DE2705677A1 - 2,4-DICHLOROPHENYL-IMIDAZOLYL-AETHANONE (OLE), METHOD FOR MANUFACTURING AND USING THEY AS A MEDICINAL PRODUCT - Google Patents

Description

2,4-dichlorophenyl-imidazolyl-ethanones (ole), process for their production and their use as pharmaceuticals

The present invention relates to new 2,4-dichlorophenylimidazolylethanones (ole), a process for their production and their use as medicaments, in particular as antimycotics. *

It is already known that comprise phenoxy-imidazolyl derivatives good antifungal activity (see German Offenlegungsschriften 2,105,490 [Le A 13 458] and 2,333,355 Q ^ _{A 15} 3:45]), however, _f is their effect, in particular against dermatophytes and in-vivo against Candida, not always entirely satisfactory.

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It has been found that the new 2,4-dichlorophenyl-imidazolylethanones (ole) the general formula

- O - CH - A - (()> - Cl (I) ^X n

in which

A stands for a keto group or a CH (OH) group,

X represents halogen, alkyl or optionally substituted phenyl and

η stands for integers from 0 to 3,

and their physiologically compatible salts have strong antifungal properties.

Those compounds of the formula (i) in which A represents the CH (OH) group have two asymmetrical carbon atoms; they can therefore exist in the two geometric isomers (erythro and threo form), which can be obtained in different proportions. In both cases, they exist as optical isomers. All isomers are claimed according to the invention.

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It has also been found that the 2,4-dichlorophenyl-imidazolylethanones (ole) of formula (I) is obtained when l-bromo-2- (2,4-dichlorophenyl) -l-phenoxy-ethan-2-one the formula

- Cl (II)

in which

X and η have the meaning given above,

with imidazole in the presence of a diluent and an acid binder, and optionally the resulting Imidazolylethanones in a manner known per se with complex borohydrides, optionally in the presence of a diluent, reduced.

Furthermore, the 2,4-dichloro-r obtainable according to the invention can be used phenyl-imidazolyl-ethanones (ols) can be converted into the salts by reaction with acids.

Surprisingly, the active ingredients according to the invention show a better antimycotic, therapeutically useful activity than the phenoxy-imidazolyl derivatives known from the prior art, which are chemically and effectively the most obvious compounds. The substances according to the invention thus represent a Enrichment of pharmacy.

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If you use l-bromo-1- (4-chlorophenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one and imidazole as starting materials, the course of the reaction can be represented by the following equation will:

Cl. _N

> -O-CH-CO- ^ 3-Cl +1 NH-Br L = /

-Cl

If you use 1- (4-chlorophenoxy) -2- (2,4-dichlorophenyl) -1-imidazole - 1 -yl) -ethan-2-one and sodium borohydride as starting materials, the course of the reaction can be indicated by the following equation be reproduced:

CI _n HO 9

^ 3 ^^ C

^NaBH *

The l-bromo-2- (2,4-dichlorophenyl) -l-phenoxy-ethan-2-ones to be used as starting materials are generally defined by the formula (II). In this formula, X preferably represents Halogens fluorine, chlorine, bromine and iodine, for straight-chain or branched alkyl with 1 to 4 carbon atoms and for optionally phenyl substituted by halogen, especially chlorine. The index η preferably stands for integers from 0 to 2.

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Examples of starting materials of the formula (II) include:

1-Bromo-1-phenoxy-2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (4-chlorophenoxy) -2- (2,4-dichlorophenyl> -ethan-2-one 1-Bromo-1- (4-fluorophenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (4-bromophenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (4-iodophenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (2,4-dichlorophenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (2,6-dichlorophenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (2,5-dichlorophenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (3-fluorophenoxy) -2- (2,4-dichiorphenyl) -ethan-2-one 1-Bromo-1- (3-chlorophenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Erom-1- (3-bromophenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (2-chlorophenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (4-methylphenoxy) -2- (2,4-dichlorophenyl) ethan-2-one 1-Bromo-1- (4-ethylphenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (3-methylphenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (2-methylphenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (2-isopropylphenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (4-chloro-2-methylphenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one

1-Bromo-1- (4-bromo-2-methylphenoxy) -2- (2,4-dichlorophenyl) ethan-2-one

1-Bromo-1- (4-fluoro-2-methylphenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one

1-Bromo-1- (4-iodo-2-methylphenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one

1-Bromo-1- (2,3-dimethylphenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (4-biphenylyloxy) -2- (2,4-dichlorophenyl) -ethan-2-one 1-Bromo-1- (4-4-chlorobiphenylyloxy) -2- (2,4-dichlorophenyl) -ethan-2-one

1-Bromo-1- (4-2 ', 4 "-dichlorobiphenylyloxy) -2- (2,4-dichlorophenyl) -ethan-2-one

1-Bromo-1- (4-2,4'-dichlorophenylyloxy) -2- (2,4-dichlorophenyl) ethan-2-one

1-Bromo-1- (4-4'-bromobiphenylyloxy) -2- (2,4-dichlorophenyl) ethan-2-one

1-Bromo-1- (4-2-chlorobiphenylyloxy) -2- (2,4-dichlorophenyl) -ethan-2-one
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The l-bromo-2- (2,4-dichlorophenyl) -l-phenoxy-ethan-2-ones to be used as starting materials of formula (II) are not yet known, but can be prepared by known processes, by taking known phenols of the formula

- OH (III)

in which

X and η have the meaning given above,

with a bromoacetophenone of the formula

Br - CH ₂ - CO - ((I) -Cl (IV)

implements. The remaining active hydrogen atom is then exchanged for bromine in the usual way.

The salts used for the compounds of the formula (i) are salts with physiologically compatible acids. These include preferably the hydrohalic acids such as the hydrogen chloride acid and hydrobromic acid, especially the Hydrochloric acid, phosphoric acid, nitric acid, mono- and bifunctional carboxylic acids and hydroxycarboxylic acids, e.g. Acetic acid, citric acid, sorbic acid, lactic acid, 1,5-naphthalene-disulfonic acid.

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Suitable diluents for the reaction according to the invention are preferably inert organic solvents. For this preferably include ketones, such as diethyl ketone, in particular acetone and methyl ethyl ketone; Nitriles, such as propionitrile, in particular Acetonitrile; Alcohols such as ethanol or isopropanol; Ethers such as tetrahydrofuran or dioxane; aromatic hydrocarbons, such as toluene and 1,3-dichlorobenzene, benzene; Formamides, such as, in particular, dimethylformamide; and halogenated hydrocarbons such as methylene chloride, carbon tetrachloride or chloroform.

The reaction is carried out in the presence of an acid binder. You can use all commonly used inorganic or add organic acid binders, such as alkali carbonates, for example sodium carbonate, potassium carbonate and sodium hydrogen carbonate, or such as lower tertiary alkylamines, cycloalkylamines or aralkylamines, for example triethylamine, Ν, Ν-dimethylcyclohexylamine, Dicyclohexylmethylamine, N, N-dimethylbenzylamine, furthermore pyridine and diazabicyclooctane. Used preferably a corresponding excess of imidazole.

The reaction temperatures can be varied over a wide range. ^{In general, one works between about 0} to about 150 ° C., preferably at 60 to 120 ° C., in the presence of a solvent such as acetone or methyl ethyl ketone.

When carrying out the method according to the invention 1 to 2 moles of azole and 1 to 2 moles of acid binder are preferably added to 1 mole of the compounds of the formula (II). For isolation of the compounds of the formula (I), the solvent is distilled off and the residue is taken up in an organic solvent and washed with water. The organic phase is dried over sodium sulfate and the solvent is removed in vacuo freed. The residue is purified by distillation or recrystallization.

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For the reduction according to the invention, polar organic solvents are suitable as diluents for the reaction according to the invention. These preferably include alcohols such as methanol, ethanol, butanol, isopropanol, and ethers such as diethyl ether or tetrahydrofuran. The reaction is preferably carried out generally at O to 3O ° C, at 0 to 20 ⁰ C. For this purpose, about 1 mole of a borohydride, such as sodium borohydride or lithium borohydride, is used per mole of the compound of the formula (II). To isolate the compounds of the formula (I), the residue is taken up, for example, in dilute hydrochloric acid, then made alkaline and extracted with an organic solvent, or only water is added and an organic solvent is extracted by shaking. The further work-up takes place in the customary manner.

As examples of particularly effective representatives of the invention In addition to the preparation examples and the examples in Table 1, the following active ingredients may be mentioned:

1- (2-chlorophenoxy) -2- (2,4-dichlorophenyl) -1- (imidazol-1-yl) ethan-2-one or oil

1- (2-isopropylphenoxy) -2- (2,4-dichlorophenyl) -1- (imidazol-1-yl) -ethane-2-one or -oil

1- (2-methylphenoxy) -2- (2,4-dichlorophenyl) -1- (imidazol-1-yl) ethan-2-one or oil

1- (2-chloro-4-methylphenoxy) -2- (2,4-dichlorophenyl) -1- (imidazole - 1 -yl) ethan-2-one or oil

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The compounds of the formula (I) which can be used according to the invention and their salts have antimicrobial, especially strong antifungal, action. You have a very broad one antifungal spectrum of activity, in particular against dermatophytes and sprout fungi as well as biphasic fungi, e.g. against Candida species, such as Candida albicans, Epidermophyton species, such as Epidermophyton floccosum, Aspergillus species, such as Aspergillus niger and Aspergillus fumigatus, such as Trichophyton species, such as Trichophyton mentagrophytes, Microsporon Species such as Microsporon felineum and Penicillium species such as Penicillium commune. The list of these microorganisms does not in any way limit the number of germs that can be combated but is only of an explanatory nature.

As indication areas in human medicine, for example to be named:

Dermatomycoses and systemic mycoses caused by Trichophyton mentagrophytes and other Trichophyton species, Mikiosporon species, Epidermophyton floccosum, sprouts and biphasic fungi as well as mold.

Ais areas of indication in veterinary medicine can, for example are listed:

All dermatomycoses and systemic mycoses, especially those caused by the above-mentioned pathogens.

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J NACHGER

The present invention includes pharmaceutical lines which, in addition to non-toxic, inert, pharmaceutically suitable ones Carriers contain one or more active ingredients according to the invention or those of one or more according to the invention There are active ingredients and processes for the production of these preparations.

The present invention also includes pharmaceutical preparations in dosage units. This means that the preparations in the form of individual parts, e.g. tablets, coated tablets, Capsules, pills, suppositories and ampoules are available whose active ingredient content is a fraction or a multiple of one Single dose. The dosage units can be, for example, 1, 2, 3 or 4 single doses or 1/2, 1/3 or 1/4 of a single dose contain. A single dose preferably contains the amount of active ingredient that is administered in one application and which usually corresponds to a whole, a half, or a third or a quarter of a daily dose.

Among non-toxic, inert pharmaceutically acceptable carriers are solid, semi-solid or liquid diluents, fillers and formulation auxiliaries of all kinds to understand.

Preferred pharmaceutical preparations are tablets, coated tablets, capsules, pills, granules, suppositories, solutions, Suspensions and emulsions, pastes, ointments, gels, creams, Called lotions, powders and sprays.

Tablets, dragees, capsules, pills and granules can contain the active ingredient (s) in addition to the usual carriers, such as (a) fillers and extenders, e.g. starches, lactose, cane sugar, glucose, mannitol and silicic acid, (b) binders, e.g. carboxymethyl cellulose, alginates, gelatine, polyvinylpyrrolidone, (c) humectants, e.g. glycerine, (d) disintegrants, e.g. agar-agar, calcium carbonate and sodium bicarbonate, (e) dissolution retarders, e.g. paraffin and (f) absorption accelerators, e.g. quaternary ammonium compounds, (g) wetting agents, e.g. cetyl alcohol, glycerol monostearate, (h) adsorbent

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LIGHT j

agents, e.g. kaolin and bentonite and (i) lubricants, ζ. b. Talc, calcium and magnesium stearate and solid polyethylene glycols or mixtures of the substances listed under (a) to (i).

The tablets, coated tablets, capsules, pills and granules can optionally contain opacifying agents with the usual Coverings and sheaths be provided and also put together in such a way be that they contain the active ingredient (s) only or preferably in a certain part of the Ir.testinaltraktes, if appropriate Delayed release, whereby e.g. polymer substances and waxes can be used as embedding compounds.

The active ingredient (s) can optionally with one or several of the above-mentioned carriers also in microencapsulated Form.

In addition to the active ingredient (s), suppositories can contain the customary water-soluble or water-insoluble carrier substances, for example polyethylene glycols, fats, for example cocoa fat and higher esters (for example C ₁₄ alcohol with C.g fatty acid) or mixtures of these substances.

Ointments, pastes, creams and gels can contain the usual carrier substances in addition to the active ingredient (s), e.g. animal ones and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, Silicic acid, talc and zinc oxide or mixtures of these substances.

Powders and sprays can contain the usual carrier substances in addition to the active ingredient (s), e.g. lactose, talc, Silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays can also be used the usual propellants e.g. chlorofluorocarbons contain.

In addition to the active ingredient (s), solutions and emulsions can contain the customary carriers such as solvents and solubilizers and emulsifiers, e.g. water, ethyl alcohol, isopropyl alcohol,

80983 ^ 0-178

gHGE R _{£) CHT} ~]

Ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, in particular cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerin, glycerin formal, tetrahydrofurfuryl alcohol, Contain polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances.

For parenteral administration, the solutions and emulsions can also be in sterile and blood isotonic form.

In addition to the active ingredient (s), suspensions can contain the usual carriers such as liquid diluents, e.g. water, Ethyl alcohol, propylene glycol, suspending agents, e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and Sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth or mixtures of these Contain substances.

The formulation forms mentioned can also contain colorants, preservatives and / or those which improve odor and taste Contains additives, e.g. peppermint oil and eucalyptus oil and sweeteners, e.g. saccharine.

The therapeutically active compounds should preferably be used in the pharmaceutical preparations listed above at a concentration of from about 0.1 to 99.5, preferably from about 0.5 to 95 percent by weight of the total mixture be.

In addition to the active ingredients according to the invention, the pharmaceutical preparations listed above can also contain other pharmaceutical preparations Contain active ingredients.

The manufacture of the pharmaceutical preparations listed above takes place in the usual way by known methods, e.g. by mixing the active ingredient (s) with the active ingredient (s) Carriers.

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The present invention also includes the use of the invention Active ingredients and pharmaceutical preparations that contain one or more active ingredients according to the invention contained in human and veterinary medicine for the prevention, amelioration and / or healing of the diseases listed above.

The active ingredients or the pharmaceutical preparations can be administered locally, orally, parenterally, intraperintally and / or rectally preferably administered parenterally, in particular intravenously.

In general, it has been found beneficial in both human and veterinary medicine active ingredients according to the invention in total amounts of about 10 up to about 300, preferably 50 to 200 mg / kg of body weight per 24 hours, optionally in the form of several individual doses to be administered to achieve the desired results.

However, it may be necessary to deviate from the dosages mentioned, depending on the type and the Body weight of the object to be treated, the type and severity of the disease, the type of preparation and application the drug and the period or interval, within which the administration takes place. So in some crazy cases it can be sufficient with less than the above Amount of active ingredient get along, while in other cases the amount of active ingredient listed above is exceeded got to. The determination of the respectively required optimal dosage and type of application of the active ingredients can be done by anyone A skilled person can easily be done based on his specialist knowledge.

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Example A. In vitro antifungal activity

Experiment description:

The in vitro tests were carried out in a serial dilution test with germ inocula averaging 5 10 germs / ml Substrate carried out. Served as a nutrient medium

a) for dermatophytes and molds Sabouraud's milieu d'epreuve

b) for yeast:
Meat extract-glucose broth.

The incubation temperature was 28 ° C and the incubation time was 24 to 96 hours.

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ORIGINAL INSPECTED

tr

Table A: In Vitro Antifungal Efficacy

Active ingredient

OO

MIC VALUES in γ / ml nutrient medium

Tricho- Candida Penicil- Asper- Micro- Torulopsis

phyton albicans lium gillus sporon glabrata

mentagr. commune species felineum

0, N-

-0-CH-CO-C (CH ₃ )

• 3 '3 100

100

40

100

co O CO OD over ca ■ * JQ

.N (known)

C ₆ H ₅

-0-CH-CO-C (CH ₃ ) ₃

I Cl.

(known)

100> 100

> 100

Cl- ,

OH -CH-CH-C (CH _{3) 3}

/ N \

(known)

OH (CH ₃ ) ₃ C - ^ - O-CH-CH-C (CH ₃ ) ₃

(known)

64

64

64

CD cn co

Table A; In Vitro Antifungal Efficacy (Continued)

Active ingredient MIC - VALUES in γ / ml nutrient medium

Tricho- Candida Penicil- Asper- Micro- Torulopsis

phyton albicans lium gillus sporon glabrata

mentagr. commune species felineum

Cl-

egg

Cl

-0-CH-CO-

x HCl

(known) 100

100

OH -O-CH-C-

HCl

N (known) 100

40

(Connections from example no.)

3 12

13th

32 32 32 4th 4th 4th 4th 32 - 32 32 1 32 8th 32 8th 8th 8th 32 8th 32 32 32 8th

Example B. In vivo antifungal activity (oral) in murine candidiasis

Experiment description

Mice of the type SPF-CF ₁ were infected intravenously with 1-2 χ 10 logaritmically growing Candida cells which were suspended in physiological saline solution. One hour before and seven hours after infection, the animals were treated orally with 100 mg / kg body weight of the preparations.

Untreated animals are vigorous 3 to 6 days after infection from the infection. The survival rate on the 6th day post infection was in the untreated control animals some %.

Explanation of symbols;

+++++ = very good effect = 90% survivors on the 6th day p.i,

++++ = good effect = 80% survivors on the 6th day p.i,

+++ = effect = 60% survivors on day 6 p.i.

++ = weak effect = 40% survivors on day 6 p.i.

+ = Trace effect
kW = no effect

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Table B t In vivo antifungal efficacy (oral)

with nasal candidiasis

Active ingredient

effect

-0-CH-CO-C (CH ₃ ) ₃

(known)

k.W.

OH -CH-CH-C (CH _{5) 3}

k.W.

(Connections from example no.)

1 2 12th

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Manufacturing examples

example 1

- Cl

To 65 (l mol) of imidazole in 650 ml of acetonitrile 103 g (0.26 mol) of l-bromo-1- (4-chlorophenoxy) -2- (2,4-dichlorophenyl) -ethan-2-one are added at the boiling point dripped. The mixture is refluxed for 40 hours. The solvent is then distilled off in vacuo, the residue is taken up in 500 ml of methylene chloride and extracted four times with 250 ml of water. The organic phase is dried over sodium sulfate and concentrated by distilling off the solvent in vacuo. The residue is taken up in 1000 ml of acetone, and 47 g (0.26 mol) of 1,5-naphthalenedisulphonic acid in 100 ml of acetone are added. The resulting precipitate is filtered off with suction and boiled with 100 ml of acetone. 200 ml of sodium hydrogen carbonate solution and 500 ml of methylene chloride are added to the residue. The organic phase is separated off, washed with 200 ml of water and concentrated by distilling off the solvent in vacuo. The residue is taken up in 200 ml of ether and an excess of dry hydrogen chloride is added. After the ether has been distilled off in vacuo, the oily residue is recrystallized from acetone. 31.6 g (29 % of theory) of 1- (4-chlorophenoxy) -2- (2,4-dichlorophenyl) -l-imidazol-1-ylethan-2-one hydrochloride with a melting point of 146-148 are obtained ⁰ C.

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Example 2

fa

Cl - <()> - O - CH - CH - (()> - Cl

ι .. OH

-N

45.5 g (0.108 mol) of 1- (4-chlorophenoxy) -2- (2,4-dichlorophenyl) -1-imidazol-1-ylethan-2-one hydrochloride (Example 1) are dissolved in 100 ml of methanol dissolved and treated with 4.32 g (0.108 mol) sodium hydroxide. At 0 to 5 ⁰ C., potionsweise 4.5 g (0.12 mol) of sodium borohydride and stirred for 15 hours at room temperature to stir. 60ml of concentrated hydrochloric acid are then added dropwise and stirred for 15 hours at room temperature again at 0 ⁰ C. The reaction mixture is then stirred into 800 ml of saturated sodium hydrogen carbonate solution and extracted with 500 ml of methylene chloride. The organic phase is dried over sodium sulfate and concentrated by distilling off the solvent in vacuo. The residue is recrystallized from ether. This gives 30 g (72.5% of theory) of l- (4-chlorophenoxy) -2- (2,4-dichlorophenyl) -l-imidazol-l-yläthan-2-ol as an isomer mixture of melting point 108-110 ⁰ C. .

The following compounds in Table 1 are obtained analogously to the above-mentioned examples.

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Table 1

E.g.
No.

- Cl

^X n

Melting point ( ⁰ C)

2,4-Cl ₂

4-4-F

2,6-Cl ₂

3-Cl

4-CH ₃

4-Cl, 2-CH ₃

2,4-Cl ₂

3-Cl

CC CO CO CO CO CO CO CO CO CH (OH)

CH (OH) CH (OH) CH (OH) 205-215

145-148

160-162

160

162-168

180

168-171

110

177-178

208-218

158-170
156-159
165-167

(x HCl) (x HCl) (x HCl) (x HCl) (x HCl) (x HCl) (x HCl) (x HCl) (x HCl)

(Mixture of isomers) (x HCl)

(Mixture of isomers) (x HCl)

ζIsomeric mixture) (x HCl)

(Mixture of isomers) (x HCl)

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Claims (4)

Claims /I./ 2,4-dichlorophenyl-imidazolyl-ethanones (ole) of the general my formula Cl o- cn -A- ^ JV- α ₍₁₎ II. in which A stands for a keto group or a CH (OH) group, X represents halogen, alkyl or optionally substituted phenyl and η stands for whole numbers from 0 to 3, and their physiologically acceptable salts. 2. Process for the preparation of 2,4-dichlorophenyl-imidazolylethanones (oils) η of the formula (I), characterized in that 1-bromo-2- (2,4-dichlorophenyl) -1-phenoxy-ethan-2-ones are used formula Cl - 0 - CH - CO -u7 ^ - ° 1 (ID Br Le A 17 830 - 22 - 809833/0175 ORIGINAL INSPECTED in which X and η have the meaning given above, with imidazole in the presence of a diluent and an acid-binding agent, optionally the resulting Imidazolyl-ethanones in a manner known per se with complex borohydrides, optionally in the presence of one Reduced thinner. 3. Medicines, characterized by a content of at least one 2,4-dichlorophenyl-imidazolyl-ethanone (ol) according to Claim 1. 4. Process for the preparation of antifungal agents, characterized in that 2,4-dichlorophenyl-imidazolylethanones (oils) according to claim 1 mixed with inert, non-toxic, pharmaceutically suitable carriers. Le A 17 830 - 23 - 809833/0175