DE102005025161A1 - New pyrimidine- and triazine derivatives are peroxisome proliferator activated receptor modulators, useful to treat e.g. diabetes, insulin resistance, obesity, hyperlipidemia, cardiovascular diseases and Alzheimer's disease - Google Patents

Abstract

Pyrimidine- and triazine derivatives (I) are new. Pyrimidine- and triazine derivatives of formula (I) and their salts are new. W1>e.g. halo, CF3, H, 1-12C alkyl, 3-8C cycloalkyl, 3-8C cycloalkyl-1-4C alkyl, 2-12C alkenyl, 2-12C alkynyl, hetero alkyl, sulfo, sulfino, sulfeno or (thio)formyl; X : e.g. N or CH; Y1>e.g. NR3>-C(O)-NR4>-L; L : 1-12C alkyl or heteroalkyl; R3>, R4>e.g. 6-10C aryl, H, CF3, 1-12C alkyl, 3-8C cycloalkyl, 3-8C cycloalkyl-1-4C alkyl or 2-12C alkenyl; Z : e.g. D-E-V1>; D : e.g. O or S; E : optionally substituted 1-6C alkyl, heterocycloalkyl, 1-12C alkylsulfonyl or imino; and V1>tetrazolyl or thiazolidindionyl. Full Definitions are given in the DEFINITIONS (Full Definitions) Field. An independent claim is included for a pharmaceutical or cosmetic composition containing (I). [Image] ACTIVITY : Antidiabetic; Anorectic; Antilipemic; Cardiovascular-Gen.; Antiarteriosclerotic; Hypotensive; Immunomodulator; Immunosuppressive; Gastrointestinal-Gen.; Neuroprotective; Nootropic; Antiinflammatory; Antiarthritic; Antirheumatic; Analgesic; Antianginal; Vasotropic; Dermatological; Cytostatic; Thrombolytic; Cerebroprotective; Cardiant; Antiallergic; Antiulcer; Vulnerary; Antipsoriatic; Endocrine-Gen. MECHANISM OF ACTION : Peroxisome proliferator activated receptor modulator. The ability of (I) to modulate peroxisome proliferator activated receptor was tested using biological assays. The results showed that [4-(4-bromo-2,3-dimethyl-phenylamino)-6-chloro-pyrimidin-2-ylsulfanyl]-phenyl-acetic acid exhibited an medium effective concentration value of 0.27 mu M.

Description

The The present invention relates to derivatives of pyrimidine and triazine and / or their physiologically acceptable salts and the use these substances for the production of a pharmaceutical or cosmetic Composition for the treatment of diseases and disease states.

The so-called peroxisome proliferator activated receptors (PPARs) belong to the family of nuclear receptors and are naturally by fatty acids and fatty acid metabolites activated. The PPARs belong to a group of nuclear receptors that are in their active form are present as heterodimers with the 9-cis retinoic acid receptor (RXR). There were three different subtypes of PPAR receptors be identified, namely PPARα, PPARγ and PPARδ. PPARδ will too referred to as PPARβ.

PPARα becomes available especially in tissues with high mitochondrial and peroxisomal β-oxidation activity, such as liver, Skeletal muscle, heart, kidney or colon, expressed and is transmitted through a number of medium and long chain fatty acids as well as fatty acid derivatives activated. PPARα is et al in the lipid catabolism (β-oxidation of fatty acids), in the control of inflammation and the proliferation and differentiation of keratinocytes involved.

PPARγ is the Main type of adipose tissue, but is also e.g. in liver, heart, skeletal muscles and macrophages expressed. PPARγ stands in connection with the differentiation of adipocytes, plays an important Role in lipid anabolism and is also involved in the control of inflammation. There are two isomeric forms of PPARγ, namely PPARγ1 and PPARγ2, which differ in that PPARγ2 at the N-terminus additional 28 amino acids includes. PPAR activators are e.g. unsaturated Fatty acids and Fatty acid derivatives.

PPARα and / or Play PPARγ in many diseases and disease states an important role, wherein the diseases and disease states by activation of said Receptors can be positively influenced. To these diseases counting especially diabetes mellitus, obesity, hyperlipidemia, dyslipidaemia, diseases, due to dysregulation of the immune system, cardiovascular diseases, in particular arteriosclerosis and hypertension, and gastrointestinal Diseases, especially intestinal inflammation, but also other inflammatory Diseases, such as Alzheimer's disease, Crohn's disease, rheumatoid Arthritis, Syndrome X and the so-called ischemia reprofusion injury, and diseases that indicate a disrupted skin barrier function are attributed. The diseases and disease states mentioned are causally related possible with the person skilled in the art Consequences to thrombosis, stroke and heart attack. There has already been a connection between the modulation of PPARs and cancer (Burstein et al., Breast Cancer Res. Treat. 2003 79 (3): 391-7; Alderd et al., Oncogene, 2003, 22 (22): 3412-6).

Further there is a connection between the activation of PPARs and diseases, the on a disturbed Barrier function of the skin, in WO 98/32444, with respect to the treatable Referenced diseases.

at Diabetes is the body unable to sufficiently convert glucose into its polymeric storage form To convert glycogen. This is due to type I diabetes in a reduced insulin production. In diabetes type II is the cause is due to an insufficient stimulating effect of insulin insufficient sensitivity the cells to be stimulated. To compensate for the weak stimulus, be increased Produces quantities of insulin, which leads to hyperinsulemia, the with elevated Blood pressure and elevated body weight accompanied. In addition, it may increase the triglyceride and LDL concentration come, what an heightened Risk for cardiovascular Illness means. The latter condition is also called "syndrome X "denotes.

to Treatment of diabetes usually became hypoglycemic agents such as sulfonyl urea compounds, e.g. Chlorpropamide, tolbutamide, Tolazamide or acetohexamide, or biguanides, e.g. Phenformin or Metformin, used, and optionally insulin injected. A Danger with this treatment, however, is that it is in Consequence of this treatment can come to a hypoglykämischen coma.

Long-chain fatty acids, leukotriene antagonists, fibrates, some herbicides and chemical softeners (phthalates) for plastics processing have long been known as PPARα activators. In particular, the fibrates (eg, clofibrate, gemfibrozil) have been used systemically in humans for more than 20 years as Li used pidsenker.

In recent years it has been found that thiazolidinediones increase the sensitivity of the cells to be stimulated by binding to the PPARγ receptor and therefore represent suitable candidates for the treatment of diabetes II ( US 4340605 . US 4342771 . US 4367234 . US 5089514 . US 5306726 ).

Furthermore, acetylphenols have been reported which could be used in obesity and diabetes (WO 97/28115, WO 97/28135, US 5895051 ). WO 97/28149 reports PPARδ agonists which can be used in cardiovascular diseases.

Farther is u.a. in WO 02/100813, WO 05/019151 and WO 05/009958 on substances reports that agonistically act on PPARs and therefore appropriate Candidates for represent the aforementioned diseases.

inflammatory changes der Hautorgans are widespread diseases. Especially psoriasis (psoriasis) belongs with a morbidity of 1 - 2% in the population the most common Skin diseases. Psoriasis is about as common as it is Diabetes mellitus. In addition to psoriasis, there is a high morbidity of an estimated 5 - 20% for the atopic Eczema (atopic dermatitis). There are clear signs that the frequency of atopic diseases increases. For symptomatic treatment the two mentioned inflammatory Skin diseases become common Steroids (cortisone) administered topically and / or systemically. These Substance class shows in addition to their anti-inflammatory efficacy also one Series of unwanted Side effects (e.g., atrophy, Cushing syndrome).

Applicant previously discovered that by treatment with the pyrimidine derivative, pirinixic acid (WY-14,643 (CAS # 50892-23-4); [[4-chloro-6- [2,3-xylidino] -2-pyrimidinyl] thio] -acetic acid or [[4-chloro-6 - [(2,3-dimethylphenyl) amino] -2-pyrimidinyl] thio] acetic acid), in particular when topically applied, a very good success in the treatment of chronic inflammatory Diseases, in particular of psoriasis and atopic eczema, can be achieved, especially in refractory forms of these diseases, that is, in forms of disease that were untreatable by conventional therapy. The pirinixic acid and other pyrimidine and triazine derivatives were originally developed for use as lipid lowering agents ( EP 0073328 . US 3901887 . US 3910910 . US 3940394 . DE 2314160 . DE 2711149 . US 3814761 . US 3876789 and US 3896129 ).

In a publication it has been reported that a pirinixic acid-containing cream prophylactically suppresses the expression of UVB-induced erythema (Kippenberger et al. (2001) J. Invest. Dermatol. 117, 1430-1436, EP1331934 ).

Surprisingly It has now been found that other pyrimidine derivatives apparently have a have better efficacy in activating PPARs as the pirinixic acid. On the basis of the applicant found particularly advantageous Effect of pirinxic acid With regard to the treatment of psoriasis, it must be assumed that that these pyrimidine and triazine derivatives in particular in terms of the treatment of inflammatory Dermatoses such as psoriasis and atopic dermatitis are particularly good are suitable.

wobei
W für Halogen, insbesondere Chlor, Brom oder Fluor, Trifluormethyl, Wasserstoff, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkyl-C_1-4-alkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, C_1-12-Alkylsulfonyl, C_1-12-Alkylsulfoxidyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, NR¹R², C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C_1-12-Alkoxysulfonyl, C_1-12-Alkoxycarbinol, Sulfo, Sulfino, Sulfeno, Formyl oder Thioformyl steht, wobei Chlor bevorzugt ist,
X für N oder CR^a steht, wobei CH bevorzugt ist,
Y für (A)_m-B-(M)_o-Q, (A)_m-B-(M)_o-L, NR³-C(O)-NR⁴-Q oder NR³-C(O)-NR⁴-L steht,
A für C_1-3-Alkyl oder CO, insbesondere Methylen, steht,
B für NR⁵, CR^bR^c, CO, O oder S, bevorzugt NH, steht,
M für C_1-3-Alkyl oder CO, insbesondere Methylen, steht,
Q für gegebenenfalls ein- oder mehrfach substituiertes, insbesondere zwei-, drei-, vier- oder fünffach substituiertes, vorzugsweise zwei- oder dreifach substituiertes, C_6-10-Aryl oder Heteroaryl, besonders bevorzugt Phenyl, steht, wobei Heteroaryl für einen mindestens ein Heteroatom ausgewählt aus O, S und N enthaltenden aromatischen Rest mit 5 bis 9, vorzugsweise 5 oder 6, Ringgliedern steht und die Substituenten vorzugsweise ausgewählt sind aus Halogen, insbesondere Chlor, Brom oder Fluor, Trifluormethyl, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkyl-C_1-4-alkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, C_1-12-Alkylsulfonyl, C_1-12-Alkylsulfoxidyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl C_1-12-Alkylsulfanylcarbonyl, Hydroxy, Carboxy, Cyan, NR⁶R⁷, C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C_1-12-Alkoxysulfonyl, C_1-12-Alkoxycarbinol, Sulfo, Sulfino, Sulfeno, Formyl oder Thioformyl, wobei mindestens zwei vicinal angeordnete Substituenten, insbesondere Alkyl-Substituenten, auch unter Ausbildung eines 5- oder 6-gliedrigen gegebenenfalls Heteroatome ausgewählt aus N, O oder S enthaltenden Ringes, insbesondere Alkyl-Ringes, miteinander verknüpft sein können,
L für C_1-12-Alkyl oder Heteroalkyl steht,
Z für D-E-C(O)-(F)_p-G oder D-E-V steht,
D für O, S, CR^dR^e oder NR⁸, bevorzugt S, steht,
E für gegebenenfalls ein- oder mehrfach substituiertes, bevorzugt ein- oder zweifach substituiertes C_1-6-Alkyl, bevorzugt Methylen oder Ethylen, besonders bevorzugt Methylen, steht, wobei die Substituenten unabhängig voneinander ausgewählt sind aus Halogen, insbesondere Chlor, Brom oder Fluor, Trifluormethyl, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkyl-C_1-4-alkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, C_1-12-Alkylsulfonyl, C_1-12-Alkylsulfoxidyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, Carboxy, Cyan, NR⁹R¹⁰, C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C_1-12-Alkoxysulfonyl, C_1-12-Alkoxycarbinol, Sulfo, Sulfino, Sulfeno, Formyl, Thioformyl, Hydroxyimino, Hydrazono oder Imino, bevorzugt aus C_1-12-Alkyl, C_3-8-Cycloalkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, NR⁹R¹⁰, C_6-10-Aryl, Heteroaryl und C_6-10-Aryl-C_1-4-alkyl, besonders bevorzugt aus C_1-8-Alkyl und C_6-10-Aryl,
F für C_1-6-Alkylen, bevorzugt Methylen oder Ethylen, steht,
G für NR¹¹R¹², NR¹²-NR¹²R¹³, OR¹¹, bevorzugt OH, steht,
V für Tetrazolyl oder Thiazolidindionyl steht,
m für 0 oder 1 steht,
o für 0 oder 1 steht,
p für 0 oder 1, bevorzugt 0, steht,
R^a, R^b, R^c, R^d und R^e unabhängig voneinander für Halogen, insbesondere Chlor, Brom oder Fluor, Trifluormethyl, Wasserstoff, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkyl-C_1-4-alkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl,C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, C_1-12-Alkylsulfonyl, C_1-12-Alkylsulfoxidyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, Carboxy, Cyan, Amino, (C_1-12-Alkyl)NH, Di-(C_1-12-Alkyl)N, C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C_1-12-Alkoxysulfonyl, C_1-12-Alkoxycarbinol, Sulfo, Sulfino, Sulfeno, Formyl oder Thioformyl, bevorzugt für Wasserstoff, Halogen, C_1-6-Alkyl oder C_6-10-Aryl, besonders bevorzugt für Wasserstoff, stehen,
R¹, R², R³, R^a, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹² und R¹³ unabhängig voneinander für Trifluormethyl, Wasserstoff, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkyl-C_1-4-alkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl, C_1-12-Alkylsulfonyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, Carboxy, Cyan, Amino, (C_1-12-Alkyl)NH, Di-(C_1-12-Alkyl)N, C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, bevorzugt für Wasserstoff, C_6-10-Alkyl oder C_6-10-Aryl, besonders bevorzugt für Wasserstoff, stehen,
wobei alle Reste des sich so ergebenden Moleküls, insbesondere die aliphatischen und aromatischen Reste, sofern nicht anders angegeben, jeweils unabhängig voneinander gegebenenfalls auch ein- oder mehrfach, insbesondere ein-, zwei- oder dreifach, vorzugsweise einfach, substituiert sein können, insbesondere durch Substituenten ausgewählt aus Halogen, insbesondere Chlor, Brom oder Fluor, Trifluormethyl, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, C_1-12-Alkylsulfonyl, C_1-12-Alkylsulfoxidyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, Carboxy, Cyan, Amino, (C_1-12-Alkyl)NH, Di-(C_1-12-Alkyl)N, C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfonyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C_1-12-Alkoxysulfonyl, C_1-12-Alkoxycarbinol, Sulfo, Sulfino, Sulfeno, Formyl, Thioformyl, Hydroxyimino, Hydrazono oder Imino, bevorzugt durch Halogen, C_1-6-Alkyl, C_1-6-Alkoxy oder Hydroxy,
und wobei die Gesamtzahl an diesen Substituenten im Molekül vorzugsweise bis zu fünf, besonders bevorzugt bis zu drei, insbesondere eins, zwei oder drei, beträgt,
und/oder physiologisch verträglicher Salze dieser Moleküle,
mit Ausnahme der Pirinixinsäure,
zur Herstellung einer pharmazeutischen oder kosmetischen Zusammensetzung zur Behandlung von entzündlichen Dermatosen, insbesondere Psoriasis oder atopischer Dermatitis.A first subject of the present invention is therefore the use of pyrimidine and triazine derivatives of the general formula (I)

in which
W is halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, hydrogen, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _3-8 -cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl, C _2-12 alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 alkoxy, C _1-12 alkylsulfanyl, C _1-12 alkylsulfonyl, C _1-12 alkyl sulfoxide, C _1-12 alkanoyl, C _1-12 Alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 -alkylaminocarbonyl, C _1-12 -alkylsulfanylcarbonyl, hydroxy, NR ¹ R ² , C _6-10 -aryl, C _6-10 -aryl-C _1-4 alkyl, C _6-10 aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxide, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy , C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl , Heteroarylsulfanylcarbonyl, C _1-12 alkoxysulfonyl, C _1-12 -Al koxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, with chlorine being preferred,
X is N or CR ^a , with CH being preferred,
Y is (A) _m -B- (M) _o -Q, (A) _m -B- (M) _o -L, NR ³ -C (O) -NR ⁴ -Q or NR ³ -C (O) -NR ⁴ -L is
A represents C _1-3 -alkyl or CO, in particular methylene,
B is NR ⁵ , CR ^{b is} R ^c , CO, O or S, preferably NH,
M is C _1-3 -alkyl or CO, in particular methylene,
Q is optionally mono- or polysubstituted, in particular di-, tri-, tetra- or quintuply substituted, preferably di- or trisubstituted, C _6-10 -aryl or heteroaryl, more preferably phenyl, where heteroaryl is at least one Heteroatom selected from O, S and N containing aromatic radical having 5 to 9, preferably 5 or 6, ring members and the substituents are preferably selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 alkyl, C _{3 -8-} cycloalkyl, C _3-8 -cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl , C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _1-12 -alkanoyloxy, C _1-12 -alkoxycarbonyl, C _1-12 -alkylaminocarbonyl, C _1-12 -alkylsulfanylcarbonyl, hydroxy , Carboxy, cyano, NR ⁶ R ⁷ , C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 -arylamino, C _6-10 - Arylsulfanyl, C _6-10 -Arylsulfonyl, C _6-10 arylsulfoxidyl, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy, C _6-10 aryloxycarbonyl, C _6-10 arylaminocarbonyl, C _6-10 arylsulfanylcarbonyl, heteroaryl, heteroaryl-C _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, wherein at least two vicinally arranged substituents, in particular alkyl substituents, may also be linked together to form a 5- or 6-membered optionally heteroatoms selected from N, O or S-containing ring, in particular alkyl ring,
L is C _1-12 -alkyl or heteroalkyl,
Z is DEC (O) - (F) _p -G or DEV,
D represents O, S, CR ^d R ^e or NR ⁸ , preferably S,
E is optionally monosubstituted or polysubstituted, preferably mono- or disubstituted C _1-6 -alkyl, preferably methylene or ethylene, more preferably methylene, wherein the substituents are independently selected from halogen, in particular chlorine, bromine or fluorine, Trifluoromethyl, C _1-12 alkyl, C _3-8 cycloalkyl, C _3-8 cycloalkylC _1-4 alkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl, heterocycloalkyl, C _{1 -12-} alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _1-12 -alkanoyloxy, C _1-12 -alkoxycarbonyl, C _{1- 12-} alkylaminocarbonyl, C _1-12 -alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, NR ⁹ R ¹⁰ , C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxidyl, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy, C _6-10 aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroaryl-C _1-4 -alky l, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl, thioformyl, hydroxyimino, hydrazono or Imino, preferably selected from C _1-12 -alkyl, C _3-8 -cycloalkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl, NR ⁹ R ¹⁰ , C _6-10 -aryl, heteroaryl and C _6-10 -aryl-C _1-4 -alkyl, particularly preferably C _1-8 -alkyl and C _6-10 -aryl,
F is C _1-6 -alkylene, preferably methylene or ethylene,
G is NR ¹¹ R ¹² , NR ¹² -NR ¹² R ¹³ , OR ¹¹ , preferably OH,
V is tetrazolyl or thiazolidinedionyl,
m is 0 or 1,
o is 0 or 1,
p is 0 or 1, preferably 0,
R ^a , R ^b , R ^c , R ^d and R ^{e are} independently halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, hydrogen, C _1-12 alkyl, C _3-8 cycloalkyl, C _3-8 cycloalkyl C _1-4 -alkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _{1- 12} alkylsulfoxidyl, C _1-12 alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _{1 -12-} alkyl) NH, di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _{6- 10-} arylamino, C _6-10 -arylsulfanyl, C _6-10 -arylsulfonyl, C _6-10 -arylsulfoxide, C _6-10 -arylcarbonyl, C _6-10 -arylcarbonyloxy, C _6-10 -aryloxy carbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _{1 12-} alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, preferably hydrogen, halogen, C _1-6 -alkyl or C _6-10 -aryl, particularly preferably hydrogen,
R ¹ , R ² , R ³ , R ^a , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are each independently trifluoromethyl, hydrogen, C _1-12 Alkyl, C _3-8 -cycloalkyl, C _3-8 -cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkylsulfonyl, C _{1 -12} alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 alkyl) NH , Di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 -aryl-amino, C _{6 -10-} arylsulfanyl, C _6-10 -arylsulfonyl, C _6-10 -arylsulfoxidyl, C _6-10 -arylcarbonyl, C _6-10 -arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _{6- 10} arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfany lcarbonyl, preferably hydrogen, C _6-10 -alkyl or C _6-10 -aryl, particularly preferably hydrogen,
wherein all the radicals of the resulting molecule, in particular the aliphatic and aromatic radicals, unless otherwise stated, may each independently be optionally mono- or polysubstituted, in particular mono-, di- or trisubstituted, preferably monosubstituted, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 - Alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _1-12 -alkanoyloxy, C _1-12 -alkoxycarbonyl, C _1-12 -alkylaminocarbonyl , C _1-12 -alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 -alkyl) NH, di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 - ArylC _1-4 alkyl, C _6-10 aryloxy, C _6-10 arylamino, C _6-10 arylsulfonyl, C _6-10 arylsulfonyl, C _6-10 aryl sulfoxide, C _6-10 arylcarbonyl C _6-10 arylcarbonyloxy, C _6-10 aryloxycarbo nyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _{1 12-} alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl, thioformyl, hydroxyimino, hydrazono or imino, preferably by halogen, C _1-6 -alkyl, C _1-6 -alkoxy or hydroxyl,
and wherein the total number of these substituents in the molecule is preferably up to five, more preferably up to three, in particular one, two or three,
and / or physiologically acceptable salts of these molecules,
with the exception of pirinixic acid,
for the preparation of a pharmaceutical or cosmetic composition for the treatment of inflammatory dermatoses, in particular psoriasis or atopic dermatitis.

wobei
W für Halogen, insbesondere Chlor, Brom oder Fluor, Trifluormethyl, Wasserstoff, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkyl-C_1-4-alkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, C_1-12-Alkylsulfonyl, C_1-12-Alkylsulfoxidyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, NR¹R², C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C_1-12-Alkoxysulfonyl, C_1-12-Alkoxycarbinol, Sulfo, Sulfino, Sulfeno, Formyl oder Thioformyl steht, wobei Chlor bevorzugt ist,
X für N oder CR^a steht, wobei CH bevorzugt ist,
Y für (A)_m-B-(M)_o-Q, (A)_m-B-(M)_o-L, NR³-C(O)-NR⁴-Q oder NR³-C(O)-NR⁴-L steht,
A für C_1-3-Alkyl oder CO, insbesondere Methylen, steht,
B für NR⁵, CR^bR^c, CO, O oder S, bevorzugt NH, steht,
M für C_1-3-Alkyl oder CO, insbesondere Methylen, steht,
Q für dreifach substituiertes Phenyl steht, wobei zwei der drei Reste unabhängig voneinander ausgewählt sind aus C_1-3-Alkyl, insbesondere Methyl, Ethyl, n-Propyl und i-Propyl, und es sich bei dem dritten Rest um Chlor, Brom, C_1-6-Alkoxy, C_1-6-Alkylsulfanyl oder Di-(C_1-6-Alkyl)N, bevorzugt um Chlor oder Brom handelt, oder Q für zweifach substituiertes Phenyl steht, wobei die beiden Substituenten, insbesondere Alkyl-Substituenten, vicinal angeordnet sind und einen 5- oder 6-gliedrigen gegebenenfalls Heteroatome ausgewählt aus N, O oder S enthaltenden Ring, insbesondere Alkyl-Ring, ausbilden,
L für C_1-12-Alkyl oder Heteroalkyl steht,
Z für D-E-C(O)-(F)_p-G oder D-E-V steht,
D für O, S, CR^dR^e oder NR⁸, bevorzugt S, steht,
E für gegebenenfalls ein- oder mehrfach substituiertes, bevorzugt ein- oder zweifach substituiertes C_1-6-Alkyl, bevorzugt Methylen oder Ethylen, besonders bevorzugt Methylen, steht, wobei die Substituenten unabhängig voneinander ausgewählt sind aus Halogen, insbesondere Chlor, Brom oder Fluor, Trifluormethyl, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkyl-C_1-4-alkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, C_1-12-Alkylsulfonyl, C_1-12-Alkylsulfoxidyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, Carboxy, Cyan, NR⁹R¹⁰, C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C_1-12-₁₂-Alkoxysulfonyl, C_1-12-Alkoxycarbinol, Sulfo, Sulfino, Sulfeno, Formyl, Thioformyl, Hydroxyimino, Hydrazono oder Imino, bevorzugt aus C_1-12-Alkyl, C_3-8-Cycloalkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, NR⁹R¹⁰, C_6-10-Aryl, Heteroaryl und C_6-10-Aryl-C_1-4-alkyl, besonders bevorzugt aus C_1-8-Alkyl und C_6-10-Aryl,
F für C_1-6-Alkylen, bevorzugt Methylen oder Ethylen, steht,
G für NR¹¹R¹², NR¹²-NR¹²R¹³, OR¹¹, bevorzugt OH, steht,
V für Tetrazolyl oder Thiazolidindionyl steht,
m für 0 oder 1 steht,
o für 0 oder 1 steht,
p für 0 oder 1, bevorzugt 0, steht,
R^a, R^b, R^c, R^d und R^e unabhängig voneinander für Halogen, insbesondere Chlor, Brom oder Fluor, Trifluormethyl, Wasserstoff, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkyl-C_1-4-alkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, C_1-12-Alkylsulfonyl, C_1-12-Alkylsulfoxidyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, Carboxy, Cyan, Amino, (C_1-12-Alkyl)NH, Di-(C_1-12-Alkyl)N, C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, _6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C_1-12-Alkoxysulfonyl, C_1-12-Alkoxycarbinol, Sulfo, Sulfino, Sulfeno, Formyl oder Thioformyl, bevorzugt für Wasserstoff, Halogen, C_1-6-Alkyl oder C_6-10-Aryl, besonders bevorzugt für Wasserstoff, stehen,
R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹² und R¹³ unabhängig voneinander für Trifluormethyl, Wasserstoff, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkyl-C_1-4-alkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl, C_1-12-Alkylsulfonyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, Carboxy, Cyan, Amino, (C_1-12-Alkyl)NH, Di-(C_1-12-Alkyl)N, C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, bevorzugt für Wasserstoff, C_1-6-Alkyl oder C_6-10-Aryl, besonders bevorzugt für Wasserstoff, stehen,
wobei alle Reste des sich so ergebenden Moleküls, insbesondere die aliphatischen und aromatischen Reste, sofern nicht anders angegeben, jeweils unabhängig voneinander gegebenenfalls auch ein- oder mehrfach, insbesondere ein-, zwei- oder dreifach, vorzugsweise einfach, substituiert sein können, insbesondere durch Substituenten ausgewählt aus Halogen, insbesondere Chlor, Brom oder Fluor, Trifluormethyl, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, C_1-12-Alkylsulfonyl, C_1-12-Alkylsulfoxidyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, Carboxy, Cyan, Amino, (C_1-12-Alkyl)NH, Di-(C_1-12-Alkyl)N, C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C_1-12-Alkoxysulfonyl, C_1-12-Alkoxycarbinol, Sulfo, Sulfino, Sulfeno, Formyl, Thioformyl, Hydroxyimino, Hydrazono oder Imino, bevorzugt durch Halogen, C_1-6-Alkyl, C_1-6-Alkoxy oder Hydroxy,
und wobei die Gesamtzahl an diesen Substituenten im Molekül vorzugsweise bis zu fünf, besonders bevorzugt bis zu drei, insbesondere eins, zwei oder drei, beträgt,
und/oder physiologisch verträgliche Salze dieser Moleküle,
sowie die Verwendung dieser Substanzen zur Herstellung einer pharmazeutischen oder kosmetischen Zusammensetzung zur Aktivierung von PPARα- und/oder PPARγ-Rezeptoren und/oder zur Behandlung von Krankheiten oder Krankheitszuständen.Another object of the present invention are therefore pyrimidine and triazine derivatives of the general formula (I)

in which
W is halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, hydrogen, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _3-8 -cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl, C _2-12 alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 alkoxy, C _1-12 alkylsulfanyl, C _1-12 alkylsulfonyl, C _1-12 alkyl sulfoxide, C _1-12 alkanoyl, C _1-12 Alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 -alkylaminocarbonyl, C _1-12 -alkylsulfanylcarbonyl, hydroxy, NR ¹ R ² , C _6-10 -aryl, C _6-10 -aryl-C _1-4 alkyl, C _6-10 aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxide, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy , C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl , Heteroarylsulfanylcarbonyl, C _1-12 alkoxysulfonyl, C _1-12 -Al koxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, with chlorine being preferred,
X is N or CR ^a , with CH being preferred,
Y is (A) _m -B- (M) _o -Q, (A) _m -B- (M) _o -L, NR ³ -C (O) -NR ⁴ -Q or NR ³ -C (O) -NR ⁴ -L is
A represents C _1-3 -alkyl or CO, in particular methylene,
B is NR ⁵ , CR ^{b is} R ^c , CO, O or S, preferably NH,
M is C _1-3 -alkyl or CO, in particular methylene,
Q is triply substituted phenyl wherein two of the three radicals are independently selected from C _1-3 alkyl, especially methyl, ethyl, n-propyl and i -propyl, and the third radical is chloro, bromo, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl or di- (C _1-6 -alkyl) N, preferably chlorine or bromine, or Q is doubly substituted phenyl, where the two substituents, in particular alkyl substituents, are vicinally arranged and form a 5- or 6-membered optionally heteroatoms selected from N, O or S containing ring, in particular alkyl ring,
L is C _1-12 -alkyl or heteroalkyl,
Z is DEC (O) - (F) _p -G or DEV,
D represents O, S, CR ^d R ^e or NR ⁸ , preferably S,
E is optionally monosubstituted or polysubstituted, preferably mono- or disubstituted C _1-6 -alkyl, preferably methylene or ethylene, more preferably methylene, wherein the substituents are independently selected from halogen, in particular chlorine, bromine or fluorine, Trifluoromethyl, C _1-12 alkyl, C _3-8 cycloalkyl, C _3-8 cycloalkylC _1-4 alkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl, heterocycloalkyl, C _{1 -12-} alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _1-12 -alkanoyloxy, C _1-12 -alkoxycarbonyl, C _{1- 12-} alkylaminocarbonyl, C _1-12 -alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, NR ⁹ R ¹⁰ , C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxidyl, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy, C _6-10 aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroaryl-C _1-4 -alky l, heteroaryloxy, heteroarylamino, Heteroarylsulfanyl, heteroarylsulfonyl, Heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C _1-12 - ₁₂ alkoxysulfonyl, C _1-12 -Alkoxycarbinol, sulfo, sulfino, sulfeno, formyl, thioformyl, hydroxyimino, Hydrazono or imino, preferably from C _1-12 -alkyl, C _3-8 -cycloalkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl, NR ⁹ R ¹⁰ , C _6-10 -aryl, heteroaryl and C _6-10 -aryl-C _1-4 -alkyl, particularly preferably from C _1-8 -alkyl and C _6-10 -aryl,
F is C _1-6 -alkylene, preferably methylene or ethylene,
G is NR ¹¹ R ¹² , NR ¹² -NR ¹² R ¹³ , OR ¹¹ , preferably OH,
V is tetrazolyl or thiazolidinedionyl,
m is 0 or 1,
o is 0 or 1,
p is 0 or 1, preferably 0,
R ^a , R ^b , R ^c , R ^d and R ^{e are} independently halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, hydrogen, C _1-12 alkyl, C _3-8 cycloalkyl, C _3-8 cycloalkyl C _1-4 -alkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _{1- 12} alkylsulfoxidyl, C _1-12 alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _{1 -12-} alkyl) NH, di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _{6- 10-} arylamino, C _6-10 -arylsulfanyl, _6-10 -arylsulfonyl, C _6-10 -arylsulfoxidyl, C _6-10 -arylcarbonyl, C _6-10 -arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 - Arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryl loxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, preferably hydrogen, halogen, C _1-6 -alkyl or C _6-10 -aryl, particularly preferred for hydrogen,
R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are each independently trifluoromethyl, hydrogen, C _1-12 Alkyl, C _3-8 -cycloalkyl, C _3-8 -cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkylsulfonyl, C _{1 -12} alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 alkyl) NH , Di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 -aryl-amino, C _{6 -10-} arylsulfanyl, C _6-10 -arylsulfonyl, C _6-10 -arylsulfoxidyl, C _6-10 -arylcarbonyl, C _6-10 -arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _{6- 10} arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfany lcarbonyl, preferably hydrogen, C _1-6 -alkyl or C _6-10 -aryl, particularly preferably hydrogen,
wherein all the radicals of the resulting molecule, in particular the aliphatic and aromatic radicals, unless otherwise stated, may each independently be optionally mono- or polysubstituted, in particular mono-, di- or trisubstituted, preferably monosubstituted, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 - Alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _1-12 -alkanoyloxy, C _1-12 -alkoxycarbonyl, C _1-12 -alkylaminocarbonyl , C _1-12 -alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 -alkyl) NH, di (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 arylC _1-4 alkyl, C _6-10 aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 aryl sulfoxide, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy, C _6-10 aryloxycarbonyl, C _6-10 arylaminocarbonyl, C _6-10 arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl , Heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl, thioformyl, hydroxyimino, hydrazono or imino, preferably by halogen, C _1-6- alkyl, C _1-6 -alkoxy or hydroxy,
and wherein the total number of these substituents in the molecule is preferably up to five, more preferably up to three, in particular one, two or three,
and / or physiologically acceptable salts of these molecules,
and the use of these substances for the preparation of a pharmaceutical or cosmetic composition for the activation of PPARα and / or PPARγ receptors and / or for the treatment of diseases or disease states.

wobei
W für Halogen, insbesondere Chlor, Brom oder Fluor, Trifluormethyl, Wasserstoff, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkyl-C_1-4-alkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, C_1-12-Alkylsulfonyl, C_1-12-Alkylsulfoxidyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, NR¹R², C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C_1-12-Alkoxysulfonyl, C_1-12-Alkoxycarbinol, Sulfo, Sulfino, Sulfeno, Formyl oder Thioformyl steht, wobei Chlor bevorzugt ist,
X für N oder CR^a steht, wobei CH bevorzugt ist,
Y für (A)_m-B-(M)_o-Q, (A)_m-B-(M)_o-L, NR³-C(O)-NR⁴-Q oder NR³-C(O)-NR⁴-L steht,
A für C_1-3-Alkyl oder CO, insbesondere Methylen, steht,
B für NR⁵, CR^bR^c, CO, O oder S, bevorzugt NH, steht,
M für C_1-3-Alkyl oder CO, insbesondere Methylen, steht,
Q für gegebenenfalls ein- oder mehrfach substituiertes, insbesondere zwei-, drei-, vier- oder fünffach substituiertes, vorzugsweise zwei- oder dreifach substituiertes, C_6-10-Aryl oder Heteroaryl, besonders bevorzugt Phenyl, steht, wobei Heteroaryl für einen mindestens ein Heteroatom ausgewählt aus O, S und N enthaltenden aromatischen Rest mit 5 bis 9, vorzugsweise 5 oder 6, Ringgliedern steht und die Substituenten vorzugsweise ausgewählt sind aus Halogen, insbesondere Chlor, Brom oder Fluor, Trifluormethyl, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkyl-C_1-4-alkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, C_1-12-Alkylsulfonyl, C_1-12-Alkylsulfoxidyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl C_1-12-Alkylsulfanylcarbonyl, Hydroxy, Carboxy, Cyan, NR⁶R⁷, C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C_1-12-Alkoxysulfonyl, C_1-12-Alkoxycarbinol, Sulfo, Sulfino, Sulfeno, Formyl oder Thioformyl, wobei mindestens zwei vicinal angeordnete Substituenten, insbesondere Alkyl-Substituenten, auch unter Ausbildung eines 5- oder 6-gliedrigen gegebenenfalls Heteroatome ausgewählt aus N, O oder S enthaltenden Ringes, insbesondere Alkyl-Ringes, miteinander verknüpft sein können,
L für C_1-12-Alkyl oder Heteroalkyl steht,
Z für S(CR^xR^y)C(O)-G steht, wobei entweder
R^x für H steht und R^y für C_1-10-Alkyl, insbesondere Methyl, Ethyl, Propyl, insbesondere n-Propyl oder i-Propyl, Butyl, insbesondere n-Butyl, i-Butyl oder t-Butyl, Pentyl, insbesondere n-Pentyl oder 2-Pentyl, Hexyl, insbesondere n-Hexyl, 2-Hexyl oder 3-Hexyl, Heptyl, insbesondere n-Heptyl, 2-Heptyl oder 3-Heptyl, oder Octyl, insbesondere n-Octyl, 2-Octyl, 3-Octyl oder 4-Octyl, C_1-10-Alkenyl, insbesondere Ethenyl, Propenyl, Butenyl, Pentenyl, Hexenyl, Heptenyl oder Octenyl, C_1-10-Alkinyl, insbesondere Ethinyl, Propinyl, Butinyl, Pentinyl, Hexinyl, Heptinyl oder Octinyl, C_3-8-Cycloalkyl, insbesondere Cyclopentyl oder Cyclohexyl, Heteroalkyl, Heterocycloalkyl, C_6-14-Aryl, insbesondere Phenyl oder Naphthyl, C_6-14-Heteroaryl, bevorzugt für Ethyl, n-Propyl, n-Butyl, n-Pentyl, n-Hexyl, n-Heptyl oder Phenyl, steht oder
R^x und R^y unabhängig voneinander für C_1-10-Alkyl, insbesondere Methyl, Ethyl, Propyl, insbesondere n-Propyl oder i-Propyl, Butyl, insbesondere n-Butyl, i-Butyl oder t-Butyl, Pentyl, insbesondere n-Pentyl oder 2-Pentyl, Hexyl, insbesondere n-Hexyl, 2-Hexyl oder 3-Hexyl, Heptyl, insbesondere n-Heptyl, 2-Heptyl oder 3-Heptyl, oder Octyl, insbesondere n-Octyl, 2-Octyl, 3-Octyl oder 4-Octyl, C_1-10-Alkenyl, insbesondere Ethenyl, Propenyl, Butenyl, Pentenyl, Hexenyl, Heptenyl oder Octenyl, C_1-10-Alkinyl, insbesondere Ethinyl, Propinyl, Butinyl, Pentinyl, Hexinyl, Heptinyl oder Octinyl, C_3-8-Cycloalkyl, insbesondere Cyclopentyl oder Cyclohexyl, Heteroalkyl, Heterocycloalkyl, C_6-14-Aryl, insbesondere Phenyl oder Naphthyl, C_6-14-Heteroaryl, bevorzugt für Methyl, Ethyl, n-Propyl oder n-Butyl stehen,
G für NR¹¹R¹², NR¹¹-NR¹²R¹³, OR¹¹, bevorzugt OH, steht,
W für Tetrazolyl oder Thiazolidindionyl steht,
m für 0 oder 1 steht,
o für 0 oder 1 steht,
R^a, R^b, R^c, R^d und R^e unabhängig voneinander für Halogen, insbesondere Chlor, Brom oder Fluor, Trifluormethyl, Wasserstoff, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkyl-C_1-4-alkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, C_1-12-Alkylsulfonyl, C_1-12-Alkylsulfoxidyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, Carboxy, Cyan, Amino, (C_1-12-Alkyl)NH, Di-(C_1-12-AlkYl)N, C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C_1-12-Alkoxysulfonyl, C_1-12-Alkoxycarbinol, Sulfo, Sulfino, Sulfeno, Formyl oder Thioformyl, bevorzugt für Wasserstoff, Halogen, C_1-6-Alkyl oder C_6-10-Aryl, besonders bevorzugt für Wasserstoff, stehen,
R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹² und R¹³ unabhängig voneinander für Trifluormethyl, Wasserstoff, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkyl-C_1-4-alkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, C_1-12-Alkylsulfonyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, Carboxy, Cyan, Amino, (C_1-12-Alkyl)NH, Di-(C_1-12-Alkyl)N, C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, bevorzugt für Wasserstoff, C_1-6-Alkyl oder C_6-10-Aryl, besonders bevorzugt für Wasserstoff, stehen,
wobei alle Reste des sich so ergebenden Moleküls, insbesondere die aliphatischen und aromatischen Reste, sofern nicht anders angegeben, jeweils unabhängig voneinander gegebenenfalls auch ein- oder mehrfach, insbesondere ein-, zwei- oder dreifach, vorzugsweise einfach, substituiert sein können, insbesondere durch Substituenten ausgewählt aus Halogen, insbesondere Chlor, Brom oder Fluor, Trifluormethyl, C_1-12-Alkyl, C_3-8-Cycloalkyl, C_2-12-Alkenyl, C_2-12-Alkinyl, Heteroalkyl, Heterocycloalkyl, C_1-12-Alkoxy, C_1-12-Alkylsulfanyl, C_1-12-Alkylsulfonyl, C_1-12-Alkylsulfoxidyl, C_1-12-Alkanoyl, C_1-12-Alkanoyloxy, C_1-12-Alkoxycarbonyl, C_1-12-Alkylaminocarbonyl, C_1-12-Alkylsulfanylcarbonyl, Hydroxy, Carboxy, Cyan, Amino, (C_1-12-Alkyl)NH, Di-(C_1-12-Alkyl)N, C_6-10-Aryl, C_6-10-Aryl-C_1-4-alkyl, C_6-10-Aryloxy, C_6-10-Arylamino, C_6-10-Arylsulfanyl, C_6-10-Arylsulfonyl, C_6-10-Arylsulfoxidyl, C_6-10-Arylcarbonyl, C_6-10-Arylcarbonyloxy, C_6-10-Aryloxycarbonyl, C_6-10-Arylaminocarbonyl, C_6-10-Arylsulfanylcarbonyl, Heteroaryl, Heteroaryl-C_1-4-alkyl, Heteroaryloxy, Heteroarylamino, Heteroarylsulfanyl, Heteroarylsulfonyl, Heteroarylsulfoxidyl, Heteroarylcarbonyl, Heteroarylcarbonyloxy, Heteroaryloxycarbonyl, Heteroarylaminocarbonyl, Heteroarylsulfanylcarbonyl, C_1-12-Alkoxysulfonyl, C_1-12-Alkoxycarbinol, Sulfo, Sulfino, Sulfeno, Formyl, Thioformyl, Hydroxyimino, Hydrazono oder Imino, bevorzugt durch Halogen, C_1-6-Alkyl, C_1-6-Alkoxy oder Hydroxy,
und wobei die Gesamtzahl an diesen Substituenten im Molekül vorzugsweise bis zu fünf, besonders bevorzugt bis zu drei, insbesondere eins, zwei oder drei, beträgt,
und/oder physiologisch verträgliche Salze dieser Moleküle,
sowie die Verwendung dieser Substanzen zur Herstellung einer pharmazeutischen oder kosmetischen Zusammensetzung zur Aktivierung von PPARα- und/oder PPARγ-Rezeptoren und/oder zur Behandlung von Krankheiten oder Krankheitszuständen.Another object of the present invention are therefore also pyrimidine and triazine derivatives of the general formula (I)

in which
W is halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, hydrogen, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _3-8 -cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl, C _2-12 alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 alkoxy, C _1-12 alkylsulfanyl, C _1-12 alkylsulfonyl, C _1-12 alkyl sulfoxide, C _1-12 alkanoyl, C _1-12 Alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 -alkylaminocarbonyl, C _1-12 -alkylsulfanylcarbonyl, hydroxy, NR ¹ R ² , C _6-10 -aryl, C _6-10 -aryl-C _1-4 alkyl, C _6-10 aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxide, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy , C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl , Heteroarylsulfanylcarbonyl, C _1-12 alkoxysulfonyl, C _1-12 -Al koxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, with chlorine being preferred,
X is N or CR ^a , with CH being preferred,
Y is (A) _m -B- (M) _o -Q, (A) _m -B- (M) _o -L, NR ³ -C (O) -NR ⁴ -Q or NR ³ -C (O) -NR ⁴ -L is
A represents C _1-3 -alkyl or CO, in particular methylene,
B is NR ⁵ , CR ^{b is} R ^c , CO, O or S, preferably NH,
M is C _1-3 -alkyl or CO, in particular methylene,
Q is optionally mono- or polysubstituted, in particular di-, tri-, tetra- or quintuply substituted, preferably di- or trisubstituted, C _6-10 -aryl or heteroaryl, more preferably phenyl, where heteroaryl is at least one Heteroatom selected from O, S and N containing aromatic radical having 5 to 9, preferably 5 or 6, ring members and the substituents are preferably selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 alkyl, C _{3 -8-} cycloalkyl, C _3-8 -cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl , C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _1-12 -alkanoyloxy, C _1-12 -alkoxycarbonyl, C _1-12 -alkylaminocarbonyl, C _1-12 -alkylsulfanylcarbonyl, hydroxy , Carboxy, cyano, NR ⁶ R ⁷ , C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 -arylamino, C _6-10 - Arylsulfanyl, C _6-10 -Arylsulfonyl, C _6-10 arylsulfoxidyl, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy, C _6-10 aryloxycarbonyl, C _6-10 arylaminocarbonyl, C _6-10 arylsulfanylcarbonyl, heteroaryl, heteroaryl-C _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, wherein at least two vicinally arranged substituents, in particular alkyl substituents, may also be linked together to form a 5- or 6-membered optionally heteroatoms selected from N, O or S-containing ring, in particular alkyl ring,
L is C _1-12 -alkyl or heteroalkyl,
Z is S (CR ^x R ^y ) C (O) -G, where either
R ^{x is} H and R ^{y is} C _1-10 -alkyl, in particular methyl, ethyl, propyl, in particular n-propyl or i-propyl, Butyl, in particular n-butyl, isobutyl or t-butyl, pentyl, in particular n-pentyl or 2-pentyl, hexyl, in particular n-hexyl, 2-hexyl or 3-hexyl, heptyl, in particular n-heptyl, 2- Heptyl or 3-heptyl, or octyl, especially n-octyl, 2-octyl, 3-octyl or 4-octyl, C _1-10 alkenyl, especially ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl or octenyl, C _{1 -10-} alkynyl, in particular ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl or octynyl, C _3-8 -cycloalkyl, in particular cyclopentyl or cyclohexyl, heteroalkyl, heterocycloalkyl, C _6-14 -aryl, in particular phenyl or naphthyl, C _{6 -14} -heteroaryl, preferably ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, or phenyl, or
R ^x and R ^y independently of one another are C _1-10 -alkyl, in particular methyl, ethyl, propyl, in particular n-propyl or i-propyl, butyl, in particular n-butyl, isobutyl or t-butyl, pentyl, in particular n -Pentyl or 2-pentyl, hexyl, especially n-hexyl, 2-hexyl or 3-hexyl, heptyl, especially n-heptyl, 2-heptyl or 3-heptyl, or octyl, especially n-octyl, 2-octyl, 3 -Octyl or 4-octyl, C _1-10 alkenyl, especially ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl or octenyl, C _1-10 alkynyl, especially ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl or octynyl , C _3-8 -cycloalkyl, especially cyclopentyl or cyclohexyl, heteroalkyl, heterocycloalkyl, C _6-14 -aryl, especially phenyl or naphthyl, C _6-14 -Heteroaryl, preferably methyl, ethyl, n-propyl or n-butyl .
G is NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ , OR ¹¹ , preferably OH,
W is tetrazolyl or thiazolidinedionyl,
m is 0 or 1,
o is 0 or 1,
R ^a , R ^b , R ^c , R ^d and R ^{e are} independently halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, hydrogen, C _1-12 alkyl, C _3-8 cycloalkyl, C _3-8 cycloalkyl C _1-4 alkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl, C _1-12 alkoxy, C _1-12 alkylsulfanyl, C _1-12 alkylsulfonyl, C _1-12 Alkyl sulfoxide, C _1-12 alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 -Alkyl) NH, di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 - Arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxidyl, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy, C _6-10 aryloxycarbonyl, C _6-10 arylaminocarbonyl , C _6-10 arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, He teroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, preferably for hydrogen, halogen, C _1-6 -alkyl or C _6-10 -aryl, more preferably for hydrogen, stand,
R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are each independently trifluoromethyl, hydrogen, C _1-12 Alkyl, C _3-8 -cycloalkyl, C _3-8 -cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, C _1-12 -alkylsulfonyl, C _1-12 Alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 alkyl) NH, di - (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 -arylamino, C _6-10 -Arylsulfanyl, C _6-10 Arylsulfonyl, C _6-10 Arylsulfoxide, C _6-10 Arylcarbonyl, C _6-10 Arylcarbonyloxy, C _6-10 Aryloxycarbonyl, C _6-10 Arylaminocarbonyl, C _6-10 - Arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl gt is hydrogen, C _1-6 -alkyl or C _6-10 -aryl, more preferably hydrogen,
wherein all the radicals of the resulting molecule, in particular the aliphatic and aromatic radicals, unless otherwise stated, may each independently be optionally mono- or polysubstituted, in particular mono-, di- or trisubstituted, preferably monosubstituted, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 - Alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _1-12 -alkanoyloxy, C _1-12 -alkoxycarbonyl, C _1-12 -alkylaminocarbonyl , C _1-12 -alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 -alkyl) NH, di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 - ArylC _1-4 alkyl, C _6-10 aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxide, C _6-10 arylcarbonyl C _6-10 arylcarbonyloxy, C _6-10 aryloxycarbo nyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _{1 12-} alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl, thioformyl, hydroxyimino, hydrazono or imino, preferably by halogen, C _1-6 -alkyl, C _1-6 -alkoxy or hydroxyl,
and wherein the total number of these substituents in the molecule is preferably up to five, more preferably up to three, in particular one, two or three,
and / or physiologically acceptable salts of these molecules,
and the use of these substances for the preparation of a pharmaceutical or cosmetic composition for the activation of PPARα and / or PPARγ receptors and / or for the treatment of diseases or disease states.

The Treatable diseases and disease states are preferred according to the invention selected Type I and Type II diabetes, hyperinsulinemia, insulin resistance, Obesity, obesity, hyperlipidemia, dyslipidemia, cardiovascular Diseases, especially arteriosclerosis and hypertension, diseases and disease states, which are due to a dysregulation of the immune system, especially autoimmune diseases and rejection reactions as a result of organ or tissue transplantation, gastrointestinal Diseases, especially intestinal inflammation, other inflammatory Diseases, such as Alzheimer's disease, Crohn's disease, multiple Sclerosis, rheumatoid arthritis, syndrome X or the so-called ischemia reprofusion injury, and diseases that indicate a disturbed barrier function derive from the skin, as well as cancer, thrombosis, stroke and heart attack.

The treatable diseases and disease states are particularly according to the invention preferably selected from skin diseases and disease states of the skin, preferably from inflammatory Dermatoses, in particular from pathological changes in the fluid and electrolyte balance, low temperature, skin infections; Inflammation of mucous membranes, such as cheilitis, rhinitis and vulvovaginitis; eczema, like atopic and seborrhea Dermatitis, allergic eczema, contact dermatitis, xerotic eczema, photoallergic and phototoxic dermatitis, phytophotodermatitis, Radiation dermatitis, stasis dermatitis; Ulcers and erosions resulting from injuries, burns, bullous (blistering) Diseases or ischemia the skin or mucous membrane; Ichthyoses (keratinization disorders of Skin); Epidermolysis bullosae; Psoriasis; hypertrophic scars and keloids; changes the skin through intrinsic aging and photoaging; skin blisters due to mechanical friction; Skin atrophy (dilution) by topical use of corticosteroids, vitiligo and alopecia areata, most preferably the disease is around Psoriasis or atopic dermatitis.

According to the invention, C _1-12 -alkyl in each case independently of one another represents all saturated linear and branched alkyl radicals having up to 12 C atoms, preference being given to C _1-6 -alkyl radicals. C _1-6 -alkyl according to the invention represents all saturated linear and branched alkyl radicals having up to 6 C atoms, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl as well as all isomers of pentyl and hexyl.

According to the invention, C _3-8 -cycloalkyl in each case independently of one another represents all cyclic alkyl radicals having 3 to 8 C atoms, preferably having 5 to 6 C atoms, where the radicals may be saturated or unsaturated, in particular cyclopentyl, cyclohexyl or cyclopentadienyl ,

C _2-12 alkenyl according to the invention in each case independently of one another for all linear and branched alkyl radicals having up to 12 carbon atoms which contain at least one double bond, wherein C _2-6 alkenyl radicals are preferred. C _2-6 alkenyl is according to the invention for all linear and branched alkyl radicals having up to 6 C atoms which contain at least one double bond, in particular ethenyl, propenyl, i-propenyl and all isomers of butenyl, pentenyl and hexenyl.

According to the invention, C _2-12 -alkynyl is, independently of one another, independently of all linear and unbranched alkyl radicals having up to 12 C atoms which contain at least one triple bond, preference being given to C _2-6 -alkynyl radicals. C _2-6 -alkynyl according to the invention represents all linear and unbranched alkyl radicals having up to 6 C atoms which contain at least one triple bond, in particular ethynyl, propynyl, i-propynyl and all isomers of butynyl, pentynyl and hexynyl.

heteroalkyl is according to the invention respectively independently each other for all saturated and mono- or polyunsaturated, linear or branched alkyl radicals, the at least one, preferably exactly one heteroatom, in particular O, S or N, where the sum of C and hetero atoms up to 12, preferably up to 6.

heterocycloalkyl is according to the invention respectively independently each other for all cyclic alkyl radicals which are at least one, preferably exactly a, heteroatom, in particular O, S or N, wherein the Ring is three to eight membered, preferably five to six membered. Examples of this are tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, 2-thiazolinyl, Tetrahydrothiazolyl, tetrahydrooxazolyl, piperidinyl, piperazinyl, Morpholinyl and thiomorpholinyl.

According to the invention, C _1-12 -alkoxy in each case independently of one another represents all saturated and unsaturated, linear and branched alkyl radicals having up to 12 C atoms which are bonded via an oxygen atom, preference being given to C _1-6 -alkoxy radicals are. According to the invention, C _1-6 -alkoxy in each case independently of one another represents all saturated and unsaturated, linear and branched alkyl radicals having up to 6 C atoms which are bonded via an oxygen atom, in particular for methoxy and ethoxy.

According to the invention, C _1-12 -alkylsulfanyl in each case independently of one another represents all saturated and unsaturated, linear and branched alkyl radicals having up to 12 C atoms which are bonded via a sulfur atom, preference being given to C _1-6 -alkylsulfanyl radicals are. According to the invention, C _1-6 -alkylsulfanyl represents all saturated and unsaturated, linear and branched alkyl radicals having up to 6 C atoms, which are bonded via a sulfur atom, in particular for methylsulfanyl and ethylsulfanyl.

According to the invention, C _1-12 -alkylsulfonyl in each case independently of one another represents all saturated and unsaturated, linear and branched alkyl radicals having up to 12 C atoms which are bonded via an SO group, preference being given to C _1-6 -alkylsulfonyl radicals are. According to the invention, C _1-6 -alkylsulfonyl represents all saturated and unsaturated, linear and branched alkyl radicals having up to 6 C atoms which are bonded via an SO group, in particular for methysulfonyl and ethylsulfonyl.

According to the invention, C _1-12 -alkylsulfoxidyl in each case independently of one another represents all saturated and unsaturated, linear and branched alkyl radicals having up to 12 C atoms which are bonded via an SO ₂ group, where C _1-6 -alkylsulfoxidyl radicals are preferred. According to the invention, C _1-6 -alkylsulfoxidyl represents all saturated and unsaturated, linear and branched alkyl radicals having up to 6 C atoms which are bonded via an SO ₂ group, in particular for methylsulfoxidyl and ethylsulfoxidyl.

According to the invention, C _1-12 -alkanoyl in each case independently of one another represents all saturated and unsaturated, linear and branched alkyl radicals having up to 12 C atoms which are bonded via a carbonyl group, preference being given to C _1-6 -alkanoyl radicals are. According to the invention, C _1-6 -alkanoyl represents all saturated and unsaturated, linear and branched alkyl radicals having up to 6 C atoms which are bonded via a carbonyl group, in particular for methycarbonyl and ethylcarbonyl.

According to the invention, C _1-12 -alkanoyloxy in each case independently of one another represents all saturated and unsaturated, linear and branched alkyl radicals having up to 12 C atoms which are bonded via a carbonyloxy group, preference being given to C _1-6 -alkanoyloxy radicals are. According to the invention, C _1-6 -alkanoyloxy represents all saturated and unsaturated, linear and branched alkyl radicals having up to 6 C atoms which are bonded via a carbonyloxy group, in particular methanoyloxy, ethanoyloxy, n-propanoyloxy and i-propanoyloxy ,

According to the invention, C _1-12 -alkoxycarbonyl in each case independently of one another represents all saturated and unsaturated, linear and branched alkyl radicals having up to 12 C atoms, which are bonded via an oxycarbonyl group, preference being given to C _1-6 -alkoxycarbonyl radicals are. C _1-6 -alkoxycarbonyl is according to the invention for all saturated and unsaturated, linear and branched alkyl radicals having up to 6 C-atoms, which are bonded via an oxycarbonyl group, in particular for methoxycarbonyl and ethoxycarbonyl.

According to the invention, C _1-12 -alkylaminocarbonyl in each case independently of one another represents an aminocarbonyl group which is monosubstituted or disubstituted by a saturated or unsaturated, linear or branched alkyl radical having up to 12 C atoms, wherein one or two times C _1-6 alkyl groups substituted aminocarbonyl radicals, especially monomethylaminocarbonyl, diemethylaminocarbonyl, monoethylaminocarbonyl and diethylaminocarbonyl, are preferred.

According to the invention, C _1-12 -alkylsulfanylcarbonyl in each case independently of one another represents all saturated and unsaturated, linear and branched alkyl radicals having up to 12 C atoms which are bonded via a thiocarbonyl group, preference being given to C _1-6 -alkylsulfanylcarbonyl radicals are. C _1-6 -alkylsulfanylcarbonyl according to the invention represents all saturated and unsaturated, linear and branched alkyl radicals having up to 6 C atoms which are bonded via a thiocarbonyl group, in particular methylthiocarbonyl and ethylthiocarbonyl.

(C _1-12 -alkyl) According to the invention, in each case independently of one another, NH 4 represents, independently of one another, all saturated and unsaturated, linear and branched alkyl radicals having up to 12 C atoms which are bonded via a hydrogenamino group, where (C _1-6 -alkyl) NH is preferred. (C _1-6 -alkyl) NH is according to the invention for all saturated and unsaturated, linear and branched alkyl radicals having up to 6 C-atoms, which are bonded via a hydrogenamino group, in particular for CH ₃ NH and C ₂ H ₅ NH.

According to the invention, di- (C _1-12 -alkyl) N is, independently of one another, independently of all saturated and unsaturated, linear and branched alkyl radicals having up to 12 C atoms, which are bonded via a (C _1-12 -alkyl) amino group wherein di (C _2-12 alkyl) N is preferred. The two alkyl radicals here may be the same or different from each other. Di- (C _2-12- alkyl) N is according to the invention for all saturated and unsaturated, linear and branched alkyl radicals having up to 6 C atoms, which are bonded via a (C _1-6 alkyl) amino group, in particular for (CH ₃ ) ₂ N and (C ₂ H ₅ ) ₂ N.

C _6-10 -aryl is according to the invention, in particular also in C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 -arylamino, C _6-10 -arylsulfanyl, C _{6- 10} -arylsulfonyl, C _6-10 -arylsulfoxidyl, C _6-10 -arylcarbonyl, C _6-10 -arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl and C _6-10 -arylsulfanylcarbonyl, preferably phenyl or Naphthyl, especially preferred for phenyl.

Heteroaryl is according to the invention, in particular also in heteroaryl-C _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl and heteroarylsulfanylcarbonyl, unless stated otherwise, for at least one heteroatom selected from O, S and N containing aromatic radical having 5 to 10, preferably 5 or 6, ring members, preferably selected from furanyl, thienyl, thiophenyl, pyrrolyl, isopyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl , Benzofuranyl, benzothiophenyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, indazolyl, pyridofuranyl and pyridothienyl.

In C _6-10 arylC _1-4 alkyl and heteroarylalkyl, the alkyl radical may be saturated or unsaturated, branched or unbranched. Preferred radicals are benzyl, phenylethyl, naphthylmethyl and naphthylethyl.

The aforementioned alkyl, cycloalkyl, alkenyl, alkynyl, heteroalkyl, heterocycloalkyl, alkoxy, alkylsulfanyl, alkylsulfonyl, alkylsulfoxidyl, alkanoyl, alkanoyloxy, alkoxycarbonyl, alkylaminocarbonyl, alkylsulfanylcarbonyl, (C _{1 -12-} alkyl) NH-, di- (C _1-12 -alkyl) N-, aryl- and heteroaryl radicals can each, independently of one another, optionally also be monosubstituted or polysubstituted, in particular mono-, di- or trisubstituted, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _{1 -12-} alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _1-12 -alkanoyloxy, C _1-12 -alkoxycarbonyl, C _{1- 12} -alkylaminocarbonyl, C _1-12 -alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 -alkyl) NH, di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _{6 -10-} aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _{6-1 0-} arylamino, C _6-10 -arylsulfanyl, C _6-10 -arylsulfonyl, C _6-10 -arylsulfoxidyl, C _6-10 -arylcarbonyl, C _6-10 -arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 -Arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, preferably by C _1-6 -alkyl, C _1-6 alkoxy, chloro, bromo, fluoro or hydroxy.

In a preferred embodiment stand
W is halogen, in particular chlorine, bromine or fluorine, hydrogen, C _1-6 -alkyl, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl or di- (C _1-6 -alkyl) N, where chlorine and bromine preferred and chlorine is particularly preferred,
X is N or CR ^a , where CH is preferred,
Y is (A) _m -B- (M) _o -Q, (A) _m -B- (M) _o -L, NR ³ -C (O) -NR ⁴ -Q or NR ³ -C (O) -NR ⁴ -L,
A is methylene or CO, preferably methylene,
B is NR ⁵ , CR ^{b is} R ^c , CO, O or S, preferably NH,
M is methylene or CO, preferably methylene,
Q is triply substituted phenyl, wherein two of the three radicals are independently selected from C _1-3 alkyl, especially methyl, ethyl, n-propyl and i-propyl, and the third radical is chlorine, bromine, C _{1 -6} alkoxy, C _1-6 alkylsulphanyl or di- (C _1-6 alkyl) N, preferably chlorine or bromine, is,
Z for DEC (O) - (F) _p -G or DEV,
L is C _1-12 -alkyl or heteroalkyl,
D is O, S, CR ^d R ^e or NR ⁸ , preferably S,
E is optionally mono- or polysubstituted, preferably mono- or di-substituted, C _1-6 -alkyl, preferably methylene or ethylene, more preferably methylene, wherein the substituents are independently selected from C _1-12 -alkyl, C _3-8 Cycloalkyl, heterocycloalkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl, C _1-12 alkoxy, C _1-12 alkylsulfanyl, NR ⁹ R ¹⁰ , C _6-10 aryl, heteroaryl, C _6-10 -aryl-C _1-4 -alkyl, more preferably from C _1-8 -alkyl, heteroalkyl, C _6-10 -aryl and heteroaryl, especially from C _2-8 -alkyl and C _6-10 -aryl .
F is C _1-3 -alkyl, preferably methylene or ethylene,
G for NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ¹¹ , preferably OH,
V is tetrazolyl or thiazolidinedionyl,
m for 0 or 1,
o for 0 or 1,
p is 0 or 1, preferably 0,
R ^a , R ^b , R ^c , R ^d and R ^{e are} independently halogen, in particular chlorine, bromine or fluorine, hydrogen, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 alkylsulfanyl, hydroxy , Amino, (C _1-6 -alkyl) NH or di- (C _1-6 -alkyl) N, preferably chlorine, bromine, hydrogen or C _1-6 -alkyl, particularly preferably hydrogen,
R ³ , R ⁴ , R ⁵ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ independently of one another represent hydrogen or C _1-6 -alkyl, preferably hydrogen,
wherein all the radicals of the resulting molecule, in particular the aliphatic and aromatic radicals, unless otherwise stated, may each independently be optionally mono- or polysubstituted, in particular mono-, di- or trisubstituted, preferably monosubstituted, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, heteroalkyl, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl, hydroxy, Amino, (C _1-6 -alkyl) NH, di- (C _1-6 -alkyl) N, preferably by chlorine, bromine, C _1-6 -alkyl or hydroxy,
and wherein the total number of these substituents in the molecule is preferably up to five, more preferably up to three, in particular one, two or three.

Particular preference is given here
W for chlorine,
X for CH,
Y for NH-Q,
Z is S (CR ^x R ^y ) C (O) -G,
Q is triply substituted phenyl, wherein two of the three radicals are independently selected from C _1-3 alkyl, especially methyl, ethyl, n-propyl and i-propyl, and the third radical is chlorine, bromine, C _{1 -6-} alkoxy, C _1-6 -alkylsulfanyl or di- (C _1-6 -alkyl) N, preferably chlorine or bromine, R ^{x is} N and R ^{y is} C _1-10 -alkyl, in particular methyl, Ethyl, propyl, in particular n-propyl or i-propyl, butyl, in particular n-butyl, i-butyl or t-butyl, pentyl, in particular n-pentyl, hexyl, in particular n-hexyl, heptyl, in particular n-heptyl, octyl , in particular n-octyl, nonyl, in particular n-nonyl, or decyl, in particular n-decyl, C _1-10 -alkenyl, in particular ethenyl, propenyl, in particular n-propenyl, butenyl, in particular n-butenyl, pentenyl, in particular n- Pentenyl, hexenyl, in particular n-hexenyl, heptenyl, in particular n-heptenyl, octenyl, in particular n-octenyl, nonenyl, in particular n-nonenyl, or decenyl, in particular n-decenyl, C _1-10 -alkynyl, in particular ethinyl, propynyl, in particular n-propynyl, butynyl, in particular n-butynyl, pentynyl, in particular n-pentynyl, hexynyl, in particular n-hexynyl, heptynyl, in particular n-heptynyl, octynyl, in particular n-octynyl, nonynyl, in particular n- Noninyl or decynyl, in particular n-decynyl, C _5-6 -cycloalkyl, in particular cyclopentyl or cyclohexyl, heteroalkyl, C _6-10 -aryl, in particular phenyl or naphthyl, or heteroaryl or
R ^x and R ^y independently of one another are C _1-6 -alkyl, preferably methyl, ethyl, propyl, in particular n-propyl or isopropyl, butyl, in particular n-butyl, isobutyl or t-butyl, pentyl, in particular n -Pentyl, or hexyl, especially n-hexyl, or phenyl,
G for NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ¹¹ , preferably OH,
R ¹¹ , R ¹² and R ¹³ independently of one another represent hydrogen or C _1-6 -alkyl, preferably hydrogen.

Very particularly preferred are here
W for chlorine,
X for CH,
Y for NH-Q,
Z is S (CH ₂ ) C (O) -G,
Q is triply substituted phenyl, wherein two of the three radicals are independently selected from C _1-3 alkyl, in particular methyl, ethyl, n-propyl or i-propyl, especially methyl, and the third radical is chlorine, Bromine, C _1-6 -alkoxy, in particular methoxy, ethoxy or propoxy, C _1-6 -alkylsulfanyl, in particular methyl-, ethyl- or propylsulfanyl, or di- (C _1-6 -alkyl) N, especially di- ( C _1-6 -alkyl) N, preferably chlorine or bromine, and wherein the two alkyl radicals are preferably located at positions 2 and 3 and the third radical at position 4 in the ring,
G for NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ¹¹ , preferably OH,
R ¹¹ , R ¹² and R ¹³ independently of one another represent hydrogen or C _1-6 -alkyl, preferably hydrogen.

In particular, the compound here is [[4-chloro-6 - [(2,3-di- (C _1-3 -alkyl) -4-halophenyl) amino] -2-pyrimidinyl] thio] acetic acid, in particular, [[4-chloro-6 - [(2,3-dimethyl-4-chlorophenyl) amino] -2-pyrimidinyl] thio] acetic acid or [[4-chloro-6 - [(2,3-dimethyl-4 bromophenyl) amino] -2-pyrimidinyl] thio] acetic acid or it is the corresponding acetamides, acethydrazides or C _1-6 alkyl esters or physiologically acceptable salts of these compounds.

In a further preferred embodiment stand
W is halogen, in particular chlorine, bromine or fluorine, hydrogen, C _1-6 -alkyl, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl or di- (C _1-6 -alkyl) N, where chlorine and bromine preferred and chlorine is particularly preferred,
X is N or CR ^a , where CH is preferred,
Y is (A) mB- (M) _o -Q, (A) _m -B- (M) _o -L, NR ³ -C (O) -NR ⁴ -Q or NR ³ -C (O) -NR ⁴ -L,
A is methylene or CO, preferably methylene,
B is NR ⁵ , CR ^{b is} R ^c , CO, O or S, preferably NH,
M is methylene or CO, preferably methylene,
Q is di-alkyl-substituted phenyl, the two substituents being vicinal and forming a 5- to 6-membered optionally heteroatom selected from N, O and S containing ring,
Z for DEC (O) - (F) _p -G or DEV,
L is C _1-12 -alkyl or heteroalkyl,
D is O, S, CR ^d R ^e or NR ⁸ , preferably S,
E is optionally mono- or polysubstituted, preferably mono- or di-substituted, C _1-6 -alkyl, preferably methylene or ethylene, more preferably methylene, wherein the substituents are independently selected from C _1-12 -alkyl, C _3-8 Cycloalkyl, heterocycloalkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl, C _1-12 alkoxy, C _2-12 alkylsulfanyl, NR ⁹ R ¹⁰ , C _6-10 aryl, heteroaryl, C _6-10 -aryl-C _1-4 -alkyl, more preferably from C _1-8 -alkyl, heteroalkyl, C _6-10 -aryl and heteroaryl, especially from C _2-8 -alkyl and C _6-10 -aryl .
F is C _1-3 -alkyl, preferably methylene or ethylene,
G is NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ^{11 is} preferably OH,
V is tetrazolyl or thiazolidinedionyl,
m for 0 or 1,
o for 0 or 1,
p is 0 or 1, preferably 0,
R ^a , R ^b , R ^c , R ^d and R ^{e are} independently halogen, in particular chlorine, bromine or fluorine, hydrogen, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 alkylsulfanyl, hydroxy , Amino, (C ^1-6 -alkyl) NH or di- (C _1-6 -alkyl) N, preferably chlorine, bromine, hydrogen or C _1-6 -alkyl, particularly preferably hydrogen,
R ³ , R ⁴ , R ⁵ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ independently of one another represent hydrogen or C _1-6 -alkyl, preferably hydrogen,
wherein all the radicals of the resulting molecule, in particular the aliphatic and aromatic radicals, unless otherwise stated, may each independently be optionally mono- or polysubstituted, in particular mono-, di- or trisubstituted, preferably monosubstituted, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, heteroalkyl, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl, hydroxy, Amino, (C _1-6 -alkyl) NH, di- (C _1-6 -alkyl) N, preferably by chlorine, bromine, C _1-6 -alkyl or hydroxy,
and wherein the total number of these substituents in the molecule is preferably up to five, more preferably up to three, in particular one, two or three.

Particular preference is given here
W for chlorine,
X for CH,
Y for NH-Q,
Z is S (CR ^x R ^y ) C (O) -G,
Q represents di-alkyl-substituted phenyl, where the two substituents are vicinal, preferably in the 2,3-position, and form a 5- to 6-membered, optionally heteroatom-containing ring,
R ^{x is} N and R ^{y is} C _1-10 alkyl, in particular methyl, ethyl, propyl, in particular n-propyl or i-propyl, butyl, in particular n-butyl, isobutyl or t-butyl, pentyl, in particular n -Pentyl, hexyl, in particular n-hexyl, heptyl, in particular n-heptyl, octyl, in particular n-octyl, nonyl, in particular n-nonyl, or decyl, in particular n-decyl, C _1-10 alkenyl, in particular ethenyl, propenyl , in particular n-propenyl, butenyl, in particular n-butenyl, pentenyl, in particular n-pentenyl, hexenyl, in particular n-hexenyl, heptenyl, in particular n-heptenyl, octenyl, in particular n-octenyl, nonenyl, in particular n-nonenyl, or decenyl , in particular n-decenyl, C _1-10 alkynyl, in particular ethynyl, propynyl, in particular n-propynyl, butynyl, in particular n-butynyl, pentynyl, in particular n-pentynyl, hexynyl, in particular n-hexynyl, heptynyl, in particular n-heptynyl , Octynyl, in particular n-octynyl, nonynyl, in particular n-nonynyl or decynyl, in particular n-decynyl, C _5-6 -cycloalkyl, in particular cyclopentyl or cyclohexyl, heteroalkyl, C _6-10 -aryl, in particular phenyl or naphthyl, or heteroaryl or
R ^x and R ^y independently of one another are C _1-6 -alkyl, preferably methyl, ethyl, propyl, in particular n-propyl or isopropyl, butyl, in particular n-butyl, isobutyl or t-butyl, pentyl, in particular n -Pentyl, or hexyl, especially n-hexyl, or phenyl,
G for NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ¹¹ , preferably OH,
R ¹¹ , R ¹² and R ¹³ independently of one another represent hydrogen or C _1-6 -alkyl, preferably hydrogen.

Very particularly preferred are here
W for chlorine,
X for CH,
Y for NH-Q,
Z is S (CH ₂ ) C (O) -G,
Q is doubly substituted phenyl, the double substitution being effected by an alkylene bridge, preferably propylene bridge, preferably in the 2,3-position,
G for NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ¹¹ , preferably OH,
R ¹¹ , R ¹² and R ¹³ independently of one another represent hydrogen or C _1-6 -alkyl, preferably hydrogen.

Above all, the compound here is [4-chloro-6- (indan-4-ylamino) -pyrimidin-2-ylsulfanyl] -acetic acid or it is the corresponding acetamides, acethydrazides or C _1-6 -alkyl esters or physiologically acceptable salts of these compounds.

In a further preferred embodiment stand
W is halogen, in particular chlorine, bromine or fluorine, hydrogen, C _1-6 -alkyl, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl or di- (C _1-6 -alkyl) N, where chlorine and bromine preferred and chlorine is particularly preferred,
X is N or CR ^a , where CH is preferred,
Y is (A) mB- (M) _o -Q, (A) _m -B- (M) _o -L, NR ³ -C (O) -NR ⁴ -Q or NR ³ -C (O) -NR ⁴ -L,
A is methylene or CO, preferably methylene,
B is NR ⁵ , CR ^{b is} R ^c , CO, O or S, preferably NH,
M is methylene or CO, preferably methylene,
Q is optionally mono- or polysubstituted, in particular di-, tri-, tetra- or quintuple-substituted, preferably di- or trisubstituted, C _6-10 -aryl or heteroaryl, more preferably phenyl, where heteroaryl is selected for at least one heteroatom from O, S and N containing aromatic radical having 5 to 9, preferably 5 or 6, ring members and the substituents are preferably selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 alkyl, C _3-8 Cycloalkyl, heterocycloalkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl, C _1-12 alkoxy, C _1-12 alkylsulfanyl, hydroxy, carboxy, NR ⁶ R ⁷ , C _6-10 aryl , Heteroaryl or C _6-10 -aryl-C _1-4 -alkyl, where at least two vicinally arranged substituents, in particular alkyl substituents, also to form a 5- or 6-membered optionally heteroatoms selected from N, O or S-containing ring , in particular alkyl ring, linked together be able to be
Z is S (CR ^x R ^y ) C (O) -G,
L is C _1-12 -alkyl or heteroalkyl,
G for NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ¹¹ , preferably OH,
m for 0 or 1,
o for 0 or 1,
R ^a , R ^b and R ^c independently of one another are halogen, in particular chlorine, bromine or fluorine, hydrogen, C _1-6 -alkyl, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl, hydroxy, amino, (C _{1 -6-} alkyl) NH or di- (C _1-6 -alkyl) N, preferably chlorine, bromine, hydrogen or C _1-6 -alkyl, particularly preferably hydrogen,
R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ¹¹ , R ¹² and R ¹³ independently of one another represent hydrogen or C _1-6 -alkyl, preferably hydrogen,
R ^{x is} H and R ^{y is} C _1-10 alkyl, in particular methyl, ethyl, propyl, in particular n-propyl or i-propyl, butyl, in particular n-butyl, i-butyl or t-butyl, pentyl, in particular n -Pentyl or 2-pentyl, hexyl, especially n-hexyl, 2-hexyl or 3-hexyl, heptyl, especially n-heptyl, 2-heptyl or 3-heptyl, octyl, especially n-octyl, 2-octyl, 3 Octyl or 4-octyl, nonyl, in particular n-nonyl, or decyl, in particular n-decyl, C _1-10 -alkenyl, in particular ethenyl, propenyl, in particular n-propenyl, butenyl, in particular n-butenyl, pentenyl, in particular n- Pentenyl, hexenyl, in particular n-hexenyl, heptenyl, in particular n-heptenyl, octenyl, in particular n-octenyl, nonenyl, in particular n-nonenyl, or decenyl, in particular n-decenyl, C _1-10 -alkynyl, in particular ethynyl, propynyl, in particular n-propynyl, butynyl, in particular n-butynyl, pentynyl, in particular n-pentynyl, hexynyl, in particular n-hexynyl, heptynyl, in particular n-heptynyl, octynyl, in particular n-octynyl, nonynyl l, in particular n-nonynyl or decinyl, in particular n-decynyl, C _5-6 -cycloalkyl, in particular cyclopentyl or cyclohexyl, heteroalkyl, heterocycloalkyl, C _6-10 -aryl, in particular phenyl or naphthyl, heteroaryl, preferably for ethyl, n- Propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl or phenyl, or
R ^x and R ^y independently of one another are C _1-10 -alkyl, in particular methyl, ethyl, propyl, in particular n-propyl or i-propyl, butyl, in particular n-butyl, isobutyl or t-butyl, pentyl, in particular n -Pentyl or 2-pentyl, hexyl, especially n-hexyl, 2-hexyl or 3-hexyl, heptyl, especially n-heptyl, 2-heptyl or 3-heptyl, or octyl, especially n-octyl, 2-octyl, 3 -Octyl or 4-octyl, C _1-10 alkenyl, especially ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl or octenyl, C _1-10 alkynyl, especially ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl or octynyl , C _3-8 -cycloalkyl, in particular cyclopentyl or cyclohexyl, heteroalkyl, Heterocycloalkyl, C _6-10 -aryl, in particular phenyl or naphthyl, or heteroaryl, preferably methyl, ethyl, n-propyl or n-butyl,
wherein all the radicals of the resulting molecule, in particular the aliphatic and aromatic radicals, unless otherwise stated, may each independently be optionally mono- or polysubstituted, in particular mono-, di- or trisubstituted, preferably monosubstituted, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, heteroalkyl, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl, hydroxy, Amino, (C _1-6 -alkyl) NH, di- (C _1-6 -alkyl) N, preferably by chlorine, bromine, C _1-6 -alkyl or hydroxy,
and wherein the total number of these substituents in the molecule is preferably up to five, more preferably up to three, in particular one, two or three.

Particular preference is given here
W for chlorine,
X for CH,
Y for NH-Q,
Z is S (CR ^x R ^y ) C (O) -G,
Q is 2,3-dimethylphenyl, 2,3-dimethyl-4-chlorophenyl or 2,3-dimethyl-4-bromophenyl,
R ^{x is} H and R ^{y is} C _1-10 alkyl, in particular methyl, ethyl, propyl, in particular n-propyl or i-propyl, butyl, in particular n-butyl, i-butyl or t-butyl, pentyl, in particular n -Pentyl or 2-pentyl, hexyl, especially n-hexyl, 2-hexyl or 3-hexyl, heptyl, especially n-heptyl, 2-heptyl or 3-heptyl, octyl, especially n-octyl, 2-octyl, 3 Octyl or 4-octyl, nonyl, in particular n-nonyl, or decyl, in particular n-decyl, C _1-10 -alkenyl, in particular ethenyl, propenyl, in particular n-propenyl, butenyl, in particular n-butenyl, pentenyl, in particular n- Pentenyl, hexenyl, in particular n-hexenyl, heptenyl, in particular n-heptenyl, octenyl, in particular n-octenyl, nonenyl, in particular n-nonenyl, or decenyl, in particular n-decenyl, C _1-10 -alkynyl, in particular ethynyl, propynyl, in particular n-propynyl, butinyl, in particular n-butynyl, pentyl, in particular n-pentyl, hexynyl, in particular n-hexynyl, heptynyl, in particular n-heptynyl, octynyl, in particular n-octynyl, noninyl, in particular n-nonynyl or decinyl, in particular n-decynyl, C _3-8 -cycloalkyl, in particular cyclopentyl or cyclohexyl, heteroalkyl, heterocycloalkyl, C _6-10 -aryl, in particular phenyl or naphthyl, or heteroaryl, preferably ethyl, n-propyl , n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl or phenyl or
R ^x and R ^y independently of one another are C _1-6 -alkyl, preferably methyl, ethyl, propyl, in particular n-propyl or isopropyl, butyl, in particular n-butyl, isobutyl or t-butyl, pentyl, in particular n -Pentyl, or hexyl, especially n-hexyl, or phenyl,
G for NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ¹¹ , preferably OH,
R ¹¹ , R ¹² and R ¹³ independently of one another represent hydrogen or C _1-6 -alkyl, preferably hydrogen.

Above all, the connection is about
2- [4-Chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -propanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidine-2 -ylsulfanyl] butanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -pentanoic acid, 2- [4-chloro-6- (2,3-dimethyl- phenylamino) -pyrimidin-2-ylsulfanyl] -hexanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -heptanoic acid, 2- [4-chloro-6- ( 2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -octanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -nonanoic acid, 2- [4 Chloro-6- (2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] decanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] - phenyl-acetic acid, [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -naphtalen-1-yl-acetic acid, 2- [4-chloro-6- (2,3- dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methylpropanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-butanoic acid, 4-Chlor2- [4-chloro-6- (2,3-dimethyl -phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethylbutanoic acid, 2- (4-chloro-6- (2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-methylpentanoic acid, 2 - [4-chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-ethylpentanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) - pyrimidin-2-ylsulfanyl] -2-propyl-pentanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-hexanoic acid, 2- [4- Chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-hexanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidine-2- ylsulfanyl] -2-propyl-hexanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-hexanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-heptanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2 ethylheptanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-heptanoic acid, 2- [4-chloro-6- (2,3 dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-heptane acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-pentyl-heptanoic acid, 2- [4-chloro-6- (2,3-dimethyl- phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyloctanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-heptanoic acid, 2- [4-Chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-heptanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidine -2-ylsulfa nyl] -2-butyl-heptanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-pentyl-heptanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) pyrimidin-2-ylsulphanyl] -2-methyloctanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) pyrimidin-2-ylsulphanyl] -2- ethyl octanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-propyloctanoic acid, 2- [4-chloro-6- (2,3- dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyloctanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl) -2-pentyloctanoic acid, 2- [4-Chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-hexyloctanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-nonanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-nonanoic acid, 2- [4 Chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-nonanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidine-2 -ylsulfanyl] -2-butyl-nonanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phen ylamino) -pyrimidin-2-ylsulfanyl] -2-pentyl-nonanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-hexyl-nonanoic acid, 2- [4-Chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-heptyl-nonanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidine -2-ylsulfanyl] -2-methyl-decanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-decanoic acid, 2- [4-chloro -6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-decanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl ] -2-butyl-decanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-pentyl-decanoic acid, 2- [4-chloro-6-one 2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-hexyl-decanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2- heptyl-decanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-octyl-decanoic acid,
2- [4-Chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-undecanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl undecanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-propyl undecanoic acid, 2- [4 Chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-undecanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidine-2 -ylsulfanyl] -2-pentyl undecanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-hexyl undecanoic acid, 2- [4-chloro-6 - (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-heptyl-undecanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] - 2-octyl undecanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-nonyl undecanoic acid, 2- [4-chloro-6- (2, 3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-methyldodecanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl- dodecanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamine o) -pyrimidin-2-ylsulfanyl] -2-propyldodecanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-butyldodecanoic acid, 2- [4-Chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-pentyl-dodecanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidine -2-ylsulfanyl] -2-hexyl-dodecanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-heptyl-dodecanoic acid, 2- [4-chloro -6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-octyldodecanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl ] -2-nonyldodecanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-decyldodecanoic acid
2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -propanoic acid, 2- [4-chloro-6- (4-chloro-2,3- dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -butanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -pentanoic acid, 2- [4 Chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -hexanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -heptanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -octanoic acid, 2- [4-chloro-6 - (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -nonanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidine-2 -ylsulfanyl] decanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -phenyl-acetic acid, [4-chloro-6- (4- chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -naphtalen-1-yl-acetic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidine -2-ylsulfanyl] -2-methyl-propanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimeth yl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-butanoic acid, 4-chloro-2- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] - 2-ethyl-butanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-pentanoic acid, 2- [4-chloro-6 - (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-pentanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-pentanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-hexanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-ethylhexanoic acid, 2- [4-chloro-6- (4-chloro) 2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-hexanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl ] -2-butylhexanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-methylheptanoic acid, 2- [4-chloro -6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-hept acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-heptanoic acid, 2- [4-chloro-6- (4- chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-heptanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidine-2 -ylsulfanyl] -2-pentyl-heptanoic, 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-methyloctanoic acid, 2- [4-chloro-6- (4-chloro) 2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-heptanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl ] -2-propyl-heptanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-heptanoic acid, 2- [4-chloro -6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-pentyl-heptanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl- phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyloctanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl- octanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-propyloctanoic acid, 2- [4-chloro-6- (4- chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-octanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidine-2 -ylsulfanyl] -2-pentyloctanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidine-2-one ylsulfanyl] -2-hexyloctanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-nonanoic acid, 2- [4- Chloro-6- (4-chloro-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-nonanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl -phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-nonanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl nonanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-pentyl-nonanoic acid, 2- [4-chloro-6- (4 -chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-hexyl-nonanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidine 2-ylsulfanyl] -2-heptyl-nonanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-decanoic acid, 2- [ 4-Chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-decanoic acid, 2- [4-chloro-6- (4-chloro-2,3 -dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-decanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimet hyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-decanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2- pentyl-decanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-hexyl-decanoic acid, 2- [4-chloro-6-one 4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-heptyl-decanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidine -2-ylsulfanyl] -2-octyl-decanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-undecanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-ethyl undecanoic acid, 2- [4-chloro-6- (4-chloro-2, 3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-undecanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] - 2-Butyl undecanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-pentyl undecanoic acid, 2- [4-chloro-6 - (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-hexyl-undeca acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-heptyl-undecanoic acid, 2- [4-chloro-6- (4- chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-octyl-undecanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidine-2 -ylsulfanyl] -2-nonyl undecanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-methyldodecanoic acid, 2- [4 Chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-dodecanoic acid, 2- [4-chloro-6- (4-chloro-2,3- dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyldodecanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2- Butyl dodecanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-pentyldodecanoic acid, 2- [4-chloro-6- ( 4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-hexyl-dodecanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidine -2-ylsulfanyl] -2-heptyl-dodecanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-p henylamino) -pyrimidin-2-ylsulfanyl] -2-octyldodecanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-nonyl- dodecanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-decyl-dodecanoic acid, 2- [4-chloro-6- (4- bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -propanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] - butanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -pentanoic acid, 2- [4-chloro-6- (4-bromo-2, 3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl-hexanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -heptanoic acid, 2- [ 4-Chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -octanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino ) -pyrimidin-2-ylsulfanyl] nonanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] decanoic acid, 2- [4-chloro 6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -phen yl-acetic acid, [4-chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -naphtalen-1-yl-acetic acid, 2- [4-chloro-6- ( 4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-propanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidine 2-ylsulfanyl] -2-methylbutanoic acid, 4-chloro [4- (chloro-6- (4-bromo-2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-ethylbutanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-methylpentanoic acid, 2- [4-chloro-6- (4-bromo) 2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-pentanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-pentanoic acid, 2- [4-chloro-6- (4-bromo) 2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-hexanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl ] -2-ethyl-hexanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-hexanoic acid, 2- [4-chloro -6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-hexanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl- phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-heptanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl- heptanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-heptanoic acid, 2- [4-chloro-6- (4- bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-heptanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidine-2 -ylsulfanyl] -2-pentylheptanoic acid, 2- (4-chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfany l] -2-methyloctanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-ethylheptanoic acid, 2- [4- Chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-propylheptanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl -phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-heptanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-pentyl -heptanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-methyloctanoic acid, 2- [4-chloro-6- (4 -bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyloctanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidine 2-ylsulfanyl] -2-propyloctanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-butyloctanoic acid, 2- [ 4-Chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-pentyloctanoic acid, 2- [4-chloro-6- (4-bromo-2,3 -dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-hexyloctanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino ) -pyrimidin-2-ylsulfanyl] -2-methyl-nonanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-nonanoic acid , 2- [4-Chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-nonanoic acid, 2- [4-chloro-6- (4-bromo 2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-nonanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidine-2-one ylsulfanyl] -2-pentyl-nonanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl-2-hexyl-nonanoic acid, 2- [4-chloro -6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-heptyl-nonanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl- phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-decanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl- decanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-decanoic acid, 2- [4-chloro-6- (4- bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-decanoic acid, 2- [4-chloro-6- (4-bromo-2,3-di methyl-phenylamino) -pyrimidin-2-ylsulfanyl-2-pentyl-decanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-hexyl decanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-heptyl-decanoic acid, 2- [4-chloro-6- (4 -bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-octyl-decanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidine 2-ylsulfanyl] -2-methyl undecanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-ethyl undecanoic acid, 2- [ 4-Chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl undecanoic acid, 2- [4-chloro-6- (4-bromo-2,3 -dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-undecanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2 penta-undecanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-hexyl undecanoic acid, 2- [4-chloro-6- ( 4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-heptyl-undecansä acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-octyl-undecanoic acid, 2- [4-chloro-6- (4- bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-nonyl undecanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidine-2 -ylsulfanyl] -2-methyldodecanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-ethyldodecanoic acid, 2- [4 Chloro-6- (4-bromo-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-propyldodecanoic acid, 2- [4-chloro-6- (4-bromo-2,3- dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-butyl-dodecanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2- pentyl-dodecanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-hexyl-dodecanoic acid, 2- [4-chloro-6-one 4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-heptyl-dodecanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidine -2-ylsulfanyl] -2-octyl-dodecanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyr imidin-2-ylsulfanyl] -2-nonyl-dodecanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-decyl-dodecanoic acid or it are the corresponding acetamides, acethydrazides or C _1-6 alkyl esters or physiologically acceptable salts of these compounds.

Among physiologically acceptable salts, especially the alkali metal salts such as the sodium or potassium salt, alkaline earth metal salts such as the calcium or magnesium salt, and ammonium salts are primary, meant secondary, tertiary or quaternary ammonium compounds. The ammonium compound may be, for example, protonated ethylamine, diethylamine, triethylamine, ethyldiisopropylamine, ethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, dimethylaminomethanol, dibenzylamine, N-methylmorpholine, dehydroabietylamine, procaine, arginine, lysine, ethylenediamine or methylpiperidine.

Pharmaceutical or cosmetic preparations

The Pyrimidine according to the invention or triazine derivative can be used especially in pharmaceutical or cosmetic Preparations for oral, peroral (e.g., sublingual), pulmonary, nasal, topical, enteral, parenteral (e.g., subcutaneous, intramuscular, intrathecal, intradermal or intravenous) or rectal administration, the topical and Parenteral administration are preferred and the topical application especially is preferred. For use of the compounds of the invention as a medicament these are preferably brought into the form of a pharmaceutical preparation, the carrier, auxiliaries and / or additives which are suitable in addition to the active substance for the contains respective application form and optionally other active ingredients. The Pyrimidine or Triazine derivative can in this case, for example, in crystalline and / or amorphous and / or lyophilized and / or dissolved and / or suspended Form be included.

The Pyrimidine or triazine derivative is hereby preferably in quantities up to 20% by weight, more preferably in amounts of 0.001 to 10 Wt .-%, in particular from 0.01 to 5 wt .-%, especially from 0.1 to 2 wt .-%, contained in the preparations. The dosage of the active ingredient may vary depending on the mode of administration and frequency, age and weight of the patient, nature and severity of the disease to be treated, individual response of the patient on the drug and similar factors vary.

Preferably the application of the pyrimidine or triazine derivative via a Period of at least two or four weeks, with the application preferably daily, especially at least twice a day. Preferably is already after a few days, especially after a few weeks one Significant improvement in the clinical picture can be seen.

The Application may be especially oral or sublingual as a solid in the form of capsules, dragees or tablets or as a liquid in the form of solutions, Tinctures, suspensions, elixirs, aerosols or emulsions or vaginal or rectal in the form of globules or suppositories.

For administration by enteral route the pharmaceutical preparations, for example in the form of tablets, Capsules, dragees, syrups, suspensions, solutions, powders, granules or emulsions are present.

For administration parenterally the preparations, for example in the form of solutions, emulsions, suspensions, Lyophilisates or sterile powders for perfusion, infusion or Injection, in particular, the active compounds of the invention as watery solutions present in polyhydroxyethoxylated castor oil.

For the pulmonary Application can Inhaled drugs such as powder inhalers or nebulizers used be, for the nasal application are for example nose drops, -solutions or sprays.

to Preparation of cosmetic or pharmaceutical compositions can be the active ingredients, optionally in combination with others Active substances, together with one or more inert usual excipients and / or diluents, z. Gelatin, gum arabic, maize starch, lactose, cane sugar, Sorbitol, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, Citric acid, tartaric acid, water, Benzyl alcohol, polyalkylene glycol, water / ethanol, water / glycerol, Water / sorbitol, water / polyethylene glycol, propylene glycol, titanium dioxide, a cellulose derivative, e.g. Carboxymethylcellulose or fatty Substances such as hard fat, talc or vegetable oils or their suitable mixtures, in usual galenic preparations such as tablets, dragees, capsules, powders, Incorporate suspensions, drops, ampoules, juices or suppositories. Possibly can about that In addition, preservatives, stabilizers, wetting agents, emulsifiers or salts for alteration osmotic pressure or buffer. As a carrier can also surfactants Auxiliaries such as salts of bile acids or animal or plant phospholipids, but also mixtures thereof as well as liposomes or their components be used.

The pharmaceutical and cosmetic preparations according to the invention may, in addition to the pyrimidine and / or triazine derivative and / or their physiologically tolerated salts, also be further active compounds hold. If it is a preparation for the treatment of psoriasis or atopic dermatitis, then in particular further active against psoriasis or against atopic dermatitis may be included.

In a preferred embodiment psoriasis is treated with a pyrimidine according to the invention or triazine derivative in combination with topically administered Active ingredients administered both simultaneously and alternately can be. The active substances may be tar, in particular coal tar, Steroids, in particular corticosteroids, more preferably glucocorticosteroids, especially cortisone to vitamins or derivatives thereof, in particular to vitamin D or derivatives thereof, especially vitamin D3 or derivatives like calcipotrienes or vitamin A or derivatives thereof Tazarotene, anthralin, fumaric acid, Salicylic acid, oleic acid, linoleic acid, um Hydrotropes such as Eucerin, Vaseline or Aquaphor or oily ones Products like with oil added porridge to vinegar, salt from the dead sea, aloe vera, Jojoba, Zinkpyrithione or Capsaicin act. Subject of the present The invention therefore also relates to compositions which comprise a pyrimidine according to the invention. or triazine derivative and / or their physiologically acceptable Salts and contain at least one of the aforementioned active substances, corticosteroids and derivatives of vitamin D being preferred.

In a further preferred embodiment psoriasis is treated with a pyrimidine according to the invention and / or triazine derivative in combination with phototherapy, both can be performed simultaneously and alternately. phototherapy can in this case, for example, using a laser (pulsed Dye or excimer laser), by sunlight, by UVB light or by UVA light in combination with psoralen. Subject of the present The invention therefore also relates to compositions which comprise a pyrimidine according to the invention. or triazine derivative and / or their physiologically acceptable Salts and psoralen contain.

In a further preferred embodiment psoriasis is treated with a pyrimidine according to the invention and / or triazine derivative in combination with systemic administration of cyclosporin, methotrexate, retinoids or biological agents Origin (so-called "biologics") as Alefacept, Efalizumab, etanercept or infliximab or drugs such as Accutane, hydroxyurea, mycophenolate mofetil, sulfasalazine or 6-thioguanine.

object The present application therefore also includes compositions which a pyrimidine invention or triazine derivative and / or their physiologically acceptable Salts and at least one of the aforementioned active ingredients.

In a further preferred embodiment Treatment of atopic dermatitis in combination with Steroids, especially corticosteroids, more preferably glucocorticosteroids, especially cortisone, or in combination with cyclosporin, in particular Cyclosporin A, or in combination with non-steroidal anti-inflammatory drugs, especially from the group of calcineurin inhibitors, especially Tacrolimus or pimecrolimus, or in combination with vitamins or derivatives thereof, in particular vitamin D, especially vitamin D3, or derivatives thereof. Subject of the present application are therefore also compositions containing a pyrimidine or triazine derivative according to the invention and / or their physiologically acceptable salts and at least contain one of the aforementioned active ingredients.

Medical are divided into five manifestations of psoriasis: In psoriasis vulgaris, also called plaque psoriasis, lie large-scale psoriasis with distinct silvery dandruff with narrow red rim in front. Psoriasis pustulosa is associated with psoriasis purulent pustules. In psoriasis punctata are psoriasis in size of matchheads, predominantly distributed on the hull, to be found. In psoriasis palmaris et plantaris These are psoriasis on the inside of the hand and on the soles of the feet. Psoriasis geographica are large-scale adults Psoriasis, often in Outlines similar a plastic map.

at Special forms of psoriasis can also only individual areas, armpits, navel, inguinal and anal area, Sex organs, head or nails or the entire skin surface (Erythroderma) to be ill. Other special forms are psoriasis in intertriginous clear (e.g., anal fold, navel), nail psoriasis, and isolated phenomena on palms and on soles.

at Around 20% of psoriatics also contract the joints (psoriatic arthritis). The joints can do this even without accompanying skin symptoms.

All are according to the invention mentioned manifestations of psoriasis and also all manifestations atopic dermatitis by treatment with a pyrimidine according to the invention or triazine derivative and in particular by topical or parenteral Application, especially by topical application, treatable.

at In particular, the disease may also be a therapy-refractory disease act, i. a disease caused by the use of today conventionally treatment methods used is untreatable.

The Severe psoriasis can be diagnosed by the severity of erythema, infiltration and the scale. The severity of atopic dermatitis can one on the basis of the expression of erythema, infiltration or induration as well as on the basis of shaping classify the Excoriationen. According to the invention by using a Pyrimidine according to the invention or triazine derivative of at least one of the said factors, preferably all three, treatable, both in terms of the diseases mentioned as well as with regard to chronic inflammatory Dermatoses, especially T-cell-mediated chronic inflammatory Dermatoses, in general.

"Treatable" in the invention means that a, preferably significant, improvement of the clinical picture is achieved, ideally the disease can be completely cured.

Topical application agent

In one according to the invention especially preferred embodiment these are the pharmaceutical or cosmetic compositions to those for topical application to the skin and its appendages and / or for application to the mucous membrane, in particular in the oral or genital area, or for intertriginous application. Hereinafter These preparations are also referred to as skin treatment agents. The application site is the entire skin and mucous membrane and especially the scalp, the skin on the elbows and knees, the skin in the genital area as well as the skin on the hands and Feet in question.

at The pharmaceutical or cosmetic composition may be in particular, a lotion, a cream, a solid or liquid Soap, an ointment, a paste, an oil, a gel, a powder, a Spray or aerosol, a solution, especially alcoholic solution, tincture, a moist dressing, an occlusion dressing, a plaster, a pencil preparation, a hair treatment or hair care product, in particular a hair shampoo, a hair lotion, a hair cure or a hair tonic, a bubble bath, a shower room or a foot bath act.

Of the physiological carriers the skin treatment agent preferably comprises one or more Ingredients, as they usually do used in such preparations, e.g. Fats, oils, superfatting agents, Waxes, silicones, emulsifiers, dispersants, pearlescent waxes, Alcohols, polyols, bodying agents, stabilizers, thickeners, Swelling agent, hydrotrope or moistening and / or moisturizing Substances, polymers, surfactants, plasticizers, foam brakes, alkalinization or acidifiers, softeners, Adsorbents, light stabilizers, electrolytes, sequestering agents, organic solvents, Preservatives, germ-inhibiting agents, especially fungicides or bactericides, plant extracts, antioxidants, biogenic agents, Vitamins, protein hydrolysates, mono-, oligo- and polysaccharides, enzyme inhibitors, in particular MMP1-inhibiting substances, deodorants or odor absorbers, Antiperspirants, antidandruff agents, α-hydroxy and α-ketocarboxylic acids, fragrances, dyes and / or pigments.

In a preferred according to the invention embodiment the use of penetration-promoting substances takes place. The penetration-promoting Substances are in this case selected in particular from substances that belong to an increased Cause skin hydration, and from penetration enhancers such as DMSO, ethanol, isopropanol, glycerol, Propylene glycol, sorbitol and azone. The substances that belong to one increased hydration state lead the skin, are preferably selected from occlusive lipophilic substances such as vaseline, paraffin, almond oil, jojoba oil, isopropyl myristate, Isopropyl palmitate, oleic acid, sunflower oil or triglycerides and from the fatty substances specified below as being suitable according to the invention Substances, and substances resulting from partial protein denaturation increase the hydration state of the skin like anionic surfactants, especially lauryl sulfate. The penetration-promoting substance is in the topical composition preferably in an amount of 0.1 - 5.0, especially preferably from 0.2 to 2.0 Wt .-%, contained.

In the composition of the invention At least one plant extract may be included. The plant extract For example, by extraction of the entire plant, but also exclusively by Extraction from flowers and / or scrolling and / or seeds and / or other parts of plants. According to the invention are available especially the extracts from the meristem, that is, the divisible formation tissue of plants, and extracts of special plants such as green tea, Hamamelis, Chamomile, Marigold, Pansy, Paeonie, Aloe Vera, Horse chestnut, sage, willow bark, cinnamon tree, chrysanthemums, Oak bark, stinging nettle, hops, burdock root, horsetail, hawthorn, lime blossom, almonds, Spruce needles, sandalwood, juniper, coconut, kiwi, guava, lime, mango, Apricot, wheat, melon, orange, grapefruit, avocado, rosemary, Birch, Beech shoots, Mallow, Meadowfoam, Yarrow, Quendel, Thyme, lemon balm, toadstool, marshmallow (Althaea), mallow (Malva sylvestris), Violets, leaves of blackcurrant, coltsfoot, five-fingered cabbage, ginseng, ginger root and sweet potato preferred as plant extract. Can also be used advantageously Algae extracts. The inventively used Algae extracts come from green algae, Brown algae, red algae or blue-green algae (cyanobacteria). The extraction used algae can both natural Origin as well as obtained by biotechnological processes and as desired across from the natural one Shape changed be. The change of Organisms can be genetically engineered, through breeding or through cultivation in with selected Nutrients enriched Media done. Preferred seaweed extracts are from kelp, blue-green algae, from the green alga Codium tomentosum and the brown algae Fucus vesiculosus. One particularly preferred algae extract is from blue-green algae of the species Spirulina, which were cultivated in a magnesium-enriched medium.

Especially the extracts of spirulina, green tea, aloe vera, meristem are preferred Hamamelis, apricot, marigold, guava, sweet potato, lime, mango, Kiwi, cucumber, mallow, marshmallow and violets. The agents according to the invention can also mixtures of several, especially two, different plant extracts contain.

When Extraction agent for the preparation of said plant extracts can For example, water, alcohols and mixtures thereof used become. Among the alcohols are lower alcohols such as ethanol and isopropanol, but especially polyhydric alcohols such as ethylene glycol, Propylene glycol and butylene glycol, both as sole Extracting agent as well as in admixture with water, preferred. plant extracts based on water / propylene glycol in the ratio 1:10 to 10: 1 have become proved to be particularly suitable. The steam distillation falls under the invention the preferred extraction methods. The extraction may but if necessary also in the form of dry extraction.

The plant extracts can be used according to the invention both in pure and in diluted form. If they are used in diluted form, they usually contain about 2 to 80 wt .-% of active substance and as a solvent used in their extraction agent or extractant mixture. Depending on the choice of extractants, it may be preferable to stabilize the plant extract by adding a solubilizer. Suitable solubilizers are, for. B. Ethoxylation products of optionally hydrogenated vegetable and animal oils. Preferred solubilizers are ethoxylated mono-, di- and triglycerides of C _8-22 fatty acids having from 4 to 50 ethylene oxide units, e.g. Hydrogenated ethoxylated castor oil, olive oil ethoxylate, almond oil ethoxylate, mink oil ethoxylate, polyoxyethylene glycol capryl / caprylic acid glyceride, polyoxyethylene glycerol monolaurate and polyoxyethylene glycol coconut fatty acid glycerides.

Farther it may be preferred in the inventive compositions of several, especially from two, different plant extracts use.

Regarding the invention usable Plant extracts continue to be referred to the extracts that in page 44 of the 3rd edition of the Guidance on the Declaration of Ingredients Cosmetic agent, published by the Industrieverband Körperpflege- and Detergents e.V. (IKW), Frankfurt, beginning table are listed.

As enzyme inhibitors, the compositions of the invention may contain, for example, esterase inhibitors. These are preferably trialkyl such as trimethyl citrate, tripropyl, triisopropyl, tributyl citrate and especially triethyl citrate (Hydagen® ^® CAT, Henkel KGaA, Dusseldorf / FRG). The substances inhibit the enzyme activity and thereby reduce odors. Further substances which are suitable as esterase inhibitors are sterol sulfates or phosphates, such as, for example, lanosterol, cholesterol, campesterol, stigmasterol and sitosterol sulfate or phosphate, dicarboxylic acids and their esters, for example glutaric acid, glutaric acid monoethyl ester, glutaric acid diethyl ester, adipic acid, Adipic acid monoethyl ester, diethyl adipate, malonic acid and diethyl malonate, Hydroxycar Bonsäuren and their esters such as citric acid, malic acid, tartaric acid or diethyl tartrate, and zinc glycinate.

Particularly suitable enzyme inhibitors are MMP-1-inhibiting substances, in particular those selected from photolyase and / or T4 endonuclease V, propyl gallate, precocenes, 6-hydroxy-7-methoxy-2,2-dimethyl-1 (2H) -benzopyran, 3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1 (2H) -benzopyran (available as a commercial product Lipochroman 6 ^™ from Lipotec SA) and mixtures thereof. Precocenes are plant-occurring chromene derivatives known as hormones (The Merck Index, 12th Edition, Merck & Co. 1996). The MMP-1-inhibiting effect of these substances is in the German Offenlegungsschrift DE 10016016 A1 described. They are used in amounts of 0.1 to 5, preferably 0.5 to 2 wt .-%, each based on the total agent.

The compositions according to the invention can, especially when used as emulsion, as surface-active solution or as cleaning agent, contain at least one surface-active substance as emulsifier or dispersant. The emulsifiers can form O / W emulsions or W / O emulsions. For W / O emulsions which can be used according to the invention and which are stabilized without hydrophilic emulsifiers, reference is made to the published patent applications DE 19816665 and DE 19801593 directed.

• – Anlagerungsprodukte von 4 bis 30 Mol Ethylenoxid und/oder 0 bis 5 Mol Propylenoxid an lineare C₈-C₂₂-Fettalkohole, an C₁₂-C₂₂-Fettsäuren und an C₈-C₁₅-Alkylphenole,
• – C₁₂-C₂₂-Fettsäuremono- und -diester von Anlagerungsprodukten von 1 bis 30 Mol Ethylenoxid an C₃-C₆-Polyole, insbesondere an Glycerin,
• – Ethylenoxid- und Polyglycerin-Anlagerungsprodukte an Methylglucosid-Fettsäureester, Fettsäurealkanolamide und Fettsäureglucamide,
• – C₈-C₂₂-Alkylmono- und -oligoglycoside und deren ethoxylierte Analoga, wobei Oligomerisierungsgrade von 1,1 bis 5, insbesondere 1,2 bis 2,0, und Glucose als Zuckerkomponente bevorzugt sind,
• – Gemische aus Alkyl-(oligo)-glucosiden und Fettalkoholen, z. B. das im Handel erhältliche Produkt Montanov^®68,
• – Anlagerungsprodukte von 5 bis 60 Mol Ethylenoxid an Rizinusöl und gehärtetes Rizinusöl,
• – Partialester von Polyolen mit 3 – 6 Kohlenstoffatomen mit gesättigten C₈-C₂₂-Fettsäuren,
• – Sterole (Sterine). Als Sterole wird eine Gruppe von Steroiden verstanden, die am C-Atom 3 des Steroid-Gerüstes eine Hydroxylgruppe tragen und sowohl aus tierischem Gewebe (Zoosterole) wie auch aus pflanzlichen Fetten (Phytosterole) isoliert werden. Beispiele für Zoosterole sind das Cholesterol und das Lanosterol. Beispiele geeigneter Phytosterole sind Beta-Sitosterol, Stigmasterol, Campesterol und Ergosterol. Auch aus Pilzen und Hefen werden Sterole, die sogenannten Mykosterole, isoliert.
• – Phospholipide, vor altem die Glucose-Phospolipide, die z. B. als Lecithine bzw. Phosphatidylcholine aus z. B. Eidotter oder Pflanzensamen (z. B. Sojabohnen) gewonnen werden,
• – Fettsäureester von Zuckern und Zuckeralkoholen wie Sorbit,
• – Polyglycerine und Polyglycerinderivate, bevorzugt Polyglyceryl-2-dipolyhydroxystearat (Handelsprodukt Dehymuls^® PGPH) und Polyglyceryl-3-diisostearat (Handelsprodukt Lameform^® TGI),
• – Lineare und verzweigte C₈-C₃₀-Fettsäuren und deren Na-, K-,Ammonium-, Ca-Mg- und Zn – Salze.

Emulsifiers which can be used according to the invention are, for example

• Addition products of 4 to 30 mol of ethylene oxide and / or 0 to 5 mol of propylene oxide onto linear C ₈ -C ₂₂ -fatty alcohols, on C ₁₂ -C ₂₂ -fatty acids and on C ₈ -C ₁₅ -alkylphenols,
• C ₁₂ -C ₂₂ -fatty acid mono- and diesters of addition products of from 1 to 30 mol of ethylene oxide onto C ₃ -C ₆ -polyols, in particular to glycerol,
• Ethylene oxide and polyglycerol addition products to methyl glucoside fatty acid esters, fatty acid alkanolamides and fatty acid glucamides,
• C ₈ -C ₂₂ -alkylmono- and -oligoglycosides and their ethoxylated analogues, preference being given to degrees of oligomerization of from 1.1 to 5, in particular from 1.2 to 2.0, and glucose as the sugar component,
• - Mixtures of alkyl (oligo) glucosides and fatty alcohols, eg. As the commercially available product Montanov ^® 68,
• Adducts of 5 to 60 moles of ethylene oxide with castor oil and hydrogenated castor oil,
• Partial esters of polyols having 3 to 6 carbon atoms with saturated C ₈ -C ₂₂ fatty acids,
• - Sterols (sterols). Sterols are understood to mean a group of steroids which have a hydroxyl group on C-atom 3 of the steroid skeleton and are isolated both from animal tissue (zoosterols) and from vegetable fats (phytosterols). Examples of zoosterols are cholesterol and lanosterol. Examples of suitable phytosterols are beta-sitosterol, stigmasterol, campesterol and ergosterol. From mushrooms and yeasts sterols, the so-called mycosterols, isolated.
• - Phospholipids, before old the glucose phospholipids, the z. B. as lecithins or phosphatidylcholines from z. Egg yolks or plant seeds (eg soybeans),
• Fatty acid esters of sugars and sugar alcohols such as sorbitol,
• - polyglycerols and polyglycerol, preferably Polyglyceryl-2 dipolyhydroxystearate (Dehymuls ^® PGPH commercial product) and polyglyceryl-3 diisostearate (Lameform ^® TGI commercial product)
• - Linear and branched C ₈ -C ₃₀ fatty acids and their Na, K, ammonium, Ca-Mg and Zn salts.

The agents according to the invention contain the emulsifiers preferably in amounts of 0.1 to 25 wt .-%, in particular 0,5 - 15 Wt .-%, based on the total agent.

In a preferred embodiment, at least one nonionic emulsifier having an HLB value of 8 and below, according to the Römpp Lexicon Chemistry (Eds .: J. Falbe, M. Regitz), 10th edition, Georg Thieme Verlag Stuttgart, New York , (1997), page 1764, listed definitions of the HLB value. Such emulsifiers are, for example, compounds of the general formula R ¹ -OR ² in which R ^{1 is} a primary linear alkyl, alkenyl or acyl group having 20-30 C atoms and R ^{2 is} hydrogen, a group having the formula - (C _n H _2n O) _x -H with x = 1 or 2 and n = 2-4 or a polyhydroxyalkyl group having 4-6 C atoms and 2-5 hydroxyl groups. Particularly preferred emulsifier of the formula R ¹ -OR ² is a behene or erucyl derivative in which R ^{1 represents} a linear, terminally substituted alkyl, alkenyl or acyl group having 22 C atoms.

Further preferred emulsifiers with an HLB value of 8 and below are the adducts of 1 or 2 moles of ethylene oxide or propylene oxide with behenyl alcohol, erucyl alcohol, arachidyl alcohol or behenic acid or erucic acid. Preferably, the monoesters of C ₁₆ -C ₃₀ fatty acids with polyols such as. As pentaerythritol, trimethylolpropane, diglycerol, sorbitol, glucose or Methyl glucose. Examples of such products are z. B. sorbitan monobehenate or pentaerythritol monoerucate.

Furthermore, at least one ionic emulsifier selected from anionic, zwitterionic, ampholytic and cationic emulsifiers may be present in the compositions according to the invention. Preferred anionic emulsifiers are alkyl sulfates, alkyl polyglycol ether sulfates and ether carboxylic acids having 10 to 18 carbon atoms in the alkyl group and up to 12 glycol ether groups in the molecule, sulfosuccinic acid mono- and dialkyl esters having 8 to 18 carbon atoms in the alkyl group and sulfosuccinic monoalkylpolyoxyethyl esters having 8 to 18 C atoms in the alkyl group and 1 to 6 oxyethyl groups, monoglyceride sulfates, alkyl and Alkenyletherphosphate and protein fatty acid condensates. Zwitterionic emulsifiers carry in the molecule at least one quaternary ammonium group and at least one -COO ^- - or -SO ₃ ^- group. Particularly suitable zwitterionic emulsifiers are the so-called betaines such as the N-alkyl-N, N-dimethylammonium glycinates, N-acyl-aminopropyl-N, N-dimethylammoniumglycinate and 2-alkyl-3-carboxymethyl-3-hydroxyethyl-imidazoline with 8 each to 18 carbon atoms in the alkyl or acyl group and Kokosacylaminoethylhydroxyethylcarboxymethylglycinat.

Ampholytic emulsifiers contain, in addition to a C ₈ -C ₂₄ -alkyl or -acyl group, at least one free amino group and at least one -COOH or -SO ₃ H group in the molecule and can form internal salts. Examples of suitable ampholytic emulsifiers are N-alkylglycines, N-alkylaminopropionic acids, N-alkylaminobutyric acids, N-alkyliminodipropionic acids, N-hydroxyethyl-N-alkylamidopropylglycines, N-alkyltaurines, N-alkylsarcosines, 2-alkylaminopropionic acids and alkylaminoacetic acids each having about 8 to 24 C Atoms in the alkyl group.

The ionic emulsifiers are in an amount of 0.01 to 5 wt .-%, preferably from 0.05 to 3 wt .-% and particularly preferably from 0.1 to 1 wt .-%, based on the total agent included.

In one according to the invention especially preferred embodiment is an emulsifier selected from the group of higher aliphatic Alcohols, in particular selected from the group consisting of cetyl, stearyl and / or cetylstearyl alcohol.

Farther can the compositions of the invention foaming nonionic, zwitterionic, anionic and cationic surfactants contain.

• – alkoxylierte Fettsäurealkylester der Formel R¹CO-(OCH₂CHR²)_xOR³, in der R¹CO für einen linearen oder verzweigten, gesättigten und/oder ungesättigten Acylrest mit 6 bis 22 Kohlenstoffatomen, R² für Wasserstoff oder Methyl, R³ für lineare oder verzweigte Alkylreste mit 1 bis 4 Kohlenstoffatomen und x für Zahlen von 1 bis 20 steht,
• – Anlagerungsprodukte von Ethylenoxid an Fettsäurealkanolamide und Fettamine,
• – Fettsäure-N-alkylglucamide,
• – C₈-C₂₂-Alkylamin-N-oxide,
• – Alkylpolygykoside entsprechend der allgemeinen Formel RO-(Z)_x wobei R für eine C₈-C₁₆-Alkylgruppe, Z für Zucker sowie x für die Anzahl der Zuckereinheiten steht. Die erfindungsgemäß verwendbaren Alkylpolyglykoside können lediglich einen bestimmten Alkylrest R enthalten. Üblicherweise werden diese Verbindungen aber ausgehend von natürlichen Fetten und Ölen oder Mineralölen hergestellt. In diesem Fall liegen als Alkylreste R Mischungen entsprechend den Ausgangsverbindungen bzw. entsprechend der jeweiligen Aufarbeitung dieser Verbindungen vor. Besonders bevorzugt sind solche Alkylpolyglykoside, bei denen R im wesentlichen aus C₈- und C₁₀-Alkylgruppen, im wesentlichen aus C₁₂- und C₁₄-Alkylgruppen, im wesentlichen aus C₈- bis C₁₆-Alkylgruppen oder im wesentlichen aus C₁₂- bis C₁₆-Alkylgruppen besteht. Als Zuckerbaustein Z können beliebige Mono- oder Oligosaccharide eingesetzt werden. Üblicherweise werden Zucker mit 5 bzw. 6 Kohlenstoffatomen sowie die entsprechenden Oligosaccharide eingesetzt, beispielsweise Glucose, Fructose, Galactose, Arabinose, Ribose, Xylose, Lyxose, Allose, Altrose, Mannose, Gulose, Idose, Talose und Sucrose. Bevorzugte Zuckerbausteine sind Glucose, Fructose, Galactose, Arabinose und Sucrose; Glucose ist besonders bevorzugt. Die erfindungsgemäß verwendbaren Alkylpolyglykoside enthalten im Schnitt 1,1 bis 5, bevorzugt 1,1 bis 2,0 besonders bevorzugt 1,1 bis 1,8 Zuckereinheiten. Auch die alkoxylierten Homologen der genannten Alkylpolyglykoside können erfindungsgemäß eingesetzt werden. Diese Homologen können durchschnittlich bis zu 10 Ethylenoxid- und/oder Propylenoxideinheiten pro Alkylglykosideinheit enthalten.

Examples of nonionic surfactants are

• - alkoxylated fatty acid alkyl esters of the formula R ¹ CO- (OCH ₂ CHR ² ) _x OR ³ , in which R ¹ CO for a linear or branched, saturated and / or unsaturated acyl radical having 6 to 22 carbon atoms, R ^{2 is} hydrogen or methyl, R ^{3 represents} linear or branched alkyl radicals having 1 to 4 carbon atoms and x represents numbers from 1 to 20,
• Adducts of ethylene oxide with fatty acid alkanolamides and fatty amines,
• Fatty acid N-alkylglucamides,
• C ₈ -C ₂₂ -alkylamine N-oxides,
• - Alkylpolygykoside according to the general formula RO- (Z) _x wherein R is a C ₈ -C ₁₆ alkyl group, Z is sugar and x is the number of sugar units. The alkyl polyglycosides which can be used according to the invention can only contain one particular alkyl radical R. Usually, however, these compounds are prepared starting from natural fats and oils or mineral oils. In this case, the alkyl radicals R are mixtures corresponding to the starting compounds or corresponding to the particular work-up of these compounds. Particular preference is given to those alkyl polyglycosides in which R consists essentially of C ₈ and C ₁₀ -alkyl groups, essentially of C ₁₂ and C ₁₄ -alkyl groups, essentially of C ₈ to C ₁₆ -alkyl groups or essentially of C ₁₂ - To C ₁₆ alkyl groups. As sugar building block Z it is possible to use any desired mono- or oligosaccharides. Usually, sugars having 5 or 6 carbon atoms and the corresponding oligosaccharides are used, for example glucose, fructose, galactose, arabinose, ribose, xylose, lyxose, allose, altrose, mannose, gulose, idose, talose and sucrose. Preferred sugar building blocks are glucose, fructose, galactose, arabinose and sucrose; Glucose is particularly preferred. The alkyl polyglycosides which can be used according to the invention contain on average 1.1 to 5, preferably 1.1 to 2.0, more preferably 1.1 to 1.8 sugar units. The alkoxylated homologs of said alkyl polyglycosides can also be used according to the invention. These homologs may contain on average up to 10 ethylene oxide and / or propylene oxide units per alkyl glycoside unit.

Zwitterionic surfactants are those surface-active compounds which carry in the molecule at least one quaternary ammonium group and at least one -COO ^(-) or -SO ₃ ^(-) group. Particularly suitable zwitterionic surfactants are the so-called betaines such as N-alkyl-N, N-dimethylammonium glycinates, for example cocoalkyldimethylammonium glycinate, N-acylaminopropyl-N, N-dimethylammonium glycinates, for example cocoacylaminopropyldimethylammonium glycinate, and 2-alkyl-3-carboxymethyl-3 -hydroxyethylimidazolines having in each case 8 to 18 carbon atoms in the alkyl or acyl group, and the cocoacylaminoethylhydroxyethylcarboxymethylglycinate. A preferred zwitterionic surfactant is the fatty acid amide derivative known by the INCI name Cocamidopropyl Betaine.

• – Acylglutamate der Formel (II),
  
  in der R¹CO für einen linearen oder verzweigten Acylrest mit 6 bis 22 Kohlenstoffatomen und 0, 1, 2 oder 3 Doppelbindungen und X für Wasserstoff, ein Alkali- und/oder Erdalkalimetall, Ammonium, Alkylammonium, Alkanolammonium oder Glucammonium steht, beispielsweise Acylglutamate, die sich von Fettsäuren mit 6 bis 22, vorzugsweise 12 bis 18 Kohlenstoffatomen ableiten, wie beispielsweise C_12/14- bzw. C_12/18-Kokosfettsäure, Laurinsäure, Myristinsäure, Palmitinsäure und/oder Stearinsäure, insbesondere Natrium-N-cocoyl- und Natrium-N-stearoyl-L-glutamat,
• – Ester einer hydroxysubstituierten Di- oder Tricarbonsäure der allgemeinen Formel (III),
  
  in der X=H oder eine -CH₂COOR-Gruppe ist, Y=H oder -OH ist unter der Bedingung, dass Y=H ist, wenn X=-CH₂OOOR ist, R, R¹ und R² unabhängig voneinander ein Wasserstoffatom, ein Alkali- oder Erdalkalimetallkation, eine Ammoniumgruppe, das Kation einer ammonium-organischen Base oder einen Rest Z bedeuten, der von einer polyhydroxylierten organischen Verbindung stammt, die aus der Gruppe der veretherten(C₆-C₁₈)-Alkylpolysaccharide mit 1 bis 6 monomeren Saccharideinheiten und/oder der veretherten aliphatischen (C₆-C₁₆)-Hydroxyalkylpolyole mit 2 bis 16 Hydroxylresten ausgewählt sind, unter der Maßgabe, daß wenigstens eine der Gruppen R, R¹ oder R² ein Rest Z ist,
• – Ester des Sulfobernsteinsäure-Salzes der allgemeinen Formel (IV),
  
  in der R¹ und R² unabhängig voneinander ein Wasserstoffatom, ein Alkali- oder Erdalkalimetallkation, eine Ammoniumgruppe, das Kation einer ammoniumorganischen Base oder einen Rest Z bedeuten, der von einer polyhydroxylierten organischen Verbindung stammt, die aus der Gruppe der veretherten (C₆-C₁₈)-Alkylpolysaccharide mit 1 bis 6 monomeren Saccharideinheiten und/oder der veretherten aliphatischen(C₆-C₁₆)-Hydroxyalkylpolyole mit 2 bis 16 Hydroxylresten ausgewählt ist, unter der Maßgabe, daß wenigstens eine der Gruppen R¹ oder R² ein Rest Z ist,
• – Sulfobernsteinsäuremono- und -dialkylester mit 8 bis 24 C-Atomen in der Alkylgruppe und Sulfobernsteinsäuremonoalkylpolyoxyethylester mit 8 bis 24 C-Atomen in der Alkylgruppe und 1 bis 6 Ethoxygruppen,
• – Ester der Weinsäure und Zitronensäure mit Alkoholen, die Anlagerungsprodukte von etwa 2-15 Molekülen Ethylenoxid und/oder Propylenoxid an Fettalkohole mit 8 bis 22 C-Atomen darstellen,
• – lineare und verzweigte Fettsäuren mit 8 bis 30 C-Atomen (Seifen),
• – Ethercarbonsäuren der Formel R-O-(CH₂-CH₂O)_x-CH₂-OOOH, in der R eine lineare Alkylgruppe mit 8 bis 30 C-Atomen und x = 0 oder 1 bis 16 ist,
• – Acylsarcosinate mit einem linearen oder verzweigten Acylrest mit 6 bis 22 Kohlenstoffatomen und 0, 1, 2 oder 3 Doppelbindungen,
• – Acyltaurate mit einem linearen oder verzweigten Acylrest mit 6 bis 22 Kohlenstoffatomen und 0, 1, 2 oder 3 Doppelbindungen,
• – Acylisethionate mit einem linearen oder verzweigten Acylrest mit 6 bis 22 Kohlenstoffatomen und 0, 1, 2 oder 3 Doppelbindungen,
• – lineare Alkansulfonate mit 8 bis 24 C-Atomen,
• – lineare Alpha-Olefinsulfonate mit 8 bis 24 C-Atomen,
• – Alpha-Sulfofettsäuremethylester von Fettsäuren mit 8 bis 30 C-Atomen,
• – Alkylsulfate und Alkylpolyglykolethersulfate der Formel R-O(CH₂-CH₂O)₂-SO₃X, in der R eine bevorzugt lineare Alkylgruppe mit 8 bis 30 C-Atomen, besonders bevorzugt mit 8 – 18 C-Atomen, z = 0 oder 1 bis 12, besonders bevorzugt 3, und X ein Natrium-, Kalium-, Magnesium-, Zink-, Ammoniumion oder ein Monoalkanol-, Dialkanol- oder Trialkanolammoniumion mit 2 bis 4 Kohlenstoffatomen in der Alkanolgruppe ist, wobei ein besonders bevorzugtes Beispiel Zinkcocoylethersulfat mit einem Ethoxylierungsgrad von z = 3 ist,
• – Gemische oberflächenaktiver Hydroxysulfonate gemäß DE-A-37 25 030,
• – sulfatierte Hydroxyalkylpolyethylen- und/oder Hydroxyalkylenpropylenglykolether gemäß DE-A-37 23 354,
• – Sulfonate ungesättigter Fettsäuren mit 8 bis 24 C-Atomen und 1 bis 6 Doppelbindungen gemäß DE-A-39 26 344,
• – Alkyl- und/oder Alkenyletherphosphate der Formel (V),
  
• – in der R¹ bevorzugt für einen aliphatischen Kohlenwasserstoffrest mit 8 bis 30 Kohlenstoffatomen, R² für Wasserstoff, einen Rest (CH₂CH₂O)_nR¹ oder X, n für Zahlen von 1 bis 10 und X für Wasserstoff, ein Alkali- oder Erdalkalimetall oder NR³R⁴R⁵R⁶, mit R³ bis R⁶ unabhängig voneinander stehend für einen C₁ bis C₄
• – Kohlenwasserstoffrest, steht,
• – sulfatierte Fettsäurealkylenglykolester der Formel R⁷CO(AlkO)_nSO₃M, in der R⁷CO- für einen linearen oder verzweigten, aliphatischen, gesättigten und/oder ungesättigten Acylrest mit 6 bis 22 C-Atomen, Alk für CH₂CH₂, CHCH₃CH₂ und/oder CH₂CHCH₃, n für Zahlen von 0,5 bis 5 und M für ein Kation steht, wie sie in der DE-OS 197 36 906.5 beschrieben sind,
• – Monoglyceridsulfate und Monoglyceridethersulfate der Formel (VI),
  
  in der R⁸CO für einen linearen oder verzweigten Acylrest mit 6 bis 22 Kohlenstoffatomen, x, y und z in Summe für 0 oder für Zahlen von 1 bis 30, vorzugsweise 2 bis 10, und X für ein Alkali- oder Erdalkalimetall steht. Typische Beispiele für im Sinne der Erfindung geeignete Monoglycerid(ether)sulfate sind die Umsetzungsprodukte von Laurinsäuremonoglycerid, Kokosfettsäuremonoglycerid, Palmitinsäuremonoglycerid, Stearinsäuremonoglycerid, Ölsäuremonoglycerid und Talgfettsäuremonoglycerid sowie deren Ethylenoxidaddukte mit Schwefeltrioxid oder Chlorsulfonsäure in Form ihrer Natriumsalze. Vorzugsweise werden Monoglyceridsulfate der Formel (VI) eingesetzt, in der R⁸CO für einen linearen Acylrest mit 8 bis 18 Kohlenstoffatomen steht.

Suitable anionic surfactants in compositions according to the invention are all anionic surfactants suitable for use on the human body. These are characterized by a water-solubilizing, anionic group such as. As a carboxylate, sulfate, sulfonate or phosphate group and a lipophilic alkyl group having about 8 to 30 carbon atoms. In addition, glycol or polyglycol ether groups, ester, ether and amide groups and hydroxyl groups may be present in the molecule. Examples of suitable foaming anionic surfactants are, in each case in the form of the sodium, potassium and ammonium as well as the mono-, di- and trialkanolammonium salts having 2 to 4 carbon atoms in the alkanol group,

• Acylglutamates of the formula (II),
  
  in which R ¹ CO is a linear or branched acyl radical having 6 to 22 carbon atoms and 0, 1, 2 or 3 double bonds and X is hydrogen, an alkali and / or alkaline earth metal, ammonium, alkylammonium, alkanolammonium or glucammonium, for example acylglutamates, which are derived from fatty acids having 6 to 22, preferably 12 to 18 carbon atoms, such as, for example, C _12/14 or C _12/18 coconut fatty acid, lauric acid, myristic acid, palmitic acid and / or stearic acid, in particular sodium N-cocoyl and sodium N-stearoyl-L-glutamate,
• Esters of a hydroxy-substituted di- or tricarboxylic acid of the general formula (III),
  
  wherein X = H or a -CH ₂ COOR group, Y = H or -OH is under the condition that Y = H, when X = -CH ₂ OOOR, R, R ¹ and R ^{2 are} independent of each other a hydrogen atom, an alkali or alkaline earth metal cation, an ammonium group, the cation of an ammonium organic base or a radical Z derived from a polyhydroxylated organic compound selected from the group of etherified (C ₆ -C ₁₈ ) alkyl polysaccharides with 1 to 6 monomeric saccharide units and / or the etherified aliphatic (C ₆ -C ₁₆ ) -hydroxyalkylpolyols having 2 to 16 hydroxyl radicals, with the proviso that at least one of the groups R, R ¹ or R ^{2 is} a radical Z,
• Esters of the sulfosuccinic acid salt of the general formula (IV),
  
  in which R ¹ and R ² independently of one another denote a hydrogen atom, an alkali metal or alkaline earth metal cation, an ammonium group, the cation of an ammonium organic base or a radical Z derived from a polyhydroxylated organic compound selected from the group of etherified (C ₆ -) C ₁₈ ) -alkyl polysaccharides having 1 to 6 monomeric saccharide units and / or the etherified aliphatic (C ₆ -C ₁₆ ) -hydroxyalkylpolyols having 2 to 16 hydroxyl radicals, provided that at least one of R ¹ or R ^{2 is} a radical Z is,
• Sulfosuccinic acid mono- and dialkyl esters having 8 to 24 C atoms in the alkyl group and sulfosuccinic monoalkylpolyoxyethyl esters having 8 to 24 C atoms in the alkyl group and 1 to 6 ethoxy groups,
• - esters of tartaric acid and citric acid with alcohols, the adducts of about 2-15 molecules Ethylene oxide and / or propylene oxide to fatty alcohols having 8 to 22 carbon atoms,
• - linear and branched fatty acids with 8 to 30 carbon atoms (soaps),
• Ether carboxylic acids of the formula RO- (CH ₂ -CH ₂ O) _x -CH ₂ -OOOH, in which R is a linear alkyl group having 8 to 30 C atoms and x = 0 or 1 to 16,
• Acylsarcosinates having a linear or branched acyl radical having 6 to 22 carbon atoms and 0, 1, 2 or 3 double bonds,
• Acyl taurates having a linear or branched acyl radical having 6 to 22 carbon atoms and 0, 1, 2 or 3 double bonds,
• Acyl isethionates having a linear or branched acyl radical having 6 to 22 carbon atoms and 0, 1, 2 or 3 double bonds,
• - linear alkanesulfonates having 8 to 24 carbon atoms,
• - linear alpha-olefin sulfonates having 8 to 24 carbon atoms,
• Alpha-sulfofatty acid methyl esters of fatty acids having 8 to 30 C atoms,
• - Alkylsulfate and Alkylpolyglykolethersulfate of the formula RO (CH ₂ -CH ₂ O) ₂ -SO ₃ X, in which R is a preferably linear alkyl group having 8 to 30 carbon atoms, more preferably having 8 - 18 carbon atoms, z = 0 or 1 to 12, more preferably 3, and X is a sodium, potassium, magnesium, zinc, ammonium or a monoalkanol, dialkanol or Trialkanolammoniumion having 2 to 4 carbon atoms in the alkanol group, with a particularly preferred example of zinc cocoyl ether sulfate with a degree of ethoxylation of z = 3,
• Mixtures of surface-active hydroxysulfonates according to DE-A-37 25 030,
• Sulfated hydroxyalkylpolyethylene and / or hydroxyalkylene-propylene glycol ethers according to DE-A-37 23 354,
• Sulfonates of unsaturated fatty acids having 8 to 24 C atoms and 1 to 6 double bonds according to DE-A-39 26 344,
• Alkyl and / or alkenyl ether phosphates of the formula (V),
  
• In which R ^{1 is} preferably an aliphatic hydrocarbon radical having 8 to 30 carbon atoms, R ^{2 is} hydrogen, a radical (CH ₂ CH ₂ O) _n R ¹ or X, n is from 1 to 10 and X is hydrogen, an alkali or alkaline earth metal or NR ³ R ⁴ R ⁵ R ⁶ , with R ³ to R ⁶ independently of one another for a C ₁ to C ₄
• - hydrocarbon radical, stands,
• Sulfated fatty acid alkylene glycol esters of the formula R ⁷ CO (AlkO) _n SO ₃ M in which R ^{7 is} CO- for a linear or branched, aliphatic, saturated and / or unsaturated acyl radical having 6 to 22 C atoms, Alk for CH ₂ CH ₂ , CHCH ₃ CH ₂ and / or CH ₂ CHCH ₃ , n is a number from 0.5 to 5 and M is a cation as described in DE-OS 197 36 906.5,
• Monoglyceride sulphates and monoglyceride ether sulphates of the formula (VI),
  
  in which R ⁸ CO is a linear or branched acyl radical having 6 to 22 carbon atoms, x, y and z are in total 0 or numbers of 1 to 30, preferably 2 to 10, and X is an alkali or alkaline earth metal. Typical examples of monoglyceride (ether) sulfates suitable for the purposes of the invention are the reaction products of lauric acid monoglyceride, coconut fatty acid monoglyceride, palmitic acid monoglyceride, stearic acid monoglyceride, oleic acid monoglyceride and tallow fatty acid monoglyceride and their ethylene oxide adducts with sulfur trioxide or chlorosulfonic acid in the form of their sodium salts. Monoglyceride sulfates of the formula (VI) in which R ⁸ CO is a linear acyl radical having 8 to 18 carbon atoms are preferably used.

According to the invention it can for certain Applications be beneficial, mild, i. particularly skin-friendly, Surfactants such as fatty alcohol polyglycol ether sulfates, monoglyceride sulfates, Mono- and / or dialkylsulfosuccinates, fatty acid isethionates, fatty acid sarcosinates, taurides, Fatty acid glutamates, α-olefinsulfonates, ether carboxylic acids, alkyl oligoglucosides, fatty acid glucamides, Alkylamidobetaines and / or protein fatty acid condensates, the latter preferably based on wheat proteins.

The Compositions of the invention can furthermore at least one organic or mineral or modified mineral sunscreen filter included. In the sunscreen filters it is liquid or crystalline at room temperature Substances that are able to absorb ultraviolet rays and the energy absorbed in the form of longer-wave radiation, z. B. heat to give up again. One differentiates between UVA filters and UVB filters. The UVA and UVB filters can used both individually and in mixtures. The use of filter mixtures is preferred according to the invention.

The organic UV filters used according to the invention are preferably selected from the derivatives of dibenzoylmethane, cinnamic esters, diphenylacrylic acid esters, benzophenone, camphor, p-aminobenzoic acid esters, o-aminobenzoic acid esters, salicylic acid esters, benzimidazoles, symmetrically or asymmetrically substituted 1,3,5-triazines, monomeric and oligomeric 4,4-Diarylbutadiencarbonsäureestern and -carbonsäureamiden, Ketotricyclo (5.2.1.0) decane, Benzalmalonsäureestern and any mixtures of the above components. The organic UV filters can be oil-soluble or water-soluble. According to the invention particularly oil-soluble UV filters preferred are 1- (4-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione (Parsol ^® 1789), 1-phenyl-3- (4'- isopropylphenyl) -propane-1,3-dione, 3- (4'-methylbenzylidene) -D, L-camphor, 4- (dimethylamino) benzoic acid 2-ethylhexyl ester, 4- (dimethylamino) benzoic acid 2-octyl ester, 4 - (dimethylamino) benzoate, 4-methoxycinnamic acid 2-ethylhexyl ester, propyl 4-methoxycinnamate, isopentyl 4-methoxycinnamate, 2-cyano-3,3-phenylcinnamic acid 2-ethylhexyl ester (octocrylene), 2-ethylhexyl salicylate, salicylic acid-4 isopropylbenzyl ester, salicylic acid homomenthyl ester (3,3,5-trimethylcyclohexylsalicylate), 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 4-methoxybenzmalonic acid 2-ethylhexyl ester, 2,4,6-trianilino- (p-carbo-2'-ethyl-1'-hexyloxy) -1,3,5-triazine (octyl triazone) and dioctyl butamido triazone ( ^Uvasorb® HEB) as well any mixtures of said K omponents.

preferred water-soluble UV filters are 2-phenylbenzimidazole-5-sulfonic acid and its alkali, alkaline earth, Ammonium, alkylammonium, alkanolammonium and glucammonium salts, sulfonic acid derivatives of benzophenones, preferably 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and their salts, sulfonic acid derivatives of the 3-benzylidene camphor, such as. B. 4- (2-oxo-3-bomylidenemethyl) benzenesulfonic acid and 2-methyl-5- (2-oxo-3-bomylidene) sulfonic acid and their salts.

Some of the oil-soluble UV filters can themselves serve as solvents or solubilizers for other UV filters. Thus, for example, solutions of the UV-A filter 1- (4-tert-butylphenyl) -3- (4'methoxyphenyl) propane-1,3-dione (z. B. Parsol ^® 1789) in various UV-B Make filters. Therefore, in a further preferred embodiment, the compositions according to the invention contain 1- (4-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione in combination with at least one UV-B filter selected from 4 2-ethylhexyl 2-ethoxycinnamate, 2-ethylhexyl 2-cyano-3,3-phenylcinnamate, 2-ethylhexyl salicylate and 3,3,5-trimethylcyclohexylsalicylate. In these combinations, the weight ratio of UV-B filter to 1- (4-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione is between 1: 1 and 10: 1, preferably between 2 : 1 and 8: 1, the molar ratio is between 0.3 and 3.8, preferably between 0.7 and 3.0.

The inventively preferred inorganic photoprotective pigments are finely dispersed or colloidally disperse metal oxides and metal salts, for example titanium dioxide, zinc oxide, iron oxide, aluminum oxide, cerium oxide, zirconium oxide, silicates (talc) and barium sulfate. The particles should have an average diameter of less than 100 nm, preferably between 5 and 50 nm and in particular between 15 and 30 nm, so-called nanopigments. They may have a spherical shape, but it is also possible to use those particles which have an ellipsoidal or otherwise deviating shape from the spherical shape. The pigments can also be surface-treated, ie hydrophilized or hydrophobized. Typical examples are coated titanium dioxides, such as. Example, titanium dioxide T 805 (Degussa) or Eusolex ^® T2000 (Merck). Suitable hydrophobic coating agents are in particular silicones and in particular trialkoxyoctylsilanes or simethicones. Particularly preferred are titanium dioxide and zinc oxide.

Furthermore, at least one protein hydrolyzate or a derivative thereof can be contained in the compositions according to the invention. Both vegetable and animal protein hydrolysates can be used according to the invention. Animal protein hydrolysates are z. B. elastin, collagen, keratin, silk and milk protein protein hydrolysates, which may also be in the form of salts. Vegetable protein hydrolysates, eg. Soy, wheat, almonds, peas, potato and rice protein hydrolysates. Corresponding commercial products are z. B. DiaMin® ^® (Diamalt) Gluadin ^® (Cognis), Lexein ^® (Inolex) and Crotein ^® (Croda).

At Place of protein hydrolysates can on the one hand, otherwise obtained amino acid mixtures, on the other hand individual amino acids as well as their physiologically compatible Salts are used. The preferred amino acids of the invention include glycine, Serine, threonine, cysteine, asparagine, glutamine, pyroglutamic acid, alanine, Valine, leucine, isoleucine, proline, tryptophan, phenylalanine, methionine, aspartic acid, glutamic acid, Lysine, arginine and histidine as well as the zinc salts and the acid addition salts the said amino acids.

Also possible is the use of derivatives of protein hydrolysates, z. In the form of their fatty acid condensation products. Corresponding commercial products are z. B. Lamepon ^® (Cognis), Gluadin ^® (Cognis), Lexein ^® (Inolex), Crolastin ^{® ®} or Crotein (Croda).

Usable according to the invention are also cationized protein hydrolysates, being the underlying protein hydrolyzate from animals, plants, marine life forms or biotechnological obtained protein hydrolysates, may originate. Preference is given to cationic Protein hydrolyzates whose underlying protein content has a molecular weight from 100 to 25,000 daltons, preferably from 250 to 5000 daltons. Furthermore, quaternized cationic protein hydrolyzates amino acids and understand their mixtures.

Furthermore, the cationic protein hydrolysates may also be further derivatized. As typical examples of inventively used cationic protein hydrolysates and derivatives, some are of the INCI - ^th names in the "International Cosmetic Ingredient Dictionary and Handbook" (seventh edition 1997, The Cosmetic, Toiletry, and Fragrance Association 1101 17 Street, NW, Suite 300, Washington, DC 20036-4702) and listed on the market: Cocodimonium Hydroxypropyl Hydrolyzed Collagen, Cocodimonium Hydroxypropyl Hydrolyzed Casein, Steardimonium Hydroxypropyl Hydrolyzed Collagen, Steardimonium Hydroxypropyl Hydrolyzed Hair Keratin, Lauryldimonium Hydroxypropyl Hydrolyzed Keratin, Cocodimonium Hydroxypropyl Hydrolyzed Rice Protein, Cocodimonium Hydroxypropyl Hydrolyzed Silk, Cocodimonium Hydroxypropyl Hydrolyzed Soy Protein, Cocodimonium Hydroxypropyl Hydrolyzed Wheat Protein, Cocodimonium Hydroxypropyl Silk Amino Acids, Hydroxypropyl Arginine Lauryl / Myristyl Ether HCl, Hydroxypropyltrimonium Gelatin. Very particular preference is given to the cationic protein hydrolysates and derivatives based on plants.

In the compositions of the invention are the protein hydrolysates and their derivatives or the amino acids and their derivatives preferably in amounts of 0.01-10% by weight, based on the total mean. Amounts of from 0.1 to 5% by weight, in particular 0.1 to 3 wt .-%, are particularly preferred.

Farther can the compositions of the invention at least one mono-, oligo- or polysaccharide or their derivatives contain.

According to the invention suitable Monosaccharides are z. Glucose, fructose, galactose, arabinose, Ribose, xylose, lyxose, allose, altrose, mannose, gulose, idose and talose, the deoxy sugars fucose and rhamnose as well as amino sugars such as z. As glucosamine or galactosamine. Preference is given to glucose, fructose, galactose, Arabinose and fucose; Glucose is particularly preferred.

According to the invention suitable Oligosaccharides are composed of two to ten monosaccharide units, z. As sucrose, lactose or trehalose. A particularly preferred Oligosaccharide is sucrose. Also particularly preferred the use of honey, the predominant Contains glucose and sucrose.

Polysaccharides which are suitable according to the invention are composed of more than ten monosaccharide units. Preferred polysaccharides are the starches made from α-D-glucose units and starch degradation products such as amylose, amylopectin and dextrins. Particularly advantageous according to the invention are chemically and / or thermally modified starches, for. Hydroxypropyl starch phosphate, dihydroxypropyldistarch phosphate or the commercial products Dry ^Flo® . Further preferred are dextrans and their derivatives, eg. B. dextran sulfate. Also preferred are nonionic cellulose derivatives such as methylcellulose, hydroxypropylcellulose or hydroxyethylcellulose, as well as cationic cellulose derivatives, e.g. , The commercial products Celquat ^® and Polymer JR ^®, and preferably Celquat ^® H 100, Celquat L 200 and Polymer JR ^{® ®} 400 (Polyquaternium-10) as well as Polyquaternium-24th Further preferred examples are polysaccharides from fucose units, e.g. B. the commercial product Fucogel ^® . Particularly preferred are the polysaccharides composed of amino sugar units, in particular chitins and their deacetylated derivatives, the chitosans, and mucopolysaccharides. The inventively preferred mucopolysaccharides include hyaluronic acid and its derivatives, e.g. As sodium hyaluronate or Dimethylsilanolhyaluronat, and chondroitin and its derivatives, for. B. chondroitin sulfate.

Farther can the compositions of the invention at least one film-forming, emulsion-stabilizing, thickening or adhesive Polymer included, selected from natural and synthetic polymers that are cationic, anionic, amphoteric charged or non-ionic.

According to the invention preferred are cationic, anionic and nonionic polymers.

Preferred among the cationic polymers are polysiloxanes having quaternary groups, e.g. , The commercial products Q2-7224 (Dow Corning), Dow Corning ^® 929 Emulsion (with amodimethicone), SM-2059 (General Electric), SLM-55067 (Wacker) and Abil ^® -Quat 3270 and 3272 (Th. Goldschmidt).

Preferred anionic polymers which can support the action of the active ingredient used according to the invention comprise carboxylate and / or sulfonate groups and as monomers, for example, acrylic acid, methacrylic acid, crotonic acid, maleic anhydride and 2-acrylamido-2-methylpropanesulfonic acid. The acidic groups may be wholly or partly present as sodium, potassium, ammonium, mono- or triethanolammonium salt. Preferred monomers are 2-acrylamido-2-methylpropanesulfonic acid and acrylic acid. Very particularly preferred anionic polymers contain 2-acrylamido-2-methylpropanesulfonic acid as the sole monomer or as a comonomer, it being possible for the sulfonic acid group to be wholly or partly in salt form. Within this embodiment, it is preferred to use copolymers of at least one anionic monomer and at least one nonionic monomer. With regard to the anionic monomers, reference is made to the substances listed above. Preferred nonionic monomers are acrylamide, methacrylamide, acrylic esters, methacrylic esters, vinylpyrrolidone, vinyl ethers and vinyl esters. Preferred anionic copolymers are acrylic acid-acrylamide copolymers and in particular polyacrylamide copolymers with sulfonic acid-containing monomers. A particularly preferred anionic copolymer consists of 70 to 55 mol% of acrylamide and 30 to 45 mol-2-acrylamido-2-methylpropanesulfonic acid, wherein the sulfonic acid groups wholly or partly as sodium, potassium, ammonium, mono- or triethanolammonium salt available. This copolymer may also be crosslinked, with crosslinking agents preferably polyolefinically unsaturated compounds such as tetraallyloxyethane, allylsucrose, allylpentaerythritol and methylene-bisacrylamide are used. Such a polymer is contained in the commercial product Sepigel ^® 305 from SEPPIC. The use of this compound has proven to be particularly advantageous in the context of the teaching of the invention. Also sold under the name Simulgel ^® 600 as a compound with isohexadecane and polysorbate-80 Natriumacryloyldimethyltaurat copolymers have proved to be particularly effective according to the invention.

Further particularly preferred anionic homopolymers and copolymers are uncrosslinked and crosslinked polyacrylic acids. Allyl ethers of pentaerythritol, sucrose and propylene may be preferred crosslinking agents. Such compounds are for example the commercial products Carbopol ^®. A particularly preferred anionic copolymer contains as monomer 80-98 an unsaturated, optionally substituted C _3-6 carboxylic acid or its anhydride and 2-20%, if desired, substituted acrylic esters of saturated C _10-30 carboxylic acids, the copolymer containing the aforementioned Networking agents can be networked. Corresponding commercial products are Pemulen ^® and Carbopol ^® grades 954, 980, 1342 and ETD 2020 (ex BF Goodrich).

Suitable nonionic polymers include polyvinyl alcohols, which may be partially saponified, for. B. the commercial products Mowiol ^® and vinylpyrrolidone / vinyl ester copolymers and polyvinylpyrrolidones z. B. under the trademark Luviskol ^® (BASF) are sold.

• – pflanzliche Öle, wie Sonnenblumenöl, Olivenöl, Sojaöl, Rapsöl, Mandelöl, Jojobaöl, Orangenöl, Weizenkeimöl, Pfirsichkernöl, Erdnussöl und die flüssigen Anteile des Kokosöls, wobei pflanzliche Öle mit einem hohen Anteil an Ölsäure- und/oder Linolsäureestern, insbesondere Erdnussöl, bevorzugt sind,
• – flüssige Paraffinöle, Isoparaffinöle und synthetische Kohlenwasserstoffe, z. B. 1,3-Di-(2-ethyl-hexyl)-cyclohexan (Cetiol^® S) oder Polydecen,
• – Di-n-alkylether mit insgesamt 12 bis 36, insbesondere 12 bis 24 C-Atomen, z. B. Di-n-octylether (Cetiol^® OE), Di-n- n-Hexyl-n-octylether und n-Octyl-n-decylether.
• – Fettsäuren, besonders lineare und/oder verzweigte, gesättigte und/oder ungesättigte C_8-30-Fettsäuren. Bevorzugt sind C_10-22-Fettsäuren. Beispiele sind die Isostearinsäuren und Isopalmitinsäuren wie die unter der Handelsbezeichnung Edenor^® vertriebenen Fettsäuren. Weitere typische Beispiele für solche Fettsäuren sind Capronsäure, Caprylsäure, 2-Ethylhexansäure, Caprinsäure, Laurinsäure, Isotridecansäure, Myristinsäure, Palmitinsäure, Palmitoleinsäure, Stearinsäure, Isostearinsäure, Ölsäure, Elaidinsäure, Petroselinsäure, Linolsäure, Linolensäure, Elaeostearinsäure, Arachidonsäure, Gadoleinsäure, Behensäure und Erucasäure sowie deren technische Mischungen. Besonders bevorzugt sind üblicherweise die Fettsäureschnitte, die aus Cocosöl oder Palmöl erhältlich sind; insbesondere bevorzugt ist der Einsatz von Stearinsäure, Ölsäure und/oder Linolsäure.
• – Fettalkohole, besonders gesättigte, ein- oder mehrfach ungesättigte, verzweigte oder unverzweigte Fettalkohole mit 6 – 30, bevorzugt 10 – 22 und ganz besonders bevorzugt 12 – 22 Kohlenstoffatomen. Einsetzbar im Sinne der Erfindung sind z. B. Decanol, Octanol, Octenol, Dodecenol, Decenol, Octadienol, Dodecadienol, Decadienol, Oleylalkohol, Erucaalkohol, Ricinolalkohol, Stearylalkohol, Isostearylalkohol, Cetylalkohol, Laurylalkohol, Myristylalkohol, Arachidylalkohol, Caprylalkohol, Caprinalkohol, Linoleylalkohol, Linolenylalkohol und Behenylalkohol, sowie deren Guerbetalkohole, z. B. 2-Ethylhexanol, wobei diese Aufzählung beispielhaften und nicht limitierenden Charakter haben soll. Bevorzugt sind Cetylalkohol und Stearylalkohol.
• – Esteröle, das heißt, Ester von C_6-30-Fettsäuren mit C_2-30-Fettalkoholen. Bevorzugt sind die Monoester der Fettsäuren mit Alkoholen mit 2 bis 24 C-Atomen. Als Alkohol- und Säurekomponenten der Esteröle können die vorstehend genannten Substanzen verwendet werden. Erfindungsgemäß besonders bevorzugt sind Isopropylmyristat, Isononansäure-C_16-18-alkylester, 2-Ethylhexylpalmitat, Stearinsäure-2-ethylhexylester, Cetyloleat, Glycerintricaprylat, Kokosfettalkoholcaprinat/-caprylat, n-Butylstearat, Oleylerucat, Isopropylpalmitat, Oleyloleat, Laurinsäurehexylester, Di-n-butyladipat, Myristylmyristat, Cetearyl Isononanoate und Ölsäuredecylester.
• – Hydroxycarbonsäurealkylester, wobei die Vollester der Glycolsäure, Milchsäure, Äpfelsäure, Weinsäure oder Citronensäure bevorzugt sind, aber auch Ester der β-Hydroxypropionsäure, der Tartronsäure, der D-Gluconsäure, Zuckersäure, Schleimsäure oder Glucuronsäure geeignet sind und besonders bevorzugt die Ester von C₁₂-C₁₅-Fettalkoholen, z. B. die Handelsprodukte Cosmacol^® der EniChem, Augusta Industriale, sind,
• – Dicarbonsäureester wie Di-n-butyladipat, Di-(2-ethylhexyl)-adipat, Di-(2-ethylhexyl)-succinat und Di-isotridecylacelaat sowie Diolester wie Ethylenglykoldioleat, Ethylenglykol-di-isotridecanoat, Propylenglykoldi(2-ethylhexanoat), Propylenglykol-di-isostearat, Propylenglykol-di-pelargonat, Butandiol-di-isostearat, Neopentylglykoldicaprylat,
• – symmetrische, unsymmetrische oder cyclische Ester der Kohlensäure mit Fettalkoholen, z. B. Glycerincarbonat oder Dicaprylylcarbonat (Cetiol^® CC),
• – Mono,- Di- und Trifettsäureester von gesättigten und/oder ungesättigten linearen und/oder verzweigten Fettsäuren mit Glycerin, z. B. Monomuls^® 90-O18, Monomuls^® 90-L12 oder Cutina^® MD,
• – Wachse, insbesondere Insektenwachse wie Bienenwachs und Hummelwachs, Pflanzenwachse wie Candelillawachs und Carnaubawachs, Fruchtwachse, Ozokerit, Mikrowachs, Ceresin, Paraffin, Triglyceride gesättigter und gegebenenfalls hydroxylierter C_16-30-Fettsäuren, wie z. B. gehärtete Triglyceridfette (hydriertes Palmöl, hydriertes Kokosöl, hydriertes Rizinusöl), Glyceryltribehenat oder Glyceryltri-12-hydroxystearat, synthetische Vollester aus Fettsäuren und Glykolen (z. B. Syncrowachs^®) oder Polyolen mit 2 – 6 C-Atomen, Ester von gegebenenfalls hydroxylierten C_2-4-Carbonsäuren mit Lanolinalkoholen und C_12-18-Fettalkoholen, Cholesterol- oder Lanosterolester von C_10-30-Fettsäuren, ethoxylierte C_12-20- Fettsäureglykolester, Fettsäuremonoalkanolamide mit einem C_12-22-Acylrest und einem C_2-4-Alkanolrest, synthetische Fettsäure-Fettalkoholestern, z. B. Stearylstearat oder Cetylpalmitat sowie Esterwachse aus natürlichen Fettsäuren und synthetischen C_20-40-Fettalkoholen (INCI-Bezeichnung C_20-40 Alkyl Stearate),
• – Siliconverbindungen, ausgewählt aus Decamethylcyclopentasiloxan, Dodecamethylcyclohexasiloxan und Siliconpolymeren, die gewünschtenfalls quervernetzt sein können, z. B. Polydialkylsiloxane, Polyalkylarylsiloxane, ethoxylierte Polydialkylsiloxane, bevorzugt die Substanzen mit der INCI-Bezeichnung Dimethicone Copolyol, sowie Polydialkylsiloxane, die Amin- und/oder Hydroxy-Gruppen enthalten.

In a further preferred embodiment of the invention, the effect of the topical compositions according to the invention by fatty substances can be further optimized. Suitable fatty substances are, for example:

• - Vegetable oils, such as sunflower oil, olive oil, soybean oil, rapeseed oil, almond oil, jojoba oil, orange oil, wheat germ oil, peach kernel oil, peanut oil and the liquid portions of coconut oil, vegetable oils with a high proportion of oleic and / or linoleic, especially peanut, preferred are,
• Liquid paraffin oils, isoparaffin oils and synthetic hydrocarbons, e.g. B. 1,3-di- (2-ethyl-hexyl) -cyclohexane (Cetiol ^® S) or polydecene,
• - Di-n-alkyl ethers having a total of 12 to 36, in particular 12 to 24 carbon atoms, for. As di-n-octyl ether (Cetiol ^® OE), di-n-n-hexyl-n-octyl ether and n-octyl-n-decyl ether.
• Fatty acids, especially linear and / or branched, saturated and / or unsaturated C _8-30 fatty acids. C _10-22 fatty acids are preferred. Examples are the isostearic and isopalmitic such as those sold under the trade name Edenor ^® fatty acids. Other typical examples of such fatty acids are caproic, caprylic, 2-ethylhexanoic, capric, lauric, isotridecanoic, myristic, palmitic, palmitoleic, stearic, isostearic, oleic, elaidic, petroselic, linoleic, linolenic as well as their technical mixtures. Particularly preferred are usually the fatty acid cuts obtainable from coconut oil or palm oil; particular preference is given to the use of stearic acid, oleic acid and / or linoleic acid.
• - Fatty alcohols, particularly saturated, mono- or polyunsaturated, branched or unbranched fatty alcohols having 6 - 30, preferably 10 - 22 and most preferably 12 - 22 carbon atoms. Applicable for the purposes of the invention are z. B. decanol, octanol, octenol, dodecenol, decenol, octadienol, dodecadienol, decadienol, oleyl alcohol, eruca alcohol, ricinoleic alcohol, stearyl alcohol, isostearyl alcohol, cetyl alcohol, lauryl alcohol, myristyl alcohol, arachidyl alcohol, caprylic alcohol, capric alcohol, linoleyl alcohol, linolenyl alcohol and behenyl alcohol, and their Guerbet alcohols, z. B. 2-ethylhexanol, this list should have exemplary and non-limiting character. Cetyl alcohol and stearyl alcohol are preferred.
• Ester oils, that is, esters of C _6-30 fatty acids with C _2-30 fatty alcohols. The monoesters of the fatty acids with alcohols having 2 to 24 carbon atoms are preferred. As the alcohol and acid components of the ester oils, the above-mentioned substances can be used. Particularly preferred according to the invention are isopropyl myristate, isononanoic acid C _16-18 alkyl esters, 2-ethylhexyl palmitate, 2-ethylhexyl stearate, cetyl oleate, glycerol tricaprylate, coconut fatty alcohol caprylate / caprylate, n-butyl stearate, oleyl erucate, isopropyl palmitate, oleyl oleate, hexyl laurate, di-n-butyl butyladipate, myristyl myristate, cetearyl isononanoate and oleic acid decyl ester.
• - Hydroxycarboxylic acid alkyl esters, wherein the full esters of glycolic acid, lactic acid, malic acid, tartaric acid or citric acid are preferred, but also esters of β-hydroxypropionic acid, tartronic acid, D-gluconic acid, sugar acid, mucic acid or glucuronic acid are suitable and particularly preferably the esters of C _12th -C ₁₅ fatty alcohols, e.g. B. the commercial products Cosmacol ^® EniChem, Augusta Industriale, are,
• Dicarboxylic esters such as di-n-butyl adipate, di (2-ethylhexyl) adipate, di- (2-ethylhexyl) succinate and di-isotridecyl acelate and diol esters such as ethylene glycol dioleate, ethylene glycol diisotridecanoate, propylene glycol di (2-ethylhexanoate), Propylene glycol di-isostearate, propylene glycol di-pelargonate, butanediol di-isostearate, neopentyl glycol dicaprylate,
• - Symmetrical, asymmetric or cyclic esters of carbonic acid with fatty alcohols, eg. As glycerol carbonate or dicaprylyl carbonate (Cetiol ^® CC),
• - mono, - di- and tri-fatty acid esters of saturated and / or unsaturated linear and / or branched fatty acids with glycerol, z. B. ^® Monomuls 90-O18, Monomuls 90-L12 ^® or Cutina ^® MD,
• Waxes, in particular insect waxes such as beeswax and bumblebee wax, plant waxes such as candelilla wax and carnauba wax, fruit waxes, ozokerite, microwax, ceresin, paraffin, triglycerides of saturated and optionally hydroxylated C _16-30 fatty acids, such as. B. hydrogenated triglyceride fats (eg Syncrowachs ^®.) (Hydrogenated palm oil, hydrogenated coconut oil, hydrogenated castor oil), glyceryl tribehenate or glyceryl tri-12-hydroxystearate, synthetic Vollester of fatty acids and glycols or polyols containing 2 - 6 carbon atoms, esters of optionally hydroxylated C _2-4 carboxylic acids with lanolin alcohols and C _12-18 fatty alcohols, cholesterol or lanosterol esters of C _10-30 fatty acids, C _12-20 ethoxylated fatty acid glycol esters, fatty acid monoalkanolamides having a C _12-22 acyl radical and a C _{2 -4} -alkanol radical, synthetic fatty acid fatty alcohol esters, eg. Stearyl stearate or cetyl palmitate and ester waxes of natural fatty acids and synthetic C _20-40 fatty alcohols (INCI name C _20-40 alkyl stearates),
• Silicone compounds selected from decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane and silicone polymers, which may be crosslinked, if desired, e.g. As polydialkylsiloxanes, polyalkylarylsiloxanes, ethoxylated polydialkylsiloxanes, preferably the substances with the INCI name dimethicone copolyol, as well as polydialkylsiloxanes containing amine and / or hydroxyl groups.

The Use amount of fatty substances is 0.1 - 50 % By weight, preferably 0.1-20 % By weight and particularly preferably 0.1-15% by weight, in each case based on the entire remedy.

As superfatting agent can Substances such as lanolin and lecithin and polyethoxylated or acylated lanolin and lecithin derivatives, polyol fatty acid esters, Monoglycerides and fatty acid alkanolamides be used, the latter also as foam stabilizers serve.

Suitable pearlescing waxes are, for example: alkylene glycol esters, especially ethylene glycol distearate; Fatty acid alkanolamides, especially coconut fatty acid diethanolamide; Partial glycerides, especially stearic acid remainder noglycerid; Esters of polybasic, optionally hydroxy-substituted carboxylic acids with fatty alcohols having 6 to 22 carbon atoms, especially long-chain esters of tartaric acid; Fatty substances, such as fatty alcohols, fatty ketones, fatty aldehydes, fatty ethers and fatty carbonates, which in total have at least 24 carbon atoms, especially lauron and distearyl ether; Fatty acids such as stearic acid, hydroxystearic acid or behenic acid, ring-opening products of olefin epoxides having 12 to 22 carbon atoms with fatty alcohols having 12 to 22 carbon atoms and / or polyols having 2 to 15 carbon atoms and 2 to 10 hydroxyl groups and mixtures thereof.

When Bodying agents are primarily fatty alcohols or hydroxy fatty alcohols with 12 to 22 and preferably 16 to 18 carbon atoms and next to it Partial glycerides, fatty acids or hydroxy fatty acids in Consideration. Preference is given to a combination of these substances with alkyl oligoglucosides and / or fatty acid N-methylglucamides same chain length and / or polyglycerol poly-12-hydroxy stearates.

When Anti-dandruff agents can Climbazole, octopirox and zinc pyrethion. Preference may be given to fight of dandruff the preparations according to the invention with at least one of these anti-dandruff agents can be used in combination.

The Skin treatment agents according to the invention may further comprise at least one α-hydroxycarboxylic acid or α-ketocarboxylic acid or their ester, lactone or salt form included. Suitable α-hydroxycarboxylic acids or α-ketocarboxylic acids are especially selected from lactic acid, Tartaric acid, citric acid, 2-hydroxybutanoic acid, 2,3-dihydroxypropanoic acid, 2-hydroxypentanoic acid, 2-hydroxyhexanoic acid, 2-hydroxyheptanoic acid, 2-hydroxyoctanoic acid, 2-hydroxydecanoic acid, 2-hydroxydodecanoic acid, 2-hydroxytetradecanoic acid, 2-hydroxyhexadecanoic acid, 2-hydroxyoctadecanoic acid, mandelic acid, 4- Hydroxymandelic acid, malic acid, erythraric acid, threaric acid, glucaric acid, galactaric acid, mannaric acid, gular acid, 2-hydroxy-2-methylsuccinic acid, gluconic acid, pyruvic acid, glucuronic acid and Galacturonic. The esters of the acids mentioned are selected from the methyl, ethyl, propyl, isopropyl-butyl, amyl, pentyl, hexyl, 2-ethylhexyl, Octyl, decyl, dodecyl and hexadecyl esters. The α-hydroxycarboxylic acids or α-ketocarboxylic acids or their derivatives are in amounts of 0.1-10% by weight, preferably 0.5-5% by weight, in each case based on the total composition.

• – Vitamine, Provitamine und Vitaminvorstufen aus den Gruppen A, C, E und F und Derivate davon, insbesondere 3,4-Didehydroretinol (Vitamin A₂), β-Carotin (Provitamin des Vitamin A₁), Ester von Retinol (Vitamin A₁) mit einer C_2-18-Carbonsäure, insbesondere Retinylacetat oder Retinylpalmitat, Ascorbinsäure (Vitamin C), sowie die Palmitinsäureester, Glucoside oder Phosphate der Ascorbinsäure, Tocopherole, insbesondere α-Tocopherol sowie seine Ester, z. B. das Acetat, das Nicotinat, das Phosphat und das Succinat; weiterhin Vitamin F, worunter essentielle Fettsäuren, besonders Linolsäure, Linolensäure und Arachidonsäure, verstanden werden,
• – Vitamine, Provitamine oder Vitaminvorstufen der Vitamin B-Gruppe oder deren Derivate sowie Derivate von 2-Furanon, insbesondere Vitamin B₁, Vitamin B₂, Vitamin B₃, Vitamin B₅, Vitamin B₆, Vitamin B₇ oder Vitamin B₁₂,
• – Allantoin,
• – Bisabolol,
• – Antioxidantien, zum Beispiel Imidazole (z. B. Urocaninsäure) und deren Derivate, Peptide wie D,L-Carnosin, D-Carnosin, L-Carnosin und deren Derivate (z. B. Anserin), Chlorgensäure und deren Derivate, Liponsäure und deren Derivate (z. B. Dihydroliponsäure), Aurothioglucose, Propylthiouracil und andere Thiole (z. B. Thioredoxin, Glutathion, Cystein, Cystin, Cystamin und deren Glycosyl-, N-Acetyl-, Methyl-, Ethyl-, Propyl-, Amyl-, Butyl- und Lauryl-, Palmitoyl-, Oleyl-, γ-Linoleyl-, Cholesteryl- und Glycerylester) sowie deren Salze, Dilaurylthiodipropionat, Distearylthiodipropionat, Thiodipropionsäure und deren Derivate (Ester, Ether, Peptide, Lipide, Nukleotide, Nukleoside und Salze) sowie Sulfoximinverbindungen (z. B. Buthioninsulfoximine, Homocysteinsulfoximin, Butioninsulfone, Penta- Hexa-, Heptathioninsulfoximin) in sehr geringen verträglichen Dosierungen (z. B. pmol bis μmol/kg), ferner (Metall)-Chelatoren (z. B. α-Hydroxyfettsäuren, Palmitinsäure, Phytinsäure, Lactoferrin), Huminsäure, Gallensäure, Gallenextrakte, Bilirubin, Biliverdin, EDTA, EGTA und deren Derivate, ungesättigte Fettsäuren und deren Derivate (z. B. γ-Linolensäure, Linolsäure, Ölsäure), Folsäure und deren Derivate, Ubichinon und Ubichinol und deren Derivate, das Koniferylbenzoat des Benzoeharzes, Rutinsäure und deren Derivate, α-Glycosylrutin, Ferulasäure, Furfurylidenglucitol, Carnosin, Butylhydroxytoluol, Butylhydroxyanisol, Nordihydroguajakharzsäure, Nordihydroguajaretsäure, Trihydroxybutyrophenon, Harnsäure und deren Derivate, Katalase, Superoxid-Dismutase, Zink und dessen Derivate (z. B. ZnO, ZnSO₄), Selen und dessen Derivate (z. B. Selen-Methionin), Stilbene und deren Derivate (z. B. Stilbenoxid, trans-Stilbenoxid) und die als Antioxidans geeigneten Derivate (Salze, Ester, Ether, Zucker, Nukleotide, Nukleoside, Peptide und Lipide) dieser Wirkstoffe,
• – Ceramide und Pseudoceramide,
• – Triterpene, insbesondere Triterpensäuren wie Ursolsäure, Rosmarinsäure, Betulinsäure, Boswelliasäure und Bryonolsäure,
• – Monomere Catechine, besonders Catechin und Epicatechin, Leukoanthocyanidine, Catechinpolymere (Catechin-Gerbstoffe) sowie Gallotannine,
• – Verdickungsmittel, z. B. Gelatine, Pflanzengumme und/oder Polysaccharide wie Agar-Agar, Guar-Gum, Guar-Guar, Alginate, Xanthan-Gum, Gummi arabicum, Karaya-Gummi, Tylosen oder Johannisbrotkernmehl, hydrophile Kieselsäuren und/oder natürliche und synthetische Tone und Schichtsilikate, z. B. Bentonit, Hectorit, Montmorillonit oder Laponite^®, Ca-, Mg- oder Zn-Seifen von Fettsäuren, Carboxymethylcellulose und Hydroxyethylcellulose, höhermolekulare Polyethylenglycolmono- und -diester von Fettsäuren, Polyacrylate, (z.B. Carbopole^® von Goodrich oder Synthalene^® von Sigma), Polyacrylamide, vollsynthetische Hydrokolloide wie Polyvinylalkohol und Polyvinylpyrrolidon, Tenside wie beispielsweise ethoxylierte Fettsäureglyceride, Ester von Fettsäuren mit Polyolen wie beispielsweise Pentaerythrit oder Trimethylolpropan, Fettalkoholethoxylate mit eingeengter Homologenverteilung oder Alkyloligoglucoside sowie Elektrolyte wie Kochsalz und Ammoniumchlorid,
• – Pflanzenglycoside,
• – Strukturanten wie Maleinsäure und Milchsäure,
• – Dimethylisosorbid,
• – Alpha-, beta- sowie gamma-Cyclodextrine, insbesondere zur Stabilisierung von Retinol,
• – Lösungsmittel, Quell- und Penetrationsstoffe wie Ethanol, Isopropanol, Ethylenglykol, Propylenglykol, Propylenglykolmonoethylether, Glycerin und Diethylenglykol, Carbonate, Hydrogencarbonate, Guanidine, Harnstoffe sowie primäre, sekundäre und tertiäre Phosphate
• – Parfümöle, Pigmente sowie Farbstoffe zum Anfärben des Mittels,
• – Substanzen zur Einstellung des pH-Wertes, z. B. α- und β-Hydroxycarbonsäuren,
• – Komplexbildner wie EDTA, NTA, β-Alanindiessigsäure und Phosphonsäuren,
• – Trübungsmittel wie Latex, Styrol/PVP- und Styrol/Acrylamid-Copolymere,
• – Perlglanzmittel wie Ethylenglykolmono- und -distearat sowie PEG-3-distearat,
• – Treibmittel wie Propan-Butan-Gemische, N₂O, Dimethylether, CO₂ und Luft.

The compositions of the invention may contain other active ingredients, auxiliaries and additives, for example:

• - Vitamins, provitamins and vitamin precursors from groups A, C, E and F and derivatives thereof, in particular 3,4-didehydroretinol (vitamin A ₂ ), β-carotene (provitamin of vitamin A ₁ ), esters of retinol (vitamin A ₁ ) with a C _2-18 carboxylic acid, in particular retinyl acetate or retinyl palmitate, ascorbic acid (vitamin C), and the palmitic acid esters, glucosides or phosphates of ascorbic acid, tocopherols, in particular α-tocopherol and its esters, for. The acetate, the nicotinate, the phosphate and the succinate; vitamin F, which is understood to mean essential fatty acids, especially linoleic acid, linolenic acid and arachidonic acid,
• Vitamins, provitamins or vitamin B precursors or derivatives thereof and derivatives of 2-furanone, in particular vitamin B ₁ , vitamin B ₂ , vitamin B ₃ , vitamin B ₅ , vitamin B ₆ , vitamin B ₇ or vitamin B ₁₂ ,
• - allantoin,
• - bisabolol,
• Antioxidants, for example imidazoles (eg urocanic acid) and their derivatives, peptides such as D, L-carnosine, D-carnosine, L-carnosine and their derivatives (eg anserine), chlorogenic acid and its derivatives, lipoic acid and their derivatives (eg dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (eg thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl , Butyl and lauryl, palmitoyl, oleyl, γ-linoleyl, cholesteryl and glyceryl esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts ) as well as sulfoximine compounds (eg buthionine sulfoximines, homocysteinesulfoximine, bithine sulfones, penta-hexa, heptathionine sulfoximine) in very low compatible dosages (eg pmol to μmol / kg), furthermore (metal) chelators (eg α Hydroxy fatty acids, palmitic acid, phytic acid, lacto ferrin), humic acid, bile acid, biliary extracts, bilirubin, biliverdin, EDTA, EGTA and their derivatives, unsaturated fatty acids and their derivatives (e.g. Gamma-linolenic acid, linoleic acid, oleic acid), folic acid and its derivatives, ubiquinone and ubiquinol and derivatives thereof, benzylic resin, rutinic acid and derivatives thereof, α-glycosylrutin, ferulic acid, furfurylideneglucitol, carnosine, butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiacetic acid, nordihydroguiaretic acid , Trihydroxybutyrophenone, uric acid and its derivatives, catalase, superoxide dismutase, zinc and its derivatives (eg ZnO, ZnSO ₄ ), selenium and its derivatives (eg selenium methionine), stilbenes and their derivatives (e.g. B. stilbene oxide, trans-stilbene oxide) and the antioxidant suitable derivatives (salts, Es ter, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these active substances,
• Ceramides and pseudoceramides,
• Triterpenes, in particular triterpenic acids such as ursolic acid, rosmarinic acid, betulinic acid, boswellic acid and bryonolic acid,
• - Monomeric catechins, especially catechin and epicatechin, leucoanthocyanidins, catechin polymers (catechin tannins) and gallotannins,
• - Thickener, z. As gelatin, plant gums and / or polysaccharides such as agar-agar, guar-gum, guar-guar, alginates, xanthan gum, gum arabic, karaya gum, tyloses or locust bean gum, hydrophilic silicic acids and / or natural and synthetic clays and phyllosilicates , z. As bentonite, hectorite, montmorillonite or Laponite ^®, Ca, Mg or Zn soaps of fatty acids, carboxymethyl cellulose and hydroxyethyl cellulose, high molecular weight polyethylene and diesters of fatty acids, polyacrylates (for example Carbopol ^® of Goodrich or Synthalens ^® of Sigma) , Polyacrylamides, fully synthetic hydrocolloids such as polyvinyl alcohol and polyvinylpyrrolidone, surfactants such as ethoxylated fatty acid glycerides, esters of fatty acids with polyols such as pentaerythritol or trimethylolpropane, fatty alcohol ethoxylates with restricted homolog distribution or alkyl oligoglucosides and electrolytes such as sodium chloride and ammonium chloride,
• - vegetable glycosides,
• - structurants such as maleic acid and lactic acid,
• - dimethyl isosorbide,
• Alpha, beta and gamma cyclodextrins, in particular for the stabilization of retinol,
• - Solvents, swelling and penetrating agents such as ethanol, isopropanol, ethylene glycol, propylene glycol, propylene glycol monoethyl ether, glycerol and diethylene glycol, carbonates, bicarbonates, guanidines, ureas and primary, secondary and tertiary phosphates
• Perfume oils, pigments and dyes for staining the agent,
• - substances for adjusting the pH, z. B. α- and β-hydroxycarboxylic acids,
• Complexing agents such as EDTA, NTA, β-alaninediacetic acid and phosphonic acids,
• Opacifiers such as latex, styrene / PVP and styrene / acrylamide copolymers,
• Pearlescing agents such as ethylene glycol mono- and distearate and PEG-3-distearate,
• - Propellants such as propane-butane mixtures, N ₂ O, dimethyl ether, CO ₂ and air.

The Skin treatment agent according to the invention are advantageously in the form of a topical administration liquid or solid oil-in-water emulsion, Water-in-oil emulsion, Multiple emulsion, microemulsion, PIT emulsion or Pickering emulsion, in the form of a hydrogel, an alkhoholic gel, a lipogel, in the form of a single- or multi-phase solution, a foam, a Ointment, a plaster, a suspension, a powder or a Mixture with at least one suitable as a medical adhesive Polymer before. The skin treatment agents according to the invention can also in anhydrous form, such as an oil or a Balm, to be presented. Here, the carrier may be a vegetable or animal oil, a mineral oil, a synthetic oil or a Mixture of such oils be.

In a particular embodiment the skin treatment agents are present as a microemulsion. Under microemulsions be in the context of the invention in addition to the thermodynamically stable Microemulsions and the so-called "PIT" emulsions Understood. These emulsions are systems with the 3 components water, oil and emulsifier which are at room temperature as an oil-in-water emulsion. At the Heat These systems are formed in a certain temperature range (referred to as phase inversion temperature or "PIT") Microemulsions that convert on further heating in water-in-oil (W / O) emulsions. When followed cooling down again O / W emulsions are formed, but also at room temperature as microemulsions or as very finely divided emulsions with a middle Particle diameter below 400 nm and in particular from about 100 to 300 nm, available. According to the invention, such Micro or "PIT" emulsions preferred be, which have a mean particle diameter of about 200 nm. Details regarding this "PIT emulsions" z. B. the publication Angew. Chem. 97, 655-669 (1985).

In one according to the invention especially advantageous embodiment the composition according to the invention is one low-fat oil-in-water emulsion. Another invention especially advantageous composition contains oleic acid and / or linoleic acid and / or their esters, in particular their glycerol esters. The oleic acid and / or linoleic can in particular as part of a vegetable oil, for example as part of soybean oil, Peanut oil, olive oil or sunflower oil, added be. Another invention especially advantageous composition contains higher aliphatic alcohols, in particular cetyl alcohol, sterol alcohol and / or cetylstearyl alcohol, as emulsifiers or coemulsifiers.

The higher aliphatic alcohol is according to the invention preferably a C ₁₂ - to C ₂₂ -alcohol, in particular a C ₁₄ - to C ₂₀ -alcohol, especially a C ₁₆ - to C ₁₈ -alcohol or mixtures thereof Alcohols in any ratio.

Linoleic acid and oleic acid are already known PPARα activators. It was therefore surprising that the addition of pirinic acid to a linoleic and oleic acid containing Basis for a significant improvement of the course of the disease leads, as in the examples is described.

A particularly preferred, according to the invention, semi-fat oil-in-water emulsion contains water in an amount between 60 and 90% by weight, more preferably in an amount between 70 and 80% by weight, especially in an amount of about 75% by weight. % and a mixture of a vegetable oil, in particular peanut oil, and higher aliphatic alcohols, in particular cetyl alcohol and cetylstearyl alcohol, in an amount between 10 and 40% by weight, preferably in an amount between 20 and 30% by weight, especially in an amount of about 25% by weight. As preservatives potassium sorbate and para-hydroxibenzoic acid ethyl esters can be used. Such a composition is for example available under the trade name Doritin ^® (AstaMedica, Germany) in trade. It has been found that such a composition is particularly well suited as a basis for the topical application of pirinixic acid.

It is also conceivable that the skin treatment compositions according to the invention are present in the form of antiperspirants and / or deodorants. Suitable antiperspirant active substances according to the invention are, for example, water-soluble astringent or protein-coagulating metallic salts, in particular inorganic and organic salts of aluminum, zirconium, zinc and titanium, and any desired mixtures of these salts. Water solubility according to the invention is understood as meaning a solubility of at least 4 g of active substance per 100 g of solution at 20 ° C. Alum (KAl (SO ₄ ) ₂ 12 H ₂ O), aluminum sulfate, aluminum lactate, aluminum chlorhydroxyallinate, aluminum chlorohydrate, aluminum sulfocarbolate, aluminum-zirconium chlorohydrate, zinc chloride, zinc sulfocarbolate, zinc sulfate, zirconium chlorohydrate, aluminum Zirconium-chlorohydrate-glycine complexes and complexes of basic aluminum chlorides with propylene glycol or polyethylene glycol. The liquid active substance preparations preferably comprise an astringent aluminum salt, in particular aluminum chlorohydrate, and / or an aluminum-zirconium compound. Aluminum chlorohydrates are playing in powder form sold in as Micro Dry ^® Ultrafine or in activated form as Reach ^® 501 or Reach ^® 103 from Reheis and in the form of aqueous solutions as Locron ^® L of Clariant ^® or as Chlorhydrol from Reheis. Under the name ^Reach® 301, an aluminum sesquihydrate hydrate from Reheis is offered. The use of aluminum-zirconium tri- or tetrachloro-hydrex glycine complexes, which are, for example, from Reheis under the name Rezal 36G ^® commercially, according to the invention is particularly advantageous.

Of the antiperspirant Active ingredient is in the compositions of the invention in one Quantity of 0.01 - 40 Wt .-%, preferably 2 - 30 Wt .-% and in particular 5 - 25 Wt .-%, based on the amount of the active substance in the whole Composition, included.

When Deodorant agents are, for example, fragrances, antimicrobial, antibacterial or germ-inhibiting substances, enzyme-inhibiting substances, Antioxidants and odor adsorbents can be used.

Suitable antimicrobial, antibacterial or antimicrobial substances are in particular C ₁ -C ₄ -alkanols, C ₂ -C ₄ -alkanediols, organohalogen compounds and halides, quaternary ammonium compounds, a range of plant extracts and zinc compounds.

The compositions of the invention may further contain at least one water-soluble polyol, in particular selected from water-soluble diols, triols and higher-grade alcohols and polyethylene glycols. Among the diols are C ₂ -C ₁₂ diols, in particular 1,2-propylene glycol, butylene glycols such. For example, 1,2-butylene glycol, 1,3-butylene glycol and 1,4-butylene glycol, pentanediols, e.g. As 1,2-pentanediol, and hexanediols, z. For example, 1,6-hexanediol. Further preferred are glycerol and technical Oligoglyceringemische with an intrinsic degree of condensation of 1.5 to 10 such as technical Diglyceringemische having a Diglycerine content of 40 to 50 wt .-% or triglycerol, further 1,2,6-hexanetriol and polyethylene glycols (PEG) with a average molecular weight of 100 to 1000 daltons, for example PEG-400, PEG-600 or PEG-1000. Other suitable higher alcohols are the C ₄ , C ₅ and C ₆ monosaccharides and the corresponding sugar alcohols, eg. Mannitol or sorbitol.

The compositions of the invention contain the water-soluble polyol in amounts of 1-50 wt .-%, preferably 1-15 wt .-% and particularly preferably 1-5 wt .-%, each based on the ge velvet composition.

Synthesis of bromo-naphthalen-1-yl-acetic acid ethyl ester

5 g (23.34 mmol) of ethyl 1-naphthylacetate (95%, ABCR), 4.98 g (28 mmol) of N-bromosuccinimide (> 99%, Merck KGaA) and 0.031 g (0.13 mmol) of dibenzoyl peroxide (70 % in H ₂ O, Sigma-Aldrich Chemie GmbH (Fluka)) in 70 mL abs. Carbon tetrachloride (> 99.9%, H ₂ O <50 ppm, Roth) and heated to 90 ° C for 3.5 h. The resulting yellow suspension was filtered and the solvent removed in vacuo. The crude product was fractionally distilled in a high vacuum (T _S = 128-130 ° C., p = 2 × 10 ^-3 mbar).
Yield: 5.5 g (80% of theory), yellow liquid.

General procedure for the synthesis of 2-alkylated (4,6-dihydroxypyrimidin-2-ylsulfanyl) acetic acid ethyl esters

• ^a 2-(4,6-Dihydroxy-pyrimidin-2-ylsulfanyl)-octansäureethylester wurde mittels Säulenchromatographie (stationäre Phase: Silicagel 60 Å, mobile Phase AcOEt/n-Hex 3:1) gereinigt.
• ^b Zersetzung.

To a suspension of 2-thiobarbituric acid (1eq) in ethanol (technically), a solution of NaOH in water (1 M, 1.08 eq) was added and then the corresponding 2-bromo-ethyl ester (1.17 eq) was added dropwise. The suspension was heated to 60 ° C and then stored in the refrigerator at +4 ° C for crystallization. The crystals were filtered off, washed with water and diethyl ether (technical) and dried in an oil pump vacuum.

• ^a 2- (4,6-Dihydroxypyrimidin-2-ylsulfanyl) octanoic acid ethyl ester was purified by column chromatography (stationary phase: silica gel 60 Å, mobile phase AcOEt / n-hex 3: 1).
• ^b decomposition.

chemicals

• 2-thiobarbituric (> 99%, Merck KGaA)
• Ethyl 2-bromoacetate (> 98%, Sigma-Aldrich Chemistry GmbH (Fluka))
• 2-bromopropanoate (99% (GC), Sigma-Aldrich Chemie GmbH (Fluka))
• 2-bromobutyrate (99%, Sigma-Aldrich Chemie GmbH (Fluka))
• 2-Brompentansäureethylester (99% (GC), Sigma-Aldrich Chemie GmbH (Fluka))
• 2-Bromhexansäureethylester (99%, Sigma-Aldrich Chemie GmbH (Fluka))
• 2-Bromctansäureethylester (97%, Sigma-Aldrich Chemie GmbH (Fluka))
• α-bromophenylacetate (97%, Sigma-Aldrich Chemie GmbH (Fluka)

General procedure for the synthesis of 2-alkylated (4,6-di-chloropyrimidin-2-ylsulfanyl) acetic acid ethyl esters

• ^a Säulenchromatographie (stationäre Phase: Silicagel 60 Å, mobile Phase n-Hex/AcOEt).
• ^b Die entstandene Lösung wurde heiss von unlöslichen Rückständen abfiltriert.
• ^c Smp. = 70 – 72 °C.
• ^d Smp. = 117°C.

A solution of the corresponding (4,6-dihydroxypyrimidin-2-ylsulfanyl) ethyl ester 1-8 (1 eq) in POCl ₃ (18 eq) was added N, N-diethylaniline (1 eq) and at 110 ° C heated to boiling. The excess POCl ₃ was distilled off and the residue was added to ice. The aqueous phase was extracted with AcOEt (technical), the combined organic phases were washed with dil. HCl, sat. NaHCO ₃ sol. and water washed. The organic phase was dried over Na ₂ SO ₄ , filtered and the solvent was distilled off in vacuo. The crude product was purified by column chromatography or by recrystallization (see table).

• ^a Column chromatography (stationary phase: silica gel 60 Å, mobile phase n-hex / AcOEt).
• ^b The resulting solution was filtered hot from insoluble residues.
• ^c mp = 70-72 ° C.
• ^d mp. = 117 ° C.

chemicals

• Phosphorus oxychloride (99%, Sigma-Aldrich Chemie GmbH (Fluka))
• N, N-diethylaniline (99%, Acros Organics BVBA)

Synthesis of 2- (4,6-dichloropyrimidin-2-ylsulfanyl) -2-methylpropanoic Acid Ethyl Ester 17

3 g (11.23 mmol) of (4,6-di-chloropyrimidin-2-ylsulfanyl) -acetic acid ethyl ester 9 in 100 ml of abs. Dissolved THF (puriss., Absolute, on molecular sieve, H ₂ O <0.005%, Sigma-Aldrich Chemie GmbH (Fluka)) and cooled to -78 ° C in a cold bath (EtOH / fl. Nitrogen). To this Solution at -78 ° C 1.96 mL (1 eq) HMPA (99% (GC), Sigma-Aldrich Chemie GmbH (Fluka)) and 11.23 mL (11.23 mmol) of a 1M solution of LiHMDS in n-hexane (Sigma-Aldrich Chemie GmbH (Fluka)) and the reaction mixture stirred at -80 ° C for 30 min. Subsequently, the reaction mixture was admixed with 1.59 g (11.23 mmol) of methyl iodide (> 99.5%, Sigma-Aldrich Chemie GmbH (Fluka)) and, after slow heating, stirred at RT for 3.5 h. The reaction solution was again cooled in a cold bath to -80 ° C, 1.96 mL (1 eq) HMPA and 11.23 mL (11.23 mmol) of a 1M solution of LiHMDS in n-hexane, stirred for 30 min at -80 ° C and 1.59 g (11.23 mmol) of methyl iodide. After 18 hours of stirring at RT, the solution was partitioned between 100 mL of water and 100 mL of AcOEt. The organic phase was separated and the aqueous phase extracted twice with 50 mL AcOEt (technically). The combined organic phases were washed once with 100 ml of water, once with 100 ml of sat. NaHCO ₃ sol. and once extracted with 100 mL of water, dried over MgSO ₄ and the solvent distilled off under reduced pressure. The residue was purified by column chromatography (stationary phase: silica gel 60 Å, mobile phase: n-hex / AcOEt 25: 1).
Yield: 1.69 g (52% of theory), yellow oil.

Synthesis of 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -propanoic acid, ethyl ester

3.16 g (11.24 mmol) ethyl 2- (4,6-dichloropyrimidin-2-ylsulfanyl) -propanoate 10, 1.44 mL (11.8 mmol) 2,3-dimethylaniline (99%, Acros Organics BVBA) and 1.25 g (11.8 mmol ) Na ₂ CO ₃ were suspended in 30 ml of ethanol (technically) and heated to boiling for 30 h under reflux. The Na ₂ CO ₃ was filtered off, the solvent was distilled off under reduced pressure and the resulting oil was dissolved in 50 mL AcOEt (technical). The organic phase was washed once with 50 mL of water, three times with 40 mL of 2N HCl each, three times with 40 mL each. NaHCO ₃ sol. and once extracted with 50 mL of water. The combined organic phases were dried over Na ₂ SO ₄ and the solvent was removed in vacuo. The oily crude product was purified by column chromatography (stationary phase: silica gel 60 Å, mobile phase n-hex / AcOEt 10: 1).
Yield: 2.15 g (52% of theory), yellow viscous oil.

Synthesis of 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -butanoic acid ethyl ester

4 g (13.55 mmol) ethyl 2- (4,6-dichloropyrimidin-2-ylsulfanyl) -butanoate 11, 1.66 mL (13.55 mmol) 2,3-dimethylaniline (99%, Acros Organics BVBA) and 1.44 g (13.55 mmol ) Na ₂ CO ₃ were suspended in 35 mL EtOH (technically) and refluxed for 29 h. The Na ₂ CO ₃ was filtered off, the solvent was distilled off under reduced pressure and the resulting oil was dissolved in 50 mL AcOEt. The organic phase was washed once with 50 mL of water, three times with 40 mL of 2N HCl each, three times with 40 mL each. NaHCO ₃ sol. and once extracted with 50 mL of water. The combined organic phases were dried over Na ₂ SO ₄ and the solvent was removed in vacuo. The oily crude product was purified by column chromatography (stationary phase: silica gel 60 Å, mobile phase n-hex / AcOEt 12: 1).
Yield: 3.18 g (62% of theory), yellow crystals.
Mp = 63-64 ° C.

Synthesis of 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -pentanoic acid, ethyl ester

4 g (12.94 mmol) ethyl 2- (4,6-dichloropyrimidin-2-ylsulfanyl) pentanoate 12, 1.58 mL (12.94 mmol) 2,3-dimethylaniline (99%, Acros Organics BVBA) and 1.37 g (12.94 mmol ) Na ₂ CO ₃ were suspended in 35 mL EtOH (technically) and heated to reflux for 28 h. The Na ₂ CO ₃ was filtered off, the solvent was distilled off under reduced pressure and the resulting oil was dissolved in 50 mL AcOEt. The organic phase was washed once with 50 mL of water, three times with 40 mL of 2N HCl each, three times with 40 mL each. NaHCO ₃ sol. and once extracted with 50 mL of water. The combined organic phases were dried over MgSO ₄ and the solvent removed in vacuo. The crude oily product was purified by column chromatography (stationary phase: silica gel 60 Å, mobile phase n-hex / AcOEt 15: 1).
Yield: 3.11 g (62% of theory), white crystals.
Mp = 89-90 ° C.

Synthesis of 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -hexanoic acid ethyl ester

4.5 g (13.92 mmol) ethyl 2- (4,6-dichloropyrimidin-2-ylsulfanyl) -hexanoate 13, 1.7 mL (13.92 mmol) 2,3-dimethylaniline (99%, Acros Organics BVBA) and 1.48 g (13.92 mmol ) Na ₂ CO ₃ were suspended in 40 mL EtOH (technically) and heated to reflux for 30 h under reflux. The Na ₂ CO ₃ was filtered off, the solvent was distilled off under reduced pressure and the resulting oil was dissolved in 50 mL AcOEt. The organic phase was washed once with 50 mL of water, three times with 40 mL of 2N HCl each, three times with 40 mL each. NaHCO ₃ sol. and once extracted with 50 mL of water. The combined organic phases were dried over MgSO ₄ and the solvent removed in vacuo. The crude oily product was purified by column chromatography (stationary phase: silica gel 60 Å, mobile phase n-hex / AcOEt 15: 1).
Yield: 3.06 g (54% of theory), yellow crystals.
Mp = 68 - 69 ° C.

Synthesis of 2- [4-chloro-6- (2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] octanoic acid ethyl ester

2.27 g (6.46 mmol) 2- (4,6-dichloropyrimidin-2-ylsulfanyl) -octanoic acid ethyl ester 14 were suspended in 20 mL EtOH (technically) and then 0.79 mL (6.46 mmol) 2,3-dimethylaniline (99%, Acros Organics BVBA). The reaction mixture was treated with 0.68 g (6.46 mmol) and heated to boiling under reflux for 44 h. The Na ₂ CO ₃ was filtered off and the solvent was removed on a rotary evaporator. The oily residue was taken up in 30 mL AcOEt, three times with 30 mL 2N HCl, twice with 30 mL total. NaHCO ₃ sol. and once extracted with 30 mL of water. The organic phase was dried over MgSO ₄ net and completely concentrated on a rotary evaporator. The resulting yellow oil was purified by column chromatography (stationary phase: silica gel 60 Å, mobile phase n-Hex / AcOEt 10: 1).
Yield: 1.13 g (40% of theory), light yellow oil.

Synthesis of 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -phenyl-ethylacetate

5 g (14.57 mmol) 2- (4,6-dichloropyrimidin-2-ylsulfanyl) -phenyl-acetic acid ethyl ester 15, 1.78 mL (14.57 mmol) 2,3-dimethylaniline (99%, Acros Organics BVBA) and 1.54 g ( 14.57 mmol) Na ₂ CO ₃ were suspended in 40 mL EtOH (technically) and heated to reflux for 28 h under reflux. The Na ₂ CO ₃ was filtered off, the solvent was distilled off under reduced pressure and the resulting oil was dissolved in 50 mL AcOEt. The organic phase was washed once with 50 mL of water, three times with 40 mL of 2N HCl each, three times with 40 mL each. NaHCO ₃ sol. and once extracted with 50 mL of water. The combined organic phases were dried over MgSO ₄ and the solvent removed in vacuo. The oily crude product was purified by column chromatography (stationary phase: silica gel 60 Å, mobile phase n-hex / AcOEt 12: 1).
Yield: 2.3 g (37% of theory), yellow crystals.
Mp = 100 ° C.

Synthesis of [4-chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -naphtalen-1-yl-acetic acid ethyl ester

3 g (7.63 mmol) 2- (4,6-dichloropyrimidin-2-ylsulfanyl) -naphtalen-1-yl-acetic acid ethyl ester 16, 0.93 mL (7.63 mmol) 2,3-dimethylaniline (99%, Acros Organics BVBA) and 0.81 g (7.63 mmol) of Na ₂ CO ₃ were suspended in 20 mL EtOH (technically) and refluxed for 45 h. The Na ₂ CO ₃ was filtered off, the solvent was distilled off under reduced pressure and the resulting oil was dissolved in 30 mL AcOEt. The organic phase was washed once with 30 ml of water, three times with 20 ml of 2N HCl each, twice with 20 ml of sat. NaHCO ₃ sol. and once extracted with 30 mL of water. The combined organic phases were dried over MgSO ₄ and the solvent removed in vacuo. The oily crude product was purified by column chromatography (stationary phase: silica gel 60 Å, mobile phase n-hex / AcOEt 10: 1).
Yield: 0.56 g (16% of theory), white crystals.
Mp = 130 ° C.

Synthesis of 2- [4-chloro-6- (2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-propanoic acid, ethyl ester

1.5 g (5.19 mmol) ethyl 2- (4,6-dichloropyrimidin-2-ylsulfanyl) -2-methylpropanoate 17, 0.67 mL (5.45 mmol) of 2,3-dimethylaniline (99%, Acros Organics BVBA) and 0.58 g (5.45 mmol) of Na ₂ CO ₃ were suspended in 15 mL of EtOH (technically) and heated to reflux for 51 h under reflux. The Na ₂ CO ₃ was filtered off, the solvent was distilled off under reduced pressure and the resulting oil was dissolved in 30 mL AcOEt. The organic phase was washed once with 30 ml of water, three times with 30 ml of 2N HCl each, twice with 30 ml of sat. NaHCO ₃ sol. and once extracted with 30 mL of water. The combined organic phases were dried over MgSO ₄ and the solvent removed in vacuo. The resulting solid was recrystallized from 2 mL EtOH.
Yield: 0.24 g (12% of theory), white crystals.
Mp = 106 ° C.

Synthesis of 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -propanoic acid

1.77 g (4.84 mmol) of the ester 18 were suspended in 35 ml of ethanol (technically) and heated to 80 ° C. To the resulting solution was added 9.68 mL (9.68 mmol) of 1 N NaOH. The reaction mixture was heated to boiling for 55 min and then the solvent was distilled off on a rotary evaporator. The oily residue was taken up in 20 mL of water and acidified with conc. HCl to pH 2 - 3 acidified. The precipitated white solid was filtered off, washed with water and recrystallized from 20 mL AcOEt / n-Hex (1: 1).
Yield: 1.33 g (82% of theory), white crystals.
Mp = 176 ° C.

Synthesis of 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -butanoic acid

At 70 ° C., to a solution of 1.5 g (3.95 mmol) of the ester 19 in 30 mL EtOH, 7.9 mL (7.9 mmol) 1 N NaOH was added rapidly. The reaction boiled for 30 min under reflux. Subsequently, the solvent was distilled off under reduced pressure, the oily residue obtained was taken up in 70 mL of water and acidified with conc. HCl to pH 2 - 3 acidified. The precipitated white solid was filtered off, washed with water and n-hexane and recrystallized from 18 mL AcOEt / n-hexane (2: 1).
Yield: 1.05 g (75% of theory), white crystals.
Mp = 178 ° C.

Synthesis of 2- (4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -pentanoic acid

To a boiling solution of 1.54 g (3.91 mmol) of ester 20 in 30 mL EtOH was added 7.82 mL (7.82 mmol) 1N NaOH. The reaction mixture was heated to boiling for 50 min, the solvent was distilled off under reduced pressure on a rotary evaporator and the oily residue was taken up in 15 ml of water. The aqueous solution was treated with conc. HCl to pH 2 - 3 acidified, the precipitated solid filtered off and washed with water and n-hexane and recrystallized from 18 mL AcOEt / n-Hex (2: 1).
Yield: 0.96 g (67% of theory), white crystals.
Mp = 166-167 ° C.

Synthesis of 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidine-2-isulfanyl] -hexanoic acid

1 g (2.45 mmol) of ester 21 was suspended in 20 mL EtOH and heated to 80 ° C. To the resulting solution was added 4.9 mL (4.9 mmol) 1N NaOH. The reaction mixture was heated to boiling for 60 min and then the solvent was distilled off on a rotary evaporator. The oily residue was taken up in 40 mL of water and acidified with conc. HCl to pH 2 - 3 acidified. The precipitated white solid was filtered off, washed with water and recrystallized from 6 mL AcOEt / n-hexane (1: 5).
Yield: 0.74 g (80% of theory), white crystals.
Mp = 120-121 ° C.

Synthesis of 2- [4-chloro-6- (2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] octanoic acid

1 g (2.29 mmol) of the ester 22 was suspended in 15 mL EtOH and heated to boiling. The resulting solution was admixed with 4.58 ml (4.58 mmol) of 1N NaOH and heated to 85 ° C. for 60 min. The solvent was distilled off under reduced pressure, the oily residue obtained was taken up in 50 ml of water and acidified with conc. HCl to pH 2 - 3 acidified. The precipitated solid was filtered off, washed with water and from 6 mL AcOEt / n-hex (1: 5).
Yield: 0.79 g (85% of theory), white crystals.
Mp = 95 ° C.

Synthesis of [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -phenyl-acetic acid

1.5 g (3.51 mmol) of the ester 23 were suspended in 25 mL EtOH and at 80 ° C heated. The resulting solution 7 mL (7 mmol) 1N NaOH were added.

The reaction mixture was heated to boiling for 55 min and then the solvent was distilled off on a rotary evaporator. The oily residue was taken up in 20 mL of water and acidified with conc. HCl to pH 2 - 3 acidified. The precipitated white solid was filtered off, washed with water and recrystallized from 12 mL AcOEt / n-Hex (1: 2).
Yield: 1.1 g (79% of theory), white crystals.
Mp = 192-200 ° C (decomposition).

Synthesis of [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -naphthalene-acetic acid

0.5 g (1.05 mmol) of the ester 24 was suspended in 8 EtOH and heated to boiling. The resulting solution was mixed with 2.1 mL (2.1 mmol) 1N NaOH and heated to 80 ° C for 60 min. The solvent was distilled off under reduced pressure, the resulting oily residue was taken up in 15 ml of water and acidified with conc. HCl to pH 2 - 3 acidified. The aqueous phase was extracted 1 x with 20 mL of ethyl acetate, the organic solvent was distilled off under reduced pressure and the resulting oil in the refrigerator at +4 ° C crystallized. The crystals were filtered off, washed with water and n-hexane and from 10 mL AcOEt / n-hex (4: 1).
Yield: 0.42 g (89% of theory), white crystals.
Mp = 150 ° C.

Synthesis of 2- [4-chloro-6- (2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-methylpropanoic acid

0.2 g (0.54 mmol) of the ester 25 was suspended in 5 EtOH and heated to boiling. The resulting solution was mixed with 1.07 mL (1.07 mmol) 1N NaOH and heated to 85 ° C for 2 ¼ h. The solvent was distilled off under reduced pressure, the oily residue obtained was taken up in 5 ml of water and acidified with conc. HCl to pH 2 - 3 acidified. The precipitated solid was filtered off, washed with water and dried on the oil pump.
Yield: 0.14 g (77% of theory), white crystals.
Mp = 162-163 ° C.

Synthesis of 4-bromo-2,3-dimethylaniline

At room temperature, to 3.64 g (30 mmol) of 2,3-dimethylaniline (99%, Acros Organics BVBA) in 10 mL of dry DMF (puriss., Absolute, 99.5% (GC), Sigma-Aldrich Chemie GmbH (Fluka)) was added Solution of 5.34 g (30 mmol) of N-bromosuccinimide (purum, 97%, Sigma-Aldrich Chemie GmbH (Fluka)) in 13 ml of dry DMF (puriss., Absolute, 99.5% (GC), Sigma-Aldrich Chemie GmbH (Fluka )). The reaction solution was stirred at RT for 24 h and then added to 80 mL of water. The aqueous phase was extracted 4 times with 25 mL methylene chloride each time (technically). The combined organic phases were washed twice with 20 ml of water, dried over Na ₂ SO ₄ and filtered. The solvent was removed completely on a rotary evaporator. The residue was purified by chromatography (eluent: n-hexane / methylene chloride 1: 1). The product was an orange oil. Yield: 3.1 g (52%), 5% Eduktverunreinigung (2,3-dimethylaniline).

Synthesis of [[4-chloro-6 - [(2,3-dimethyl-4-bromophenyl) amino] -2-pyrimidinyl] thio] ethyl acetate

1.97 g (7.1 mmol) of (4,6-dichloropyrimidin-2-ylsulfanyl) -acetic acid ethyl ester (Reference 6) were suspended in 25 ml of ethanol (technical grade). Subsequently, 1.5 g (7.5 mmol) of 4-bromo-2,3-dimethylaniline and 0.79 g (7.5 mmol) of Na ₂ CO ₃ (anhydrous pa, Merck KgaA) were added. The reaction was heated to boiling for 80 h. The Na ₂ CO ₃ was filtered off and the filtrate was completely concentrated on a rotary evaporator. The oily residue was taken up with 50 ml of diethyl ether (technical grade) and shaken out with 35 ml of water. The organic phase was extracted twice with 20 mL 2N HCl each, twice with 20 mL saturated NaHCO ₃ solution and once with 30 mL water. The ethereal solution was dried over Na ₂ SO ₄ , filtered and the solvent removed on a rotary evaporator. The residue was purified by chromatography (eluent: n-hexane / ethyl acetate 8: 1). White crystals. Yield: 498 mg (17%), m.p .: 92-95 ° C.

Synthesis of [[4-chloro-6 - [(2,3-dimethyl-4-bromophenyl) amino] -2-pyrimidinyl] thio] acetic acid

400 mg (0.91 mmol) of [[4-chloro-6 - [(2,3-dimethyl-4-bromophenyl) amino] -2-pyrimidinyl] thio] ethyl acetate suspended in 6 mL of ethanol and boiling at an oil bath temperature of 90 ° C heated. At boiling heat, 1.82 mL (1.82 mmol) 1N NaOH was added quickly. The reaction solution became refluxed for another 45 min. Subsequently, the solvent became completely removed on a rotary evaporator. The white solid residue was taken up in water and concentrated with concentrated hydrochloric acid (37%) pH 2 - 3 brought the product precipitated in the form of white crystals. Of the Solid was filtered off, several times with water, n-hexane and diethyl ether and recrystallized from n-hexane / ethyl acetate (5: 3) for purification. White crystals. Yield: 298 mg (82%), melting point: 181 ° C.

Synthesis of 4-chloro-2,3-dimethylaniline

At room temperature, 4.24 g (35 mmol) of 2,3-dimethylaniline (99%, Acros Organics BVBA) in 10 mL of dry DMF (puriss., Absolute, 99.5% (GC), Sigma-Aldrich Chemie GmbH (Fluka)) Solution of 4.67 g (35 mmol) of N-chlorosuccinimide (for synthesis, Merck Schuchardt) in 24 mL of dry DMF (puriss., Absolute, 99.5% (GC), Sigma-Aldrich Chemie GmbH (Fluka)) was added dropwise. The reaction solution was stirred at RT for 24 h and then added to 100 ml of water. The aqueous phase was extracted 4 times with 40 mL methylene chloride each time (technically). The combined organic phases were washed twice with 30 ml of water and twice with 30 ml of saturated NaHCO ₃ solution, dried over MgSO ₄ and filtered. The solvent was removed completely on a rotary evaporator.

Of the Residue was purified by chromatography twice (eluent: n-hexane / methylene chloride 1: 1). The product was an orange oil. Yield: 2.12 g (39%), 2% educt contamination (2,3-dimethylaniline).

Synthesis of [[4-chloro-6 - [(2,3-dimethyl-4-chlorophenyl) amino] -2-pyrimidinyl] thio] ethyl acetate

3:37 g (12.2 mmol) of (4,6-dichloro-2-pyrimidin-2-ylsulfanyl) -acetate (own preparation) were suspended in 50 mL ethanol (technically).

Subsequently, 2 g (12.9 mmol) of 4-chloro-2,3-dimethylaniline and 1.36 g (12.9 mmol) of Na ₂ CO ₃ (anhydrous pa, Merck KgaA) were added. The reaction was heated to boiling for 52 h. The Na ₂ CO ₃ was filtered off and the filtrate was completely concentrated on a rotary evaporator. The oily residue was taken up with 50 ml of diethyl ether (technical grade) and extracted by shaking with 40 ml of water. The organic phase was extracted twice with 35 ml of 2N HCl each time, twice with 40 ml of saturated NaHCO ₃ solution and once with 50 ml of water. The ethereal solution was dried over MgSO ₄ , filtered and the solvent removed on a rotary evaporator. The residue was purified by chromatography (eluent: n-hexane / ethyl acetate 5: 1). The resulting red crystals were further recrystallized from ethanol. White crystals. Yield: 1.7 g (37%), melting point: 96 ° C.

Synthesis of [[4-chloro-6 - [(2,3-dimethyl-4-chlorophenyl) amino] -2-pyrimidinyl] thio] acetic acid

1.2 g (3.12 mmol) of [[4-chloro-6 - [(2,3-dimethyl-4-chlorophenyl) amino] -2-pyrimidinyl] thio] ethyl acetate were suspended in 15 ml of ethanol and heated to an oil bath temperature of 90 ° C. heated to boiling. At boiling heat, 6.24 mL (6.24 mmol) 1N NaOH were rapidly added using a syringe. The reaction solution was refluxed for another 45 minutes. Subsequently, the solvent was removed completely on a rotary evaporator. The white solid residue was taken up in 500 mL of water, but did not dissolve completely. It was brought to pH 2-3 with concentrated hydrochloric acid (37%), the product precipitated as white crystals. The aqueous suspension was extracted 3 times with 100 ml of ethyl acetate. The combined organic phases were dried over MgSO ₄ , filtered and the solvent removed on a rotary evaporator. The resulting solid was recrystallized from n-hexane / ethyl acetate (1: 3). White crystals. Yield: 679 mg (61%), m.p .: 189-190 ° C.

Synthesis of [4-chloro-6- (indan-4-ylamino) -pyrimidin-2-ylsulfanyl] -acetic acid ethyl ester

6.89 g (24.97 mmol) of (4,6-dichloropyrimidin-2-ylsulfanyl) -acetic acid ethyl ester 9 and 3.5 g (26.28 mmol) of 4-aminoindan (97%, Sigma-Aldrich Chemie GmbH (Fluka)) were dissolved in 80 mL of EtOH suspended. After adding 2.79 g (26.28 mmol) of Na ₂ CO ₃ , the reaction mixture was refluxed for 24 h. Na ₂ CO ₃ was filtered off and the solvent was distilled off under reduced pressure. The oily residue was taken up in 70 ml of diethyl ether and washed with 30 ml of water. The ethereal solution was washed three times with 30 mL 2N HCl each, three times with 30 mL each. NaHCO ₃ sol. and extracted twice with 30 mL each of water and dried over Na ₂ SO ₄ . The solvent was removed in vacuo and the crude product purified by column chromatography (stationary phase: silica gel 60 Å, mobile phase: n-hex / AcOEt 8: 1).
Yield: 5.02 g (55% of theory), colorless crystals.
Mp = 78-80 ° C.

Synthesis of [4-chloro-6- (indan-5-ylamino) -pyrimidin-2-ylsulfanyl] -acetic acid ethyl ester

6 g (21.73 mmol) of (4,6-di-chloropyrimidin-2-ylsulfanyl) -acetic acid ethyl ester 9 and 3.04 g (22.82 mmol) of 5-aminoindan (95%, Sigma-Aldrich Chemie GmbH (Fluka)) were dissolved in 70 mL EtOH suspended. After adding 2.42 g (22.82 mmol) of Na ₂ CO ₃ , the reaction mixture was refluxed for 24 h. Na ₂ CO ₃ was filtered off and the solvent was removed completely on a rotary evaporator. The oily residue was dissolved in 50 mL diethyl ether and washed with 30 mL water. The organic phase was washed three times with 30 ml of 2N HCl, three times with 30 ml of sat. NaHCO ₃ sol. and once extracted with 50 mL of water and dried over MgSO ₄ . Two-thirds of the diethyl ether was distilled off in vacuo. The crude product crystallized in the refrigerator at + 4 ° C in the form of yellow crystals. These were filtered off, washed with n-hexane and recrystallized from 40 mL EtOH.
Yield: 3.8 g (48% of theory), colorless crystals.
Mp = 89-90 ° C.

Synthesis of [4-chloro-6- (indan-4-ylamino) -pyrimidin-2-ylsulfanyl] -acetic acid

1.5 g (4.12 mmol) of [4-chloro-6- (indan-4-ylamino) -pyrimidin-2-ylsulfanyl] -acetic acid ethyl ester were suspended in 15 mL EtOH and heated to boiling. At boiling heat, 8.24 mL (8.24 mmol) 1N NaOH was added. The reaction was refluxed for 40 minutes. The solvent was removed on a rotary evaporator and the oily residue was taken up in 20 ml of water. The aqueous phase was extracted three times with 30 ml of diethyl ether and then with conc. HCl brought to pH 2 - 3. The precipitated solid was filtered off, washed with water and n-hexane and recrystallized from 5 mL AcOEt / n-Hex (3: 2).
Yield: 1.1 g (80% of theory), colorless crystals.
Mp = 164 - 165 ° C.

Synthesis of [4-chloro-6- (indan-5-ylamino) -pyrimidin-2-ylsulfanyl] -acetic acid

2 g (5.5 mmol) of [4-chloro-6- (indan-5-ylamino) -pyrimidin-2-ylsulfanyl] -acetic acid ethyl ester were suspended in 20 mL of EtOH and heated to boiling. At boiling heat, 11 mL (11 mmol) 1N NaOH was added. The reaction was refluxed for 1 h under reflux. The solvent was removed on a rotary evaporator and the oily residue was taken up in 20 ml of water. The aqueous phase was extracted three times with 30 ml of diethyl ether and then with conc. HCl brought to pH 2 - 3. The precipitated solid was filtered off, washed with water and n-hexane and recrystallized from AcOEt / n-hex (10: 1).
Yield: 1.45 g (79% of theory), yellowish crystals.
Mp = 193-195 ° C.

Synthesis of [4-chloro-6- (octylamino) -pyrimidin-2-ylsulfanyl] -acetic acid ethyl ester

4.5 g (16.85 mmol) of (4,6-dichloropyrimidin-2-ylsulfanyl) -acetic acid ethyl ester were suspended in 60 ml of EtOH and 2.28 ml (17.07 mmol) of 1-aminooctane (95%, Sigma-Aldrich Chemie GmbH (Fluka)) added. After adding 1.81 g (17.07 mmol) of Na ₂ CO ₃ , the reaction mixture was refluxed for 5 h. Na ₂ CO ₃ was filtered off and the solvent was distilled off under reduced pressure. The oily residue was taken up in 60 ml of diethyl ether and washed with 40 ml of water. The ethereal phase was washed three times with 30 ml of 2N HCl, three times with 30 ml of sat. NaHCO ₃ sol. and once extracted with 50 ml of water and dried over Na ₂ SO ₄ . The solvent was removed in vacuo and the resulting oil purified by column chromatography (stationary phase: silica gel 60 Å, mobile phase: n-hex / AcOEt 5: 1). For further purification, the product was recrystallized from EtOH.
Yield: 2.64 g (45% of theory), colorless crystals.
Mp = 33-34 ° C.

Synthesis of [4-chloro-6- (octylamino) -pyrimidin-2-ylsulfanyl] -acetic acid

1.7 g (4.72 mmol) of the ester [4-chloro-6- (octylamino) -pyrimidin-2-ylsulfanyl] -acetic acid ethyl ester were suspended in 20 ml of EtOH and heated to boiling. The reaction mixture was admixed with 9.45 ml (9.45 mmol) of 1N NaOH and refluxed for 1 h. The solvent was distilled off under reduced pressure and the resulting solid was suspended in 400 ml of water. The aqueous phase was acidified with conc. HCl to pH 2 - 3 acidified and extracted twice with 150 ml of AcOEt. The combined organic phases were dried over Na ₂ SO ₄ , the solvent was removed on a rotary evaporator and the resulting solid was recrystallized from AcOEt.
Yield: 1.28 g (82% of theory), white crystals.
Mp = 95 ° C.

Synthesis of [4-chloro-6- (4-bromo-3-methyl-phenylamino) -pyrimidin-2-ylsulfanyl] -acetic acid ethyl ester

3.5 g (13.11 mmol) of ethyl (4,6-dichloropyrimidin-2-ylsulfanyl) acetate, 2.56 g (13.77 mmol) of 4-bromo-3-methylaniline (97%, Sigma-Aldrich Chemie GmbH (Fluka)) and 1.46 g (13.77 mmol) Na ₂ CO ₃ were suspended in 50 ml EtOH and heated at reflux for 28 h. The Na ₂ CO ₃ was filtered off, the solvent was distilled off under reduced pressure and the residue was dissolved in 50 ml of AcOEt. The organic phase was washed once with 40 ml of water, three times with 40 ml of 2N HCl, twice with 40 ml of NaHCO ₃ solution. and once extracted with 40 ml of water and then dried over MgSO ₄ . The resulting solid was recrystallized from EtOH.
Yield: 2.43 g (45% of theory), yellow crystals.
Mp = 125 ° C.

Synthesis of [4-chloro-6- (4-bromo-3-methyl-phenylamino) -pyrimidin-2-ylsulfanyl] -acetic acid

1 g (2.4 mmol) of [4-chloro-6- (4-bromo-3-methylphenylamino) -pyrimidin-2-ylsulfanyl] -acetic acid ethyl ester was suspended in 20 ml of EtOH and heated to boiling. The reaction mixture was admixed with 4.8 ml (4.8 mmol) of 1 N NaOH and refluxed for 45 min. The solvent was distilled off under reduced pressure and the resulting solid was taken up in 300 ml of water. The aqueous phase was acidified with conc. HCl to pH 2 - 3 acidified, the precipitated solid was filtered off and recrystallized from AcOEt / n-hex.
Yield: (67% of theory), white crystals.
Mp = 185-186 ° C.

Synthesis of ethyl 2- [4-chloro-6- (heptylamino) -pyrimidin-2-ylsulfanyl] -hexanoate

5.75 g (17.79 mmol) ethyl 2- (4,6-dichloropyrimidin-2-ylsulfanyl) -hexanoate, 2.05 g (17.79 mmol) 1-aminoheptane (99%, Sigma-Aldrich Chemie GmbH (Fluka)) and 1.89 g ( 17.79 mmol) of Na ₂ CO ₃ were suspended in 50 ml of ethanol and heated to boiling for 2.5 h under reflux. The Na ₂ CO ₃ was filtered off and the solvent was distilled off under reduced pressure. The oily residue was taken up in 50 ml AcOEt and the organic phase once with 50 ml of water, twice with 50 ml of 2N HCl, twice with 50 ml of sat. NaHCO ₃ sol. And once extracted with 50 ml of water. The organic phase was dried over MgSO ₄ and the solvent removed in vacuo.
Yield: 6.24 g (87% of theory), yellow oil.

Synthesis of 2- [4-chloro-6- (heptylamino) -pyrimidin-2-ylsulfanyl] -hexanoic acid

2.5 g (6.22 mmol) of 2- [4-chloro-6- (heptylamino) -pyrimidin-2-ylsulfanyl] -hexanoic acid ethyl ester were suspended in 40 ml of EtOH and heated to boiling. The reaction mixture was treated with 12.44 ml (12.44 mmol) of 1N NaOH and refluxed for 1 h. The solvent was distilled off under reduced pressure, and the resulting oil was taken up in 30 ml of water. The aqueous phase was acidified with conc. HCl to pH 2 - 3 acidified, the precipitated solid was filtered off and recrystallized from AcOEt.
Yield: 0.38 g (16% of theory), white crystals.
Mp = 93 ° C.

Synthesis of [4-chloro-6- [3- (2,4-difluoro-phenyl) -1 (2,3-dimethyl-phenyl) -ureido] -pyrimidin-2-ylsulfanyl] -acetic acid

0.31 g (0.96 mmol) of [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -acetic acid, 0.15 g (0.96 mmol) of 2,4-difluorophenyl isocyanate (98%, Sigma-Aldrich Chemie GmbH (Fluka)) and catalytic amounts of di-n-butyl phosphate (97%, Sigma-Aldrich Chemie GmbH (Fluka)) were in 10 ml abs. Toluen suspended and heated to 100 ° C for 3 h. The solvent was distilled off under reduced pressure. The oily crude product was purified by chromatography (n-Hex / AcOEt 5: 1).
Yield: 0.13 g (28% of theory), white crystals.
Mp = 135 ° C.

Synthesis of (4,6-dibromo-pyrimidin-2-ylsulfanyl) -acetic acid ethyl ester

A mixture of 3.5 g (15.19 mmol) of (4,6-dihydroxypyrimidin-2-ylsulfanyl) -acetic acid ethyl ester and 18.07 g (63.04 mmol) of POBr ₃ (98%, Merck KGaA) in 75 ml of acetonitrile was refluxed for 3 h Boil boiling. The solvent was removed in vacuo, the residue taken up in 90 ml of methylene chloride and then carefully diluted with 100 ml of water. The organic phase was washed three times with 50 ml of water, dried over Na ₂ SO ₄ and the solvent was distilled off under reduced pressure. The crude product was recrystallized from n-hexane.
Yield: 2.81 g (52% of theory), white crystals.
Mp = 120 ° C.

Synthesis of [4-bromo-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -acetic acid ethyl ester

2.5 g (7 mmol) of ethyl (4,6-dibromo-pyrimidin-2-ylsulfanyl) acetate, 0.89 g (7.35 mmol) of 2,3-dimethylaniline (99%, Acros Organics BVBA) and 0.78 g (7.35 mmol) of Na ₂ CO ₃ was suspended in 20 ml of EtOH and heated to reflux for 7 h. The Na ₂ CO ₃ was filtered off and the solvent was removed in vacuo. The solid residue was taken up in 50 ml AcOEt and the organic phase once with 50 ml of water, three times with 30 ml of 2N HCl, three times with 30 ml of sat. NaHCO ₃ sol. And once extracted with 50 ml of water. The organic phase was dried over Na ₂ SO ₄ , filtered and the solvent was distilled off under reduced pressure. The crude product was purified by chromatography (n-Hex / AcOEt 5: 1).
Yield: 2.02 g (73% of theory), white crystals.
Mp = 84 ° C.

Synthesis of [4-Bromo-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -acetic acid

1.5 g (3.78 mmol) of the ester [4-bromo-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -acetic acid ethyl ester were suspended in 27 ml of EtOH and heated to boiling. The reaction mixture was admixed with 7.57 ml (7.57 mmol) of 1N NaOH and heated under reflux for 1 h. The solvent was distilled off under reduced pressure and the resulting white solid was dissolved in 100 ml of water. The aqueous phase was extracted twice with 40 ml of diethyl ether and then with conc. HCl brought to pH 2 - 3. The precipitated solid was filtered off, washed with n-hexane and recrystallized from AcOEt / n-Hex.
Yield: 0.67 g (48% of theory), white crystals.
Mp = 156 ° C.

Test for PPARα activity

The Pyrimidine derivatives as well as WY-14643 were screened for their PPAR⧠ activators by a reporter gene assay Effect examined. The assay is based on the fact that PPAR⧠ after binding of a ligand activates the transcription of genes, under the control of a "PPAR Response Elements "(PPRE) stand. The assay used a plasmid which was for a promoter with three PPRE in a row, the Firefly-Luciferase gene as a reporter. The activity of the luciferase gene is directly related to PPAR activation and can therefore used as a measure for them become. Furthermore, an expression plasmid for murine PPAR⧠ the Cos-7 cells used have no endogenous PPARα- and a control plasmid carrying the Renilla luciferase gene under the control of a under the test conditions constitutive promoter, im Test used.

Cos-7 cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM (Gibco), high glucose, glutamax I) with 10% fetal calf serum and penicillin / streptomycin (100 U / ml) at 37 ° C and 8-10% CO ₂ up to a confluency 80-90% in 96-well plates attracted the cells were 2000 (Invitrogen) using Lipofectamine ^™ transiently For each well 0,8μl of the reagent were mixed with 25 .mu.l Optimem I (Gibco).. During this time, the PPARα expression plasmid (0.02 μg), the control vector (0.002 μg) and the reporter gene plasmid (0.28 μg) were mixed with 25 μl Optimem I for each well and then added to the Lipofectamine solution After incubation for 20 min at room temperature, the culture medium of the Cos-7 cells was replaced by 50 μl of this mixture and 100 μl of Optimem I. After four to six hours of incubation at 37 ° C. and 8-10% CO ₂ , the transfection mixture became by 100 μl of DMEM (Gibco; High glucose, without phenol red, with pyridoxine hydrochloride) with penicillin / streptomycin (100 U / ml), glutamax I or L-glutamine (2 mM) and Na-pyruvate (1 mM) and the cells are replaced at 37 ° C. and 8-10% CO ₂ incubated overnight. The test substances (dissolved in DMSO) were added the next day fresh in DMEM (Gibco, high glucose, without phenol red, with pyridoxine hydrochloride) with penicillin / streptomycin (100 U / ml), glutamax I or L-glutamine (2 mM) and sodium pyruvate ( 1 mM). The cells were then incubated for more than 18 hours with various concentrations of the test substances (volume 75 μl / well). Following this incubation, the activities of the Renilla and Firefly luciferases were determined using Promega's "Dual-Glo ^™ luciferase assay system", which was incubated with "Dual-Glo ^™ luciferase reagent" according to the manufacturer's instructions for 10 min Room temperature lysed and then the activity of firefly luciferase (reporter gene, PPAR-dependent) determined in the plate luminometer. The reaction of the firefly luciferase was stopped by the addition of per 75μl "Dual-Glo ^TM Stop & Glow ^® Reagent" per well and after 10 minutes incubation at room temperature, the activity of Renilla luciferase (control, PPAR-dependent) in the luminometer analyzed ,

The activity of firefly luciferase in one well was normalized by the activity of Renilla luciferase of the same well and the average activation factor (average of at least three measurements per concentration of test substance) compared to the control without test substance was calculated. After semi-logarithmic plots of the relative activation factors (Y-axis) of at least three independent experiments against the concentration of the test substance (X-axis), the EC ₅₀ value was determined by means of a logistic regression (four parameters). The EC ₅₀ value is the concentration at which half maximal PPAR activation is observed. The lower this value, the stronger the binding of the test substance to PPARα. For WY-14643, an EC ₅₀ value of 0.98 μM was found to be good with the the literature value of 0.63 μM (Wilson et al., 2000). In addition to some derivatives, which have a significantly higher EC ₅₀ value, it was also possible to identify derivatives which have a stronger PPAR⧠-activating effect than WY-14643 (see Table 1);

Test for PPARy activity

The Pyrimidine derivatives, like WY-14643, were PPARγ-activating by reporter gene assay Effect examined. Instead of the complete PPAR⧠ was for this Assay a fusion protein consisting of the Gal4 DNA binding domain (Gal4 is a transcription factor from the yeast) as well as the hinge region and the ligand-binding domain (LBD) used by human PPARγ. The assay is based on the fact that the fusion protein after binding a ligand to the LBD activates the transcription of genes that under the control of a "Gal4 Response Elements ". In the assay, this results in a very high subtype specificity, since the activation of endogenous PPARs is not included, as a corresponding PPRE is not present on the reporter plasmid. Rather contains the reporter gene plasmid controls the firefly luciferase gene a promoter that is five times Repeat of the Gal4 Response element and a TATA box. The activity of the luciferase gene is directly related to activation PPAR⧠ LBD and can therefore be used as a measure of the activation of PPARγ. Furthermore, an expression plasmid for the fusion protein and a Control plasmid containing the Renilla luciferase gene under control involves a promoter constitutive of the test conditions, used in the test.

For this assay, Cos-7 cells were also used, which were in Dulbecco's Modified Eagle's Medium (DMEM (Gibco), high glucose, glutamax I) with 10% fetal calf serum and penicillin / streptomycin (100 U / ml) at 37 ° C and 8-10% CO ₂ were cultured to a degree of confluence of 80-90% in 96-well plates The cells were transiently transfected using Lipofectamine ^™ 2000 (Invitrogen) For each well, O, 8 μl of the reagent was co-administered 25μl Optimem I (Gibco) was mixed and incubated for 5 min at room temperature, while for each well the expression plasmid (0.014μg), the control vector (0.002μg) and the reporter gene plasmid (0.28μg) were mixed with 25μl Optimem I each and then After incubation for 20 min at room temperature, the culture medium of the Cos-7 cells was replaced by 5 μl each of this mixture and 1 μl Optimem I. After 4 hours incubation at 37 ° C. and 8-10% CO ₂ , the Transfektionsmis per 100 μl of DMEM (Gibco; High glucose, without phenol red, with pyridoxine hydrochloride) with penicillin / streptomycin (100 U / ml), glutamax I or L-glutamine (2 mM), Na pyruvate (1 mM) and corresponding concentrations of test substance (dissolved in DMSO) and the cells at 37 ° C and 8 - 10% CO ₂ incubated for 18 hours (volume 75μl / well). After incubation, the activities of the Renilla and Firefly luciferases were determined using Promega's "Dual-Glo ^™ luciferase assay system", which was incubated with "Dual-Glo ^™ luciferase reagent" according to the manufacturer's instructions for 10 min Room temperature lysed and then determined the activity of firefly luciferase (reporter gene) in the plate luminometer. The reaction of the firefly luciferase was stopped by addition of 75μl per "Dual-Glo Stop & Glow ^{TM ®} Reagent" per well and after 10 minutes incubation at room temperature, the activity of Renilla luciferase (control) in the luminometer analyzed.

The activity of firefly luciferase in one well was normalized by the activity of Renilla luciferase of the same well and the average activation factor (average of at least three measurements per concentration of test substance) compared to the control without test substance was calculated. After semi-logarithmic plots of the relative activation factors (Y-axis) of at least three independent experiments against the concentration of the test substance (X-axis), the EC ₅₀ value was determined by means of a logistic regression (four parameters). For WY-14643, an EC ₅₀ value of about 60 μM was found, which corresponds to the value known from the literature (Wilson et al., 2000). In addition to some derivatives, which have a significantly higher EC ₅₀ value, it was also possible to identify derivatives which have a stronger PPARγ-activating effect than WY-14643 (see Table 1).

Table 1: Results of PPAR activity tests

Claims (27)

Pyrimidine and triazine derivatives of the general formula (I)

where W is halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, hydrogen, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _3-8 -cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl , C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _{1- 12} alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, NR ¹ R ² , C _6-10 aryl, C _6-10 aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 -aryl-amino, C _6-10 -arylsulfanyl, C _6-10 -arylsulfonyl, C _6-10 -arylsulfoxidyl, C _6-10 -arylcarbonyl, C _6-10 - Arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroaryl carbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 alkoxysulfonyl, C _1-12 alkoxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, with chlorine being preferred, X is N or CR ^a , where CH Y is (A) _m -B- (M) _o -Q, (A) _m -B- (M) _o -L, NR ³ -C (O) -NR ⁴ -Q or NR ³ -C (O) -NR ⁴ -L, A is C _1-3 -alkyl or CO, in particular methylene, B is NR ⁵ , CR ^b R ^c , CO, O or S, preferably NH, M is C _{1-3 is} alkyl or CO, in particular methylene, Q is triply substituted phenyl, where two of the three radicals are selected independently of one another from C _1-3 -alkyl, in particular methyl, ethyl, n-propyl and i-propyl, and the third radical is chlorine, bromine, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl or di- (C _1-6 -alkyl) N, preferably chlorine or bromine, or Q is di-substituted Phenyl, wherein the two substituents, in particular alkyl substituent enten, vicinal and form a 5- or 6-membered optionally heteroatoms selected from N, O or S containing ring, in particular alkyl ring form, L is C _1-12 alkyl or heteroalkyl, Z is DEC (O) - (F) _p -G or DEV, D is O, S, CR ^d R ^e or NR ⁸ , preferably S, E is optionally mono- or polysubstituted, preferably monosubstituted or disubstituted C _1-6 - Alkyl, preferably methylene or ethylene, more preferably methylene, wherein the substituents are independently selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 alkyl, C _3-8 cycloalkyl, C _3-8 -Cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _1-12 alkyl sulfoxide, C _1-12 alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, NR ⁹ R ¹⁰ C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 -arylamino, C _6-10 -arylsulfanyl, C _6-10 -arylsulfonyl, C _6-10 arylsulfoxide, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy, C _6-10 aryloxycarbonyl, C _6-10 arylaminocarbonyl, C _6-10 arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl, thioformyl, hydroxyimino, hydrazono or imino, preferably selected from C _1-12 alkyl, C _3-8 cycloalkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl, C _1-12 alkoxy, C _1-12 alkylsulfanyl, NR ⁹ R ¹⁰ , C _6-10 -aryl, heteroaryl and C _6-10 -aryl-C _1-4 -alkyl, more preferably from C _1-8 -alkyl and C _6-10 -aryl, F for C _1-6 Alkylene, preferably methylene or ethylene, G is NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ , OR ¹¹ , preferably OH, V is tetrazolyl or thiazolidinedionyl, m is 0 or 1, o is 0 or 1, p is 0 or 1, preferably 0, R ^a , R ^b , R ^c , R ^d and R ^e independently of one another are halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, hydrogen, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _3-8 -cycloalkyl-C _{1- 4-} alkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 alkoxy, C _1-12 alkylsulfanyl, C _1-12 alkylsulfonyl, C 1-6 alkyl sulfoxide, C _{1- 12} alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 alkyl) NH, Di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 -aryl-amino, C _{6- 10} -arylsulfanyl, C _6-10 -arylsulfonyl, C _6-10 -arylsulfoxide, C _6-10 -arylcarbonyl, C _6-10 -arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 Arylsulfanylcarbonyl, heteroaryl, HeteroarylC _1-4 alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, preferably hydrogen, halogen, C _1-6 -alkyl or C _6-10 -aryl, more preferably hydrogen, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ^{13 are} independently trifluoromethyl, hydrogen, C _1-12 alkyl, C _3-8 cycloalkyl, C _3-8 cycloalkyl-C _1-4 -alkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 alkylsulfonyl, C _1-12 alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12- alkylaminocarbonyl, C _1-12 -alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 -alkyl) NH, di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 arylC _1-4 alkyl, C _6-10 aryloxy, C _{6-1 0-} arylamino, C _6-10 -arylsulfanyl, C _6-10 -arylsulfonyl, C _6-10 -arylsulfoxidyl, C _6-10 -arylcarbonyl, C _6-10 -arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 -Arylaminocarbonyl, C _6-10 - arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, preferred for hydrogen, C _1-6 - Alkyl or C _6-10 -aryl, particularly preferably hydrogen, where all the radicals of the resulting molecule, in particular the aliphatic and aromatic radicals, Unless otherwise indicated, in each case independently of one another, it is alsopreferably mono- or polysubstituted, in particular mono-, di- or trisubstituted, preferably monosubstituted, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _{1 12-} alkyl, C _3-8 -cycloalkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _1-12 -alkanoyloxy, C _1-12 -alkoxycarbonyl, C _1-12 -alkylaminocarbonyl, C _1-12 -alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 -alkyl) NH, di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxidyl, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy, C _6-10 aryloxycarbonyl, C _6-10 arylaminocarbonyl, C _6-10 arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 alkyl, heteroa ryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl, thioformyl, hydroxyimino, hydrazono or imino, preferably by halogen, C _1-6 -alkyl, C _1-6 -alkoxy or hydroxy, and wherein the total number of these substituents in the molecule is preferably up to five, more preferably up to three, in particular one, two or three, and / or physiologically acceptable salts of these molecules. Pryimidine and triazine derivatives according to claim 1, characterized in that W is halogen, in particular chlorine, bromine or fluorine, hydrogen, C _1-6 -alkyl, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl or di- (C _1-6 -alkyl) N, with chlorine and bromine being preferred and chlorine being particularly preferred, X is N or CR ^a , where CH is preferred, Y is (A) _m -B- (M) _o - Q (A) _m -B- (m) _o -L, NR ³ -C (O) -NR ⁴ -Q _O of the NR ³ -C (O) -NR ⁴ -L, A is methylene or CO, Preferably, methylene, B is NR ⁵ , CR ^b R ^c , CO, O or S, preferably NH, M is methylene or CO, preferably methylene, Q is triply substituted phenyl, wherein two of the three radicals independently are selected from C _1-3 alkyl, in particular methyl, ethyl, n-propyl and i-propyl, and wherein the third radical is chlorine, bromine, C _1-6 alkoxy, C _1-6 alkylsulfanyl or Is di (C _1-6 alkyl) N, preferably chlorine or bromine, Z is DEC (O) - (F) _p -G or DEV, L is C _1-12 alkyl l is heteroalkyl, D is O, S, CR ^d R ^e or NR ⁸ , preferably S, E is optionally mono- or polysubstituted, preferably mono- or di-substituted, C _1-6 -alkyl, preferably methylene or ethylene , particularly preferably methylene, where the substituents are selected independently of one another from C _1-12 -alkyl, C _3-8 -cycloalkyl, heterocycloalkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, C _{1- 12} -alkoxy, C _1-12 -alkylsulfanyl, NR ⁹ R ¹⁰ , C _6-10 -aryl, heteroaryl, C _6-10 -aryl-C _1-4 -alkyl, more preferably from C _1-8 -alkyl, heteroalkyl , C _6-10 -aryl and heteroaryl, especially from C _2-8 -alkyl and C _6-10 -aryl, F is C _1-3 -alkyl, preferably methylene or ethylene, G is NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ¹¹ , preferably OH, V is tetrazolyl or thiazolidinedionyl, m is 0 or 1, o is 0 or 1, p is 0 or 1, preferably 0, R ^a , R ^b , R ^c , R ^d and R ^{e are} independently halogen, esp chlorine, bromine or fluorine, hydrogen, C _1-6 -alkyl, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl, hydroxy, amino, (C _1-6 -alkyl) NH or di- (C _{1- 6-} alkyl) N, preferably chlorine, bromine, hydrogen or C _1-6 -alkyl, particularly preferably hydrogen, R ³ , R ⁴ , R ⁵ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ independently of one another are hydrogen or C _1-6 -alkyl, preferably hydrogen, where all radicals of the resulting molecule, in particular the aliphatic and aromatic radicals, unless otherwise stated, are each independently or multiply, in particular mono-, di- or trisubstituted, preferably monosubstituted, substituents, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, C _1-6 -alkyl, C _2-6 -alkenyl, C _{2- 6-} alkynyl, heteroalkyl, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl, hydroxy, amino, (C _1-6 -alkyl) NH, di- (C _1-6 -alkyl) N, preferably by chlorine, Bromine, C _1-6 alkyl or Hydroxy, and wherein the total number of these substituents in the molecule is preferably up to five, more preferably up to three, especially one, two or three. Pyrimidine and triazine derivatives according to claim 2, characterized in that W is chlorine, X is CH, Y is NH-Q, Z is S (CH ₂ ) C (O) -G, Q is triply substituted Phenyl, wherein two of the three radicals are independently selected from C _1-3 -alkyl, in particular methyl, ethyl, n-propyl or i-propyl, especially methyl, and the third radical is chlorine, bromine, C _1-6 -alkoxy, in particular methoxy, ethoxy or propoxy , C _1-6 alkylsulfanyl, in particular methyl, ethyl or propylsulfanyl, or di (C-alkyl) N, in particular di- (C _1-6 alkyl) N, preferably chlorine or bromine, and wherein the two alkyl radicals are preferably located at positions 2 and 3 and the third radical at position 4 in the ring, G is NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ¹¹ , preferably OH, R ¹¹ , R ¹² and R ¹³ independently of one another represent hydrogen or C _1-6 -alkyl, preferably hydrogen. Pyrimidine and triazine derivatives according to claim 3, characterized in that the compound is [[4-chloro-6 - [(2,3-di- (C _1-3 -alkyl) -4-halo-phenyl) -amino ] -2-pyrimidinyl] thio] acetic acid, in particular [[4-chloro-6 - [(2,3-dimethyl-4-chlorophenyl) amino] -2-pyrimidinyl] thio] acetic acid or [[4-chloro-6 - [(2,3-dimethyl-4-bromophenyl) amino] -2-pyrimidinyl] thio] acetic acid or the corresponding acetamides, acethydrazides or C _1-6 -alkyl esters or physiologically acceptable salts of these compounds. Pyrimidine and triazine derivatives according to claim 1, characterized in that W is halogen, in particular chlorine, bromine or fluorine, hydrogen, C _1-6 -alkyl, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl or di- (C _1-6 alkyl) N, with chlorine and bromine being preferred and chlorine being particularly preferred, X is N or CR ^a , with CH being preferred, Y is (A) mB- (M) oQ, (A ) mB- (M) _o -L, NR ³ -C (O) -NR ⁴ -Q or NR ³ -C (O) -NR ⁴ -L, A is methylene or CO, preferably methylene, B is NR ⁵ , CR ^b R ^c , CO, O or S, preferably NH, M is methylene or CO, preferably methylene, Q is di-alkyl-substituted phenyl, wherein the two substituents are arranged vicinal and a 5- forming 6-membered optionally heteroatoms selected from the group consisting of N, O and S, Z is DEC (O) - (F) _p -G or DEV, L is C _1-12 -alkyl or heteroalkyl, D is O, S, CR ^d R ^e or NR ⁸ , preferably S, E is optionally one or more times substituted, preferably monosubstituted or disubstituted C _1-6 -alkyl, preferably methylene or ethylene, more preferably methylene, where the substituents are independently selected from C _1-12 -alkyl, C _3-8 -cycloalkyl, heterocycloalkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl, C _1-12 alkoxy, C _1-12 alkylsulfanyl, NR ⁹ R ¹⁰ , C _6-10 aryl, heteroaryl, C _6-10 aryl C _1-4 alkyl, more preferably from C _1-8 alkyl, heteroalkyl, C _6-10 aryl and heteroaryl, especially from C _2-8 alkyl and C _6-10 aryl, F for C _{1 3 is} alkyl, preferably methylene or ethylene, G is NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ¹¹ , preferably OH, V is tetrazolyl or thiazolidinedionyl, m is 0 or 1, o is 0 or 1, p is 0 or 1, preferably 0, R ^a , R ^b , R ^c , R ^d and R ^e independently of one another are halogen, in particular chlorine, bromine or fluorine, hydrogen, C _1-6 - Alkyl, C _1-6 alkoxy, C _1-6 alkylsulfanyl, hydroxy, amino, (C _1-6 al kyl) NH or di- (C _1-6 -alkyl) N, preferably chlorine, bromine, hydrogen or C _1-6 -alkyl, particularly preferably hydrogen, R ³ , R ⁴ , R ⁵ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ independently of one another are hydrogen or C _1-6 -alkyl, preferably hydrogen, where all radicals of the resulting molecule, in particular the aliphatic and aromatic radicals, if not in each case independently of one another, if appropriate also mono- or polysubstituted, in particular mono-, di- or trisubstituted, preferably monosubstituted, substituted, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, C _1-6 -alkyl, C ₂ _ ₆ alkenyl, C ₂ _ ₆ alkynyl, heteroalkyl, C _1-6 alkoxy, C _1-6 alkylsulfanyl, hydroxy, amino, (C _1-6 alkyl) NH, di- (C _{1- 6-} alkyl) N, preferably by chlorine, bromine, C _1-6 alkyl or hydroxy, and wherein the total number of these substituents in the molecule preferably up to five, particularly preferably up to three, in particular one, two or three. Pyrimidine and triazine derivatives according to claim 5, characterized in that W is chlorine, X is CH, Y is NH-Q, Z is S (CH ₂ ) C (O) -G, Q is di-substituted Phenyl, wherein the two-fold substitution by an alkylene bridge, preferably propylene bridge, preferably in the 2,3-position takes place, G is NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ¹¹ , preferably OH . R ¹¹ , R ¹² and R ¹³ independently of one another represent hydrogen or C _1-6 -alkyl, preferably hydrogen. Pyrimidine and triazine derivatives according to claim 6, characterized in that the compound is [4-chloro-6- (indan-4-ylamino) -pyrimidin-2-ylsulfanyl] -acetic acid, the corresponding acetamides, acethydrazides or C _1-6 alkyl esters or physiologically acceptable salts of these compounds. Pyrimidine and triazine derivatives of the general formula (I)

where W is halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, hydrogen, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _3-8 -cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl , C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _{1- 12} - alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, NR ¹ R ² , C _6-10 aryl, C _6-10 aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 -aryl-amino, C _6-10 -arylsulfanyl, C _6-10 -arylsulfonyl, C _6-10 -arylsulfoxidyl, C _6-10 -arylcarbonyl, C _6-10 - Arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, Heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _{1 -12-} alkoxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, with chlorine being preferred, X is N or CR ^a , where CH is preferred, Y is (A) mB- (M) _o -Q, (A ) _m -B- (M) _o -L, NR ³ -C (O) -NR ⁴ -Q or NR ³ -C (O) -NR ⁴ -L, A is C _1-3 alkyl or CO, in particular methylene, B is NR ⁵ , CR ^b R ^c , CO, O or S, preferably NH, M is C _1-3 -alkyl or CO, in particular methylene, Q is optionally mono- or polysubstituted , in particular 2-, 3-, 4- or 5-substituted, preferably di- or trisubstituted, C _6-10 -aryl or heteroaryl, more preferably phenyl, wherein heteroaryl is selected from O, S and N as at least one heteroatom containing aromatic radical having 5 to 9, preferably 5 or 6, ring members and the substituents are preferably selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _{3- 8} -cycloalkyl-C _1-4 -alkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 alkoxy, C _1-12 alkylsulfanyl, C _1-12 alkylsulfonyl, C _1-12 alkyl sulfoxide, C _1-12 alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, NR ⁶ R ⁷ , C _6-10 aryl C _6-10 arylC _1-4 alkyl, C _6-10 aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxide, C _6-10 -arylcarbonyl, C _6-10 -arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, Heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, where at least two vicinally arranged substituents, esp special alkyl substituents, even to form a 5- or 6-membered optionally heteroatoms selected from N, O or S containing ring, in particular alkyl ring, may be linked together, L is C _1-12 alkyl or heteroalkyl, Z is is S (CR ^x R ^y ) C (O) -G, where either R ^{x is} H and R ^{y is} C _1-10 alkyl, in particular methyl, ethyl, propyl, in particular n-propyl or i-propyl, Butyl, in particular n-butyl, isobutyl or t-butyl, pentyl, in particular n-pentyl or 2-pentyl, hexyl, in particular n-hexyl, 2-hexyl or 3-hexyl, heptyl, in particular n-heptyl, 2- Heptyl or 3-heptyl, or octyl, especially n-octyl, 2-octyl, 3-octyl or 4-octyl, C _1-10 alkenyl, especially ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl or octenyl, C _{1 -10-} alkynyl, in particular ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl or octynyl, C _3-8 -cycloalkyl, in particular cyclopentyl or cyclohexyl, heteroalkyl, heterocycloalkyl, C _6-14 -aryl , in particular phenyl or naphthyl, C _6-14 heteroaryl, preferably ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl or phenyl, or R ^x and R ^y are each independently C _1-10- alkyl, in particular methyl, ethyl, propyl, in particular n-propyl or i-propyl, butyl, in particular n-butyl, i-butyl or t-butyl, pentyl, in particular n-pentyl or 2-pentyl, hexyl, in particular n-hexyl, 2-hexyl or 3-hexyl, heptyl, in particular n-heptyl, 2-heptyl or 3-heptyl, or octyl, in particular n-octyl, 2-octyl, 3-octyl or 4-octyl, C _1-10 alkenyl, in particular ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl or octenyl, C _1-10 alkynyl, in particular Ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl or octynyl, C _3-8 -cycloalkyl, especially cyclopentyl or cyclohexyl, heteroalkyl, heterocycloalkyl, C _6-14 -aryl, especially phenyl or naphthyl, C _6-14 -heteroaryl is methyl, ethyl, n-propyl or n-butyl, G is NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ , OR ¹¹ , preferably OH, W is tetrazolyl or thiazolidinedionyl, m is 0 or 1 , o is 0 or 1, R ^a , R ^b , R ^c , R ^d and R ^e independently of one another are halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, hydrogen, C _1-12 -alkyl, C _3-8 - Cycloalkyl, C _3-8 -cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl, C _1-12 Alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 alkyl) NH, di- (C _1-12- alkyl) N, C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 -arylamino, C _6-10 -arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxidyl, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy, C _6-10 aryloxycarbonyl, C _6-10 arylaminocarbonyl, C _6-10 arylsulfanylcarbonyl, heteroaryl , HeteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, Formyl or thioformyl, preferably hydrogen, halogen, C _1-6 -alkyl or C _6-10 -aryl, more preferably hydrogen, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ^7, R ^8, R ^9, R ^10, R ^11, R ¹² and R ¹³ are independently separately of each other is trifluoromethyl, hydrogen, C _1-12 alkyl, C _3-8 cycloalkyl, C _3-8 cycloalkyl-C _1-4 alkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl , C _1-12 -alkylsulfonyl, C _1-12 -alkanoyl, C _1-12 -alkanoyloxy, C _1-12 -alkoxycarbonyl, C _1-12 -alkylaminocarbonyl, C _1-12 -alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino , (C _1-12 -alkyl) NH, di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxidyl, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy, C _6-10 aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, preferred for hydrogen, C _1-6- alkyl or C _6-10 -aryl, more preferably hydrogen f, wherein all the radicals of the resulting molecule, in particular the aliphatic and aromatic radicals, unless otherwise stated, in each case independently of one another may optionally also be mono- or polysubstituted, in particular mono-, di- or trisubstituted, preferably monosubstituted , in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _1-12 -alkanoyloxy, C _1-12 -alkoxycarbonyl, C _{1 -12-} alkylaminocarbonyl, C _1-12 -alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 -alkyl) NH, di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 arylC _1-4 alkyl, C _6-10 aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 aryl sulfoxide, C _{6 -10-} arylcarbonyl, C _6-10 -arylcarbonyloxy, C _6-10 -A ryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _{1 12} -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl, thioformyl, hydroxyimino, hydrazono or imino, preferably by halogen, C _1-6 alkyl, C _1-6 alkoxy or hydroxy, and wherein the Total number of these substituents in the molecule preferably up to five, more preferably up to three, especially one, two or three, and / or physiologically acceptable salts of these molecules. Pyrimidine and triazine derivatives according to claim 8, characterized in that W is halogen, in particular chlorine, bromine or fluorine, hydrogen, C _1-6 -alkyl, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl or di- (C _1-6 -alkyl) N, with chlorine and bromine being preferred and chlorine being particularly preferred, X is N or CR ^a , where CH is preferred, Y is (A) _m -B- (M) _o - Q (A) _m -B- (m) _o -L, NR ³ -C (O) -NR ⁴ -Q _O of the NR ³ -C (O) -NR ⁴ -L, A is methylene or CO, preferably methylene, B is NR ⁵ , CR ^b R ^c , CO, O or S, preferably NH, M is methylene or CO, preferably methylene, Q is optionally mono- or polysubstituted, in particular double, tri-, tetra- or pentasubstituted, preferably two or three times substituted, C _6-10 aryl or heteroaryl, more preferably phenyl, wherein heteroaryl is a at least one heteroatom selected from O, S and N-containing aromatic radical having 5 to 9, preferably 5 or 6, Ringg the substituents are preferably selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 -alkyl, C _3-8 -cycloalkyl, heterocycloalkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, Heteroalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl, hydroxy, carboxy, NR ⁶ R ⁷ , C _6-10 -aryl, heteroaryl or C _6-10 -aryl-C _1-4 -alkyl, wherein at least two vicinally arranged substituents, in particular alkyl substituents, also to form a 5- or 6-membered optionally heteroatoms selected from N, O or S containing ring, in particular alkyl ring, may be linked together, Z is S (CR ^x R ^y ) C (O) -G, L is C _1-12 alkyl or heteroalkyl , G is NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ¹¹ , preferably OH, m is 0 or 1, o is 0 or 1, R ^a , R ^b and R ^c are each independently halogen , in particular chlorine, bromine or fluorine, hydrogen, C _1-6 -alkyl, C _1-6 -alkoxy, C _1-6 -alkylsulfanyl, hydroxy, amino, (C _1-6 -alkyl) NH or di- (C _{1 -6-} alkyl) N, preferably chlorine, bromine, hydrogen or C _1-6 -alkyl, more preferably hydrogen, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ¹¹ , R ¹² and R ¹³ independently of one another represent hydrogen or C _1-6 -alkyl, preferably hydrogen R ^{x is} H and R ^{y is} C _1-10 alkyl, in particular methyl, ethyl, propyl, in particular n-propyl or i-propyl, butyl, in particular n-butyl, i-butyl or t-butyl, pentyl , in particular n-pentyl or 2-pentyl, hexyl, in particular n-hexyl, 2-hexyl or 3-hexyl, heptyl, in particular n-heptyl, 2-heptyl or 3-heptyl, octyl, in particular n-octyl, 2-octyl , 3-octyl or 4-octyl, nonyl, in particular n-nonyl, or decyl, in particular n-decyl, C _1-10 -alkenyl, in particular ethenyl, propenyl, in particular n-propenyl, butenyl, in particular n-butenyl, pentenyl, in particular n-pentenyl, hexenyl, in particular n-hexenyl, heptenyl, in particular n-heptenyl, octenyl, in particular n-octenyl, nonenyl, in particular n-nonenyl, or decenyl, in particular n-decenyl, C _1-10 -alkynyl, in particular ethynyl , Propinyl, especially n-propynyl, butynyl, in particular n-butynyl, pentynyl, in particular n-pentynyl, hexynyl, in particular n-hexynyl, heptynyl, in particular n-heptynyl, octynyl, in particular n-octyl l, nonynyl, in particular n-nonynyl or decynyl, in particular n-decynyl, C _5-6 -cycloalkyl, in particular cyclopentyl or cyclohexyl, heteroalkyl, heterocycloalkyl, C _6-10 -aryl, in particular phenyl or naphthyl, heteroaryl, preferably for ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl or phenyl, or R ^x and R ^y independently of one another are C _1-10 -alkyl, in particular methyl, ethyl, propyl, in particular n-propyl or i-propyl, butyl, in particular n-butyl, i-butyl or t-butyl, pentyl, in particular n-pentyl or 2-pentyl, hexyl, in particular n-hexyl, 2-hexyl or 3-hexyl, heptyl, in particular n Heptyl, 2-heptyl or 3-heptyl, or octyl, especially n-octyl, 2-octyl, 3-octyl or 4-octyl, C _1-10 alkenyl, especially ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl or octenyl, C _1-10 alkynyl, in particular ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl or octynyl, C _3-8 -cycloalkyl, in particular cyclopentyl or cyclohexyl, heteroalkyl, heterocyclo alkyl, C _6-10 -aryl, in particular phenyl or naphthyl, or heteroaryl, preferably methyl, ethyl, n-propyl or n-butyl, where all radicals of the resulting molecule, in particular the aliphatic and aromatic radicals, if not in each case independently of one another, if appropriate also mono- or polysubstituted, in particular mono-, di- or trisubstituted, preferably monosubstituted, substituted, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, C _1-6 -alkyl, C ₂ _ ₆ alkenyl, C _2-6 alkynyl, heteroalkyl, C _1-6 alkoxy, C _1-6 alkylsulfanyl, hydroxy, amino, (C _1-6 alkyl) NH, di- (C _{1- 6-} alkyl) N, preferably by chlorine, bromine, C _1-6 alkyl or hydroxy, and wherein the total number of these substituents in the molecule is preferably up to five, more preferably up to three, in particular one, two or three. Pyrimidine and triazine derivatives according to claim 9, characterized in that W is chlorine, X is CH, Y is NH-Q, Z is S (CR ^x R ^y ) C (O) -G, Q is 2,3-dimethylphenyl, 2,3-dimethyl-4-chlorophenyl or 2,3-dimethyl-4-bromophenyl, R ^{x is} H and R ^{y is} C _1-10 -alkyl, in particular methyl, ethyl, propyl, in particular n Propyl or i-propyl, butyl, in particular n-butyl, i-butyl or t-butyl, pentyl, in particular n-pentyl or 2-pentyl, hexyl, in particular n-hexyl, 2-hexyl or 3-hexyl, heptyl, in particular n-heptyl, 2-heptyl or 3-heptyl, octyl, in particular n-octyl, 2-octyl, 3-octyl or 4-octyl, nonyl, in particular n-nonyl, or decyl, in particular n-decyl, C _{1 10} alkenyl, in particular ethenyl, propenyl, in particular n-propenyl, butenyl, in particular n-butenyl, pentenyl, in particular n-pentenyl, hexenyl, in particular n-hexenyl, heptenyl, in particular n-neptenyl, octenyl, in particular n-octenyl, nonenyl , in particular n-nonenyl, or decenyl, in particular n-dece nyl, C _1-10 alkynyl, in particular ethynyl, propynyl, in particular n-propynyl, butynyl, in particular n-butynyl, pentynyl, in particular n-pentynyl, hexynyl, in particular n-hexynyl, heptynyl, in particular n-heptynyl, octynyl, especially n-octynyl, nonynyl, in particular n-nonynyl or decynyl, in particular n-decynyl, C _3-8 -cycloalkyl, in particular cyclopentyl or cyclohexyl, heteroalkyl, heterocycloalkyl, C _6-10 -aryl, in particular phenyl or naphthyl, or heteroaryl, are preferred for ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl or Phe nyl or R ^x and R ^y independently of one another are C _1-6 -alkyl, preferably methyl, ethyl, propyl, in particular n-propyl or isopropyl, butyl, in particular n-butyl, isobutyl or t-butyl, pentyl , in particular n-pentyl, or hexyl, in particular n-hexyl, or phenyl, G is NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ or OR ¹¹ , preferably OH, R ¹¹ , R ¹² and R ^{13 are} independent each other is hydrogen or C _1-6 alkyl, preferably hydrogen. Pyrimidine and triazine derivatives according to claim 10, characterized in that the compound is 2- (4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -propanoic acid, 2- [4-Chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -butanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl ] -pentanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -phenyl-acetic acid, [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -naphtalen-1-yl-acetic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-propanoic acid, 2- [4-Chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-butanoic acid, 4-chloro [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethylbutanoic acid, 2- [4-chloro-6- (2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-methylpentanoic acid, 2- [4 Chloro-6- (2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-pentanoic acid, 2- [4-chloro-6- (2,3-dimethyl-phenylamino) -pyrimi din-2-ylsulfanyl] -2-propyl-pentanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -propanoic acid, 2- [4- Chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -butanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) - pyrimidin-2-ylsulfanyl] -pentanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -phenyl-acetic acid, [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -naphtalen-1-yl-acetic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino ) -pyrimidin-2-ylsulfanyl] -2-methylpropanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-methylbutanoic acid , 4-Chloro 2- [4-chloro-6- (4-chloro-2,3-dimethylphenylamino) -pyrimidin-2-ylsulfanyl] -2-ethyl-butanoic acid, 2- [4-chloro-6- (4 -chloro-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-pentanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl-phenylamino) -pyrimidine 2-ylsulfanyl] -2-ethyl-pentanoic acid, 2- [4-chloro-6- (4-chloro-2,3-dimethyl -phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-pentanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -propanoic acid, 2 - [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -butanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl -phenylamino) -pyrimidin-2-ylsulfanyl] -pentanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -phenyl-acetic acid, [4 Chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -naphthalen-1-yl-acetic acid, 2- [4-chloro-6- (4-bromo-2,3 -dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-propanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2 methyl butanoic acid, 4-chloro-2- (4-chloro-6- (4-bromo-2,3-dimethylphenylamino) pyrimidin-2-ylsulfanyl] -2-ethylbutanoic acid, 2- [4-chloro 6- (4-bromo-2,3-dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-methyl-pentanoic acid, 2- [4-chloro-6- (4-bromo-2,3-dimethyl-phenylamino ) -pyrimidin-2-ylsulfanyl] -2-ethyl-pentanoic acid, 2- [4-chloro-6- (4-bromo-2,3 -dimethyl-phenylamino) -pyrimidin-2-ylsulfanyl] -2-propyl-pentanoic acid or corresponding acetamides, acethydrazides or C _1-6 -alkyl esters or physiologically acceptable salts of these compounds. Pyrimidine and triazine derivatives according to one of claims 1 to 11, characterized in that the physiologically acceptable Salts selected are from alkali metal salts, alkaline earth metal salts and ammonium salts primary, secondary, tertiary or quaternary Ammonium compounds. Pharmaceutical or cosmetic composition, containing at least one compound according to claims 1 to 12. Pharmaceutical or cosmetic composition according to claim 13, characterized in that it comprises at least one selected further active ingredient from the group consisting of psoralen, tar, steroids, vitamins or derivatives thereof, anthralin, fumaric acid, salicylic acid, hydrotropes, oil-containing Products, wine vinegar, salt from the Dead Sea, aloe vera, jojoba, zinc pyrithione and capsaicin. Pharmaceutical or cosmetic composition according to claim 13, characterized in that it comprises at least one selected further active ingredient from the group consisting of cyclosporin, methotrexate, retinoids or of active ingredients of biological origin (so-called "biologics") such as Alefacept, Efalizumab, etanercept or infliximab or drugs such as Accutane, hydroxyurea, mycophenolate mofetil, sulfasalazine and 6-thioguanine. Pharmaceutical or cosmetic composition according to claim 13, characterized in that it comprises at least one selected further active ingredient from the group consisting of non-steroidal anti-inflammatory drugs, in particular from the group of calcineurin inhibitors. Pharmaceutical or cosmetic composition according to one of the claims 13 to 16, characterized in that they at least one further Component selected from the group consisting of fats, oils, superfatting agents, waxes, Silicones, emulsifiers, dispersants, pearlescent waxes, alcohols, Polyols, bodying agents, stabilizers, thickeners, swelling agents, Hydrotropes or moisturizing and / or moisturizing substances, Polymers, surfactants, plasticizers, foam brakes, alkalization or Acidifiers, softeners, Adsorbents, light stabilizers, electrolytes, sequestering agents, organic solvents, Preservatives, germ-inhibiting agents, especially fungicides or bactericides, plant extracts, antioxidants, biogenic agents, Vitamins, protein hydrolysates, mono-, oligo- and polysaccharides, Enzyme inhibitors, in particular MMP1-inhibiting substances, deodorants or odor absorbers, antiperspirants, antidandruff agents, α-hydroxy and α-ketocarboxylic acids, fragrances, Contains dyes and pigments. Pharmaceutical or cosmetic composition according to one of the claims 13 to 17, characterized in that it is a means for topical application is. Use of pyrimidine and triazine derivatives according to one of the claims 1 to 12 for the preparation of a pharmaceutical or cosmetic Composition for the treatment of diseases or disease states. Use according to claim 18, characterized that the diseases and conditions are selected from type I diabetes and type I, hyperinsulinemia, insulin resistance, obesity, obesity, hyperlipidemia, dyslipidemia, cardiovascular Diseases, especially arteriosclerosis and hypertension, diseases and disease states, which are due to a dysregulation of the immune system, especially autoimmune diseases and rejection reactions as a result of organ or tissue transplantation, gastrointestinal Diseases, especially intestinal inflammation, other inflammatory Diseases, such as Alzheimer's disease, Crohn's disease, multiple Sclerosis, rheumatoid arthritis, syndrome X or the so-called ischemia reprofusion injury, and diseases that indicate a disturbed barrier function Skin are due, as well as cancer, thrombosis, stroke and heart attack. Use according to claim 19 or 20, characterized that the diseases and conditions are selected from skin diseases and disease states skin, in particular from pathological changes in the fluid and electrolyte balance, low temperature, skin infections; Inflammation of mucous membranes, such as cheilitis, rhinitis and vulvovaginitis; Eczema, how Atopic and seborrhea Dermatitis, allergic eczema, contact dermatitis, xerotic eczema, photoallergic and phototoxic dermatitis, phytophotodermatitis, Radiation dermatitis, stasis dermatitis; Ulcers and erosions resulting from injuries, burns, bullous (blistering) Diseases or ischemia the skin or mucous membrane; Ichthyoses (keratinization disorders of Skin); Epidermolysis bullosae; Psoriasis; hypertrophic scars and keloids; changes the skin through intrinsic aging and photoaging; skin blisters due to mechanical friction; Skin atrophy (dilution) by topical use of corticosteroids, vitiligo and alopecia areata. Use of pyrimidine and triazine derivatives of the general formula (I)

where W is halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, hydrogen, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _3-8 -cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl , C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _{1- 12} alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, NR ¹ R ² , C _6-10 aryl, C _6-10 aryl-C _1-4 alkyl, C _6-10 aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxidyl, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy, C _6-10 aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl , C _1-12 alkoxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, with chlorine being preferred, X is N or CR ^a , where CH is preferred, Y is (A) _m -B- (M) _o -Q, (A) _m -B- (m) _o -L, NR ³ -C (O) -NR ⁴ -Q _O of the NR ³ -C (O) -NR ⁴ -L, A is C _{1- 3} -alkyl or CO, in particular methylene, B is NR ⁵ , CR ^b R ^c , CO, O or S, preferably NH, M is C _1-3 alkyl or CO, in particular methylene, Q is optionally mono- or polysubstituted, in particular, two, dre i-, four- or five-membered, preferably di- or trisubstituted, C _6-10 -aryl or heteroaryl, more preferably phenyl, where heteroaryl is an aromatic radical containing at least one heteroatom selected from O, S and N with 5 to 9, preferably 5 or 6, ring members and the substituents are preferably selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _3-8 -cycloalkyl-C _1-4 alkyl, C _2-12 alkenyl, C _2-1 alkynyl _2, heteroalkyl, heterocycloalkyl, C _1-12 alkoxy, C _1-12 alkylsulfanyl, C _1-12 alkylsulfonyl, C _1-12 Alkylsulfoxidyl, C _1-12 alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, NR ⁶ R ⁷ , C _{6 -10-} aryl, C _6-10 -aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 -aryl-amino, C _6-10 -arylsulfanyl, C _6-10 -arylsulfonyl, C _{6- 10} -arylsulfoxide, C _6-10 -arylcarbonyl, C _6-10 -arylcarbon yloxy, C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, Heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, wherein at least two vicinally arranged substituents, in particular alkyl substituents, also to form a 5- or 6-membered optionally heteroatoms selected from N, O or S containing ring, in particular alkyl ring, may be linked together, L is C _1-12 alkyl or heteroalkyl, Z is DEC (O) - (F) _p -G or DEV , D is O, S, CR ^d R ^e or NR ⁸ , preferably S, E is optionally mono- or polysubstituted, preferably mono- or di-substituted, C _1-6 -alkyl, preferably methylene or ethylene , particularly preferably methylene, where the substituents are independently selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _3-8 -cycloalkyl-C _{1- 4-} alkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 alkoxy, C _1-12 alkylsulfanyl, C _1-12 alkylsulfonyl, C _1-12 alkyl sulfoxide, C _1-12 alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12 alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, NR ⁹ R ¹⁰ , C _6-10 -Aryl, C _6-10 arylC _1-4 alkyl, C _6-10 aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 - Arylsulfoxidyl, C _6-10 -arylcarbonyl, C _6-10 -arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, Heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, hetero aryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl, thioformyl, hydroxyimino, hydrazono or imino, preferably from C _1-12 -alkyl, C _3-8 - Cycloalkyl, C _2-12 alkenyl, C _2-12 alkynyl, heteroalkyl, C _1-12 alkoxy, C _1-12 alkylsulfanyl, NR ⁹ R ¹⁰ , C _6-10 aryl, heteroaryl and C _6-10 -Aryl-C _1-4 -alkyl, more preferably from C _1-8 -alkyl and C _6-10 -aryl, F is C _1-6 -alkylene, preferably methylene or ethylene, G is NR ¹¹ R ¹² , NR ¹¹ -NR ¹² R ¹³ , OR ¹¹ , preferably OH, V is tetrazolyl or thiazolidinedionyl, m is 0 or 1, o is 0 or 1, p is 0 or 1, preferably 0, R ^a , R ^b , R ^c , R ^d and R ^e are each independently halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, hydrogen, C _1-12 -alkyl, C _3-8 -cycloalkyl, C _3-8 -cycloalkyl-C _1-4 -alkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkoxy, C _1-12 alkylsulfanyl, C _1-12 alkylsulfonyl, C _1-12 alkyl sulfoxide, C _1-12 alkanoyl, C _1-12 alkanoyloxy, C _1-12 alkoxycarbonyl, C _1-12 alkylaminocarbonyl, C _1-12- alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 -alkyl) NH, di (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 -aryl C _1-4 alkyl, C _6-10 aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxide, C _6-10 arylcarbonyl, C _6-10 arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, Heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl or thioformyl, preferably hydrogen, halogen, C _1-6 alkyl or C _6-10 aryl, more preferably hydrogen, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ^{13 are} independently trifluoromethyl, hydrogen, C _1-12 alkyl, C _3-8 cycloalkyl, C _3-8 cycloalkyl-C _1-4 alkyl, C _2-12 alkenyl , C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkylsulfonyl, C _1-12 -alkanoyl, C _1-12 -alkanoyloxy, C _1-12 -alkoxycarbonyl, C _1-12 -alkylaminocarbonyl, C _{1- 12-} alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, (C _1-12 -alkyl) NH, di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _6-10 -aryl-C _{1 4-} alkyl, C _6-10 aryloxy, C _6-10 arylamino, C _6-10 arylsulfanyl, C _6-10 arylsulfonyl, C _6-10 arylsulfoxidyl, C _6-10 arylcarbonyl, C _{6- 10} -arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl, heteroarylsulfoxidyl, heteroarylcarbonyl, heteroaryl carbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, preferably hydrogen, C _1-6 -alkyl or C _6-10 -aryl, particularly preferably hydrogen, where all radicals of the resulting molecule, in particular the aliphatic and aromatic radicals, if not stated otherwise, in each case independently of one another, if appropriate also mono- or polysubstituted, in particular mono-, di- or trisubstituted, preferably monosubstituted, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C _1-12 -Alkyl, C _3-8 -cycloalkyl, C _2-12 -alkenyl, C _2-12 -alkynyl, heteroalkyl, heterocycloalkyl, C _1-12 -alkoxy, C _1-12 -alkylsulfanyl, C _1-12 -alkylsulfonyl, C _1-12 -alkylsulfoxidyl, C _1-12 -alkanoyl, C _1-12 -alkanoyloxy, C _1-12 -alkoxycarbonyl, C _1-12 -alkylaminocarbonyl, C _1-12 -alkylsulfanylcarbonyl, hydroxy, carboxy, cyano, amino, ( C _1-12 -alkyl) NH, di- (C _1-12 -alkyl) N, C _6-10 -aryl, C _{6 -10-} aryl-C _1-4 -alkyl, C _6-10 -aryloxy, C _6-10 -arylamino, C _6-10 -arylsulfanyl, C _6-10 -arylsulfonyl, C _6-10 -arylsulfoxidyl, C _{6- 10} -arylcarbonyl, C _6-10 -arylcarbonyloxy, C _6-10 -aryloxycarbonyl, C _6-10 -arylaminocarbonyl, C _6-10 -arylsulfanylcarbonyl, heteroaryl, heteroarylC _1-4 -alkyl, heteroaryloxy, heteroarylamino, heteroarylsulfanyl, heteroarylsulfonyl , Heteroarylsulfoxidyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylsulfanylcarbonyl, C _1-12 -alkoxysulfonyl, C _1-12 -alkoxycarbinol, sulfo, sulfino, sulfeno, formyl, thioformyl, hydroxyimino, hydrazono or imino, preferably by halogen, C _{1 6-} alkyl, C _1-6 -alkoxy or hydroxy, and wherein the total number of these substituents in the molecule is preferably up to five, more preferably up to three, especially one, two or three, and / or physiologically acceptable salts of these molecules , with the exception of pirinixic acid, for the manufacture of a pharmaceutical hen or cosmetic composition for the treatment of inflammatory dermatoses, in particular psoriasis or atopic dermatitis. Use according to one of claims 19 to 22, characterized that the composition is selected from other active ingredients the group consisting of psoralen, tar, steroids, vitamins or derivatives of which, anthralin, fumaric acid, Salicylic acid, oleic acid, linoleic acid, hydrotrope, oil-containing Products, wine vinegar, salt from the Dead Sea, aloe vera, jojoba, zinc pyrithione and capsaicin. Use according to one of claims 19 to 22, characterized that the composition selected from at least one other active ingredient the group consisting of cyclosporin, methotrexate, retinoids or of active ingredients of biological origin (so-called "biologics") such as alefacept, efalizumab, etanercept or infliximab or of active substances such as Accutane, hydroxyurea, Mycophenolate contains mofetil, sulfasalazine and 6-thioguanine. Use according to one of claims 19 to 22, characterized that the composition selected from at least one other active ingredient the group consisting of non-steroidal anti-inflammatory drugs, in particular from the group of calcineurin inhibitors. Use according to one of claims 19 to 22, characterized that the composition is selected from at least one other ingredient the group consisting of fats, oils, superfatting agents, waxes, Silicones, emulsifiers, dispersants, pearlescent waxes, alcohols, Polyols, bodying agents, stabilizers, thickeners, swelling agents, Hydrotropes or moisturizing and / or moisturizing substances, Polymers, surfactants, plasticizers, foam brakes, alkalinization or acidifiers, softeners, Adsorbents, light stabilizers, electrolytes, sequestering agents, organic solvents, Preservatives, germ-inhibiting agents, especially fungicides or bactericides, plant extracts, antioxidants, biogenic agents, Vitamins, protein hydrolysates, mono-, oligo- and polysaccharides, Enzyme inhibitors, in particular MMP1-inhibiting substances, deodorants or odor absorbers, antiperspirants, antidandruff agents, α-hydroxy and α-ketocarboxylic acids, fragrances, Contains dyes and pigments. Use according to one of claims 19 to 26, characterized in that it is in the Zu composition is a means of topical application.