CA1155459A - Decaprenylamine derivatives - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
New decaprenylamines having the general formula:

(I) wherein R1 represents a hydrogen atom, a decaprenyl group, a lower alkyl group or a hydroxy-lower alkyl group, and R2 represents a lower alkyl or alkenyl group optionally sub-stituted with at least one hydroxy, amino or alkylamino group, or a cycloalkyl group, and the pharmaceutically acceptable acid addition salts thereof, are prepared by (a) converting decaprenol of the formula:

(II) into a corresponding halide or sulfonic acid ester which is thereafter reacted with a primary or secondary amino compound having the general formula:

(III) wherein R1 and R2 have the aforesaid meanings, in the pre-sence or absence of a base, to obtain the desired decaprenyl-amine of the formula (I), or (b) oxidizing decaprenol to a corresponding aldehyde which is then condensed with a primary amino compound having the general formula:
H2N - R2 (III') wherein R2 has the aforesaid meanings, to form a correspond-ing imino compound which in turn is reduced to obtain a decaprenylamine of the formula (I) in which R1 is hydrogen and R2 has the aforesaid meanings. When a pharmaceutically acceptable acid addition salt is desired, the decaprenylamine of the formula (I) thus obtained is further reacted with a pharmaceutically acceptable acid to provide the desired salt.

The decaprenylamines of the formula (I) are useful for controlling virus infection of vertebrate animals.

Description

~ ~L55459 This invention relates to new pharmaceutieally aetive decaprenylamines, their pharmaeeutically aeceptable aeid addition salts as weil as to a process for their preparation. The new compounds with which the invention is eoncerned are useful for controlling virus infection of vertebrate animals.
There are known heretofore various substances whieh have been found to have preventive or alleviative effects on diseases caused by virus whose host is a verte-brate animal, or whieh have been recognized as being capableof alleviating symptoms of the diseases by significantly enhancing antibody activity in the animal. Antivirotics reported so far include interferon, substances capable of inducing interferon, i.e. inducers (interferon inducers), amantadine hydrochloride or synthetic substances, such as methysazone, which directly exert inhibitory effect on the virus propagation. Interferon is a glycoprotein having anti-viral and antitumor activity, which is produced in situ by cells of a vertebrate animal when the cells are infected with virus, it has been suggested for the therapy o~ infectious viral disease and also for the therapy of cancer. Known indueers, whieh induce interferon in vertebrate animals by a process other than the virus infection, include natural high molecular substances such as double chain ribonueleic acid of bacteriophage of a certain species, or synthetie high molecular substances such as double chain ribonucleie acid, typical of which is polyinosinic acid-polycytidylic acid, or low molecular inducers such as tyrolone.
In the production of interferon, however, there is involved a problem how to carry out the purification there-11554~g ' ' of, and in fact no economical process for the productionthereof has not been established yet. On the other hand,con-ventional interferon inducers have not been put to practical use mainly ~ecause of toxicity thereof. Synthetic antiviral agents which directly exert inhibitory effect on the virus propagation, which are commercially available at present, have a rather narrow range of virus-infected diseases which are curable by administration of said agent, and thus the advent of novel synthetic antiviral agents is earnestly desired Taking such circumstances into consideration, the present inventors extensively conducted studies in find-ing compounds capable of producing interferon of high potency and, moreover, having antiviral activity on the biological level, and as the result they have eventually found that compounds represented by the following general formula (I) and pharmaceutically acceptable acid addition salts thereof show excellent interferon inducing ability and, at the same time, demonstrate excellent antiviral activity even in the biological test.
According to one aspect of the present invention, there is thus provided a new class of decaprenylamine derivatives represented by the following general formula:

IH3 ~ / Rl H ( CH2-C=cH-cH2 )10 \ (I) wherein Rl represents a hydrogen atom, a decaprenyl group, a lower alkyl group or a hydroxy-lower alkyl group, and R2 represents a lower alkyl or alkenyl group optionally sub-stituted with at least one hydroxy, amino or alkylamino group, or a cycloalkyl group, and the pharmaceutically acceptable acid addi`tion salts thereof.

,~
~ -2-1 155~9 Suitable lower alkyl groups which Rl may represent include straight or branched chain alkyls with up to 4 carbon atoms. The same can apply to the lower alkyl portion of a ~ydroxy-lower alkyl group which ~1 may also represent.
Further, suitable lower alkyl or alkenyl groups which R2 may represent also have up to 4 carbon atoms. These group may be further mono- or poly-substituted with hydroxy,amino or tmono- or di-) alkylamino. The substitution with any com-bination of these also is possible as is apparent to those skilled in the art.
The dccaprenylamines having the general formula (I3 and their pharmaceutically acceptable acid addition salts may be prepared in accordance with known procedures for amine synthesis, starting from decaprenol represented by the formula:

fH3 H ( CH2-C=CH-CH2 )10 OH (II) According to a further aspect of the invention, there is thus provided a process for the preparation of the decaprenylamines having the general formula (I), which com-prises:
a) converting decaprenol of the formula:

H--~- CH2-C=CH-CH2 )10 OH (II) into a corresponding halide or sulfonic acid ester which is thereafter reacted with a primary or secondary amino compound having the general formula: ~ 1 HN (III) \R2 30 wherein Rl and R2 have the aforesaid meanings, in the pre-sence or absence of a base, to obtain the desired decaprenyl-5 ~ 5 9 amine of the formula (I), or b) oxidizing decaprenol to a corresponding aldehyde which is then condensed with a primary amino compound having the general formula:
H2N - R2 (III') wherein R2 has the aforesaid meanings, to form a correspond-ing imino compound which in turn is reduced to obtain a decaprenylamine of the formula ~I) in which Rl is hydrogen and R2 has the a~oresaid meanings, and c) when a pharmaceutically acceptable acid addition salt is desired, further reacting the decaprenylamine of the formula (I) thus obtained with a pharmaceutically acceptable acid to provide the desired salt.
The reduction in step (b) can be effected using sodium borohydride as reducing agent.
The pharmaceutically acceptable acid addition salts can be isolated by crystallizing the salt out of the solution by evaporation or by other means to recover the same. The acid addition salts suitable for use as medicines include, for example, those formed with hydrochloric acid, acetic acid, citric acid, fumaric acid and the like.
The compounds of the general formula (I) and their j pharmaceutically acceptable acid addition salts are illustrated hereinbelow with reference to preparative examples, Preparative Example 1 N-methyl-didecaprenylamine hydrochloride ICH3 ,,,CH3 CH3 H--t- CH2-C=CH-CH2 ~ N \ ¦ ~HCl ~CH2CH=C-CH2 31oH

To a mixture of a methanol solution (25 g.) of 40% methylamine with benzene (400 ml) a solution of decaprenyl ~ 155~S~

bromide (33 g.~ in benzene (100 ml) was added dropwise at room temperature for 1 hour with stirring, which was continued for further 16 hours. The resulting reaction mixture was washed successively with 2N NaOH (100 ml~ water and saturated saline, dried over anhydrous soaium sulfate and then concen-tràted under reduced pressure_ The residue (28 g.) was puriied by column chromatography using silica gel (280 g.).
Elution was carried out with benzene-ethyl acetate-methanol.
The initially--eluted 1 ~554~9 fraction (705 go ) was dissolved in ethyl acetate9 added with ether containing HCl to weakly acidic and then cooledO
~he crystallized mass was separated by filtration to recover N-methyl~-didecaprenylamine hydrochloride (305 go )9 5 mOpo 69 ~ 72Co Elementary analysis as C101H165NoHCloE20 showed the following:
C% H? ~/
CalcdO o 83~ 78 11 o 70Oo 97 Found o 830 90 11 A 911o08 Preparative l~xample 2 ~-methyl~decaprenylamine hydrochloride ICH3 H-~-CH2`-C=CH-CH2 ~ ~T \ O HCl The lastly eluted fraction (1301 go ) obtained in Preparative ~xample 1 was dissolved in acetone and then added with e-ther containing HClo ~he mixture was worked up in the same manner as in Example 1 9 thereby to obtain ~-methyl-decaprenylamine hydrochloride (6.5 g. )9 mOpo 68 ~ 70Co ~lementary analysis as C51H85N-HCl-3,~2H20 showed the followingO
C~o H~o ~_ CalcdO o78~ 96 11.561081 ~ound o780 60 1lo 381 o 68 Preparative ~xamples 3 to 13 ~ he same procedures as in Example 1 were carried out for the reaction of decaprenyl bromide with a primary 1 ~5~59 or secondary amino compound thereby to produce the below-: indicated compounds 7 the structural formula9 molecular formula9 melting point and elementary analysis o~ which also ar~ listed in ~able 10 . .

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~ 155459 Physiological effects of the compounds of the present invention are illustrated below in detail.
(1) Interferon inducing activity test ~ ach test compound suspended in water with a surfactant was intraperitoneally administered to each group consisting of 5 ICR female mice weighing about 25 g.
~wenty hours after administration9 blood was collected from the mice and serum was separa-ted therefrom to obtain a serum interferonO ~he following steps were taken in order to determine potency of the serum interferon thus induced~ ~-g29 cells derived from mice and incubated previously in a monolayer was brought into contact with the test serum solution diluted 10 times9 incubated overnight at 37C in an incubator placed in carbon dioxide atmosphere and the dilute tes-t serum solution was removed therefrom~ ~`hereafter9 the cells were inoculated with vesicular stomatitis virus and placed on a tissue culture medium containing 1~o agar. After incubation at 37C for 24 hours, the cells were dyed with neutral red solution diluted to an appropriate concentration to count the number of plaques formed thereon and thereby to calculate the .
plaque inhibition rate in each of the test groups against a group to which no test compound had been administeredO :~
~he plaque inhibition ra-te of each -test compound is shown in Table 2.

(2) ~ffect on mice infected with vaccinia virus Groups9 each consisting of 10 ICR female mice9 were intravenously injected vaccinia virus (DIE strain) ~rom the vein of tail~ On the 8th day after the inocula-tion9 the number of lesions in form of small pocks on - lO

the tail surface was counted after dyeing the tail with an ethanol solution containing 1~o fluorescein and 0.5 methylene blue. In this test 9 each test compound was administered intraperitoneally to the mice on the day just before inoculation of the virus 9 whereby antivirus activity of the test compound was evaluated in terms of inhibition of tail lesions as calculated in each test group against a group to which no test compbund had been administered.
~he rate of tail lesion inhibition of each test compound is shown in ~able 2.

(3) ~ffect on mice infected with influenza virus Groups, each consisting of 10 ICR female mice weighing about 25 g. were challenged by intrala-tion of neblyzed influenza virus A/PR-8. A solution of each test t5 compound in an aqueous solution containing a surfactant was intraperitoneally administered to the mice 24 hours and 3 hours before the virus infection~ and 5 times every other day from the second day after the infection. ~he mice that survived 21 days after the challenge were regarded as survivors 9 and survival rate was obtained according to the following equation.

Number of survivors - x 100 = sur~ival rate Number of mice treated 1 155~59 o o .,, ~
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(4) Toxicity In order to investigate acute toxicity of the compounds of the present invention, 50% le-thal dose of each compound was obtained by using ddY male mice weighing 20 - 25 g. From the results shown in Table 3, it is understood that the compounds had high safety margin by intraperitoneal administration.
Table 3 50% Lethal dose (mq/kq) Intravenously Intraperitoneally Test Compound administered adminlstered N-allyl-decaprenylamine 10.0> 500 hydrochloride ~-(2-diethylamino-ethyl)-decaprenylamine 30.6 > 500 hydrochloride ~-cyclohexyl-decaprenylamine 21.0 230 hydrochloride N-cyclohexyl-N-methyl- 82.0> 500 decaprenylamine hydrochloride As is clear from the foregoing test results, the active ingredients of the present invention have interferon inducing activity in vivo and are low in toxicity with showing excellent antiviral activity. In the light of the fact that the strict correlation of interferon activity with the individual antivirus activities is not always observed for the present ingredients, there is considered also a possibility

5 ~

that the antivirus activities of said ingredients at biological level are concerned not only in inter~eron but also in other defensive mechanism o~ hostO
Accordingly9 when the active ingredients of the presen-t invention are used for treatment of ~irus-infected diseases 9 they are administered to patients by such techniques in~olving oral 9 inhalan-t9 or the like administration as well as subcutaneous9 intramascular and intravenous injection. According to the condition of patient such as age9 symptom and route by which the ingredient is administered 9 the active ingredient o~
the present invention is used in a dose o~ 0~5 - 20 mg/kg, preferably 3 ~ 5 mg/kg se~eral times (~ - 4 ti~es) per da~.
The active ingredients of the present invention can be ~ormulated into compositions for medication9 for example 9 tablets9 capsules9 granules9 powder9 liquid preparation for oral use9 eye lotions9 suppositories, ointments, injections and the like~
When the present active ingredients are orally administered, they may be formulated into tablets, capsules, granules or powderO These solid preparations for oral use may contain commonly used excipients9 ~or example, silicic anhydride, metasilicic acid9 magnesium alginate, synthetic aluminum silicate9 lactose9 cane sugar9 corn starch9 microcrystalline cellulose9 hydroxy-propylated starch or glycine9 and the like9 binders 9 ~or example, gum arabic9 gelatin9 tragacanth~ hydroxypropyl cellulose or polyvinylpyrrolidone9 lubricants 9 ~or example 9 magnesium stearate9 talc or silica9 disintegrating agents, ~ 14 -~ ~55~59 ~or exampleg potato starch and carboxymethyl cellulose9 or wetting agents9 for exampleg polyethylene glycol9 sorbitan monooleate 9 hydrogenated castor oil9 sodium laurylsulfate. In preparing soft capsules9 in particular9 the present active ingredients may be formulated by dissolving or suspending them in commonly used oily substrates such as sesame oil9 peanut oil9 germ oil9 fractionated coconut oil such as Miglyol ~ y or the like.
lablet or granule preparations may be coated according to the usual method.
~ iquid preparation for oral use may be in the form of aqueous or oily emulsion or syrup9 or alter-natively in the form of dry product which can be re-dissolved before use by means of a suitable vehicle.
~o these liquid preparations9 there may be added commonly used additives, for example9 emulsifying aids such as sorbitol syrup, methyl cellulose9 gelatin9 hydroxyethyl cellulose and the like9 or emulsifiers 9 for example9 lecithin, sorbitan monooleate9 hydrogenated castor oil, non-aqueous vehicles9 for example9 fractionated coconut oil9 almond oil9 peanut oil and the like9 or antiseptics9 ~or example, methyl p-hydroxybenzoate9 propyl p-hydroxy-benzoate or sorbic acidO ~urther9 these preparations for oral use may contain9 if necessary9 preservatives9 stabilizers and the like addi-tivesO
In case where the present active ingredients are administered in the form of non-oral suppository9 they may be formulated according to the ordinary method using oleophilic substrates such as cacao oil or Witepsol ~ , or may be used in -the ~orm of rectum capsule 11~5~59 obtained by wrapping a mixture of polyethylene glycol9 sesame oil, germ oil9 fractionated coconut oil and the like in a gelatin sheet~ ~he rectum capsule may be coated9 if necessary7 with waxy materialsO
l~hen the present active ingredients are used in the form of injection9 they may be formulated into preparations of oil solution9 emulsified solution or aqueous solution9 and these solutions may contain commonly used emulsifiers9 stabilizers or -the like additives.
According to the method of administration, the above-mentioned compositions can contain the present active ingredients in an amount of at least 1%9 preferably 5 to 50%.
~he procedure of formulating the present active ingredients into various preparations is illustra-ted below with reference to Pharmaceutical Examples.
Pharmaceutical Example 1 Hard capsule preparations for oral use A mixture of 25 g. of N-allyl decaprenylamine hydrochloride and 7.5 g. of polyoxyethylene castor oil in acetone was mixed with 25 g. of silicic anhydride.
After e~aporation of the acetone9 -the mixture was mixed further with 5 g. of calcium carboxymethylcellulose9 5 g.
of corn starchg 7O5 g. of hydroxypropylcellulose and 20 g~
of microcrystalline cellulose 9 and 30 ml of water was added whereto and kneaded to gi~e a granular massD ~he mass was pelletized by means of a pelletizer (ECX pelletter of F~lài Paudal ~o.9 Japan) equipped with No~ 2~ mesh (~OSo) screen to obtain granules. ~he granules were dried to less than 5~ moisture content and screened with No. 16 mesh (B.S.) screen. ~he screened granules were capsuled - 16 ~

1 1~5459 by means of a capsule filling machine so as to be contained in an amount of 190 mg per capsule.
Pharmaceutical Example 2 Soft capsule preparations for oral use A homogeneous solution was preparea by mixing 50 g. of N-(2-diethylaminoethyl)-decaprenylamine hydro-chloride with 130 gO of polyethylene glycol (Macrogol 400).
Separately, a gelatin solution was prepared which contained 93 g. of gelatin, 19 g. of glycerine, 10 g. of D-sorbitol, 0.4 g of ethyl p-hydroxybenzoate, 0.2 g. of propyl p-hydroxy-benzoate and 0.4 g. of titanium oxide and which was used as a capsule film forming agent. The previously obtained solution, together with the capsule film forming agent, was treated with a manual type flat punching machine to obtain capsules each having the contents of 180 mg.
Pharmaceutical Example 3 Injections A mixture of 5 g. of N-cyclohexyl-N-methyl-decaprenylamine hydrochloride, an appropriate amount of peanut oil and 1 g. of benzyl alcohol was made a total volume of 100 cc by addition of peanut oil. The solution was portionwise poured in an amount of 1 cc under asepsis operation into an ampule which was then sealed.
Pharmaceutical Example 4 Injections A mixture of 1.0 g. of N-cyclohexyl-decaprenylamine hydrochloride, 5.0 g. of Nikkol HCo-60 (a tradename) (hydrogenated castor oil polyoxyethylene-60 mols-ether), 20 g. of propylene glycol, 10 g. of glycerol and 5.0 g. of ethyl alcohol was mixed with 100 ml of distilled water and stirred. Under asepsis operation, the solution was portionwise poured in an amount of 1.4 ml into an ampule which was then sealed.

Claims (18)

The embodiments of the invention, in which an exclusive property or privilege is claimed, are defined as follows:-

1.- A process for the preparation of the deca-prenylamines having the general formula:

(I) wherein R1 represents a hydrogen atom, a decaprenyl group, a lower alkyl group or a hydroxy-lower alkyl group, and R2 represents a lower alkyl or alkenyl group optionally substituted with at least one hydroxy, amino or alkyl-amino group, or a cycloalkyl group,and the pharmaceutically acceptable acid addition salts thereof, which comprises:
a) converting decaprenol of the formula:

(II) into a corresponding halide or sulfonic acid ester which is thereafter reacted with a primary or secondary amino compound having the general formula:

(III) wherein R1 and R2 have the aforesaid meanings, in the presence or absence of a base, to obtain the desired deca-prenylamine of the formula (I); or b) oxidizing decaprenol to a corresponding aldehyde which is then condensed with a primary amino compound having the general formula:
H2N - R2 (III') wherein R2 has the aforesaid meanings, to form a corresponding imino compound which in turn is reduced to obtain a deca-prenylamine of the formula (I) in which R1 is hydrogen and R2 has the aforesaid meanings; and c) when a pharmaceutically acceptable acid addi-tion salt is desired, further reacting the decaprenylamine of the formula (I) thus obtained with a pharmaceutically acceptable acid to provide the desired salt.

2.- A process according to claim 1, wherein decaprenol of the formula (II) is converted into a correspond-ing halide or sulfonic acid ester which is thereafter reacted with a primary or secondary amino compound of the formula (III), in the presence or absence of a base, to obtain a decaprenylamine of the formula (I) which, when a pharma-ceutically acceptable acid addition salt is desired, is further reacted with a pharmaceutically acceptable acid to provide the desired salt.

3.- A process according to claim 2, wherein use is made of a primary amino compound of the formula (III) in which R1 is hydrogen and R2 has the aforesaid meanings, whereby to obtain a decaprenylamine of the formula (I) in which R1 is hydrogen and R2 has the aforesaid meanings, which, when a pharmaceutically acceptable acid addition salt is desired, is further reacted with a pharmaceutically acceptable acid to provide the desired salt.

4.- A process according to claim 1, wherein deca-prenol of the formula (II) is oxidized to a corresponding aldehyde which is then condensed with a primary amino compound of the formula (III') to form a corresponding imino compound which in turn is reduced to obtain a decaprenyl-amine of the formula (I) in which R1 is hydrogen and R2 has the aforesaid meanings, which, when a pharmaceutically acceptable acid addition salt is desired, is further reacted with a pharmaceutically acceptable acid to provide the desired salt.

5.- A process according to claim 4, wherein the reduction is effected using sodium borohydride as reducing agent.

6.- A process according to claim 3, wherein use is made of a primary amino compound of the formula (III) in which R1 is hydrogen and R2 is a lower alkenyl group.

7.- A process according to claim 4, wherein use is made of a primary amino compound of the formula (III') in which R2 is a lower alkenyl group.

8.- A process according to claim 6, for the preparation of N-allyl-decaprenylamine and the pharmaceutic-ally acceptable acid addition salts thereof, wherein use is made of allylamine as said amino compound of formula (III), whereby to obtain a product mixture comprising N-allyl-decaprenylamine and N-allyl-didecaprenylamine, from which N-allyl-decaprenylamine is thereafter isolated and, when desired, is further reacted with a pharmaceutically accept-able acid to obtain the corresponding acid addition salt.

9.- A process according to claim 7, for the preparation of N-allyl-decaprenylamine and the pharmaceutic-ally acceptable acid addition salts thereof wherein use is made of allylamine as said amino compound of formula (III').

10.- A process according to claim 3, wherein use is made of a primary amino compound of the formula (III) in which R1 is hydrogen and R2 is a cycloalkyl group.

11.- A process according to claim 4, wherein use is made of a primary amino compound of the formula (III') in which R2 is a cycloalkyl group.

12.- A process according to claim 10, for the preparation of N-cyclohexyl-decaprenylamine and the pharma-ceutically acceptable acid addition salts thereof, wherein use is made of cyclohexylamine as said amino compound of formula (III), whereby to obtain a product mixture compris-ing N-cyclohexyl-decaprenylamine and N-cyclohexyl-dideca-prenylamine, from which N-cyclohexyl-decaprenylamine is thereafter isolated and, when desired, is further reacted with a pharmaceutically acceptable acid to obtain the corresponding acid addition salt.

13.- A process according to claim 11, for the preparation of N-cyclohexyl-decaprenylamine and the pharma-ceutically acceptable acid addition salts thereof, wherein use is made of cyclohexylamine as said amino compound of formula (III').

14.- A process according to claim 3, wherein use is made of a primary amino compound of the formula (III) in which Rl is hydrogen and R2 is dialkylaminoalkyl or dialkyl-aminohydroxyalkyl group.

15.- A process according to claim 4, wherein use is made of a primary amino compound of the formula (III') in which R2 is a dialkylaminoalkyl or dialkylaminohydroxyalkyl group.

16.- A process according to claim 14, for the preparation of N-(2-diethylaminoethyl)-decaprenylamine and the pharmaceutically acceptable acid addition salts thereof, wherein use is made of 2-diethylaminoethylamine as said amino compound of the formula (III), whereby to obtain a product mixture comprising N-(2-diethylamino-ethyl)-decaprenylamine and N-(2-diethylaminoethyl)-di-decaprenylamine, from which N-(2-diethylaminoethyl)-decaprenylamine is thereafter isolated and, when desired, is further reacted with a pharmaceutically acceptable acid to obtain the corresponding acid addition salt.

17.- A process according to claim 15, for the preparation of N-(2-diethylaminoethyl)-decaprenylamine and the pharmaceutically acceptable acid addition salts thereof, wherein use is made of 2-diethylaminoethylamine as said amino compound of formula (III').

18.- A process according to claim 14, for the preparation of N-(3-diethylamino-2-hydroxypropyl)-decapre-nylamine and the pharmaceutically acceptable acid addition salts thereof, wherein use is made of 3-diethylamino-2-hydroxypropylamine as said amino compound of the formula (III), whereby to obtain a product mixture comprising N-(3-diethylamino-2-hydroxypropyl)-decaprenylamine and N-(3-diethylamino-2-hydroxypropyl)-didecaprenylamine, from which N-(3-diethylamino-2-hydroxypropyl)-decaprenyl-amine is thereafter isolated and, when desired, is further reacted with a pharmaceutically acceptable acid to obtain the corresponding acid addition salt.

19.- A process according to claim 15, for the preparation of N-(3-diethylamino-2-hydroxypropyl)-deca-prenylamine and the pharmaceutically acceptable acid addition salts thereof, wherein use is made of 3-diethylamino-2-hydroxypropylamine as said amino compound of formula (III').

20.- The decaprenylamines having the general formula:

(I) wherein R1 represents a hydrogen atom, a decaprenyl group, a lower alkyl group or a hydroxy-lower alkyl group, and R2 represents a lower alkyl or alkenyl group optionally substituted with at least one hydroxy, amino or alkylamino group, or a cycloalkyl group, and the pharmaceutically acceptable acid addition salts thereof whenever prepared by a process according to claim 1 or its obvious chemical equivalents.

21.- The decaprenylamines of the formula (I) as defined in claim 20, wherein R1 and R2 have the aforesaid meanings, and their pharmaceutically acceptable acid addition salts, whenever prepared by a process according to claim 2 or its obvious chemical equivalents.

22.- The decaprenylamines of the formula (I) as defined in claim 20, wherein Rl is hydrogen and R2 has the aforesaid meanings, and their pharmaceutically acceptable acid addition salts, whenever prepared by a process according to claim 3 or its obvious chemical equivalents.

23.- The decaprenylamines of the formula (I) as defined in claim 20, wherein Rl is hydrogen and R2 has the aforesaid meanings, and their pharmaceutically acceptable acid addition salts, whenever prepared by a process according to claims 4 or 5, or their obvious chemical equivalents.

24.- The decaprenylamines of the formula (I) as defined in claim 20, wherein Rl is hydrogen and R2 is a lower alkenyl group, and their pharmaceutically acceptable acid addition salts, whenever prepared by a process according to claims 6 or 7, or their obvious chemical equivalents.

25.- N-Allyl-decaprenylamine and the pharmaceutic-ally acceptable acid addition salts thereof, whenever prepared by a process according to claims 8 or 9,or their obvious chemical equivalents.

26.- The decaprenylamines of the formula (I) as defined in claim 20, wherein Rl is hydrogen and R2 is a cycloalkyl group, and their pharmaceutically acceptable acid addition salts, whenever prepared by a process according to claims 10 or 11, or their obvious chemical equivalents.

27.- N-Cyclohexyl-decaprenylamine and the pharma-ceutically acceptable acid addition salts thereof, whenever prepared by a process according to claims 12 or 13, or their obvious chemical equivalents.

28.- The decaprenylamines of the formula (I) as defined in claim 20, wherein R1 is hydrogen and R2 is dialkyl-aminoalkyl or dialkylaminohydroxyalkyl group, and theirpharmaceutically acceptable acid addition salts, whenever prepared by a process according to claims 14 or 15, or their obvious chemical equivalents.

29.- N-(2-Diethylaminoethyl)-decaprenylamine and the pharmaceutically acceptable acid addition salts there-of, whenever prepared by a process according to claims 16 or

17, or their obvious chemical equivalents.

30.- N-(3-Diethylamino-2-hydroxypropyl)-decaprenyl-amine and the pharmaceutically acceptable acid addition salts thereof, whenever prepared by a process according to claims

18 or l9, or their obvious chemical equivalents.