Substituted n-benzyl-indol-3-yl glyoxylic acid derivatives having antitumoral effect

BACKGROUND OF THE INVENTION Indole-3-glyoxylamides have a variety of applications as pharmacologically active active compounds and as basic synthetic substances in pharmaceutical chemistry. BACKGROUND OF THE INVENTION In patent application No. 1, Appl. 6502481 discloses compounds having an anti-inflammatory and antipyretic profile as well as an analgesic activity. British patent application GB-PS 1,028,812 mentions indolyl-3-glyoxylic acid derivatives and their amides as analgesically effective, anticonvulsive and beta-adrenergic compounds. 6. Oxazine is also described as 3-indolyl-glyoxylamides, which have not yet been characterized pharmacologically (Eur., 94, 2353 (1961)), E. Woolmann reported in J. Med. 1252 (1968) for the indolyl-3-glyoxylic acid derivative which act inhibitory on glycerophosphate dehydrogenase and lactate dehydrogenase. European patent application EP 675110 discloses 1H-indole-3-glyoxylamides which are profiled as? 1 -A2-inhibitors and are used in the treatment of septic shock, pancreatitis, treatment allergic rhinitis and rheumatoid arthritis. In addition, in German patent application No. 19814 838.0 the use of the compounds of DE-05 196 36 150 A1 as anti-tumor agents is provided. SUMMARY OF THE INVENTION It is an object of the present invention to provide novel indole-3-ylglyoxyl compounds of the general Formula I which possess good antitumour activity and can be used to produce antitumor agents. Formula I wherein the residues P, P1, P2, P3, K4 and Z have the following meanings: (C 1 -C 6) -alkylamino, mono- or di (C 1 -C 6) -cycloalkylamino, (C 1 -C 4) -acylamino-, phenyl (C 1 -C 6) -alkylamino- , arylamino, heteroaroylamino, (C 1 -C 6) -alkylsulfonamido, arylsulfonamido, maleimido, succinimido, phthalimido, benzylcyclocarboylamino- (Z- amino), tert- butoxycarbonylamino- (BOC- amino-), 9- fluorenylmethoxycarbonylamino- (Eto-amino), triphenylmethylamino- (N-amino-), 2- (4'-pyridyl) -ethoxycarbonylamino (roos-amino), diphenylmethylsilylamino (CFM5-amino) to be replaced and to the C-atoms 2, 3 and 4 of the phenyl ring, B can also mean, in the case where B 1 = hydrogen, methyl or phenylmethyl, as well as a benzyloxycarbonyl residue (Z-residue), a tertiary butoxycarbonyl residue (BOC- ) and an acetyl group, the following residues: -NH-CH2-COOH; -NH-OH (CH3) -COCH3; - (CH 3) 2 CH-CH 2 -CH 2 -CH (NH) -COCON-; H3C-CH3CH (CH3) -CH (NH) -COOH-; HOCH2 OH-OH (NH) -COCH-; phenyl-CH2-CH (lH) -COOH-; (4-imidazolyl) -CH2-CH (NH) -COOH-; HN = O (NH2) -NH- (CH2) 3-NH (NH) -000H-; H2N- (CH2) 4-OH (NH) -000H-H2N-CO-CH2-OH (NH) -COOH; HOOC- (CH2) 2-OH (NH) -COCH-; R 1 is hydrogen, (C 1 -C 6) -alkyl, the alkyl group being optionally mono- or polysubstituted by the phenyl ring, and the tosenynyl ring, in turn, may be mono- or polysubstituted by halogen, (C 1 -C 6) -, (C 3 -C 7) -cycloalkyl-, carboxyl groups, C 3 -C 6 -alkanolecarboxyl-esterified groups, trifluoromethyl groups, hydroxyl groups, methoxy groups, ethoxy groups, benzyloxy groups as well as a benzene group, or the multiple-substituted phenyl group with (C1-C6) -alkyl groups, halogen atoms or trifluoromethyl groups, P1 also means the benzyloxycarbonyl group (Z-group), the androutyl butoxycarbonyl residue (Boc residue), as well as the acetyl group. P2 may also mean a phenyl ring which may be mono- or polysubstituted by (C1-C6) -alkyl, (C1-C6) -alkoxy-cyano, halogen, - (C 1 -C 6) -alkylamino-, (C 1 -C 6) -alkoxycarbonylamino-carboxyl group, respectively esterified by a (C 1 -C 6) -alkanol carboxyl group, or a pyridinone structure of Formula 2 and its N-oxide, if desired, may be attached to the ring 2, 3 and 4 carbon atoms and substituted with the substituents P5 and P6. The residues P 5 and P 6 may be the same or different and have the meaning (C 1 -C 6) alkyl as well as the meaning (C 3 -C 7) -cycloalkyl, (C 1 -C 6) alkoxy, nitro, amino, hydroxyl, halogen and trifluoromethyl, as well as the alkoxycarbonyl radical and the carboxyalkoxy group, since the alkyl group has 1-4 C atoms. K2 may furthermore be a 2- or 4-pyrimidinyl-heterocycle, with the 2-pyrimidinyl ring being optionally mono- or polysubstituted by a methyl group; (C1-C6) -alkyl, by halogen, by nitro, by amino, by a (C1-C6) -alkylamino radical 2-, 3-, 4-, -, 7- and 8-quinolyl structure; represents a 2-, 3- and 4-quinolylmethyl group, the carbon atoms ring the pyridylmethyl moiety of the quinolyl group and the quinolylmethyl moiety may be substituted with (C 1 -C 6) -alkyl, (C 1 -C 6) -alkoxy, nitro, amino- and (C1-C6) -alkoxycarbonylamino. P2 may, in addition, when K + = hydrogen, methyl or benzene group, as well as a benzyloxycarbonyl residue (Z-residue), a tert-butoxycarbonyl residue (Boc residue) and an acetyl group, to denote the residues: -CH2-COOH; -CH (CH3) -COOH; - (CH 3) 2 CH-CH 2 -CH 2 -CH (COOH) -; H 3 C-CH 2 -CH (CH 3) -CH (COOH) - HO-H 2 C -CH (COOH) - phenyl-CH 2 -CH (4-imidazolyl) -CH2-CH (COOH) -; HN = O (NH2) -NR- (CH2) 3-OH (COOH) -; H 2 N - (CH 2) 4 -OH (COOH) -; H 2 M -CO-CH 2 -CH (COOH) -; HOCO- (CH 2) 2 -CH (COOH) -; P2 may furthermore, in the case where P is hydrogen, Z-group, Boc residue, acetyl or benzene group, denote the acid moiety of a natural or non-natural amino acid, for example, a-glycyl-, α-sarcosyl-, , α-leucyl-, α-isoleucyl-, α-seryl-, α-phenylalanyl-, α-histidyl-, α- prolyl-, α- arginyl-, α-lysyl-, α- asparagyl- and α- glutamyl residue, the amino groups of the corresponding amino acids being unprotected or protected. A protecting group of the amino functionality in the consideration includes the carbobenzoxy residue (Z-residue) and the tert-butoxycarbonyl residue (Boc residue) as well as the acetyl moiety group. In the case where an asparagyl or glutamyl residue is used for the P2, the second unbound carboxyl group is a free carboxyl group or a carboxyl group esterified with C1-C6-alkanols, for example methyl, ethyl or t-butyl ester, respectively. In addition, CC2 can mean allylaminocarbonyl-2-methyl-prop-1-yl group. P1 and B2 may also form, together with the nitrogen atom to which they are attached, a piperazine ring of Formula 3 -N-P7 Formula 3 or a homopiperazine ring, in that P2 is an aminoalkylene group, wherein P7 is an alkyl moiety, a phenyl ring , which may be mono- or polysubstituted by (C 1 -C 6) -alkyl, (C 1 -C 6) -alkoxy, halogen, nitro, amino and may be substituted by a (C 1 -C 4) -alkylamino group. , a benzhydryl group and a bis-p-fluorobenzylhydryl group, P3 and K4 may be the same or different and represent hydrogen, (C1-C6) -alkyl-, (C3-C7) -cycloalkyl-, (C1-C6) (C 1 -C 4) -mono-alkyl substituted with an amino amino group, and (C 1 -C 6) alkoxy-carbonyl-, amino- fun (C1-C6) -alkyloxy- (C1-C6) -alkyl function, Z represents O and 8. By the name alkyl-, alkanol-, alkoxy- or alkylamino group at the radicals P, R7, R7 are to be understood as both "straight" and "branched" alkyl groups, such as methyl, ethyl, n -propyl, n-butyl, n-pentyl, n-hexyl, and branched alkyl groups, for example, radicals such as isopropyl or tert- cyclohexyl or cycloheptyl The term & quot; halogen & quot; refers to fluorine, chlorine, bromine or iodine The "alkoxy group" designates residues such as methoxy -, ethoxy-, propoxy-, butoxy-, isopropoxy-, and the like the heteroaryl heteroaryl group of the heteroaroylamino radicals signifies the co-thioyl, isonicotinoyl, thenoyl and furoyl. The name aryl of the arylsulfonamido group is understood to mean phenyl, tolyl and naphthyl. The compounds can also be used as acid addition salts, for example as salts of mineral acids such as hydrochloric acid, sulfuric acid, phosphoric acid, saline organic acids such as acetic acid, lactic acid, malonic acid, maleic acid, fumaric acid, gluconic acid, glucuronic acid, citric acid, ascorbic acid, embonic acid, methanesulfonic acid, trifluoroacetic acid, succinic acid, 2-hydroxyethanesulfonic acid, nicotinic acid and p- sulfonic acid. Both the compounds of Formula I and their salts are safibologically active. The compounds of Formula 1 may be applied in free form or as salts with physiologically acceptable acids. Administration can be done orally, parenterally, intravenously, transdermally or inhaled. Furthermore, the invention relates to pharmaceutical compositions containing at least one compound of Formula I or its salts with physiologically acceptable inorganic or organic acids and optionally with pharmaceutically acceptable carriers and / or diluents or excipients. Formulations for administration include, for example, tablets, dragees, capsules, infusion solutions or ampoules, suppositories, plasters, inhalable powder compositions, suspensions, creams and pasties. The methods for producing the compounds of the invention are described in the following Reaction Schemes 1 and 2 (Steps 1-3) as well as the general descriptions. All compounds can be obtained as described or analogously. The compounds of the general Formula 1 with Z = O, P = NO 2 and NH 2, R 2 = aryl, aralkyl and heteroaryl are prepared according to the following scheme 1. Scheme 1

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Step 1. The indole derivative, which may be unsubstituted or mono- or polysubstituted at C-2 in the phenyl structure, is dissolved in a protonic dipolar aprotic or non-polar organic solvent such as isopropanol, tetrahydrofuran, dimethylsulfoxide, dimethylformamide, N-methylpyrrolidone, dioxane, toluene or methylene chloride and added dropwise to a 3-neck flask prepared in a 3-necked flask or molar solvent or an excess of a suspension of a base such as sodium hydride, pulverized potassium hydroxide, potassium tert-butoxide for example 30 minutes to 12 hours, maintaining the temperature range from 0 ° C to 120 ° C, preferably between 30 ° C and 80 ° C, especially between 50 ° C and 65 ° C. After completion of the reaction, the reaction mixture was added to water, the solution was extracted, for example, with diethyl ether, dichloromethane, chloroform, methyl tert-butyl ether or tetrahydrofuran, and the resulting organic phase was dried with anhydrous sodium sulfate. The organic phase is dried in vacuo, the resulting residue is crystallized on the walls of the flask, or the oily dry residue is purified by recrystallization, distillation or by column chromatography, respectively, by flash chromatography on Kieselgel or alumina. As an eluent, of dichloromethane / diethyl ether in an 8: 2 (v / v) ratio or a mixture of dichloromethane and ethanol in a ratio of 9.1 (v / v). 2. Step N-Substitutedindole prepared in accordance with the above Step 1 is dissolved in a nitrogen atmosphere in a non-proton or non-organic solvent such as diethyl ether, methyl tert-butyl ether, tetrahydrofuran, dioxane, toluene, xylene, methylene chloride and chloroform. a nitrogen atmosphere, a solution of a simple molar amount or with up to 60 percent excess of oxalyl chloride in an aprotic or non-polar solvent such as diethyl ether, methyl t-butyl ether, tetrahydrofuran, dioxane, toluene, xylene, methylene lithium, maintaining the temperature between -5 ° C and 20 ° C. The reaction solution is then heated at a temperature between 10 ° C to 130 ° C, preferably between 20 ° C and 80 ° C, particularly preferably between 30 ° C and 50 ° C for a period of 30 minutes to 5 hours, then evaporating the solvent. The resulting dry residue of the thus-called "indolyl-3-glyoxyl chloride" is dissolved in an aprotic solvent such as tetrahydrofuran, dioxane, diethyl ether, toluene or a dipolar aprotic solvent such as dimethylformamide, dimethylacetamide or dimethylsulfoxide, cooled to a temperature between 10 C to -15 ° C, preferably between -5 ° C and 0 ° C, and is mixed in the presence of an acidic trap with a solution of a primary or secondary amine in a diluent. As diluents include those applied above for dissolving indolyl-3-glycolyl chloride solvents. Acid traps are triethylamine, pyridine, dimethylaminopyridine, basic exchangers, sodium carbonate, potassium carbonate, pulverized potassium hydroxide, and applied in excess to the primary or secondary amine reaction. The reaction is carried out at a temperature ranging from 0 ° C to 120 ° C, preferably between 20 ° C and 80 ° C, particularly preferably between 40 ° C and 60 ° C. After a 1-3 hour reaction time and 24 hours at room temperature, the acid chloride trap acid chloride obtained is filtered off, the filtrate is dried under vacuum and the dry residue is recrystallized from an organic solvent or purified by column chromatography on Kieselgel or alumina. Eluent, for example, is a mixture of dichloromethane and ethanol (95: 5, v / v). 3. Step The N-nitrobenzyl-substituted indole-glyoxyl amide prepared according to the above description is dissolved in a protic solvent such as methanol, ethanol, propanol, isopropanol, butanol or in a non-polar solvent such as tetrahydrofuran, dioxane or glycol-dimethylether, or in a dipolar aprotic solvent such as, for example, dimethylsulfoxide, dimethylformamide, dimethylacetamide or N-methylpyrrolidone respectively, with stirring, the solution is mixed under a nitrogen atmosphere with a hydrogenating catalyst such as Raney nickel, palladium / carbon or platinum.In the suspension with gentle shaking, from 1-15 bar, preferably 2-10 bar, particularly preferably at 4-6 bar, and the temperature is raised to about 20 ° C to 80 ° C, preferably 30 ° C to 60 ° C, particularly preferably 45 ° C to 55 ° C C. Alternatively, after about 1 hour is added After reaction time of 4 - 10 hours, hydrogenation is complete. The catalyst is filtered through a vacuum, the solution dried in vacuo to dryness and then the colorless or yellowish dry residue is dried in vacuo at 40 ° C. EXAMPLES According to this general description of steps 1-3, based on Synthetic Scheme 1, the following compounds are also synthesized upon presentation of the corresponding chemical name in the following review: Example 1 N- (Pyridin-4 yl) -N- (4-aminobenzyl) -indol-3-yl] glyoxyl amide (P-68838) 1. Step 1- (4-Nitrobenzyl) indole A mixture of 5.28 g of sodium hydride (0.22 mol, oil suspension) in 200 ml of dimethylsulfoxide is mixed with a solution of 23.4 g (0.2 mol) of indole in 100 ml of dimethylsulfoxide. Heat 1 mass at 65 ° C, then allow to cool and then dropwise add 37.7 g (0.22 mole) of 4-nitrobenzyl chloride. The solution was heated to 60 ° C, stored for 14 hours at room temperature and then poured into 700 ml of water. It is extracted in portions with a total of 300 ml of methylene chloride, the organic phase is dried with anhydrous sodium sulfate, filtered and the filtrate is dried in vacuo. The dry residue was purified on a column of Kieselgel (Kieselgel 60, Merck Gl., Ratzel; eluent methylene chloride / ethanol 9: 1, v / v). Yield: 43.9 g (87% of theoretical value) MS: m / e 253 (M + H) 2. Step N- (Pyridin-4- yl) - [1- (4nitrobenzyl) indol- amide (P-68836) A solution of 4.50 ml of oxalyl chloride in 50 ml of ether was dropwise added dropwise at 0 ° C under a nitrogen atmosphere with a solution of 10.09 g (0.04 mole) of 1- (4-nitrobenzyl) indole in 50 ml of ether. Heat for 2 hours at reflux and then evaporate the solvent. To the residue was added 100 ml of tetrahydrofuran, cooled to -5 ° C, and a solution of 9.32 g (0.099 mol) of 4-aminopyridine in 400 ml of tetrahydrofuran was added dropwise. Heat for 3 hours at reflux and leave overnight at room temperature. The 4-aminopyridine was filtered off under suction, the precipitate was washed with tetrahydrofuran, the filtrate was dried in vacuo and the solid residue crystallized back in the presence of a sodium salt. Yield: 13.5 g (84% of theoretical value) M3: m / e 401 (M + H) 3. Step N- (Pyridin- 4- yl) - [1- (4-aminobenzyl) indol- amide (P-68838) A mixture of 200 mg of rape-nickel in 50 ml of dioxane is mixed with a suspension of 320 mg (0.8 mmole) of N- (pyridin4- yl) - [1- (4-nitrobenzyl) yl} glyoxyl amide in a mixture of solvents containing 150 ml of dioxane and 20 ml of isopropanol. In this shake suspension, hydrogen is hydrogenated at a pressure of 5 bar and the temperature is maintained at 30-35 ° C. After about 3 hours, 400 mg of Raney nickel was added once more by vigorous shaking for an additional 8 hours at 35 ° C and 5 bar. The catalyst was filtered on a M2-atmosphere, the filtrate was dried in vacuo to dryness and the precipitate was dried in vacuo at 40 ° C. 15 Yield: 273 g (92% of theoretical value) M3: m / e 371 (M + H) Furthermore, compounds of the general formula 1 with Z = O, P = NO2 and NH2 P2 = aryl, heteroaryl, heteroarylarylarylaminocarbonyl- 2-methyl-prop-1-yl group can be synthesized by the synthesis route of Scheme 2 Scheme 2

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H21 Kappe-Nickel H. Stage

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4-yl) - (indol-3-yl) glycyl-amide To a solution of 9 mL of 4-aminobenzylidene- oxalyl chloride in 100 ml of anhydrous ether at 0 ° C was added a solution of 10 g (85.3 mmol) of indole in 100 ml of ether. The mixture was heated at reflux for 3 hours. A suspension of 12 g (127.9 mmol) of 4-amino-pyridine in 500 ml of tetrahydrofuran is then added dropwise at -5 ° C. the reaction mixture is heated under stirring for 3 hours to boiling temperature and left overnight at room temperature. The precipitate was triturated with water, and the dried compound was purified on a column of Kieselgel (Kieselgel 60, Megsk AC, Carbide) using 10: 1 v / v methanol / ethanol). Yield: 9.8 g (43.3% of theoretical value) M5: m / e 266 (M + H) +. Step 1 N- (Pyridin-4-yl) - [1- (4-nitrobenzyl) indol-3yl] glyoxyl amide (P-68836) (pyridin-4-yl) - [1- (4-nitrobenzyl) -pyridin-4-yl) nitrobenzyl) -indol-3-yl] glyoxylamide. Yield of N- (pyridin-4-yl) - [1- (4-aminobenzyl) indol-3-ylglyoxyl amide (P- 68838) N- (pyridin-4-yl) - [1- (4-nitrobenzyl) -indol-3-yl] glyoxylamide obtained according to Step 2 (Scheme 2) is hydrogenated catalytically according to &amp; quot; Hydration Description &amp; quot; and the resulting compound N- (pyridin-4-yl) - [1- (4-aminobenzyl) -indol-3-yl] glyoxylamide is isolated. Yield: 94% of the theoretical value of M3: m / e 371 (M + H) GENERAL PREPARATION FOR PREPARING THE COMPOUNDS OF GENERAL FORMULA 1 According to Scheme 2 1. Step To a solution of oxalyl chloride prepared in a nitrogen atmosphere in a simple molar amount or in a 60% excess of a non-propylene or non- such as diethyl ether, methyl tert-butyl ether, tetrahydrofuran, dioxane or dichloromethane, at a temperature between -5 ° C and + 5 ° C, the dissolved indole derivative which may be unsubstituted or substituted on the C-2 or the phenyl ring . The reaction mixture is melting? 18 is heated for 1 to 5 hours at a temperature between 10 ° C and 120 ° C, preferably between 20 ° C and 80 ° C, and particularly preferably between 30 ° C and 60 ° C, finally evaporating the solvent. The resulting dry residue of (indol-3-yl) glyoxyl chloride is dissolved, optionally in a non-protic solvent such as tetrahydrofuran, dioxane, diethyl ether, toluene or in a dipolar aprotic solvent such as dimethylformamide, dimethylacetamidyl dimethylsulfoxide, cooled to between -10 ° C and + 10 ° C, preferably between -5 ° C to 0 ° C; is mixed in the presence of an acid trap with a solution of a primary or secondary amine in a diluent. As diluents in a recital are those applied above for the dissolution of indolyl-3-glyoxyl chloride solvents. Triethylamine, pyridine, dimethylaminopyridine, basic ion exchangers, sodium ferricarbonate, potassium carbonate, atomized potassium hydroxide and the excess of the primary or secondary amine are used as acid traps. The reaction is carried out at a temperature of 0 ° C to 120 ° C, preferably at 20 ° C - 80 ° C, particularly preferably between 40 ° C and 60 ° C. After 1-4 hours of reaction time and 24 hours at room temperature, filtration is carried out, the precipitate is digested with the arc, filtered and dried under vacuum. The desired compound is purified by recrystallization in an organic solvent or by column chromatography on Kieselgel or alumina. For example, a mixture of dichloromethane and ethanol (10: 1, v / v) is used as the eluent. Step 2: The indole-3-ylglyoxylamide is prepared in a protonic, dipolar aprotic or 19 non-polar organic solvent such as isopropanol, tetrahydrofuran, dimethylsulfoxide, dimethylformamide, dimethylacetamide, N- methylpyrrolidone, dioxane, toluene or methylene chloride, and dropwise added to a molar solution prepared in a three-necked flask or an excess suspension of a base such as sodium hydride, pulverized potassium hydroxide, potassium tert-butoxide, dimethylaminopyridine or sodium amide, in a suitable solvent. For example, the desired alkyl-, aralkyl-, or heteroaralkyl halide, undiluted or diluent, which is, for example, used in the dissolution of "indol-3-ylglyoxyl amide", optionally with the addition of a catalyst such as copper, is allowed to react for some time, for example 30 minutes to 12 hours, maintaining the temperature in the range of from 0 ° C to 120 ° C, preferably between 30 ° C and 80 ° C, particularly preferably between 50 ° C and 70 ° C. Upon completion of the reaction, the reaction mixture is poured into water, the solution is extracted, for example, with diethyl ether, dichloromethane, chloroform, methyl tert-butyl ether, tetrahydrofuran, n-butanol, respectively, and the resulting organic phase is dried over sodium sulphate. The organic phase is dried in vacuo, the resulting dry residue is crystallized by scratching on the walls or, respectively, the oily dry residue is purified by distillation either by column chromatography or flash chromatography on Kieselgel or alumina, respectively. As a eluent, for example, a mixture of methylene chloride and diethyl ether in a ratio of 8: 2 (v / v) or a mixture of methylene chloride and ethanol in a ratio of 9: 1 (v / v) is used. 3. Step 20 The N-nitrobenzyl-substituted indole-glyoxyl amide prepared according to the above description is dissolved in a protic solvent such as methanol, ethanol, propanol, isopropanol, butanol or in a non-polar solvent such as tetrahydrofuran, dioxane or glycol dimethylether or in a dipolar aprotic solvent such as dimethylsulfoxide, dimethylformamide, dimethylacetamide or N-methylpyrrolidone, respectively, and the solution is mixed under a nitrogen atmosphere with stirring with a hydrogenating catalyst such as, for example, Raney nickel, palladium / charcoal or platinum. moderately shaking, hydrogen is added at a gas pressure of 1-15 bar, preferably 2-10 bar, particularly preferably 4-6 bar, and the temperature is raised to about 20 ° C to 80 ° C, preferably 30 ° C to 60 ° C, preferably 45 ° C - 55 ° C but, after about 1 hour, the amount of catalyst was added again and the hydrogenation was continued. After a reaction time of 4-10 hours, hydrogenation is complete. The catalyst is filtered through a vapor atmosphere, the solvent is dried to dryness in vacuo and then the colorless or yellowish dry residue is dried in vacuo at 40 ° C. According to the generalFor the steps 1-3, based on Synthesis Scheme 2, compounds 0-68836 and 0-68838 are synthesized which have already been synthesized according to the synthesis procedure of Reaction Scheme 1. In the tubulin polymerization assay, the activity of the advanced compounds is shown. Of particular importance is that 0-68838 suppresses the polymerization of tubulin and thus exerts a stabilizing effect on the microtubules, respectively the superimposed spindles.