DE2127982A1 - Virustatic indane-1,3-dione-2,2-derivs - from indanedione and two reagents or from diethylphthalate and methylsulphones - Google Patents

Abstract

Cpds. of formula (I): their salts and pharmaceutical compsns. (where X1 = O, S or SO2; R11 = (pref. 1-4C) alkyl or Ph; R12 = NH2 opt. substd. by 1-4C (alkyl or alkenyl), bicycloalkenylalkyl or Ph (opt. substd. by halo) or (Y1 = alkoxy or NH2 opt. mono- or di-substd. like R12)). If X1=O or SO2, R12 = (opt.) also halogen or 1-4C alkoxy, are virustatics active against both RNS- and DNS-viruses. Prepd. from indane-dione-(1,3) and (successively) H-X1-R1 and ZY1 (Z = COOH or derivs.) or (if X1 = SO2 or S) from diethylphthalate and methylsulphones in presence of sodium ethoxide.

Description

Indanedione derivatives The present invention relates to pharmaceutical preparations, in particular virustatics, characterized in that they are an indanedione derivative of the general formula I. in which a halogen atom or the group -X-R1, in which X is an oxygen or sulfur atom or a sulfonyl group and R1 is a lower alkyl, aralkyl or aryl radical and R2 is hydrogen, a halogen atom, a hydroxy, alkoxy or a optionally substituted amino group or the group represents, in which Y denotes hydrogen, an alkoxy or alkyl group, an optionally substituted amino group, or an optionally substituted aryl radical, or contain their pharmacologically acceptable salts as an active ingredient they act against both RNA and DNA viruses. The substances 5-iodo-2'-deoxyuridine and N-methyl-isatin-ß-thiosemicarbazone known as virustatics only act against DNA viruses, the known aminoadamantane only act against RNA viruses. The broad spectrum action of the virustatics according to the invention against RNA and DNA viruses of different virus groups is therefore surprising and could not be foreseen.

That these preparations are antiviral substances acts with virustatic effectiveness, results from the proven effectiveness in vitro and in vivo.

The investigation and evaluation of the virustatic effect took place according to the following methods: 1. Cell culture tests In cell cultures, the virustatic Effectiveness of the substances in comparative infection titer determinations in the test tube, tested in plaque inhibition and plaque reduction tests. The evaluation of the tests was carried out in comparison to virus-free and substance-free cell controls and substance-free Virus controls.

For the evaluation of the tube tests, the tables after Procedure by Kärber (Kärber, G .: Naunyn-Schmiedeberg's Arch. Exp. Path. Pharmak. 162, 480, 1931, calculated by R.J. Lorenz, Federal Research Institute for Virus Diseases der Tiere, Tübingen 1960), while the plaque test results according to Lorenz (Lorenz, R.J .: Zur Statistik des Plaque-Tester. Arch. ges. Virusforschg. 128 108-137p 1963).

The probability of error is less than 5%.

a) Comparative infection titer determinations in the test tube Each Test tube contains 1 ml of maintenance medium with 100 µg of test substance. After a two hour Exposure time is added 1 ml virus dilution. Any Virsu dilution level is occupied with 6 test tubes, the test is after two days of greening at 36 0C read.

The mean infection dose of the substance series is calculated as well the substance-free control.

b) Plaque inhibition test After 24 hours, adult cell cultures in Plastic dishes are inoculated with 0.5 ml of an appropriate virus dilution and after an incubation time of 2 hours at 360 ° C. in a CO 2 incubator with an ion agar layer covered. After the agar has solidified, a test disc with a diameter of 0.6 cm and a test substance content of 33 mg. The test plates are after a two-day incubation at 360C with a second layer of agar, which is used for Staining of the still intact cells neutral red or containing tetrazolium chloride is overlaid. After another overnight incubation, the plates are evaluated. The virus effectiveness a substance is shown as a ring-shaped anti-plague around the substance-containing test disc.

c) Plaque Reduction Test Cell cultures grown out after 24 hours in plastic dishes are inoculated with 0.5 ml of a suitable virus dilution and after a two-hour incubation period at 36 ° C in a CO2 incubator with 5 ml ion agar covered, 'the contains between 100 and 300 µg test substance per ml. After a further two days of incubation, 4 ml of ion agar is overlaid, which is used for Staining of the still intact cells contains neutral red or tetrazolium chloride. To another. Incubation overnight, the plaques formed by virus are counted. The viral effectiveness of a substance is shown in its ability to reduce plaque count compared to the substance-free irus control.

2. Animal experiments All influenza tests were carried out in mice weighing 13-15 g of the NMRI strain carried out the parainfluenza 3 test in Syrian hamsters with a weight between 40 and 50 g.

a) Influenza experiments in the mouse Each mouse receives at least 4 consecutive days in a single dose of 5 mg test substance (-350 mg / kg / day) per os.-Two hours after the first administration of the substance, the mouse is put under mild Xthernesthesia infected intranasally with 5dlm (mean infection dose). They are recorded Death advice within 10 days.

Each substance group consists of 10 mice, the virus control consists of 30 mice.

b) Parainfluenza 3 experiments in hamsters Each hamster receives 4 consecutive days in a single dose of 15 mg test substance (# 300 mg / kg / day) per os. One hour after the first administration of the substance, the hamster is under a light Xthernesthetic infected intranasally with 0.1 ml of a suitable dilution of virus.

On the 5th day of the experiment, the hamsters are bled after anesthesia, the lungs are removed and the virus content of the lungs is checked in a plaque test. Effectiveness of the test substance means significantly reduced virus content in the hamster lung.

The results of the investigations are compiled in the following tables. In the tables: + = effective in the dose tested (+) = weakly effective in the tested dose.

Table 1 Overview of our test viruses and their culture Testine Virus type cell culture animal HeLa Hep 2 HEZ *) mouse hamster Influenza A2 - Mannheim / 57 RNS + Influenza A2 - Japan / 305/57 RNS + Influenza A2 - Hong Kong / 50/68 RNS + Influenza B - Iowa / 1/69 RNA + Parainfluenza 3 RNA + + Vesicular stomatitis + Indiana RNA Polio II MEF 1 RNA + Herpes simplex - CAM 13 DNS + Vaccinia - Ankara DNS + Adeno 2 DNS + *) primary chicken embryonic cell Cell culture tests on animals Inf.A2 Parainfl. Vesic. Polio Herpes Vaccinia Adeno 2 Infl.A2 Infl.A2 Infl. B Parainfl. 57 3 Stomat. RNS simpl. DNS DNS Iowa / 1/69 3 RNA RNA Virus DNS 57 68 RNA RNA RNA RNA RNA a + + (+) + + (+) + b (+) (+) + c + + + + + + + + d + (+) + + e + + + f + + + + g + + + + + h + + (+) + I + + + + + + a = 2-formyloxy-2-methylmercapto-indandione- (1,3) b = 2-acetoxy-2-methylmercapto-indanedione- (1,3) c = @ 2-N-dimethylamino-carbonyloxy-2-methylmercaptoindanedione (1 , 3) d = 2-phenylsulfonyl-indandione- (1,3) e = 2-N-phenylamino-carbonyloxy-2-methylmercapto indandione- (1,3) f = 2-N-diethylamino-carbonyloxy-2-methylmercaptoindanedione- (1,3) g = 2-N- (3,4-dichlorophenylamino-carbonyloxy) -2-methylmercapto-indanedione- (1,3) h = 2-bicyclo- (2,2,1) -heptene- (2 ) -6-methylaminocarbonyloxy-2-methylmercapto-indandione- (1,3) i = 2-allylamino-carbonyloxy-2-methylmercaptoindanedione- (1,3) Of the compounds falling under the general formula 1, those are new which are of the general formula IX includes: (II), in which X 'an oxygen or sulfur atom or a sulfonyl group, R1' a lower 'alkyl or phenyl group, æR' an optionally substituted amino group or the group represents in which Y 'represents an alkoxy group or a mono- or disubstituted amino group, where, in the event that X' represents an oxygen atom or a sulfonyl group, R2 'can also be halogen or a lower alkoxy group.

The amino groups R2 and Y or R2 'and Y' can be used in compounds of Formula I or II, for example, by lower alkyl, lower alkenyl, bicycloalkenylalkyl or phenyl radicals, the phenyl radicals additionally being substituted by halogen atoms can be substituted.

As lower alkyl or alkoxy groups, radicals with 1-6, preferably 1-4 carbon atoms are understood.

The compounds II and their pharmacologically acceptable salts are prepared in a manner known per se by one mole of indanedione (1,3) or a reactive derivative of this compound in succession a) with one mole of a compound of the formula III, H - X'-R1 '(III), in which X' and R1 'have the meaning given above, or with a reactive derivative thereof and b) with one mole of a compound of the general formula IV, Z - Y '(IV) in which Z represents a carboxyl group or a reactive derivative thereof and Y 'has the meaning given above, ~ or with one mole of an optionally substituted Amine or a lower aliphatic alcohol reacts' or in the event that X 'should be a sulfonyl group or a sulfur atom c) phthalic acid diester with Methyl sulfones or methyl sulfines of the general formula V H3C - S (O) m R11 (V), in which R1 'has the abovementioned meaning and m represents the numbers 1 or 2, condensed and in the indanedione derivatives obtained in this way, the radical R2 'in the 2-position and, in the event that m = 1, the sulfinyl group is reduced or oxidized and the compounds II obtained in this way, if desired, with non-toxic organic compounds or inorganic acids converted into their pharmacologically acceptable salts.

For the reaction with derivatives of the formula III are particularly suitable 2-mono- or 2,2-dihalides of indanedione (1,3) and / or the corresponding 2-mono- or 2,2-dihydroxy-indanedione (1,3).

The production of these starting products is described in the literature (Reports 37, 1789t J. org. Chem. 29, 1358ff (1964); DBB 1,229,080] As reactive Derivatives of the formula III come, in the event that in the 2-position of the indanedione (l, 3) a halogen atom is to be substituted, those compounds in question, whose Hydrogen atom is replaced by an alkali metal atom.

For the reaction with derivatives of the formula IV are particularly suitable 2-Hydroxy derivatives of indanedione (1.3), the reaction here preferably takes place in a tertiary amine, e.g. Pyridine, the reactive derivative of the formula IV for example an acid halide is used.

Chlorocarbonic acid esters are also suitable as reactive derivatives IV, Carbonic acid amide chlorides and isocyanates.

In the latter case, the reaction is preferably carried out in a non-polar one organic solvents, for example in benzene or carbon tetrachloride.

The condensation of the phthalic acid diester with the compounds V takes place in the presence of a strong base, such as B. alkali alcoholate.

To reduce the sulfine group to the mercapto group in process c) for example, the so-called Pummerer reaction [cf. . J. org, Chem, 29, 1358 (1964)], while the oxidation to the sulfonyl group with conventional oxidizing agents, for example, can be carried out with nitric acid or hydrogen peroxide. The radical R2 is introduced in the manner described in process b).

The halogenation of compounds which are in the 2-position of the indanedione (1,3) have a hydrogen atom, or their sodium salts, can in aqueous solution, for example with elemental bromine.

The substances 1 can be used orally and parenterally in liquid or solid form be applied. The preferred injection medium is water, which is the usual additives for injection solutions such as stabilizers and solubilizers and / or contains buffers. Such additives are z. B. tartrate or borate buffer, Ethanol, Timethylsulfoxyd, complexing agents (such as ethylenediaminetetracetic acid), high molecular weight Polymore (like liquid polyethylene oxide) to regulate viscosity. Solid carriers are e.g. Starch., Lactose, mannitol, methyl cellulose, talc, highly dispersed silica, higher molecular fatty acids (such as stearic acid), gelatine, agar-agar, calcium phosphate, Magnesium stearate, vegetable and vegetable fats, solid high molecular weight polymers (such as polyethylene glycols). Preparations suitable for oral administration can if desired contain flavors and sweeteners. For external treatment The substances I are in the form of ointments with the usual Ointment Grondlage or as Tinctures applied.

As pharmacologically acceptable salts of the compounds I and II come in the event that R2 represents an amino group, compounds with harmless inorganic or organic acids, such as. B.

the hydrochlorides, hydrobromides, sulfates, phosphates, tartrates, citrates, Acetates or oxalates are possible.

The invention is explained in more detail in the following examples: , B e i s p i e 1 1 2-N-Dimethylamino-carbonyloxy-2-methylmercapto-indandione- (1, 3) 20 g of 2-hydroxy-2-methylmercapto-indandione- (1,3) are in 60 ml of anhydrous pyridine dissolved and treated dropwise with 10.8 g of dimethylcarbamyl chloride while cooling with ice.

The solution remains overnight and is then poured into ice water. The crystalline precipitate that forms is filtered off with suction and recrystallized from methanol. 20 g of 2-N-dimethylamino-carbonyloxy-2-methylmercapto-indandione (1.3X melting point) are obtained. 155.5-1570C.

Example 2 2-Ethoxycarbonyloxy-2-methylmercapto-indandione- (1,3) 15 g of 2-hydroxy-2-methylmercapto-indandione- (1, 3) are in 45 ml of anhydrous pyridine dissolved and 21.5 g of ethyl chlorocarbonate were added dropwise while cooling with ice. The mixture is left to stand overnight and is then poured into ice water. The deposited crystals are recrystallized from ethanol. 18.5 is obtained g of 2-ethoxycarbonyloxy-2-methylmercapto-indandione- (1,3); M.p. 67-680C.

Example 1 3 2-Phenylamineq-2-methylmercapto-indandione- (1,3) 5 g of 2-chloro-2-methylmercapto-indandione- (1,3) (cf. H.D.BECKER u.

G.A. RUSSEL, J. org. Chem. 28, 1896 (1963)) in 25 ml of anhydrous dissolved benzene and mixed with 4.52 g of aniline.

After standing for 2 hours, the crystals formed (aniline hydrochloride) suctioned off and the filtrate evaporated to dryness.

A crystalline product is formed when triturated with methanol.

After recrystallization from methanol, 2 g of 2-phenylamino-2-methylmercapto-indanedione (1,3) are obtained.

Mp: 122.5-123.50 C 16 H 13 O 2 NS (283.28) Calcd .: C 67.83 H 4.62 N 4.92 S 11.29 Measured values: C 68.0 H 4.4 N 5.3 S ll, i.d.

Ex. 1 4 2-Bromo-2-methylsulfonyl-indanedione- (1,3) In one 100 ml round bottom flask is stirred into a suspension of 5 g of 2-methylsulfonyl-indanedione-1, 3-sodium salt (cf. H. D. Becker u.

G.A. Russel, J. org. Chem. 28, 1897; (1963) added dropwise elemental bromine, until the bromine color persists. The reddish colored, flaky precipitate is suctioned off and freed from bromine by washing with petroleum ether and recrystallized from benzene.

Yield: 4.4 g.

M.p .: 160-161 ° C ClOH704BrS (303.14) Calcd .: C 39.6 H 2.3 Br 26.3 S 10.57 Found: C 39.5 H 2.7 Br 26.1 S 10.5.

EXAMPLE 5 2-Bromo-2-phenylsulfonyl-indanion- (1,3) In elnem 100 ml round-bottom flasks are 5 g of 2-phenyl-sulfonyl-indandione- (l, 3) -sodium salt (manufacture see under Example 13) suspended in 50 ml of water and elemental with stirring Bromine was added dropwise until the bromine color persists. The crystalline product will Sucked off, freed from excess, adhering bromine with petroleum ether and off Benzene recrystallized.

Yield: 5.7 g. Mp: 193-194 ° C. C15H9O4BrS (365.1) Calcd .: C 49.33 H 2.48 S 8.77 Br 21.8 Measured values: C 48.8 H 2.8 S 9.0, Br 21.0.

EXAMPLE 6 2,2-Diethoxy-indandione- (1, 3) 10 g of ninhydrin heated to 80 ° C for 30 minutes with 70 ml of saturated ethanolic hydrochloric acid. At the On cooling, 2,2-diethoxy-indandione- (1,3) separates into pale yellowish colored ones Crystals.

M.p .: 86-870C.

B-e i s p i e 1 7 2-N-phenylamino-carbonyloxv-2-methylmercapto-indandione- (1,3) 10.1 g of 2-hydroxy-2-methylmercapto-indanedione- (1, 3) and 5 g of phenyl isocyanate are heated to 80 ° C in 60 ml of anhydrous benzene for 2 hours.

After standing overnight, the crystals of 2-N-phenylamino-carbonyloxy-2-methylmercapto-indandione- (1, 3) suctioned off and washed with benzene.

Yield: 12.5 g mp: 202-205 ° C.

B e i s p i e 1 8 '2-N-phenyl-N-methyl-amino-carbonyloxy-2-methylmercapto-indandione- (1, 3) 20 g of 2-hydroxy-2-methylmercapto-indandione- (1,3) are in 30 ml anhydrous Pyridine dissolved and with ice cooling with a solution of 16.2 g of N-methyl-N-phenyl-carbamyl chloride added in 30 ml of pyridine.

After standing overnight, it is poured into ice water. The one that forms crystalline precipitate is filtered off with suction and recrystallized from methanol. you get 15 g of 2-N-phenyl-n-methyl-amino-carhonyloxy-2-methylmercapto-indandione- (1, 3).

Mp 150-152 ° C C18H1504NS (341.3) Calcd .: C 63.3 H 4.42 0 18.74 N 4.13 S 9.41 Measured values: C 63.2 H.4.4 0 19.0 N 4.2 S 9.6.

B e i s p i e 1 9 -2-N-diethylamino-carbonyloxy-2-methyl-mercapto-indandione- (1, 3) 20 g of 2-hydroxy-2-methylmercapto-ibndandione- (1, 3) are in 60 ml of anhydrous Pyridine dissolved and 13.1 g of diethyl carbamyl chloride added dropwise with ice cooling offset.

The solution stays there overnight. It is then poured into ice water. The krastalline precipitate that forms is filtered off with suction and recrystallized from methanol. 17 g of 2-N-diethylamino-carbonyloxy-2-methyl-mercapto-indandione (1,3) are obtained.

Mp: 122-124 ° C C15H17NO4S (307.4) Calcd .: C 58.63 H 5.56 0 20.82 N 4.55 S 10.45 Measured values: C 58.0 H 5.3 0 20.8 N 4.8- S 10.9.

Ex. 10 2-N- (3,4-dichlorophenylamino-carbonyloxy) -2-methylmercato-indanedione-10 g of 2-hydroxy-2-methylmercapto-indandione- (1, 3) and 15 g of 3,4-dlelllor- ' phenyl isocyanate are dissolved in 100 ml of carbon tetrachloride with the addition of 2 drops of pyridine and heated to 450C for 5 hours.

The precipitate that forms is filtered off with suction and recrystallized from ethanol. 13 g of 2-N- (3,4-dichlorophenylamino-carbonyloxy) -2-methylmercapto-indanedione (1,3) are obtained.

M.p .: 221-222 ° C C17H11Cl2NO4S (396.2) calc. : C 51.5 H 2.8 C1 17.9 0 16.2 found C 52.0 II 3.3 C1 18.1 0 16.3; B e i s p i e l 11 2-bicyclo- (2,2,1) -heptene- (2) -6-methylamino-carbonyloxy-2-methylmercapto-indandione- (1,3) 10 g of 2-hydroxy-2-methylmercapto-indandione- (1,3) are dissolved in 100 ml of anhydrous benzene dissolved and treated with 7.8 g of 6-isocyanato-methylbicycLo-2,2,1-hepten- (2). The mixture is heated to 80 ° C. for 8 hours and left to stand for 24 hours.

The crystalline precipitate is filtered off with suction and recrystallized from ethanol. 9 g of 2-bicyclo- (2,2,1) -hepten- (2) -6-methylamino-carbonyloxy-2-methylmercapto-indanedione- (1,3) are obtained.

M.p .: 227-229 ° C C19H19NO4S (357.4) Calcd .: C 63.8 H 5.4 N 3.9 S 9.0 Found: C 64.0 H 5.0 N 3.8 S 8.8.

B e i s p i e l 12 2-Allylamino-carbonyloxy-2-methylmercapto-indandione- (1,3) 20 g of 2-hydroxy-2-methylmercapto-indandione- (1,3) are dissolved in 200 ml of anhydrous benzene dissolved and with 8.8 g of allyl isocyanate and '5 drops of pyridine are added. The solution is heated to 80 ° C. for 4 hours and then left to stand overnight.

The precipitated crystal mass is filtered off with suction and washed with benzene and recrystallized from ethanol. 7 g of 2-allylamino-carboyloxy-2-methylmercapto-indanedione (1,3) are obtained.

Mp: 193-195 ° C C14H13NO s (291.3) Calcd .: C 57.7 H 4.5 N 4.8 S 11.0 Found: C 58.2 H 4.4 N 5.0 S 11.5.

B e i s i e 1 13 2-Phenylaulfonyl-indanedione- (1, 3) 22.2 g of diethyl phthalate and 58 g of phenylmethylsulfone are dissolved in 100 ml of anhydrous toluene at 80 ° C heated and about 50 ml of toluene distilled off under a weak vacuum. To. cooling down 6 g of dry sodium methylate are added. With slow heating to 1500C and pressure of 40-50 torr becomes excess toluene and the alcohol that forms distilled off. The residue is used to remove excess phenylmethyl sulfone boiled with approx. 400 ml of toluene and filtered hot. The residue will be in about 150 ml of water and acidified with 10% hydrochloric acid. The crystalline that forms The precipitate is recrystallized twice from benzene.

Yield: 10 g of pale yellow crystals.

F.: 160-161.5 ° C C15H10O4S (286, 3) Calc .: C 63.1 H 3.17 S 11.2 found. : C 62.8 II 3.6 511.3.

For the production of 2-phenylsulfonyl-indandione- (1, 3) -sodium salt can the above product in the warmth in an equivalent amount of baking soda lye be solved. In the cold, the salt crystallizes from this solution in the form of yellow crystals.

B e i s p i e 1 14 Pharmaceutical preparations in juice form a.) 1000g 2-Hydroxy-2-methylmercapto-indandione- (1,3) [preparation according to; Org. Chem. 29, 1358 (1964) 7 is in 60 liters of demineralized water at 300C in a batch kettle dissolved from acid-proof steel with stirring.

Then dissolve 20 g of p-hydroxybenzoic acid butyl ester (nipabutyl) in 10 liters of water at 80 ° C and cools to 10 ° C. The two solutions are then combined and one after the other after complete dissolution with 2 g of dye (Amaranth) 35 kg sucrose DAB 7 and 200 g aroma (raspberry) added. The approach is adjusted to pH 3.5-4.3 with a 25% aqueous citric acid solution and made up to 100 liters with demineralized water. The solution is final stirred well, filtered and bottled.

b.) 500 g formyloxy-2-methylmercapto-indandione- (1,3) (preparation according to DBP 1 229 080) are micronized (grain size 1-5 p and in 10 liters one 300C warm solution of 500 g polyoxyethylene stearate (Myri 52) and 500 g starch syrup finely suspended by means of an intensive stirrer. The active ingredient suspension is in 60 liters of a solution of nipabutyl, dye (tartrazine) prepared according to a.), Sugar and flavor (vanillin) mixed in homogeneously and by adding water and starch syrup brought to a viscosity of about 500 cp to prevent segregation.

EXAMPLE 1 15 Pharmaceutical products in tablet form a.) 50. 2-acetoxy-2-methylmercapto-indandione (1, 3) [manufactured according to DBP 1 229 0807 be mixed with 40 g milk sugar and 40 g corn starch and with the addition of 10% corn starch paste granulated. The finished granulate is passed through a sieve with a mesh size of 0.8 mm sifted. Then 10 g of methyl cellulose, 10 g talc and 2 g magnesium stearate mixed in. The mixture is then homogenized and to tablets with a diameter of 9 mm with a total weight of 202 mg pressed.

b.) Are 100 g of 2-benzoyloxy-2-methylmercapto-indandione- (1,3) gProduction according to DBP 1 229 0807 processed into a tablet mass according to a.}, this gives tablets with a diameter of 10 mm and a total weight of 252 mg.

B e i s p i e 1 16 Pharmaceutical preparations in tablet form a.) 30 g of 2-thoxy-2-methylmercapto-indandione [manufactured according to J. Org. Chem. 29, 1362 (1964) 7 are according to Example 15 with 25 g lactose, 25 g corn starch, 5 g methyl cellulose, 5 g of talc and 1 g of magnesium stearate processed into a base mass, which becomes curved Dragé cores with a total weight of 110 mg are pressed. The so obtained Cores are then coated in a known manner with a sugar coating and then waxed.

b.) Using 50 g of 2,2-dichloro-indandione- (1,3) [preparation According to reports 21, p. 5017, tablet cores are produced according to a.), which then be coated with a layer of Eudragit lacquer.

Claims (7)

P a t e n t a n s p r ü-c h e 1. Pharmaceutical preparation mit.virustatlscher effectiveness consisting of a pharmacologically acceptable carrier and at least one active ingredient, characterized in that it is one or more indanedione derivatives of the general formula I as the active ingredient in which V is a halogen atom or the group -X-R1, in which X is an oxygen or sulfur atom or a sulfonyl group and R1 is a lower alkyl, aralkyl or aryl radical and R2 is hydrogen, a halogen atom, a hydroxy -, - alkoxy- or an optionally substituted amino group or the group represents, in which Y denotes a hydrogen, e alkoxy or ar alkyl group, amines optionally substituted amino group, or an optionally substituted aryl radical, or contains their pharmacologically acceptable roller. 2. Use of indanedione derivatives of the general formula I. in which V is a halogen atom or the group -X-R1, in which X is an oxygen or sulfur atom or a sulfonyl group and R1 is a lower alkyl, aralkyl or aryl radical and R2 is hydrogen, a halogen atom, a hydroxy, alkoxy or an optionally substituted amino group or the group represents, in which M is a hydrogen, an alkoxy or alkyl group, a substituted amino group, or an optionally substituted aryl radical, or of their pharmacologically compatible for the production of drugs with virustatic activity 3. Indanedione derivatives of the general formula II in which X 'is an oxygen or sulfur atom or a sulfonyl group, R1 is a lower alkyl or phenyl group, R;' an optionally substituted amino group or the group represents, in which Y 'represents an alkoxy group or a mono- or disubstituted amino group, where, in the event that X' represents an oxygen atom or a sulfonyl group, R2 'can also be halogen or a lower alkoxy group, as well as their pharmacologically acceptable salts. 4. indanedione derivatives according to claim 3, characterized in that the radicals R2 and / or Y 'by lower alkyl, lower alkenyl, bicycloalkenylalkyl or phenyl radicals are substituted, the phenyl radicals additionally by halogen atoms can be substituted. 5. Process for the preparation of indanedione derivatives of the general formula II in which X 'is an oxygen or sulfur atom or a sulfonyl group, R1 is a lower alkyl or phenyl group, R2' is an optionally substituted one of the general amino group or the group represents, in which Yz represents an alkoxy group or a mono- or disubstituted amino group, where, in the event that X 'represents an oxygen atom or a sulfonyl group, R2' can also be halogen or a lower alkoxy group, as well as pharmacologically acceptable ones of these Salts, characterized in that one mole of indanedione- (1,3) or a reactive derivative of this compound, in any order a) with one mole of a compound of the formula IIP, H-X'-R1 'in which X' and R1 'have the abovementioned meaning', or with a reactive derivative thereof and b) with one mole of a compound of the general formula IV, Z -in which Z represents a carboxyl group or a reactive derivative thereof and Y 'has the abovementioned meaning, or is reacted with one mole of an optionally substituted amine or a lower aliphatic alcohol, where X' represents a sulfonyl group or a sulfur atom , also react a phthalic acid diester with a corresponding methyl sulfone or methyl sulfine, reduce the sulfonyl or sulfinyl group if desired and then introduce the radical R2, or in the event that X 'should be a sulfonyl group or a sulfur atom c.) Phthalic acid diester with methyl sulfones or methyl sulfines of the general Formula V H3C - S (O) m 1 R11 (V) in which R1 'has the abovementioned meaning and m represents the numbers 1 or 2 condensed, then introduces the radical R2t in the 2-position into the indanedione derivatives thus obtained and in the event that m = 1, the sulfinyl group is reduced or oxidized and the compounds II thus obtained are, if desired, converted into their pharmacologically acceptable salts with non-toxic organic or inorganic acids. 6. The method according to claim 56, characterized in that as reactive Derivatives of the formula IV, acid halides, in particular chlorocarbonic acid esters, carbonic acid amide chlorides or isocyanates can be used. 7. The method according to claim 5, characterized in that the residues R2 'and / or Y' by lower alkyl, lower alkenyl, bicycloalkenylalkyl or Phenyl radicals are s'ubstituiert, the phenyl radicals additionally by halogen atoms can be substituted.