NO842577L - NEW 2-SUBSTITUTED BENZOFURAND DERIVATIVES. - Google Patents

Description

The invention relates to a process for the production of 2-substituted benzofuran derivatives with formula I

in which

Y means -CH= or -N=,

R.j and R.sup., independently of each other, are hydrogen, halogen, C 1 -C 4 -alkyl or -C 4 -C 4 -alkyloxy;

A and B mean -Cj 2_alkyl or together mean one of the following

alkylene bridges

or

while

R, and R^ independently of each other means hydrogen, one with halogen or a group of the formula -Z-Rg substituted or unsubstituted -C^2~alkyl, one with halogen or -C4~alkoxy and/or C^-C^- alkyl substituted or unsubstituted phenyl, where Z means oxygen or sulfur and

R 8 means hydrogen, a C 1 -C 6 -alkyl substituted or unsubstituted C 1 -C 8 -alkyl, C 1 -C 4 -alkenyl, 2-propynyl or 3-halo-2-propynyl; one with halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy, nitro and/or trifluoromethyl substituted or unsubstituted phenyl or one with halogen, C₁-C₄-alkyl, C₄-C₄- alkoxy substituted or unsubstituted benzyl;

R1-, Rg and R7 independently mean hydrogen or C1-C2-alkyl, as the total number of carbon atoms in R1, R2 and R7 must not exceed the number 6, and

Rg means hydrogen or C₁-C₁-alkyl,

and their salts.

With alkyl or the alkyl portion of another substituent

depending on the number of carbon atoms indicated, for example the following groups are understood: Methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl or dodecyl and their isomers, such as e.g. isopropyl, isobutyl, tert.-butyl, isopentyl etc.. Alkenyl means e.g. propenyl-(1), allyl, butenyl-(1), butenyl-(2), butenyl-(3), etc. By halogen here and in the following is meant fluorine, chlorine, bromine or iodine, preferably chlorine or bromine.

The invention encompasses both the free compounds of formula I, as well as their addition salts with inorganic or organic acids.

Salts according to the invention are in particular addition salts with pharmacologically tolerable inorganic or organic acids.

Physiologically tolerable acids, i.e. pharmaceutically usable acids, are for example pharmaceutically usable mineral acids, such as halogenated acids, e.g. hydrochloric, bromic or hydroiodic acids, sulfuric or phosphoric acid, pharmaceutically usable carboxylic and sulphonic acids, such as aliphatic mono-

and optionally hydroxylated dicarboxylic acids, e.g. acetic acid, fumaric acid, maleic acid, malic acid or tartaric acid, as well as aliphatic or aromatic sulphonic acids, such as lower alkane or optionally substituted benzenesulphonic acids, e.g. methane, ethane, benzene, p-toluene and p-bromobenzenesulfonic acid, further sulfamic acids, e.g. N-cyclohexylsulfamic acid.

The compounds of formula I and their salts are biologically active substances that can be used to influence plant growth as well as to combat harmful, especially phytopathogenic microorganisms, above all, however, have beneficial pharmacological, especially antifungal properties as well as beneficial effects on the central nervous system, especially anticonvulsant, anxiolytic and/or antidepressant properties. They can therefore be used as antifungal and/or anticonvulsant anxiolytic and/or antidepressant active substances in pharmaceuticals, for example to combat mycoses, i.e. parasitic fungus, as well as to treat epilepsy, anxiety, anxiety and depression conditions. The compounds of formula I are also, compared to other anticonvulsant and antidepressant active drugs, very tolerable. Thus

is LD^Q in mice and rats certainly clearly higher than 1000 mg/ kg<p.>o. Nor were there any on the mentioned small rodent species up to a dosage of 200 mg/kg p.o. established any disturbance of the motor skills.

The antifungal properties which justify the applicability of the compounds of formula I and their pharmaceutically usable acid addition salts for combating parasitic fungi on warm-blooded animals can, for example, be demonstrated in vitro by means of ordinary microbiological examination methods, for example by means of their toxic effect on fungal strains parasitizing warm-blooded animals which Trycho<p>hyton menta-grophytes, Microsporum canis, Sporotrichum schenkii, Asper-gillus fumigatus and Candida albicans, likewise in vivo on guinea pigs by means of healing effect on experimental infestations of the dorsal skin with Trychophyton, e.g. T. rubrum, after oral resp. local application.

The anticonvulsant effect of the compound of formula I and their pharmaceutically usable acid addition salts can be demonstrated in vivo, for example, on mice and on rats in the electroshock test in the dose range from 10 to 100 mg/kg p.o., also on mice in the pentatetrazol convulsion test at the corresponding dose -area. The anxiolytic effect can be demonstrated on mice and other small rodents using the Quatre-Plaques test in the dose range from approx. 10 to 100 mg/kg p.o. The substances also affect benzodiazepine receptors in vivo (Chang and Snyder, Eur.J. Pharmac. 48, (1978), 213-218. Moreover, already at doses below 30 mg/kg p.o. they stimulate the motility of mice and act antagonistically on the temperature effect of apomorphine Anticonvulsant, anxiolytic and antidepressant effects can be derived from the aforementioned action profile.

Preferred because of their good antimycotic as well as very good anticonvulsant, anxiolytic and/or antidepressant effects are compounds of formula I, in which R 1 and 1*2 independently of each other mean hydrogen, C1-C4-alkyl, such as methyl, C1- C₁-Alkoxy, such as methoxy, or halogen of atomic number up to and including 35, such as chlorine, A and B independently mean C₁-C₂-alkyl, such as methyl, |or together form an alkylene bridge of formula Ia or ibj

wherein R, means hydrogen, C1-C4-alkyl, such as methyl, or hydroxy-C1-C4-alkyl, such as hydroxymethyl, and R^ means hydrogen, C1-C4-alkyl, such as methyl or ethyl, -C ^-Alkoxy-C^-C4~alkyl, such as methoxy- or ethoxymethyl, or unsubstituted or in phenyl with C^-C^-alkyl, such as methyl, -C^-Alkoxy, such as methoxy, or halogen having atomic numbers up to 35, as chlorine, substituted phenoxy-C1 -C3-alkyl, as phenoxymethyl, resp. R^, Rg and R^ independently mean hydrogen, C^-C^-alkyl, such as methyl, ethyl, propyl or butyl, and Y means a group -CH= or -N=, especially those in which R^ and R ~either means hydrogen or halogen of atomic number up to and including 35, such as chlorine, which is especially bonded in the 5- and 7-position, as well as their salts, especially pharmaceutically usable salts.

Due to their antifungal and/or anticonvulsant, anxiolytic resp. antidepressant effect, it is above all preferred: 2-(benzofuran-2-yl)-2-/T-(1H-1, 2, 4-triazolyl)-methyl7-1,3-dioxolane,

2-(benzofuran-2-yl)-2-[T-(1H-1,2,4-triazolyl)-methyl-7-5-ethyl-5-methyl-1,3-dioxane,

2-(Benzofuran-2-yl)-2-(T-(1H-1,2,4-triazolyl)-methyl-7''5,5-dimethyl-4-propyl-1,3-dioxane,

2-(Benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-5,5-diethyl-1,3-dioxane,

2-(Benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-4-methyl-1,3-dioxane,

2-(Benzofuran-2-yl)-2-^T-(1H-1,2,4-triazolyl)-methyl7-5-ethyl-5-butyl-1,3-dioxane,

2-(Benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-5-ethyl-4-propyl-1,3-dioxane,

2-(Benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-1,3-dioxane,

2-(Benzofuran-2-yl)-2-(T-(1H-1m2m4-triazolyl)-methyl7~4-methoxymethyl-1,3-dioxolane,

2-(Benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-4-ethoxymethyl-1,3-dioxolane,

2-(Benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-4,5-dimethyl-1,3-dioxolane,

2-(Benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7"4-phenoxymethyl-1,3-dioxolane,

2-(Benzofuran-2-yl)-2-(1-iraidazolyl-methyl)-1,3-dioxolane, 2-(benzofuran-2-yl)-2-(1-imidazolyl-methyl)-5,5- dimethyl-1,3-dioxane,

2-(benzofuran-2-yl)-2-(1-imidazolyl-methyl)-4-methoxymethyl-1,3-dioxolane,

2-(5,7-dichloro-benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-4-ethyl-1,3-dioxolane,

2-(5,7-dichloro-benzofuran-2-yl)-2-(T-(1H-1,2,4-triazolyl)-methyl-1,3-dioxolane,

2-(5,7-dichloro-benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-4-methyl-1,3-dioxolane,

2-(5,7-dichloro-benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7~5,5-dimethyl-1,3-dioxane,

2-(5,7-dichloro-benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-4-ethoxymethyl-1,3-dioxolane,

2-(5,7-dichloro-benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-4-methoxymethyl-1,3-dioxolane,

2-(5,7-dichloro-benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-4-methyl-4-propyl-1,3-dioxane,

2-(5,7-dichloro-benzofuran-2-yl)-2-(1-imidazolylmethyl)-1,3-dioxolane,

2-(5,7-dichloro-benzofuran-2-yl)-2-(1-imidazolylmethyl)-4-methoxymethyl-1,3-dioxolane,

2-(5,7-dichloro-benzofuran-2-yl)-2-(1-imidazolylmethyl)-4-ethoxymethyl-1,3-dioxolane and 1-(benzofuran-2-yl)-1,1-dimethoxy -2-(T-(1H-1,2,4-triazolyl)-7-ethane,

as well as salts, especially pharmaceutically usable acid addition salts thereof. The process according to the invention for producing compounds of formula I and their salts is characterized by

A) a compound of formula II

in which Me is hydrogen or a metal cation, is condensed with a compound of formula III in which X is a nucleofuge leaving group, or B) in a compound of formula IV, the carbonyl group is transferred to a group of formula V

or

C) for the preparation of compounds of formula I, in which A and B together mean a group of formula -Ct^-CH (Ct^ZRg) - and Rg means a residue Rg different from hydrogen, compounds of formula VI and VII are condensed with each other ,

in which one of the residues X. and X_ means optionally present in salt form hydroxy or mercapto, e.g. that formula -Z-Me, and the other means a nucleofuge leaving group X or both X.j which also X2 means hydroxy groups, or

D) a compound with formula

in which one of the radicals X^ and X^ means a group of formula in which X,, means an optionally functionally modified oxo group and the other means hydrogen or X^ means a group of formula and X. means hydrogen, is cyclized or E) a compound with formula

dehydrogenated

and, if desired, a compound obtained according to the method is converted into another compound of formula I and/or a free compound obtained according to the method is transferred into a salt or a salt obtained according to the method is transferred into the free compound or into another salt.

Metal cations Me are thereby, for example, alkali metal, e.g. lithium, sodium or potassium cations, or alkaline earth metal groups with the formula /&^/ 2~ 7+ resp. /M<II->Hal7<+>/wherein M<11>means an alkaline earth metal, e.g. calcium or magnesium atom and Hal means a halogen, e.g. chlorine, bromine or iodine.

Nucleofuge leaving groups X are, for example, reactive esterified hydroxy groups, esterified with a halogen hydrogen acid, e.g. with hydrochloric, bromic or hydroiodic acid or a lower alkane, optionally substituted benzene or halosulfonic acid, e.g. with methane, ethane, ethylene, benzene, p<->toluene or fluorosulphonic acid.

The reaction of an azole of formula II in which Me preferably means a metal atom, especially an alkali metal atom, with a compound of formula III, in which X for example means halogen, especially chlorine, bromine or iodine, or benzenesulfonyloxy, p-tosyloxy, trifluoroacetyloxy or preferably lower alkylsulfonyloxy such as e.g. mesyloxy, is preferably carried out in a relatively polar but reaction-inert organic solvent, e.g. N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, acetonitrile, benzonitrile and others. Such solvents can be used in combination with other reaction-inert solvents such as aliphatic or aromatic hydrocarbons, e.g. benzene, toluene, xylene, hexane, petroleum ether, chlorobenzene, nitrobenzene and the like.

If X is chlorine or bromine, alkali iodide (such as NaJ or kJ) can be appropriately added to accelerate the reaction. Elevated temperatures from 0° to 220°C, preferably 80-170°C, are advantageous. The reaction mixture is suitably heated under reflux.

In those cases where formula II Me means hydrogen, the process is carried out in the presence of a base. Examples of such bases are inorganic bases such as the oxides, hydroxides, hydrides, carbonates and bicarbonates of alkali and alkaline earth metals such as e.g. tert.-amines such as triethylamine, triethylenediamine, pyridine, 4-dimethylaminopyridine, 4-pyrrolidylpyridine, etc.

In these and the following manufacturing variants, the intermediate and final products can be isolated from the reaction medium and, if desired, purified using one of the generally common methods, e.g. by extraction, crystallization, chromatography, distillation, etc.

The transfer of the carbonyl group in compounds of formula IV to the group of formula V takes place by reaction with an orthocarboxylic acid tri-C^-C^2~ alkyl ester or in the presence of an acid with at least 2 mol of a monohydric alcohol of formula A-OH ( Va), as a compound with formula I is obtained in which A and

B means equal -C₁₂ alkyl groups, or by reaction with a diol of formula Vb whereby a compound of formula I is obtained in which A and B together mean one of the initially defined alkylene bridges.

This ketalization reaction can be carried out analogously to already known ketalization reactions, for example analogously to the preparation of 2-bromomethyl-2,4-diphenyl-1,3-dioxolane /Synthesis, 1974 (I), 23/.

In the preferred embodiment of the ketalization, both reaction participants are heated for several hours together with an azeotrope former in one of the usual organic solvents under reflux. As azeotrope formers, there are e.g. namely benzene, toluene, xylene, 1,1,1-trichloroethane, tri- or tetrachloromethane, as it may be advantageous to add a strong acid such as e.g. p-toluenesulfonic acid. Usable organic solvents in this case are e.g. aromatic hydrocarbons such as benzene, toluene, xylene, etc. and saturated hydrocarbons such as n-hexane.

Other ketalization methods are also feasible, e.g. by reacting a ketone IV that is ketalized with one from alkanols or diols of formulas Va and Vb different alcohol, e.g. with an optionally substituted phenol or pyrocatechin and reketalize this by reaction with excess alkanol Va resp. diols (Vb) to (I). The output product is e.g. available according to one of the method variants A) and D).

The preparation of the compounds of formula I in which the substituents A and B together mean -CH2-CH(CH2ZRg)-, according to variant C) takes place, for example, by reaction of compounds with the formulas VI and VII in which a group -ZH and X2 means a group X. The reaction is carried out preferably in reaction-inert organic solvents. It is suitable for this e.g. N,N-Dimethylformamidem N,N-Dimethylacetamide, Hexamethylphosphorustriamide, Dimethylsulfoxide, 4-Methyl-4-pentanone, etc.

Mixtures with other reaction-inert solvents can also be used, e.g. with aromatic hydrocarbons such as benzene, toluene, xylene, etc. In many cases it can prove advantageous to accelerate the reaction rate to work in the presence of a base. Such bases are e.g. alkali metal hydrides or alkali metal carbonates. In certain cases, it may also be advantageous to first transfer the compound VI in a known manner to a suitable metal salt.

It preferably takes place by reaction of VI with a Na compound, e.g. sodium hydride, sodium hydroxide, etc.. This salt of VI is then reacted with the compound of formula VII. To increase the reaction rate, in many cases work can also be done at an elevated temperature, preferably 80°C to 130°C, resp. at the boiling point of the solvent.

In an analogous way, one can also react compounds with the formulas VI and VII, in which X^ means a group X and X^ means a group -ZH.

In the case of the condensation reaction of compounds of formula I, in which Z is oxygen, of compounds of formulas VI and VII, in which X^ and X^ are hydroxy, the reaction participants can be heated in a suitable solvent under reflux, while at the same time the water formed is distilled off aze- unextracted from the reaction mixture. Solvents include aromatic hydrocarbons such as toluene or the alcohol VII itself. With this reaction, you work appropriately in the presence of a strong acid, e.g. p-toluenesulfonic acid.

The cyclization of compounds of formula VIII according to variant D) takes place in the usual way if necessary in the presence of a condensing agent during cooling or heating, e.g.

in the temperature range from approx. 0° to approx. 150°C and/or below )

.inert gas such as nitrogen. As condensing agents, acid condensing agents such as proton acids or their anhydrides or acid salts, e.g. mineral acids, such as hydrohalic acids, e.g. hydrochloric or hydrobromic acid, sulfuric acid or phosphoric acid or polyphosphoric acid, preferably in the presence of a solvent or diluent inert to the reaction participants. Thus, the cyclization of the compounds of formula VIII is carried out in which one of the residues X^ and X^ represents a group of formula VIIIa and X^

means oxo or thioxo, for example by means of sulfuric acid or polyphosphoric acid while carrying out the cyclization of a compound of formula VIII in which X^ means a group of formula VIIIa and X,, means optionally substituted imino in an acetic acid solution of hydrogen chloride. The cyclization of compounds of formula VIII in which X^ denotes a group of formula VHIb takes place spontaneously under their conditions of formation, e.g. on standing, possibly under gentle heating in pyridine.

Functionally modified oxo groups X,- are thereby, for example, thioxo- and optionally substituted imino groups such as dilavealkylimino or optionally substituted anilo.

The dehydrogenation of compounds of formula IX according to variant E) takes place in the usual way, for example before treatment with sulfur or selenium, with noble metal catalysts, e.g. palladium on charcoal or by means of N-bromosuccinimide.

According to the method, compounds obtained can be transferred into other compounds of formula I by methods known per se.

Thus, for example, compounds obtained according to the method can be ketalized to other compounds of formula I. For example, in compounds of formula I in which A and B mean the same Cj -C^ 2-a-alkyl radicals by reaction with 1 mol of another -C^2 -alkanol of formula B-OH (Vc) replace a group A with a group B or by reaction with a diol of formula Vb replace both groups A with a divalent residue. The re-ketalization takes place in the usual way, for example in the presence of an acidic condensation agent such as a mineral, sulphonic or strong carboxylic acid, e.g. of hydrochloric or bromic acid, sulfuric acid, p<->toluenesulfonic acid or trifluoroacetic acid, advantageously under distillative resp. azeotrope-distillative removal of easily volatile reaction products.

Furthermore, in the carbocyclic aryl part of the compound obtained according to the method, you can possibly introduce additional substituents and/or R^- Thus, you can e.g. by reaction with a halogen in the presence of a Lewis acid such as an iron, zinc, boron or antimony halide, or by treatment with N-chlorosuccinimide introduce halogen.

Furthermore, halogen can be replaced by reaction with an alkyl metal compound, e.g. with alkyl lithium or alkyl magnesium halide with alkyl.

If the compounds of formula I are obtained as bases, they can be transferred with the help of inorganic or organic acids into the corresponding salts or preferably with equimolar amounts of metal salts to metal complexes of formula I. Conversely, the salts of formula I can be transferred, for example, in reaction with alkali ( hydrogen)carbonate or alkali hydroxide to the free bases of formula I.

The starting ketals of formula III can be prepared from ketones of formula X

by reaction with the desired alkanol, diol or orthocarboxylic acid ester in an inert solvent, e.g. a halogenated hydrocarbon such as methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, etc., and simultaneous or subsequent halogenation, since it is advantageous to add p-toluenesulfonic acid to accelerate the reaction. The intermediates of formula IV are prepared, e.g. by reaction of a ketone of formula X with halogen and further reaction of halogen ketones of formula XI

with an azole of formula II analogous variant A. Thereby Hal preferably means chlorine or bromine.

Ketals III, VI, VIII and IX are obtained analogously to variant B) by reaction of starting ketones, e.g. of formula IV with a suitable alcohol or diol.

The intermediates of formulas III, IV, VI, VIII and

IX, which was developed specifically for the production of the compounds according to the invention with formula I, are also new and are covered by the invention.

The compounds with formula I can exist in stereoisomeric forms, for example depending on the number of asymmetric carbon atoms in the form of an individual enantiomer or diastereomers or as mixtures thereof. Thus, in the mentioned ketalization reaction of a ketone with a substituted diol, mixtures of enantiomers or diastereomers of the resulting ketal. To illustrate a diastereomer pair of compounds of formula I, the following example will serve:

The configuration Ia shall be referred to here and in the following as the "cis" isomer.

The configuration Ib shall accordingly be designated as the "trans" isomer. The characterization of the two configurations can e.g. take place by means of NMR spectroscopy or X-ray structural analysis. The invention relates to all isomeric compounds and their salts. The separation of the diastereomers e.g. of Ia and Ib can, for example, take place by fractional crystallization or by means of chromatography (thin, thick-layer, column chromatography, liquid high-pressure chromatography, etc.). The two isomers show different biological effects. Enantiomeric pairs can be resolved by crystallization from an optically active solvent, chromatography on an optically active mobile or stationary phase or formation of diastereomeric auxiliaries, e.g. acid addition salts with optically active acids, separation of the diastereomers and liberation of the desired enantiomer. Generally, for practical purposes, the stereo-isomer mixtures are used.

The compounds of formula I and their pharmaceutically usable acid addition salts can be used for topical resp. local and systemic control of fungi parasitizing warm-blooded animals or for the systemic treatment of convulsive and tense states, especially those of epilepsy of anxiety and depression states, especially as an active substance in resp. for the production of pharmaceutical preparations as well as such pharmaceutical preparations.

In the case of pharmaceutical preparations which contain compounds of formula I or pharmaceutically usable salts thereof, it is consequently concerned with such for enteral, such as oral or rectal, and parenteral administration as well as for topical resp. local application to warm-blooded animals and containing the pharmacologically active substance alone or together with a pharmaceutically usable carrier material. The dosage of the active substance depends on the disease to be treated, warm blood type, age and the individual condition as well as the method of application.

In the normal case, it is for an approx. 75 kg heavy warm-blooded animal oral application to suggest an approximate daily dose of approx. 50-500 mg, preferably divided into several equal partial doses.

The pharmaceutical preparations contain e.g. from

about. 10% to approx. 80%, preferably from approx. 20% to approx. 60% of the active substance. Pharmaceutical preparations for enteral resp. parenteral administration is e.g. such in dosage unit forms such as dragees, tablets, capsules or suppositories, further ampoules. These are produced in a manner known per se, e.g. using conventional mixing, granulating, coating, dissolving or lyophilizing methods.

Thus, pharmaceutical preparations for oral use can be obtained by combining the active substance with solid carriers, possibly granulating a formed mixture and processing the mixture or the granulate if desired or necessary after adding suitable excipients for tablets or dragé cores.

Suitable carriers are especially fillers, such as sugar, e.g. lactose, sucrose, mannitol or sorbitol, cellulose preparations and/or calcium phosphate, e.g. tricalcium phosphate or calcium hydrogen phosphate, further binders such as starch pastes when using e.g. of corn, wheat, rice or potato starch, gelatins, tragacanth, methylcellulose and/or polyvinylpyrrolidone, and/or, if desired, explosives,

such as the above-mentioned starches, further carboxymethyl starch, cross-linked polyvinylpyrrolidone, agar, alginic acid or a salt thereof, such as sodium alginate. Auxiliaries are primarily floaters, regulators and lubricants, e.g. silicic acid, talc, stearic acid or salts thereof, such as magnesium or calcium stearate, and/or polyethylene glycol. Dragé cores are coated with suitable, possibly gastric juice-resistant coatings, using, among other things, concentrated sugar solutions that may contain gum arabic, talc, polyvinylpyrrolidone, polyethylene glycol and/or titanium dioxide, lacquer solutions in suitable organic solvents or solvent mixtures, or for the production of gastric juice-resistant coatings , solutions of suitable cellulose preparations, such as acetyl cellulose phthalate or hydroxypropyl methyl cellulose phthalate. Dyes or pigments can be added to the tablets or dragé coatings, e.g. for identification or characterization of different active substance doses.

Further orally usable pharmaceutical preparations are stick capsules of gelatin as well as soft, closed capsules of gelatin and a plasticizer such as glycerol or sorbitol. Stingable capsules can contain the active substance in the form of a granulate, e.g. in a mixture with fillers such as lactose, binders such as starches and/or lubricants such as talc or magnesium stearate, and possibly stabilizers. IN; soft capsules, the active substance is preferably dissolved or suspended in suitable liquids such as fatty oils, paraffin oil or liquid polyethylene glycols, as they may also have added stabilizers.

As rectally applicable pharmaceutical preparations, there are e.g. considering suppositories which consist of a combination of the active substance with a suppository base. As a suppository base material, it is suitable, e.g. natural or synthetic triglycerides, paraffin hydrocarbons, polyethylene glycols or higher alkanols. Furthermore, gelatin rectal capsules containing a combination of the active substance with a base mass can also be used; as base materials there are e.g. namely liquid triglycerides, polyethylene glycols or paraffin hydrocarbons.

For parenteral administration, aqueous solutions of an active substance in water-soluble form are primarily suitable, e.g. a water-soluble salt, further suspensions of the active substance as corresponding oily injection suspensions, using suitable lipophilic solvents or carriers such as fatty oils, e.g. sesame oil, or synthetic fatty acid esters, e.g. ethyl oleate, or triglycerides or other injection suspensions containing viscosity-increasing substances, e.g. sodium carboxymethylcellulose, sorbitol and/or dextran and optionally also stabilizers.

As a topical resp. locally applicable pharmaceutical preparations primarily include creams, ointments, pastes, powders, foams, tinctures and solutions containing from approx. 0.5 to approx. 20% of the active substance.

Creams are oil-in-water emulsions that have more than 50% water. Fatty alcohols are primarily used as oily bases, e.g. lauryl, cetyl or stearyl alcohol, fatty acids, e.g. palmitic or stearic acid, liquid to solid waxes, e.g. isopropyl myristate, wool wax or beeswax, and/or hydrocarbons, e.g. petroleum jelly (Petrolatum) or paraffin oil. Emulsifiers include surfactants with predominantly hydrophilic properties such as corresponding non-ionic emulsifiers, e.g. fatty acid esters of polyalcohols or ethylene oxide adducts thereof, such as polyglycerol fatty acid esters, polyethylene sorbitan fatty acid esters or polyoxyethylene fatty alcohol ethers or fatty acid esters or corresponding ionic emulsifiers such as alkali metal salts of fatty alcohol sulphates, e.g. sodium lauryl sulfate, sodium cetyl sulfate or sodium stearyl sulfate, which are usually used in the presence of fatty alcohols, e.g. ceryl alcohol or stearyl alcohol. Additions to the water phase include agents that reduce the drying out of the creams, e.g. polyalcohols such as glycerol, sorbitol, propylene glycol and/or polyethylene glycols, further preservatives, fragrances etc.

Ointments are water-in-oil emulsions that contain up to 70%, preferably, however, from approx. 20% to approx. 50% water or aqueous phases.

The fatty phase primarily refers to hydrocarbons, e.g. vaseline, paraffin oil and/or hard paraffins which, to improve the water-binding capacity, preferably contain suitable hydroxy compounds such as fatty alcohols or esters thereof, e.g. cetyl alcohol or wool wax alcohols or wool wax. Emulsifiers are equivalent lipophilic substances such as sorbitan fatty acid esters (Spans), e.g. sorbitan oleate and/or sorbitan iso-stearate. Additions to the water phase include humectants such as polyalcohols, e.g. glycerol, propylene glycol, sorbitol and/or polyethylene glycol as well as preservatives, fragrances etc.

Fatty ointments are anhydrous and contain hydrocarbons in particular as a basis, e.g. paraffin, vaseline and/or liquid paraffins, further natural or partially synthetic fat, e.g. coconut fatty acid triglyceride or preferably hardened oils, e.g. hydrogenated peanut or castor oil, further fatty acid partial esters of glycerol, e.g. glycerol mono- and -distearate, as well as e.g. the water absorption increasing fatty alcohols, emulsifiers and/or additives mentioned in connection with the ointments.

Pastes are creams and ointments with secretion-absorbing powder ingredients such as metal oxides, e.g. titanium oxide or zinc oxide, further talc and/or aluminum silicates which have the task of binding the moisture or secretions present.

Powders contain, in addition to the active substance, e.g. above-mentioned secretion-absorbing powder ingredients.

Foams are administered from pressure vessels and are liquid oil-in-water emulsions in aerosol form, with halogenated hydrocarbons such as chlorofluorolower alkanes, e.g. dichlorodifluoromethane or dichlorotetrafluoroethane. Hydrocarbons are used as the oil phase, e.g. paraffin oil, fatty alcohols, e.g. cetyl alcohol, fatty acid esters, e.g. isopropyl myristate and/or other waxes. Emulsifiers used include mixtures of those with predominantly hydrophilic properties such as polyoxyethylene sorbitan fatty acid esters (Tweens) and those with predominantly lipophilic properties such as sorbitan fatty acid esters (Spans). In addition, there are the usual additives such as preservatives etc.

Tinctures and solutions mostly have aqueous-ethanolic bases such as polyalcohols, e.g. glycerol, glycols and/or polyethylene glycol, as a humectant to reduce evaporation and re-greasing substances such as fatty acid esters with lower polyethylene glycols, i.e. lipophilic substances soluble in an aqueous mixture as a replacement for the fatty substances that are removed from the skin with ethanol and, if necessary, other aids - and additives.

The preparation of the topically applicable pharmaceutical preparations takes place in a manner known per se, e.g. by dissolving or suspending the active substance in the base or in a part thereof, if necessary. When administering the active substance as a solution, this is usually dissolved before emulsification in one of the two phases; when processed as a suspension, it is mixed after emulsification with part of the base and then the rest of the formulation is added.

In the following examples, temperatures are given in degrees Celsius, percentages are always referred to weight.

If nothing else is noted, when naming an active substance with formula I, the racemic or diastereomeric mixture. If a targeted synthesis of pure isomers takes place, a product of formula I can be obtained in the form of a mixture of the possible isomers.

Production examples:

Eczema Gel_1_

Manufacture of

2-( benzofuran- 2- yl)- 2-/ T-( TH- 1, 2, 4- triazolyl)- methyl7- 5, 5-dimethyl- T, 3- dioxane

a) Production of intermediate products

2-( benzofuran-2- yl)- 2- bromomethyl- 5, 5- dimethyl- 1, 3- dioxane

48 g of 2-acetylbenzofuran and 55 g of 2,2-dimethyl-

1,3-propanediol in 400 ml of 1,1,1-trichloroethane is heated in the presence of 2 g of catalytically active p-toluenesulfonic acid for 30 hours under reflux, while the water formed is separated by means of a water separator. Then, 49.6 g of bromine in 50 ml of 1,1,1-trichloroethane are added dropwise over the course of 45 minutes and the reaction mixture is heated for a further 2 hours under reflux. After cooling to room temperature, the reaction mixture is washed three times with 100 ml of water each time, dried over sodium sulfate, filtered, the solvent is evaporated and the oily crude product is purified by fractional distillation under high vacuum. Boiling point 130-140°C/0.04 mbar.

b) Production of the final product:

18.4 g /1,2,4-triazole, 11.7 9 / potassium carbonate

and a catalytically effective amount of sodium iodide in 100 ml of dimethylsulfoxide is stirred together with 18.4 g of the 2-(benzofuran-2-yl)-2-bromomethyl-5,5-dimethyl-1,3-dioxane produced from a) in 30 hours at an internal temperature of +120°C. After cooling to room temperature, 600 ml of water are added, extracted three times with 200 ml of ethyl acetate each time, the combined extracts are washed twice with 100 ml of water each time, dried over sodium sulphate, filtered and the solvent is evaporated. The oily residue is purified by column chromatography over silica gel 60 with ethyl acetate as eluent. After the eluent has evaporated, the oily residue is brought to crystallization by adding diethyl ether. The colorless crystals melt at 102.5-106°C.

Example_el_2

Nitrate of 2-(benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7~5,5-dimethyl-1,3-dioxane 5 g j2-(benzofuran-2 -yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7~5,5-dimethyl-1,3-dioxane in 100 ml diisopropyl ether and 20 ml dioxane are mixed with 5 ml 65%-ig nitric acid. After completion of the slightly exothermic reaction, the salt falls out as colorless crystalline powder, which is filtered off and washed with diisopropyl ether. After removal of the solvent in vacuo, the nitrate melts at 169-171°C during decomposition.

Example_3

Manufacture of

Hydrochloride of 2-(benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7~1,3-dioxane

3.13g; 2-(Benzofuran-2-yl)-2-(T-(1H-1,2,4-triazolyl)-methyl7-1,3-dioxane is dissolved in 50 ml of ethyl acetate and mixed with 100 ml of diethyl ether. By instilling 1.1 g; concentrated hydrochloric acid with stirring, a beige crystalline suspension forms which is filtered off after 20 minutes and washed with 100 ml of diethyl ether. After drying in vacuum, the hydrochloride melts at 192-197°C.

Example_el_4

Manufacture of

1-(benzofuran-2-yl)-1,1-dimethoxy-2-/T-(1H-1,2,4-triazolyl)1-ethane

a) Production of intermediate product

1 -( benzofuran-2- yl)- 1, 1- dimethoxy- 2- bromo- ethane

33.2 g of 2-(2-bromoacetyl)-benzofuran, 29.5 g of trimethyl orthoformic acid and 2.6 g of /p-toluenesulfonic acid in 275 ml of methanol are heated for 15 hours under reflux. Methanol is then removed in vacuo and the residue is dissolved in 250 ml of diethyl ether. The ethereal solution is washed once with 125 ml of 1N caustic soda and twice with each time 125 ml of water, dried over sodium sulphate, filtered and the solvent is removed in vacuo. The oily residue is brought to crystallisation by adding hexane. After recrystallization from ethanol, the yellow crystals melt at 72-73°C.

b) Production of the final product:

9 g (1,2,4-triazole, 18 g potassium carbonate, 1 g potassium iodide and 28.5 parts of the 1-(benzofuran-2-yl)-1,1-dimethoxy-2-bromoethane produced under point a) in 150 ml of dimethylsulfoxide is stirred at an internal temperature of 120°C for 15 hours. After the addition of a further 3.5 g of 1,2,4-triazole and 1 q/potassium iodide, the mixture is further stirred at an internal temperature of 140°C for a further 20 hours. The brown reaction mixture is then cooled to room temperature and poured into 600 ml of ice water and extracted three times with 200 ml of ethyl acetate each time. The combined extracts are washed twice with 200 ml of water each time, dried over sodium sulphate, filtered and the solvent is removed in vacuo. The oily residue is brought to crystallisation by the addition of petroleum ether. After recrystallization from isopropanol, compound No. 1.37 melts at 120-123°C. Example_el_5

2-( 5, 7- dichloro- benzofuran- 2- yl)- 2-/ T-( 1H- 1, 2, 4- triazolyl)-methyl7~ 4- ethyl- 1, 3- dioxolane

10.8 g of the nitrate of 1 -(benzofuran-2-yl)-2-(1H-1,2,4-triazolyl-1-yl)-ethanone, 7 g of 1,2-butanediol, 4.9 g of p -toluenesulfonic acid, 20 g of 1-pentanol and 200 ml of xylene are heated for 3 days under reflux while the water formed is separated by means of a water separator. After cooling to room temperature, wash twice with 200 ml of diluted caustic soda each time, twice with 100 ml of water each time, dry over sodium sulfate, filter and evaporate the solvent.

The oily residue is purified by column chromatography over J silica gel with ethyl acetate as eluent. After evaporation of the eluent, the oily residue slowly crystallizes out. The beige crystals melt at 102.5-105°C.

Example_el_6

Manufacture of

2-( benzofuran-2- yl)- 2-/ 1 -( 1H- 1, 2, 4- triazolyl)- methyl7- 4- metoxymethyl- 1, 3- dioxolane

12.5 g of (2-(benzofuran-2-yl)-2-[1-(1H-1,2,4-triazolyl)-methyl7-4-hydroxymethyl-1,3-dioxolane is dissolved in 150

ml of N,N-dimethylformamide, mixed under nitrogen and stirring with 1.9 g of a 55% sodium hydride dispersion and heated for 2 hours at 80°C. After cooling to room temperature, add 6.3 dropwise while stirring over the course of 1 hour

g Imethyl iodide. The reaction mixture is heated for 2 hours at 60°C and cooled to room temperature, diluted with 800 ml of ice water, extracted three times with 300 ml of ethyl acetate each time. The combined extracts are washed twice with each time 30 ml of water, dried over sodium sulfate, filtered. The solvent is evaporated and the residue is purified by column chromatography on silica gel with acetone/ethyl acetate (1:1) as eluent. After evaporation of the eluent mixture, a

25

viscous oil; nQ = 1.5540.

Example_7

Analogously to what is discussed in examples 1 to 6, the following compounds of formula I can be prepared (if nothing is specifically noted, as diastereomer mixtures with different mixing ratios):

Example_8

Formulation examples for pharmaceutical preparations:

A. Ointments:

An ointment containing 5% 2-(benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-5,5-dimethyl-1,3-dioxane can be prepared as follows:

Composition:

The fats and emulsifiers are melted together. The preservative is dissolved in water and the solution is emulsified in the fat melts at an elevated temperature. After cooling, a suspension of the active substance is incorporated into part of the fat melt in the emulsion.

B. Cream

Cream containing 10% 2-(benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7~5,5-dimethyl-1,3-dioxane can be prepared as follows:

Composition:

The acrylic acid polymer is suspended in a mixture of demineralized water and 1,2-propylene glycol. While stirring, triethanolamine is added to this, with which a slime is obtained. A mixture of isopropyl palmitate, cetyl palmitate, silicone oil, sorbitan monostearate and polysorbate is heated to approx. 75°C and incorporated while stirring in Idet likewise at approx. 75°C heated mucus. The cream base layer, cooled to room temperature, is then used to produce a concentrate with the active substance. The concentrate is homogenised using a continuous homogeniser and then added in portions to the base.

Cream containing 5% 2-(2-benzofuran-2-yl)-2-/1-(1H-1,2,4-triazolyl)-methyl7~5,5-dimethyl-1,3-dioxane can be prepared as follows :

Composition:

Cetyl alcohol, cetyl palmitate, the triglyceride mixture, stearic acid and glycerine stearate are combined. The micro-crystalline cellulose is dispersed in part of the water. Cetomacrogol is dissolved in the remaining part of the water and the propylene glycol and the mucus are mixed there. The fat phase is then added while stirring to the water phase and stirred cold. Finally, the active ingredient is rubbed in with part of the base and then incorporated by rubbing into the rest of the cream.

C. Hydrogels:

A transparent hydrogel containing 5% 2-(2-benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7"5,5-dimethyl-1,3-dioxane is prepared as following:

Composition:

The hydroxylpropyl methylcellulose swells in water. The active substance is dissolved in a mixture of isopropanol and <p>propylene glycol. The active substance solution is then mixed with a swollen cellulose derivative and, if desired, mixed with odorous substances (0.1%).

D. Foam spray

A foam spray containing 1% 2-(benzofuran-2-yl)-2-(T-(1H-1,2,4-triazolyl)-methyl-7-5,5-dimethyl-1,3-dioxane can be prepared as follows:

Composition:

Cetyl alcohol, paraffin oil, isopropyl myristate, Cetomacrogol and sorbitan stearate are combined. Methyl and propyl paraben dissolve in warm water. The melt and the o<p>solution are then mixed. The active substance suspended in propylene glycol is incorporated into the foundation. Chemoderm is then added and topped up with water to the final weight.

Filling:

20 ml of the mixture is filled in an aluminum block box. The box is equipped with a valve and the propellant gas is filled in under pressure.

E. Capsules

Gelatin capsules containing 200 mg 2-(benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7~5,5-dimethyl-1,3-dioxane as active substance can e.g. e.g. produced as follows:

Composition (for 1000 capsules)

The active substance and the lactose (finely ground) mix well with each other. The resulting powder is sieved and filled in portions of 0.20 g each in gelatin capsules.

F. Tablets

Tablets containing 25 mg of active substance, e.g. 2-(Benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7~5,5-dimethyl-1,3-dioxane can be obtained in the following way:

Ingredients (for 1000 tablets)

Manufacturing:

All solid ingredients are first passed through a sieve with a mesh size of 0.6 mm. The active substance, lactose, talc, magnesium stearate and half of the starch are then mixed. The other half of the starch is suspended in 40 ml of water and this suspension is added to a boiling solution of polyethylene glycol in 100 ml of water, and the mixture is granulated, if necessary, with the addition of water. The granulate is dried overnight at 35°C, passed through a sieve with a mesh size of 1.2 mm and pressed into concave tablets of approx. 6 mm diameter.

Tablets containing 100 mg of active substance, e.g. 2-(Benzofuran-2-yl)-2-^T-(1H-1,2,4-triazolyl)-methyl-7-5,5-dimethyl-1,3-dioxane can be prepared as follows:

Ingredients (for 1000 tablets)

Manufacturing:

All solid ingredients are first passed through a sieve with a mesh size of 0.6 mm. The active substance, the lactose, talc, magnesium stearate and half of the starch are then mixed. The other half of the starch is suspended in 40 ml of water, and this suspension is added to a boiling solution of polyethylene glycol in 100 ml of water, the mixture is granulated, if necessary while adding water. The granulate is dried overnight at 35°C, passed through a sieve with a mesh size of 1.2 mm and pressed into concave tablets of approx.

6 mm diameter.

Tablets containing 75 mg of active substance, e.g. 2-(Benzofuran-2-yl)-2-^T-(1H-1,2,4-triazolyl)-methyl-7-5,5-dimethyl-1,3-dioxane can be prepared as follows:

Ingredients (for 1000 tablets)

Manufacturing:

All solid ingredients are first passed through a sieve with a mesh size of 0.6 mm. The active substance, the lactose, talc, magnesium stearate and half of the starch are then mixed. The other half of the starch is suspended in 40 ml of water, and this suspension is added to a boiling solution of polyethylene glycol in 100 ml of water, and the mixture is granulated, if necessary, with the addition of water. The granulate is dried overnight at 35°C, passed through a sieve with a mesh size of 1.2 mm and pressed into concave tablets of approx.

6 mm diameter.

In an analogous manner, pharmaceutical preparations containing another compound obtained according to one of examples 1 to 7 can also be prepared.

Claims (7)

1. Process for the preparation of compounds of formula I in which Y means -CH= or -N=; R 1 and R 2 independently of one another mean hydrogen, halogen, C 1 -C 4 alkyl or -C 4 alkyl; A and B mean C₁-C₁-alkyl or together mean one of the following alkylene bridges or while R^ and R^ independently of each other mean hydrogen, one with halogen or a group of the formula -Z-Rg- substituted or unsubstituted C^-C^-alkyl or one with halogen or -C^-alkoxy and/or C^ - C4~ alkyl substituted or unsubstituted phenyl, where Z means oxygen or sulfur and Rg means hydrogen, a Cj -C6 -alkyl substituted or unsubstituted Cj -C8 -alkyl, C3~ C4~ alkenyl, 2-propynyl or 3-halo- 2-propynyl; one with halogen, C 1 -C 3 -alkyl, -C 3 - alkoxy, nitro and/or trifluoromethyl ' substituted or unsubstituted phenyl or one with halogen, C 1 -C 3 -alkyl and/or -C 3 - alkoxy substituted or unsubstituted benzyl; R 1 , R 8 and R 1 independently mean hydrogen or C 1 -C^ -alkyl, as the total number of carbon atoms in R^, Rg and Ry must not exceed the number 6, and Rg means hydrogen or C₁ -C₁ -alkyl, and their salts, characterized by A) a compound of formula II in which Me means hydrogen or a metal cation, is condensed with a compound of formula III wherein X means a nucleofuge cleavable group, orB) in a compound of formula IV the carbonyl group is transferred to a group of formula V orC) for the preparation of compounds of formula I, in which A and B together mean a group of formula -CF^-CH (CI^ZRg) - and Rg means a residue different from hydrogen Rg, are condensed with each other, compounds of formula VI and VII in which one of the residues and X^ means optionally present in salt form hydroxy or mercapto, e.g. of formula -Z-Me and the other means a nucleofuge cleavable group X or X^ as well as X^ means hydroxy groups or D) a compound with formula wherein one of the residues X^ and X^ means a group of formula in which X,, means an optionally functionally modified oxo group and the other hydrogen or X^ means a group of formula and X^ means hydrogen, is cyclized, or E) a compound of formula dehydrogenated, and, if desired, a compound obtained according to the method is converted into another compound of formula I and/or a free compound obtained according to the method is transferred into a salt or a salt obtained according to the method is transferred into the free compound or into another salt. 2. Process according to claim 1 for the preparation of compounds of formula I, in which R1 and R2 independently of each other mean hydrogen, C1 -C4 -alkyl, -C4 - alkoxy or halogen atomic number up to and including 35, A and B mean independently of each other C 1 -C 2 -alkyl \or together form an alkylene bridge of formula Ia or Ic in which R 3 means hydrogen, C 1 -C 4 -alkyl or hydroxy-C 1 -C 4 -alkyl and R 4 means hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl or unsubstituted or in phenyl with -C4-alkyl, Cj -C4~ alkoxy or halogen with atomic number up to and including 35 substituted phenoxy-C1 -C4 -alkyl, resp. R 5 , R 8 and R 7 independently mean hydrogen or C 1 -C 4 alkyl and Y means a group -CH= or -N= as well as their salts. 3. Method according to claim 1 for the preparation of compounds of formula I in which R 1 and R 2 either mean hydrogen or halogen of atomic number up to and including 35, which is especially bound to the 5- and 7-position, A and B are independently of each other Cj -C 1 -alkyl combine to form an alkylene bridge with formulas Ia or Ic wherein R^ means hydrogen, C^ -C^ -alkyl or hydroxy-C^ -C^ -alkyl and R^ means hydrogen, Cj -C^ -alkyl, Cj -C^ -alkoxy-Cj -C^ -alkyl or unsubstituted or in phenyl with C 1 -C 2 -alkyl, C.J. -C.sub.3 -Alkoxy or halogen with atomic number up to and including 35, substituted phenoxy-C.sub.1 -C.sub.3 -alkyl, resp. R5 , Rg and R? independently of each other means hydrogen or C 1 -C 4 -alkyl and Y means a group -CH= or -N= and their salts. 4. Process according to claim 1 for the preparation of 2-(benzofuran-2-yl)-2-^T-(1H-1,2,4-triazolyl)-methyl7~ 1,3-dioxolane, 2-(benzofuran-2 -yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-5-ethyl-5-methyl-1,3-dioxane, 2-(benzofuran-2-yl)-2-/ T-(1H-1,2,4-triazolyl)-methyl7-5,5-dimethyl-4-propyl-1,3-dioxane, 2-(benzofuran-2-yl)-2-/T-(1H- 1,2,4-triazolyl)-methyl7-5,5-dimethyl-1,3-dioxane, 2-(benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)- methyl7-4-methyl-1,3-dioxane, 2-(benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-5-ethyl-5-butyl-1 ,3-dioxane, 2-(benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-5-ethyl-4-propyl-1,3-dioxane, 2- (benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7~ 1,3-dioxane, 2-(benzofuran-2-yl)-2-/T-(1H -1,2,4-triazolyl)-methyl7-4-ethoxymethyl -1,3-dioxolane, 2-(benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7 -4,5-dimethyl-1,3-dioxolane, 2-(Benzofuran-2-yl)-2-(T-(1H-1,2,4-triazolyl)-methyl7-4,5-dimethyl-1,3-dioxolane, 2-(Benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-4-phenoxymethyl-1,3-dioxolane, 2-(Benzofuran-2-yl)-2 -(1-imidazolyl-methyl)-1,3-dioxolane, 2-(benzofuran-2-yl)-2-(1-imidazolyl-methyl)-5,5-dimethyl-1,3-dioxane, 2-( benzofuran-2-yl)-2-(1-imidazolyl-methyl)-4-methoxymethyl-1,3-dioxolane, 2-(5,7-dichloro-benzofuran-2-yl)-2-/T-(1H -1,2,4-triazolyl)-methyl7-4-ethyl-1,3-dioxolane, 2-(5,7-dichloro-benzofuran-2-yl)-2-/T-(1H-1,2, 4-triazolyl)-methyl7~ 1,3-dioxolane, 2-(5,7-dichloro-benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-5, 5-dimethyl-1,3-dioxane, 2-(5,7-dichloro-benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7_4-ethoxymethyl-1,3 -dioxolane, 2-(5,7-dichloro-benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-4-methoxymethyl-1,3-dioxolane, 2- (5,7-dichloro-benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl7-5-methyl-5-propyl-1,3-dioxane, 2-( 5,7-dichloro-benzofuran-2-yl)-2-(1-imidazolylmethyl)-1,3-dioxolane, 2-(5,7-dichloro-benzofuran-2-yl)-2-(1-imidazolylmethyl) -4-Methoxymethyl-1,3-dioxolane, 2-(5,7-dichloro-benzofuran-2 -yl)-2-(1-imidazolylmethyl)-4-ethoxymethyl-1,3-dioxolane, or 1 -(benzofuran-2-yl)-1,1-dimethoxy-2-/T-(1H-1,2,4-triazolyl)-ethane or in each case a salt thereof. I i i 5. Process according to claim 1 for the preparation of 2-(5,7-dichloro-benzofuran-2-yl)-2-/T-(1H-1,2,4-triazolyl)-methyl-7-4-methyl-1,3- dioxolane or a salt thereof. 6. The compounds formed according to the method according to claim 1. 7. Process for the production of pharmaceutical preparations, characterized in that a compound obtained according to claims 1-6 is mixed with common pharmaceutical excipients and/or carriers.