Title of Invention

2-(2,6-DICHLOROPHENYL)-DIARYLIMIDAZOLES

Abstract

The present invention relates to compounds of the general formula (I) are valuable therapeutics for the treatment of cancer and cancer related diseases. The invention also relates to a new 2-(2,6-Dichlorophenyl)-Diarylimidazoles and their pharmaceutically acceptable salts. The compounds are protein-tyrosine kinase inhibitors, especially inhibitors of c-met kinase and are therefore excellent therapeutics for the treatment of cancer. The invention relates also to pharmaceutical compositions, which contain these new compounds as active agents for the treatment of cancer and cancer related diseases.

Full Text

2-(2,6-Dichlorophenyl)-Diarylimidazoles This invention relates to new 2-(2,6-dichlorophenyl)-diarylimidazoles and their pharmaceutical^ acceptable salts. The compounds are protein-tyrosine kinase inhibitors, especially inhibitors of c-met kinase and are therefore excellent therapeutics for the treatment of cancer. The invention relates also to pharmaceutical compositions which contain these new compounds as active agents for the treatment of cancer and cancer related diseases. Background of the Invention Protein-tyrosine kinases (PTKs), enzymes that catalyse the transfer of the 7-phosphate of ATP to tyrosine residues of protein substrates, are critical components of signalling pathways that control cellular proliferation and differentiation. PTKs can be subdivided into two large families, receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs). RTKs span the plasma membrane and contain an extra-cellular domain, which binds ligand, and an intracellular portion, which possesses catalytic activity and regulatory sequences. Most RTKs, like the hepatocyte growth factor receptor c-met possess a single polypeptide chain and are monomeric in the absence of ligand. Ligand binding to the extracellular portion of RTKs, leads to dimerisation of monomeric receptors resulting in autophosphorylation of specific tyrosine residues in the cytoplasmic portion (for review see: Blume-Jensen, P., and Hunter, T., Nature 411 (2001) 355-365; Hubbard, S.R., et al, J. Biol. Chem. 273 (1998) 11987-11990; Zwick, E., et al., Trends Mol. Med. 8 (2002) 17-23). In general, tyrosine autophosphorylation either stimulates the intrinsic catalytic kinase activity of the receptor or generates recruitment sites for downstream signalling proteins containing phosphotyrosine-recognition domains, such as the Src homology 2 (SH2) domain or the phosphotyrosine-binding (PTB) domain. protein tyrosine kinases play a critical role in intracellular signal transduction pathways leading to diverse cellular responses such as proliferation, apoptosis and differentiation . Consequently these enzymes have become primary targets for the development of novel therapeutics designed to block cancer cell proliferation, metastasis, angiogenesis and promote apoptosis. The strategy that has progressed farthest in clinical development is the use of monoclonal antibodies to target growth factor receptor tyrosine kinases. The use of small molecule tyrosine kinase inhibitors however could have significant theoretical advantages over monoclonal antibodies. Small molecule inhibitors could have better tissue penetration, could have activity against intracellular targets and mutated targets and could be designed to have oral bioavailability. Several lead compounds have shown promising activity against such targets as the EGFR, the vascular endothelial cell growth factor receptor and bcr-abl. The hepatocyte growth factor receptor c-met was first identified as an activated oncogene in an N-methyl-N'-nitrosoguanidinic treated human osteogenic sarcoma cell line (M^NG-HOS) by its ability to transform NIH 3T3 mouse fibroblasts. The receptor encoded by the c-met protooncogene (located on chromosome 7) is a two-chain protein composed of 50 kDa(a) chain disulfide linked to a 145 kDa(p) chain in an a(3 complex of 190 kDa. The a chain is exposed at the cell surface whilst the (5 chain spans the cell membrane and possesses an intracellular tyrosine kinase domain. The presence of this intracellular tyrosine kinase domain groups c-met as a member of the receptor tyrosine kinase (RTK) family of cell surface molecules. Hepatocyte growth factor (HGF), also known as Scatter Factor (SF), is a multifunctional cytokine that elicits diverse responses in different cells and tissues. Since its initial discovery and characterisation HGF/SF has been the subject of intense research, particularly regarding its role in cancer development and progression. Much evidence now points to its role as a regulator of carcinogenesis, cancer invasion and metastasis (for review see: Herynk, M.H., and Radinsky, R., In Vivo 14 (2000) 587-596; Jiang, W., et al., Crit. Rev. Oncol. Hematol. 29 (1999) 209-248; Longati, P., et al, Curr. Drug Targets 2 (2001)41-55; Maulik, G., et al., CytokineGrowth Factor Rev. 13 (2002) 41-59; Parr, C, and Jiang> W.G., Histol. Histopathol. 16 (2001)251-268. HGF/SF binds to and induces tyrosine phosphorylation of the mature c-met receptor (5 chain. Such events are thought to promote binding of intracellular signalling proteins containing src homology (SH) regions such as PLC-Y, Ras-GAP, PI-3 kinase pp60c'src and the GRB-2 Socs complex to the activated receptor. Each SH2-containing protein may activate a different subset of signalling phosphopeptides thus eliciting different responses within the cell. C-met mutations have been well-described in hereditary and sporadic human papillary renal carcinomas and have been reported in ovarian cancer, childhood hepatocellular carcinoma, metastatic head and neck squamous cell carcinomas, and gastric cancer. C-met is also over-expressed in both non-small cell lung cancer and small cell lung cancer cells, in breast, colon and prostate tumors. Since c-met appears to play an important role in oncogenesis of a variety of tumors, various inhibition strategies have been employed to therapeutically target this receptor tyrosine kinase. The usefulness of inhibiting the protein-tyrosine kinase c-met for inhibiting tumor growth and invasion has been shown in many well documented preclinical experiments (e.g.: Abounader, R., et al, J. Natl. Cancer Inst. 91 (1999) 1548-1556; Laterra, J., et al., Lab. Invest. 76 (1997) 565-577; Tomioka, D., Cancer Res. 61 2001) 7518-7524; Wang, R., et al., J. Cell Biology 153 (2001) 1023-1033). WO 96/18626 describes inhibitors of tyrosine kinases and c-met kinase which are derivatives of 2-(2,6-dichlorophenyl)-4-phenyl-5-(pyridin-4yl)-lH-imidazole (examples 5, 6 and 55). However they show unfavorable cytochrome P450 interactions and also some undesirable physical properties like low bioavailability. It has now been found, that the 2-(2,6-dichlorophenyl)-4-phenyl-5-(pyrimidin-4yl)-lH-imidazoles according to this invention avoid these disadvantages and show improved properties as protein-tyrosine kinase inhibitors. Summary of the Invention The invention relates to compounds of the general formula (I) wherein X is hydrogen; OR1; SR2; (SO)R2; (S02)R2; or a group A*-Q; A1 represents a Q-C3-alkylen group; Q is OR1; SR2; SOR2; S02R2; NR3R4; NHCH2CH2NR3R4 or halogen; R1 is selected from the group consisting of hydrogen; Ci-C3-alkyl; allyl; dimethylphosphonylmethyl; 2,3-epoxy-l-propyl; (R)-2,3-dihydroxy-l- propyl; (S)-2,3-dihydroxy-l-propyl; l,3-dihydroxy-2-propyl; 3- hydroxy-2-hydroxymethyl-l-propyl; 2-methoxyethoxymethyl; 2,2- dimethyl-l,3-dioxolan-4-ylmethyl or a group Al-Q'; Q1 represents Ci-C2-alkoxy; cyano; carboxyl; Q-Q-alkoxycarbonyl; carboxamide; -CO-NR R ; CrC6-alkylsulfanyl; Ci-Ce-alkylsulfenyl; Cj- Ce-alkylsulfonyl and in case that A1 represents an 1,2-ethylen- or 1,3-propylen group, Q1 is hydroxy or NR3R4; R2 is CrQ-alkyl; dimethylphosphonylmethyl; 2,3-epoxy-l-propyl; 2,3- dihydroxy-1-propyl; 2,2-dimethyl-l,3-dioxolan-4-ylmethyl or AJ-Q]; are independendy selected from the group consisting of hydrogen; Ci-Ce-alkyl or together form a 5 to 7 membered, saturated or unsaturated ring, optionally substituted by a methyl group and containing one or two heteroatoms, independently selected from N or O; Y is hydrogen or a group A -R; A2 is CrC5-alkylen> which may be optionally substituted by Ci-C6-alkyl; phenyl or by hydroxy; R represents hydroxy; linear or branched Ci-C6-alkoxy; amino; dimethylamino; diethylamino; f-butyloxycarbonylamino; carboxyl; Q-Ce-alkoxycarbonyl; triazolyl; cyano; piperidino; 1-pyrrolidinyl; morpholino; 4-methylpiperazin-l-yl; OA]-NR3R4; S-A'-NR^4; 4-carboxyphenyl; furan-3-yl; thiophen-2-yl or 3-methylthiophen-2-yI; Z represents one or two substituents independently selected from the group consisting of halogen; hydroxy; allyloxy; methyl; Q-Cs-alkoxy; methoxymethoxy; (2-methoxyethoxy)methyloxy; methylthio; ethoxymethoxy; methylendioxy; ethynyl; trimethylsilylethynyl and benzyloxy which is optionally substituted by halogen; methoxy; cyano; nitro; methylendioxy; carboxy or ethoxy; and to pharmaceutical^ acceptable salts thereof. It was surprisingly found that the pharmaceutical and anti-tumorigenic activities, due to the c-met inhibition of the compounds according to this invention are especially Provided by the presence of a 2,6-dichlorophenyl residue in 2-position of the imidazole ring. ■■' • '-■** Detailed Description of the Invention Preferred Ci-C6-alkyl groups with regard to R1, R2, R3, R4 and A2 are methyl, ethyl and propyl. Preferred Q-Ce-alkoxy groups with regard to Q , R and Z are methoxy, ethoxy or isopropyloxy. Preferred ring systems, formed by R3 and R4 together represent 1-pyrrolidinyl-, piperidino-, morpholino- or 4-methylpiperazin-l-yl. Preferably X = A*-Q represents -CH2OH or -CH2-CH2-OH. Preferably X = -O-A'-Q1 is -0-CH2-CH2-OH; -O-CH2-CO0H or -0-CH2-CN. Preferred groups for Y = A2-R are 2-hydroxyethyl; 3-hydroxypropyl, 2-methoxyethyl; 3-methoxypropyl; (R)-2,3-dihydroxy-l-propyl; (S)-2,3-dihydroxy-1-propyl; (R)-3-hydroxybutyl; (S)-3-hydroxybutyl; 2-morpholinoethyl; 3- morpholinopropyl; (CH2)3COOH; 2-(4-methylpiperazin-l-yl)ethyl; 3-Hydroxy-2,2-dimethylpropyl; 3-hydroxy-1-phenylpropyl; 3-tert-butyloxyethyl; 2-aminoethyl; 3-aminopropyI; 4-aminobutyl; 2-(N,N-dimethylamino)ethyl; 3-(N,N-dimethylamino)propyl; 3-(pyrrolidin-l-yl)propyl; CH2COOH; (CH2)2COOH; CH(C2H5)COOH; (CH2)3COOC(CH3)3; (CH2)2-N-COOC(CH3)3; (CH2)3-N-COOC(CH3)3; (CH2)2-0-(CH2)2-N(CH3)2; (CH2)2-0-(CH2)2-NH2; (CH2)2-S-(CH2)2-N(CH3)2; (CH2)2-S-(CH2)3-N(CH3)2; (CH2)rS-(CH2)rN(CH3)2; (CH2)3-S-(CH2)3-N(CH3)2; (1,2,4-triazol-l-yl)ethyI;3-(l,2,4-triazol-3-yl)propyl; Halogen is fluorine, chlorine, bromine or iodine. Preferably said substituent X is located in the 4-position of the phenyl ring, whereas said substituent Z is preferably located in the 3- or 4-position. If Z represents benzyloxy or a substituted benzyloxy group, Z is preferably located in the 3-position. Especially preferred are compounds of the general formula (I) and pharmaceutically acceptable salts thereof, wherein Z is selected from the group consisting of 3-chloro; 4-chloro; 3-bromo; 3-iodo; 3-ethynyl; 3-methoxymethoxy; 3-(2-methoxyethoxy)methyloxy; 3-methylthio; 3-ethoxymethoxy; 3,4-methylendioxy or 3-benzyloxy which is optionally substituted by halogen; methoxy; cyano; nitro; methylendioxy; carboxy or ethoxy. Also especially preferred are compounds of the general formula (I), wherein X is hydrogen; OR1; (SO)CH3; (S02)CH3; or a group CH2-Q; Q is OH; NR3R4 or NHCH2CH2NR3R4; R1 is selected from the group consisting of hydrogen; dimethylphosphonylmethyl; (R)-2,3-dihydroxy-l-propyl; (S)-2,3- dihydroxy-1-propyl; l,3-dihydroxy-2-propyl; 3-hydroxy-2- hydroxymethyl-1 -propyl; 2-methoxyethoxymethyl; 2,2-dimethyl-l,3-dioxolan-4*ylmethyl or a group A^Q1; A1 represents a methylen, ethylen or propylen group; Q1 is cyano; carboxyl; carboxamide; -CO-NR3R4 and in case that A1 represents an 1,2-ethylen- or 1,3-propylen group, also can be hydroxy or NR3R4; R3, R4 are independently selected from the group consisting of hydrogen, methyl, ethyl, 2-morpholinoethyl or together form a 5 to 7 membered, saturated or unsaturated ring, optionally substituted by a methyl group and containing one or two heteroatoms, independently selected from N or O; Y represents 2-hydroxyethyl; 3-hydroxypropyl; 2-methoxyethyl; 3-methoxypropyl; (R)-2,3-dihydroxy-l -propyl; (S)-2>3-dihydroxy-l-propyl; (R)-3-hydroxybutyl; (S)-3-hydroxybutyl; 3-Hydroxy-2,2-dimethylpropyl; 2-morpholinoethyl; 3-morphoIinopropyl; 2-(4-methylpiperazin-l-yl)ethyl; 3-hydroxy-l-phenylpropyl; 2-aminoethyl; 3-aminopropyl; 4-aminobutyl; 2-(N,N-dimethylamino)ethyl; 3-(N,N-dimethylamino)propyl; 3-(pyrrolidine l-yl)propyl; CH2COOH; (CH2)2COOH; (CH2)3COOH; CH(C2H5)COOH; (CH2)2-0-(CH2)2-N(CH3)2; (CH2)2-0-(CH2)2-NH2; (CH2)rS-(CH2)2-N(CH3)2; (CH2)2-S-(CH2)3-N(CH3)2; (CH2)3-S-(CH2)2-N(CH3)2 or (CH2)3-S-(CH2)3-N(CH3)2; Z is selected from the group consisting of 3-chloro; 4-chloro; 3-bromo; 3-iodo; 3-ethynyl; 3-methoxymethoxy or 3-benzyloxy which is optionally substituted by halogen; methoxy; cyano; nitro; methylendioxy; carboxy or ethoxy; with said substituent X being located in the 4-position of the phenyl ring, and pharmaceutically acceptable salts thereof. Also especially preferred are compounds of the general formula (I), wherein X is hydrogen; OR1; (SO)CH3; (S02)CH3; or a group CH2-Q; Q is OH; NR3R4 or NHCH2CH2NR3R4; R1 is selected from the group consisting of hydrogen; dimethylphosphonylmethyl; (R)-2,3-dihydroxy-l-propyl; (S)-2,3- dihydroxy-1-propyl; l,3-dihydroxy-2-propyl; 3-hydroxy-2- hydroxymethyl-1-propyl; 2-methoxyethoxymethyl or a group A^Q1; A1 represents a methylen, ethylen or propylen group; Ql represents cyano, carboxyl and in case that A1 represents an 1,2-ethylen- or 1,3-propylen group, also can be hydroxy or NR'R4; R3, R4 are independently selected from the group consisting of hydrogen, methyl, ethyl or together form a 5 to 7 membered, saturated or unsaturated ring, optionally substituted by a methyl group and containing one or two heteroatoms, independently selected from N or O; Y is 2-hydroxyethyl; 3-hydroxypropyl; (R)-2,3-dihydroxy-l-propyl; (S)-2,3-dihydroxy-1-propyl; 2-morpholinoethyl; 3-morpholinopropyI; 2-(4-methylpiperazin-l-yl)ethyl; 2-aminoethyl; 3-aminopropyl; 2-(N,N-dimethylamino)ethyl; 3-(N,N-dimethylamino)propyl or 3-(pyrrolidin-l-yl)propyl; Z is selected from the group consisting of 3-chloro; 4-chloro; 3-bromo; 3-iodo; 3-ethynyl; 3-methoxymethoxy or 3-benzyloxy which is optionally substituted by halogen; methoxy or cyano; with said substituent X being located in the 4-position of the phenyl ring, and pharmaceutical^ acceptable salts thereof. Most preferred are the compounds of the general formula (I), as defined by the non-limiting examples HI. 1.1 till HI7.3.5 and pharmaceutical^ acceptable salts thereof. Formula (I) represents 2-(2,6-dichlorophenyl)-4-phenyl-5-(4-pyrimidinyl)-lH-imidazoles which are the tautomers of 2-(2,6-dichlorophenyl)-5-phenyl-4-(4-pyrimidinyI)-lH-imidazoles. Both tautomers represent the same structure, their nomenclature may be used interchangeably and both tautomers are part of the invention. The compounds of the present invention may contain one or more chiral centers and may occur as racemates, racemic mixtures, and as individual diastereomers, with all possible isomers, including optical isomers, being included within the scope of the present invention. Compounds of the general formula (I) can be prepared by reacting a compound of the general formula (VI) or (VII) with an amine Y-NH2, wherein X, Y and Z have the significance as defined herein before, at a temperature in the range of 80 to 180°C and subsequent isolation of said compound. Preferably stoichiometric amounts or an excess of said amines are used. The reaction can be performed without solvent or in a solvent like dioxane, dimethoxyethane, N-methylpyrrolidone or toluene. Y-NhL heat 1 ^ I neat or with solvent Compounds of the general formula (VI) and (VII) can be obtained by oxidation of the sulfide group of the thioethers, described by the general formula (V). To obtain the sulfoxides of the general formula (VI) the oxidation is preferably carried out by using 3-chloroperbenzoic acid. For the synthesis of the sulfones of the general formula (VII) oxone™ is preferably used. The thioethers of the general formula (V) can be obtained by N-deoxygenation of compounds of the general formula (IV). This reaction is preferably carried out using ethyl bromoacetate in the presence of triethylamine (Chem. Pharm. Bull. 1981, 29, 3145). Alternatively, this reduction can be achieved by the use of triethylphosphite in dimethylformamide. A compound of the general formula (IV) can be obtained by reacting a compound of the general formula (III) with a compound of the general formula (II), wherein the substituents X and Z have the significance as defined hereinbefore. This reaction is a condensation and is preferably carried out in the presence of ammonia, using methods which are known for other aldehydes. A further embodiment of the invention is the use of a compound of the general formula (II), wherein the substituent X has the significance as defined hereinbefore, for the manufacture of a compound of the general formula (I) as described in the above-mentioned process. A further embodiment of the invention is a compound of the general formula (II), wherein X is OR1; SR2; (SO)R2; (S02)R2 or CH2-Q; Q represents OR1; SR2; SOR2; S02R2; NR3R4; NH-CH2-CH2NR3R4 or halogen; Rl is selected from the group consisting of hydrogen; CrC3-alkyl; allyl; dimethylphosphonylmethyl; (R)-2,3-dihydroxy-l-propyl; (S)-2,3-dihydroxy-l-propyl; l,3-dihydroxy-2-propyl; 3-hydroxy- 2-hydroxymethyl-l-propyl; 2-methoxyethoxymethyl; 2,2- dimethyl-l,3-dioxolan-4-ylmethyl; trifluoromethylsulfonyl; trimethylsilanyl; triisopropylsilanyl; t-butyldimethylsilanyl; phenyldimethylsilanyl; l,3-di-t-butyldimethylsilanyloxy-2- propyl; 3-t-butyldimethylsilanyloxy-2-t- butyldimethylsilanyloxymethyl-1-propyl or a group A^Q1; A1 represents a methylen, ethylen or propylen group; Q1 means cyano; carboxyl; COOCH3; COOCH2CH3; R2 is CrC6-alkyl; CH2-COO-CHrCH3; dimethylphosphonylmethyl; 2,3-epoxy-l-propyl; 2,3-dihydroxy-l-propyl; 2-hydroxy-l-ethyl; 2,2-dimethyl-l,3-dioxolan-4-ylmethyl or A^Q1; are independendy selected from the group consisting of hydrogen; methyl; ethyl; 2-morpholinoethyl or together form a 5 to 7 membered, saturated or unsaturated ring, optionally substituted by a methyl group and containing one or two heteroatoms, independently selected from N or O, with the proviso, that X = OR1 is not OH or O-allyi. Preferably said substituent X is located in the 4-position of the phenyl ring. 2,6-dichlorobenzaldehydes are valuable intermediates for the manufacture of the compounds of the general formula (I) according to the invention. 2,6-dichloro-3-hydroxybenzaldehyde and 2,6-dichloro-4-hydroxybenzaldehyde are known from the state of the art. The 2,6-dichloro-3-hydroxybenzaldehyde has been synthesized from 3-hydroxybenzaldehyde (Eur. J. Med. Chem. 1993, 28, 103-115), but this requires the use of highly toxic chlorine gas and leads to side products because of overoxidation. The procedure disclosed in this invention (example A2) avoids these disadvantages. 2,6-dichloro-4*hydroxybenzaldehyde can be prepared from 3,5-dichlorophenol by either a Reimer-Tiemann reaction (J. Med. Chem. 1988, 31, 72-83) or by a bromination/Grignard sequence (WO 01/44154). The Reimer-Tiemann procedure does not allow an economically preparation due to very low yields ( This invention provides an improved process for the manufacture of 2,6-dichloro- 3-hydroxybenzaldehyde and 2,6-dichloro-4-hydroxybenzaldehyde. This process is characterized by the metallation of protected 2,4-dichlorophenol or 3,5- dichlorophenol with a lithium base, followed by reaction with an ester or amide of formic acid and the deprotection and isolation of said compounds. A suitable lithium base is methyllithium, n-butyllithium, sec-butyllithium, t-butyllithium, lithiumdiisopropylamide or lithium bistrimethylsilylamide, prefered is butyllithium. An appropriate solvent is diethyl ether, tetrahydrofurane or 1,2- dimethoxyethane, preferred is tetrahydrofurane. The metallation step is performed at -100°C to -60°C, preferably at -80°C to -70°C. Suitable protecting groups are triisopropylsilanyl, t-butyldimethylsilanyl or phenyldimethylsilanyl, prefered is triiso-propylsilanyl. Suitable derivatives of formic acid are methyl formate, ethylformate, dimethylformamide or N-formylpiperidine, preferred is dimethylformamide. This procedure can also be applied for the manufacture of 2,6- dichloro-3-hydroxymethylbenzaldehyde and 2,6-dichloro-4- hydroxymethylbenzaldehyde according to this invention. The term "pharmaceutically acceptable salt" as used herein before refers to conventional acid-addition salts or base-addition salts that retain the biological effectiveness and properties of the compounds of formula (I) and are formed from suitable non-toxic organic or inorganic acids or organic or inorganic bases. Sample acid-addition salts include those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, phosphoric acid and nitric acid, and those derived from organic acids such as p-toluenesulfonic acid, salicylic acid, methanesulfonic acid, oxalic acid, succinic acid, citric acid, malic acid, lactic acid, fumaric acid, and the like. Sample base-addition salts include those derived from ammonium, potassium, sodium and, quaternary ammonium hydroxides, such as for example, tetramethylammonium hydroxide. The chemical modification of a pharmaceutical compound (i.e., a drug) into a salt is a technique well known to pharmaceutical chemists to obtain improved physical and chemical stability, hygroscopicity, flowability and solubility of compounds (see, e.g., H. Ansel et. al, Pharmaceutical Dosage Forms and Drug Delivery Systems, 6th ed., (1995), pp. 196 and 1456-1457. The compounds of formula (I) and the pharmaceutically acceptable salts of the compounds of formula (I) can be used as medicaments, e.g. in the form of pharmaceutical preparations. The pharmaceutical preparations can be administered orally, e.g., in the form of tablets, coated tablets, drag£es, hard and soft gelatine capsules, solutions, emulsions or suspensions. The administration can, however, also be effected rectally, e.g. in the form of suppositories, parenterally, e.g. in the form of injection solutions. The compounds of formula (I) can be processed with pharmaceutically inert, inorganic or organic carriers for the production of pharmaceutical preparations. Lactose, corn starch or derivatives thereof, talc, stearic acids or its salts and the like can be used, for example, as such carriers for tablets, coated tablets, drag£es and hard gelatine capsules. Suitable carriers for soft gelatine capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like. Depending on the nature of the active substance no carriers are, however, usually required in the case of soft gelatine capsules. Suitable carriers for the production of solutions and syrups are, for example, water, polyols, glycerol, vegetable oil and the like. Suitable carriers for suppositories are, for example, natural or hardened oils, waxes, fats, semi-liquid or liquid polyols and the like. The pharmaceutical preparations can, moreover, contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorants, salts for varying the osmotic pressure, buffers, masking agents or antioxidants. They can also contain still other therapeutically valuable substances. Medicaments containing a compound of formula (I) or a pharmaceutically acceptable salt thereof and a therapeutically inert carrier are also an object of the present invention, as is a process for their production, which comprises bringing one or more compounds of formula (I) and/or pharmaceutically acceptable salts and, if desired, one or more other therapeutically valuable substances into a galenical administration form together with one or more therapeutically inert carriers. Because of their activity as tyrosine kinase inhibitors, preferably of c-met kinase, compounds of the general formula (I) are valuable ingredients of therapeutics aiming at the treatment of cancer and other diseases that correspond with enhanced expression of the c-met receptor or related kinase receptors. Typically compounds of the general formula (I) block the phosphorylation activity of c-met kinase with an IC50 of 0.5 nM to 5 ^M. Therefore the dosage of a compound according to this invention can vary within wide limits and will also have to be adjusted to the individual requirements in each particular case. In the case of oral administration the dosage for adults can vary from about 0.01 mg to about 1000 mg ^i day of a compound of general formula (I) or of the corresponding amount of a pharmaceutically acceptable salt thereof. The daily dosage may be administered as single dose or in divided doses and, in addition, the upper limit can also be exceeded when this is found to be indicated. The following examples and preparations illustrate the invention but are not intended to limit its scope. Examples A Synthesis of substituted 2,6-dichlorobenzaldehydes Example Al 2,6-dichloro-4-hydroxybenzaldehyde (Al) Preparation of 3,5-dichlorotriisopropylsilyloxybenzene (Al.l) To a stirred solution of 4.08 g (25 mmol) 3,5-dichlorophenol and 6.70 g (62.5 mmol) 2,6-lutidine in 75 ml dry CH2CI2 9.96 g (32.5 mmol) triisopropylsilyltriflate was added at 0°C and the mixture was stirred for 2 hours at this temperature. After hydrolysis with water (15 ml) the organic layer was washed with saturated NaCl, dried over MgSC>4 and evaporated to dryness. Chromatography of the crude product on SiGel using iso-hexane as eluent returned Al.l as a colorless oil in quantitative yield. !H-NMR (250 MHz, CDC13) 6 = 1.03-1.15 (m, 18 H, CH3); 1.16-1.35 (m, 3 H CH); 6.73-6.80 (m, 2 H, CHarom.); 6.92-6.98 (m, 1 H, CHarom.) Scale-up To a solution of 200 g 3,5-dichlorophenol and 330 ml 2,6-lutidine in 3.0 1 dry CH2CI2 400 g triisopropyl-silyltriflate was added at 0°C within 1 h and the mixture was stirred for additional 3 hours at this temperature. After hydrolysis with 1.0 1 water the organic layer was washed with saturated NaCl, dried over MgS04 and evaporated to dryness (70°C/80 mbar). The residue was taken up in petrol ether and filtrated through SiGel to yield 360 g (92%) Al.l as colorless oil. Preparation of 2,6-dichloro-4-hydroxybenzaldehyde (Al) and 2,6-dichloro-4-triisopropylsilyloxy-benzaldehyde (Al.2) A solution of n-BuLi (2.5 M in hexane, 9.4 ml, 23 mmol) was added to a stirred solution of 7.49 g (23 mmol) Al.l in dry THF (30 ml) under nitrogen keeping the temperature below -67°C. After stirring for 45 minutes at -78°C 2.14 g (29 mmol) dry dimethylformamide was added keeping the temperature below -65°C. The mixture was allowed to warm up to -10°C. After hydrolysis with NaCl-saturated 2 N HC1 (25 ml) the phases were separated and the organic layer was dried over MgS04 evaporated to dryness. To the residue hexane (20 ml) was added and the precipitated Al (4.37 g, 23 mmol) was filtered off and washed with hexane (5ml), m.p. 229-230°C l3C-NMR (62.9 MHz, CDC13) 5 = 12.7 (CH); 17.9 (CH3); 121.5 (CHarom.); 123.4, 138.9,160.4 (Carom.); 187.9 (CH=0) Deprotection of the phenolic hydroxy group can be achieved by a standard procedure using n-Bu4NF in THF and purification by column chromatography on SiGel (iso-hexane/ethyl acetate 1:1) (see example A3). Scale-up To a solution of 360 g Al.l in 2.6 1 dry tetrahydrofurane 440 ml n-BuLi (2.7 M in hexane) was added under nitrogen keeping the temperature below -65°C. After stirring for 2 h at -70°C 120 ml dry dimethylformamide was added keeping the temperature below -65°C. The mixture was allowed to warm up to room temperature overnight. After addition of 700 ml 4 M HC1 the mixture was stirred vigorously for 1 h at room temperure. Then the phases were separated (addition of solid NaCl may be necessary) and the organic layer was dried over sodium sulphate and was reduced in vacuo. Recrystallization of the precipitate from toluene/tetrahydrofurane yielded 154 g (70%) Al. Example A2 2,6-dichloro-3-hydroxybenzaldehyde (A2) Preparation of 2,4-dichlorotriisopropylsilyloxybenzene (A2.1) An analogous reaction to that described in example Al.l, but starting with 2,4-dichlororphenol gave the title compound as a colorless oil in quantitative yield. 'H-NMR (250 MHz, CDCI3) 8= 1.07-1.18 (m, 18 H> CH3); 1.20-1.40 (m, 3 H CH); 6.82 (d, 8.8 Hz, 1 H, CHarom.); 7.07 (dd, 8.8 Hz, 2.5 Hz, 1 H, CHarom.); 7.34 (d, 2.5 HZ, 1 H, CHarom.) 13C-NMR (62.9 MHz, CDC13) 5 = 13.0 (CH); 18.0 (CH3); 120.8 (CHarom.); 125.9 (Carom.); 126.2 (Caron,); 127.6,130.1 (CHarom.); 151.0 (Carom.) dried over sodium sulphate. The solution was reduced to about 100 g and 200 ml warm petrol ether were added and shortly warmed up to 50°C. After standing at room temperature overnight the precipitated A3 was filtered off and washed with petrol ether/ethyl acetate (15:1). Yield: 24.3 g (66%). Purification of the mother liquor by column chromatography yielded another 4 g A3. Example A4 Preparation of methyl (3,5-dichloro-4-formylphenoxy)acetate (A4) A mixture of 382 mg (2.0 mmol) Al> 337 mg (2.2 mmol) methyl bromoacetate and 387 mg (2.8 mmol) potassium carbonate in 6 ml dry acetone were stirred for 2 h at 60°C. After filtration and removal of the solvent the residue was purified by column chromatography on SiGel (hexane/ethyl acetate 4:1). Yield: 508 mg (97 %) A4, colorless solid. Example A5 Preparation of ethyl (3,5-dichloro-4-formylphenoxy)acetate (A5) dry 2-butanone at -78°C 7.1 g (101 mmol) sodium thiomethylate was added and the stirred suspension was allowed to warm up to room temperature overnight. All volatile components were removed in vacuo, water (200 ml) was added and the mixture was extracted three times with CH2CI2 (100 ml each). The combined organic layers were dried over Na2S04 and concentrated under reduced pressure to 1/3. 12.0 g (59%) A9.1 precipitated on overnight standing at -78°C and was used without further purification. An analytical sample was purified by column chromatography on SiGel (iso-hexane/ethyl acetate 9:1). 'H-NMR (250 MHz, CDC13) 5 = 2.52 (s, 3 H, SCH3); 7.18 (s, 2 H, CHarom.) 13C-NMR (62.9 MHz, CDC13) 5 = 14.9 (SCH3); 109.5 (CaromJ; 113.8 (CN); 124.0 (CHarom.); 138.4,149.0 (Carom.) Preparation of 2,6-dichloro-4-thiomethylbenzaldehyde (A9) A solution of 11.82g (54 mmol) A9.1 in 65 ml dry CH2CI2 was cooled to -3°C and a solution of 9.24 g (65 mmol) diisobutylaluminium hydride in 65 ml dry CH2CI2 was added slowly keeping the temperature below 1°C. After 30 minutes under stirring at 0°C the reaction was allowed to warm up to room temperature and stirred for additional 75 minutes. The reaction mixture was poured on a mixture of ice (250 g) and HCl (300 ml, 1:1) and vigorously stirred for 1 hour. The phases were separated and the aqueous layer was extracted twice with CH2CI2 (200 ml each). The combined organic layers were washed twice with 5% NaHC03 (250 ml each) once with saturated NaCl (250 ml) dried over Na2SC>4 and evaporated to dryness. Column chromatography on SiGel (iso-hexane/ethyl acetate 9:1) returned 10.7 g (48 mmol) A9 as a pale yellow solid, m.p. 87.5-89.5°C. 'H-NMR (250 MHz, CDC13) 8 = 2.53 (s, 3 H, SCH3); 7.16 (s, 2 H, CHarom.); 10.43 (s,lH,CH=0) I3C-NMR (62.9 MHz, CDCI3) 5 = 14.8 (SCH3); 125.6 (CHarom.); 125.7, 137.8, 148.4 (Carom.); 188.0 (CH=0) acetate 1:1). The solvent was removed in vacuo and the residue was partitionated between ethyl acetate and water. The organic layer was dried over sodium sulphate and evaporated to dryness. The residue was treated with ether and filtered off to yield 3.03 g (82%) A12, m.p. 83-85°C. *H-NMR (250 MHz, CDC13) 6 = 4.02(t, 2H, 2'-H)> 4.13(t, 2H, l'-H), 6.96(s, 2H, 3-H,5-H),10.50(s, 1H>CH0). 13C-NMR (62.9 MHz, CDC13) 5 = 60.9 (C-2')> 70.3 (C-l')> 116.2 (C-3,C-5), 123.1 (C-l), 139.1 (C-2,C-6), 161.9 (C-4), 187.7 (CHO). Example Al 3 2,6-dichloro-4-(2,3-dihydroxy- l-propoxy)benzaldehyde (Al 3) An analogous reaction to that described in example A12, but reacting with 3-bromo-propane-l,2-diol and sodium hydride and purification by preparative scale HPLC on RP 18 (methanol-water-gradient) yielded 25% A13, m.p. 52-55°C. ]H-NMR (250 MHz, CDC13) 5 = 1.5-2.8 (br, 2H, OH), 3.75 (mc, 1H, 3'-H), 3.88 (mc, 1H, 3'-H), 4.11 (mc, 1H, 2'-H), 4.11 (s, 2H, l'-H), 7.92 (s, 2H, 3-H/5-H), 10.40 (s, 1H, CHO). 13C-NMR (62.9 MHz, CDC13) 5 = 63.6 (C-3'), 70.26 (C-l'), 70.34 (C-2'), 116.6 (C-3/C-5), 123.7 (C-l), 139.5 (C-2/C-6), 162.0 (C-4), 188.1 (CHO). Example Al 4 3,5-dichloro-4-formylphenyl trifluoromethanesulfonate (A14) A solution of 500 mg (2.62 mmol) Al in 4.0 ml dry pyridine was cooled to 0°C and 812 mg (2.88 mmol) trifluoromethanesulfonate anhydride was added and stirred at room temperature overnight. The mixture was poured on a mixture of ice and 8 ml 6 M HC1 and extracted with ethyl acetate. The organic layer was dired over sodium sulphate, evaporated to dryness and the residue was purified by column chromatography on SiGel (heptane/ethyl acetate 5:1) yielding 680 mg (80%) A14 as a colorless oil. ]H-NMR (250 MHz, CDC13) 5 = 7.40 (s, 2H, 2-H/6-H), 10.47 (s, 1H, CHO). 13C-NMR (62.9 MHz, CDC13) 6 = 121.1 (q, CF3), 123.3 (C-2/C-6), 130.9 (C-4), 138.7 (C-3/C-5), 151.0 (C-l), 187.4 (CHO). Example Al 5 Preparation of ethyl 3,5-dichloro-4-formylbenzyloxyacetate (A15) A solution of 500 mg (2.4 mrnol) A3 in 5 ml dry dimethyl formamide under nitrogen was cooled in an ice bath and 73 mg (3.0 mmol) sodium hydride was added and the mixture was stirred for 10 minutes. After addition of 410 mg (2.6 mmol) ethyl bromoacetate the mixture was heated to 110°C for 8 h. The solvent was removed in vacuo and the residue was taken up in ethyl acetate and washed with water. The organic layer was dried over sodium sulphate and evaporated to dryness. Purification of the residue by column chromatography on SiGel (heptane/ethyl acetate 4:1) yielded 40 mg (6%) A15. 'H-NMR (500z, CDCI3) 5 = 1.24 (t, 6 Hz, 3 H, CH3); 4.11 (s, 2 H, CH2); 4.19 (q, 6 Hz, 2 H, CH2); 4.60 (s, 2 H, CH2); 6.96 (s, 2 H, CHarom.); 10.42 (CH=0) l3C-NMR (125.8 MHz, CDC13) 6 = 12.7 (CH3); 60.5 (CH2), 66.9 (CH2); 70.2 (CH2); 126.5 (C-2/C-6); 128.3 (C-4); 136.1 (C-3/C-5); 143.4 (C-l); 168.7 (COOR), 187.4 (CH=0) Example Al 6 Preparation of 2,6-dichloro-4-bromomethylbenzaldehyde (A16) To a stirred solution of 480 mg (2.3 mmol) A3 in 20 ml dry tetrahydrofurane 21.0 mg (0.8 mmol) phosporous tribromide was added and the solution was stirred for 3 hours at room temperature. After hydrolysis (15 ml) the phases were separated and the organic layer was washed with saturated NaCl (10 ml) and dried over magnesium sulphate. 236 mg (0.9 mmol) A16 was obtained by column chromatography on SiGel (iso-hexane/ethyl acetate 9:1). 'H-NMR (250 MHz, CDC13) 8 = 4.38 (s, 2 H, CH2Br); 7.42 (s, 2 H, CHarom.); 10.46 (s, 1 H, CH=0) J3C-NMR (62.9 MHz, CDC13) 8 = 29.9 (CH2Br); 130.0 (Carom.);130.2 (CaromH); 137.3,144.1 (Carom.); 188.3 (CH=0) Example Al 7 Preparation of 2>6-dichloro-4-chloromethylbenzaldehyde (A17) To a stirred solution of 470 mg (2.3 mmol) A3 and 255 mg (2.5 mmol) triethylamine in dry 20 ml dichloromethane 289 mg (2.5 mmol) methansulfonylchloride was added and the solution was stirred at room temperature overnight. After hydrolysis (15 ml) the phases were separated and the organic layer was washed with saturated NaCl (10 ml) and dried over magnesium sulphate. 236 mg (0.9 mmol) A17 was obtained by column chromatography on SiGel (iso-hexane/ethyl acetate 9:1). !H-NMR (250 MHz, CDC13) 8 = 4.52 (s, 2 H, CH2C1); 7.42 (s, 2 H, CHarom.); 10.46 (s, 1 H, CH=0) I3C-NMR (62.9 MHz, CDC13) 5 = 43.8 (CH2C1); 129.6 (CaromH); 130.0, 137.3, 143.7 (Carom.); 188.3 (CH=0) Example Al8 Preparation 2,6-dichloro-4-p-toluenesulfonyloxybenzaldehyd (A18) To a solution of 500 mg (2.44 mmol) A3 and 617 mg triethylamine in 20 ml dry dichloromethane a solution of 488 mg (2.56 mmol) p-toluenesulfonyl chloride in 5 ml solvent was added at 0-5°C and was allowed to warm up to room temperature within 1 h. The organic layer was washed with water for several times, dried over sodium sulphate and evaporated to dryness. Chromatography of the residue on SiGel (heptane/ethyl acetate 3:1) yielded 180 mg (21%) A18, m.p. 77-80°C. *H-NMR (250 MHz, CDC13): 5 = 2.48 (s, 3H, CH3), 5.03 (s, 2H, OCH2), 7.24 (s, 2H, 3-H/5-H), 7.38 (d, 2H, 2'-H/6'-H), 7.79 (d, 2H, 3'-H/5'-H), 10.42 (s, 1H, CHO). 13C-NMR (62.9 MHz, CDC13): 5 = 22.1 (CH3), 69.2 (CH2), 128.4 (C-27C-6')> 129.0 (C-3/C-5), 130.5 (C-37C-5'), 130.7, 133.0, 137.5, 140.4, 146.0 (Carom.)> 188.5 (CHO). Example AI9 Preparation of N-(3,5-dichloro-4-formyl)benzyl morpholine (A19) To a solution of 215 mg (0.8 mmol) A16 and 75 mg (0.9 mmol) morpholine in 5 ml acetonitrile 119 mg (0.9 mmol) potassium carbonate was added and the resulting mixture was strirred at 80°C for 4 hours. After filtration and removal of the solvent in vacuo 94 mg (0.3 mmol) A19 was obtained by column chromatography on SiGel (iso-hexane/ethyl acetate 4:1). lH-NMR (250 MHz, CDC13) 8 = 2.45 (d, 4.6 Hz, 4 H, OCH2); 3.48 (s, 2 H, NCH2); 3.72 (d, 4.6 Hz, 4 H, NCH2); 7.39 (s, 2 H, CHarom.); 10.46 (s, 1 H, CH=0) 13C-NMR (62.9 MHz, CDC13) 5 = 53.7 (OCH2); 62.0, 67.0 (NCH2); 129.0 (Carom.);129.9 (CaromH); 137.1,145.8 (Carom.); 188.7 (CH=0) Example A20 Preparation ethyl 3>5-dichloro-4-formylbenzylthioacetate (A20) A solution of 200 mg (0.75 mmol) A16, 98 mg (0.97 mmol) triethylamine and 99 g (0.82 mmol) ethyl thioacetate in 4.0 ml dry tetrahydrofurane was stirred at room temperature for 8 h. After removal of the solvent in vacuo the residue was partitionated between ethyl acetate and water. The organic layer was dried over sodium sulphate and evaporated to dryness. Chromatography of the residue on SiGel (heptane/ethyl acetate 10:1) yielded 180 mg (79%) A20. 'H-NMR (500Z, CDC13) 5 = 1.31 (t, 6 Hz, 3 H, CH3); 3.08 (s, 2 H, SCH2); 3.62 (s, 2 H, Ar-CH2); 4.25 (q, 6 Hz, 2 H, CH2); 7.41 (s, 2 H, CHar0m.); 10.48 (CH=0) 13C-NMR (125.8 MHz, CDC13) 5 = 14.2 (CH3); 32.3 (CH2), 35.1 (CH2); 61.6 (CH2); 129.4 (C-4); 130.0 (C-2/C-6); 137.1 (C-3/C-5); 144.6 (C-l); 169.8 (COOR), 188.3 (CH=0) Example A21 Preparation of 2,6-dichlor-4-(2-hydroxyethyl-thiomethyl)benzaldehyde (A21) To a solution of 100 mg (0.373 mmol) A16 und 32 mg (0.41 mmol) 2-thioethanol in 4 ml dry acetonitrile 67 mg (0.48 mmol) potassium carbonate was added and stirred for 4 h at 80°C. After removal of the solvent in vacuo the residue was partitionated between ethyl acetate and water. The organic layer was dried over sodium sulphate and evaporated to dryness. Chromatography of the residue on SiGel (heptane/ethyl acetate 5:1) yielded 30 mg (30%) A21. 'H-NMR (250 MHz, CDC13) 5 = 2.05 (br, 1H, OH), 2.68 (t, 2H, SCH2), 3.72 (s, 2H, Ar-CH2), 3.79 (t, CH2OH), 7.38 (s, 2H, 3-H/5-H), 10.47 (s, 1H, CHO). 13C-NMR (62.9 MHz, CDC13) 6 = 34.5 (SCH2), 35.0 (Ar-CHrS), 60.9 (CH2OH), 128.9 (C-l), 130.0 (C-3/C-5), 137.2 (C-2/C-6), 145.6 (C-4), 188.4 (CHO). Example A22 Preparation of 4-(2-morpholinoethyl)-3,5-dichloro-4-formylbenzylamine (A22) An analogous reaction to that described in example A21, but reacting with 4-(2-aminoethyl)morpholine and eluting with ethyl acetate yielded 19% All. 'H-NMR (500z, CDC13) 5 = 2.41; 2.52; 2.68; 3.66; 3.74; 7.44 (CHarom.); 10.48 (CH=0); (poor resolution in aromatic range) 13C-NMR (125.8 MHz, CDCI3) 5 = 50.8 (CH2-CH2); 54.0 (CH2-N); 56.7 (CH2-CH2); 57.9 (Ar-CH2); 66.8 (CH20); 129.1 (C-4); 129.6 (C-2/C-6); 137.0 (C-3/C-5); 146.5 (C-l); 188.3 (CH=0) Example A23 Preparation of 2,6-dichloro-4-(2-methoxy-ethoxymethoxy)-benzaldehyde (A23) To an ice cooled solution of 500 mg (2.6 mmol) Al and 342 mg (2.7 mmol) methoxyethoxymethylchloride in 5 ml dry dimethylformamide 82 mg (3.4 mmol) sodium hydride were added and the mixture was stirred at 60°C for 8 hours. The solvent was distilled off and the residue was partitionated between aqueous ammonia and ethyl acetate. The organic layer was dried over sodium sulphate and evaporated to dryness yielding 370 mg (51%) A23, which was used without further purification. 'H-NMR (250 MHz, CDC13) 5 = 3.38 (s, 3H, CH3), 3.52-3.62 (m, 2H, OCH2), 3.78-3.88 (m, 2H, OCH2), 5.32 (s, 2H, OCH20), 7.09 (s, 2H, 3-H/5-H), 10.42 (s, 1H, CHO). l3C-NMR (62.9 MHz, CDC13) 5 = 59.5 (CH3), 68.8, 71.8 (OCH2), 93.8 (OCH20), 118.0 (C-3/C-5), 124.1 (C-l), 139.2 (C-2/C-6), 160.8 (C-4), 188.1 (CHO). Example A24 Preparation of 2,6-dichloro-4-[2-(fert-butyldimethylsilanyloxy)-l-(ferf- butyldimethyl-silanyloxyrnethyl) -ethoxy] -benzaldehyde (A24) An analogous reaction to that described in example A8, but reacting with 1,3-bis-(tert-butyldimethyl-silanyloxy)propan-2-ol and eluting wifh heptane/etiiyl acetate (5:1) yielded 86% A24. 'H-NMR (400 MHz, CDCI3) 5 = -0.01 (s, 6 H, Si-CH3), 0.02 (s, 6 H, Si-CH3), 0.82 (s, 18H, 'Bu), 3.71-3.89 (m, 4H, CH2OSi), 4.71-4.79 (m, 1H, CH), 7.22 (s, 2H, 3-H/5-H), 10.27 (s, 1H, CHO). 13C-NMR (100.6 MHz, CDC13) 5 = -5.16, -5.14 (SiCH3), 18.2 (C(CH2)3), 26.0 (C(CH2)3), 62.2 (CH2OSi), 80.4 (OCH), 117.6 (C-3/C-5), 122.6 (C-l), 138.0 (C-2/C-6), 162.6 (C-4), 187.9 (CHO). Example A25 Preparation of 2,6-dichloro-4- (2-hydroxy-1 -hydroxymethyl-ethoxy) - benzaldehyde (A25) 200 mg (0.4 mmol) A24 and 1 ml (13 mmol) trifluoroacetic acid were stirred in 1 ml dichloromethane at room temperture for two hours. The mixture was evaporated to dryness and purified by preparative scale HPLC on RP 18 (methanol -water-gradient) to yield A25. 'H-NMR (400 MHz, CDC13) 5 = 3.44-3.66 (m, 4H, CH2OH), 4.44-4.56 (m, 1H, CH), 4.90 (t, 2H, OH), 7.23 (s, 2H, 3-H/5-H), 10.28 (s, 1H, CHO). 13C-NMR (100.6 MHz, CDC13) 5 = 60.1 (CH2OH), 81.5 (OCH), 117.1 (C-3/C-5), 122.0 (C-l), 137.4 (C-2/C-6), 162.4 (C-4), 187.5 (CHO). Example A26 Preparation of 2,6-dichloro-4-[3-((fert-butyldimethylsilanyloxy))-2-(terf- butyldimethy!silanyloxymethyl)-propoxy)-benzaldehyde(A26) 3.43 g (18 mmol) Al, 7.40 g (18 mmol) methanesulfonic acid 3-(tert-butyldimediylsilanyloxy)-2-(tert-butyldimet±iylsilanyloxymethyl)propyl ester (Kim, H.S., et al., J. Med. Chem. 44 (2001) 3092-3108), 3.72 g (27 mmol) potassium carbonate and 41 mg (0.15 mmol) 18-crown-6 were stirred in 40 ml dimethylformamide at 40°C overnight. 600 ml ethyl acetate and 250 ml aqueous NaCl were added. The organic layer was washed four times with saturated aqueous NaCl (80 ml each), dried over sodium sulphate and evaporated to dryness. Column chromatography of the residue on SiGel (heptane/ethyl acetate 10:1) yielded 508 mg (27%) A26. *H-NMR (400 MHz, CDC13) 5 = 0.00 (s, 12 H, Si-CH3), 0.83 (s, 18H, lBu), 2.00-2.10 (m, IH, CH), 3.60-3.73 (m, 4H, CH2OSi), 4.05-4.14 (m, 2H, 0-CH2), 7.19 (s, 2H, 3-H/5-H), 10.26 (s, IH, CHO). I3C-NMR (100.6 MHz, CDC13) 5 = -5.19, -5.14 (SiCH3), 18.3 (C(CH2)3), 26.1 (C(CH2)3), 43.6 (CH), 60.0 (CH2OSi), 67.0 (0-CH2), 116.6 (C-3/C-5), 122.7 (C-1), 138.0 (C-2/C-6), 162.5 (C-4), 188.0 (CHO). Example A27 Preparation of 2,6-dichloro-4-(3-hydroxy-2-hydroxymethyl-propoxy)- benzaldehyde (A27) An analogous reaction to that described in example A25 but starting with A26 yielded A27. Example A28 2,6-dichloro-3-hydroxymethylbenzaldehyde (A28) Preparation of 2,4-dichloro(triisopropylsilyloxymethyl)benzene (A28.1) An analogous reaction to that described in example A3.1, but starting with 2,4-dichlorobenzylic alcohol gave the title compound as a colorless oil in quantitative yield. 'H-NMR (400 MHz, CDC13) 8 = 1.1 (d, 7 Hz, 18 H, CH3); 1.15-1.29 (m, 3 H, CH); 4.83 (s, 2 H, OCH2); 7.28 (dd, 8 Hz, 2 Hz, 1 H, C5-H); 7.32 (d, 2 Hz, 1 H, C3-H); 7.59 (d, 8 Hz, 1 H, C6-H) 13C-NMR (100.6 MHz, CDC13) 8 = 12.4 (CH); 18.4 (CH3); 62.5 (OCH2); 127.4, 128.5, 128.9 (Carom.H); 132.0,133.1,138.1 (Carom.) Preparation of 2>6-dichloro-3-(triisopropylsilyloxymethyl)benzaldehyde (A28.2) An analogous reaction to that described in example A3.2, but starting with A28.1 yielded the title compound as a colorless oil that solidifies on overnight standing (eluent: fso-hexane/ethyl acetate 20:1). 'H-NMR (400 MHz, CDC13) 8 = 1.03-1.15 (m, 18 H, CH3); 1.15-1.29 (m, 3 H, CH); 4.88 (s, 2 H, OCH2); 7.44 (d, 8 Hz, 1 H, C5-H); 7.80 (d, 8 Hz, 1 H, C6-H), 10.50 (s, 1 H, C=0) 13C-NMR (100.6 MHz, CDC13) 8 = 12.3 (CH); 18.4 (CH3); 62.3 (OCH2); 129.8 (CaromH); 130.4 (Carom); 131.6 (Carom.H); 133.4, 135.0,140.3 (Carom.); 189.5 (C=0) Preparation of 2,6-dichloro-3-hydroxymethylbenzaldehyde (A28) 3.3 g (9.1 mmol) A28.2 was dissolved in dry tetrahydrofiirane (80 ml) and a solution of n-Bu4NF (10.0 ml, 1 M in THF, 10.0 mmol) was added at room temperature and stirred for 15 Minutes. After concentration in vacuo 600.0 mg (32%) A28 were isolated by column chromatography on SiGel (fso-hexane/ethyl acetate 2:1), as a colorless solid, m.p. 93-95°C. 'H-NMR (400 MHz, CDC13) 8 = 4.82 (s, 2 H, OCH2); 7.41 (d, 8 Hz, 1 H, C5-H); 7.67 (d, 8 Hz, 1 H, C6-H), 10.48 (s, 1 H, C=0) 13C-NMR (100.6 MHz, CDC13) 8 = 61.7 (OCH2); 129.5 (Carom.H); 130.5 (Carom.); 132.1(Carom.H); 134.2,135.2,139.1 (Carom.); 189.2 (C=0) B Synthesis of the "Weinreb"-type amides Example Bl 3-bromo-iV-methoxy-N-methylbenzamide (Bl) To an ice cooled solution of 48.9 g (0.491 mol) N,0-dimethylhydroxylamine hydrochloride and 140.0 ml (1.00 mol) triethylamine in 650 ml dry dichloromethane 100.0 g (0.447 mol) 3-bromobenzoyI chloride was added over a period of 30 minutes. After additional strirring for 30 minutes 370 ml water was added and the organic layer dried over sodium sulphate. Fractionated distillation in vacuo yielded 101.4 g (93%) Bl, b.p. 114-129°C/0.07 mbar, as a colorless oil. MS: 246 (API+) 'H-NMR (250 MHz, CDC13): 6 = 3.35 (s, 3H, NCH3), 3.56 (s, 3H, OCH3), 7.27 (t, 1H, 5-H), 7.58 (m, 1H, 4-H), 7.60 (m, 1H, 6-H), 7.82 (t, 1H, 2-H). Example B2 S-iodo-N-methoxy-iV-methylbenzamide (B2) An analogous reaction to that described in example Bl, but starting with 3-iodobenzoyl chloride yielded B2. MS:292(API+) Example B3 3-chloro-N-methoxy-N-methylbenzamide (B3) An analogous reaction to that described in example Bl, but starting with 3-chlorobenzoyl chloride yielded B3. MS:200(API+) Example B4 3-benzyloxy-N-methoxy-iV-methylbenzamide (B4) To a suspension of 136.8 g (0.60 mol) 3-benzyloxybenzoic acid in 1200 ml dichloromethane 60.6 g (0.6 mol) triethylamine was added at 10°C. A solution of 64.8 g (0.60 mol) ethyl chloroformiate in 100 ml dichloromethane was added over a period of 15 minutes keeping the temperature between 10°C and 15°C. After stirring for 40 minutes and addition of 58.2 g (0.60 mol) N,0-dimethylhydroxylamine hydrochloride a solution of 60.6 g (0.60 mol) triethylamine was added over a period of 20 minutes at 10-15°C. The further workup is the same as described in example Bl. Yield: 131.9 g (81%) B4. MS: 273 (API+) Example B5 3-hydroxy-N-methoxy-N-methylbenzamide (B5) To a solution of 100 g (0.37 mol) B4 in 750 ml tetrahydrofurane 10 g Pd/C (10%) were added and the mixture was hydrogenated at atmospheric pressure for 2 hours. The catalyst war filtered off and the filtrate was evaporated to yield 66.0 g B5 (98%). M&182(API+),180(API-) Example B6 3-methoxymethoxy-N-methoxy-iV-methylbenzamide (B6) 69.0 g (380 mmol) of B5 were dissolved in 500 ml of dry dimethylformamide, cooled to 0°C and 11.5 g (480 mmol) sodium hydride were added and the mixture was allowed to stirr for 10 minutes. A solution of 31.2 ml (418 mmol) (chloromethyl)methylether in 100 ml of dry diemthylformamide was added at this temperature over a period of 30 minutes. After stirring at room temperature overnight the solvent was distilled off and the residue was partitionated between 400 ml of dichloromethane and 100 ml of water. The organic layer was washed with 50 ml of aqueous sodium hydrogencarbonate and two times with water (80 ml each) and finally dried over sodium sulphate. Removing the solvent in vacuo yielded 73.5 g.(87%) B6 as a colorless oil which was used without further purification. MS: 226 (API+) Example B7 3-(4'-cyanobenzyloxy)-N-methoxy-iNT-methylbenzamid^ (B7) An analogous reaction to that described in example B6, but starting with 4-cyanobenzylic bromide yielded B7. MS: 297 (API+) Exajnple B8 3-(4'-chlorobenzyloxy)-JV-methoxy-N-methylbenzamide (B8) 1.81 g (10.0 mmol) B5, 1.57 g (11.0 mmol) 4-chlorobenzylic alcohol and 3.03 g (15.0 mmol) tributylphosphine were dissolved in 100 ml tetrahydrofurane and 3.78 g (15.0 mmol) azodicarbonylpiperidine was added at 10°C. The mixture was stirred at room temperature overnight. After removal of the precipitate the mother liquor was evaporated to dryness and the residue was taken up with ethyl acetate. After filtration and washing with aqueous sodium hydrogencarbonate, 2 N HCl and water, the organic phase was dried over sodium sulphate end the solvent was removed in vacuo. Chromatography of the residue on SiGel (n-heptane/ethyl acetate 2:1) yielded 2.8 g (90%) B8. MS: 306 (API+) Example B9 3-(4'-methoxybenzyloxy)-N-methoxy-N-methylbenzamide (B9) An analogous reaction to that described in example B8, but starting with 4-methoxybenzylic alcohol yielded B9. MS: 302 (API+) Example BIO 3-(allyloxy)-N-methoxy-N-methylbenzamide (BIO) To a solution of 10.8 g (59.6 mmol) B5 and 5.42 ml (71.5 mmol) allylic bromide in 300 ml 2-butanone 41.1 g (298 mmol) potassium carbonate were added. After stirring at 60°C for 15 hours the solvent was distilled off and the residue partitionated between ethyl acetate and water. The organic layer was dried over sodium sulphate and the solvent removed in vacuo. Yield: 12.1 g (92%) BIO as a yellowish oil which was used without further purification. MS: 222 (API-h) Example Bll 4-chloro-N-methoxy-N-methylbenzamide (Bl 1) An analogous reaction to that described in example Bl, but starting with 4-chlorobenzoyl chloride yielded Bll. MS: 200 (API+) Example B12 4-fluoro-N-methoxy-N-methylbenzamide (Bll) An analogous reaction to that described in example Bl> but starting with 4-fluorobenzoyl chloride yielded B12. MS:184(API+) Example B13 4-chloro-3-methoxy-N-methoxy-N-methylbenzamide (B13) An analogous reaction to that described in example Bl, but starting with 4-chloro-3-methoxybenzoyl chloride yielded B13. MS: 230 (API+) Example B14 3-benzyloxy-4-fluoro-N-methoxy-N-methylbenzamide (B14) An analogous reaction to that described in example B4, but starting with 3-benzyloxy-4-fluorobenzoic acid yielded B14. MS: 290 (API+) Example Bl5 3-benzyloxy-4-methyl-N-methoxy-N-methylbenzamide (B15) An analogous reaction to that described in example B4, but starting with 3-benzyloxy-4-methoxybenzoic acid yielded B15. MS: 286 (API+) Example B16 3-methylthio-N-methoxy-N-methylbenzamide (B16) An analogous reaction to that described in example B4, but starting with 3-methylthiobenzoic yielded acid B16. MS:212(API+) C Synthesis of the "ethanones" Example CI l-(3-bromophenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone (CI) 19.8 ml (140 mmol) diisopropylamine were dissolved in 250 ml dry tetrahydrofurane and cooled to -75°C and 87.6 ml of a solution of n-butyllithium (1.6 M in hexane, 140 mmol) was added over a period of 20 minutes. After stirring for 15 minutes at -75°C a solution of 13.1 g (93 mmol) 2-methylthio-4-methylpyrimidine in 80 ml dry tetrahydrofurane was added within 30 minutes at -75°C and the mixture was stirred for additional 15 minutes. Then a solution of 25.1 g (103 mmol) Bl was added within 30 minutes at -75°C The mixture was allowed to warm up to room temperature and was poured on 600 ml ethyl acetate/water (1:1). The aqueous layer was extracted with 50 ml ethyl acetate and the combined organic layers were dried over sodium sulphate. Removal of the solvent in vacuo yielded 23.3 g (77%) CI, m.p. 98-101°C. MS: M = 325 (ESI+), M = 323 (ESI-). 'H-NMR f250 MHz, CDCK): "enole" (75%) 5 = 2.62 (s, 3H, SCH3)> 5.97 (s, 1H, CH=C), 6.66 (s, 1H, 5-H-pyrimidine), 8.34 (d, 1H, 6-H-pyrimidine), 14.7 (s, 1H, OH). "keto" (25%) 5 = 2.52 (s, 3H, SCH3), 4.35 (s, 2H, CH2), 6.97 (d, 1H, 5-H-pyrimidin), 8.46 (d, 1H, 6-H-pyrimidin). Example C2 l-(3-iodophenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone (C2) An analogous reaction to that described in example CI, but starting with B2 yielded C2. MS:371(API+) Example C3 l-(3-chlorophenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone (C3) An analogous reaction to that described in example CI, but starting with B3 yielded C3. MS: 279 (API+) Example C4 l-(3-benzyloxyphenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone (C4) An analogous reaction to that described in example CI, but starting with B4 yielded C4. MS: 351 (API+) Example C5 l-(3-hydroxyphenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone (C5) Example C6 l-(3-metJioxymethoxyphenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone(C6) An analogous reaction to that described in example CI, but starting with B6 yielded C6. MS: 305 (API+) Example C7 l-(3-[4'-cyanobenzyloxy]phenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone (C7) An analogous reaction to that described in example CI, but starting with B7 yielded C7. MS: 376 (API+) Example C8 l«(3-[4'-chlorobenzyloxy]phenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone (C8) An analogous reaction to that described in example CI, but starting with B8 yielded C8. MS: 385 (API+) Example C9 l-(3-[4'-methoxybenzyloxy]phenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone (C9) An analogous reaction to that described in example CI, but starting with B9 yielded C9. MS: 381 (API+) Example CIO l-(3-alIyloxyphenyl)-2-(2-methyltiiiopyrimidin-4-yl)-ethanone(C10) An analogous reaction to that described in example Cl, but starting with BIO yielded CIO. MS: 301 (API+) Example Cll l-(4-cUorophenyl)-2-(2-methyllhiopyrimidin-4-yl)-ethanone (Cll) An analogous reaction to that described in example Cl, but starting with Bll yielded Cll. MS: 279 (API+) Example Cl2 l-(4-fluorophenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone(C12) An analogous reaction to that described in example Cl, but starting with B12 yielded C12. MS: 263 (API+) Example C13 l-(4-chloro-3-methoxyphenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone(C13) An analogous reaction to that described in example Cl, but starting with B13 yielded C13. MS:309(API+) Example C14 l-(3-benzyloxy-4-fluorophenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone (C14) An analogous reaction to that described in example Cl, but starting with B14 yielded C14. MS: 369 (APR) Example C15 l-(3-benzyloxy-4-methylphenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone (C15) An analogous reaction to that described in example Cl, but starting with B15 yielded C15. MS: 365 (API+) Example C16 l-(3-methylthiophenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone(C16) An analogous reaction to that described in example Cl, but starting with B16 yielded C16. MS: 291 (APR) Example C17 l-(3-trimetiiylsUylacetylenyl)-2-(2-methylthiopyrimidin-4-yl)-ethanone (C17) To a solution of 16.3 g (44.0 mmol) C2 in 260 ml dry THF at 10°C under nitrogen 1.5 g (2.2 mmol) bis-(triphenylphosphine)palladium-II-chloride, 900 mg (4.7 mmol) copper-I-iodide, 12 ml (85 mmol) trimethylsilylacetylene and 30 ml diisopropylamine were added and the mixture was stirred and successively allowed to warm up to room temperature. After stirring at room temperature overnight 260 ml water were added and the mixture was extracted twice with ether. The organic layer was separated, dried and evaporated to dryness. Column chromatography of the residue on SiGel (iso-hexane/ethyl acetate 3:1) yielded 12.5 g (83%) C17. MS: 341 (APR) D Synthesis of the "ketoximes" Example Dl l-(3-bromophenyl)«2-(2-methylthiopyrimidin-4-yl)-2-hydroxyiminoethanone(D 1) 12.75 g (39.5 mmol) CI were dissolved in a mixture of 173 ml glacial acid, 136 ml tetrahydrofurane and 17 ml water. After cooling to 5°C a solution of 3.24 g (47.0 mmol) sodium nitrite in 25 ml water was added keeping the temperature between 5°C and 10°C. The cooling was removed and the mixture stirred for 6 hours at room temperature. After removal of the solvent in vacuo 320 ml water and 320 ml ethyl acetate were added. The pH was adjusted to 8 with 3 N NaOH. The phases were separated and the aqueous layer was extracted with 50 ml ethyl acetate. The comined organic layers were dried over sodium sulphate and the solvent was removed in vacuo. The residue was treated with diethylether, filtered off and dried. Yield: 8.33 g (60%) Dl, m.p. 156-158°C. MS: M = 352 (ESI+), M = 340 (ESI-). *H-NMR (250 MHz, D*-DMSO):5 = 2.20 (s, 3H, SCH3)> 7.54 (t, 1H, 5-H-BrPh), 7.66 (d, 1H, 5-H-pyrimidine), 7.81(m, 1H), 7.92 (m, 2H), 8.70 (d, 1H, 6-H-pyrimidine), 12.9 (s, 1H, OH). Example D2 l-(3-iodophenyl)-2-(2-methylthiopyrimidin-4-yl)-2-hydroxyiminoethanone(D2) An analogous reaction to that described in example Dl, but starting with C2 yielded D2 in 88% yield. MS: 400 (API+), 398 (API-) Example D3 l-(3-chlorophenyl)-2-(2-methylthiopyrimidin-4-yl)-2- hydroxyiminoethanone(D3) An analogous reaction to that described in example Dl, but starting with C3 gave D3 in 76% yield. MS: 308 (API+) Example D4 l-(3-benzyloxyphenyl)-2-(2-methylthiopyrimidin-4-yl)-2- hydroxyiminoethanone(D4) An analogous reaction to that described in example Dl, but starting with C4 gave D4 in 86% yield. MS: M = 380 (API+), M = 378 (API-)- Example D5 l-(3-hydroxyphenyl)"2-(2-methylthiopyrimidin-4-yl)-2- hydroxyiminoethanone(D5) 334 mg (1.0 mmol) D6 were dissolved in 20 ml methanol, 200 \jl 37% HC1 were added and the mixture was stirred at room temparture overnight. After removal of the solvent column chromatography on SiGel using a heptane-ethyl acetate gradient returned 190 mg (65 %) D5 as a white solid. MS:290(API+),288(API-) ]H-NMR (400 MHz, D*-DMSO):5 = 2.22 (s, 3H, SCH3)> 7.08-7.11 (m, IH), 7.16-7.20 (m, IH), 7.20-7.24 (m, IH), 7.37 (t, 7.8 Hz, IH), 7.64 (d, 5.1 Hz, IH, 5-H-pyrimidine), 8.70 (d, 5.1 Hz, IH, 6-H-pyrimidine), 9.91 (s, IH, OH), 12.73 (s, IH, OH). 13C-NMR (101 MHz, D*-DMSO):5 = 13.6 (SCH3), 111.6, 114.7,119.9, 121.9, 130.7, 136.4, 154.2, 158.2,158.8,159.4, 171.8, 193.5 Example D6 l-(3-methoxymethoxyphenyl)-2-(2-methyltiiiopyrimidin-4-yl)-2-hydroxyiniino- ethanone(D6) An analogous reaction to that described in example Dl, but starting with C6 gave D6 in 79% yield. MS: 334 (API+), 332 (API-) Example D7 l-(3-[4,-cyanobenzyloxy]phenyl)-2-(2-methylthiopyrimidin-4-yl)-2-hydroxyimino-ethanone (D 7) An analogous reaction to that described in example Dl, but starting with C7 gave C7 in 72% yield. MS: 405 (API+) Example D8 l-(3-[4/-chlorobenzyloxy]phenyl)«2-(2-methylthiopyrimidin-4-yl)-2- hydroxyimino-ethanone(D8) An analogous reaction to that described in example Dl, but starting with C8 gave D8 in 66% yield. MS: M = 414 (API+), 412 (API-) Example D9 l-(3-[4'-methoxybenzyIoxy]phenyl)-2-(2-methylthiopyrimidin-4-yl)-2-hydroxyimino-ethanone(D9) An analogous reaction to that described in example Dl, but starting with C9 gave D9 in 74% yield. MS: 410 (API+) Example DIP l-(3-allyloxyphenyl)-2-(2-methylthiopyrimidin-4-yl)«2- hydroxyiminoethanone(DlO) An analogous reaction to that described in example Dl, but starting with CIO gave D10 in 84% yield. MS: 330 (API+), 328 (API-) Example Dll l-(4-chlorophenyl)-2-(2-methylthiopyrimidin-4-yl)-2-hydroxyiminoethanone(Dl 1) An analogous reaction to that described in example Dl, but starting with Cll gave Dll in 85% yield. MS: 308 (API+), 306 (API-) Example D12 l-(4-fluorophenyl)-2-(2-methylthiopyrimidin-4-yl)-2- hydroxyiminoethanone(D12) An analogous reaction to that described in example Dl, but starting with C12 gave D12 in 72% yield. MS: 292 (API+), 290 (API-) Example D13 l-(4 ethanone(D13) An analogous reaction to that described in example Dl, but starting with C13 gave D13 in 98% yield. MS:338(API+).336(APIO Example D14 l-(3-benzyloxy-4-fluorophenyl)-2-(2-methylthiopyrimidin-4-yl)-2-hydroxyimino- ethanone(D14) An analogous reaction to that described in example Dl, but starting with C14 gave D14 in 74% yield. MS:398(API+),396(API-) Example Dl5 l-(3-benzyloxy-4-methylphenyl)-2-(2-methylthiopyrimidin-4-yl)-2- hydroxyimino-ethanone(D15) An analogous reaction to that described in example Dl, but starting with CI5 gave D15 in 79% yield. MS:394(API+),392(API-) Example D16 l-(3-methylthiophenyl)-2-(2-methylthiopyrimidin-4-yl)-2-hydroxyiminoethanone(D16) An analogous reaction to that described in example Dl, but starting with C16 gave D16 in 71% yield. MS:320(AP1+),318(API-) Example D17 l-(3-trimethylsilylacetylenyl)-2-(2-methylthiopyrimidin-4-yl)-2-hydroxyimino- ethanone(D17) An analogous reaction to that described in example Dl, but starting with C17 gave D17 in 54% yield, m.p. 140-145°C MS:370(AP1+),368(API-) E Synthesis of the "2,6-dichlorophenvI-N-hydroxy imidazoles" Example ELI 2-(2,6-dichlorophenyl)-4-(3-bromophenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (El.l) 27.9 g (79.3 mmol) Dl, 14.6 g (83.2 mmol) 2,6-dichlorobenzaldehyde and 61.0 g (793 mmol) ammonium acetate were dissolved in 550 ml glacial acid and stirred at 100°C for 150 minutes. The glacial acid was distilled off in vacuo and the residue was treated with ethyl acetate/water and justified at pH 8 with concentrated aqueous ammonia. The precipitate was filtered off, washed with ethyl acetate and dried to yield 24.8 g (62%) El, m.p. 251-253°C. The aqueous layer was extracted with ethyl acetate and the combined organic layers dried over sodium sulphate. Removal of the solvent in vacuo and treatment with diethylether yielded another 8.9 g (22%) El.l. MS: M = 509 (API+), 507 (API-) Example El .2 2-(2,6-dicUoro-4-hydroxyphenyl)-4-(3-bromophenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (El.2) An analogous reaction to that described in example El.l, but starting with Al gave E1.2in85%yield. MS: M = 525 (API+), 523 (API-) Example El.3 2-(2,6-dichloro-4-hydroxymethylphenyl)-4-(3-bromophenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (El .3) An analogous reaction to that described in example El.l, but starting with A3 gave EL3 in 99% yield. MS: M = 539 (API+), 537 (API-) Example E 1.4 2-(2,6-dichloro-4-(2-methoxy-ethoxymethoxy)phenyl)-4-(3-bromophenyl)-5-(2- methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (El.4) An analogous reaction to that described in example El.l, but starting with A23 gave El.4in72%yield. MS: M = 613 (API+), 611 (API-) Example E2.1 2-(2,6-dicUorophenyI)-4-(3-iodophenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E2.1) An analogous reaction to that described in example El.l, but starting with D2 gave E2.1in76%yield. MS: M = 555 (API+), 553 (API-) Example E2.2 2-(2,6-dichloro-4-hydroxyphenyl)-4-(3-iodophenyl)»5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E2.2) An analogous reaction to that described in example El.l, but starting with D2 and Al gave E2.2 in 99% yield. MS: M = 571 (API+), 569 (API-) Example E2.3 2-(2,6-dichloro-4-hydroxymethylphenyl)-4-(3-iodophenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E2.3) An analogous reaction to that described in example El.l, but starting with D2 and A3 gave E2.3 in 99% yield. MS: M = 585 (API+), 583 (API-) Example E3.1 2-(2,6-dichlorophenyl)«4-(3-chlorophenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E3.1) An analogous reaction to that described in example El.l, but starting with D3 gave E3.1in85%yield. MS: M = 465 (API+),463 (API-) Example E3.2 2-(2,6-dichloro-4-hydroxyphenyl)-4-(3-cUorophenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E3.2) Example E3.3 2-(2,6-dichloro-4-hydroxymethylphenyl)-4-(3-chlorophenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E3.3) An analogous reaction to that described in example El.l, but starting with D3 and A3 gave E3.3 in 67% yield. MS: M = 495 (API+), 493 (API-) Example E4.1 2-(2,6-dichlorophenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E4.1) An analogous reaction to that described in example El.l, but starting with D4 gave E4.1in63%yield. MS: M = 535 (API+), 533 (API-) Example E4.2 2-(2,6-dichloro-4-hydroxyphenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E4.2) An analogous reaction to that described in example El.l, but starting with D4 and Al gave E4.2 in 82% yield. MS: M = 551 (API+), 549 (API-) Example E4.3 2-(2,6-dicUoro-4-hydxoxymethylphenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E4.3) An analogous reaction to that described in example El.l, but starting with D4 and A3 gave E4.3 in 74% yield. MS: M = 563 (API-) Example E4.4 2-(2,6-dichloro-4-[methoxycarbonylmethoxy]phenyl)-4*(3-benzyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E4.4) An analogous reaction to that described in example ELI, but starting with D4 and A4 gave E4.4 in 72% yield. MS: M = 623 (API+), 621 (API-) Example E4.5 2-(2,6-dichloro-4-[ethoxycarbonylmethoxy]phenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E4.5) An analogous reaction to that described in example ELI, but starting with D4 and A5 gave E4.5 in 73% yield. MS: M = 635 (API-) Example E4.6 (rac)-2-(2,6-dichloro-4-(2,2-dimethyl-[l,3]-dioxolane-4-ylmethoxy)phenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E4.6) Example E4.6.1 (R)-2- (2,6-dichloro-4- (2,2-dimethyl- [ 1,3 ] -dioxolane-4-ylmethoxy)phenyl)-4- (3- benzyIoxyphenyI)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E4.6.1) An analogous reaction to that described in example ELI, but starting with D4 and A8.1 gave E4.6.1 in 38% yield. MS: M = 665 (API+), 663 (API-) Example E4.6.2 (S)-2-(2,6-dichloro-4-(2,2-dimethyH^ benzyloxyphenyl)-5-(2-methylthiopyr™ An analogous reaction to that described in example El.l, but starting with D4 and A8.2 gave E4.6.2 in 41% yield. MS: M = 665 (API+), 663 (API-) Example E4.7 (rac)-2-(2,6-dichloro-4-(2,3-dihydroxypropoxy)phenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E4.7) Example E4.7.1 (R)-2-(2,6-dichloro-4-(2,3-dihydroxypropoxy)phenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-iniidazole (E4.7.1) E4.7.1 was isolated as a byproduct (partly deprotection of the ketal in glacial acid) from example E4.6.2 in 42% yield MS: M = 625 (API+), 623 (API-) Example E4.7.2 (S)-2-(2,6-dichloro-4-(2,3-dihydroxypropoxy)phenyl)-4-(3-benzyloxyphenyl)-5- (2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E4.7.2) E4.7.2 was isolated as a byproduct (partly deprotection of the ketal in glacial acid) from example E4.6.1 in 37% yield MS: M = 625 (API+), 623 (API-) Example E4.8 2-(2,6-dichloro-4-(dimethylphoshinoyImethoxy)phenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E4.8) An analogous reaction to that described in example El.l, but starting with D4 and A7 gave E4.8 in 79% yield. MS: M = 641 (API+), 639 (API-) Example E4.9 2-(2,6-dichloro-4-methylthiophenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthiopyrimidin-4-yI)-N-hydroxy-imidazole (E4.9) Example E4.10 2-(2,6-dichloro-4-methanesulfinylphenyl)-4-(3-benzyloxyphenyl)-5-(2-methyIthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E4.10) An analogous reaction to that described in example El.l, but starting with D4 and A10 gave E4.10 in 54% yield. MS: M = 599 (API+), 597 (API-) Example E4.11 2-(2,6-dichloro-4-methanesulfonylphenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E4.11) Example E4.12 2-(2>6-dichloro-4-cyanomethyIoxyphenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E4.12) An analogous reaction to that described in example ELI, but starting with D4 and A6 gave E4.12 in 68% yield. MS: M = 590 (API+), 588 (API-) Example E4.13 2-(2,6-dichloro-4-(N-morpholino)methylphenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E4.13) Example E4.14 2-(2,6-dichloro-4-ethoxycarbonylmethylthiomethylphenyl)-4-(3- benzyloxyphenyl)-5-(2-methylthiopyriniidin-4-yI)-N-hydroxy-imidazole (E4.14) Example E4.15 2-(2,6-dichloro-4-hydroxyethylthiomethylphenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E4.15) Example E4.16 2-(2,6-dichloro-4-(N-morpholinoethylaminomethyl)phenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E4.16) Example E4-17 2-(2,6-dichloro-4-[2-(tert-butyldimethylsilanyloxy)-l-(tert-butyldimethylsilanyloxymethyl)-ethoxy]-phenyl)-4-(3-benzyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E4J7) An analogous reaction to that described in example El.l, but starting with D4 and A24 gave E4.17 which was used without further purification, MS: M = 853 (API+) Example E4> 18 2-(2,6-dichloro-4-[3-(tert-butyldimethylsilanyloxy)-2-(tert-butyldimethylsilanyl-oxymethyl)-propoxy]-phenyl)«4-(3-benzyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E4.18) Example E5.1 2-(2,6-dichlorophenyl)-4-(3-hydroxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E5.1) Example E5.2 2-(2,6-dichloro-4-hydroxyphenyl)-4-(3-hydroxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E5.2) Example E5.3 2-(2,6-dichloro-4-hydroxymethylphenyl)-4-(3-hydroxyphenyl)-5-(2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E5.3) An analogous reaction to that described in example El.l, but starting with D5 and A3 gave E5.3 in 76% yield. MS: M = 475 (API+), 473 (API-) Example E6.1 2-(2,6-dichlorophenyl)-4-(3-methoxymethoxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E6.1) An analogous reaction to that described in example El.l, but starting with D6 gave E6.1in99%yield. MS: M = 487 (API-) Example E6.2 2-(2,6-dichloro-4-hydroxyphenyl)-4-(3-methoxymethoxyphenyl)-5-(2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E6.2) An analogous reaction to that described in example El.l, but starting with D6 and Al gave E6.2 in 99% yield. MS: M = 505 (API+), 503 (API-) Example E6.3 2-(2,6-dichloro-4-hydroxymethylphenyl)-4-(3-methoxymethoxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E6.3) An analogous reaction to that described in example El.l, but starting with D6 and A3 gave E6.3 in 99% yield. MS: M = 519 (API-h), 517 (API-) Example E6.4 2-(2,6-dichloro-4-[methoxycarbonylmethoxy]phenyl)-4-(3- methoxymethoxyphenyl)-5-(2-methylthio«pyrimidin-4-yl)-N-hydroxy-imidazole (E6.4) Example E6.5 2-(2,6-dichloro-4-[ethoxycarbonylmethoxy]phenyl)-4-(3- methoxymethoxyphenyl)-5-(2-methyltWo-pyrimidin-4-yl)-N-hydroxy-imidazole (E6.5) An analogous reaction to that described in example El.l, but starting with D6 and A5 gave E6.5 in 71% yield. MS: M = 591 (API+), 589 (API-) Example E6.6 (rac)-2-(2)6-dichloro-4-(2,2-dimethyl-[l,3]-dioxolane-4-ylmethoxy)phenyl)-4-(3-methoxymethoxy-phenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E6.6) Example E6-6.1 (R)-2-(2,6-dichloro-4-(2,2-dimethyl-[l,3]-dioxolane-4-ylmethoxy)phenyl)-4-(3-methoxy-methoxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E6.6.1) Example E6.6.2 (S)-2-(2,6"dichloro-4-(2,2-dimethyl-[l,3]-dioxolane-4-ylmethoxy)phenyl)-4-(3- methoxy-methoxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E6.6.2) Example E6.7 (rac)-2-(2,6-dichloro-4-(2,3-dihydroxypropoxy)phenyl)-4-(3-methoxymetiioxyphenyl)-5-(2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E6.7) Example E6.7.1 (R)-2-(2,6-dichloro-4-(2,3-dihydroxypropoxy)phenyl)-4-(3- metiioxymethoxyphenyl)-5-(2-methylthio-pyr^ (E6.7) Example E6.7.2 (S)-2-(2,6-dichloro-4-(2,3-dihydroxypropoxy)phenyl)-4-(3- methoxymethoxyphenyl) - 5- (2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E6.7) Example E6.8 2-(2,6-dichloro-4-(dimethyIphoshinoylmethoxy)phenyl)-4-(3- methoxymedioxyphenyl)-5-(2-metftylthio-^^ (E6.8) An analogous reaction to that described in example ELI, but starting with D6 and A7 gave E6.8 in 86% yield. MS: M = 595 (API+), 593 (API-) Example E6.9 2-(2,6-dichloro-4-methanesulfinylphenyl)-4-(3-methoxymethoxyphenyl)-5-(2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E6.9) An analogous reaction to that described in example El.l, but starting with D6 and A10 gave E6.9 in 73% yield. MS: M = 551 (API+), 549 (API-) Example E7.1 2-(2,6-dichlorophenyl)-4-(3-[4'-cyanobenzyIoxy]phenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E7.1) Example E7.2 2-(2,6-dichloro-4-hydroxyphenyl)-4-(3-[4'-cyanobenzyloxy]phenyl)-5-(2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E7.2) Example E7.3 2-(2,6-dichloro-4-hydroxymethylphenyl)-4-(3-[4'-cyanobenzyloxy]phenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E7.3) Example E7.4 2-(2,6-dichloro-4-(2-hydroxyethox)yphenyl)-4-(3-[4/-cyanobenzyloxy]phenyl)-5-(2-metliylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E7.4) An analogous reaction to that described in example ELI, but starting with D7 and A12 gave E7.4 in 84% yield. MS: M = 620 (API+), 618 (API-) Example E8.1 2-(2,6-dichlorophenyl)-4-(3-[4'-chlorobenzyloxy]phenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E8.1) An analogous reaction to that described in example ELI, but starting with D8 gave E8.1in99%yield. MS: M = 571 (API-h), 569 (API-) Example E8.2 2-(2,6-dichloro-4-hydroxyphenyl)-4-(3-[4'-chlorobenzyloxy]phenyl)-5-(2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E8.2) An analogous reaction to that described in example ELI, but starting with D8 and Al gave E8.2 in 99% yield. MS: M = 587 (API+), 585 (API-) Example E8.3 2-(2,6-dichloro-4-hydroxymethylphenyl)-4-(3-[4'-chlorobenzyloxy]phenyl)-5-(2- methylthiopyrimidin-4-yl)-N-hydroxy-imidazole(E8.3) Example E9J 2-(2,6-dichlorophenyl)-4-(3-[4^methoxybenzyloxy]phenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E9.1) Example E9.2 2-(2>6-dichloro-4-hydroxyphenyl)-4-(3-[4/-methoxybenzyloxy] phenyl)-5-(2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E9.2) Example E9.3 2-(2,6«dichloro-4-hydroxymethylphenyl)-4-(3-[4,-methoxybenzyloxy]phenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E9.3) Example El0.1 2-(2,6-dichlorophenyl)-4-(3-aUyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (E10.1) An analogous reaction to that described in example El.l, but starting with D10 gave E10.1 in 94% yield. MS: M = 485 (API+), 483 (API-) Example El 0.2 2-(2,6-dichloro-4-hydroxyphenyl)-4-(3-allyloxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (El 0.2) Example El0.3 2-(2,6-dichloro-4-hydroxymethylphenyI)-4-(3-allyloxyphenyl)-5-(2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E10.3) Example El 1,1 2-(2,6-dichlorophenyl)-4-(4-chlorophenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (El 1.1) An analogous reaction to that described in example El.l, but starting with Dll gave El 1.1 in 96% yield. MS: M = 465 (API+), 463 (API-) Example El 1.2 2-(2,6-dicMoro-4-hydroxyphenyl)-4-(4-cUorophenyl)-5-(2-methylthiopyrimidin- 4-yl)-N-hydroxy-imidazole (El 1.2) Example El 1.3 2-(2,6-dichloro-4-hydroxymethylphenyl)-4-(4-chlorophenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (El 1.3) Example El2.1 2-(2,6-dichlorophenyl)-4-(4-fluorophenyl)-5-(2-methylthiopyrunidin-4-yl)-N-hydroxy-imidazole (El 2.1) Example El 2.2 2*(2,6-dicUoro-4-hydroxyphenyl)-4-(4-fluorophenyl)-5-(2-methyllWopyrimidin-4-yl)-N-hydroxy-imidazole (E12.2) Example E12.3 2-(2,6-dichloro-4-hydroxymethylphenyl)-4-(4-fluorophenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (El2.3) Example E13.1 2-(2,6-dichlorophenyl)-4-(4-chloro-3-methoxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (El3.1) An analogous reaction to that described in example ELI, but starting with D13 gave E13.1 in 88% yield. MS: M = 495 (API+), 493 (API-) Example El3.2 2-(2,6-dichloro-4-hydroxyphenyl)-4-(4-chloro-3-methoxyphenyl)-5-(2-methylthio-pyrimidin-4-yl)-N-hydroxy-imidazole (E13.2) Example El3.3 2-(2,6-dichloro-4-hydroxymethylphenyl)-4-(4-chloro-3-methoxyphenyl)-5-(2-methylthiopyrimidin-4-yl)-N-hydroxy-imidazole (El3.3) WE CLAIM: L A compound of the general formula (I) wherein X is hydrogen; OR1; SR2; (SO)R2; (S02)R2; or a group A!-Q; A1 represents a CrC3-alkylen group; Q is OR1; SR2; SOR2; SO2R2; NR3R4; NHCH2CH2NR3R4 or halogen; R1 is selected from the group consisting of hydrogen; CrC3-alkyl; allyl; dimethylphosphonylmethyl; 2,3-epoxy-l-propyl; (R)-2,3- dihydroxy-1-propyl; (S)-2)3-dihydroxy-l-propyl; 1,3-dihydroxy- 2-propyl; 3-hydroxy-2-hydroxymethyl-l-propyl; 2- methoxyethoxymethyl; 2,2-dimethyl-l,3-dioxolan-4-ylmethyl or a group A^Q1; Q1 represents CrC2-alkoxy; cyano; carboxyl; CrC6-allcoxycarbonyl; carboxamide; -CO-NRV; CrC6-alkylsulfanyl; CrC6- alkylsulfenyl; Ct-Cg-alkylsulfonyl and in case that A1 represents an 1,2-ethyIen- or 1,3-propyIen group, Q1 is hydroxy or NR3R4; R is CrCe-alkyl; dimethylphosphonylmethyl; 2,3-epoxy-l-propyI; 2,3-dihydroxy-l-propyl; 2,2-dimethyl-l,3-dioxolan-4-ylmethyl or Al-Q!; R3, R4 are independently selected from the group consisting of hydrogen; CrQ-alkyl or together form a 5 to 7 membered, saturated or unsaturated ring, optionally substituted by a methyl group and containing one or two heteroatoms, independently selected from N or O; Y is hydrogen or a group A -R; A2 is Q-Cs-alkylen, which may be optionally substituted by Ci-C6- alkyl; phenyl or by hydroxy; R represents hydroxy; linear or branched CpCe-alkoxy; amino; dimethylamino; diethylamino; t-butyloxycarbonylamino; carboxyl; CrCg-alkoxycarbonyl; triazolyl; cyano; piperidino; 1- pyrrolidinyl; morpholino; 4-methylpiperazin-l-yl; O-A -NR R ; S-A'-NR^4; 4-carboxyphenyl; furan-3-yl; thiophen-2-yl or 3- methylthiophen-2-yl; Z represents one or two substituents independendy selected from the group consisting of halogen; hydroxy; allyloxy; methyl; Ci-Cs-alkoxy; methoxymethoxy; (2-methoxyethoxy)methyloxy; methylthio; ethoxymethoxy; methylendioxy; ethynyl; trimethylsilylethynyl and benzyloxy which is optionally substituted by halogen; methoxy; cyano; nitro; methylendioxy; carboxy or ethoxy; and pharmaceutical^ acceptable salts thereof. 2. A compound according to claim 1> wherein alkyl groups with regard to R , R~, R* T R and A are methyl, ethyl or propyl; alkoxy groups with regard to Q\ R and Z are methoxy, ethoxy or isopropyloxy; ring systems, formed by R and R together represent 1-pyrrolidinyl-, piperidino-, morpholino- or 4-methylpiperazin-l-yl; X = A'-Q represents -CH2OH or -CHrCH2-OH; X = -O-A'-Q1 is ~0-CH2-CH2-OH; -0-CHrCOOH or -0-CHrCN; Y = A2-R is 2-hydroxyethyl; 3-hydroxypropyl; 2-methoxyethyl; 3-methoxypropyl; (R)-2,3-dihydroxy-l~propyl; (S)-2,3-dihydroxy-l- propyl; (R)-3-hydroxybutyi; (S)-3-hydroxybutyl; 2-morpholinoethyl; 3- morpholinopropyl; (CHa^COOH; 3-(4-methylptperazin-l-yI)ethyl; 3- Hydroxy~2,2-dimethylpropyl; 3-hydroxy-1-phenylpropyl; 3~tert- butyloxyethyl; 2-aminoethyl; 3-aminopropyl; 4-aminobutyl; 2-(N,N- dimethylamino)ethyl; 3-(N,N-dimethylamino)propyl; 3-(pyrrolidin-l- yl)propyl; CH2COOH; (CH2)2COOH; CH(C2H5)COOH ; (CH2)3COOC(CH3)3; (CH2)rN-COOC(CH3)3; (CH2)3-N- COOC(CH3)3; (CH2)2-0-(CH2)2-N(CH3)2; (CH2)rO-(CH2)rNH2; (CH2)rS-(CH2)rN(CH3)2; (CH2)rS-(CH2)3-N(CH3)2; (CH2)rS-(CH2)rN(CH3)2; (CH2)3-S-(CH2)3-N(CH3)2; (l,2,4-triazol-l-yl)ethyl or 3-(l,2»4-triazol~3-yl)propyl; and said substituent X is located in the 4-position of the phenyl ring, whereas said substituent Z is located in the 3- or 4-position, with the proviso that, if Z represents benzyloxy or a substituted benzyloxy group, Z is located in the 3-position. 3. A compound according to claim 1 or 2, wherein Z is selected from the group consisting of 3-chloro; 4-chloro; 3-bromo; 3-iodo; 3-ethynyl; 3-methoxymethoxy; 3-(2-methoxyethoxy)methyloxy; 3-methylthio; 3-ethoxymethoxy; 3,4-methylendioxy; 3-benzyloxy which is optionally substituted by halogen; methoxy; cyano; nitro; methylendioxy, carboxy or ethoxy. 4. A compound according to claim 1, wherein X is hydrogen; OR1; (SO)CH3; (S02)CH3; or a group CH2-Q; Q is OH; NR3R4 or NHCH2CH2NR3R4; R1 is selected from the group consisting of hydrogen; dimethylphosphonylmethyl; (R)-2>3-dihydroxy-l-propyl; (S)-2,3-dihydroxy-1-propyl; l,3-dihydroxy-2~propyl; 3-hydroxy-2-hydroxymethyl-1-propyl; 2-methoxyethoxymethyl; 2,2-dimethyl-l,3-dioxolan-4-yimethyl or agroupA^Q1; A1 represents a methylen, ethylen or propylen group; Q1 is cyano; carboxyl; carboxamide; -CO-NR3R4 and in case that A1 represents an 1,2-ethylen- or 1,3-propylen group, also can be hydroxy or NR3R4; R3, R4 are independently selected from the group consisting of hydrogen, methyl, ethyl> 2-morpholinoethyl or together form a 5 to 7 membered, saturated or unsaturated ring, optionally substituted by a methyl group and containing one or two heteroatoms, independently selected from N or O; Y represents 2-hydroxyethyl; 3-hydroxypropyl; 2-methoxyethyl; 3- methoxypropyl; (R)-2»3-dihydroxy-l-propyl; (S)-2,3-dihydroxy-l- propyl; (R)-3-hydroxybutyl; (S)-3-hydroxybutyl; 3-Hydroxy-2>2- dimethylpropyl; 2-morpholinoethyl; 3morpholinopropyl; 2-(4- methylpiperazin-l-yl)ethyl; 3-hydroxy-l-phenylpropyl; 2-aminoethyl; 3-aminopropyl; 4-aminobutyl; 2~(N,N-dimethylamino)ethyI; 3-(N,N- dimethylamino)propyl; 3-(pyrrolidin-l-yl)propyl; CH2COOH; (CH2)2COOH; (CH2)3COOH; CH(C2H5)COOH; (CH2)rO~(CH2)2- N(CH3)2; (CH2)2-0-(CH2)2-NH2; (CH2)2-S-(CH2)2-N(CH3)2; (CH2)2~ S-(CH2)rN(CH3)2; (CH2)3-S-(CH2)2-N(CH3)2 or (CH2)3-S-(CH2)3~ N(CHS)2; Z is selected from the group consisting of 3-chloro; 4-chloro; 3-bromo; 3-iodo; 3-ethynyl; 3-methoxymethoxy or 3-benzyloxy which is optionally substituted by halogen; methoxy; cyano; nitro; methylendioxy; carboxy or ethoxy; said substituent X being located in the 4-position of the phenyl ring, and pharmaceutical^ acceptable salts thereof. 5. A compound according to claim 1, wherein X is hydrogen; OR1; (SO)CH3; (S02)CH3; or a group CHrQ; Q is OH; NR3R4 or NHCH2CH2NR3R4; Rx is selected from the group consisting of hydrogen; dimethylphosphonylmethyl; (R)-2,3-dihydroxy-l-propyl; (S)-2,3~ dihydroxy-1-propyl; l,3-dihydroxy~2-propyl; 3-hydroxy-2-hydroxymethyl-1-propyl; 2-methoxyethoxymethyl or a group A1 -Q1; A1 represents a methylen, ethylen or propylen group; Q! represents cyano, carboxyl and in case that A1 represents an 1,2-ethylen- or 1,3-propyIen group, also can be hydroxy or NR3R4; R3, R4 are independently selected from the group consisting of hydrogen, methyl, ethyl or together form a 5 to 7 membered, saturated or unsaturated ring, optionally substituted by a methyl group and containing one or two heteroatoms, independently selected from N or O; Y is 2-hydroxyethyl; 3-hydroxypropyI; (R)-2,3-dihydroxy-l-propyl; (S)- 2,3-dihydroxy-l~propyl; 2-morpholinoethyl; 3-morpholinopropyl; 2- (4~methylpiperazin~l-yl)ethyl; 2-aminoethyl; 3-amtn^propyi; 2-(N,N- dimethylarnxno)ethyl; 3-(N,N-dimethylamino)propyl or 3-(pyrrolidin- l-yl)propyl; Z is selected from the group consisting of 3-chloro; 4-chloro; 3-bromo; 3- iodo; 3-ethynyl; 3-methoxymethoxy or 3-benzyloxy which is optionally substituted by halogen; methoxy or cyano; and said substituent X is located in the 4-position of the phenyl ring; and pharmaceutical^ acceptable salts thereof. 6. A compound according to claim 1, which is represented in the examples Hl.l.ltoH17.3.5. 7. A compound of the general formula (II), wherein X is OR1; SR2; (SO)R2; (S02)R2 or CH2-Q; Q represents OR1; SR2; SOR2; S02R2; NR3R4; NH-CH2-CH2NR3R4 or halogen; R1 is selected from the group consisting of hydrogen; Ci-Cj-alkyl; allyl; dimethylphosphonylmethyl; (R)-2,3-dihydroxy-l -propyl; (S)-2>3-dihydroxy-l-propyl; l,3-dihydroxy-2-propyI; 3-hydroxy- 2 -hydroxymethyl- 1 -propyl; 2-methoxyethoxymethyl; 2,2- dimethyl-l,3-dioxolan-4-ylmethyl; trifluoromethylsulfonyl; trimethylsilanyl; triisopropylsilanyl; t-butyldimethylsilanyl; phenyldimethylsilanyl; l,3-di-t-butyldimethylsilanyloxy-2- propyl; 3-t-butyldimethylsilanyloxy-2-t- butyldimethylsilanyloxymethyl-1-propyl or a group A:-Ql; A1 represents a methyl en, ethylen or propylen group; Q1 means cyano; carboxyi; COOCH3; COOCH2CH3; R2 is CrC6~alkyl; CHrCOO~CH2-CH3; dimethylphosphonylmethyl; 2,3-epoxy-l-propyl; 2,3-dihydroxy-l-propyl; 2-hydroxy-l-ethyl; 2,2-dimethyI-l,3-dioxolan-4-ylmethyl or Al-Ql; are independently selected from the group consisting of hydrogen; methyl; ethyl; 2-morpholinoethyl or together form a 5 to 7 membered, saturated or unsaturated ring, optionally substituted by a methyl group and containing one or two heteroatorns, independently selected from N or O, with the proviso, that X = OR1 is not OH or O-allyl. 8t A process for the manufacture of a compound of the general formula (VI) whereby said compounds of the general formula (IV) are obtained by reacting a compound of the general formula (II) according to claim 8 with a compound of the general formula (III) and the substituents X and Z having the significance given in one of the claims 1 to 5. 9. A process for the manufacture of a compound as claimed in one of claims 1 to 5, characterized by heating a compound of the general formula (VI) or (VII) according to claim 9 with an amine Y-NH2 and subsequent isolation of said compound; the substituents X> Y and Z having the significance given in one of the claims 1 to 5. 10. A process for the manufacture of 2,6-dichloro-3-hydroxybenzaidehyde and 2,6-dicbJoro-4-hydroxybenzaldehyde> characterized by the metallation of protected 2,4-dichlorophenoI or 3,5-dichlorophenol with a lithium base, followed by reaction with an ester or amide of formic acid and the deprotection and isolation of said compounds. 11. A process for the manufacture of 2,6-dichloro-3-hydroxymethylbenzaldehyde and 2,6-dichloro-4-hydroxymethylbenzaldehyde, characterized by the metallation of protected 2,4-dichlorobenzyl alcohol or 3,5-dichIorobenzyl alcohol with a lithium base, followed by reaction with an ester or amide of formic acid, deprotection with an acid or a fluorine salt and the isolation of said compounds. 12. A composition, containing a compound as claimed in one of claims 1 to 7 and usual adjuvants. 13, A pharmaceutical composition, containing a compound as claimed in one of claims 1 to 7 as the active ingredient and usual pharmaceutical adjuvants. Dated this 13th day of October 2004

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