DE2348525A1 - 2-ANGULAR CLAMP ON 2- (2-METHYL-5NITRO-1-IMIDAZOLYL) -AETHYL ANGLE CLAMP FOR -2-THIO-PSEUDOHARN MATERIAL - Google Patents

Description

RECHTSANV / OLD? O A O C O C

DR. JUR. DIOL-CMEM. WALTER BEIT

ALFRCO: o-: ht-; m; -;

Sep 12 1973

ί ^; ™ *! ^AT WALN HIGH?

Our No. 13 381

G.D. dearie et go. Skokie, 111., V. ".St.A.

2- (2-Kethyl-5-nitro-1-inadazolyl) -ethy "l7-2-thio-pseudo-

ureas.

The present invention relates to 2 - [_ 2- (2-kethyl-5-nitro-1-iHidazol ^ l) -äthy3.7-2-th.iopseudoureas and related compounds. In particular, the invention relates to compounds of the general formula

NO "

N-CH ₀ GH ₀ -LS-C

NR ¹

GH ₇ .

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where α is hydrogen or an .alky Ire st with 1 to 7 carbon atoms and Ii 'and It ¹ ' represent individually hydrogen or alkyl radicals with 1 to 7 carbon atoms or together represent a vinylene, nitrovinylen or 'i'rimethylene resin.

The alkyl radicals that come under the symbols K, H ¹ and R ¹ 'include the methyl, ethyl, propyl, butyl, pentyl, hexyl and heptyl radical and their branched-chain isomers.

The compounds of formula I above are for the purpose present invention the non-toxic pharmacologically permissible acid addition salts are equivalent. The acid addition salts can ir. with numerous organic or inorganic acids such as sulfuric acid, phosphoric acid, Hydrochloric acid, hydrobromic acid, hydriodic acid, Sulfamic acid, citric acid, lactic acid, maleic acid, Malic acid, succinic acid, tartaric acid, cinnamic acid, is.setic acid, Benzoic acid, gluconic acid, ascorbic acid and similar acids.

The compounds according to the invention are useful because of their anti-microbial action; they are particularly effective for inhibiting the growth of protozoa, which is why they can be used for the treatment of diseases such as x'richomoniase. They also act against anaerobic bacteria such as Clostridium perfringens Ai ¹ OC 13124 and Propionibacterium acnes ATCO 6919

The anti-protozoal effect of the present compounds is shown by the results of standardized tests, designed to determine the ability of the test compounds to inhibit the growth of Trichomonas vaginalis became. These x'ests are carried out as follows:

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A modified diamond medium is made by one 1200 parts trypticase, 600 parts yeast extract, 300 parts Maltose, 60 parts L-oysteine hydrochloride, 12 parts L-asoorbic acid, 48 parts dihydrogen potassium phosphate, 43 parts Ivonohydrogenpotassium phosphate and 45,000 parts distilled “Vasser mixed up. The pH value is adjusted with 40% sodium hydroxide solution adjusted to 6.8, and 3o parts iigar are incorporated. The mixture is boiled to 1 luinute Dissolve the agar, then place it in an autoclave sterilized. 80 parts by volume of the resulting medium are aseptically added 20 parts by volume of sterile Duboskedium serum admitted. The resulting tedium is mixed with 1 volume of a 72 hour culture of x'richomonas vaginalis, whereupon 1 ml of the inoculated itedium is mixed with 10 mg of the test compound. The G-emic is incubated anaerobically at 37 0 48 otunden and then under examined with the likroscope for the presence of motile trichomonads; all such trichomonads are observed Connection considered inactive. If no motile trichomonads are observed, 0.1 ml of the incubated Mixture diluted in series and with !! narrow of the inoculated Medium mixed, which are sufficient for the production of the concentrations 1000, 100, 10 and 1 Ivikrogramm fixed connection per milliliter. The resulting G-emics are grounded again "? · Incubated anaerobically at 37 0 43 hours and then microscopically examined for the presence of motile trichomonads, tiei The procedure for the comparison samples is identical with the exception that the test compound is missing.

Due to their pharmacological properties, the compounds according to the invention combined with carriers and in various known pharmaceutical forms suitable for oral, local or parenteral administration administered.

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Lie erf indungsgeir> äl3en compounds are conveniently prepared by a can Iciidazol the general .formel

ClU

with a connection of the general formula

NH '
Z-3-U (III)

^ N-R "

implements.

In the above i'Ormulas, Λ denotes hydrogen or a the ^ 'orjn riots

wherein X is a halogen, the l'oluenesulfonyloxy or methanesulfonyloxy radical, Z is hydrogen, if A is -OH ₂ OH ₂ X, or an itest of the formula -CH ₂ OH ₂ X, if A is hydrogen, while R, R ¹ and H '' have the above meaning with the proviso that Ii ¹ and H * 'can only form a close nitrovini-1 group if Z means -OKgCHgX. If Z in formula III is hydrogen, the compounds of the iPorinel I, in which R ¹ and R "form a nitrovinylene group, can be obtained by corresponding compounds of the formula III, in which R ^f and H" represent a vinylene group, the subjects the above coupling reaction and then the resulting compounds of the formula I in per se

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known to be nitrided.

The U symbol X includes the halogens chlorine, bromine and iodine. If λ means chlorine or bromine, the coupling reaction can be carried out in the presence of a suitable is.a ta Iy sat or such as sodium or potassium iodide.

The person skilled in the art recognizes that compounds of the formula III, in which Z is hydrogen, represent 2-1 ¹ hiopseudoureas or cyclic i'hiols, depending on the nature of the substituents It ¹ and Ji ¹ '. Such compounds can, under favorable conditions, at an equilibrium with the corresponding i'hiohamstoffen of the formula

NI. ¹

N-Ii ¹¹ (IV)

H ^

participate, where £, Jx ¹ and ix ¹ 'have the above meaning. The relative lengths of the two tautomeric elements depend on the physical state of the substances in question and their environment, on whether they are solid or liquid and, if dissolved, in which solvent, at which temperature and at which pH Value are available. Since the various forms in which i'outomers can exist cannot easily be represented by a single formula, for the sake of simplicity the compounds of formula III, in which Z is hydrogen, are represented exclusively as 2-2hiopseudoureas or cyclic thiols. The use of the tautomeric ^v orm of these compounds according to .Formula IV nevertheless falls within the scope of the present process.

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Reaction time, temperature and pressure are not critical factors in performing the above process. Suitable solvents for carrying out the coupling of the compounds II and III are familiar to those skilled in the art. Of course, the choice of solvent depends on the respective starting materials. If α in x'Onr.el II means, for example, hydrogen, the process is typically carried out in an acidic solvent such as acetic acid or formic acid. If, on the other hand, λ in formula II is a kest of the formula -UHpUiUX, the reaction can conveniently be carried out in an alcohol, e.g. 2-propanol, in dimethylsulfoxide or in dimethyl! Other suitable solvents are, for example, iiexanethylphosphoramide, acetone, ethyl ethyl ketone and potassium carbonate; , if A in formula II means -CHpÜlipOl). The free base of the u'orinel I can be prepared by neutralizing the acid addition salt with a liase , it is also possible to prepare the free base directly by coupling in the presence of a base such as i'riethylamine, sodium bicarbonate or sodium or potassium carbonate drives through.

Starting materials of the formula II, wherein a -CJi ^ Cip means, are zv / eckmäliig from 1- (2-II ^ hydroxyethyl) -2-methylb-nitroimidazole manufactured. The uhloräthyl-imidazol is obtained, for example, by the above iyuroxyäthylverbindungen Reacts with l'hionyj chloride, l'osylate and Iv, e sy la t can be obtained by adding the hydroxyethyl compound cit i'osyl chloride or mesyl chloride to react.

Looking at starting materials of the formula III, in which Z -ϋίΐρϋίίρΛ means, one can use the appropriate for this purpose Compounds of -L'Ormel III, wherein Z 'is hydrogen

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" ¹ L"

is to react with 2-i3ronethanol. The resulting connection the formula

N-Ii '

is then converted into the corresponding halide, iosylate or kesylate of the i; 'orrael III by treatment with a ^ hionyl halide, ir, it J- ¹ Os;,'! - or lesyl chloride, with the exception of this general process the production of the starting material of the -ü'orrriel III, in which Z denotes -Cu ₂ OH ₂ A and IV and K ¹ together form the Mitrcvin ^ lengruppe. iJiese starting materials are best obtained by nitration of the corresponding compounds of formula III wherein κ ¹ and It's ¹ to Vin, ylenrest represent.

In the following examples, Iv ': narrow is indicated by parts by weight.

example 1

4.5 parts of 1-Iv ethyl thiourea and 9.5 parts of 1- (2-chloroethyl) -2-methyl-5-nitroiniidazole dissolved in 39.5 parts of 2-propanol. The resulting solution is heated for 72 hours and then cooled. The addition of 20 parts of acetone and 18 parts of ethyl ether leads to the crystallization of 1-ethyl-2- / ~ 2- (2-ynethyl-5-nitro-1-imidazolyl) ethyl7-2-thiopseudourea hydrochloride, which occurs at about 2o5 -2o6.5 ° melts.

^ replaces the 1-ke among the above starting materials ttiylthioharnatoff by an equivalent kenge of that below The following products are obtained when the above method of operation is repeated:

L.it 1,3-.DiEethylthioharnsi.off das 1, 3-X> imeth.yl-2 - / "" 2- (2-Eethyl-5-nitro-1-imidazoiyl) -äthyl7-2-thiopseudourea hydrochloride, a \ approx. 2o2-2o5 ° 0,

with 1,3-diethylthiourea the 1,3-ΰiäthyΠ <2 -, / ~ 2- (2-Ee 5-nitro-1-iII! Idazolyl) ethyl7-2-thiopseudourea hydrochloride,

with 1 - butyl-1,4,5> 6-tetrahydro-2-pyrimidinthiol the 1-ßutyl-2- _< / ~ 2- (2-methyl-5-nitro-1-yne: idazolyl) -äthylthi £ / ^r -1, 4,5,6-tetrahydropyrimidine hydrochloride from Jj ¹ . approx. 1 ^ o-131 ° above sea level,

with thiourea the 2- _/ / ~ 2- (2-methyl-5-nitro-1-imidazolyl) -ethyl7-2-thiopseudourea hydrochloride from h \ approx. 234-236 ⁰ O In this year the i- Reaction mixture heated for 84 hours and then cooled to give the desired product. Using 1.4.5> 6-tetrahydro-2-pyriinidine thiol gave the 2 ~ / _ 2- (2-methyl-5-nitro-1- imidazolyl) -äthyltliio7-1,4 »5iö-tetrahydropyrimidine hydrochloride, b \ approx. 208-211 G. In this Ji'all the iieaction participants were dissolved in a mixture of 2-propanol and methanol, the solution was 24 hours heated and the solid that separated out on cooling was crystallized from acetone.

The use of 1-Ikethy 1-1, 4> 5 , 6-tetrahydro-2-pyrimidinthiol gave the 1-Lethyl-2- _< / T2- (2-methyl-5-nitro-1-imidazolyl) -äthylthio / - 1, 4t 5, ö-tetrahydropyrimidine hydrochloride from ü ¹ . approx. 136-138 ° E. In this ^v all, the reaction mixture was heated for 24 hours.

Since 1-Iv «ethyl-imidazol-2-thiol, 1-methyl-2- ^ ~ 2- (2-

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methyl-5-nitro-1-imidazolyl) ethylthio / imidazole hydrochloride from jtf ¹ . about 2o1-2o2.5 ° above sea level. Heated in reaction agemiscli for 24 hours

from JÖ ¹ . about 2o1-2o2.5 ° above sea level. In this! '' It all became

Using i-tiexylimidazole-2-thiol gave 1-llexyl-2- ^ ~ 2- (2-methyl-5-nitro-1-imida2olyl) -ethylthio7-imidazole in / orm of an ul. In these; ü'all the mixture was 24 ütd. heated to 90-95 ° ö. Then the solvent was evaporated and the chopping stand was dissolved in .Benzol, washed with aqueous sodium carbonate solution and attached to oilikagei using ethyl acetate as a solvent chromatographed.

Example 2

3.6 parts of i-IvLethyl-2- / 2- (2-methyl-5-nitro-1-imidazolyl) ethylthi £ 7-iKidazole hydrochloride were dissolved in 100% water and tied with 1.3 ropes Sodium hydroxide added. The resulting 1-methyl-2- £ ~ 2- (2-methyl-5-nitro-1-iir, idazolyl ethyj ^ imidazole, which separated as a solid with a melting point of about 112.5 to 1H ° 0, was 35 » 5 hone cialpetersäure concentrated and mixed 1o ieilen water and one hour erwärrrt on 9o G ^ü. the solution was then share with 460 water and diluted with .rbonat Natriuir.c £ ^j partially neutralized. the solid which formed was filtered and washed with!.! Triturated ethanol, the 1-luebhyl-2- _/ / ~ 2- (2-methyl-5-nitro-1-imidazolyl) -äthylthio7-5-nitro- • imidazole with a melting point of about 220-214 ° U was obtained.

Example 3

11.4 parts 1-l,; ethylimidazole-2-thiol, 12.5 parts 2-isromathanol

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and 39.5 parts of 2-propanol were combined and then about Heated for 16 hours on a steam bath. Jja's solvent was evaporated and the residue was dissolved in water and K.it sodium carbonate neutralized. The separating Oil was extracted with chloroform, the chloroform extract v. was dried and concentrated, the 2- (2-hydroxyethylthio) -1-r.ethylimidazole was obtained.

15.3 parts of 2- (2-hydroxyethylthio.1-irethylirridazole were made in 49 files .Py rid in, which 19 parts of p -'-Dcluenesulfonyl chloride contained, solved. The reaction mixture was about 43 hours left to stand and then diluted with 25o parts of water. The mixture was extracted 2 with chloroform, the combined Extracts were washed, initially with 1n -._> hydrochloric acid and then with water, then v. the chloroform solution was dried and concentrated, the 2- (2-ii ^ Ωroxyäthylthio) -1-Π) ethyllate eruöxten \ - / urue.

5Λ, o £ hurry 2 - {Ζ-λ Ij ύ i-oxyätlij ^. t hi ο ) -i-mettiyl-iEcidazol-toaylat were combined with 12.6 parts of 2-ivethyl-5-nitroimidazole and 52.5 parts of ijssiga acid, then the mixture was boiled for about 1 hour at the refluiJ, and then the Solution in the / ükuun. distilled off, the residue was extracted several times with boiling water, the aqueous extracts were cooled and filtered. The filtrate was made basic, and the 1-iv: ethyl-2- _l / 2- (2-ffiethyl-5-nitro-1-eidazolyl) -äth ^ lthi £ / -imidazole precipitated. The product melted at 112.5 to 1 H ° C.

Example 4

15.3 parts of 2- (2-hydroxyethylthio) -1-ynethyliniidazole become Dissolved benzene in S3, and the solution is cooled to 10 ° C

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and with cooling and ferries, 2o.3 parts of thionyl bromide added dropwise. The crystals which form are separated off and dried, and in this way 2 ~ (2-uroiriäthylthio) -1-methylircidazole hydrobromide is obtained.

i'Jine 3o, 2 parts of 2- (2-lirottäthylthio) -l-ethyliinidazole hydrobronaid containing aqueous solution is made with sodium carbonate neutralized. The ul that forms is in uhloroform dissolved and carefully washed with water, then the solvent is evaporated. The Itäckstand is in a solution of 142 parts of concentrated nitric acid and 4o Share 'dissolved water and put on a steam bath for about 30 minutes heated. Then the reaction mixture is diluted with water and neutralized with sodium carbonate. Daa separating Product is recrystallized from iithyl ether, thereby obtained ran the 2- (2-ßromäthylthio) -1-methyl-5-nitroimidazole.

A mixture of 26.4 parts of 2- (2-Broniäthylthio) -1-methyl-5-nitroimidazole, 12.6 parts of 2-diethyl-5-nitroimidazole and 79 parts of acetic acid is boiled for about 16 hours on the junction. After the solvent has been removed under reduced pressure, a mince stand is obtained which, when triturated with hot ethanol, yields 1-Itetb.yl-2- _< / ~ 2 ~ (2-methyl-5-nitro-1-iiriidazolyl) ethylthio / -5 -nitroimidazole of a \ about 2o9-214 ° 0 results.

Example 5

The procedure of the first paragraph of Example 1 is repeated with the difference that 2.7 parts of sodium carbonate are added to the reaction mixture. In this way, 1-methyl-2- ₍ / "" 2- (2-methyl_5-nitro-1-imidazolyl2-ethyl7-2-thiopseudourea). The compounds ' d- £ ~ 2- (2-ethyl -5-nitro-i-imidazolyl) -ethyl7-2-thiopseudourea

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and i-Lethyi-2- ^ 2- (2-methyl-5-nitro-1-imidazolyl) -ethylthio / -imidazole shown.

Example 6

Typical pharmaceutical preparations for oral administration, the compounds of the present invention, are shown below contain, described, are further pharmaceutical containers suitable for the oral administration of these compounds Lozenges, dragees, pills, powders, solutions, ouspensions, Jirups and emulsions.

l'ablett e

Ingredient ltenge / tablet

Compound of formula I 500 mg

Lactose 235 mg

corn starch 27b mg

Polyvinylpyrrolidone 3o mg

Iwagnesium stearate. 2o mg

The active ingredient is in a mixture of 2-propanol and water solved and on. Lactose distributed. The resulting mixture is dried in the air and then through a sieve with 37 mm clearer! /! ashes width happened. Then cornstarch will be and polyvinylpyrrolidone are added, the components are carefully mixed and the mixture is again through a thief with o, 37 now led to Liaschenweit. Then it will Mixture granulated with 2-propanol, spread out on trays and dried at 490 for 16 hours. The dried granules is sifted, the grains are carefully mixed with iuagnesiuin stearate mixed and the mixture is compressed into tablets.

capsule

! Part of iv.enge / capsule

Compound of the formula I 2! 50 mg

Imperial strength 13o.mg

Lactose 18o Eg

Talc 2ο mg

The active ingredient is carefully made with ivory starch and lactose mixed, passed through a sieve of 0.37 cm clear mesh size and mixed again. Then talc is added and the resulting mixture is made by hand or by machine using 63o mg of filling per capsule in appropriate hard gelatine capsules filled.

Particularly advantageous compounds for use in preparations of the type described above are the 2 - ^ "~ 2- (2-methyl-5-nitro-1-imidazolyl) -ethyl7-2-thiopseudo-urate, the 1-kethyl-2- £ ~ 2- (2-methyl-5-nitro-1-imidazolyl) -äthylthio7-iir.idazol and the 1-Iv; ethyl-2- _i / ~ 2- (2-ffiethyl-5-nitroi-imidazolylJ-ethylthioJ-S -nitroiinidazole, especially in ii'orin their hydrochloride.

Other permitted pharmaceutical carriers for use in formulations of the type described above are, for example: sugars such as cane sugar, mannitol and oorbitol, starches such as tapioca starch and potato starch, cellulose derivatives such as sodium carboxymethyl cellulose, ethyl celulose and methyl cellulose, gelatine, calcium phosphates such as dicalcium phosphate and tricalcium phosphate, sodium sulfate, sodium sulfate, tricalcium phosphate, sodium sulfate , Stearic acid, alkaline earth metal stearates such as calcium stearate, vegetable oils such as peanut oil, cotton wool oil,

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tv

oesauj oil, olive oil and iv.ais oil, non-ionic, cationic and anionic surfactants, ethylene glycol polymers, ^ -cyclodextrin, fatty alcohols and hydrolyzed grain solids as well as other, non-toxic and compatible / Ulistoffe, binders, oprengmittel and lubricants, which are commonly used in pharmaceutical preparations.

In the formulations of the type described above are the new compounds of the formula I in the to achieve the desired effect assumed ikenge. Although 25o or 500 mg per dose unit are often appropriate, considerably larger or smaller amounts of active ingredient can be used be incorporated into a dose unit. The l'agesdose depends on various actuators, e.g. the one in question Connection, the state of illness and the individual reaction of the patient. Typical doses if used as -rinljii protozoan agents can range between about 500 and 500 mg per day for oral administration.

Example 7

Below is a typical formulation for vaginal suppositories specified:

r component . iüenge / suppository

Compound of formula I 100 mg

fheobroma-ül (Kak & ocutter) 1200 mg

The cocoa butter is melted, preferably on a ^ m water or steam bath, and the active ingredient is in the melt emulsified or suspended. The cash register is then chilled

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chrome-plated metal molds cast in which the Solidify duppositories.

Other permissible carriers and basic materials for the production of suppositories of this type are, for example, triglycerides of oleic acid, palmitic acid and stearic acid, partially hydrogenated cottonseed oil, branched-chain, saturated fatty alcohols such as, for example, the suppository base G, hydrogenated coconut oil triglycerides and triglycerides of coconut oil and triglycerides of palm oil 0 "^ ettsauren -Up- water-dispersible carrier such as polyethylene glycols, glycerol, gelatin," Polyxyl-4o-stearate, polyethylene-4-öorbit monostearate and substances which increase the melting point of suppository ,, as .Bienenwachs and "valrat .

Particularly advantageous compounds for use in preparations of this type are mentioned in Example 6. Although 100 mg of active ingredient per suppository is often a suitable one They can also be larger or smaller The quantities of active ingredients may be incorporated into a dose unit will. Typical doses of the compounds according to the invention when administered in vaginal suppositories are between 100 and 100 mg per day.

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Claims (1)

Patent claims 1. Association of General Cornel or a non-toxic, pharmaceutically acceptable acid addition salt thereof, in which it. hydrogen or an alkyl radical ix: it 1 to 7 carbon atoms and it 'and li ¹ ' individually hydrogen or alkyl radicals with 1 to 7 carbon atoms or together a vinylene , Nitrovinylen or x'rimethylene radical. 2. 1-J..ethyl-2- £ _ ~ 2- (2-i ;; ethj.l-5-nitro-1-iinidazolyl) -äthyl7-2-thio · pseudohurstoi "! '. 3. 1,3-dimethyl-2- ₍ ^ ~ 2- (2-irethyl-5-nitro-1- _yne) ida2; olyl) -ethyl7-2-thiopseudourea. 4. ^ - ^ ~ 2- (2-iLethyl-5-nitro-1-iEidazoiyl2-äthyl7-2-thiopseudburea. 5. 1 -XU tyl-2- _< / ~ 2- (2-methyl-5-nitro-1 -imidazo IyI) -ethylthio / -1,4,5,6-tetrahydropyryridine. 6. , 2- £ ~ 2- (2-ivlethyl-5-nitro-1-yne) idazolyl) ethylthi £ 7-1 »4,5,6-tetrahydropyriicidine. 7. i-Lethyl-2 -, / 2- (2-methyl-5-nitro-1-iffiidazolyl) -ethylthio7 1,4,5,6-tetrahydropyrimidine. S. 1-Methyl-2 - ^ / ~ 2- (2-icethyl-5-nit ro-1-iiriid imidazole. -ät hylthi £ 7- 9. 1-I ^ / 5-nitroimiduzole. 1o. Process for the preparation of a compound according to claim 1, characterized in that dai-3 man (a) a compound of the general -L'Orm U-A in which the -i-'Ormel reads A »iasserstoif or one represents, wherein X is a halogen, the ioluenesulfonyloxy or Methanesulfonyloxyrest means sit a compound of general - &quot; ornel NK ¹ NK ¹ ' brings into contact, where 'Δ means hydrogen, if a 409815/1174 -UHpkiip-Λ-, and an itest of the formula -CHpOHpX, if A is hydrogen, and R, k ¹ and it ¹ 'have the above meaning, with the fc'abgabe that H ¹ and Ki' are only one ^ Titrovinylenrest can mean when Z is -OilpOiipÄ, or (fr) a compound of the general formula I, where Ii 'and it.''together represent a vinylene radical, nitrated to form a compound of the formula I in which K' and R ¹ 'represent an iJitrovinylenrest. 11. The method according to claim 1o, characterized in that 1- (2- <chloroethyl) -2-methyl-5-nitroimidazole with i'hiourea to 2- £ ~ 2- (2-Lethyl-5-nitro-1-iaidazolyl) -äthyl7-2-thiopseudourea implements. 12. The method according to .anopruch 1o, characterized by dai-i 1- (2-chloroethyl) -2-kethyl-5-nitroiir; idazole with 1-iv.ethylimidazole-2-thiol to 1-L.ethyl-2- £ _ 2- (2-methyl-5-nitro-1-iinidazolyl) -ethylthio7imidazole implements. 15. The method according to claim 1o, characterized in that 2-i..ethyl-5-nit roiuiidazol tnit 2- (2-liydroxyäthylthio) -1-c.ethjlimidazol-tosyl ^ t zurr, 1-l, ethyl-2 - £ ~ 2- (24meth, yl-5-nitro-1-iiriidazolyl) ethylthio_7-icidazole. 14. Method according to claim 1o, characterized in that 1-Leth \ l-2- £ ~ * 2- (2-c :: ethyl- ^I j-nitro-1-iridazolyl) -äthylthi_o7'-iridazole nitrated to form 1 -i; ethyl-2- _< / ~ 2- (2-met hy 1-5-ni ü ro-1 -iir <ida zoly 1) -ät hy 11 h io / -5 -nit ro ircid a ζ oil. 15. The method according to claim 1o, characterized in that 2-b ethyl-5-nitroimidazole ßit 2- (2-j3roinäthjlthio) -1-methjl-5-nitroiniidazole zurr; 1 -Lethyl-2- £ ~ 2- (2-ri _; ethy 1-5-nitro-1-yne: id3solyl) -i - ». Tu ^ lthi_o7 ~ 5-r ⁱ it ^: roir: .idcizol. 409815 / 117Λ 16. Pharmaceutical preparations for human medical use or veterinary use, containing as «.irkytoxf one or more compounds of claims 1 to 9 17. Preparation according to ^ ropruch 16, characterized by a content of 2- £ ~ 2- (2-kethyl-5-nitro-1-imidazoi / L) -eth,> '17-2-thiopseudourea or a non-toxic pharmaceutically acceptable acid addition salt thereof. 13. Preparation according to claim 16, characterized by a content of 1-Iv ^: ethyl-2- ^ ~ 2-r (2-ir; ethyl-5-nitro-1-imidazolyl) · eth,) 'lthio7-yne; idazole or one; non-toxic pharmaceutically acceptable acid addition salt 19 · Preparation according to claim 16, characterized by a G-c-h-'ilt on 1-kethyl-2- / ~ 2- (2-irethyl-5-nitro-1-iaidazolyl) -äthylthi £ 7-5-nitroicidozcl or a non-toxic pharmaceutically acceptable acid addition ^ salt thereof .. ^ ¹ IIr: G.Ii. Jearle L Go. Ukokia, ill., V.ot.A. Dr. Hefts Chr. Bei! Lawyer BATH