MXPA97003634A - Derivatives of antibacterial benzymidazole - Google Patents

Abstract

The present invention relates to compounds useful as antibacterial agents, characterized in that they are selected from the group consisting of: 2-fluoro-4- [2 '- (3-fluoro-4-hydroxyphenyl) -6,6'-dibe nzimidazole-2 -yl] -phenol, 4- [2 '- (4-hydroxy-3-methoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -2-methoxy-phenol, 5- [2' - ( 3-hydroxy-4-methoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -2-methoxy-phenol, 2,2'-bis- (4-methoxy-phenyl) -6,6'-dibenzimidazole , 2,2'-bis (4-ethoxy-phenyl) -6,6'-dibenzimidazole, 4- [2 '- (4-ethoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -fe nol , 4- [2 '- (4-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] - benzonitrile, 2,2'-difuran-2-yl-6,6'-dibenzimidazole, as well as pharmaceutically acceptable salts of the same

Description

DERIVATIVES OF DIBENCIMIDAZOL ANT? BACTERIALS Description of the invention The invention is concerned with the dibenzimidazole derivatives. In particular, it is concerned with the 2,2'-bis-substituted 6,6-dibenzimidazoles of the general formula wherein R 1 and R 2 may be the same or different and mean C 3 H 3", C 6 H 3 (OH) R 4" or heterocyclyl, R 3 signifies hydroxy, amino, lower alkoxy or cyano and R 4 signifies halogen, lower alkyl or lower alkoxy, also as usable salts pharmaceutically of compounds of general formula I. These compounds are new with the exception of: 4- [2 '- (4-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol, 3- [2, - (3-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol, 4- [2 '- (4-amino-phenyl) -6,6'-dibenzimidazol-2-yl] -phenylamine and 4- [2 '- (4-cyano-phenyl) -6,6, -dibenzimidazol-2-yl] -benzonitrile. The compounds of formula I and their pharmaceutically usable salts exhibit a good antibacterial activity, mainly against the REF: 24677 gram-positive pathogens such as Staphylococcus and Enterococcus faecalis. In addition, they also exhibit good activity against Helicobacter pylori. Accordingly they are suitable for the prophylaxis and treatment of diseases that are caused by such pathogens. The symmetrical bis-benzimidazoles have been described in the literature as starting materials for the preparation of polybenzimidazoles (J. Org. Chem., 42, 3485-3491 [1977]). The use of these compounds as therapeutically active substances, especially for the prevention or treatment of bacterial diseases is new. The objects of the present invention are the compounds of general formula I and the pharmaceutically usable salts thereof for use as therapeutically active substances, especially as active substances against bacterial pathogens; medicaments containing one or more compounds of general formula I defined in claim 1 or pharmaceutically usable salts thereof; the use of these compounds in the control or prevention of diseases which are caused by bacterial pathogens and for the production of drugs for the mentioned indications; also as the new compounds of formula I, their pharmaceutically usable salts, as well as the manufacture of these novel compounds and their salts. The term "lower alkyl" used in the present description conveniently denotes those with up to 7, preferably up to 4, carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t- butyl and the like. Halogen means chlorine, bromine, fluorine or iodine. The term "lower alkoxy" denotes a lower alkyl residue linked via an oxygen atom. According to the present invention, the term "heterocyclyl" means a 5- or 6-membered unsaturated ring with at least one heteroatom such as O, S, N, for example furyl, pyranyl, thienyl, pyrrolyl or pyridyl. Especially preferred for use as therapeutically active substances are those compounds of formula I in which R.sup.1 and R.sup.2 are the same or different and mean C.sub.HH.sub.3"or R.sub.3 and R.sub.4 have the meaning given above and wherein a substituent preferably occupies a 4- position. or optionally a 3-position on the phenyl ring It has been found that the antibacterial activity is especially high when the substituent R3 or R4 or the hydroxy group in CßHaíOHJR4", for R1 or R2 is located in the 4- position. Thus, compounds in which a hydroxy group is located in the 4- position on the phenyl ring are particularly preferred. The following compounds are particularly preferred for use as therapeutically active substances. 4- [2 '- (4-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol, 3- [2' - (3-hydroxy-phenyl) -6,6'-dibenzimidazole-2 -yl] -phenol, 4- [2 '- (4-amino-phenyl) -6,6'-dibenzimidazol-2-yl] -phenylamine and 2-fluoro-4- [2' - (3-fluoro-4) -hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol; 4- [2 '- (4-hydroxy-3-methoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -2-methoxy-phenol; 5- [2 '- (3-hydroxy-4-methoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -2-methoxy-phenol; 2,2'-bis- (4-methoxy-phenyl) -6,6'-dibenzimidazole; 2,2'-bis- (4-ethoxy-phenyl) -6,6'-dibenzimidazole; 4- [2 '- (4-ethoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol; 4- [2, - (4-hydroxy-phenyl) -616'-dibenzimidazol-2-yl] -benzonitrile.

The symmetrically substituted compounds of formula I in which R 1 and R 2 have the same meaning, can be manufactured according to the invention by reacting the compound of formula with an excess of a reactive compound which produces the residue R1 or R2. The asymmetrically substituted compounds of formula I in which R1 and R2 do not have the same meaning can be manufactured according to the invention by reacting the compound of formula II simultaneously with two different reactive compounds which produce the residues R1 and R2. A further possibility for the manufacture of the symmetrical and asymmetric compounds of formula I comprises reacting a compound of formula wherein R1 has the above meaning, with a reactive agent which produces the residue R1 or R2. Not only the symmetrically substituted compounds, but also the asymmetrically substituted compounds of formula I, can be converted, if desired, to a pharmaceutically utilizable salt. The following can be used, for example, as reactive compounds which are suitable for the manufacture of the compounds of formula I: 3- or 4-hydroxy-benzaldehyde, ethyl imide ester of 4-hydroxybenzoic acid, 4-amino- benzaldeh gone, 3-fluoro-4-hydroxy-benzaldehyde, 4-hydroxy-3-methyl-benzaldehyde, 4-hydroxy-3-methoxy-benzaldehyde, 4-methoxy-benzaldehyde, 4-ethoxy-benzaldehyde, 3-hydroxy -4-methoxy-benzaldehyde, ethyl imide ester of furancarboxylic acid, 4-cyano-benzaldehyde.

Other appropriately substituted aldehydes, acids, esters, anhydrides, alkyl imides or acyl halides (described in Chem. Rev. 74, 279-314; The Chemistry of Heterocyclic Compounds, Part I, Vol. 40, pp. 1-286, 1981; Comprehensive Heterocyclic Chemistry, Vol. 5, pp. 457-487) are also appropriate. For the manufacture of the symmetrically substituted compounds of formula I, 3,3'-diamino-benzidine (II) is reacted with a reactive compound which produces the residue R1 or R2. This is conveniently carried out by reacting the 3,3'-diamino-benzidine with a 2-fold amount of the reactive derivative in a solvent, for example ethanol, for several hours at the boiling temperature of the solvent which is used. Na2S2O5 or nitrobenzene is especially suitable as an additive for the manufacture of the compounds of formula I when aldehydes are used as the reactive derivatives. When acids, esters, anhydrides, alkyl imides or acyl halides are used, HCl, (J. Chem. Soa, 2393-2399, [1928]), polyphosphoric acid (J. Amer. Chem. Soc. 79, 427- 429 [1957]) or optionally nitrobenzene (Synth Commun. 20, 955-963 [1960]) are appropriate. The manufacture of asymmetrically substituted dibenzimidazoles can be carried out in a similar manner. Starting from 3,3'-diamino-benzidine (II) the reaction is carried out with two different reactive compounds, for example with two different substituted aldehydes. Thus, the compound 4- [2 '- (4-ethoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol is obtained, for example, by reacting 3,3'-diamino-benzidine with 4-hydroxy-benzaldehyde and 4-ethoxy-benzaldehyde in ethanol and the addition of Na2S2? S after stirring for several hours at reflux. The reaction solution also contains the corresponding symmetrical compounds in addition to the asymmetrically substituted dibenzimidazoles. The symmetrically or asymmetrically substituted dibenzimidazole derivatives are also obtained by reacting a compound of formula pr with a reactive compound mentioned above which produces the residue R1 or R2. The reaction is carried out analogously to the process described above. The pharmaceutically utilizable salts can be manufactured according to known methods. For example, the free bases of formula I can be converted to the corresponding salts with the following inorganic or organic acids: hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, maleic acid, acetic acid, succinic acid, tartaric acid, methanesulfonic acid, p-toluenesulfonic acid and the like. Preferred salts are hydrochlorides which can be manufactured from basic compounds of formula I, for example with a methanolic HCl solution. The starting compounds required for the manufacture of the compounds of formula I are known commercially available products, for example, compound II, or they can be easily prepared according to methods known per se. Thus, for example, compound III can be obtained by reacting the 3-amino-3'-nitrobenzidine with a reactive compound which produces the residue R1, for example with 4-hydroxy-benzaldehyde, with the nitro group of the isolated intermediate which it is hydrogenated subsequently to the amino group. The hydrogenation is carried out according to the processes described in the literature, for example with hydrogen or hydrazine in the presence of Raney nickel. Then the compound III obtained can be, as described, converted with an additional compound, which produces the residue R1 or R2 to the dibenzimidazoles of formula I. All the reactive compounds which contain the residue R1 or R2 and which are required for the manufacture of compound I are known compounds and / or can be prepared in an analogous manner according to the procedures described in the literature. For example, the ethyl imide ester of 4-hydroxybenzoic acid can be prepared as follows: The 4-hydroxybenzonitrile, in a mixture of solvents, for example in a mixture of chloroform-ethanol, is treated several times at room temperature with gas of anhydrous HCl, the resulting hydrochloride is separated at intervals. Then the resulting ester can be converted to the compounds of formula I without further purification. As mentioned above, the substituted 6,6'-dibenzimidazoles of formula I and their pharmaceutically usable salts have extremely valuable pharmacological properties. Table 1 shows its activity (in vitro) against several bacterial strains, mainly its very good activity against gram-positive bacteria.

Evaluation of anti-bacterial activity The minimum inhibitory concentration (MIC) of the substances investigated against Gram-positive and Gram-negative strains was determined using standard agar methods. The compounds were dissolved in a small amount of dimethyl sulfoxide, diluted with water and incorporated into liquid DST agar at 50 ° C. The agar plates thus produced were used immediately after the test. The test concentrations are between 128 and 0.06 μg / ml. Bacterial inoculation solutions were prepared from overnight pre-cultured cultures, diluted and applied to the agar surface when using an inoculation device (Denley A400). The plates were incubated at 35 ° C for 20 hours. MIC was determined at the lowest concentration of the substance which prevented visible growth. A barely visible turbidity and the growth of less than 5 colonies were ignored. The determinations of the antibacterial activities (Table 1) were carried out not only for the free bases, but also for the hydrochloride salt of each compound. The same values were obtained within the experimental error. The antibacterial activities against Helicobacter pylori were carried out analogously to the method described above with the following variations: The compounds were incorporated into Müller-Hinton agar containing 5% sheep blood additive. The test concentrations were between 10 and 0.1 μg / ml. The pre-incubation time was 5 days. The incubation time was 4 days for H. pylori K 1585 and 7 days for H. pylori PN 81.

Table 1 In vitro antibacterial activity Minimum inhibitory concentration (MIC) in micrograms / ml The products according to the invention can be used as medicaments, for example in the form of pharmaceutical preparations which contain them or their salts, in admixture with a pharmaceutical, organic or inorganic carrier material which is suitable for parenteral or enteral administration, such as, for example, water, gelatin, gum arabic, lactose, starch, magnesium stearate, talcum, vegetable oils, polyalkylene glycols, petrolatum, etc. The pharmaceutical preparations can be present in solid form, for example as tablets, coated tablets, suppositories, capsules or in liquid form, for example as solutions, suspensions or emulsions. They can be sterilized and / or contain adjuvants such as preservatives, stabilizers, wetting agents or emulsifiers, salts for varying the osmotic pressure, anesthetics or buffers. The compounds of formula I and their salts are preferably considered for parenteral administration and for this purpose are preferably formulated as lyophilizates or dry powders for dilution with customary agents such as water or isotonic saline. The dosage of the compounds of general formula I and the pharmaceutically compatible salts thereof with bases can vary within wide limits and in each individual case will of course be adjusted to the individual requirements and to the pathogen to be controlled. As mentioned above, medicaments containing a compound of general formula I or a pharmaceutically compatible salt thereof are also an object of the present invention, in addition, also a process for the production of such medicaments, which is characterized by bringing to one or more compounds of general formula I or pharmaceutically compatible salts thereof and, if desired, one or more therapeutically valuable substances to a medicinal administration form. The following examples are proposed to illustrate the present invention in more detail.

Synthesis of symmetrically substituted bis-benzimidazoles Example 1 2-Fluoro-4- [2 '- (3-fluoro-4-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] phenol Method A 0.43 g (2 mmol) of 3, 3'-diamino-benzidine and 0.56 g (4 mmol) of 3-fluoro-4-hydroxy-benzaldehyde are dissolved in 50 ml of ethanol and treated with a solution of 0.38 g (2 mmoles) of Na2S2O5 and 5 ml of Water. The reaction solution is stirred at reflux for 16 hours. The insoluble products are filtered. The product is precipitated by the addition of 60 ml of water and then filtered and treated with 100 ml of hot methanol. The methanolic solution is filtered and the filtrate is treated with a methanolic HCl solution. After partial distillation of the solvent, the hydrochloride salt is separated in the form of beige crystals. Yield 610 mg (58%).

Example 2 2,2'-dimethyl-6,6'-dibenzimidazole-2,2, -ylene-diphenol 2.14 g (10 mmol) of 3,3'-diaminobenzidine, 2.72 g (20 mmol) of 4-hydroxy -3-methylbenzaldehyde and 1.9 g (10 mmoles) of Na2S2? S provide 1.1 g of dihydrochloride in the form of colorless crystals analogously to method A. Yield: 47%.

Example 3 4- [2'-hydroxy-3-methoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -2-methoxy-phenyl 1.07 g (5 mmol) of 3,3'-diamino-benzidine, 1.54 g (10 mmoles) of 4-hydroxy-3-methoxybenzaldehyde and 0.95 g (5 mmoles) of Na? S? provide 0.2 g of dihydrochloride in the form of beige crystals in a manner analogous to method A. Yield: 8%.

EXAMPLE 4 5- [2X3-Hydroxy-4-methoxy-phenyl) -6,6'd-benzamidazol-2-yl] -2-methoxy-phenol 1.07 g (5 mmol) of S.S'-diamino- benzidine, 1.54 g (10 mmol) of 3-hydroxy-4-methoxybenzaldehyde and 0.95 g (5 mmol) of Na2S2? s provide 0.4 g of dihydrochloride as beige crystals in a manner analogous to method A. Yield: 17% .

Example 5 4- [2 '- (4-Hydroxy-phenyl) -6,6'dibenzimidazol-2-yl) -phenol hydrochloride 4.29 g (20 mmol) of 3,3'-diamino-benzidine, 4.88 g (40 g) mmoles) of 4-hydroxybenzaldehyde and 3.8 g (20 mmoles) of Na? S? give 2.09 g of dihydrochloride in the form of beige crystals analogously to method A. Yield: 25%.

Method B 2.14 g (10 mmol) of 3,3'-diamino-benzidine and 4.05 g (20 mmol) of ethyl ester hydrochloride 4-hydroxy-benzoic acid are dissolved in 300 ml of ethanol and boiled at reflux for 2 hours. The reaction solution is subsequently cooled to room temperature. After the addition of 200 ml of water, a fine white precipitate is separated. The precipitate is filtered and recrystallized from a methanolic HCl solution. The dihydrochloride salt is obtained in the form of beige crystals. Yield: 1.45 g (25%).

Example 6 3- [2 '- (3-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol 1.07 g (5 mmol) of 3,3'-diamino-benzidine, 1.22 g (10 mmol) ) of 3-hydroxy-benzaldehyde and 0.95 g (5 mmoles) of Na2S2? 5 give 1.2 g of dihydrochloride in the form of beige crystals analogously to method A. Yield: 57%.

Example 7 4- [2'-Amino-phenyl) -6,6'-dibenzimidazol-2-yl] -phenylamine 5.35 g (25 mmoles) of 3,3'-diamino-benzidine, 5.55 g (50 mmoles) of 4 -amino-benzaldehyde and 4.75 g (25 mmol) of Na 2 S 2 O 5 give 0.35 g of dihydrochloride in the form of beige crystals in a manner analogous to method A Yield: 5%.

Example 8 2,2'-bis- (4-methoxy-phenyl) -6,6'-dibenzimidazole 1.07 g (5 mmol) of 3,3'-diamino-benzidine, 1.36 g (10 mmol) of 4-methoxy- benzaldehyde and 0.95 g (5 mmoles) of Na S2O5 give 0.41 g of dihydrochloride in the form of beige crystals in a manner analogous to method A. Yield: 18%.

Method C A mixture of 1.07 g (5 mmoles) of 3,3'-diamino-benzidine and 1.49 g (11 mmoles) of 4-methoxy-benzaldehyde dissolved in 50 ml of nitrobenzene is stirred at 140 ° C for 24 hours. After cooling to room temperature the reaction solution is concentrated by vacuum distillation. The obtained residue is purified chromatographically on a Florosil column. The elution agent used consisted of CH2Cl2 / CH3OH (98: 2-90: 10). The corresponding fraction was collected and gave 1.34 g of 2,2'-bis- (4-methoxy-phenyl) -6,6'-dibenzimidazole as a beige solid. Performance 56%.

Example 9 2,2'-bis- (4-ethoxy-phenyl) -6,6'-dibenzimidazole 2.14 g (10 mmol) of 3,3'-diamino-benzidine, 3.0 g (20 mmol) of 4-ethoxybenzaldehyde and 1.9 (10 mmoles) of Na 2 S 2 5 5 give 3.4 g of dihydrochloride in the form of white crystals in a manner analogous to method A. Yield: 72%.

EXAMPLE 10 2,2-Difuran-2-yl-6,6'-dibenzimidazole 0.64 g (3 mmoles) of 3,3'-diamino-benzidine and 1.05 g (6 mmoles) of ethyl imido ester of furan-2 acid -carboxylic give 0.16 g of hydrochloride in the form of beige crystals in a manner analogous to method B. Yield 12%.

Synthesis of asymmetrically substituted bis-benzimidazoles Example 11 4- [2'-ethoxy-phenyl) -6, 6'-dibenzimidazol-2-yl-phenol 3.15 g (15 mmol) of 3,3'-diamino-benzidine, 1.83 g (15 mmol) of 4-hydroxybenzaldehyde and 2.75 g (15 mmol) of 4-ethoxybenzaldehyde are dissolved in 100 ml of ethane and treated with 2.85 g (15 mmoles) of Na2S2? s dissolved in 20 ml of water. The reaction mixture is boiled under reflux for 24 hours and subsequently filtered. 100 ml of water are added to the filtrate in order to precipitate the product. The solid is filtered and purified by column chromatography (400 g of silica gel; Methylene chloride: methane (9: 1) is used as the eluent). The product is recrystallized from methanol. 0.4 g of yellowish crystals are formed. Performance 6%.

Example 12 4- [2'-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl-benzonitrile 4.28 g (20 mmol) of 3,3'-diamino-benzidine, 2.44 g (20 mmol) of 4- hydroxybenzaldehyde and 2.62 g (20 mmoles) of 4-cyanobenzaldehyde are dissolved in 500 ml of ethanol and treated with 3.8 g (20 mmoles) of Na2S2? s dissolved in 100 ml of water. The reaction mixture is boiled under reflux for 16 hours and subsequently filtered. The product is precipitated by the addition of 500 ml of water to the filtrate and the mixture is filtered again. The crude product (6.7 g) is purified by column chromatography (silica gel, methylene chloride: methanol (9: 1) is used as the eluent). The product is recrystallized from methanol. 0.8 g of yellowish crystals of 4- [2 '- (4-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -benzonitrile are obtained. 10% yield.

Preparation of the intermediates Example 13 Ethyl imido ester of 4-hydroxybenzoic acid 22.4 g (188 mmol) of 4-hydroxybenzonitrile are dissolved in 200 ml of chloroform and 50 ml of ethanol. HCl gas is introduced as it is stirred and cooled (the temperature of the solution should never exceed 20 ° C) until the solution is saturated. The hydrochloride is separated as a white crystalline precipitate. After 2 hours the reaction solution is filtered and the crude product is suspended in 150 ml of ethanol. Anhydrous HCl gas is again conducted to the solution while stirring and cooling (the temperature of the solution should never exceed about 20 ° C) until it becomes saturated.

The white crystals are filtered and used without further purification.

Yield: 18.0 g. Melting point 207-209 ° C (decomposes).

EXAMPLE 14 Ethyl imido furan-2-carboxylic acid ester The synthesis is carried out analogously to example 13. 9.3 g (0.2 mol) of 2-cyano-furan gave 4.8 g of colorless crystals. Yield: 27% of the corresponding imido hydrochloride ester. Melting point 117-119 ° C.

Table 2 Characteristics of the compounds of examples 1-12 * The 1 H NMR spectra were taken at 250 MHz in DMSO-d6 at a temperature of 298 ° K. The concentration of the compounds was 2 mmol. Chemical shifts d (± 0.02 ppm) were measured in relation to d (TMS) = 0.0 ppm; S = singlet, d = doublet, t = triplet, q = quartet, m = multiplet.

** The Rf values were measured on a silicon-coated glass plate (Merck). The eluent used consisted of a mixture of 9 parts by volume of methylene chloride and 1 part of methanol (9: 1) or a solution of 3 parts by volume of methylene chloride and 1 part of methanol (3: 1).

EXAMPLE A Ampoules are produced for intramuscular administration in the usual manner. A lyophilisate of 1 g of 4- [2 '- (4-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol (1: 2) hydrochloride is produced in the usual manner and filled in an ampule. Before administration, the lyophilisate is treated with 2.5 ml of 2% lidocaine hydrochloride solution.

Example B Tablets of the following composition are produced in the usual manner: mg / tablet 4- [2 '- (4-amino-phenyl) -6,6'-dibenzimidazol-2-yl] -phenylamine 1 Lactose 103 Corn starch 25 Microcrystalline cellulose 70 Magnesium stearate _1 Total 200 Example C Capsules of the following composition are produced: mg / capsule 2,2'-dimethyl-6,6'-dibenzimidazol-2,2'-ilen-diphenol 1 Lactose 164 Corn starch 30 Talc _5 Total 200 The active substance, lactose and corn starch are first mixed in a mixer and then in a grinding machine. The mixture is returned to the mixer, talc is added and the mixture is mixed thoroughly. The mixture is machine filled into hard gelatin capsules.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Having described the invention as above, property is claimed as contained in the following

Claims (11)

1. Claims 1. The compounds of general formula wherein R1 and R2 may be the same or different and signify C6H R3", CβHaíOHJR4" or heterocyclyl, R3 signifies hydroxy, amino, lower alkoxy or cyano and R4 signifies halogen, lower alkyl or lower alkoxy, also as pharmaceutically acceptable salts of the same, for use as therapeutically active substances, especially as active substances against bacterial pathogens.
2. 2. The compounds according to claim 1, characterized in that R1 and R2 can be the same or different and mean C6H4R3"or CßHaiOHJR4", R3 and R4 have the same meanings given in formula I and wherein a substituent preferably occupies a position 4- or optionally a 3- position on the phenyl ring.
3. 3. 4- [2 '- (4-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol, 3- [2' - (3-hydroxy-phenyl) -6,6'-dibenzimidazole-2 -yl] -phenol, 4- [2 '- (4-amino-phenyl) -6,6'-dibenzimidazol-2-yl] -phenylamine; 2-fluoro-4- [2, - (3-fluoro-4-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol; 4- [2 '- (4-hydroxy-3-methoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -2-methoxy-phenol; 5- [2 '- (3-hydroxy-4-methoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -2-methoxy-phenol; 2,2'-bis- (4-methoxy-phenyl) -6,6'-dibenzimidazole; 2,2'-bis- (4-ethoxy-phenyl) -6,6, -dibenzimidazole; 4- [2 '- (4-ethoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol; 4- [2 '- (4-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -benzonitrile, as compounds according to claim 1.
4. 4. The compounds of general formula I according to claim 1, except for: 4- [2 '- (4-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol, 3- [2'] - (3-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol, 4- [2 '- (4-amino-phenyl) -6,6'-dibenzimidazol-2-yl] -phenylamine and 4- [2 '- (4-cyano-phenyl) -6,6'-dibenzimidazol-2-yl] -benzonitrile, and pharmaceutically acceptable salts thereof.
5. 5. The compounds according to claim 4, characterized in that R1 and R2 can be the same or different and mean C6H R3"or C6H3 (OH) R4", R3 and R4 have the same meanings given in formula I and of which a The substituent preferably occupies a 4- position or optionally a 3- position on the phenyl ring.
6. 6. 2-fluoro-4- [2 '- (3-fluoro-4-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol; 4- [2 '- (4-hydroxy-3-methoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -2-methoxy-phenol; 5- [2 '- (3-hydroxy-4-methoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -2-methoxy-phenol; 2,2'-bis- (4-methoxy-phenyl) -6,6'-dibenzimidazole; 2,2'-bis- (4-ethoxy-phenyl) -6,6'-dibenzimidazole; 4- [2 '- (4-ethoxy-phenyl) -6,6'-dibenzimidazol-2-yl] -phenol; 4- [2 '- (4-hydroxy-phenyl) -6,6'-dibenzimidazol-2-yl] -benzonitrile.
7. 7. A process for the manufacture of the compounds according to claims 4-6, characterized in that it comprises: (a) reacting the compound of formula with an excess of a reactive compound which produces the residue of R1 or R2 (b) to react the compound of formula II simultaneously with two different reactive compounds, which produce the residues R1 and R2 or (c) reacting a compound of formula wherein R1 has the meaning given in claim 1, with a reactive compound which produces the residue R1 or R2 and (d) if desired, converting a basic compound to a pharmaceutically utilizable salt by means of an acid.
8. 8. A medicament, especially an antibacterial medicament, characterized in that it contains one or more compounds of general formula I defined in claim 1 or pharmaceutically acceptable salts thereof and one or more therapeutically inert excipients.
9. 9. The use of the compounds of general formula I and pharmaceutically acceptable salts thereof, characterized in that they are used for the production of medicaments for the treatment of bacterial diseases, especially infections with Staphylococcus, Enterococcus faecalis and Helicobacter pylori.
10. 10. The use of the compounds of general formula I and pharmaceutically acceptable salts thereof, characterized by the control of diseases or for the improvement of health, especially in the prophylaxis or treatment of bacterial diseases or respectively for the production of the corresponding drugs .
11. 11. The compounds according to claims 4-6, characterized in that they are manufactured according to the process according to claim 7 or a process equivalent thereto.