DE1965481A1 - New adamantane derivatives - Google Patents

Description

The invention relates to new adamantane derivatives of the formula I ■

in which R represents hydrogen, methyl or ethyl and m and η = 0, 1 or 2, while m + η = 1 or 2 and their salts formed with pharmaceutically acceptable acids.

It was found that these compounds

have strong antiviral effects. It also turned out that the substances in relation to their antiviral Effectiveness only to a very small extent, side effects

v.i.en. 008829/1898

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The antiviral effectiveness of the compounds was found in experiments with mice. Ten mice were given a dose of the twice daily for 5 days test substance administered orally. On the first day after the first administration of the substance, the animals were infected with a virus that was found in the cages in which when the mice were located, was splashed. Because it's hard to tell whether the animals get sick or not, a dose of the virus was administered such that all mice die during the experiment. These The dose is naturally many times greater than that of one natural infection.

The mice that died were counted twice a day. The number of dead mice and the timing of theirs The deaths were compared with the data obtained with a group of 10 mice that were infected but to which no test substance was administered. With the help of the method according to Milcoxon could be calculated that the substances have a strong antiviral effect.

These compounds in particular against

Influenza viruses, in particular against A strains, such as, for example, A2-Japan, of the compounds of the formula I are those in which R is hydrogen and in which η = 0, m = 1 and in particular η = 1, m = 1 is most effective.

As examples, pharmaceutically acceptable

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BATH OWQINAL

Acids with which the amino bases according to., The invention salts can form, the following can be mentioned: inorganic acids, such as hydrohalic acids, sulfuric acid, nitric acid, phosphoric acid, 5 organic acids such as acetic acid, citric acid, Tartaric acid, sulfanilic acid, p-toluenesulfonic acid, succinic acid, Fumaric acid, oxalic acid, benzoic acid and the like.

The compounds according to the invention can

to fight virus infections and in particular to prevent them to be used by viral infections · One can start giving humans or animals a substance according to the invention to be administered as soon as a viral infection has emerged. Particularly good results are achieved when the The substance is administered as soon as there is a risk of infection or as soon as the weather conditions make an imminent infection likely do. It is therefore advisable to administer a dose of one of the compounds daily during the winter months.

Since vaccination only causes immunity after 3 weeks, the compounds can also be used together with a Vaccine are administered so that they protect against infection during the first three weeks after vaccination.

The compounds can be injected as well as administered orally or rectally. The oral Administration is preferred.

The adult dose is 50 per day

to 300 mg, preferably 150 mg. A one-time daily Administration of the entire dose is possible. Children are treated with half the dose. The most suitable dose for

009829 / $ 188

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Animals is from 10 to 60 mg / kg / day and preferably 25 mg / kg / Day.

The compounds of formula I can be prepared by methods known for preparing these types of compounds and processes analogous to this process can be obtained.

Accordingly, the invention also relates to a process for the preparation of new adamantane derivatives, characterized in that compounds of the formula I

in which m and η = 0, 1 or 2 and m + η = 1 or and R is hydrogen, methyl, ethyl, and their salts formed with pharmaceutically acceptable acids by processes known for the preparation of this type of compounds and processes analogous to these processes getting produced.

Thus, the compounds of the formula I can be prepared in that a compound of Formula II

II

009829/1888

in which the symbols have the same meaning as in formula I, is reduced. This reduction can be done with Using hydrides like LiAlH ^, NaAlH ^ or NaBH. + A1C1 ", be performed. The reaction is preferably carried out in an inert solvent such as diethyl ether, dioxane, Tetrahydrofuran, diglyme, etc.

The starting materials of the formula II can e.g. can be obtained in the following ways:

The substance where m = 1 and η = 0: Adamantanone is coupled with cyanoacetic acid according to Cope. The reaction product is with KCN in methanol 2-cyano-2-cyanomethyladamantan _f which is hydrolyzed with concentrated sulfuric acid to dicarbonamide. With concentrated hydrochloric acid, an anhydride is obtained therefrom, which is converted into 2-carboxy-2-methoxycarbonyl-methyl-adamantane with methanol. After reduction with LiAlHr and subsequent heating of the 2- /} -hydroxyethyladamantane-carboxylic acid-2, the corresponding lactone is obtained. The latter is boiled with KCN in dimethyl sulfoxide and the nitrile obtained is saponified. The dicarboxylic acid produced in this way is converted by heating into the anhydride, which is converted with ammonia, methyl or ethylamine in benzene into the hemiamide, from which the desired imide of the formula II is obtained by heating. The substance where m = 1 and η = 1: 2-bromomethyl-2- ^ bromoethyladamantane is boiled with technical grade NaCN in methyl cellosolve and converted into the dinitrile, which is saponified to the diamide with sulfuric acid. With hydrochloric acid

009829/1898

a dicarboxylic acid can be obtained based on the above-described Way can be converted into an imide .. The substance in which m = 0 and η = 1: 2-carboxy-2-methoxycarbonylmethyl-adamantane (see above) is esterified with dimethyl sulfate. At room temperature it can be converted into 1 VaI NaOH the other half-ester can be obtained in methanol. The methoxycarbonyl group this compound is converted into a hydroxymethyl group with LiAlH ^. Then by heating a lactone obtained with KCN in dimethyl sulfoxide in 2-cyanomethyl-2-carboxymethyladamantane is converted, from which a dicarboxylic acid is obtained with lye, which on is converted into an imide in the manner described above. The substance in which m = 2 and η = 0: 2-carboxy-2-y # hydroxyethyladamantane (see above) is esterified with diethyl sulfate. The hydroxyl compound is then converted into the Bromide converted with sodium diethyl malonic ester in absolute Ethanol is coupled. The triester is saponified and decarboxylated by boiling in 50% sulfuric acid. The dicarboxylic acid thus produced is converted into an imide in the manner described above.

The compounds of the formula Ia

NH

Yes

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-7- 196548V PHN. 3774

in which ρ and q = 0 or 1 and ρ + 1 = 1, and Their salts can also be obtained by reduction with a hydride of a compound of the formula III

can be obtained in which ρ and q = 0 or = 1 and ρ + q = 1, while either Y or Y ^{1 represents} a carbonyl group and the other symbol then a methylene group.

The compounds of formula II can be obtained in the following way:

p = O, q = 1, Y = "CO, Y '= CH ₂ :

2-Carboxy-2- ₍ $ -cyanoethyladamantane is reduced with Pt / H. After conversion of the carboxyl group with thionyl chloride, the substance is obtained by ring closure.

ρ = 0, q = 1, Y = CH ₂ , Y «= CO and ρ = 1, q = 0, Y = ^CH ₂ ' ^Y ' = ^C0: 2-carboxy-2-carboxymethyladamantane is converted into the anhydride by heating , which is reduced to dialcohol with LiAlHj. The substance is cyclized under the action of 48% HBr and converted into 2-bromomethyl-2- / 3-bromoethyladamantane with triphenylphosphine and bromine. This substance is reacted with anhydrous NaCN and then with sulfuric acid. The ketone obtained is coupled with hydroxylamine and then heated in polyphosphoric acid. The two compounds are formed through a Beckmann transformation.

The tertiary amines of the formula I can also be obtained by alkylating the secondary amines.

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-8- lSb $ 4S'l ^ΡΗΝ 3774

The secondary amines can be with a halide (RHaI) or a dialkyl sulfate (r “SOk), preferably in an alkaline one inert solvents, e.g. triethylamine, pyridine, KOH or K_CO_ in benzene or methanol, are made to react.

The secondary amines can also be reduced with formaldehyde or acetaldehyde and e.g. Pt / H ", Raney nickel / H", Formic acid, NaBHr and the like can be alkylated.

Finally, the tertiary amines can too

by acylation with formic acid, acetic acid halide or -anhydride and reduction with e.g. LiAlH ^.

The substances can be converted into a

be brought into a suitable form for administration. So they can with inert solid or liquid carrier materials mixed or dissolved in these materials. Tablets, pills, coated tablets, suppositories, powders, suspensions, Injection liquids, capsules and the like can be produced. If necessary, it can contain other medicinal products Vitamins or dyes are processed.

As carrier materials, e.g. water, glycerine, microcrystalline cellulose, calcium phosphate, Lactose and powdered sugar (sucrose), carboxymethyl cellulose, cocoa butter and other suppository masses are used will.

Tablets and coated tablets can also contain swelling agents

which make the preparation easily disintegrate in water. The following can be used as such: potato starch, corn starch, arrowroot (Amylum Marantae). Furthermore can

009 8 2 9/1898

Lubricants such as talc, magnesium stearate and calcium stearate, Find application.

As preservatives, compounds such as methyl p-hydroxybenzoate, propyl p-hydroxybenzoate and benzyl alcohol, can be added.

Examples:

1a) ethyl adamantylidene-2rcyanessigsäureäthylester

95 g of adamantanone were boiled in 320 ml of benzene with 72 g of ethyl cyanoacetate, 5 g of ammonium acetate and 7-25 ml of acetic acid for 6 hours, the water formed being azeotropic
was distilled off. The solution was then washed with water, dried over sodium sulfate and concentrated. The residue was crystallized by dissolving it in 110 ml of alcohol and adding 32 ml of water to this solution
after which crystallization was initiated by shaking. Melting point 81-82 ° C.
1b) 2-cyano-2-cyanomethyladamantane

100 g of ethyl adamantylidenecyanoacetate were dissolved in 800 ml of ethanol; 6k g of KCN, dissolved in 140 ml of water, were added to this solution. This mixture was stirred at 65 ° C. for 16 hours. After cooling, the material which had crystallized out was filtered off with suction. Some fractions were still obtained by concentration in vacuo. The crystal masses were washed neutral with 0.2 η KOH and then with water and dried. Melting point 126-127 ° C.

00982971898

-ιυ- ι;? Qα ** ο ι pun. 37/4

1c) 2 ', 5'-adamantanspiro-3'-tetrahydrofuran

76. g of 2-cyano-2-cyanomethyladamantane were dissolved in 750 ml of concentrated H ₂ ^SO 4 ^at 90.degree. The temperature rose to about 110 ° C. during this process. The solution was shaken for 5 minutes and then poured onto about 10 liters of ice. The mixture obtained was neutralized with 50 $ NaOH and the solid formed was filtered off with suction and washed with water. This mass was brought into 2100 ml of concentrated HCl and heated to 80 ° C. for 2 hours with vigorous stirring. After cooling, the solid formed was filtered off with suction, washed with water and crystallized from benzene. Melting point 226-229 C. 1d) 2-carboxy-2-carbomethoxymethyl-adamantane 15.6 g of 2x, 5'-diketo-adamantanspiro-3'-tetrahydrofuran were dissolved in 250 ml of methanol and, after addition of 15 nil pyridine, 3 hours boiled on reflux. The solvent was distilled off in vacuo and the residue was dissolved in ether. The ether solution was extracted with 2N KOH, the alkaline solution was acidified and extracted with ether. The ether extract was steamed to dryness. Melting point after crystallization from hexane: 102-106 C. 1e) 2-carboxy-2- (2 ^t -hydroxyethyl) adamantane 2.0 g of 2-carboxy-2-carbomethoxymethyl adamantane were added to a suspension of 1.0 g of LiAlHr in 100 ml of ether added. The reaction mixture was refluxed for 10 minutes, then cooled and decomposed with alcohol-water. The precipitate was filtered off and washed with warm ether. The ether solution was extracted with 2N KOH, the alkaline one

009829/1888

-η- 1300 ^ 0 1 PHN. 3774

"The solution was acidified and the precipitate sucked off. The material was recrystallized from acetone-hexane. Melting point 188-191 ° C.

After evaporation of the ethereal solution, 2-

Hydroxymethyl-2- (2'-hydroxyethyl) adamantane as a by-product isolated. After recrystallization from hexane, the melting point was 108-110 ° C.

1f) 2'-keto-adamantanspiro-3'-tetrahydrofuran 9.0 g of 2-garboxy-2- (2'-hydroxyethyl) adamantane, suspended in 150 ml of benzene, 50 mg of p-toluenesulfonic acid were added. The mixture was heated to the boiling point and the water formed was azeotropically distilled off. After cooling, dry K “CO” was added. The solid was filtered off and the solution was evaporated to dryness. Melting point after crystallization from acetone-hexane: 173-175 ° C. 1g) 2-carboxy-2- (2'-cyanoethyl) adamantane 5i5 g of KCN were suspended in 110 ml of dimethyl sulfoxide; then 5.5 g of 2'-keto-adamantanspiro-3'-tetrahydrofuran were added. The mixture was refluxed for h hours, then cooled, poured into 500 ml of water and acidified with 2N HCl. The precipitate was filtered off with suction and recrystallized from benzene. Melting point 150-152 ° C. 1h) 2-carboxy-2- (2 ^f -carboxyethyl) adamantane 6.0 g of 2-carboxy-2- (2 -cyanoethyl) adamantane were dissolved in 250 ml of 2N NaOH and refluxed for 18 hours. After cooling, it was acidified with 2N HCl. The precipitate was filtered off with suction and recrystallized from ethanol. Melting range 265 - 280 ° C.

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"Ii) 2 ', 6' -diketo-adamantanspiro-3 '-tetrahydropyran 3.2 g of 2-carboxy-2- (2'-carboxyethyl) adamantane were suspended in 50 ml of acetic anhydride and refluxed for 2 hours. The solvent was evaporated in vacuo, melting point after crystallization from acetone-hexane: 126-128 C. 1 j) 2- (2'-N-methyl-carboxamidoethyl) -2-carboxy-adamantane 0 »50 g of 2 ', 6'-diketo -adamantanspiro-3'-tetrahydropyran was dissolved in 60 ml of dry benzene, after which an excess of methylamine was introduced under reflux cooling. After cooling, the methylammonium salt was suctioned off, dissolved in water and acidified with 2N HCl. The precipitate formed was suctioned off and removed from ethanol. Benzene recrystallized, melting point 236-239 ° C.

1k) N-methyl-2 ', 6'-diketo-adamantanspiro-3'-piperidine 0.50 g of 2-2 · - (N-methyl-carboxamido) -ethyl-2-carboxyipadamantane was in a sublimation apparatus in a nitrogen atmosphere 250-300 ° C heated. The sublimate and the residue were extracted with methylene chloride; the substance insoluble in methylene chloride was heated again, the filtrate was evaporated to dryness and sublimed at 200-3OO ° C./15 mm Hg. Melting point after recrystallization from ethanol-water: 119 - 121 ° C.

11) N-methyl-adamantanspiro-3'-piperidine hydrochloride 0.50 g of N-methyl-2 ', 6'-diketo-adamantanspiro-3'-piperidine was a suspension of 0.25 g of LiAlHj, in 100 ml of ether added. The mixture was refluxed for 5 hours, after cooling it was decomposed with water and extracted with ether.

009829/1868

The ether extract was evaporated to dryness, the residue was dissolved in ethanol and a small excess of a solution of HCl in ethanol was added. After evaporation to dryness, the residue was then sublimed into Hg at 250-300 C / 15. Melting point after crystallization: 301-3O5 ° C. 2a) 2- β- hydroxyethyl-2-hydroxymethyladamantane To 1300 ml of absolute tetrahydrofuran, 73 g of 2 ', 5'-diketoadamantane spiro-3'-tetrahydrofuran and then 21.3 g of LiAlHr were added. This suspension was boiled with stirring for 18 hours. After cooling in an ice bath, 50 ml of water in 200 ml of tetrahydrofuran was slowly added dropwise. Then another 500 ml of 2N HpSOr were added. The precipitated salts were filtered off with suction and washed with tetrahydrofuran. The filtrate was saturated with NaCl and the organic layer was deposited. The water layer was washed with 3 × 100 ml of tetrahydrofuran. The combined organic layers were washed with 500 ml of 1N NaOH and dried with. After evaporation a crystalline material resulted. Melting point 109-111 ° C.

2b) Adamantanspiro-3'-tetrahydrofuran 59.7 g of 2- / d-hydroxyethyl-2-hydroxymethyladamantane and then 11.4 ml of concentrated H ₂ SOk were placed in 114 ml of 48 # HBr. This equipment was stirred at 110-115 ° C. for 3 hours. After cooling, 100 ml of distilled water were added and this reaction mixture was extracted with 150 ml methylene chloride χ k. The methylene chloride solution was concentrated with 120 ml of 10% bicarbonate solution and 100 ml

009829/1898

Washed with saline. After drying over MgSOjL was Evaporated dry to give an oil.

2c) 2- / 9-Bromoethyl-2-bromomethyl-adamantan in 265 ml of benzonitrile, 72.05 g of Triph.enyXpl10spl1.x11 were dissolved.

With cooling and stirring, 14 ml = hh g bromine were added dropwise. Then the mixture was heated to 125 C and were

50.7 S adamantane spiro-3'-tetrahydrofuran added. The mixture was then stirred at 125 ° C. for a further k hours. To. After cooling, the reaction mixture was poured into 2 g 1 diethyl ether. The precipitate of triphenylphosphine oxide formed was filtered off and washed with ether. The ethereal solution was then evaporated to dryness, during which the benzonitrile was also distilled off. The residue was suspended in 250 ml of boiling hexane and filtered hot. The hexane filtrate was then evaporated to dryness and the residue was chromatographed over SiO_, the eluent consisting of methylene chloride. The solutions of the above-mentioned substance were evaporated to dryness, the residue was recrystallized from hexane. Melting point 79 --81 ⁰ C.

2d) 2 - cy anomethyl - 2- β - cyan ο Ä thyl - adamantan and 2-bromomethyl-2- / 3 -cyanoethyl-adamantan

16.8 g of 2-bromomethyl- 2-ß- bromoethyl-adamantane and 5.1 g of NaCN were boiled for 5 hours in 50 ml of methyl cellosolve with stirring. After cooling, the mixture was filtered off and the filtrate was evaporated to dryness in vacuo. The residue was then chromatographed on a column of 750 g of silica gel with the aid of methylene chloride. After a little a side

009829/1898

product-containing fraction were obtained successively:

2-bromomethyl-2-> $ -cyanoethyl-adamantane, melting point 70-74 C, and 2-cyanomethyl-2-y3 -cyanoethyl-adamantane, melting point. - '

113-115 ° C.

2e) ■ 2- <f -aminopropyl-2-bromomethyl-adamantane hydrochloride 2.4 g of 2-bromomethyl-2- / 3 -cyanoethyl-adamantane were mixed with 0.7 g of PtO and 3 ml of 4.5 η ethanolic HCl in 100 ml Ethanol hydrogenated over N.aclit with an initial pressure of + _ 4 atm.

After the catalyst had been filtered off, the mixture was concentrated to a small volume in vacuo and diethyl ether was added added until crystallization started. Melting point 210-211 ° C.

2f) Adamantanspiro-3 ^f -piperidine hydrochloride 2.93 g of 2-y'-aminopropyl-2-bromomethyl-adamantane hydrochloride, dissolved in 300 ml of butanol, were added dropwise to a boiling solution of 1.5 g of KOH in 200 ml of butanol over the course of one hour . The mixture was then boiled for a further 12 hours while stirring. After cooling, the precipitate of KBr and KCl was filtered off and, after acidification with alcoholic HCl, the filtrate was evaporated to dryness in vacuo.

The residue would be taken up in 70 ml of water and 20 ml Diethyl ether extracted. Then the water layer was made alkaline with 2N NaOH and extracted with methylene chloride. After drying over magnesium sulfate, it was acidified with alcoholic HCl and evaporated to dryness. Your stuff was out Ethanol ether crystallizes. Melting point 249-251 ° C,

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3a) 2- / 3-aminoethyl-aminomethyl-adamantane dihydrochloride 2j8 g of 2-cyanomethyl-2- _/ $ -cyanoethyl-adamantane were monitored with 1.2 g of PtO and 10 ml of 4.1% alcoholic HCl in 16O ml of ethanol Hydrogenated with an initial pressure of + 4 Atm H _0. The catalyst was then filtered off and the filtrate was concentrated in vacuo. The residue was crystallized from tetrahydrofuran. The crystals were filtered off and washed with ether-tetrahydrofuran in a mixing ratio of 1 :. Melting point 290-292 C. 3b) Adamantanspiro-4'-hexahydroazepj, n -? »Hydrochloride

0.1 g of 2 / j- aminoethyl-2-aminomethyl-adamantane dihydrochloride

was heated to 290 ° C. for 4 hours in a sublimation apparatus. The sublimate was dissolved in water and extracted with ether. Then the water layer became alkaline with 2N NaOH made and extracted with diethyl ether. The ether fraction was dried over magnesium sulfate and then acidified with alcoholic HCl. After evaporation, the obtained crystalline substance stirred with tetrahydrofuran and then filtered off. Melting point 255-262 ° C.

4) Injection liquid

25 mg adamantane spiro-3'-piperidine hydrochloride 15 mg benzyl alcohol
Water ad 1 ml

5) tablet

200 mg adamantane spiro-4'-hexahydroazepine hydrochloride 335 mg of lactose

60 mg potato starch

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25 mg talc

5 mg magnesium stearate

about 5 mg of gelatin

6) Supp ο sit ο rium

200 mg adamantane spiro-4'-hexahydroazepine hydrochloride 1320 mg of suppository mass

7) Preparation of an injection liquid

250 mg Adaraantanspiro-3'-piperidine hydrochloride are in 9 1 ¥ dissolved water for injection. Then 150 g of benzyl alcohol added.

The mixture is stirred until a homogeneous liquid is obtained is. The pH value is adjusted to 4.5-5.5 with 0.1 η hydrochloric acid p.a., after which with water for injection up to a volume of 10 1 is filled. The solution is filtered through a bacterial filter and capsules of 2 ml are made filled in under aseptic conditions with the obtained substance.

8) Manufacture of tablets

200 g adamantane spiro-4-hexahydroazepine hydrochloride, 335 g lactose and

30 g potato starch

are mixed until a homogeneous mixture is obtained. The mixture is made with a 10% solution of gelatin in water wetted. The moist mass is granulated with the aid of a granulator provided with an 8-mesh sieve. That moist granulate is dried at 45 C and then is the dry granules using one with a 12 mesh

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-is-

Sieve grate provided granulator broken. The granules are then mixed with a mixture of 25 g talc, 5 g magnesium stearate and 30 g potato starch which has been sieved in a 40 mesh sieve. The mixture obtained in this way is compressed to tablets weighing 650 mg. 9 ") Manufacture of coated tablets

The cores of dragees are made in the same way as tablets. Instead of flat tablets, biconvex tablets are used with a weight of 325 mg. These kernels will be coated with talc and sugar layers and then with a glossy layer.

10) Making suppositories

200 g of adamantane spiro-4'-hexahydroazepine hydrochloride are in sifted through a 60-mesh sieve and added, with stirring, an amount of 1320 g of suppository mass heated to 37 ° C. After a homogeneous mixture has been obtained, suppository forms of 1.5 ml are filled with the mixture.

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Claims (1)

PATENT CLAIMS ; . Ij) process for the production of new adamant other i- vate, characterized in that compounds of the formula I -NO in which m and η = 0, 1 or 2 and m + η = 1 or 2 and R is hydrogen, methyl or ethyl, and their salts formed with pharmaceutically acceptable acids " by processes known for the preparation of this type of compounds and processes analogous to these processes getting produced. 2. The method according to claim I _1, characterized in that a compound of formula II C = O in which n, m and R have the same meaning as in formula I, is reduced . 3 · The method of claim 1 characterized gekennzeichne _$ t, that compounds of formula Ia 009829/1898 NH < ^CH 2> p (OH ₂ ) Yes in which ρ and q = 0 or 1 and ρ + q = 1, and their salts are prepared by making a compound of formula III -NH (CH ₂ ) _p (CH ₂ ) Y ' III in which formula ρ and q = 0 or 1 and ρ + q = 1 and either Y or Y ^{1 represents} a carbonyl group and the other symbol a methylene group, is reduced. k. Process according to Claim 1, characterized in that the tertiary amines of the formula I and their salts are prepared by alkylating the secondary amines. 5. The method according to claim 1, characterized in that that the tertiary amines of the formula I and their salts are prepared by reductive alkylation of the secondary amines will. 6. The method according to claim 1, characterized in that that the tertiary amines of the formula I and their salts by acylation and subsequent reduction of the secondary amines are produced. 0 09829/1898 Compounds of Formula I. in which η and m = 0, 1 or 2 and η + m = 1 or 2 and R represents hydrogen, methyl or ethyl, and their salts formed with pharmaceutically acceptable acids. 8. N-methyladamantane spiro-3'-piperidine and its Salts with pharmaceutically acceptable acids. 9 · Adamantane spiro-3'-piperidine and its salts with pharmaceutically acceptable acids. 10. Adamantane spiro-4'-hexahydroazepine and its Salts with pharmaceutically acceptable acids. 11. A method for producing antiviral preparations, characterized in that a compound of formula I or a salt thereof is contacted with a pharmaceutically acceptable acid in a form suitable for administration {. 12. The method according to claim 11, characterized in that a compound of formula I or a salt the same with a pharmaceutically acceptable acid dissolved in liquid or solid carrier materials or with mixed with these materials. 009829/1898 13 · Method according to claim 11 or 12, characterized characterized in that N-methyladamantane spiro-3 -'-piperidine or a salt thereof with a pharmaceutically acceptable one Acid is used as an active ingredient. 1 h. Method according to claim 11 or 12, characterized characterized that adamantane spiro-3'-piperidine or a Salt of the same with a pharmaceutically acceptable acid is used as an active ingredient. 15 · The method according to claim 11 or 12, characterized characterized that adamantane spiro-4'-hexahydroazepine or a salt thereof with a pharmaceutically acceptable acid is used as an active ingredient. 16. Antiviral preparations containing one Compound of formula I or a salt thereof with a pharmaceutically acceptable acid as active ingredient. 17 Antiviral preparations with a content of N- Methyladamantane spiro-3'-piperidine or a salt thereof with a pharmaceutically acceptable acid as the active ingredient. 18. Antiviral preparations containing Adamantane spiro-3'-piperidine or a salt thereof with a pharmaceutically acceptable acid as an active ingredient. 19 · Antiviral preparations containing Adamantane spiro-4'-hexahydroazepine or a salt thereof with a pharmaceutically acceptable acid as the active ingredient. 20. Methods of combating viral infections, characterized in that a compound of formula I or a salt thereof with a pharmaceutically acceptable Acid is administered, 009829/1898 Abstract; New adamantane compounds with relative to their antiviral effects have very few side effects. The substances can be produced by processes known per se will. 009829/1898