Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-11-16
2003-09-23
Celsa, Bennett (Department: 1639)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S369000, C422S028000, C422S037000
Reexamination Certificate
active
06624182
ABSTRACT:
The present invention relates to the use of hydroxyphenylvinylthiazoles in the antimicrobial treatment of surfaces, as an antimicrobial active ingredient against gram-positive and gram-negative bacteria, yeasts and fungi, as well as in the preservation of cosmetics, household products, textiles, plastics and disinfectants.
The hydroxyphenylvinylthiazoles used according to the invention have the formula
R
1
, R
2
, R
3
and R
4
are each independently of the others hydrogen; halogen; hydroxy, C
1
-C
16
-alkyl, C
1
-C
16
alkoxy, phenyl; phenyl-C
1
-C
3
alkyl; C
6
-C
10
aryloxy, amino, mono-C
1
-C
5
alkyl-amino, di-C
1
-C
5
alkylamino or -NO
2
; wherein at least one of the radicals R
1
, R
2
, R
3
and R
4
is hydroxy;
R
5
is C
1
-C
5
alkyl; C
1
-C
5
alkoxy; or unsubstituted or halo-, C
1
-C
5
alkyl-, C
1
-C
5
alkoxy-, hydroxy- or pyrrolidinyl-substituted phenyl.
C
1
-C
16
Alkyl radicals are straight-chain or branched alkyl radicals, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, un-decyl, dodecyl, tetradecyl, pentadecyl or hexadecyl.
C
1
-C
16
Alkoxy is, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy or pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy, undecyloxy, do decyloxy, tetradecyloxy, pentadecyloxy or hexadecyloxy.
Halogen is fluorine, chlorine, bromine or iodine.
The hydroxyphenylvinylthiazoles used according to the invention may be in the form of E or Z isomers. They are preferably in the form of E isomers.
Compounds that are of interest are hydroxyphenylvinylthiazoles of formula (1) wherein
R
1
, R
2
, R
3
and R
4
are each independently of the others hydrogen, hydroxy, C
1
-C
5
alkyl, C
1
-C
5
-alkoxy or phenyl-C
1
-C
3
alkyl.
Also of interest are compounds of formula (1) wherein
R
5
is C
1
-C
5
alkyl; or unsubstituted or halo- or pyrrolidinyl-substituted phenyl.
Compounds that are of very special interest have the formula
Further hydroxyphenylvinylthiazoles according to the invention are listed by way of example in Table 1 below:
TABLE 1
General formula:
Compound of
formula
R
1
R
2
R
3
R
4
R
5
(5)
H
OH
H
H
4-F—Ph
(6)
H
OH
OMe
H
4-F—Ph
(7)
H
OEt
OH
H
4-F—Ph
(8)
H
OMe
OH
H
4-F—Ph
(9)
OH
H
OMe
H
4-F—Ph
(10)
OH
H
H
H
4-F—Ph
(11)
H
OH
OMe
OMe
4-F—Ph
(12)
H
Me
OH
Me
4-F—Ph
(13)
OH
Me
H
H
4-F—Ph
(14)
OH
H
OBzl
H
4-F—Ph
(15)
OMe
H
OH
H
4-F—Ph
(16)
H
H
OH
H
t. but
(17)
H
OH
H
H
t. but
(18)
H
OH
OMe
H
t. but
(19)
H
OEt
OH
H
t. but
(20)
H
OMe
OH
H
t. but
(21)
OH
H
OMe
H
t. but
(22)
H
OH
OMe
OMe
t. but
(23)
H
Me
OH
Me
t. but
(24)
OH
Me
H
H
t. but
(25)
OH
H
OBzl
H
t. but
(26)
OMe
H
OH
H
t. but
(27)
H
H
OH
H
(28)
H
OH
H
H
(29)
H
OH
OMe
H
(30)
H
OEt
OH
H
(31)
H
OMe
OH
H
(32)
OH
H
OMe
H
(33)
OH
H
H
H
(34)
H
OH
OMe
OMe
(35)
H
Me
OH
Me
(36)
OH
Me
H
H
(37)
OH
H
OBzl
H
(38)
OMe
H
OH
H
(39)
H
H
OH
H
Et
(40)
H
OH
H
H
Et
(41)
H
OH
OMe
H
Et
(42)
H
OEt
OH
H
Et
(43)
H
OMe
OH
H
Et
(44)
OH
H
OMe
H
Et
(45)
OH
H
H
H
Et
(46)
H
OH
OMe
OMe
Et
(47)
H
Me
OH
Me
Et
(48)
OH
Me
H
H
Et
(49)
OH
H
OBzl
H
Et
(50)
OMe
H
OH
H
Et
(51)
H
OH
H
H
Ph
(52)
H
OH
OMe
H
Ph
(53)
H
OEt
OH
H
Ph
(54)
H
OMe
OH
H
Ph
(55)
OH
H
OMe
H
Ph
(56)
OH
H
H
H
Ph
(57)
H
OH
OMe
OMe
Ph
(58)
H
Me
OH
Me
Ph
(59)
OH
Me
H
H
Ph
(60)
OH
H
OBzl
H
Ph
(61)
OMe
H
OH
H
Ph
The preparation of the hydroxyphenylvinylthiazoles used according to the invention is pre-ferably carried out in a solid-phase synthesis using a trityl resin. The preparation is carried out according to the following scheme:
In the above scheme, R
1
, R
2
, R
3
, R
4
and R
5
are as defined for formula (1).
The method of synthesis is based on that specified in the literature by R
1
Willard et al., Chemistry & Biology, 2, 1995, 45-51. The preparation process according to the invention differs in that a trityl resin is used and the method of loading the resin is different.
Further details regarding the preparation process according to the invention will be found in the corresponding Examples.
The thiazol-2-ylmethylphosphonates (compound of formula (1c)) used as starting materials in the preparation according to the invention are prepared according to the known Hantzsch thiazole synthesis:
Diethyl (2-amino-2-thioxoethyl)phosphonate (2.1 g; 10 mmol) and bromomethyl ketone (10.5 mmol) are dissolved in methanol (10 ml) under a protective gas atmosphere. The reaction mixture is subsequently heated for 5 hours under reflux and then concentrated to dryness. The residue is taken up in dichloromethane (100 ml) and washed with saturated aqueous NaHCO
3
solution (2×50 ml) and NaCl solution (50 ml). The washing solutions are extracted with dichloromethane (25 ml) and the combined organic extracts are concentrated to dry-ness.
Yields: R
2
=4-F-Ph (87.1%); R
2
=t. but (84.7%); R
2
=4-(pyrrolidin-1-yl)-phenyl (98%); R
2
=Et (86.2%); R
2
=Ph (100%).
All the compounds are characterised by
1
H-NMR and show the corresponding chemical shifts.
The hydroxyphenylvinylthiazoles used according to the invention exhibit a pronounced anti-microbial action, especially against pathogenic gram-positive and gram-negative bacteria and also against bacteria of skin flora and, additionally, against yeasts and moulds. Accordingly, they are especially suitable in the disinfection, deodorisation and also the general and antimicrobial treatment of the skin and mucosa and of integumentary appendages (hair), more especially in the disinfection of the hands and of wounds.
Accordingly, they are suitable as antimicrobial active ingredients and preservatives in personal care preparations, for example shampoos, bath additives, hair-care products, liquid and solid soaps (based on synthetic surfactants and salts of saturated and/or unsaturated fatty acids), lotions and creams, deodorants, other aqueous or alcoholic solutions, for example cleansing solutions for the skin, moist cleansing cloths, oils or powders.
Accordingly, the invention relates also to a personal care preparation comprising at least one compound of formula (1), and cosmetically tolerable carriers or adjuvants.
The personal care preparation according to the invention comprises from 0.01 to 15% by weight, preferably from 0.1 to 10% by weight, based on the total weight of the composition, of a hydroxyphenylvinylthiazole compound of formula (1), and cosmetically tolerable adjuvants.
Depending on the form of the personal care preparation, it comprises further components in addition to the hydroxyphenylvinylthiazole compound of formula (1), for example sequestering agents, colourants, perfume oils, thickeners or strengthening agents (consistency regulators), emollients, UV absorbers, skin-protecting agents, antioxidants, additives that improve the mechanical properties, such as dicarboxylic acids and/or Al, Zn, Ca, Mg salts of C
14
-C
22
fatty acids, and optionally preservatives.
The personal care preparation according to the invention may be formulated as a water-in-oil or oil-in-water emulsion, as an alcoholic or alcohol-containing formulation, as a vesicular dispersion of an ionic or non-ionic amphiphilic lipid, as a gel, as a solid stick or as an aerosol formulation.
In the case of a water-in-oil or oil-in-water emulsion, the cosmetically tolerable adjuvant contains preferably from 5 to 50% of an oily phase, from 5 to 20% of an emulsifier and from 30 to 90% water. The oily phase may contain any oil suitable for cosmetic formulations, e.g. one or more hydrocarbon oils, a wax, a natural oil, a silicone oil, a fatty acid ester or a fatty alcohol. Preferred mono- or poly-ols are ethanol, isopropanol, propylene glycol, hexylene glycol, glycerol and sorbitol.
Cosmetic formulations according to the invention are used in a variety of fields. Especially the following preparations, for example, come into consideration:
skin-care preparations, e.g. skin-washing and cleansing preparations in the form of tablet-form or liquid soaps, soapless detergents or washing pastes;
bath preparations, e.g. liquid (foam baths, milks, shower preparations) o
Haap Wolfgang
Hölzl Werner
Ochs Dietmar
Puchtler Karin
Schnyder Marcel
Celsa Bennett
Ciba Specialty Chemicals Corporation
Epperson Jon
Mansfield Kevin T.
LandOfFree
Hydroxyphenylvinylthiazoles does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Hydroxyphenylvinylthiazoles, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Hydroxyphenylvinylthiazoles will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3089177