CA1150268A - Decaprenylamine derivatives - Google Patents

Abstract

ABSTRACT

New decaprenylamines having the general formula:

(I) wherein n represents an integer of 0 - 2, R1 represents a hydrogen atom, a lower alkyl group or a decaprenyl group, and R2 represents a phenyl group or a pyridyl 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, R2 and n 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:
(III') wherein R2 and n have the aforesaid meanings, to form a corresponding imino compound which in turn is reduced to obtain a decaprenylamine of the formula (I) in which R1 is hydrogen and R2 and n have the aforesaid meanings. When a pharmaceuti-cally acceptable acid addition salt is desired, the decaprenyl-amine 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 controll-ing virus infection of vertebrate animals.

Description

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This invention relates to new pharmaceutically active decaprenylamines, their pharmaceutically acceptable acid addition salts as well as to a process for their prepa-ration. The new compounds with which the invention is concerned are useful for controlling virus infection of vertebrate animals.
There are known heretofore various substances, which have been decided to have preventive or alleviative effects on diseases caused by virus whose host is a vertebrate animal, or which have been recognized to be capable of alle-viating symptoms of the diseases by significantly enhancing antibody activity in the animal. Antivirotics reported so far include interferon, substances capable of inducing inter-feron, i.e. inducers tinterferon inducers), amantadine hydro-chloride or synthetic substances, such as methysazone, whichdirectly exert inhibitory effect on the virus propagation.
Interferon is glycoprotein having antiviral and antitumor activity, said glycoprotein being produced in situ by cells of a vertebrate animal when the cells are infected with virus, and has been suggested for the therapy of infectious viral disease and also for the therapy of cancer. Known inducers, which induce interferon in vertebrate animals by a process other than the virus infection, include natural high molecular substances such as double chain ribonucleic acid of bacterio-phage of a certain species, or synthetic high molecularsubstances such as double chain ribonucleic 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-of, and in fact no economical process for the production there-of has not been established yet. On the other hand, conven-tional interferon inducers have not been put to practical use mainly because 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 finding 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 pharma-ceutically acceptable acid addition salts thereof showexcellent interferon inducing ability and, at the same time, demonstrate excellent antiviral activity even in the biological !
test.
According to one aspect of the present inven-tion, there is thus provided a new class of decaprenylamine derivatives represented by the following general formula:
CH3 Rl H ( CH2-C=CH-CH2 )10 N ( CH2 )n 2 wherein n represents an integer of O - 2, Rl represents a hydrogen atom, a lower alkyl group or a decaprenyl group, and R2 represents a phenyl group or a pyridyl group, and the pharmaceutically acceptable acid addition salts thereof.
The decaprenylamines having the general formula (I) and their pharmaceutically acceptable acid addition salts may be prepared in accordance with known procedures for amine synthesis, starting from ~ecaprenol represented by the formula:

ICH3 (II) H~ CH2-C=CH-CH2 ~10 OH
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:
ICH3 (II) H ( CH2-C=CH-CH2 )10 OH
into a corresponding halide or sulfonic acid ester which is thereafter reacted with a primary or secondary amino compound having the general formula:
Rl ¦ (III) H-N ( CH2 )n R2 wherein Rl, R2 and n 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 ( CH2 )n R2 (III') wherein R2 and n have the aforesaid meanings, to form a corresponding imino compound which in turn is reduced to obtain a decaprenylamine of the formula (I) in which Rl is hydrogen and R2 and n have the aforesaid 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.

~Z68 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 pharmaceutically acceptable acid addition salts are illustrated hereinbelow with reference to preparative examples.
PreParative ExamPle 1 N-benzyl-didecaprenylamine hydrochloride fH3 ~ CH2 ~
H ( CH2-C=CH-CH2 310 N lCH3 .HCl ( CH2cH=c-cH2tlo To a solution of benzylamine (10 g.) in ethanol (100 ml) a solution of decaprenyl bromide (20 g.) in benzene (40 ml) was added dropwise at room temperature for 1 hour with stirring, which was continued for further 2 hours, Thereafter, the resulted mixture was heated at reflux for 2 hours with stirring. The resulting reaction mixture after cooling was added with a 2N sodium hydroxide aqueous solution (100 ml) and then extracted with isopropylether. The liquid extract ob~ained was washed with water and saturated saline, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue (21,4 g.) was purified by column chromatography using silica gel (200 g.). Elution was carried out with a mixture of isopropylether and benzene. The initial-ly eluted fraction (7.0 g.) was dissolved in ethyl acetate, added with ether containing HCl to weakly acidic and then cooled. The crystallized mass was separated by filtratiGn to recover N-benzyl-didecaprenylamine hydrochloride (4.9 g.), ~J!

~5~268 m.p. 52-54C. Elementary analysis as C107H169N~HC1 showed the following:

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Calcd. : 85.3411.38 0~93 Found : 85.0811.23 0.94 Preparative Example 2 N-benzyl~decaprenylamine hydrochloride I~I3 / H
H-~ CH2-C=CH CH2 )10 N \ . HCl ~ he lastly eluted fraction (7.3 g.) obtained in Preparative ~xample 1 was diæsolved in acetone and then added with ether containing HClo ~he mixture was worked up in the same manner as in ~xample 1? thereby to obtain N-benzyl-decaprenylamine hydrochloride (5.8 g.), m.p. 105 - 107C. ~lementary analysis as C57H89~HCl showed the following-Calcd. : 83.00 11.00 1.70 ~ound : 82.82 10.87 1.65 Preparative Examples 3 to 9 ~ he same procedures as in ~xample 1 were carriedou-t for the reaction of decaprenyl bromide with a primary or secondary amino compound thereby to produce the below indicated compounds 9 the structural formula 9 molecular formula9 melting point and elementary analysis of which also are listed in ~able 1.

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~15~3Z68 Preparative ~xamples 10 to 13 ~ o a solution of 3-aminomethylpyridine (25 g.) in ethanol (100 ml) a solution of decaprenyl bromide (30 g.) in chloroform was added dropwise at room temperature for 1 hour with stirring, which was continued for ~urther 3 hoursO ~he resulting reaction mixture after cooling was added with a 2~ sodium hydroxide aqueous solution (1Q0 ml) and extracted with isopropyletherO ~he liquid extract obtained was washed with water and saturated saline9 dried over anhydrous sodium sulfate and then concentrated under reduced pressure. ~he residue (21 gO) was purified by column chromatography using silica gel (200 g.). Elution was carried out with a mixture of 20~ ethylacetate 80%
hexane. 3-~idecaprenylaminomethylpyridine (Ca. 1.38 g.) was obtained as an oily substanceD
The above-said column was further eluted with a mixture of 20~ ethanol ! 80% ethylacetateO The fraction ~ 8.6 g. ) was recrystallized ~rom acetone to recover crystalline 3-decaprenylaminomethylpyridine (7.8 gO)~
~ollowing the substantially same procedures as mentioned above 9 2-(2-decapxenylamino)-ethylpyridine,

2-(2-didecaprenylamino)-ethylpyridine and 3-(N-decaprenyl-N-methylamino)-methylpyridine were obtainedO
~he physicochemical properties of these compounds are indicated in ~able 2.

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- _ g ~5~Z6~3 Preparative Example 14 ~ o a solution of N9~-dimethylbenzylamine (10 g.) in ethanol (100 ml) 9 decaprenyl bromide (20 gO ) was added dropwise at room temperature for 30 minutes. Stirring is continued for 1.5 hours at room temperatureO ~he resulting reaction mixture is extracted with isopropylether, and the extracted phase was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressureO ~he residue (2200 gO ) obtained was purified by column chromatography on a silica gelO ~hen9 through the column the mixtures of ethylacetate/chloroform with a concentration gradient of 1 to 10~o ethylacetate. ~he eluted fraction (180~ g.) was dissolved in acetone and the resulting solution was allowed to stand overnight in a refrigerator to recover crystalline N-benzyl-decaprenylammonium bromide (15.8 g.) m.p~ 51.2 - 53.1C~
Physiological effects of the compouns of the present invention are illustrated below in detailO
(1) Interferon inducing activity test ~ach test compound suspended in water with a surfactant was intraperitoneally administered to each group consisting of 5ICR female mice weighing about 25 g. Twenty hours after administration, blood was collected from the mice and serum was separated therefrom to obtain a serum interferon. ~he following steps were taken in order to determine potency of the serum interferon thus induced.
~-929 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.

~0 in an incubator placed in carbon dioxide atmosphere and - 10 _ ~ ~5~Z6~

the dilute test serum solution was removed therefrom.
~hereafter 9 the cells were inocula-ted with vesicular stomatitis virus and placed on a tissue culture medium containing 1% agar. After incubation a-t 37C. for 2~
hours 9 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 administered. The plaque inhibition rate of each test compound is shown in ~able 3.
(2) ~ffect on mice infected with vaccinia virus Groups 9 each consisting of 10 ICR female mice 9 were intravenously injected vaccinia virus (DI~ strain) from the vein of tail. On the 8th day after the inoculation9 the number of lesions in form of small pocks on the tail surface was counted after dyeing the tail with ethanol solution containing 1% fluorescein and 0.5~ methylene blue. In thi~ test9 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 compound had been administered.
~he rate of tail lesion inhibition of each test compound is shown in ~able 3.

(3) ~ffect on mice infected with influen~a virus Groups 9 each consisting of 10 IC~ female mice weighing about 25 g. were challenged b~ inhalation of neblyzed influenza virus A/PR-8. A solution of each test ~ ~5g~X~8 compound in an aqueous solution containing a surfactant was intraperitoneally administered to the mice 24 hours and 3 hours before the virus infection9 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 survivors9 and survival rate was obtained according to the following equationO

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(4) ~oxicity In order to investigate acute toxicity of the compounds of the present invention 9 50~ lethal dose of each compound was obtained by using ddY male mice weighing 20 - 25 g. ~rom the results shown in ~able 4, it is understood that the compounds had high safety margin by intraperitoneal administrationO

~able 50% ~ethal dose ~
Intravelously Intraperitoneally ~est comE~ administered administered N-methyl-N-phenyl- 180 ~500 decaprenylamine N-benzyl-decaprenylamine 220 315 hydrochloride N-methyl N-benzyl-decaprenylamine 377 ~500 hydrochloride N-phenethyl_ decaprenylamine 110 ~500 hydrochloride 3-decaprenylamino- _ >500 methylpyridine 2-(2-decaprenylamino)-_ >500 ethylpyridine As is clear from the foregoing test resultsg 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 9 there is considered also a possibility that ~.~5~268 the antivirus activities of said ingredients at biological level are concerned not only in interferon but also in other defensive mechanism of host. ~ccordingl y9 when -Ghe active ingredients of -the present invention are used for treatment of virus infected diseases9 they are administered to patients by such techniques involving oral9 inhalant, or the like administration as well as subcutaneous 9 intramascular and intravenous injectionO According to the condition of patient such as age9 symptom and route by which the ingredient is administered9 the active ingredient of the present invention is used in a dose of 0O5 - 20 mg/kg, preferably 3 - 5 mg/kg several times (2 - ~ times) per day.
~he active ingredients of the present invention can be formulated into compositions for medication9 for example, tablets9 capusules9 granules 9 powder9 liquid preparation for oral use 9 eye lotions9 suppositories9 ointments9 injections and the like D
When the present active ingredients are orally administered9 they may be formulated into tablets 9 capsules, granules or powder. These solid preparations for oral use may contain commonly used excipients 9 for example9 silicic anhydride9 metasilicic acid9 magnesium alginate, synthetic aluminum silicate9 lactose9 cane sugar 9 corn starch9 microcrystalline cellulose9 hydroxypropylated starch or glycine 9 and the like 9 binders9 for example9 gum arabic9 gelatin9 tragacanth9 hydroxyp-ropyl cellulose or polyvinylpyrrolidone~ lubricants, for example9 magnesium stearate9 talc or silica9 disintegrating agents9 for example, potato starch and carboxymethyl cellulose 9 or ~15~Z~8 wetting agents, for example 9 polyethylene glycol9 sorbitan monooleate9 hydrogenated castor oil 9 sodium laurylsulfate.
In preparing soft capsules 9 in particular 9 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 ~ 9 or the like. ~ablet 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 alternatively in the form of dry product which can be re~dissolved before use by means of a suitable vehicle. ~o these liquid preparations, there may be added commonly used additives9 for example9 emulsifying aids such as sorbitol syrup9 methyl cellulose9 gelatin9 hydroxyethyl cellulose and the like9 or emulsifiers9 for example9 lecithin9 sorbitan monooleate9 hydrogenated castor oil9 non-aqueous vehicles9 for example 9 fractionated coconut oil9 almond oil9 peanut oil and the like 9 or antiseptics9 for example9 methyl p-hydroxybenzoate9 propyl p-hydroxybenzoate or sorbic acid. ~urther9 these preparations for oxal use may contain9 if necessary9 preservatives 9 stabilizers and the like additives.
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 ~ 9 or may be used in the form of rectum capsule obtained by wrapping a mixture of polyethylene glycol9 seame oil, germ oil9 fractionated coconut oil and the like in a gelatin sheet, The rec-tum capsule may be coated9 if necessary9 with waxy materials.
When 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 administration9 the above-mentioned compositions can contain the present active ingredients in an amount of at least 1%9 preferably

5 to 50%.
The procedure of formulating the present active ingredients into various preparations is illustrated below with reference to Pharmaceutical ExamplesO

5 Pharmaceutical Example 1 Hard capsule preparations for oral use A mixture of 25 g. of N-benzyl decaprenylamine hydrochloride and 7.5 g. of polyoxyethylene castor oil in acetone was mixed with 25 g. of silicic anhydride~
After evaporation of the acetone 9 the mixture was mixed further with 5 g. of calcium carboxymethylcellulose9 5 g.
of corn starch9 7.5 g. of hydroxypropylcellulose and 20 g.
of microcrystalline cellulose 9 and 30 ml of water was added thereto and kneaded to give a gra~ular mass. The mass was pelletized by means of a pelletizer (ECK pelletter of Fuji Paudal Co. 9 Japan) eauipped with No. 24 mesh (B.S~) screen to obtain granules. The granules were dried to less than 5~0 moisture content and screened with NoO 16 mesh (~OS.) screen. The screened granules were capsuled by means of a capsule filling machine so as to be con-tained in an 6l~3 amount of 190 mg per capsuleO

Pharmaceutical Example 2 Soft capsule preparations for oral use A homogeneous solution was prepa-red by mixing 50 g. of N-methyl-N-benzyl-decaprenylamine hydrochloride with 130 g. of polyethylene glycol (Macrogol 400).
Separately9 a gelatin solution was prepared which contained 93 g. of gelatin9 19 g. of glycerineg 10 g. of D-sorbitol9 0.4 g. of ethyl p-hydroxybenzoate, 0.2 g. of propyl p-hydroxybenzoate and 0.4 g. of titanium oxide and which was used as a capsule film forming agent. ~he previously obtained solutiony together with the capsule film forming agent9 was treated with a manual type flat punching machine to obtaine capsules each having the contents of 180 mg.
Pharmaceutical Example 3 Injections A mixture of 5 g. of N-methyl-N-phenyl-decaprenylamine hydrochloride9 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. ~he 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~phenethyl-decaprenylamine hydrochloride9 5.0 g. of ~ikkol HC0 60 (a tradename) (hydro-genated castor oil polyoxyethylene-60 mols-ether), 20 g.
of propylene glycol9 10 gO of glycerol and 5.0 g. of ethyl alcohol was mixed with 100 ml of distilled water and stirred. Under asepsis operation9 the solution was portionwise poured in an amount of 1.4 ml into an ampule which was then sealedO

Claims (25)

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 decaprenylamines having the general formula:

(I) wherein n represents an integer of 0 - 2, R1 represents a hydrogen atom, a lower alkyl group or a decaprenyl group, and R2 represents a phenyl group or a pyridyl 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, R2 and n 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:

(III') wherein R2 and n have the aforesaid meanings, to form a corresponding imino compound which in turn is reduced to obtain a decaprenylamine of the formula (I) in which R1 is hydrogen and R2 and n have the aforesaid 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.

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 decaprenyl-amine of the formula (I) which, when a pharmaceutically accept-able 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 and n have the aforesaid meanings, whereby to obtain a decaprenylamine of the formula (I) in which R1 is hydrogen and R2 and n have the aforesaid meanings, which when a pharmaceutically acceptable acid addition salt is desired, is further reacted with a pharmaceutically accept-able acid to provide the desired salt.

4.- A process according to claim 1, wherein decaprenol 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 decaprenylamine of the formula (I) in which R1 is hydrogen and R2 and n have 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 2, for the preparation of N-benzyl-decaprenylamine, wherein use is made of benzylamine as said amino compound of formula (III), where-by to obtain a product mixture comprising N-benzyl-decaprenyl-amine and N-benzyl-didecaprenylamine, from which N-benzyl-decaprenylamine is thereafter isolated.

7.- A process according to claim 6, wherein the N-benzyl-decaprenylamine thus obtained is reacted with hydrochloric acid to obtain the corresponding hydrochloride salt.

8.- A process according to claim 4, for the preparation of N-benzyl-decaprenylamine, wherein use is made of benzylamine as said amino compound of formula (III').

9.- A process according to claim 8, wherein the N-benzyl-decaprenylamine thus obtained is reacted with hydrochloric acid to obtain the corresponding hydrochloride salt.

10.- A process according to claim 2, for the preparation of N-benzyl-didecaprenylamine, wherein use is made of benzylamine as said amino compound of formula (III), where-by to obtain a product mixture comprising N-benzyl-decaprenyl-amine and N-benzyl-didecaprenylamine, from which N-benzyl-didecaprenylamine is thereafter isolated.

11.- A process according to claim 10, wherein the N-benzyl-didecaprenylamine thus obtained is reacted with hydrochloric acid to obtain the corresponding hydrochloride salt.

12.- A process according to claim 2, for the preparation of 3-decaprenylaminomethylpyridine, wherein use is made of 3-aminomethylpyridine as said amino compound of the formula (III), whereby to obtain a product mixture comprising 3-decaprenylaminomethylpyridine and 3-didecaprenylaminomethyl-pyridine, from which 3-decaprenylaminopyridine is thereafter isolated.

13.- A process according to claim 4, for the preparation of 3-decaprenylaminomethylpyridine, wherein use is made of 3-aminomethylpyridine as said amino compound of formula (III').

14.- A process according to claim 2, for the preparation of 2-decaprenylaminomethylpyridine, wherein use is made of 2-aminomethylpyridine as said amino compound of formula (III), whereby to obtain a product mixture comprising 2-decaprenylaminomethylpyridine and 2-didecaprenylaminomethyl-pyridine, from which 2-decaprenylaminopyridine is thereafter isolated.

15.- A process according to claim 4, for the preparation of 2-decaprenylaminomethylpyridine, wherein use is made of 2-aminomethylpyridine as said amino compound of formula (III').

16.- The decaprenylamines having the general formula:

(I) wherein n represents an integer of 0 - 2, R1 represents a hydrogen atom, a lower alkyl group or a decaprenyl group, and R2 represents a phenyl group or a pyridyl group, and the phar-maceutically acceptable acid addition salts thereof, whenever prepared by a process according to claim 1, or its obvious chemical equivalents.

17.- The decaprenylamines of the formula (I) as defined in claim 16, wherein R1, R2 and n 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.

18.- The decaprenylamines of the formula (I) as defined in claim 16, wherein R1 is hydrogen and R2 and n have the aforesaid meanings, and their pharmaceutically acceptable acid addition salts, whenever prepared by a process according to claim 3 or its obvious chemical equivalents.

19.- The decaprenylamines of the formula (I) as defined in claim 16, wherein R1 is hydrogen and R2 and n have 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 equiva-lents.

20.- N-Benzyl-decaprenylamine whenever prepared by a process according to claims 6 or 8, or their obvious chemical equivalents.

21.- N-Benzyl-decaprenylamine hydrochloride whenever prepared by a process according to claims 7 or 9, or their obvious chemical equivalents.

22.- N-Benzyl-didecaprenylamine whenever prepared by a process according to claim 10, or its obvious chemical equivalents.

23.- N-Benzyl-didecaprenylamine hydrochloride whenever prepared by a process according to claim 11, or its obvious chemical equivalents.

24.- 3- Decaprenylaminomethylpyridine whenever prepared by a process according to claims 12 or 13, or their obvious chemical equivalents, .

25.- 2-Decaprenylaminomethylpyridine whenever prepared by a process according to claims 14 or 15, or their obvious chemical equivalents.