DE2459666A1 - DINITRO-2,2 HIGH 1 -BITHIOPHEN DERIVATIVES AND THEIR USES - Google Patents

Description

1. Kuibyshevsky Politechnichesky Institute imeni
VV Kuibyshev

2. Kuibyshevsky Medical Institute imeni D.I. Uljanowa

3. Nautschno-Issledowatelskij Institute po Biologitscheskim Ispytanyam
Khimitscheskich Sojedineniy

DINITRO-2,2 ¹ -BITHIOPHENE DERIVATIVES AND THEIR USES

27.12. 1973 USSR. No. 1977301 Priority ι 26. 3. 197A- USSR No. 2005053

March 26, 1974 USSR No. 2005054

The present invention relates to new substances Dinitro-2,2-bithiophen derivatives, and their use.

The dinitro-2,2-bithiophene derivatives according to the invention have the general formula

wherein R ^ a NO ₂ when R ₂ = H; R, = SOrmyl-i ketone or

Azomethine group} R ₁ = H, when R ₂ = IiO ₂ and R ^ = formyl, ketone or azomethine group.

The mentioned dinitro-2,2 "-bithiophene derivatives represent crystalline, preferably yellow, odorless, bitter Tasting crystalline substances are useful in water

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insoluble., very little soluble in alcohol, in vegetable oils sparingly soluble, soluble in chloroform, easily soluble in dimethylformamide and in dimethyl sulfoxide. Me fabrics are sensitive to the effects of direct sunlight.

The compounds mentioned have pharmacological properties Activity and find use in medicine as antifungal agents.

The characteristic peculiarity of the biological! Effect the substances of this group is the pronounced selective antifungal activity, mainly against the dermatomyzeten. That is why the field of their practical use is chemotherapy of dermatocytes in humans (epi-. dermophytia, trichophytia, microsporia, oidiomycosis).

The fungicidal dose versus Dermatomyzeten two isomers of Dinitrobithiophen-aldehyde, 3 ^X, 3 ^f dinitro-5 ~ formyl - ^^ - bithiophene and 5 _'f 2-dinitro-5- £ ormy 1-2.2 »-bithiophen , is 2 to 5 / fg / ml, for dinitrobithiophene methyl ketone, of the isomer, y, 3'-dinitro-5-acetyl-2,2 ^f -bithiophene, 1 to J // g / Jttlf for dinitrobithiophenazomethine, for example B - (^ ^1, 3 ^l dinitro-2,2'-dithienyliden-5) meta-aminobenzoic acid 5 to 5 / V g / ml. With relatively equal levels of antifungal activity in dinitrobithiophene methyl ketone and dinitrobithiophenaldehyde, the latter is of less medical value.

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This is due to the fact that dinitrobithiophenaldehyde has a higher toxicity for the animal organism (when administered intraperitoneally to white mice, LD ₀ = 45 mg / kg) and has a pronounced heating effect when applied to the skin of animals and humans, especially in occlusive dressings and theirs Application in people with allergic change.

^{Chemical compounds obtained on its basis, for example such a dinitrobithiophenazomethine as -N- (5 f} , J5 ^f -dinitro-2,2 * - <iithienylidene-5) -raeta-aminobenzoic acid, have a much lower toxicity and irritant effect compared to the pure dinitrobithiophenaldehyde .

CH =

This substance is a highly active antifungal agent that those known in medicine according to the degree of activity Antifungal drugs such as Mtrofungin (Czechoslovakia company "SPOFA") and undecylenic acid is superior. a fungistatic dose when titrating in vitro on dense and liquid Saburo medium compared to the dermatomyzetes is 1 to 3 / 'g / ml and the fungicidal 2 to 5 / ^ g / ml. The fungistatic and fungicidal dose against candidiasis is 6 // g / ml.

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The bactericidal dose against the gram-positive bacteria species, which are more sensitive than other bacteria species against this substance, especially against Staphylococcus auerus, is 25/6 g / ml.

The N- (5 ^l , 3 ^t -dinitro «2 _i 2 ^l -dithienylidene-5)« - meta-amino-

Benzoic acid does not belong to the category of highly toxic substances (with intraperitoneal injection in white mice LD ₅₀ = 100 mg / kg.

This substance has a weak irritant effect when introduced into the eye of an ointment consisting of 0.1 g Substance, 2 ml of dimethyl sulfoxide and 8 g of lanolin (1% ointment), however, has no irritating effect when the ointment of the above composition is repeatedly applied to the skin of eggs and Human up.

The 1% solution of the named substance in dimethyl sulfoxide in 11 cases of I3 prevents the development of the Experimental mycosis in guinea pigs caused by the virulent strain of the fungus Trichophyton gypseum under the condition of therapeutic application from the third day after infection within five days daily lubrication of the infected surfaces (the nitrofungin is in able to prevent the development of experimental mycosis in 7 cases of I3).

On the set of such main characteristics as

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Antifungal activity against dermatomyzetes and the harmlessness for the organism of animals and humans is a particularly important and valuable representative of this group of substances, dinitrobithiophene _{methyl ketone, whose particularly active isomer is 5 * $} ^ * - i) initro-5-acetyl-2.2 ^l -bithiophene with the empirical formula
formula

of molecular weight 298.29, which is used as an active ingredient for Medicinal is used.

The chemotherapeutic antifungal preparation according to the invention for the treatment of dermatomycoses consists of the Active ingredient 5 ·, J'-Dinitro - ^ - azethyl ^^ - bithiophene of the formula

in combination with a pharmaceutical vehicle. »

The active ingredient of the proposed preparation stops crystalline, yellow-colored, odorless, bitter-tasting Powder that is practically insoluble in water, very little soluble in alcohol, sparingly soluble in sunflower oil (up to 1%),

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soluble in chloroform, easily soluble in dimethylformamide and dimethyl sulfoxide, from melting point 122 to 122.5 ° C with absorption in the UV range of the spectrum at \ =

J J <

273 nm - ^ max = ¹⁴ ^ ° ^{and at} \

C "= 14010, with the absorption in the IR region of the spectrum with ^ cm""¹; I663, I552, I5I5, I500, 1423, 1390, 1335» I3IO, 1263, 1072, 878, 808, 778, 724. the material is sensitive to the effect of direct sunlight, however, is stable when stored in a bottle of dark glass. the temperature of the decomposition of the substance is 89 ⁰ C.

When adding a few drops of the saturated alcoholic solution to an alcoholic solution of the substance caustic soda turns a dark red color. Such a color test can successfully identify the substance in the Pharmaceutical form as well as in the experimental investigation of the penetration of the same from the pharmaceutical form into the skin of the Animals and are applied to the internal medium of the organism. The use of photoelectrocolorimeters, added by setting up a comparison scale, it is possible to evaluate the content in terms of quantity after the color test of the substrate to give dinitrobithiophene methyl ketone.

In vitro titration on dense and liquid Saburo medium the fungistatic and fungicidal doses of the ge. .-called connection to the mushrooms Tr. rubrum, Tr.inter-

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digital, Microsporon lanosum, Tr.gypseum showed a high antifungal activity of the substance mentioned against the dermatomyzeten, which is the activity of such in medicine • known antimycotics such as nitrofungin (E-Czechoslovakia, Company "SPOFA") and undecylenic acid.

In particular, for 5 ¹ »3 * -dinitro-5-acetyl-2.2 ^l bithiophene, the fungistatic dose is 0.5 to 2 // g / ml and the fungicidal dose is 1 to 5 μfg / ml; for the nitrofungin, whose active ingredient is 2-chloro-4-nitrophenyl, 5 // g / ml or 5 to 10 Ag / ml and finally for the uhdezylenic acid 5 to 10 to 20 μ / g / ml or 5 to 20 up to £ 0 // g / ml. The antifungal activity of 5- ^f »3 * -Dinitro-5-acetyl ~ 2.2 ^l bithiophene. in biological media decreases only insignificantly (no more than by 20%). .

The antimycotic effect of the compound mentioned extends to the oidiomycetes, which in the microbiological tests by the fungi of the genus Kandida (Candida albicons). were represented, whereby according to the degree of activity this substance is superior to nitrofungin and undecylenic acid. ao the fungicidal dose against candidiasis for 5 ', J'-dinitro - ^ - acetyl ^^' - bithiophene is 2 to> to 'iü ^ / fg / iux, xur «itrofungin 20> µg / ml and for indecylenic acid 20 to 50 if g / ml.

As for the antibacterial activity of the 5 », J 'aζety1-2,2 ¹ ^ bIthiophene in vitro, this is

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weakly pronounced. For example, the bactericidal dose for 5 ¹ , J'-Dinitro - ^ - acetyl-S ^ '- bithiophene against Staphylococcus aureus, which is more sensitive to this substance than other bacteria, is 15 to 35 MsMl (the staphylocidal dose of nitrofungin is 150 M g / ml and for indecylenic acid 550 μVg / ml). The low antibacterial activity of the substance mentioned underlines the selectivity of the antifungal effect of this substance.

The substance mentioned does not belong to the category of highly toxic substances. In oily solutions, LD ^ q for 5 ¹ , J'-dinitro ^ -acetyl ^^ '- bithiophene is 446 mg / kg when introduced per os in white mice,> 500 mg / kg when administered subcutaneously and> 500 mg / kg when administered peritoneally 213 mg / kg.

Rabbits weighing 2.5 to 5 kg tolerate subcutaneous injections of 1% oily solution (sunflower oil) 5 ¹ »3 ^f -dinitro-5-acetyl-2,2'-bithiophene in an amount of 5 ml without any deviations from the norm and dogs weighing 10 to 12 kg in an amount of 10 ml. In a 1% oily solution, the substance mentioned has no irritating effect when it is instilled once a day into the rabbits' eyes for 5 days and when it is applied to the skin. of animals and humans.

The field of practical application of 5 ^f , 3'-dinitro-5-acetyl-2,2 ^f -bithiophene as a highly active antimycotic

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is the chemotherapy of dermatomycoses in humans. In In this context, the substance is intended for external use in the form of preferably oily solutions or ointments, the latter being a preferred dosage form.

According to the invention, it is used as a pharmaceutical vehicle for the chemotherapeutic antimycotic preparation preferably an ointment base, which consists of vegetable oil and anhydrous lanolin in a ratio of 1: 1. It is expedient to use a preparation which contains 0.5 percent by weight of active ingredient.

It is used as an antifungal medicine, an ointment of the the following composition is recommended: active ingredient 0.5 g »vegetable oil 50 g; anhydrous lanolin to fill on 100 g.

To prepare ointments of the above-mentioned composition, an initial weight of 5 ^f , 5 ^l -dinitro-5-acetyl-2.2 ^t -bithiophene is dissolved in an appropriate amount of, for example, sunflower oil with constant stirring and heating on a water bath to a temperature not above 80 ° to the maximum, then adds molten lanolin in the appropriate amount with constant stirring until a homogeneous mass is achieved, fills bottles made of dark glass with a lid and lets them cool down at room temperature. The filled bottles are stored in a cool bar.

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A 0.5% yellow-brown ointment of homogeneous consistency, without a specific odor, with a bitter taste is obtained.

Long-term (in the course of 45 days) daily skin applications of C5% saloe voa 5 ¹ ^ "- dinitro - ^ - acetyl- -2,2'-bithiophene in guinea pigs and rabbits due to no toxic appearance" *, no decrease in doa Weight of the animals, no changes in blood values, no disturbances in the condition and aging of the animals accompanied.

ti

The mild effect of the ointments äsü; on the low ability of the active ingredient, through the haste in the inner Uexlien

■ SSB. '"

penetrate the organism, lead back. With the help of

■ The above-mentioned color sample wuxsLe the 5 ^f , 3 ^f ~ dinitro ~ 5 ~ acetyl ~ 2,2'-bithiophene in the blood, in the extracts from the

internal organs and in the urine of the esgerimentary animals (Guinea pigs and rabbits), the longer chewing treatments the dosage form (0.5% ointment of the stated composition) were subjected, not proven.

With numerous Eautapplikatlsnen the drug fora (the 0.5% ointment) vdrd the 5 ¹ ^ '- Dinilro ^ -acetyl ^^' - bithiophene in the skin by color test legally proven. which testifies to the relatively easy penetration of the active ingredient. In particular, using the

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Photoelectrocolourimetry according to the comparison scale a quantitative content of the skin of the guinea pigs and rabbits in 5 *, ^^ - dinitro-5-acetyl-2.2 ^l -bithiophene after one and a half months of application of the ointment in an amount of J3 »24 to

5.27 lbs / g / cm detected. Much more, the active ingredient is able to be retained in the skin for a longer period of time after the application of the dosage form has been interrupted (traces of 5 ¹ , ^ '- dinitro ^ -acetyl ^^ - bithiophene are in the skin by color test even after 10 to 14 days detectable).

Experiments using human cadaver skin revealed that 24 hours after the application of a 0.5% Ointment of y, ^f 2 -dinitro-5-acetyl-2,2 ^f -bithiophen the active ingredient into the skin in an amount of 0, 5% + based on the applied dose, penetrates.

The ability of the 5 ', J ¹ -dinitro-5-acetyl-2.2 ^t -bithiophene to penetrate the hair was also verified by means of a color test. .

The good ability of the active ingredient from the dosage form penetrate the skin, combined with the ability of the same to accumulate in the skin and retained for a long time to be, is supposed to inevitably affect the state of affairs. affect the skin. Like the histological examinations the skin of the guinea pigs from the areas on which 0.5% ointment has been applied for a long time,

5 0 9 8 2 8.7 10 16

Some reactive changes on the part of the epidermis of the skin actually took place under the action of 5 *, 3 * -Dinitro-5-acetyl-2.2 ^{l -bithiophene.} They are expressed through phenomena of excessive horn formation and a certain thinning of the germinal layer. These changes are not destructive in nature.

The chemotherapy of experimental mycosis in guinea pigs, caused by the virulent strain of the fungus Trichophyton gypseum, which is particularly resistant to the action of the preparation, confirmed that the antifungal properties of 5 ¹ , J'-dinitro - ^ - acetyl - ^^ '- bithiophene are preserved in vivo, A single daily application of the 0.5% ointment of 5 *, ^ - Dimtro - ^ - acetyl-ajE ¹ bithiophene for 25 days to infected areas causes the animals to heal in a shorter time than Uitrofungin.

In the mechanism of the healing effect of 5 *, 3'-dinitro-5-azety1-2,2 ^f -bithiophenes, in addition to the direct fungicidal effect, factors such as the sufficiently high ability of the same to penetrate into the skin and hair, or that is infested with fungi, the property of being retained in the skin for a long time, and the lack of immunodepressant effect. The latter was established by comparative determination of the immunological properties in the group of animals with experi-

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ι - ^

j SUBMITTED j

- ■ 13-

mental mycosis, which is the curative effect of the 0.5% ointment des ■ Subject to or not subject to preparation became.

The results of the clinical application of the 0 ", fig ointment of 5 ', 3 * -Dinitro ~ 5-acetyl ~ 2.2 ^t -bithiophene suggest a high chemotherapeutic effectiveness of the preparation in many forms of dermatomycosis, including the infiltrative festering Triclaophytia, microsporia, inguinal epiderinophytia, rubr'ophytia of the smooth skin and the needle, candidiasis of the skin folds.

In patients with inter-toe and dishydrotic form

the foot mycoses caused by Trichophyton rubrum with similar clinical picture, v / o in the. Wrinkles between the toes Maceration, horn exfoliation, edema and hyperemia of the skin and on the butt vault in edema, hyperemia and hyperkeratosis elongated erosions with bright red green, outlined by fringes of the detached epidermis, were noted, the complete occurred clinical healing (in the case of negative results from the usual and microscopic laiinine examination as well as the microbiological examination) in five cases of the five cases after a twenty-five day treatment with 0.5% ointment of the preparation. In doing so, the ointment was applied occlusively once a day to all infected foci. Of the residual symptoms, only hyperkeratosis was observed

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areas for the elimination of which keratolytic agents had to be used.

In all patients, marked disappearances within 5 to 4 days from the beginning of the application of the ointment Symptoms of inflammation, epithelialization of the erosions and cracks occurred, indicating the anti-inflammatory and the reparative effect of the preparation.

In all patients of this group there was at the time of the start of treatment with 0.5% ointment of the preparation allergic rashes on individual skin areas (lower legs, Hand, upper arm). However, the application of the preparation did not increase the allergic symptoms and no generation of parasitic reactions accompanied at all

In a patient suffering from diabetes with an infection of the inter-tenes candidiasis (intertrigo blastomicetica) twice daily application of the ointment of the preparation led to the disappearance of acute symptoms in the affected focus after three days and to a complete clinical healing (with negative results of the microbiological Examination) after 10 days.

Treatment of onychomycosis with the ointment of the proposed Preparation is tedious. The duration of treatment is several months.

The proposed preparation was used for the

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- 15 -

Treatment of Singer's onychomycosis, caused by Trichophyton rubrum, which affects seven nail plates.

The clinical picture of mycosis of the extremities of the fingers composed of the attack on the nails and the nail walls. On the affected limbs of four fingers were the nail plates were completely destroyed and missing, the nail beds were uneven and, as a result, unevenly pronounced Hyperkeratosis thickened. The horn scales were gray-yellow colored. The nail plates were retained on the other three fingers, but their edge zone was destroyed and jagged. Hyperkeratosis of the sub-nail was pronounced.

The skin of the nail walls on all affected fingers was hyperemic and infiltrated. When pressed, drops of pus emerged from under the nail walls.

Sensations of skin tension on the nail walls were subjective and sensation of pain on palpation.

The 0.5% ointment of the preparation was applied once a day with an occlusion bandage for treatment purposes. To the The application of the ointment was preceded by a bath for the affected limbs with a solution of potassium permanganate 1: 10000.

The manifestations of paronychia disappeared 12-16 Days after the start of the application of the ointment of the preparation. The growth of the nails was clearly evident for 5 to 4 weeks after the start of the specific treatment.

The application of the preparation lasted three months. Against

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At the end of this period, the nails began to develop and the clinical signs of healing were complete, confirmed by microspoci and microbiological examinations, in four cases out of seven one, in two cases the one was observed Symptoms of onychomycosis in the area of the free edge of the nail and in only one case the treatment was ineffective.

In the last three cases, where complete healing had not occurred, the microbiological Investigate cultures of the yeast-like pathogenic fungi obtained earlier when inoculating the material from was not excreted from the infected herds.

In none of the cases was skin application (even lengthy) of 0.5% ointment of the preparation in humans accompanied by any side effects. The results of blood and urinalysis in the sick undergoing treatment were subjected to the preparation with the ointment, confirmed the absence of any disturbances to the general condition specific character. The preparation is well tolerated by the sick, does not cause skin irritation or allergic reactions Appearances not only in healthy people and lycosis sufferers, but also in patients with eczema with high general allergic changes in the organism iiervox ·.

The proposed new substances, the dinitro-2,2 ^f -bithiophene derivatives, are preferably prepared as follows.

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The starting products, the 5-substituted 2.2 ^f -ithiophenes of the general formula

wherein R = H; CH ₅ , is subjected to cold nitration with a nitration mixture consisting of concentrated nitric acid and concentrated sulfuric acid, which are taken in a ratio of 1: 2 to 2.5, followed by recirculation of the dinit ro-2 , 2'-MtIrLophen derivatives from appropriate organic solvents. The dinitro ^^ - bithiophene derivatives which contain azomethine group are obtained from dinitro ~ 5-formyl-2,2 ^t -bithiophene by condensation of the same with amino compounds with subsequent recrystallization. The yield of the end product is up to 80 percent by weight.

For a better understanding of the present invention, the following examples are given, which ^{illustrate the new substances, dinitro-2,2 f} -bithiophene derivatives, and their preparation.

Example 1 . 141.6 g of 5-acetyl-2,2 "-bithiophen is dissolved at a temperature of from ⁰ to G minus 5 ⁰ C in 1 $ 16 ml of concentrated sulfuric acid (specific gravity 1 ₉ 84), cools

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to a temperature of minus 1O ⁰ C., dropwise a cooled to a temperature of minus 1O ⁰ C nitrating mixture consisting of 62.8 ml of concentrated nitric acid (specific gravity 1.51) and 125.7 ml of concentrated sulfuric acid (specific gravity of 1, 84) to, by keeping the temperature in a range of from minus 9 ° to minus 11 ⁰ C. The reaction mass is kept in the cooling bath for JO minutes. It is then poured onto broken ice in a thin stream with stirring (do not allow lump formation), the precipitate is filtered off, washed with water until a neutral medium is obtained and dried.

The nitration product is crystallized from dioxane, with the addition of activated charcoal (for 20 g of the product 100 ml of dioxane consumed) "After distilling off the excess dioxane to obtain a first fraction (yield 30 weight percent) as a yellow-colored crystals of melting point 121-122 ⁰ C. After another recrystallization, first from dioxane and then from heptane, 100 g of pure 5 ¹ , 3V-di ^ to phen with a melting point of 122 to 122.5 oil end product are obtained (yield 75 to 80 percent by weight).

Bffi spectrum: OIL 7.9 * -Mio " ^1. S" 8.41 million " ¹ , O H ^ 7.73 million" ¹ , O _0n 2.78 million " ¹ , 6 ^ ^L

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Found, in% by weight: O 4-0.21; H 2.18; N 9 »28.

Calculated, in% by weight: 040.26; H 2.02; Ή 9 »38.

Also obtained from the mother liquor a second crop of crystals of melting point 101 to 104 ⁰ C and then a third crop of crystals of melting point 84 to 96 ⁰ C. The second and the third fraction (the total yield is 4-5-50 wt. %) each represent a mixture of two isomers of dinitrobitol hi opheniiet hy lket on, namely 5 *, ^ '- Di

and 5 ^r _f 5 * -dinitro-5-acety1-2,2 * -bithiophene

The ratio of the isomers mentioned in the second fraction is, according to the information from the PMR spectrum, 86.5 percent by weight: 13.5 percent by weight and in the third 51 percent by weight: 49 percent by weight.

The separation of the named isomers is carried out by repeated Recrystallization made from the isopropyl alcohol.

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In this case, the 5 ', 3'-dinitro-5-acetyl-2,2'-bithiophene initially precipitates when the solution is slowly cooled. Accordingly, one obtains in the further from the mother liquor, a certain amount of the second isomer of 5 * »3 * - ^D iEdtr acetyl-2,2 ^f -bithiophens, a melting point of 136 to 136.5 ⁰ with an absorption in the UV range of the spectrum at

= 280 nm - £ J ^ = 10210 and at l ' _ffiax «376 nm

= 11010, with an absorption in the IR region of the spectrum with Vcm "¹; 1663, 1520, 1412, I365, I332, I296, 1262, II50, 1040, 860, 802, 775, 745, 723.

Bffi spectrum: S _n = 8.03 million * ¹ , O = 8.48 million * " ¹ ,

"4 ⁿ 4

7.62 million " ¹ , S _GE 2.81 million" ¹ ,

_f5 , = 5 Hz.

Found, in% by weight: 0.40.40; H 2.12; N 9.40

Calculated, in% by weight: C 40.26; H 2.02; W 9.38.

Example 2 158.4 g of 5 "-nitro-5-formy1-2,2" -bithiophen is dissolved in 1584 ml of concentrated sulfuric acid (specific gravity 1.84) at a temperature of from ⁰ ° C. A nitration mixture consisting of 60.4 ml of concentrated nitric acid (specific gravity 1.348) and 148.5 ml of concentrated sulfuric acid (specific gravity 1.84) is added dropwise to the resulting solution by changing the temperature in a

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.Range from O ⁰ C to minus 5 ⁰ C holds. The reaction mass is kept in a cooling bath for 30 minutes with periodic stirring, poured onto broken ice, the precipitate is filtered off, washed with water until a neutral medium is obtained and dried.

The nitration product is recrystallized from a mixture consisting of 1 part of benzene and 2 parts of hexane with the addition of activated charcoal. 100 g of end product (4-3 percent by weight) are obtained, which is a mixture of two isomers, namely 5 », 3 ^l -dinitro-5-formyl-2.2 ^l -bithiophene

M ₁ . and

5 ', 5 Dinitro-S-formyl ^^ - bithiophene

represents.

The isomers mentioned are separated by subsequent recrystallizations.

Found, in% by weight: C 38.14; H 1.38-, H 9.97.

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Calculated, in% by weight: C 38.02? H 1.41? N 9.85.

Example 5 . 120 g of 5 \ y - Dinitro-5-formy 1-2,2'-bitMo phen are dissolved with heating in 600 ml of dry benzene, 60 g of metaaminobenzoic acid, also previously dissolved in 6000 ml of dry benzene, are added. The reaction mixture is kept in a boiling water bath for 2 hours, the excess solvent is distilled off and the precipitate is filtered off. Cool and recrystallize from alcohol.

100 g of N- (5 ", 5'-dinitro-2,2" -dithienylidene ~ 3) - metaaminobenzoic acid of the empirical formula C ^ _{1 Λ} Η _α 1Τ ₇ O ^ S ^ and the structural formula are obtained

SO ₁

of molecular weight 405.58, which is a crystalline, red-orange, odorless, bitter-tasting, practical in water Insoluble, sparingly soluble in alcohol, lanolin and castor oil, soluble in dimethylformamide and dimethyl sulfoxide Powder with a melting point of 195 ° C represents that against the Sensitive to the effects of direct sunlight, but the

Display in placons made of dark glass is resistant. Found, in% by weight: H "10.56.

Calculated, in% by weight j N 10.41.

" ¹

IR spectrum, cm " ¹ s ^ _{c = 0} 1685? V _{c = N} 1614? ^ _M 1520,

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Claims (1)

PATENT CLAIMS: 1. Dinitr0-2,2 · -bithiophene derivatives of the general formula wherein R, - = NO ₂ when R ₂ = H; R 1 = lormyl group, ketone group, azomethine group \ R * = H, when R ₂ = NO ₂ ; R 1 = formyl group, ketone group or azomethine group. 2. Chemotherapeutic antifungal preparation for the treatment of dermatomycoses in humans, thereby marked that it consists of 5 '»J' 5-acetyl-2,2'-bithiophene of the structural formula according to claim 1 as an active ingredient in combination with a pharmaceutical vehicle. J. Chemotherapeutic antifungal preparation according to Claim 2, characterized in that 509828/1016 ? 459666 that it contains as a pharmaceutical vehicle an ointment base made from vegetable oil and anhydrous lanolin in a ratio of 1: 1. 4. Chemotherapeutic antifungal preparation according to claims 2-3, characterized in that it contains 0.5 percent by weight of active ingredient contains. 509828/1016