton), Ph) 76 2(.gamma.(C--H), Ph) MS(70eV):m/e(%) =
365[M.sup.+](100), 364(61), 319(37), 262(7), 217(2), 183(6),
102(9), 90(8), 65(12), 28(7) 300MHz .sup.1H-NMR(DMSO): .delta. =
8.17 (m.sub.c, 1H, hetaryl arom.) 8.05-8.08 (m.sub.c, 2H, arom.)
7.99 (m.sub.c, 1H, hetaryl arom.) 7.73-7.77 (m.sub.c, 2H, hetaryl
arom.) 7.56-7.57 (m.sub.c, 1H, arom.) 7.53 (m.sub.c, 1H, arom.)
7.42-7.48 (m.sub.c, 1H, arom.) 7.22 (s, 1H, hetaryl arom.)
.sup.13C-NMR(DMSO): .delta. = 166.65 (C.dbd.O) 150.94 (C.sub.quat,
arom.) 142.61 (C.sub.quat, arom.) 140.74 (C.sub.quat, arom.) 139.59
(C.sub.quat, arom.) 138.49 (C.sub.quat, arom.) 131.13 (C--H, arom.)
130.12 (C--H, arom.) 129.81 (C--H, arom.) 129.59 (C--H, arom.)
129.01 (C--H, arom.) 128.67 (C--H, arom.) 128.44 (C--H, arom.)
127.99 (C--H, arom.) 127.27 (C--H, arom.) 102.02 (C-3, pyrrole)
Characterisation of 2-(triisopropyl)silylpyrrolo[2,3-b]quinoxaline
(D) Wavenumber[cm-1] = 3467 cm.sup.-1 (.nu.(NH), NR.sub.2) 3138
(.nu.(C--H), hetaryl) 2967 (.nu.(C--H), alkyl) 1637
(.gamma.(C.dbd.C), hetaryl) 1558 (.gamma.(C.dbd.C), hetaryl) 1440
(.gamma.(C.dbd.C), hetaryl) 1387 ((skeleton), hetaryl) 1249
((skeleton), hetaryl) 880 (.gamma.(Si--C), SiR.sub.3) 762
(.gamma.(C--H), hetaryl) MS(70eV):m/e(%) = 325[M.sup.+](42),
282(100), 254(20), 240(18), 226(16), 212(24), 196(5), 181(1),
153(3), 113(11), 84(16), 74(6), 43(7) 300MHz
.sup.1H-NMR(CDCl.sub.3): .delta. = 7.68-7.80 (m.sub.c, 1H, hetaryl
arom.) 7.51-7.56 (m.sub.c, 2H, hetaryl arom.) 7.35-7.40 (m.sub.c,
1H, hetaryl arom.) 7.09 (s, 1H, hetaryl arom.) Characterisation of
N-[4-(acetyl)phenyl]pyrrolo[2,3-b]quinoxaline (E) IR(KBr):
Wavenumber[cm.sup.-1] = 3131 (.nu.(NH), NR.sub.2) 3052 (.nu.(C--H),
Ph) 1690 (.gamma.(C.dbd.O), COCH.sub.3) 1611 (.gamma.(C.dbd.C), Ph)
1499 (.gamma.(C.dbd.C), Ph) 1420 ((skeleton), Ph) 1348 ((skeleton),
Ph) 848 (.gamma.(Si--C), SiR.sub.3) 782 (.nu.(C--H), Ph)
MS(70eV):m/e(%) = 364[M.sup.++1](35), 363[M.sup.+](100),
362[M.sup.+-1](46), 348(9), 320(69), 294(5), 174(5), 127(12),
84(13), 70(48), 43(34) 300MHz .sup.1H-NMR(CDCl.sub.3): .delta. =
8.36 (m.sub.c, 1H, hetaryl arom.) 8.04-8.08 (m.sub.c, 3H, hetaryl
arom.) 7.69-7.70 (m.sub.c, 2H, arom.) 7.50-7.52 (m.sub.c, 2H,
arom.) 7.38-7.42 (m.sub.c, 5H, arom.) 6.82 (s, 1H, hetaryl arom.)
2.64 (s, 3H, CH.sub.3) 300MHz .sup.13C-NMR(CDCl.sub.3): .delta. =
197.03 (C.sub.quat, arom.) 151.41 (C.sub.quat, arom.) 144.40
(C.sub.quat, arom.) 141.72 (C.sub.quat, arom.) 140.08 (C.sub.quat,
arom.) 139.50 (C.sub.quat, arom.) 135.87 (C.sub.quat, arom.) 130.69
(C--H, arom.) 129.78 (C--H, arom.) 129.22 (C--H, arom.) 128.86
(C--H, arom.) 128.76 (C--H, arom.) 128.05 (C--H, arom.) 128.02
(C--H, arom.) 127.72 (C--H, arom.) 127.36 (C--H, arom.) 102.75
(C-3, pyrrole) 26.63 (CH.sub.3)
Example C
Synthesis of 1-H-pyrrolo(2,3-b]quinoxaline,
2-phenyl-1H-pyrrolo-[2,3-b]quinoxaline and
2-(triisopropyl)silyl-1-H-pyrrolo[2,3-b]quinoxaline
[0174] ##STR20##
[0175] Preparation: KOtBu (potassium tert-butoxide, 1.95 mmol) is
added under an inter-gas atmosphere to a solution of (1.5 mmol) of
3-alkynyl-2-aminoquinoxaline in 1.5 ml of NMP (N-methylpyrrolidone;
anhydrous), and the mixture is left to stir at room temperature for
4-6 hours. 1.5 ml of H.sub.2O are subsequently added, and the
mixture is extracted with dichloromethane (3.times.10 ml). After
washing with NaCl solution and drying over MgSO.sub.4, the residue
is purified by column chromatography on silica gel using
cyclohexane/ethyl acetate (2:1). the 1-H-pyrrolo[2,3-b]quinoxalines
can be obtained in yields of 64-97%. TABLE-US-00005
Characterisation of 2-phenyl-1H-pyrrolo[2,3-b]quinoxaline (A)
IR(KBr): Wavenumber[cm.sup.-1] = 3107 (.nu.(N--H), NH) 3085
(.nu.(C--H), Ph) 1604 (.nu.(C.dbd.C), Ph) 1564 (.nu.(C.dbd.C), Ph)
1499 (.nu.(C--H), Ph) 1341 ((skeleton), Ph) 848 (.gamma.(C--H), Ph)
759 (.gamma.(C--H), Ph) 300MHz .sup.1H-NMR(DMSO): .delta. = 12.55
(br. s, 1H, NH) 8.14-8.17 (m, 2H, hetaryl arom.) 8.07-8.10 (m, 1H,
hetaryl arom.) 8.03-8.05 (m, 1H, hetaryl arom.) 7.68-7.72 (m, 2H,
arom.) 7.53-7.60 (m, 3H, arom.) 7.30 (s, 1H, hetaryl arom.) 75MHz
.sup.13C-NMR(DMSO): .delta. = 149.30 (C.sub.quat, arom.) 143.65
(C.sub.quat, arom.) 140.32 (C.sub.quat, arom.) 138.78 (C.sub.quat,
arom.) 130.13 (C--H, arom.) 129.14 (C--H, arom.) 128.54 (C--H,
arom.) 127.83 (C--H, arom.) 127.09 (C--H, arom.) 126.43 (C--H,
arom.) 126.32 (C--H, arom.) 95.56 (C-3, pyrrole) MS(70eV):m/e(%) =
246(15)[M.sup.++1], 245(100)[M.sup.+], 244(6), 142(11), 128(7),
116(8), 102(24), 90(22), 77(21) Characterisation of
1-H-pyrrolo[2,3-b]quinoxaline (B) IR(KBr): Wavenumber[cm.sup.-1] =
3105 (.nu.(N--H), NH) 2940 (.nu.(C--H), pyrrole) 1564
(.nu.(C.dbd.C), hetaryl) 1535 (.nu.(C.dbd.C), hetaryl) 1341
((skeleton), hetaryl) 762 (.gamma.(C--H), hetaryl) 300MHz
.sup.1H-NMR(CDCl.sub.3): .delta. = 12.07 (br.s, 1H, NH) 8.30-8.31
(m, 1H, hetaryl arom.) 8.12-8.15 (m, 1H, hetaryl arom.) 8.05-8.09
(m, 1H, hetaryl arom.) 7.68-7.75 (m, 1H, hetaryl arom.) 7.58-7.64
(m, 1H, H-2) 6.74-6.76 (m, 1H, H-3) MS(70eV):m/e(%) =
169(100)[M.sup.+], 168(6), 142(14), 129(1), 118(7), 102(8), 90(5),
76(2) Characterisation of
2-(triisopropyl)silyl-1-H-pyrrolo[2,3-b]quinoxaline (C) IR(KBr):
Wavenumber[cm.sup.-1] = 3302 (.nu.(N--H), NH) 2966 (.nu.(C--H),
i-R) 1637 (.nu.(C.dbd.C), hetaryl) 1611 (.nu.(C.dbd.C), hetaryl)
1558 (.nu.(C.dbd.C), hetaryl) 1505 (.nu.(C.dbd.C), hetaryl) 1249
((skeleton), hetaryl) 880 (.gamma.(Si--C), SiR.sub.3) 762
(.gamma.(C--H), hetaryl) 300MHz .sup.1H-NMR(CDCl.sub.3): .delta. =
7.83-7.85 (m, 1H, hetaryl arom.) 7.50-7.53 (m, 2H, hetaryl arom.)
7.37-7.39 (m, 1H, hetaryl arom.) 7.34 (s, 1H, hetaryl arom.) 5.51
(br.s, 1H, NH) 1.15 (sep, 3H, CH) 1.13 (s, 9H, CH.sub.3) 1.09 (s,
9H, CH.sub.3) MS(70eV):m/e(%) = 325[M.sup.+](36), 298(9), 282(100),
266(1), 254(31), 240(8), 226(14), 212(20), 196(5), 170(1), 153(9),
112(14), 98(3), 84(26), 76(8)
Example D
Synthesis of
A: 1,4-dihydropyrazino[2,3-b]quinoxaline-2,3-dione
B: 1-hydropyrazino[2,3-b]quinoxalin-2,3-one
[0176] ##STR21##
[0177] Preparation: Glyoxalic acid monohydrate or oxalic acid
dihydrate (1.10 mmol) is added to a solution of
2,3-diaminoquinoxaline (1.0 mmol) in ethanol (anhydrous), and the
mixture is left to stir at room temperature for 48 hours with
addition of a few drops of glacial acetic acid. After evaporation
of the solution, a precipitate deposits, which can be purified by
washing with cold ethanol (A) or by column chromatography (B) on
silica gel using an ethyl acetate/ethanol eluent mixture. The
condensed quinoxalines are obtainable in the form of pale-yellow
powders in a yield of 68% (A) and 79% (B). TABLE-US-00006
Characterisation of 1,4-dihydropyrazino[2,3-b]quinoxaline-2,3-(A)
IR(KBr): Wavenumber[cm.sup.-1] = 3309 (.nu.(N--H), NH) 3052
(.nu.(C--H), hetaryl) 1690 (.nu.(C.dbd.O)) 1624 (.nu.(C.dbd.C),
hetaryl) 1506 (.nu.(C.dbd.C), hetaryl) 1249 ((skeleton), hetaryl)
755 (.gamma.(C--H), hetaryl) 300MHz .sup.1H-NMR(CDCl.sub.3):
.delta. = 11.96 (br.s, 2H, NH) 7.16-7.21 (m, 2H, hetaryl arom.)
7.09-7.14 (m, 2H, hetaryl arom.) 75MHz .sup.13C-NMR(CDCl.sub.3):
.delta. = 154.43 (C.sub.quat, C.dbd.O) 126.27 (C.sub.quat arom.)
124.54 (C.sub.quat arom.) 124.78 (C--H, arom.) 123.12 (C--H, arom.)
122.17 (C--H, arom.) 114.31 (C--H, arom.) MS(70eV):m/e(%) =
214(2)[M.sup.+], 186(1), 160(100), 144(10), 133(88), 116(4),
106(51), 90(25), 79(26) Characterisation of
1-hydropyrazino[2,3-b]quinoxaline-2,3-(B) IR(KBr):
Wavenumber[cm.sup.-1] = 3374 (.nu.(N--H), NH) 3058 (.nu.(C--H),
hetaryl) 1703 (.nu.(C.dbd.O)) 1644 (.nu.(C.dbd.N), hetaryl) 1585
(.nu.(C.dbd.C), hetaryl) 1493 ((skeleton), hetaryl) 1341
((skeleton), hetaryl) 1262 ((skeleton), hetaryl) 762
(.gamma.(C--H), hetaryl) 300MHz .sup.1H-NMR(CDCl.sub.3): .delta. =
11.93 (br.s, 1H, NH) 9.21 (s, 1H, H-3) 7.61-7.73 (m.sub.c, 2H, H-5,
H-8) 7.43-7.56 (m.sub.c, 2H, H-6, H-7) MS(70eV):m/e(%) =
198(96)[M.sup.+], 186(16), 170(76), 158(7), 143(100), 133(5),
116(52), 102(19), 90(34), 76(14), 63(12)
Example E
Synthesis of 2-aryl-1H-imidazo[4,5-b]quinoxalines or
2-aryl-1-methylimidazo[4,5-b]quinoxalines
[0178] ##STR22##
[0179] Preparation: 0.98 mmol of the aroyl chloride (freshly
distilled) is added to a solution of 1.00 mmol of
diaminoquinoxaline (160 mg) in 15.0 ml of a polar aprotic solvent
(preferably THF or dioxane/dried), and the mixture is refluxed for
48-72 hours. After cooling, the solvent is removed, and the residue
is purified by column chromatography on silica gel using a
cyclohexane/ethyl acetate.fwdarw.ethyl acetate/ethanol
solvent/eluent mixture. The products can be obtained as pale-yellow
powders in a yield of 33-76%.
A: 2-phenyl-1H-imidazo[4,5-b]quinoxaline
B: 2-[4-[(ethyl)phenyl]-1H-imidazo[4,5-b]quinoxaline
C:
2-[3,5-bis(trifluoromethyl)phenyl]-1H-imidazo[4,5-b]quinoxaline
D: 2-[4-(carboxy)phenyl]-1H-imidazo[4,5-b]quinoxaline
E: 2-[4-[(t-butyl)phenyl]-1H-imidazo[4,5-b]quinoxaline
F: 2-[4-[(t-butyl)phenyl]-1-methylimidazo[4,5-b]quinoxaline
G: 2-(2-furyl)-1H-imidazo[4,5-b]quinoxaline
[0180] TABLE-US-00007 Characterisation of
2-phenyl-1H-imidazo[4,5-b]quinoxaline (A) IR(KBr):
Wavenumber[cm.sup.-1] = 3058 (.nu.(C--H), Ph) 1611 (.nu.(C.dbd.C),
Ph) 1538 (.nu.(C.dbd.C), Ph) 1348 ((skeleton), Ph) 755
(.gamma.(C--H), Ph) 300MHz .sup.1H-NMR(CDCl.sub.3): .delta. = 12.86
(br. s, 1H, NH) 8.42-8.45 (m, 2H, hetaryl arom.) 8.11-8.16 (m, 2H,
hetaryl arom.) 7.75-7.80 (m, 2H, arom.) 7.66-7.72 (m, 3H, arom.)
MS(70eV):m/e(%) = 247(16.2)[M.sup.++1], 246(100)[M.sup.+], 245(4),
219(5), 143(52), 116(24), 104(4), 90(6), 77(4) Characterisation of
2-[4-[(ethyl)phenyl]-1H-imidazo[4,5-b]quinoxaline (B) IR(KBr):
Wavenumber[cm.sup.-1] = 3039 (.nu.(C--H), Ph) 2960 (.nu.(C--H),
C.sub.2H.sub.5) 1617 (.nu.(C.dbd.C), Ph) 1545 (.nu.(C.dbd.C), Ph)
1492 (.nu.(C.dbd.C), Ph) 1335 ((skeleton), Ph) 769 (.gamma.(C--H),
Ph) 300MHz .sup.1H-NMR(CDCl.sub.3): .delta. = 13.84 (br. s, 1H, NH)
8.32-8.35 (m, 2H, arom.) 8.12 (m, 2H, hetaryl arom.) 7.74-7.78 (m,
2H, hetaryl arom.) 7.52 (m, 2H, arom.) 2.74 (q, 2H, CH.sub.2) 1.25
(t, 3H, CH.sub.3 75MHz .sup.13C-NMR(CDCl.sub.3): .delta. = 167.23
(C.sub.quat., arom.) 166.27 (C.sub.quat., arom.) 161.97
(C.sub.quat., arom.) 155.12 (C.sub.quat., arom.) 149.03
(C.sub.quat., arom.) 147.18 (C.sub.quat., arom.) 131.63
(C.sub.quat., arom.) 130.15 (C--H, arom.) 129.35 (C--H, arom.)
128.64 (C--H, arom.) 128.15 (C--H, arom.) 127.99 (C--H, arom.)
127.88 (C--H, arom.) 127.73 (C--H, arom.) 127.50 (C--H, arom.)
28.17 (CH.sub.2CH.sub.3) 15.29 (CH.sub.2CH.sub.3) MS(70eV):m/e(%) =
275(19)[M.sup.++1], 274(100)[M.sup.+], 273(14), 245(3), 259(39,
143(11), 116(14), 102(2), 89(3), 77(1) (HRMS)(high resolution
mass)C.sub.17H.sub.14N.sub.4[M.sup.+] Calc. for: 274, 1219 Found
for: 274, 1217 Characterisation of
2-[3,5-bis(trifluoromethyl)phehyl]-1H-imidazo[4,5- b]quinoxaline
(C) IR(KBr): Wavenumber[cm.sup.-1] = 3065 (.nu.(C--H), Ph) 1657
(.nu.(C.dbd.C), Ph) 1282 (.nu.(C.dbd.F), Ph) 1181 ((skeleton), Ph)
781 (.gamma.(C--H), Ph) 300MHz .sup.1H-NMR(CDCl.sub.3): .delta. =
11.83 (br. s, 1H, NH) 9.94 (m, 2H, arom.) 8.25 (m, 1H, arom.)
8.00-8.06 (m, 2H, hetaryl arom.) 7.65-7.70 (m, 2H, hetaryl arom.)
MS(70eV):m/e(%) = 383(20)[M.sup.++1], 382(100)[M.sup.+], 381(3),
363(9), 313(1), 220(2), 170(2), 143(90, 116(39), 102(5), 90(19),
76(2) Characterisation of 2-[4-(carboxy)phenyl]-1H-imidazo[4,5-
b]quinoxaline (D) IR(KBr): Wavenumber[cm.sup.-1] = 3472
(.nu.(O--H), OH) 3056 (.nu.(C--H), Ph) 1697 (.nu.(C.dbd.O),
CO.sub.2H) 1637 (.nu.(C.dbd.C), Ph) 1512 (.nu.(C.dbd.C), Ph) 1472
(.nu.(C.dbd.C), Ph) 1341 ((skeleton), Ph) 1288 ((skeleton), Ph) 755
(.gamma.(C--H), Ph) 300MHz .sup.1H-NMR(CDCl.sub.3): .delta. = 11.93
(br. s, 1H, NH) 8.49-8.52 (m, 1H, arom.) 8.13-8.14 (m, 1H, arom.)
8.10-8.12 (m, 2H, hetaryl arom.) 7.71-7.75 (m, 2H, hetaryl arom.)
7.30-7.34 (m, 1H, arom.) 7.12-7.10 (m, 1H, arom.) 6.75 (br. s, 1H,
OH) MS(70eV):m/e(%) = 290[M.sup.+](5), 169(7), 160(97), 149(16),
133(100), 116(8), 105(13), 91(34), 79(23) Characterisation of
2-(2-furyl)-1H-imidazo[4,5-b]quinoxaline (G) IR(KBr):
Wavenumber[cm.sup.-1] = 3111 (.nu.(C.dbd.H), furyl) 2960
(.nu.(C--O--C), furyl) 1623 (.nu.(C.dbd.C), hetaryl) 1525
(.nu.(C.dbd.C), hetaryl) 1327 ((skeleton), hetaryl) 1268
((skeleton), hetaryl) 775 (.gamma.(C--H), hetaryl) 300MHz
.sup.1H-NMR(CDCl.sub.3): .delta. = 14.06 (br. s, 1H, NH) 8.26-8.27
(m, 1H, furyl arom.) 8.14-8-19 (m, 2H, hetaryl arom.) 7.98-8.04 (m,
2H, hetaryl arom.) 7.78-7.74 (m, 1H, furyl arom.) 6.96-6.98 (m, 1H,
furyl arom.) MS(70eV): m/e(%) = 238(13)[M.sup.++1],
237(100[M.sup.+], 236(3), 208(2), 161(25), 143(62), 133(11),
116(32), 105(9), 95(12), 90(7), 77(5) Characterisation of
2-[4-[(t-butyl)phenyl]-1-methylimidazo[4,5- b]quinoxaline (F)
(HRMS)(high Calc. for: 316.1697 resolution Found for: 316.1701
mass) (EI) C.sub.20H.sub.20N.sub.4[M.sup.+] IR(KBr):
Wavenumber[cm.sup.-1] = 3065 (.nu.(C--H), Ph) 2960 (.nu.(C--H),
alkyl) 1617 (.gamma.(C.dbd.C), Ph) 1545 (.gamma.(C.dbd.C), Ph) 1485
(.gamma.(C.dbd.C), Ph) 1446 (.gamma.(C.dbd.C), Ph) 1382
((skeleton), Ph) 1341 ((skeleton), Ph) 1123 ((skeleton), Ph) 867
(.gamma.(C--H), Ph) 755 (.gamma.(C--H), Ph) MS(70eV): m/e(%) =
317[M.sup.++1], 316[M.sup.+](65), 301(100), 273(7), 258(5),
150(12), 128(21), 103(9), 90(6), 77(3), 57(1) 300MHz
.sup.1H-NMR(CDCl.sub.3): .delta. = 8.17-8.20 (m.sub.c, 1H, H-8',
hetaryl arom.) 8.03-8.07 (m.sub.c, 1H, H-7', hetaryl arom.)
7.88-7.91 (m.sub.c, 2H, H-2, H-6, arom.) 7.61-7.64 (m.sub.c, 1H,
H-6', H-9' hetaryl arom.) 7.52-7.55 (m.sub.c, 2H, H-3, H-5, arom.
4.09 (s, 3H, CH.sub.3) 1.30 (s, 9H, C(CH.sub.3).sub.3)
.sup.13C-NMR(CDClHD 3): .delta. = 163.49 (C-2') 155.44 (C-4) 150.17
(C-5') 143.43 (C-4') 141.79 (C-10') 139.95 (C-9') 129.68 (C--H)
128.13 (C--H) 128.05 (C--H) 127.43 (C--H) 126.13 (C-3) 125.72 (C-5)
35.24 (C(CH.sub.3).sub.3) 31.24 (C(CH.sub.3).sub.3) 29.85
(CH.sub.3)
Example F
Synthesis of 2-aryl-4-methylimidazo[4,5-b]quinoxalines
[0181] TABLE-US-00008 ##STR23## A: R = Me; R.sup.1 =
C(CH.sub.3).sub.3 Characterisation of
2-[4-[[(t-butyl)phenyl]-4-methylimidazo[4,5-b] quinoxaline (A) IR
(KBr): Wavenumber [cm.sup.-1]= 3058 (.nu. (C--H), Ph) 2954 (.nu.
(C--H), alkyl) 2861 (.nu. (C--H), alkyl) 1604 (.gamma. (C.dbd.C),
Ph) 1486 (.gamma. (C.dbd.C), Ph) 1454 (.gamma. (C.dbd.C), Ph) 1354
((skeleton), Ph) 1259 ((skeleton), Ph) 769 (.gamma. (C--H), Ph)
MS(7OeV):m/e (%)= 317 [M.sup.+ + 1] (32), 302 (100), 273 (3), 158
(1), 131 (2) 300 MHz .sup.1H-NMR (CDCl.sub.3): .delta.= 8.51-8.54
(m.sub.c, 2H, H-2, H-6, arom.) 8.23-8.26 (m.sub.c, 1H, H-8',
hetaryl arom.) 7.74-7.78 (m.sub.c, 1H, H-7', hetaryl arom.)
7.67-7.70 (m.sub.c, 1H, H-6', hetaryl arom.) 7.59-7.65 (m.sub.c,
1H, H-9', hetaryl arom.) 7.48-7.51 (m.sub.c, 2H, H-3, H-5, arom.)
4.43 (s, 3H, CH.sub.3) 1.28 (s, 9H, C(CH.sub.3).sub.3) .sup.13C-NMR
(CDCl.sub.3): .delta.= 163.51 (C-2') 156.35 (C-4) 138.21 (C-5')
131.26 (C-4') 130.50 (C-H) 129.79 (C-H) 128.92 (C-H) 125.83 (C-H)
114.73 (C-5') 35.24 ((CH.sub.3).sub.3) 34.28 (CH.sub.3) 31.26
(C(CH.sub.3).sub.3)
Example G
Synthesis of 2-tett-butyl-1H-imidazoquinoxaline
[0182] ##STR24##
[0183] Preparation: 0.98 mmol of the pivaloyl anhydride (206 mg) is
added to a solution of 1.00 mmol of diaminoquinoxaline (160 mg) in
15.0 ml of a polar aprotic solvent (preferably THF or
dioxane/dried), and the mixture is refluxed for 48-72 hours. After
cooling, the solvent is removed in a rotary evaporator, and the
residue is purified by column chromatography on silica gel using a
cyclo-hexane/ethyl acetate.fwdarw.ethyl acetate/ethanol
solvent/eluent mixture. The 2-tert-butyl-1H-imidazoquinoxaline can
be obtained as a beige-white powder. TABLE-US-00009 IR(KBr):
Wavenumber[cm.sup.-1] 3355 (.nu.(N--H), NH) 3085 (.nu.(C--H), Ph)
2980 (.nu.(C--H), CH.sub.3) 1623 (.nu.(C.dbd.N), hetaryl) 1611
(.nu.(C.dbd.C), Ph) 1518 (.nu.(C.dbd.C), Ph) 1334 ((skeleton), Ph)
768 (.gamma.(C--H), aryl) .sup.1H-NMR(300MHz, d-CDCl.sub.3):
.delta. = 11.13 (br.s, 1H, NH) 8.16-8.18 (m, 2H, hetaryl, arom.)
7.71-7.74 (m, 2H, hetaryl, arom.) 1.60 (s, 9H, CH.sub.3)
.sup.13C(75.4MHz) .delta. = 158.27; 140.44; (C.sub.quat, hetaryl,
arom.) 128.40; 125.18 128.80; 127.89 (C--H, hetaryl, arom.) 34.92
(C.sub.quat, C(CH.sub.3).sub.3)) 28.88 (C(CH.sub.3)) MS: m/e(%) =
226(32)[M.sup.+], 211(100), 184(17), 161(5), 144(14), 133(3),
116(14), 102(3), 90(10), 71(18)
Example H
Preparation of
1-(2-ethylhexyl)-2-phenylimidazo[3,4-b]quinoxaline
a) Route A: Preparation of 2-amino-3-chloroquinoxaline
[0184] ##STR25##
[0185] 2.1 g (10.4 mmol) of 2,3-dichloroquinoxaline are stirred for
8 hours with 50 ml of 20% ethanolic ammonia in an autoclave at
80''-85.degree. C. and autogenous pressure. The reaction solution
is evaporated to dryness in a rotary evaporator, and the crude
product is chromatographed over silica gel using toluene/ethyl
acetate. The product-containing fractions are collected and
evaporated in a rotary evaporator. Yield: 1.18 g (63%)
b) Route B: Preparation of
2-chloro-3-(2-ethylhexylamino)quinoxaline
[0186] ##STR26##
[0187] 12 g (60.3 mmol) of 2,3-dichloroquinoxaline are dissolved in
125 ml of THF with 9.5 g (72.1 mmol) of diisopropylethylamine. 8.5
g (66 mmol) of 2-ethylhexylamine are added dropwise to the
solution, and the reaction is refluxed for a total of 48 hours
until starting material is no longer visible according to TLC
(silica gel: n-heptane/MTB ether). The reaction solution is
evaporated to dryness in a rotary evaporator, and the crude product
is chromatographed over silica gel using n-heptane/MTB ether. The
product-containing fractions are collected and evaporated in a
rotary evaporator. Yield: 11.8 g (67%)
c) Route A: Preparation of 2-amino-3-(2-ethylhexylamino)quinoxaline
from 2-amino-3-chloroquinoxaline
[0188] ##STR27##
[0189] 1.8 g (10 mmol) of 2-amino-3-chloroquinoxaline are dissolved
in 85 ml of THF with 2.5 g (19 mmol) of diisopropylethylamine. 1.6
g (12 mmol) of 2-ethylhexylamine are added dropwise to the
solution, and the reaction is refluxed for a total of 48 hours
until starting material is no longer visible according to TLC
(silica gel: n-heptane/MTB ether). The reaction solution is
evaporated to dryness in a rotary evaporator, and the crude product
is chromatographed over silica gel using toluene/ethyl acetate. The
product-containing fractions are collected and evaporated in a
rotary evaporator. Yield: 1.9 g (71%)
d) Route B: Preparation of 2-amino-3-(2-ethylhexylamino)quinoxaline
from 2-chloro-3-(2-ethylhexylamino) quinoxaline
[0190] ##STR28##
[0191] 11.5 g of 2-chloro-3-(2-ethylhexylamino)quinoxaline are
stirred for 48 hours with 200 ml of 20% ethanolic ammonia at
90.degree.-100.degree. C. and autogenous pressure. After the
autoclave has been cooled, the methanol is distilled off, and the
crude product is separated off from the starting material (10%) by
chromatography over silica gel using toluene/ethyl acetate. Yield:
7.9 g (73%)
e) Preparation of
1-(2-ethylhexyl)-2-phenylimidazo[3,4-b]quinoxaline
[0192] ##STR29##
[0193] 1.38 g (5.1 mmol) of
2-amino-3-(2-ethylhexylamino)quinoxaline are dissolved in 20 ml of
DMF, and 0.94 g (5 mmol) of sodium disulfite is added to the
solution. 0.57 g (5.3 mmol) of benzaldehyde is added to the
suspension, and the reaction is heated at 110.degree. C. for 8
hours until the conversion is complete. After the reaction solution
has been cooled to room temperature, 50 ml of MTB ether and 50 ml
of water are added, the phases are separated, the aqueous phase is
subsequently extracted with 30 ml of MTB ether, and the organic
phases are evaporated to dryness (1.73 g; 96% yield) in a rotary
evaporator. For further purification, the crude product is
recrystallised from n-heptane. Yield: 0.98 g (54%)
[0194] The spectra (MS and .sup.1H-NMR) available for the
individual reactions a)-e) in each case correspond to
expectations.
Example J
[0195] The following table shows the structural formulae of
quinoxaline derivatives which can be employed in accordance with
the invention and the maxima of their UV-A and UV-B absorption. The
measurement was carried out in 2-propanol at a concentration of 1
mg of substance per 100 ml of solvent. TABLE-US-00010 UV-A UV-B
(400 320 nm) (280 320 nm) Structural formula Max. abs. .lamda. [nm]
Max. abs. .lamda. [nm] ##STR30## 0.5227 328.0 ##STR31## 0.5824
327.5 ##STR32## 0.4875 327.5 ##STR33## 0.3754 0.3381 0.3707 342.0
335.0 327.5 ##STR34## 0.6290 330.0 ##STR35## 0.9293 0.9565 368.0
354.0 ##STR36## 1.478 1.4581 0.7467 0.7403 372.0 358.0 372.0 358.0
##STR37## 0.7037 358.0 ##STR38## 0.4067 359.0 ##STR39## 0.4496
358.0 0.5643 269.0 ##STR40## 0.7158 367.0 0.8710 268.0 ##STR41##
0.6909 327.0 ##STR42## 0.5381 338.0 ##STR43## 0.5774 403.0 0.4246
318.0 ##STR44## 0.3685 358.0
USE EXAMPLES
Example 1
[0196] Preparation of a sunscreen spray (O/W) according to the
invention TABLE-US-00011 % A 2-tert-Butyl-1H-imidazoquinoxaline (1)
1.00 Eusolex 2292 (Art. No. 105382) (1) 7.50 (Octyl
Methoxycinnamate) Eusolex HMS (Art. No. 111412) (1) 7.00
(Homosalate) Volpo S-2 (Steareth-2) (2) 0.40 Volpo S-10
(Steareth-10) (2) 0.80 Pemulen TR-2 (3) 0.18 (Acrylate/C10-39Alkyl
Acrylate Crosspolymer) Hetester PHA (4) 5.00 (Propylene Glycol
Isoceteth-3 Acetate) Performa V 825 (5) 0.80 (Synthetic Wax) Dow
Corning 200 (100 cs) (6) 1.00 (Dimethicone) Oxynex K Liquid (Art.
No. 108324) (1) 0.10 (PEG-8 (and) Tocopherol (and) Ascorbyl
Palmitate (and) Ascorbic Acid (and) Citric Acid) B Eusolex 232
(Art. No. 105372) (1) 1.00 (Phenylbenzimidazole Sulfonic Acid)
Triethanolamine (Art. No. 108379) (1) 0.90 Propane-1,2-diol (Art.
No. 107478) (1) 2.00 Preservatives q.s. Water, Demineralised to
100.00
Preparation:
[0197] For neutralisation of Eusolex 232, the triethanolamine is
introduced into the water of phase B, and Eusolex 232 is added with
stirring. After complete dissolution, the remaining raw materials
of phase B are added and heated to 80.degree. C. Add phase A apart
from the Pemulen and heat to 80.degree. C. Stir Pemulen into phase
A. Add phase B slowly to phase A with stirring, homogenise and cool
with stirring.
Notes:
[0198] The preservatives used are:
0.05% of propyl 4-hydroxybenzoate (Art. No. 107427)
0.15% of methyl 4-hydroxybenzoate (Art. No. 106757)
Sources of Supply:
(1) Merck KGaA, Darmstadt
(2) Croda, Nettetal
(3) Goodrich, Neuss
(4) ROVI, Schluchtern
(5) New Phase, N.J. 08554
(6) Dow Corning, Wiesbaden
Example 2
[0199] Preparation of a Sunscreen Gel (ONV) According to the
Invention TABLE-US-00012 % A 2-tert-Butyl-1H-imidazoquinoxaline (1)
1.00 Eusolex 6300 (Art. No. 5385) (1) 10.00 Luvitol EHO (2) 2.00
Dow Corning 200 (100 cs) (3) 2.00 Shea Butter (4) 5.00 Antaron
V-220 (5) 2.00 Oxynex K Liquid (Art. No. 8324) (6) 1.00 B Eusolex
232 (Art. No. 5372) (1) 0.75 Tris(hydroxymethyl)aminomethane (Art.
No. 8386) (1) 0.33 Preservatives q.s. Water, Demineralised 20.00 C
Tris(hydroxymethyl)aminomethane (Art. No. 8386) (1) 1.20 Water,
Dem. 10.00 D Pemulen TR-1 (6) 0.60 Water, Dem. to 100.00
Preparation:
[0200] For phase D, homogeneously disperse the Pemulen TR-1 in the
water and add the pre-dissolved phase C with stirring. For
neutralisation of Eusolex 232, the tris(hydroxymethyl)aminomethane
is dissolved in the water of phase B, and the Eusolex 232 is added
with stirring. After complete dissolution, the remaining raw
materials of phase B are added. Stir phase B into phase C/D.
Dissolve phase A with warming and stir into phase B/C/D.
Homogenise.
Notes:
[0201] The preservatives used are:
0.05% of propyl 4-hydroxybenzoate (Merck Art. No. 7427)
0.15% of methyl 4-hydroxybenzoate (Merck Art. No. 6757)
Sources of Supply:
(1) Merck KGaA, Darmstadt
(2) BASF, Ludwigshafen
(3) Dow Corning, Dusseldorf
(4) H. Erhard Wagner, Bremen
(5) GAF, Frechen
(6) Goodrich, Neuss
Example 3
[0202] Preparation of a Sunscreen Lotion (W/O) with UV-A/B
Protection TABLE-US-00013 % A
2-[4[(Ethyl)phenyl]-1H-imidazo[4,5-b]quinoxaline (1) 1.00 Eusolex
2292 (Art. No. 1.05382) (1) 3.00 Eusolex 4360 (Art. No. 1.05376)
(1) 2.00 (Benzophenone-3) Dehymuls E (2) 6.00 (Dicocoyl
Pentaerythrityl Citrate (and) Sorbitan Sesquioleate (and) Cera Alba
(and) Aluminium Stearate) Arlacel 989 (3) 1.00 (PEG-7 Hydrogenated
Castor Oil) Beeswax (Art. No. 1.11544) (2) 2.00 Cetiol J 600 (2)
6.00 (Oleyl Erucate) Cetiol V (2) 6.00 (Decyl Oleate) Cetiol OE (2)
5.00 (Dicaprylyl Ether) Dow Corning 200 (100 cs) (4) 1.00
(Dimethicone) B Glycerin (about 87%) (Art. No. 1.04091) (1) 5.00
Magnesium Sulfate Heptahydrate (Art. No. 1.05882) (1) 1.00
Preservatives q.s. Water, Dem. to 100.00
Preparation: Heat phase B to 80.degree. C. and phase A to
75.degree. C. Stir phase B slowly into phase A. Homogenise and cool
with stirring. Notes:
[0203] The preservatives used are:
0.05% of propyl 4-hydroxybenzoate (Art. No. 1.07427)
0.15% of methyl 4-hydroxybenzoate (Art. No. 1.06757)
Sources of Supply:
(1) Merck KGaA, Darmstadt
(2) Henkel KGaA, Dusseldorf
(3) ICI, Essen
(4) Dow Corning, Dusseldorf
Example 4
[0204] Preparation of a Sunscreen Lotion with IR3535.TM.
TABLE-US-00014 % A 2-Phenyl-1H-imidazo[4,5-b]quinoxaline (1) 3.00
Eusolex 6300 (1) 1.00 (4-Methylbenzylidene Camphor) IR 3535 .TM.
(Art. No. 111887) (1) 10.00 (Ethyl Butylacetylaminopropionate)
(-)-.alpha.-Bisabolol (Art. No. 130170) (1) 0.30 Montanov 68 (2)
4.00 (Cetearyl Alcohol (and) Cetearyl Glucoside) Myritol 312 (3)
2.00 (Carprylic/Capric Triglyceride) Mirasil CM 5 (4) 2.00
(Cyclomethicone) Mirasil DM 350 (4) 1.00 (Dimethicone) B Demin.
Water to 100.00 Glycerin, 87% (Art. No. 104091) (1) 3.00
Preservatives q.s. C Rhodicare S (4) 0.50 (Xanthan Gum)
Preparation:
[0205] Heat phases A and B separately to 75.degree. C. Slowly add C
to B at 75.degree. C. with stirring and stir until a homogeneous
mixture has formed. Subsequently add A to B/C with stirring and
homogenise. Cool with stirring.
Notes:
[0206] The preservatives used are:
0.05% of propyl 4-hydroxybenzoate (Merck KGaA, Art. No.
130173),
0.15% of methyl 4-hydroxybenzoate (Merck KGaA, Art. No.
130174),
0.30% of Germall 115 (ISP, Frechen)
Sources of Supply:
(1) Merck KGaA, Darmstadt
(2) Interorgana, Cologne
(3) Henkel, KGaA, Dusseldorf
(4) Rhodia, Frankfurt
Example 5
[0207] Preparation of a sunscreen milk with IR3535.TM.
TABLE-US-00015 % A 2-[4[(Ethyl)phenyl]-1H-imidazo[4,5-b]quinoxaline
(1) 1.00 Eusolex 6300 (1) 1.00 (4-Methylbenzylidene Camphor) IR
3535 .TM. (Art. No. 111887) (1) 15.00 (Ethyl
Butylacetylaminopropionate) Eusolex 2292 (1) 3.00 (Octyl
Methoxycinnamate) Dow Corning 5225 C (2) 12.00 (Cyclomethicone
(and) Dimethicone Copolyol) Dow Corning 345 (2) 5.00
(Cyclomethicone) Gilugel Sil 5 (3) 12.00 (Cyclomethicone (and)
Al/Mg Hydroxide Stearate) Solvent ID (4) 13.00 (Isododecane)
Wiconol 14 (5) 2.50 (Polyglyceryl-4 Oleate) Beeswax, Bleached (Art.
No. 111544) (1) 1.60 Carnauba Wax (6) 0.40 B Demin. Water to 100.00
Propane-1,2-diol (Art. No. 107478) (1) 2.00 Sodium chloride (Art.
No. 106400) (1) 2.00 Preservatives (1) q.s. C Perfume Oil Bariton
(10607) (7) 0.30
Preparation:
[0208] Heat phase A to 80.degree. C., cool to 30.degree. C. with
stirring. Slowly add phase B to phase A with stirring, stir until a
homogeneous mixture has formed and homogenise. Add phase C.
Notes:
[0209] The preservative used is:
0.20% of Euxyl K400 (Schulke & Mayr, Norderstedt)
[0210] Sources of Supply:
(1) Merck KGaA, Darmstadt
(2) Dow Corning, Dusseldorf
(3) Nordmann, Rassmann GmbH&Co, Hamburg
(4) BP, Dusseldorf
(5) Witco Chemical, Frankfurt
(6) Aug. Schmidt Nachfolger, Bremen
(7) Haarmann & Reimer, Holzminden
Examples 6-9
[0211] The following formulations can be prepared with all
quinoxaline derivatives according to the invention. TABLE-US-00016
Substance INCI 6 7 8 9 A Quinoxaline -- 2.0 2.0 2.0 2.0 derivative
Eusolex .RTM. 6300 4-METHYLBENZYLIDENE 4.0 -- -- -- CAMPHOR Eusolex
.RTM. 2292 OCTYL -- 6.0 7.0 -- METHOXYCINNAMATE, BHT Eusolex .RTM.
9020 BUTYL METHOXY- -- 1.0 -- -- DIBENZOYLMETHANE Eusolex .RTM. OCR
OCTOCRYLENE -- -- -- 7.0 Hostaphat CG ISOSTEARYL PHOSPHATE 3.00
3.00 3.00 3.00 120 Cetiol SN CETEARYL 5.00 4.00 4.00 4.00
ISONONANOATE Cetiol OE DICAPRYL ETHER 5.00 4.00 4.00 4.00 Cetiol
868 OCTYL STEARATE 5.00 4.00 4.00 4.00 Carbopol Ultrez CARBOMER
0.15 0.15 0.15 0.15 10 Propyl 4-hydroxy- PROPYLPARABEN 0.05 0.05
0.05 0.05 benzoate B Glycerol (about GLYCERIN 5.00 5.00 5.00 5.00
87%) Tris(hydroxy- TROMETHAMINE 0.15 0.15 0.15 0.15 methyl)amino-
methane RonaCare .RTM. ALLANTOIN 0.30 0.30 0.30 0.30 Allantoin
Methyl 4-hydroxy- METHYLPARABEN 0.15 0.15 0.15 0.15 benzoate Water,
demin. AQUA (WATER) to to to to 100 100 100 100 INCI =
International Nomenclature for Cosmetic Ingredients
[0212] Preparation: Phase A without the Carbopol is mixed together
and heated to 80.degree. C. The Carbopol is added to phase. A with
stirring. Phase B is mixed together and added to phase A with
stirring. The mixture is subsequently homogenised.
[0213] The working examples shown here confirm by way of example
the feasibility of the claimed invention, it being possible to
carry out the present invention in the entire range claimed.
* * * * *