MXPA97004263A - Derivatives of imidazol as inhibitors of laprotein kinase, in particular the tyrosin kinase of eg - Google Patents

Abstract

The present invention relates to a compound of the formula: characterized in that R1 means alkyl of 1 to 6 carbon atoms or halogen, R2 means hydrogen, hydroxyl, nitro, alkoxycarbonyl of 1 to 6 carbon atoms, di (alkyl of 1 to 6 atoms of carbon) -amino- (alkyl of 1 to 6 carbon atoms), morpholino- (alkyl of 1 to 6 carbon atoms) or 4-metipiperazinyl- (alkyl of 1 to 6 carbon atoms), R3 means hydrogen or alkyl of 1 to 6 atoms of carbon, R5 means amino or alkyl of 1 to 6 carbon atoms, R7 means hydrogen or alkyl of 1 to 6 carbon atoms and R8 means hydrogen or halogen, or a pharmaceutically acceptable salt of the same

Description

DERIVATIVES OF IMIDAZOL AS INHIBITORS OF PROTEIN KINASE, IN PARTICULAR THE TYROSIN KINASE OF EGF-R The invention relates to novel imidazole derivatives of the general formula: wherein R <R8> each independently means hydrogen, lower alkyl, substituted lower alkyl, lower alkenyl, lower alkoxy, substituted lower alkoxy, lower alkoxycarbonyl, halogen, hydroxy, amino, mono- or di (lower alkyl) to or nitro, and pharmaceutically acceptable salts thereof. The term "lower alkyl" used herein, alone or in combination, means a straight or branched chain alkyl group with 1-6 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl and n-hexyl. The terms "substituted lower alkyl" and "alkoxy" REF: 24885"substituted lower" means lower alkyl and, respectively, lower alkoxy groups which are substituted, for example, by lower alkoxy, lower acyloxy, azido, cyano, amino, di (lower alkyl) amino, heterocyclyl, hydroxy, or halogen. The term "halogen" or "halo" includes fluorine, chlorine, bromine and iodine Heterocyclyl means a saturated 5- or 6-membered N-heterocycle optionally containing an additional nitrogen atom or an oxygen atom, for example morpholino, piperazino, piperidino or pyrrolidino and which may be substituted by lower alkyl, substituted lower alkyl or lower alkoxycarbonyl, such as 2, β-dimethylmorpholino, N4-substituted piperazino, substituted C4-piperidino or substituted C2-pyrrolidino Preferred compounds of Formula I are those in which R1 means lower alkyl, lower haloalkyl or halogen, especially lower alkyl or halogen, R2 means hydrogen, lower alkyl, lower alkyl substituted, lower alkoxy, lower alkoxy substituted lower alkoxycarbonyl, halogen, hydroxy, amino or nitro, especially hydrogen, hydroxy, nitro, lower alkoxycarbonyl, di- (lower alkyl) amino-lower alkyl, morpholino-lower alkyl or 4-methylpiperazinyl-alkyl lower, R3 signifies hydrogen, lower alkyl, substituted lower alkoxy or hydroxy, especially hydrogen or lower alkyl, R4 signifies hydrogen, lower alkyl or nitro, especially hydrogen, R5 signifies lower alkyl, lower alkoxyalkyl, lower haloalkyl, allyl, amino, di ( lower alkyl) amino, halogen or nitro especially amino or lower alkyl, R6 signifies hydrogen, substituted alkyl or halogen, especially hydrogen, R7 signifies hydrogen, lower alkyl, lower alkoxy, hydroxy or halogen, especially hydrogen or lower alkyl and R8 signifies hydrogen or halogen Methyl and isopropyl are preferred lower alkyl groups. Chlorine is a preferred halogen. Examples of preferred compounds of Formula I are: 4- [5- (4-chlorophenyl) -2- (2,4,6-trimethylphenyl) imidazol-4-yl] pyridine, 4- [5- (3-methylphenyl) - 2- (2,4,6-Trimethylphenyl) imidazol-4-yl] pyridine, 3-chloro-2- [4- (4-chlorophenyl) -5-pyridin-4-yl-imidazol-2-yl] phenylamine, 4- [5- (4-chlorophenyl) -2- (2,6-diisopropylphenyl) imidazol-4-yl] pyridine 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] Methyl-2, 4,6-trimethylbenzoate, 4- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,, 6-trimethylbenzyl] morpholine, [ 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzyl] dimethylamine, 1- [3- [5- (4-chlorophenyl) - 4-pyridin-4-yl-imidazol-2-yl] -2,, 6-trimethylbenzyl] -4-methylpiperazine, 4- [5- (4-chlorophenyl) -2- (2,4,6-trimethyl-3-nitrophenyl) -imidazol-4-yl] pyridine and 3- [5- (4-chlorophenyl) -4-pyridine- 4-yl-imidazol-2-yl] -2,4,6-trimethylphenol.

Compounds of Formula I containing acidic functions can form pharmaceutically acceptable salts with bases such as alkali metal hydroxides (e.g. sodium hydroxide and potassium hydroxide), alkaline earth metal hydroxides (for example calcium hydroxide and magnesium hydroxide) and ammonium hydroxide and the like. Compounds of Formula I that contain basic functions can form pharmaceutically acceptable salts with acids. Such salts include not only salts with inorganic acids such as hydrochloric acid or hydrobromic acid, sulfuric acid, nitric acid and phosphoric acid, but also salts with organic acids such as acetic acid, tartaric acid, succinic acid, fumaric acid, maleic acid, malic acid, salicylic acid, citric acid, methanesulfonic acid, p-toluene- sulphonic, etc. The present invention therefore relates to compounds of Formula I and their pharmaceutically acceptable salts per se and for use as substances, therapeutically active, a process for the preparation of these compounds and their salts, medicaments containing these compounds or salts and the production of these drugs and the use of the compounds and their salts for the control of diseases, especially hyperproliferative disorders such as arteriosclerosis, psoriasis and tumors and for the treatment of alopecia, or for the production of a medicament for the treatment and prevention of such disorders. The pharmacological activity of the compounds according to the invention can be determined on the basis of their activity as protein kinase inhibitors and inhibitors of HaCaT cell proliferation. In particular, the compounds according to the invention are selective tyrosine kinase inhibitors of the epidermal growth factor receptor (EGF-R) .The EGF-R has the role in the development and formation of metastases of certain human malignancies. such as breast cancer, liver cancer and prostate cancer For all known functions and activities of EGF-R their tyrosine kinase activity is a determining factor The inhibition of this enzymatic activity by the compound of Formula I can be considered Therefore, as a measure of the effectiveness in the therapeutic treatment of hyperproliferative diseases mediated by EGF-R such as certain forms of cancer and psoriasis, in contrast to the stimulating role of the EGF receptor in keratinocyte proliferation, in vivo studies in vitro show that the activation of this receptor is a negative regulator of hair follicle activity. EGF inhibits hair growth in newborn mice (Moore et al., J. Endocrinol. 88, 293 [1981]) and sheep (Chapman &; Hardy by J. Biol. Sci. 41, 261 [1988]) and the treatment of human hair follicles cultured with EGF induce a catagen-like state (Philpott et al., J. Cell, Sci. 97, 463 [1990]) with inhibition. of hair fiber production. These findings suggest that the inhibition of EGF-R tyrosine kinase stimulates hair growth and prolongs the duration of the anagen phase of the hair cycle in vivo. The biological activity of the compounds according to the invention was tested in several test models described below.

Tyrosine protein kinases Inhibition of tyrosine kinase receptor EGF The tyrosine kinase activity of the EGF receptor is determined by measuring the 32 P-labeled phosphate transfer of 32 P-α-ATP (10 μm) to the substrate RR-scr peptide * (0.75 mM). A membrane fraction of human A431 cells is used as the enzyme. It is isolated according to Thom et al., Biochem. J. 168, 187 (1977) and stored at -75 ° C (4-6 mg protein / ml). The compounds are tested in 10% DMSO at a concentration of 0.001-100 μM. Incubation is performed at 30 ° C for a period of 30 minutes in Tris pH (25 mM, pH 7.4) containing magnesium acetate (30 mM), sodium vanadate (0.5 mM), 0.5% BSA and 0.05% Triton X-100 The membranes are pre-incubated with 2 μM of EGF at 4 ° C for 90 minutes. The test is started by adding the enzyme (2 μg of membrane protein) and finished by adding ice cold KG2P04 (1 M, pH 3. 0). After centrifugation the labeled peptide is separated from the excess ATP in the supernatant by Reverse phase HPLC. The peptide fraction is collected and the radioactivity is measured in a standard ß counter or connected in the working line ("on-line") with a radiometer (Berthold). The inhibitory activity of the test compound is expressed as the micromolar concentration that is required for a 50% inhibition (CIso.uM.).

** RR-src peptide = [Arg-Arg-Leu-Ile-Glu-Asp-Ala-Glu-Tir-Ala-ala-Arg-Gly].

Inhibition of p56lck tyrosine kinase The activity of the p56lck tyrosine kinase is determined by measuring the 32p-labeled phosphate transfer of 32p-α-ATP (10 μm) to the substrate RR-scr peptide * (0.75 mM). Human recombinant p56lc is used (expressed in E. coli) as the enzyme. It is purified from the soluble fraction by means of a column of monoclonal antibodies and stored at -75 ° C. The compounds are tested in 10% DMSO at a concentration of 0.001-100 μM. Incubation is carried out at 30 ° C for a period of 30 minutes in HEPES buffer (50 mM, pH 6.9) containing manganese chloride (11 mM) and 0.5% BSA. The test is started by adding the enzyme and it is finished by adding ice cold KH2P04 (1 M, pH 3.0). After centrifugation the labeled peptide is separated from the excess ATP in the supernatant by reverse phase HPLC. The peptide fraction is collected and the radioactivity is measured in a standard ß counter or connected in the working line ("on-line") with a radiometer (Berthold). The inhibitory activity of the test compound is expressed as the micromolar concentration that is required for a 50% inhibition (IC 50 [μM]).

Serine / threonine protein kinases Inhibition of protein kinase (PKA) dependent on cAMP The activity of PKA is measured by measuring the transfer of 32 P-labeled phosphate from 32P-α-ATP (10 μM) to the substrate histone Hl (333 μg / ml) using partially purified PKA from brain and pig (DAEAE chromatography according to U. Kikkawa et al., Methods Enzymol 99, 288, 1983). PKA is activated by 2 μm of cAMP in Tris HCl buffer (20 mM, pH 7.4). the compounds are tested in DMSO / buffer at a concentration of 0.001-100 μM. The test is started by adding the enzyme, takes 2 minutes at 32 ° C and ends up adding 20% trichloroacetic acid (containing 1% SDS and 1% sodium pyrophosphate). The precipitated protein containing the histone labeled with radium is separated from the excess ATP by filtration, through a nitrocellulose membrane filter. The radioactivity in the filter is determined in a scintillation counter. The inhibitory activity of the test compounds is expressed as the micromolar concentration that is required for a 50% inhibition (IC 50 [μM]).

Inhibition of protein kinase C (PKC) PKC activity is measured by measuring the transfer of 32 P-labeled phosphate from 32P-α-ATP (10 μm) to the histone Hl substrate (200 μg / ml) using partially purified PKC from pig brain (DEAE chromatography according to U. Kikkawa et al., Methods Enzymol, 99, 288, 1983). The PKC is activated by a phospholipid vesicle prepared by sonication of a mixture of 0.05 ml of phosphatidylserine (10 mg / ml) and 0.005 ml of diolein (10 mg / ml) in 5 ml of Tris HCl buffer (20 mM, pH 7.4) . the compounds are tested in DMSO / buffer at a concentration of 0.001-100 μM. The test is started by adding the enzyme, takes 2 minutes at 32 ° C and ends up adding 20% trichloroacetic acid (containing 1% SDS and 1% sodium pyrophosphate). The precipitated protein containing the labeled histone is separated from the excess ATP by filtration through a nitrocellulose membrane filter. The radioactivity in the filter is determined in a scintillation counter. The inhibitory activity of the test compounds is expressed as the micromolar concentration that is required for a 50% inhibition (CI5o [μM]).

Inhibition of HaCaT cell proliferation HaCaT is a cell line of spontaneous immortalized human keratinocytes (Boukamp et al. 1988) that has been used many times as a model system for hyperproliferative keratinocytes. The incorporation of [3 H] -thymidine was used to quantify the growing cells in the S phase of the cell cycle. The cells were cultured with a 3: 1 mixture of DMEM / F12 medium that had been supplemented with 5% FCS, EGF (10 μg / 1), hydrocortisone (400 μg / 1), cholera toxin (8.5 μg / 1) , insulin (5 μg / 1), L-glutamine (2 mM) and penicillin / streptomycin. 200 μl of the medium was placed in microtitre plates such that each sample contained 5000 cells. The test compounds were added in serial dilutions in the range of 1 × 10 ~ 8 M to 1 × 10 ~ 5 M at the start of the culture. The cells were incubated at 37 ° C for 48 hours. During the last 6 hours [3H] -thymidine (1 mCi / sample) was added. After digesting the cells with trypsin, the amount of radioactivity incorporated with a liquid scintillation counter was quantified. Inhibition of selected protein kinases in vitro and inhibition of cell proliferation in HaCaT cells by these compounds is set forth in the following Table. n.p. : not tested Stimulation of cell proliferation in mouse hair follicles cultured Mouse hair follicles are isolated and cultured according to the method described by Buhl et al., J. Invest. Dermatol. 92, 315 (1989). Parts of the whiskers of 4-day-old CD-1 mice are taken and the hair follicles are carefully separated from the surrounding tissue under the microscope. The hair follicles are cultured in M199 medium containing 20% FBS and cell proliferation is determined by the incorporation of [3H] -thymidine into DNA. The test compounds are dissolved in DMSO and added in serial dilutions in the range of 1 x 10"8 to 1 x 10" 6 M at the start of the culture. After 1 day, 5 μCi / ml of [3 H] -thymidine is added to the culture medium and the follicles are incubated for an additional 3 days. The hair follicles are then washed with phosphate buffer saline to remove unincorporated radioactivity and the DNA is solubilized by alkali incubation overnight. The radioactivity incorporated in the follicular DNA is then measured using a liquid scintillation counter. Incubation of hair follicles of the mouse with the compound of Example 1 results in a stimulation of cell proliferation with a maximum DNA synthesis value of 211 ± 17% (compared to controls) at a concentration of 0.3 μM. The concentration that resulted in a semi-maximal stimulation of DNA synthesis (EC50 value) WAS 0.1 μm. The activity of the compound of Example 1 in this culture system exceeded that of known hypothricotic agents. For example, minoxidil stimulates DNA synthesis of the hair follicle at 160 ± 15% (compared to controls) and has an EC50 value of 200 μM. According to the invention, the compounds of Formula I and their pharmaceutically acceptable salts can be prepared according to the invention by reacting a diketone of the general formula: wherein R6, R7 and R8 have the meaning indicated above, with an aldehyde of the general formula: wherein R1, R2, R3, R4 and R5 have the meaning given above and wherein a hydroxy group in the compounds of formulas II and III may be present in protected form, in the presence of ammonium, separating a hydroxy protecting group that can be present and, if desired, functionally modifying reactive groups present in a compound of Formula I obtained and, if desired, converting a compound of Formula I to a pharmaceutically acceptable salt. The reaction of a diketone of Formula II with an aldehyde of Formula III and with ammonium can be carried out in a manner known per se. For example, a diketone of Formula II can be reacted with an aldehyde of formula III and with ammonium acetate (a reactant that liberates ammonium) in an organic acid such as acetic acid at an elevated temperature, for example, at about 50 to about 100 ° C. Hydroxy groups in the compounds of formulas II and / or III can be present in the reaction according to the invention in protected form, for example as a benzyl ether, which can be removed from the reaction product in a manner known per se, in the case of benzyl ether for example by catalytic hydrogenation. The diketones of Formula II and aldehydes of Formula III are known or can be prepared in a manner known per se as described in the Examples or in an analogy thereto.

The functional modification of reactive groups can comprise, for example, the saponification of ester groups, the reduction of nitro groups to amino groups and the alkylation of amino groups. These functional modifications can be performed in a manner known per se, for example, as described in the examples or in analogy thereto. Acid compounds of Formula I can be converted to pharmaceutically acceptable salts by treatment with acids. Such reactions may be carried out in a manner known per se. The compounds of Formula I and their salts can be used as medicaments, for example, in the form of pharmaceutical preparations. Medications can be administered enterally, parenterally or topically. Medicaments in the form of tablets, capsules, dragees, syrups, suspensions, solutions and suppositories are suitable for example for enteral administration. Medications in the form of infusion or injectable solutions are suitable for parenteral administration. The dosages to which the preparations can be administered can vary according to the mode of use and the route of use as well as according to the requirements of the patient. In the case of oral administration of the compounds according to the invention, dosages of approximately 0.1-100 mg / kg, preferably 0.5-50 mg / kg, per day are considered in the case of adults. The preparations can be administered in one or more doses. Capsules containing about 5-500 mg of active ingredient comprise a preferred administration form. The preparations may contain inert or pharmacodynamically active additives. Tablets or granules, for example, may contain a series of binders, fillers, vehicles or diluents. Liquid preparations may be present, for example, in the form of sterile water miscible solutions. The capsules may contain a filler or thickener in addition to the active ingredient. In addition, flavor enhancing additives may be present, as well as substances which are generally used as preservatives, stabilizers, wetting agents and emulsifiers as well as salts for modifying the osmotic pressure, buffers and other additives.

The vehicles and diluents mentioned above may comprise organic or inorganic substances, for example water, gelatin, lactose, starch, magnesium stearate, talc, gum arabic, polyalkylene glycols and the like. A prerequisite is that all adjuvants used in the production of the preparations are not toxic. For topical application the active ingredients are conveniently used in the form of ointments, tinctures, creams, solutions, lotions, sprays, suspensions, gels and the like. Ointments and creams as well as solutions are preferred. These preparations adapted for topical application can be produced by mixing the process products as active ingredients with inert, non-toxic solid or liquid carriers, which are suitable for topical treatment and which are commonly found in such preparations. For topical application there are conveniently suitable solutions of approximately 0.1-10%, preferably 0.3-2%, as well as ointments and creams of approximately 0.1-10%, preferably approximately 0.3-2%. If desired, an antioxidant, for example tocopherol, N-methyl-α-tocophermine, as well as t-butyl-hydroxyanisole or t-butyl-hydroxytoluene, can be mixed with the preparations. The following Examples illustrate the invention in more detail.

EXAMPLE 1 A mixture of 12.3 g of 1- (4-chlorophenyl) -2-pyridin-4-yl-ethanedione and 7.4 g of 2,4,6-trimethylbenzaldehyde in 125 ml of acetic acid containing 40 g of ammonium acetate was stirred at room temperature. 100 ° C for 2 hours, then allowed to cool to room temperature. The mixture was poured into a mixture of 300 ml of ice water and 200 ml of concentrated ammonium solution and the mixture was extracted three times with ethyl acetate. After drying over anhydrous magnesium sulfate, the solvent was evaporated. The residue was purified by chromatography on silica gel with dichloromethane / methanol (9: 1) and crystallized from ethyl acetate to give 6.7 g of 4- [5- (4-chlorophenyl) -2- (2, 4 , 6-trimethylphenyl) -imidazol-4-yl] pyridine, mp 275 ° C.

EXAMPLES 2-63 The following compounds were prepared in analogy to Example 1: 2. 4- [5- (3-chlorophenyl) -2- (2,4,6-trimethylphenyl) imidazol-4-yl] pyridine, m.p. 235-237 ° C (dichloromethane / hexane). 3. 4- [5- (3,4-dichlorophenyl) -2- (2,4,6-trimethylphenyl) -imidazol-4-yl] pyridine, m.p. 252-254 ° C (dichloromethane / diethyl ether). 4. 4- [5- (4-fluorophenyl) -2- (2,4,6-trimethylphenyl) -imidazol-4-yl] pyridine, m.p. 252-254 ° C (diethyl ether), 5- 4- [5- (4-chlorophenyl) -2- (2,6-dichlorophenyl) -imidazol-4-yl] pyridine, m.p. > 280 ° C (ethanol), 4- 4- [5- (2,4-dichlorophenyl) -2- (2,6-dicyclorenyl) - "imidazol-4-yl] pyridine, mp 270-272 ° C (ethyl acetate). ethyl / hexane), 7. 4- [5- (4-chlorophenyl) -2- (2,6-dimethylphenyl) -imidazol-4-yl] pyridine, mp 290-292 ° C (ethyl acetate / hexane), 8. 4- [5- (4-chlorophenyl) -2- (2,3,4,5,6-pentamethylphenyl) -imidazol-4-yl] pyridine, mp> 280 ° C (ethanol), 4- [ 5- (2-fluorophenyl) -2- (2,4,6-trimethylphenyl) -imidazol-4-yl] pyridine, mp> 260 ° C (hexane),. 4- [5- (3-methoxyphenyl) - 2- (2,4-, 6-trimethylphenyl) -imidazol-4-yl] pyridine, mp> 260 ° C (diethyl ether / hexane),. 4- [5- (3-bromophenyl) -2- (2, 4,6-trimethylphenyl) -imidazol-4-yl] pyridine, mp 248-250 ° C (ethyl acetate / hexane),. 4- [5- (chlorophenyl) -2- (2,6-dibromophenyl) -. imidazol-4-yl] pyridine, mp> 260 ° C (diethyl ether), 4- [5- (3-methylphenyl) -2- (2,4,6-trimethylphenyl) -imidazol-4-yl] pyridine. , mp 251-253 ° C (diethyl ether), 4- [5- (4-chlorophenyl) -2- (2-chloro-6-). methylphenyl) -imidazol-4-yl] pyridine, m.p. > 260 ° C (acetone),. 4- [5- (4-chlorophenyl) -2- (2-chloro-6-nitrophenyl) -imidazol-4-yl] pyridine, m.p. > 260 ° C (ethyl acetate / hexane),. 4- [5- (4-chlorophenyl) -2- (2-methyl-6-nitrophenyl) -imidazol-4-yl] pyridine, m.p. > 260 ° C (acetone / hexane),. 4- [5- (4-chlorophenyl) -2- (2-chloro-6-fluorophenyl) -imidazol-4-yl] pyridine, m.p. 285 ° C (ethyl acetate), 18. 4- [5- (3-chlorophenyl) -2- (2-chloro-6-nitrophenyl) -imidazol-4-yl] pyridine, m.p. 259-260 ° C (acetone / hexane), 19. 4- [5- (3,4-dichlorophenyl) -2- (2-chloro-6-nitrophenyl) -imidazol-4-yl] pyridine, m.p. > 260 ° C (ethyl acetate / hexane), 20. 4- [5- (4-fluorophenyl) -2- (2-chloro-6-nitrophenyl) -imidazol-4-yl] pyridine, m.p. ** - 260 ° C (acetone / hexane), 21. 4- [5- (4-chlorophenyl) -2- (2-bromo-6-methylphenyl) -imidazol-4-yl] pyridine, m.p. > 260 ° C (acetone / hexane), 22. 4- [5- (4-bromophenyl) -2- (2-chloro-6-nitrophenyl) -imidazol-4-yl] pyridine, m.p. > 260 ° C (acetone / hexane), 23. 4- [5- (4-chlorophenyl) -2- (2,3,5,6-tetramethylphenyl) -imidazol-4-yl] pyridine, m.p. > 260 ° C (acetone), 24. 4- [5- (4-chlorophenyl) -2- (2-bromo-6-chlorophenyl) -imidazol-4-yl] pyridine, m.p. > 260 ° C (acetone), 25. 4- [5- (3-bromophenyl) -2- (2-chloro-6-nitrophenyl) -imidazol-4-yl] pyridine, m.p. 238-239 ° C (acetone / hexane) 26. 4- [5- (3-methoxyphenyl) -2- (2-chloro-6-nitrophenyl) -imidazol-4-yl] pyridine, m.p. 232-234 ° C (tetrahydrofuran / hexane), 7. 4- [5- (4-chlorophenyl) -2- (2,6-diisopropylphenyl) -imidazol-4-yl] pyridine, m.p. > 260 ° C (acetone / hexane) 28. 4- [5- (4-fluorophenyl) -2- (2-bromo-6-methylphenyl) -imidazol-4-yl] pyridine, m.p. > 260 ° C (dichloromethane), 29. 4- [5- (4-chlorophenyl) -2- (2-bromo-3-methylphenyl) -imidazol-4-yl] pyridine, m.p. >; 260 ° C (diethyl ether), 30. 4- [5- (4-fluorophenyl) -2- (2-methyl-6-nitrophenyl) -imidazol-4-yl] pyridine, m.p. > 250 ° C (dichloromethane / hexane), 31. 4- [5- (4-chlorophenyl-2- (2-bromophenyl) -imidazol-4-yl] pyridine, mp 206-208 ° C (ethyl acetate / hexane) , 32. 4- [5- (3-Bromophenyl) -2- (2-bromophenyl) -imidazol-4-yl] pyridine, mp 141-143 ° C (ethyl acetate / hexane), 33. dimethyl- [2 - [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -3-methylphenyl] amine, mp 230-232 ° C (diethyl ether / hexane), 34. 3- [5 Methyl (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzoate, mp 228 ° C (ethyl acetate / isopropyl ether), 35. 4- E2 - (3-Bromo-2, 6-dimethylphenyl) -5- (4-chlorophenyl-imidazol-4-yl) pyridine, mp 300-305 ° C (ethyl acetate), 36. 4- [5- (4- chlorophenyl) -2- (2,6-dipfethyl-3-nitrophenyl) -imidazol-4-yl] pyridine, mp 295-298 ° C (ethyl acetate / hexane), 37. 4- [5- (4-chlorophenyl ) -2- (2-fluoro-6- trifluorornethylphenyl) -imidazol-4-yl] pyridine, mp 264-266 ° C (acetone / hexane), 38. 4- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzyl] morpholine, pf 239-240 ° C (ethyl acetate), 39. 4- [5- (4-chlorophenyl) -2- (2-allyl-6-methylphenyl) -imidazol-4-yl] pyridine, m.p. 96-98 ° C, 40. [3- [5, (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzyl] dimethylamine, m.p. 222 ° C (acetonitrile), 41. 4- [5- (4-chlorophenyl) -2- (2-methoxymethyl-6-methylphenyl) -imidazol-4-yl] pyridine, pfl38-140 ° C (acetone / hexane), 42 4- [5- (4-chlorophenyl) -2- (3-methoxy-2,6-dimethylphenyl) -imidazol-4-yl] pyridine, mp. 283-285 ° C (ethyl acetate), 43. 4- [5- (4-chlorophenyl) -2- (2,6-dimethyl-3,5-dinitrophenyl) -imidazol-4-yl] pyridine, m.p. 300-305 ° C, 44. 4- [5- (4-chlorophenyl) -2- (2-chloro-6-trifluoromethylphenyl) -imidazol-4-yl] pyridine, m.p. > 260 ° C (acetone / hexane), 45. 1- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzyl] -4 -methylpiperazine, mp 280 ° C (ethyl acetate), 46. 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4-dimethylphenol, m.p. > 300 ° C (ethanol), 47. 4- [4- (4-chlorophenyl) -5-pyridin-4-yl-imidazol-2-yl] -3,5-dimethylphenol, m.p. 189-191 ° C (dichloromethane / diethyl ether), 48. 1 - [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzyl ] ethyl piperidine-4-carboxylate, mp 210 ° C (ethyl acetate), 49. [4- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -3,5-dimethylphenoxy] ethyl acetate, m.p. 210-211 ° C (tetrahydrofuran / hexane), '50. 4- [2- (3-Azidomethyl-2,4,6-trimethylphenyl) -5- (4-chlorophenyl) imidazol-4-yl] pyridine, m.p. 230 ° C (ethyl acetate), 51. [3- [5, (4-chlorophenyl) -4-pyrin-4-yl-imidazol-2-yl] -2,4,6-trimethylphenyl] acetonitrile, m.p. 250 ° C (acetonitrile),. 3- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4-dimethylphenoxy] propan-1-ol, m.p. 260-263 ° C (ethyl acetate),. [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -benzyl] -diethylamine, m.p. 142 ° C (ethyl acetate),. 4- [5- (4-chlorophenyl) -2- (2,4,6-trimethy1-3-nitrophenyl) -imidazol-4-yl] pyridine, m.p. 295-299 ° C (methanol / ethyl acetate),. 4- [5- (4-chlorophenyl) -2- (2,3,6-trichlorophenyl) imidazol-4-yl] pyridine, m.p. > 260 ° C (acetone / hexane),. 4- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -3,5-dimethylphenoxy] acetamide, m.p. > 260 ° C (water),. [3- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4-dimethylphenoxy] propyl] dimethylamine, m.p. 145-149 ° C (ethyl acetate / isopropyl ether / hexane),. 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylphenol, m.p. > 300 ° C (ethanol),. (2RS, 6RS) - and (2R, 6S) -4- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzyl] 2,6-dimethylmorpholine, mp 163-170 ° C (ethyl acetate),. 4- [5- (4-chlorophenyl) -2- (2,4,6-trimethyl-3-piperidin-1-yl-methylphenyl) -imidazol-4-yl] pyridine, m.p. 156-165 ° C (ethyl acetate / hexane), 61. (S - [l- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2, 4,6-trimethylbenzyl] pyrrolidin-2-yl] methanol, mp 165-168 ° C (ethyl acetate / hexane), 62. 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4-dimethylbenzyl acetate, m.p. 232-234 ° C (ethyl acetate / isopropyl ether), 63. 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2, 4, 6- acetate. trimethylbenzyl, mp 234-236 ° C (ethyl acetate / hexane), EXAMPLE 64 (i) 4- [5- (3-Benzyloxyphenyl) -2- (2,4,6-trimethylphenyl) imidazol-4-yl] pyridine, m.p. 247-248 ° C (ethyl acetate / hexane) in analogy to Example 1 from 1- (3-benzyloxyphenyl) -2-pyridin-4-yl-ethanedione, m.p. 79-80 ° C (dichloromethane / hexane). (ii) A solution of 4.4 g of 4- [5- (3-benzyloxyphenyl) -2- (2,4,6-trimethylphenyl) imidazol-4-yl] pyridine in 500 ml of methanol was hydrogenated in the presence of 0.4 g. of palladium on carbon at 10% for 3 hours. The catalyst was filtered and the solution was evaporated. Recrystallization of the residue from ethyl acetate / hexane gave 3.0 g of 3- [4-pyridin-4-yl-2- (2,4,6-trimethylphenyl) imidazol-5-ylphenol, m.p. 338-340 ° C.

EXAMPLE 65 (i) 4- [5- (2-Benzyloxyphenyl) phenyl-2- (2,4,6-trimethylphenyl) imidazol-4-yl] pyridine, m.p. 125-127 ° C (diethyl ether) in analogy to Example 1 from 1- (2-benzyloxyphenyl) -2-pyridin-4-yl-ethanedione. (ii) A solution of 1.0 g of 4- [5- (2-benzyloxyphenyl) phenyl-2- (2,4,6-trimethylphenyl) imidazol-4-yl] pyridine in 40 ml of acetic acid was hydrogenated in the presence of 0.1 g of palace / coal at 10% for 3 hours. It was filtered and the catalyst was poured into a mixture of 200 g of ice and 150 ml of concentrated ammonium hydroxide. It was filtered and the solid was dissolved in dichloromethane. After drying over anhydrous magnesium sulfate, the solvent was evaporated and the residue was recrystallized from tetrahydrofuran / hexane. 0.3 g of 2- (4-pyridin-4-yl-2- (2,4,6-trimethylphenyl) imidazol-5-yl] phenyl-methanol, mp 215-217 ° C were obtained.

EXAMPLE 66 A solution of 0.2 g of 4- [5- (4-chlorophenyl) -2- (2-chloro-6-nitrophenyl) -imidazol-4-yl] pyridine in 20 ml of methanol was hydrogenated in the presence of 0.1 g of palladium / 10% carbon for 2 hours. The catalyst was filtered and the solution was evaporated to dryness. Recrystallization from ethyl acetate gave 0.1 g of 3-chloro-2- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -phenyla ina, m.p. 220-222 ° C.

EXAMPLE 67 A solution of 480 mg 4- [5- (4-chlorophenyl) -2- (2,6-dimethyl-3-nitrophenyl) imidazol-4-yl] pyridine in 100 ml of methanol was hydrogenated in the presence of 35 mg of oxide of platinum for 2 hours. The catalyst was filtered and the evaporated. solvent. Recrystallization from acetonitrile gave 280 mg of 3- [5- (4-chlorophenyl-4-pyridin-4-yl-imidazol-2-yl] -2,4-dimethyl] phenylamine, mp 302-306 ° C.

EXAMPLE 68 A solution of 90 mg of sodium in 70 ml of methanol was treated with 1.95 g of 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4 acetate, 6-trimethylbenzyl. The mixture was stirred at room temperature for 3 hours, then treated with 0.3 ml of acetic acid. The solvent was evaporated and the residue was crystallized from ethyl acetate to give 1.1 g of 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2, 4, 6-trimethylphenyl) methanol, mp 282-285 ° C.

EXAMPLE 69 3- [5- (4-Chlorophenyl) -4-pyridin-4-yl-imidazl-2-yl] -2,4-dimethylphenyl) methanol, m.p. > 300 ° C, in analogy to Example 67 from 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4-dimethylbenzyl acetate.

EXAMPLE 70 A solution of 0.63 g of 4- [5- (4-chlorophenyl) -2- (2,4,6-trimethyl-3-nitrophenyl) imidazol-4-yl] pyridine in 100 ml of methanol was hydrogenated in the presence of 0.8 g of platinum oxide for 24 hours. The catalyst was filtered and the solution was evaporated. The residue was chromatographed on silica gel using dichloromethane / methanol as the eluent. Recrystallization from methanol / water gave 0.14 g of 3- [5- (4-chlorophenyl) -4-pyridin-4-yl) imidazol-2-yl] -2,4,6-trimethyl-phenylamine, m.p. > 300 ° C. The starting materials that are used in Example 1-70, whose preparation has not been described thus far, can be prepared as described below or in analogy to these descriptions: A. Etanone derivatives (compounds of Formula II) 1- (4-chlorophenyl) -2-pyridin-4-yl-ethanedione (i) 19.4 of 4-pyridimethyl isocyanide was added dropwise at -5 ° C, while stirring, to a solution of 37.8 g of potassium tert-butylate in 400 ml of tetrahydrofuran. The mixture was then treated with 23.1 g of 4-chlorobenzaldehyde and stirred at -5 ° C for another 2 hours. Then 19.7 g of acetic acid were added dropwise at 0 ° C while stirring and the solid was filtered. The residue was chromatographed on silica gel with dichloromethane / methanol (95: 5) as the eluent and recrystallized from dichloromethane / hexane. 25.0 g of (E / Z) -N- [2- (4-chlorophenyl) -l-pyridin-4-yl-vinyl] formamide, m.p. 155-156 ° C. (ii) A solution of 39.0 g of (E / Z) -N- [2- (4-chlorophenyl) -l-pyridin-4-yl-vinyl] formamide in 430 ml of methanol was treated with 112 ml of hydrochloric acid concentrated. The mixture was stirred at 32-35 ° C for 16 hours. The mixture was cooled to 0 ° C and added dropwise while stirring at 0 ° C to a solution of 82.2 g of potassium hydroxide in 100 ml of water. The solid was filtered and recrystallized from dichloromethane / hexane. 25.0 g of l- (4-chlorophenyl) -2-pyridin-4-yl-ethanone were obtained, p.f. 85-86 ° C. (üi) A solution of 25 g of 1- (4-chlorophenyl) -2-pyridin-4-yl-ethanone in 285 ml of dioxane was treated with 20 g of selenium dioxide. The mixture was stirred at 100 ° C for 1 hour and filtered. The solvent was evaporated and the residue was dissolved in dichloromethane. The solution was washed three times with water, dried over anhydrous magnesium sulfate and evaporated. The residue was dissolved in ethyl acetate, the solution was filtered on silica gel and evaporated to give 23.7 g of 1- (4-chlorophenyl) -2-pyridin-4-yl-ethanedione, m.p. 119-120 ° C.

B. Derivatives of benzaldehyde (compound of Formula III 2-brorno-6-ptetilbenzaldehyde (i) A solution of 9.52 g of (2-bromobenzylidene) -phenylamine in 150 ml of acetic acid was treated with 7.9 g of palladium (II) acetate. The mixture was refluxed for 1 hour, then poured into 150 ml of water and extracted three times with dichloromethane. The combined organic extracts were washed in water, dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was chromatographed on silica gel with dichloromethane / methanol (99: 1) as the eluent and gave 10.3 g of bis [acetate (3-bromo-2-phenyliminomethylphenyladladium] (Pd-Pd), mp 199-200 ° C. (ii) A solution of 10.3 g of bis [acetate (3-bromo-2-phenylimino-methylphenyl) palace] (Pd-Pd) in 80 ml of dichloromethane and 80 ml of acetone was treated with 90 ml of sodium chloride solution. saturated sodium, while stirring.After 10 minutes the solid was filtered and gave 6.1 g of bis [chloro (3-bromo-2-phenyl-iminomethylphenyl) palladium] (Pd-Pd), mp 280-282 ° C. iii) A solution of 6.1 g of bis [chloro-bromo-2-phenylimino-methylphenyl) palladium] (Pd-Pd) in 225 ml of pure benzene was treated with 7.9 g of triphenylphosphine under argon. The mixture was then stirred at room temperature for another 30 minutes. 12.5 ml of a solution of 1.6 M methyllithium in diethyl ether was added dropwise at 0 ° C while stirring and the mixture was then stirred at room temperature for 1 hour. The mixture was then treated at 0 ° C with 225 ml of 1N hydrochloric acid, filtered and the solid was washed with diethyl ether. The combined organic extracts were washed twice with water, dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was chromatographed on silica gel with hexane / ethyl acetate (98: 2) as the eluent and gave 0.7 g of 2-bromo-6-methylbenzaldehyde, m.p. 48-49 ° C. 2,6-diisopropylbenzaldehyde 6.8 ml of a 1.6 M solution of butyllithium in hexane was added dropwise at -78 ° C while stirring, to a solution of 2.6 g of 2-bromo-l, 3-diisopropylbenzene in 16 ml of tetrahydrofuran. The mixture was stirred at the same temperature for 30 minutes and then treated with a solution of 1.3 g of N-formyl-piperidine in 1.5 ml of tetrahydrofuran. The mixture was then allowed to warm to room temperature over a period of 6 hours. The mixture was cooled to 0 ° C and treated with 12 ml of 3N hydrochloric acid. The aqueous solution was extracted four times with diethyl ether and the combined organic extracts were washed with saturated sodium chloride solution, dried over sodium sulfate, anhydrous magnesium and evaporated to dryness. The residue was chromatographed on silica gel with dichloromethane as the eluent and gave 1.07 g of 2,6-diisopropylbenzaldehyde as an oil. 2-Dimethylamino-6-methylbenzaldehyde (i) A solution of 3 g of 2-amino-6-methylbenzoic acid in 30 ml of acetic acid and 15 ml of 33% formaldehyde hydrogenated at room temperature for 22 hours in the presence of 1 g of palladium / 10% carbon . The catalyst was filtered and the solution was evaporated to dryness. The residue was treated with 200 ml of methanol and the mixture was stirred at 50 ° C for 20 minutes, cooled to -20 ° C and filtered. The solvent was evaporated and the residue was chromatographed on silica gel with dichloromethane / methanol (95: 5) as the eluent. 1.5 g of 2-dimethylamino-6-methylbenzoic acid, m.p. 117-119 ° C. (ii) A solution of 1.3 g of 2-dimethylamino-6-methyl-benzoic acid in 15 ml of tetrahydrofuran was added dropwise while stirring at room temperature to a suspension of 0.5 g of lithium aluminum hydride in 15 ml of tetrahydrofuran. The mixture was stirred at room temperature for 4 hours. The mixture was then treated successively with 15 ml of 50% ammonium chloride solution and 5 ml of water at 10 ° C while stirring, filtered and extracted twice with dichloromethane. The combined organic solutions were dried over anhydrous magnesium sulfate and evaporated to give 0.8 of 2-dimethylamino-6-methylbenzyl alcohol as an oil. (iii) A solution of 1.5 g of 2-dimethylamine-6-methylbenzyl alcohol in 7 ml of dichloromethane was added dropwise while stirring at room temperature to a suspension of 2.88 g of pyridinium chlorochromate in 12 ml of dichloromethane. The mixture was then stirred at room temperature for another 18 hours, treated with 50 ml of diethyl ether, filtered over Florisil and the residue was washed twice with 50 ml portions of diethyl ether. The combined organic extracts were evaporated and the residue was chromatographed on silica gel with diethyl ether / hexane (1: 4) as the eluent. 0.5 g of 2-dimethylamino-6-methylbenzaldehyde was obtained as an oil. 2, -Dimethyl-3, 5-dinitrobenzaldehyde and 2,6-dimethyl-3-nitrobenzaldehyde 2 g of 2,6-dimethylbenzaldehyde were added at room temperature over a period of 15 minutes to a mixture of 20 ml of concentrated nitric acid and 10 ml of acetic acid. The mixture was then stirred at room temperature for 5 minutes and poured into ice water. The mixture was stirred for another 5 minutes, filtered and the residue was dissolved in dichloromethane. After drying over anhydrous magnesium sulfate, the solvent was evaporated. The residue was chromatographed on silica gel with hexane / ethyl acetate as the eluent and gave 1.23 g of 2,6-dimethyl-3-nitrobenzaldehyde, m.p. 54-57 ° C (from hexane), and 0.33 g of 2,6-dimethyl-3,5-dinitrobenzaldehyde, m.p. 119-122 ° C (from toluene / hexane). 2, 4, 6-Trimethyl-3-morpholin-4-yl-methylbenzaldehyde A solution of 0.98 g of 3-chloromethyl-2,4,6-trimethyl-benzaldehyde in 20 ml of acetonitrile was treated with 0.87 ml of morpholine. The mixture was stirred at room temperature for 4 hours and then filtered. . The solvent was evaporated and the residue was dissolved in ethyl acetate. The solution was washed twice with water, dried over anhydrous magnesium sulfate and evaporated to dryness. Distillation of the residue gave 1.05 g of 2,4,6-trimethyl-3-morpholin-4-yl-methyl-benzaldehyde, m.p. 150 ° C / 0.3 Torr. 2-Allyl-6-methylbenzaldehyde (i) 38 ml of a solution of 1 M vinylmagnesium bromide in tetrahydrofuran was added over a period of 5 minutes while stirring and under an argon atmosphere at 0-5 ° C to a mixture of 7.1 g of 2-bromine -l-bromomethyl-3-methylbenzene, 0.51 g of copper iodide (I) and 0.42 g of 2,2-bipyridyl in 20 ml of benzene. The temperature rose to 42 ° C. The mixture was then stirred at room temperature overnight. The mixture was then treated successively with 183 ml of saturated ammonium chloride solution and 2 ml of concentrated ammonium hydroxide solution at 0 ° C while stirring and extracted four times with diethyl ether. The combined organic extracts were washed successively with 1N hydrochloric acid, saturated sodium hydrocarbonate solution and water, dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was purified on silica gel with cyclohexane / dichloromethane (99: 1) and gave 3.1 g of 1-allyl-2-bromo-3-methyl-benzene as an oil. (ii) A solution of 2.3 g of l-allyl-2-bromo-3-methylbenzene in 10 ml of tetrahydrofuran was added dropwise at 0 ° C while stirring, to a suspension of 0.287 g of magnesium in 10 ml of tetrahydrofuran . The mixture was then heated to reflux for 2 hours and finally allowed to cool to 0 ° C. Then a mixture of 1 ml of N, N-dimethylformamide and 5 ml of tetrahydrofuran was added dropwise at 0 ° C while stirring. After stirring at 0 ° C for a further 2 hours and at room temperature overnight, the mixture was again allowed to cool to 0 ° C and heated successively in 80 ml of saturated ammonium chloride solution and 2 ml of concentrated ammonium hydroxide solution. . The mixture was then extracted four times with diethyl ether and the combined organic extracts were washed successively with 1N hydrochloric acid, saturated sodium hydrocarbonate solution and water, dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was purified on silica gel with dichloromethane / hexane (1: 1) as the eluent and gave 6.2 g of 2-allyl-6-benzaldehyde as an oil. 3-Dimethylaminomethyl-2,4,6-trimethylbenzaldehyde 3-Dimethylaminomethyl-2,4,6-trimethyl-benzaldehyde, boiling point 150 ° C / 0.3 Torr, was prepared in analogy to the procedure described above for the preparation of 2,4,6-trimethyl-3-morpholine- 4-yl-methylbenzaldehyde. 2-Methoxymethyl-6-methylbenzaldehyde (i) A solution of 14.7 g of 2-bromo-l-bromomethyl-3-methylbenzene in 100 ml of acetic acid was treated with 5.2 g of anhydrous sodium acetate and heated at reflux overnight. Mix it was evaporated to dryness and the residue extracted with dichloromethane. The extract was evaporated to dryness and the residue was chromatographed on silica gel with dichloromethane / hexane (1: 1) as the eluent. 10.1 g of 2-bromo-3-methylbenzyl acetate was obtained as an oil. (ii) A solution of 10.1 g of 2-bromo-3-methylbenzyl acetate in 75 ml of ethanol was treated with a solution of 13 g of potassium hydroxide in 25 ml of water and the mixture was heated to reflux overnight . The mixture was allowed to cool to room temperature, it was acidified with 3N hydrochloric acid and extracted three times with dichloromethane. The combined organic extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated. The residue was chromatographed on silica gel with dichloromethane as eluent and gave 6.9 g of 2-bromo-3-methylbenzyl alcohol, m.p. 80-81 ° C. (iii) _ A solution of 2.01 g of 2-bromo-3-methylbenzyl alcohol in 10 ml of tetrahydrofuran was added dropwise at 0 ° C while stirring, to a suspension of 0.48 of sodium hydride 55-65% by volume. my tetrahydrofuran. The mixture was stirred at 0 ° C for another 30 minutes and treated with 0.75 ml of methyl iodide. After stirring at 4 ° C for 30 minutes and at room temperature for 40 minutes the mixture was again cooled to 0 ° C, treated with 2 ml of water and poured into 40 ml of diethyl ether. The organic solution was washed with 30 ml of saturated sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated to give 2.0 g of 2-bromo-l-methoxymethyl-3-methylbenzene as an oil. (iv) 5.9 ml of a 1.6 M solution of butyllithium in hexane were added dropwise at -78 ° C while stirring, to a solution of 2.0 g of 2-bromo-l-methoxymethyl-3-methyl-benzene in 13 ml of tetrahydrofuran. Then a solution of 0.75 ml of N, N-dimethylformamide in 1 ml of tetrahydrofuran was added at the same temperature. After the temperature rose slowly to -10 ° C the mixture was treated with 10 ml of 3N hydrochloric acid and poured into 30 ml of diethyl ether. The aqueous solution was extracted twice with diethyl ether and the combined organic extracts were washed with 30 ml of saturated sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated. 1.5 g of 2-methoxymethyl-6-methyl-benzaldehyde was obtained as an oil. 3-Methoxy-2, 6-dimethylbenzaldehyde (i) 30.3 ml of a 1.2 M solution of diisobutylaluminum hydride in toluene at 10 ° C was added while stirring for a period of 10 minutes, to a solution of 2.8 g of methyl 3-methoxy-2,6-dimethylbenzoate in 50 ml of tetrahydrofuran. The mixture was stirred at room temperature for 30 minutes, then cooled to 0 ° C and treated successively at 0 ° C while stirring with 5 ml of ethyl acetate and 50 ml of 1 N hydrochloric acid. The mixture was stirred at room temperature for 15 minutes and extracted twice with ethyl acetate. After drying over anhydrous magnesium sulfate the solvent was evaporated and the residue crystallized from hexane. 1.9 g of 2,6-dimethyl-3-methoxybenzyl alcohol, m.p. 88-89 ° C. (ii) A solution of 1.9 g of 2,6-dimethyl-3-methoxy-benzyl alcohol in 70 ml of dichloromethane was treated with 9.9 g of magnesium dioxide and stirred at room temperature for 18 hours. The mixture was filtered and the solvent was evaporated. The residue was chromatographed on silica gel with hexane / ethyl acetate (9: 1) as the eluent and gave 0.7 g of 3-methoxy-2,6-dimethylbenzaldehyde, m.p. 59-64 ° C. 2,4,6-Trimethyl-3- (4-methylpiperazin-1-ylmethyl) -benzaldehyde 2, 4, 6-Trimethyl-3- (4-methylpiperazin-1-yl-methyl) -benzaldehyde, m.p. 90 ° C (from acetonitrile) in analogy to the manner described above for the preparation of 2,4,6-trimethyl-3-morpholin-4-yl-methylbenzaldehyde. 3-Hydroxy-2, 6-dimethylbenzaldehyde (i) A solution of 2.8 g of 2,6-dimethyl-3-nitrobenzaldehyde in 150 ml of toluene was treated with 5 ml of ethylene glycol and 20 mg of p-toluenesulfonic acid. The mixture was heated to reflux for 18 hours, separating the water using a separator. The mixture was allowed to cool to room temperature and was washed twice with water. After drying over anhydrous magnesium sulfate, the solvent was evaporated and the crystalline residue was crystallized from hexane. 3.0 g of 2- (2,6-dimethyl-3-nitrophenyl) -1,3-dioxolane, m.p. 69-71 ° C (ii) A solution of 2.7 g of 2- (2,6-dimethyl-3-nitrophenyl) -1,3-dioxolane in 30 ml of ethyl acetate was hydrogenated in the presence of 0.2 g of sodium oxide. platinum for 45 minutes. The catalyst was filtered and the solution was concentrated to a crystalline residue. Recrystallization from hexane gave 2.35 g of 2- (3-amino-2,6-dimethylphenyl) -1,3-dioxolane, m.p. 100-103 ° C. (iii) A solution of 0.73 g of sodium nitrite in 2 ml of water was added at 0 ° C for a period of 15 minutes while stirring, to a suspension of 2.0 g of 2- (3-amino-2,6). -dimethylphenyl) -1, 3-dioxolane in 1.9 ml of concentrated sulfuric acid and 5.5 ml of water. The mixture was then stirred at room temperature for a period of 5 minutes at 110 ° C to a mixture of 1 ml of sulfuric acid and 15 ml of water. The mixture was heated to reflux while stirring for 1 hour, then allowed to cool to room temperature, filtered and washed with water to give 1.55 g of 3-hydroxy-2,6-dimethylbenzaldehyde, m.p. 159-165 ° C (from isopropyl ether).

Ethyl 1- (3-formyl-2,4,6-trimethylbenzyl) -piperidine-4-carboxylate Ethyl 1- (3-formyl-2,4,6-trimethylbenzyl) piperidine-4-carboxylate, m.p. 78 ° C (from hexane), in analogy to the preparation of -2,4, 6-trimethyl-3-morpholin-4-yl-methylbenzaldehyde described above. (4-formyl-3, 5-dimethylphenoxy) acetate A mixture of 0.7 g of 4-hydroxy-2,6-dimethylbenzaldehyde, 2.4 g of ethyl bromoacetate and 2.1 g of anhydrous potassium carbonate in 10 ml of acetone was heated to reflux for 2 hours, then filtered and evaporated. Recrystallization of the residue from hexane gave 0.7 ethyl (4-formyl-3,5-dimethylphenoxy) acetate, m.p. 78-80 ° C. 3-Azidomethyl-2,4,6-trimethylbenzaldehyde A solution of 9.8 g of 3-chloromethyl-2,4,6-trimethyl-benzaldehyde in 125 ml of dimethyl sulfoxide was treated with 3.8 g of sodium azide, the mixture was stirred at room temperature for 3 hours and the solvent was evaporated. The residue was dissolved in ethyl acetate and the solution was washed with water. After drying over anhydrous magnesium sulfate, the solvent was removed and 9.1 g of 3-azidomethyl-2,4,6-trimethylbenzaldehyde, m.p. 60 ° C. (3-Formyl-2,4,6-trimethylphenyl) acetonitrile A solution of 9.8 g of 3-chloromethyl-2,4,6-trimethyl-benzaldehyde in 500 ml of ethanol / water (1: 1) was treated with 3.6 g of potassium cyanide. The mixture was stirred at room temperature for 18 hours and the solvent was evaporated. The residue was dissolved in ethyl acetate and the solution was washed with water. After drying over anhydrous magnesium sulfate the solvent was evaporated and the residue was crystallized from isopropyl ether. 4.8 g of (3-formyl-2,4,6-trimethylphenyl) acetonitrile, m.p. 83 ° C. 3- (3-Hydroxypropoxy) -2,6-dimethylbenzaldehyde A solution of 1.5 g of 3-hydroxy-2,6-dimethylbenzaldehyde in 15 ml of water was treated with 0.4 g of sodium hydroxide and 0.87 ml of 3-bromo-2-propanol. The solution was stirred at 100 ° C for 18 hours and then cooled to room temperature. The solution was extracted three times with dichloromethane and the combined organic extracts were washed three times with water. After drying over anhydrous magnesium sulfate, the solvent was evaporated. The residue was chromatographed on silica gel with ethyl acetate / hexane as the eluent and subsequently recrystallized from isopropyl ether / hexane. 0.9 g of 3- (3-hydroxypropoxy) -2,6-dimethylbenzaldehyde, m.p. 68-70 ° C. 3-Diethylaminomethyl-2,4,6-trimethylbenzaldehyde 3-Diethylaminomethyl-2,4,6-trimethylbenzaldehyde, m.p. 200 ° C / 0.2 Torr in analogy to the procedure described for the synthesis of 2,4,6-trimethyl-3-morpholin-4-yl-methylbenzaldehyde. 2- (4-formyl-3, 5-dimethylphenoxy) acetamide A solution of 1.2 g of 4-hydroxy-2,6-dimethylbenzaldehyde in 12 ml of N, N-dimethylformamide was treated while stirring, with 0.32 g of 55-65% sodium hydride and heated at 40 ° C for 15 hours. minutes Then, a solution of 1.6 g of iodoacetamide in 4 ml of N, N '-dimethylformamide was added dropwise and the mixture was heated at 40 ° C for a further 4 hours while stirring. The mixture was poured into 80 ml of ice water and the solid was filtered and washed successively with water and diethyl ether. The residue was dissolved in ethyl acetate and the solution was washed once with 3 N aqueous sodium hydroxide solution, dried over anhydrous magnesium sulfate and evaporated. Crystallization from diethyl ether gave 0.9 g of 2- (4-formyl-3,5-dimethylphenoxy) acetamide, m.p. 157-158 ° C. 3- (3-Dimethylaminopropoxy) -2,6-dimethylbenzaldehyde A solution of 1.5 g of 3-hydroxy-2,6-dimethylbenzaldehyde in 14.4 ml of ethanol and 0.6 ml of water was treated with 2.94 g of potassium carbonate. The mixture was stirred at 60 ° C and treated for a period of 20 minutes with 1.58 g of 3-dimethyl-amino-1-chloropropane hydrochloride in several portions. The mixture was heated to reflux for 18 hours and then cooled to room temperature. The solids were filtered and the solvent was evaporated. The residue was dissolved in ethyl acetate and the solution was washed successively with water, 2N sodium hydroxide solution and water. The organic phase was dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was chromatographed on silica gel with chloroform / methanol as the eluent. Distillation gave 1.56 g of 3- (3-dimethylamino-propoxy) -2,6-dimethylbenzaldehyde, p.e1. 115 ° C / 0.1 Torr. (2RS, 6RS) - and (2R, 6S) -3- (2,6-dimethylmorpholin-4-ylmethyl) -2,4,6-trimethylbenzaldehyde Prepared (2RS, 6RS) - and (2R, 6S) -3- (2,6-dimethylmorpholin-4-yl-methyl) -2,4,6-trimethylbenzaldehyde, m.p. 130 ° C (hexane) in analogy to the procedure described above for the synthesis of 2,4,6-trimethyl-3-morpholin-4-yl-methyl-1-benzaldehyde. 2, 4, 6-trimethyl-3-piperidin-l-yl-methylbenzalehyde 2, 4, 6-Trimethyl-3-piperidin-1-yl-methyl-benzaldehyde, m.p. 70 ° C (hexane) in analogy to the procedure described above for the synthesis of 2,4,6-trimethyl-3-morpholin-4-yl-methylbenzaldehyde.

(S) -3- (2-hydroxymethyl-pyrrolidin-1-yl-methyl) -2,4,6-trimethylbenzaldehyde (S) -3- (2-Hydroxymethyl-pyrrolidin-1-yl-methyl) -2,4,6-trimethylbenzaldehyde, m.p. 250 ° C / 0.2 Torr, in analogy to the procedure described above for the synthesis of 2,4,6-trimethyl-3-morpholin-4-yl-methylbenzaldehyde. 2- (Benzyloxymethyl) benzaldehyde (i) A solution of 66.4 g of benzyl 2 (benzyloxymethyl) benzoate of 200 ml of ethanol was treated with a solution of 16.0 g of sodium hydroxide in 50 ml of water. The mixture was heated to reflux for 16 hours while stirring, and concentrated to a small volume. The residue was diluted with 400 ml of water and the solution was extracted twice with diethyl ether. The aqueous solution was acidified with concentrated hydrochloric acid and extracted twice with diethyl ether. The organic extracts mentioned above were combined, dried over anhydrous magnesium sulfate and the solution was evaporated to dryness. Recrystallization of the residue from hexane gave 19.8 g of 2- (benzyloxymethyl) benzoic acid, m.p. 90-92 ° C. (ii) A solution of 19.8 of 2- (benzyloxymethyl) -benzoic acid in 165 ml of diethyl ether was added dropwise at room temperature while stirring, to a suspension of 4.66 g of lithium aluminum hydride in 490 ml of diethyl ether. The mixture was refluxed for 1 hour and then cooled to room temperature. Then 35 ml of water was added dropwise, the mixture was stirred at room temperature for 10 minutes and filtered. The organic solution was dried over anhydrous magnesium sulfate and evaporated to give 18.2 g of 2- (benzyloxymethyl) -benzyl alcohol as an oil. (iii) 3.4 ml of dimethyl sulfoxide was added dropwise at -60 ° C over a period of 5 minutes while stirring, to a solution of 2 ml of oxalyl chloride in 50 ml of dichloromethane. The mixture was stirred at -60 ° C for 10 minutes and then treated at -60 ° C for a period of 5 minutes while stirring, with a solution of 4.56 g of 2- (benzyloxymethyl) benzyl alcohol in 20 ml of dichloromethane . Then triethylamine was added dropwise and the mixture was allowed to warm to room temperature. The mixture was diluted with 100 ml of water, the phases were separated and the aqueous solution was extracted with 100 ml of dichloromethane. The combined organic solutions were dried over anhydrous magnesium sulfate and concentrated to give 4.1 g of 2- (benzyloxymethyl) benzaldehyde as an oil. 3-Chloromethyl-2,6-dimethylbenzaldehyde (i) A suspension of 5 g of 3-chloromethyl-2,6-dimethylbenzoic acid in 5 ml of thionyl chloride was stirred at room temperature for 2.5 hours. The excess thionyl chloride was evaporated and the residue was purified by distillation. 4.6 g of 3-chloromethyl-2,6-dimethylbenzoyl chloride, p..e were obtained. 165V12 Torr. (ii) 4.5 g of 3-chloromethyl-2,6-dimethylbenzoyl chloride were added dropwise at room temperature while stirring to 70 ml of methanol. The mixture was then stirred at room temperature for 3 hours and the excess methanol was evaporated. Purification of the residue by distillation gave 4.1 g of methyl 3-chloromethyl-2,6-dimethylbenzoate, eg 90 ° C / 0.08 Torr, which crystallized after resting (mp 38-41.5 ° C). (iii) 50 ml of a 1.2 M solution of diisobutylaluminium hydride in toluene was added while stirring at 0 ° C for a period of 10 minutes, to a solution of 3.2 g of methyl 3-chloromethyl-2,6-dimethylbenzoate. in 50 ml of tetrahydrofuran. The mixture was then stirred at 0 ° C for another 3.5 hours, then treated successively with 5 ml of ethyl acetate and 25 ml of 2N hydrochloric acid at 0 ° C while stirring. The mixture was stirred at room temperature for another hour and extracted twice with ethyl acetate. After drying over anhydrous magnesium sulfate, the solvent was evaporated. Recrystallization of the residue from hexane gave 2.3 g of 3-chloromethyl-2,6-di-ethylbenzyl alcohol, m.p. 96-98 ° C. (iv) A solution of 1.5 g of 3-chloromethyl-2,6-dimethylbenzyl alcohol in 50 ml of dichloromethane was treated with 6.9 g of manganese dioxide and stirred at room temperature for 18 hours. The mixture was filtered and the solvent was evaporated. The residue was chromatographed on silica gel with hexane / ethyl acetate and gave 0.6 g of 3-chloromethyl-2,6-dimethylbenzaldehyde, m.p. 52-56 ° C. Examples A-E illustrate the production of pharmaceutical preparations.

EXAMPLE A Hard gelatine capsules can be produced as follows: Ingredient mg / capsule 1. Spray-dried powder containing 75% compound I 20 2. Sodium dioctyl sulfosuccinate 0.2 3. Sodium carboxymethylcellulose 4.8 4. Microcrystalline cellulose 86.0 . Talcum 8.0 6. Magnesium Stearate 1.0 Total 120 The spray-dried powder, which is based on the active ingredient, gelatin and microcrystalline cellulose and having an average active ingredient particle size of < 1 μ (measured using autocorrelation spectroscopy), moistened with an aqueous solution of sodium carboxymethylcellulose and sodium dioctylsulfosuccinate and dough. The resulting mass is granulated, dried and sieved and the granulate obtained is mixed with microcrystalline cellulose, talc and magnesium stearate. The powder is filled into size 0 capsules.

EXAMPLE B Tablets can be produced as follows: Ingredient mg / capsule 1. Compound I as finely ground powder 20. Lactose powder 100 3. White corn starch 60 4. Povidona K30 8 . White corn starch 112 6. Talc 16 7. Magnesium stearate 4 Total 320 The finely ground substance is mixed with lactose and a portion of the corn starch. The mixture is moistened with an aqueous solution of Povidone K30 and kneaded, and the resulting mass is granulated, dried and sieved. The granulate is mixed with the rest of the corn starch, talc and magnesium stearate and compressed into tablets of suitable size.

EXAMPLE C Soft gelatin capsules can be produced as follows: Ingredient mg / capsule 1. Compound I 5 2. Triglycerides 450 Total 455 g of compound I were dissolved in 90 g of medium chain triglycerides while stirring and with inert gasification and light protection. This solution was processed as a capsule filling mass for soft gelatine capsules containing 5 mg of active ingredient.

EXAMPLE D A cream can be produced in a manner known per se from the components indicated below Weight% Compound Of Formula I 0.1-5 Cetyl Alcohol 5.25-8.75 Arlacol 165 (Glyceryl / PGE 100 Stearate) 3.75-6.25 Miglyol 818 (Triglycerides Capric Acid / Capric / Linoleic Triglyceride) íl.25-18.75 Sorbitol solution 3.75-6.25 Na2-EDTA 0.075-0.125 Carbopol 934P (Carbomer 934P) 0.15-0.25 Butylated Hydroxyanisole 0.0375-0.0625 Methylparaben 0.135-0.225 Propylparaben 0.0375-0.0625 NaOH (10% solution) 0.15-0.25 Water c.s. ioo.oo EXAMPLE E A gel can be produced in a manner known per se from the components indicated below: Weight % Compound of formula I 0.1-5 Pluronic L 101 (poloxamer 331) 10.00 Aerosil 200 (silicon dioxide) 8.00 Liquid PCL (fatty acid ester) 15.00 Cetiol V (decyl oleate) 20.00 Neobee oil (medium chain length triglyceride) 15.00 Eutanol 6 (octyldodecanol), q.s. 100.00 The physical properties of the preparations can be altered by varying the ratio between the adjuvants in Examples D and E. It is noted that with respect to this date, the best method known to the applicant to carry out the present invention, is the which is clear from the present description of the invention. Having described the invention as above, the content of the following is claimed as property:

Claims (19)

1. Imidazole derivatives of the general formula characterized in that R <R8> each independently means hydrogen, lower alkyl, substituted lower alkyl, lower alkenyl, lower alkoxy, substituted lower alkoxy, lower alkoxycarbonyl, halogen, hydroxy, amino, mono- or di- (lower alkyl) amino or nitro, and pharmaceutically acceptable salts thereof.
2. 2. Imidazole derivatives according to claim 1, characterized in that R1 means lower alkyl, or halogen, R2 means hydrogen, hydroxy, nitro, lower alkoxycarbonyl, di- (lower alkyl) amino-lower alkyl, morpholino-lower alkyl or -methylpiperazinyl-lower alkyl, R3 signifies hydrogen or lower alkyl, R4 signifies hydrogen, RD signifies amino or lower alkyl, R6 signifies hydrogen, R7 signifies hydrogen or lower alkyl and R8 signifies hydrogen or halogen.
3. 3. 4- [5- (4-chlorophenyl) -2- (2,4,6-trimethyl-1-phenyl) imidazol-4-yl] pyridine.
4. 4. 4- [5- (3-methylphenyl) -2- (2,4,6-trimethyl-phenyl) imidazol-4-yl] pyridine.
5. 5. 3-chloro-2- [4- (4-chlorophenyl) -5-pyridin-4-yl-imidazol-2-yl] phenylamine.
6. 6. 4- [5- (4-chlorophenyl) -2- (2,6-diisopropyl-phenyl) imidazol-4-yl] pyridine.
7. 7. 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzoate methyl.
8. 8. 4- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzyl] morpholine.
9. 9. [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzyl] dimethylamine.
10. 10. 1- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzyl] -4-methylpiperazine.
11. 11. [4- [5- (4-chlorophenyl) -2- (2,4,6-trimethy1-3-nitrophenyl) -imidazol-yl] pyridine and
12. 12. 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylphenol.
13. 13. 4- [5- (3-chlorophenyl) -2- (2,4,6-trimethyl-enyl) -imidazol-4-yl] pyridine. 4- [5- (3,4-dichlorophenyl) -2- (2,4,6-trimethylenyl) -imidazol-4-yl] pyridine. 4- [5- (4-fluorophenyl) -2- (2,4,6-trimethylphenyl) -imidazol-4-yl] pyridine, 4- [5- (4-chlorophenyl) -2- (2,6-dichlorophenyl) ) -imidazol-4-yl] pyridine, 4- [5- (2, 4-dichlorophenyl) -2- (2,6-dichlorophenyl) -imidazol-4-yl] pyridine, 4- [5- (4-chlorophenyl) -2- (2,6-dimethylphenyl) -imidazol-4-yl] pyridine 4- [5- (4-chlorophenyl) -2- (2, 3, 4, 5, 6-pentamethylphenyl) -imidazol-4-yl ] pyridine, 4- [5- (2-fluorophenyl) -2- (2,4,6-trimethylphenyl) -imidazol-4-yl] pyridine, 4- [5- (3-methoxyphenyl) -2- (2, 4,6-trimethylphenyl) -imidazol-4-yl] pyridine, 4- [5- (3-bromophenyl) -2- (2,4,6-trimethylphenyl) -imidazol-4-yl] pyridine, 4- [5 - (4-chlorophenyl) -2- (2,6-dibromophenyl) -imidazol-4-yl] pyridine, 4- [5- (4-chlorophenyl) -2- (2-chloro-6-methylphenyl) -imidazole -4-yl] pyridine, 4- [5- (-chlorophenyl) -2- (2-chloro-6-nitrophenyl) -imidazol-4-yl] pyridine, 4- [5- (4-chlorophenyl-2- ( 2-methyl-6-nitrophenyl) -imidazol-4-yl] pyridine 4- [5- (4-chlorophenyl) -2- (2-chloro-6-fluorophenyl) -imidazol-4-yl] pyridine, 4- [5- (3-chlorophenyl) -2- (2-chloro-6-nitrophenyl) -imidazol-4-yl] pyridine, 4- [5- (3,4-dichlorophenyl) -2- (2-chloro) - 6-nitrophenyl) -imidazol-4-yl] pyridine, 4- [5- (4-fluorophenyl) -2- (2-chloro-6-nitrophenyl) -imidazol-4-yl] pyridine, 4- [5- (4-chlorophenyl) -2- (2-bromo-6-methylphenyl) -imidazol-4-yl] pyridine, 4- [5- (4-bromophenyl) -2- (2-chloro-6-nitrophenyl) -imidazole -4-yl] pyridine, 4- [5- (4-chlorophenyl) -2- (2,3,5,6-tetramethylphenyl) -imidazol-4-yl] pyridine, 4- [5- (4-chlorophenyl) -2- (2-bromo-6-cloforophenyl) -imidazol-4-yl] pyridine, 4- [5- (3-bromophenyl) -2- (2-chloro-6-nitrophenyl) -imidazol-4-yl] pyridine, 4- [5- (3-methoxyphenyl) -2- (2-chloro-6-nitrophenyl) -imidazol-4-yl] pyridine, 4- [5- (4-fluorophenyl) -2- (2-bromo) -6-methylphenyl) -imidazo1-4-yl] pyridine, 4- [5- (4-chlorophenyl) -2- (2-bromo-3-methylphenyl) -imidazol-4-yl] pyridine, 4- [5- (4-fluorophenyl) -2- (2-methyl-6-nitrophenyl) -imidazol-4-yl] pyridine, 4- [5- (4-chlorophenyl) -2- (2-bromophenyl) -imidazol-4-yl ] pyridine, 4- [5- (3-bromophenyl) -2- (2-bromophenyl) -imidazol-4-yl] pyridine, dimethyl- (2- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -3-methyl-phenylamine, 4- [2- (3-bromo-2,6-dimethylphenyl) ) -5- (4-chlorophenyl) -imidazol-4-yl] pyridine 4- [5- (4-chlorophenyl) -2- (2,6-dimethyl-3-nitrophenyl) -imidazol-4-yl] pyridine, 4- [5- (4-chlorophenyl) -2- (2-fluoro-6-trifluoromethyl-phenyl) -imidazol-4-yl] pyridine, 4- [5- (4-chlorophenyl) -2- (2-allyl- 6-methylphenyl) -imidazol-4-yl] pyridine, 4- [5- (4-chlorophenyl) -2- (2-methoxymethyl-6-methylphenyl-imidazol-4-yl] pyridine, 4- [5- (4 -chlorophenyl) -2- (3-methoxy-2,6-dimethylphenyl) -imidazol-4-yl] pyridine, 4- [5- (4-chlorophenyl) -2- (2,6-dimethyl-3, 5- dinitrophenyl) -imidazol-4-yl] pyridine, 4- [5- (4-chlorophenyl) -2- (2-chloro-6-trifluoromethyl-phenyl) -imidazol-4-yl] pyridine, 1- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzyl] -4-methylpiperazine, 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2, 4, -dimethylphenol, 4- [4- (4-chlorophenyl) -5-pyridin-4- il-imidazol-2-yl] -3,5-dimethylphenol, 1- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2, 4, 6 ethyl trimethylbenzyl] piperidine-4-carboxylate, [4- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -3,5-dimethylphenoxy] ethyl acetate, 4- [ 2- (3-Azidomethyl-2,4,6-trimethylphenyl) -5- (4-chloro-phenyl) imidazol-4-yl] pyridine, [3- [5- (4-chlorophenyl) -4-pyridin-4 -yl-imidazol-2-yl] -2, 4, 6-trimethylphenyl] acetonitrile, 3- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2 , 4-dimethylphenoxy] propan-1-ol, [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -benzyl] -diethylamine, 4- [5- (4- chlorophenyl) -2- (2, 3, 6-trichlorophenyl) imidazol-4-yl] pyridine, 4- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -3, 5-dimethylphenoxy] acetamide, [3- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4-dimethylphenoxy] propyl] dimethylamine, (2RS, 6RS) ) - and (2) R, 6S) -4- [3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzyl] -2,6-dimethyl-morpholine 4- [5- (4-chlorophenyl) -2- (2,4-6-rimethyl-3-piperidin-1-yl-methylphenyl) -imidazol-1-yl] pyridine, (S) - [I- [3 - [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylbenzyl] pyrrolidin-2-yl] methanol, 3- [5- (4-chlorophenyl) ) -4-pyridin-4-yl-imidazol-2-yl] -2,4-dimethylbenzyl acetate, 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2, 4, 6-trimethylbenzyl acetate, 3- [4-pyridin-4-yl-2- (2,4,6-trimethylphenyl) imidazol-5-ylphenol, 2- [4-pyridin-4-yl-2] - (2,4,6-trimethylphenyl) imidazol-5-yl] -phenylmethanol, 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2, 4, - dimethylphenylamine, 3- [5- (4-chlorophenyl) -4-pyridin-4-yl-imidazol-2-yl] -2,4,6-trimethylphenyl) methanol, 3- [5- (4-chlorophenyl) -4 -pyridin-4-yl-imidazol-2-yl] -2, 4, -dimethyl-phenylmethanol, 3- [5- (4-chlorophenyl) -4-pyridin-4-yl) imidazol-2-yl] -2 , 4, 6-trimethylphenylamine.
14. 14. Pharmaceutical preparations, characterized in that they contain compounds according to any of claims 1-13 and pharmaceutically acceptable vehicles.
15. 15. A process for the preparation of compounds according to claim 1, characterized in that it comprises reacting a diketone of the general formula: wherein RD, R7 and R8 have the meaning indicated in claim 1, with an aldehyde of the general formula: wherein R1, R2, R3, R4 and R5 have the meaning given in claim 1 and wherein a hydroxy group in the compounds of Formulas II and III may be present in protected form, in the presence of ammonium, separating a hydroxy protecting group which may be present and, if desired, functionally modifying reactive groups present in a compound of Formula I obtained and, if desired, by converting a compound of Formula I to a pharmaceutically acceptable salt.
16. 16. Compounds according to claim 1, characterized in that they are prepared according to the method claimed in claim 15 or an obvious chemical equivalent thereof.
17. 17. The use of the compounds according to claim 1, as medicaments.
18. 18. The use of the compounds according to claim 1, for the production of pharmaceutical preparations for the treatment and prophylaxis of arteriosclerosis, psoriasis, tumors or alopecia.
19. 19. The invention as described here above.