GB2108105A

GB2108105A - Polyisoprenylamine derivatives

Info

Publication number: GB2108105A
Application number: GB08214241A
Authority: GB
Inventors: Reiko Kubota; Teruhito Yamaguchi; Toshihiro Takahashi; Yoshiyuki Tahara; Yasuhiro Komatsu; Hiroyasu Koyama
Original assignee: Nisshin Seifun Group Inc
Current assignee: Nisshin Seifun Group Inc
Priority date: 1981-05-18
Filing date: 1982-05-17
Publication date: 1983-05-11
Also published as: FR2505823B1; DE3218757C2; DE3218757A1; GB2108105B; JPS57192341A; JPH0128737B2; FR2505823A1

Abstract

Compounds of formula <IMAGE> wherein n is 9 or 10, (Alkylene) is an alkylene chain of 2 or more carbon atoms, optionally substituted by hydroxy, and Y is NH2, diethanolamino or benzylamino which is optionally nucleically substituted, and their acid addition salts have interferon-inducing activity and hence anti-viral activity.

Description

trifluoroacetic anhydride (45 ml) while cooling with ice-water with stirring. After completion of the dropwise addition, the mixture was stirred at room temperature for 3 hours with cooling. After the completion of the reaction, the reaction liquid was filtered to remove insolubles therefrom and the filtrate was concentrated under reduced pressure. The thus obtained concentrate was charged with benzene (about 50 ml) and further concentrated under reduced pressure. The thus obtained concentrate (119.3 g) was chromatographed with a mixture of benzene-ethyl acetate over a column packed with silica gel (1000 g) to obtain 2-trifluoroacetoxy-N-solanesyl-N,N'-ditrifluoroacetyl- propylenediamine (51.3 g).The thus obtained 2-trifluoroacetoxy-N-solanesyl-N,N'-ditrifluoroacetylpropylenediamine (51.3 g) was charged with an ethanol solution (200 ml) of 10% potassium hydroxide and heated under reflux for 1 hour. The reaction liquid was charged with water (500 ml) and then extracted with ethyl acetate. The extract was washed with water and saturated saline, dried over anhydrous sodium sulfate and then concentrated under reduced pressure to obtain an oily 1-amino-3solanesylamino-2-propanol (45.8 9). The thus obtained oily product (45.8 g) was dissolved in acetone (200 ml), charged with a hydrogen chloride-ether solution to weakly acidic and then allowed at room temperature overnight. The crystallized mass was separated by filtration and then dried to obtain 1amino-3-solanesylamino-2-propanol dihydrochloride (31.3 g) represented by the following formula.

Given below are measured values of physical properties of the title compound.

Melting point: Caramel-like; 1 87.90C (Decomposition) N.M.R. ( value in CDCI3) (Free base): 4.84-5.44 (9H, br) 4.05-4.48 (1 H, br) 2.32 (2H, d, J=7HZ) 2.41--2.89 (4H, br) 2.00 (32H, br) 1.60 (30H, s) Elementary analysis (as C48H82N20 2HCI 2H20): Calcd.Found C (%) 70.99 70.83 H (%) 10.92 10.76 N (%) 3.45 3.30 Preparative Example 4 1 -(3,4-DimethoxybenzytXalmino)-3-solanesylamino-2-propanol To a chloroform solution (100 ml) containing 1-amino-3-solanesylamine-2-propanol dihydrochloride (25 g) obtained in Preparative Example 3 was added pyridine (20 ml), and further thereto was added dropwise with stirring over a period of 1 hour a chloroform solution (30 ml) containing 3,4-dimethoxybenzoyl chloride (6.5 g) while cooling on an ice bath (0 C), followed further by stirring at room temperature for 2 hours.The reaction liquid was extracted with isopropyl ether, the extract was washed with water, 5% hydrochloric acid, 5% aqueous sodium hydrogen carbonate solution and saturated saline in that order, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The concentrate (24.3 g) was chromatographed with a chloroform-ethyl acetate mixture over a column packed with silica gel (300 g) to obtain 1 -(3,4-dimethoxybenzoyl)-3 solanesyiamino-2-propanol (10.3 g).To an anhydrous diethyl ether solution (100 ml) containing the thus obtained 1 -(3,4-dimethoxybenzoylamino)-3-solanesylamino-2-propanol (10.3 g) was added in small portions at room temperature lithium aluminum hydride (2.0 g) with stirring and then stirred at room temperature for 1 hour, followed further by heating under reflux for 3 hours with stirring. After the completion of the reaction, the reaction liquid was charged with a 109/0 aqueous sodium hydroxide solution (100 ml) and then extracted with isopropyl ether. The extract was washed with water and saturated saline, dried over anhydrous sodium sulfate and then concentrated under reduced pressure.

The concentrate (9.1 g) was dissolved in acetone (100 ml), charged with a hydrogen chloride-ether solution to weakly acidic and then allowed to stand at room temperature overnight. The crystallized mass was separated by filtration and dried to obtain 1 (3,4-dimethoxybenzylamino)-3-solanesyl- amino-2-propanol dihydrochloride (7.1 g) represented by the following formula.

trifluoroacetic anhydride (40 ml) over a period of 1 hour with stirring, and after the completion of the addition, the mixture was further stirred for 3 hours with cooling. After the completion of the reaction, the reaction liquid is filtered to separate insolubles and the filtrate was concentrated under reduced pressure. The concentrate was charged with benzene (50 ml) and further concentrated under reduced pressure. This concentrate (93.5 g) was chromatographed with a benzene-ethyl acetate mixture over a column packed with silica gel (1000 g) to obtain N-solanesyl-N,N'-ditrifluoroacetylethylenediamine (47.1 g). This N-solanesyl-N,N'-ditrifluoroacetylethylenediamine (47.1 g) was charged with an ethanol solution (200 ml) containing 10% potassium hydroxide and then heated under reflux for 1 hour. The reaction liquid was charged with water (300 ml) and then extracted with ethyl ether.The extract was washed with water and saturated saline, dried over anhydrous sodium sulfate and then concentrated under reduced pressure to obtain an oily N-solanesylethylenediamine (44.5 g). To a chloroform solution (100 ml) containing the thus obtained N-solanesylethylenediamine (23.5 9) was added pyridine (20 ml) and was further added dropwise with stirring over a period of 1 hour a chloroform solution (30 ml) containing 3,4-dimethoxybenzoyl chloride (6.1 g) while cooling on a water bath, followed further by stirring at room temperature for 2 hours.The reaction liquid was extracted with isopropyl ether, the extract was washed with water, 5% hydrochloric acid, 5% aqueous sodium hydrogen carbonate solution and saturated saline in that order, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The concentrate (24.5 g) was chromatographed with a chloroform-ethyl acetate mixture over a column packed with silica gel (300 g) to obtain N-solanesyl N'-(3,4-dimethoxybenzoyl)ethylenediamine (9.5 g).To an anhydrousdiethyl ether solution (100 ml) containing the thus obtained N-solanesyl-N'-(3,4-dimethoxybenzoyl)ethylenediamine (9.5 g) was added in small portions at room temperature lithium aluminum hydride (1.5 g) with stirring.The resulting mixture was stirred at room temperature for 1 hour and further heated under reflux for 3 hours with stirring. After completion of the reaction, the reaction liquid was charged with a 10% aqueous sodium hydroxide solution (100 ml) and then extracted with isopropyl ether. The extract was washed with water and saturated saline, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The concentrate (8.2 g) was dissolved in acetone (100 ml), charged with an ether solution of hydrogen chloride to weakly acidic, and allowed to stand overnight. The crystallized mass was separated by filtration and then dried to obtain N-solanesyl-N'-(3,4-dimethoxybenzyl)ethylenediamine dihydrochloride (5.8 g) represented by the following formula.

The measured values of physical properties of the title compound are as shown below.

Melting point: Caramel-like; 1 87.80C (Decomposition) N.M.R. (s value in CDCI3) (Free base): 6.70-6.93 (3H, br) 4.86-5.57 (9H, br) 3.85, 3.82 (6H, s) 3.71 (2H,s) 3.20 (2H, d, J=7Hz) 2.73 (4H, s) 2.00 (32H, br) 1.60 (30H, s) Elementary analysis (as C56H90N202 2HCI H20): Calcd. Found C (%) 73.57 73.31 H (%) 10.36 10.27 N (%) 3.06 3.01 Preparative Example 3 1-Amino3-solanesylamino-2-propanol dihydrochloride To a chloroform solution (400 ml) containing 1,3-diamino-2-propanol (100 g) was added dropwise at room temperature a chloroform solution (100 ml) containing solanesyl bromide (100 g) over a period of 1 hour with stirring, and the mixture was stirred for additional 3 hours at room temperature. The reaction liquid was concentrated under reduced pressure to remove the chloroform therefrom and the concentrate was extracted with ethyl acetate. The extract was washed with water and saturated saline, dried over anhydrous sodium sulfate and then concentrated under reduced pressure to obtain a concentrate (101.8 g).This concentrate was dissolved in isopropyl ether (200 ml), charged with sodium carbonate (50 g) and thereto was then added dropwise over a period of 1 hour contain benzylamino groups, there may be adopted another process in which a compound represented by the general formula R' COX (V) wherein R' represents a substituted phenyl and X represents halogen, is allowed to undergo reaction at a temperature of from 0 up to 500C. in the presence of a base (e.g. tertiary amine such as pyridine or triethylamine) to obtain a compound in which only a primary amino group has been acylated, and the thus obtained N-acylated compound is further reduced with a reducing agent (e.g. lithium aluminum hydride).The above-mentioned reduction reaction is preferably carried out at a temperature ranging from room temperature up to 600C. in such organic solvent as tetrahydrofuran, ether and the like.

After the completion of the reaction, a desired isoprenylamine derivative can be produced by treating the resultant reaction liquid according to usual isolation and purification procedures such as extraction, concentration, column chromatography, crystallization and the like.

An acid addition salt of the isoprenylamine derivative thus obtained can be obtained by mixing said derivative in an appropriate solvent (e.g. acetone or ethyl acetate) with a desired acid to form a salt and applying such means as concentration, crystallization and the like to the salt. The acid addition salts suitable for use as medicines include, for example, those with hydrochloric acid, acetic acid, citric acid, fumaric acid, lactic acid and the like.

Illustrated below are preparative examples of isoprenylamine derivatives of the present invention.

Preparative Example 1 N-(3-decaprenylaminopropyl)diethanolamine To an ethanol solution (100 ml) containing N-(3-aminopropyl)diethanolamine (25 g) an isopropyl ether solution (100 ml) containing decaprenyl bromide (30 g) was added dropwise at room temperature over a period of 1 hour, and the mixture was stirred at room temperature for additional 3 hours. The reaction liquid was poured in a 5% aqueous sodium hydroxide solution (500 ml) and extracted with isopropyl ether. The extract was washed with water and saturated saline, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The concentrate (30.1 g) was chromatographed with a chloroform-methanol mixture over a column packed with silica gel (300 g) to obtain an oily product (10.5 g) from the initially eluted fraction.The oily product thus obtained was dissolved in acetone (50 ml) and then allowed to stand in a refrigerator overnight. The crystallized mass was separated by filtration and then dried to obtain N-(3-decaprenylaminopropyl)diethanolamine (6.3 g) represented by the following formula

Given below are measured values of physical properties of the title compound.

Melting point: 45.2---49.40C N.M.R. (S value in CDCl3): 4.85-5.16 (1 OH, br) 3.60 (4H, t, J=6Hz) 3.22 (2H, d, J=7Hz) 2.23-2.85 (8H, m) 1.98 (38H, br-s) 1.60 (33 H, s) Elementary analysis (as C57Hg8N204 1/2H20): Calcd.Found C (%) 80.32 80.36 H(%) 11.70 11.53 N (%) 3.29 3.08 Preparative Example 2 N-solanesyl-N'-(3,4-dimethoxybenzyl)ethylenediamine dihydrochloride To a chloroform solution (200 ml) containing ethylenediamine (100 g) a chloroform solution (200 ml) containing solanesyl bromide (89 9) was added dropwise at room temperature over a period of 1 hour, and the mixture was stirred at room temperature for additional 3 hours. From the reaction liquid, the chloroform was removed under reduced pressure and the resulting concentrate was extracted with ethyl acetate. The extract was washed with water and saturated saline, dried over anhydrous sodium sulfate and then concentrated under reduced pressure to obtain a concentrate (88.3 g).The concentrate was dissolved in isopropyl ether (200 ml) and sodium carbonate (40 g) was added thereto. To the resulting mixture while cooling with ice-water was added dropwise SPECIFICATION Isoprenylamine derivatives This invention relates to new isoprenylamine derivatives and acid addition salts thereof, which 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 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), and synthetic substances, such as amantadine hydrochloride or methisazone, which directly exert inhibitory effect on virus propagation. Interferon is glycoprotein having antiviral and antitumor activities, said glycoprotein being produced in situ by cells of a vertebrate animal when the cells are infected with virus, and has been known to be effective in therapy of infectious viral disease as well as of cancer.Known inducers, which induce interferon in vertebrate animals through a process other than virus infection, include natural high molecular substances such as double strand ribonucleic acid of bacteriophage of a certain species, or synthetic high molecular substances such as double strand ribonucleic acid, typical of which is polyinosinic acidpolycytidylic acid, or low molecular inducers such as tilorone.

In the production of interferon, however, there is involved a problem how to carry out purification thereof, and in fact, no economical process for the production thereof has not been established yet. On the other hand, conventional interferon inducers have not been put to practical use mainly because of toxicity thereof. Synthetic antiviral agents which directly exert inhibitory effect on virus propagation, which are commercially available at present, have a rather narrow range of virus-infected diseases which are curable by administration of said agents, 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 general formula (I) and acid addition salts thereof show excellent interferon-inducing ability and, at the same time, demonstrate excellent antiviral activity even in the biological test.

Thus, the present invention is to provide a new class of isoprenylamine derivatives represented by the following general formula

CH3 H+CH2-C=CH-CH2+NH-(AIkylene)-Y (I) wherein n is 9-10, (Alkylene) is an alkylene chain of 2 or more carbons, particularly 2 to 3 carbon atoms, and may have a hydroxy-substituent on the carbon atoms, and Y is NH2, diethanolamino, or benzylamino which may optionally be substituted nucleically, and acid addition salts thereof.For the production of isoprenylamine derivatives represented by the general formula (I) and acid addition salts thereof, there may be adopted the known procedure in which isoprenyl alcohol (e.g. decaprenol or solanesol) represented by the general formula

wherein n is as defined above, is converted into a corresponding halide (e.g. solanesyl bromide or decaprenyl bromide) or arylsulfonic acid ester (e.g. decaprenyl tosylate or solanesyl tosylate) and the resulting halide or ester is then allowed to react in the presence or absence of a base with a compound represented by the general formula H2N-(Alkylene)-Y (III) wherein (Alkylene) and Y are as defined above. This reaction is usually carried out in an organic solvent.

Preferably usable as organic solvents in the reaction are common solvents such as methanol, ethanol, chloroform, isopropyl ether, benzene and ethyl acetate. In the practice of the above-mentioned reaction, it is preferable that a large excess of an amino compound represented by the general formula (III) is used, or the reaction is carried out at a temperature ranging from room temperature up to 1000C. in the presence of a base (e.g. sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate). After the completion of the reaction, a desired isoprenylamine derivative can be obtained by treating the resultant reaction liquid according to usual isolation and purification procedures such as extraction, concentration, column chromatography, crystallization and the like.

For the production of compounds represented by the general formula (I), which compounds Given below are measured values of physical properties of the title compound.

Melting point: 73.5-77.80C N.M.R. (6 value in CDCI3) (Free base): 6.70-6.94 (3H br) 4.80--5.53 (9H, br) 3.87, 3.81 (6H, s) 3.70 (2H, s) 3.20 (2H, d, J=7Hz) 2.41--2.89 (4H, br) 2.00 (32H, br) 1.60 (30H, s) Elementary analysis (as C57H92N2O3 - 2HCl - H2O): Calcd. Found C (%) 72.50 72.38 H (%) 10.25 10.46 N (%) 2.97 2.79 Physiological effects of the compounds of the present invention are illustrated below in detail. In the chemical structural formulas mentioned in the following test results, "D" represents decaprenyl and "S" represents solanesyl.

(1) Effect on mice infected with vaccinia virus Groups, each consisting of 10 ICR female mice weighing about 1 5 g, were intravenously injected with a dilute solution (0.1 ml) of vaccinia virus at a portion 2 cm from the base of a tail. On the 8th day after the inoculation, the number of lesions in the form of small pocks on the tail surface was counted after dyeing the tail with an ethanol solution of 1% fluorescein and 0.5% methylene blue. A test compound suspended in a surfactant solution was administered intraperitoneally at a rate of 50 mg/kg to the mice 24 hours before inoculation of the virus, 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 only the surfactant solution had been administered.The rate of tail lesion inhibition of the test compound is shown below.

Prevention from vaccinia infection Test compound (pock inhibition rate /0) D-NH /Nt ZOH) 2 54.8 (2) Anti-tumor activity Groups, each consisting of 6 Balb/c male mice weighing about 20 g, were intraperitoneally administered 5x 105 of tumor cells KN7-8. A test compound suspended in a surfactant solution was intraperitoneally administered (each time at a rate of 30 mg/kg) to the mice 24 hours before inoculation of the tumor cells and on the second day and the fifth day after the inoculation, totalling 3 times, and the anti-tumor activity was evaluated in terms of number of survivors on the 30th day after the inoculation. The number of survivors relative to the test compound is shown below.

Anti-tumor activity Test compound (survivor on the 3th day) D-NH /NwoH) 2 5/6 (3) Human interferon inducing activity (in vitro) Interferon was induced according to the method of Edward A. Havel et al. by treating normal diploid cells (fibroblast) originated from human being with a test compound in the form of an ethanol solution diluted with PBS (-), (25 n molar suspension). Using the radioisotope microassay method of H.

Ishitsuka et al., interferon was measured in terms of 3H-uridine-uptake inhibition rate. The rate of 3Huridine-uptake inhibition of the test compound as measured is shown below.

Human interferon Test compound 3K-uddine-uptake inhibition rate % D-NH /N m/OH) 2 0.6 (4) Anti-vaccinia virus activity (in vitro) Virus plaque-formation inhibition rate of a test compound was obtained by treating vero cells originated from the kidney of African green monkey with the test compound suspension (the compound in the form of ethanol solution was suspended in Hanks cuiture liquid, 50 n molar concentration) and the virus diluted solution. The inhibition rate of the test compound as measured is shown below.

Anti-vaccinia virus activity Test compound (plaque inhibition rate /0) D-NH NOH) 2 66.8 2 (5) Toxicity Using ddY male mice weighing 20-25 g, 50% lethal dose of a test compound when intravenously administered was obtained, the results of which are shown below.

LD50 In tra venous administration Test compound LD50 (mg/kg) D-NH ANOH) ) 2 34 As is clear from the foregoing test results, the active ingredients of the present invention have interferon inducing activity in vivo and, at the same time, 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 that the antivirus activities of said ingredients at biological level are concerned not only in interferon but also in other defensive mechanism of host.As diseases of human being caused by virus, there are known a number of symptons, for example, herpes-infected diseases such as herpes simplex, influenza, measles, etc. Accordingly, when the active ingredients of the present invention are used for prevention from virus-infection and for the treatment of virus-infected diseases, they are administered to patients by such technique involving oral, inhalant or the like administration as well as subcutaneous, intramuscular and intravenous in injection. According to the condition of patient such as age, symptom and route by which the ingredient is administered, the active ingredient of the present invention is used in a dose of 0.5-20 mg/kg, preferably 3-5 mg/kg several times (2-4 times) per day.

The active ingredients of the present invention can be formulated into compositions for medication, for example, tablets, capsules, granules, powder, liquid preparation for oral use, eye lotions, suppositories, ointments, injections and the like.

When the present active ingredients are orally administered, they may be formulated into tablets, capsules, granules or powder. These solid preparations for oral use may contain commonly used excipients, for example, silicic anhydride, metasiiicic acid, magnesium alginate, synthetic aluminum silicate, lactose, cane sugar, corn starch, microcrystalline cellulose, hydroxypropylated starch or glycine and the like; and binders, for example, gum arabic, gelatin, tragacanth, hydroxypropyl cellulose, or polyvinyl pyrrolidone; lubricants, for example, magnesium stearate, talc or silica; disintegrating agents, for example, potato starch and carboxymethyl cellulose calcium; or wetting agents, for example, polyethylene glycol, sorbitan monooleate, polyoxyethylene hydrogenated castor oil, sodium lauryl sulfate and the like.In preparing soft capsules, in particular, the present active ingredients may be formulated by dissolving or suspending them in polyethylene glycol or commonly used oily substrates such as sesame oil, peanut oil, germ oil, fractionated cocounut oil such as Miglyol (registered Trade Mark), or the like. Tablet or granule preparations may be coated according to the usual method.

Liquid preparation for oral use may be in the form of aqueous or oily emulsion or syrup, or alternatively in the form of dry product which can be re-dissolved before use by means of a suitable vehicle. To these liquid preparations, there may be added commonly used additives, for example, emuisifying aids such as sorbitol syrup, methyl cellulose, gelatin, hydroxyethyl cellulose and the like; or emulsifiers, for example, lecithin, sorbitan monooleate, polyoxyethylene hydrogenated castor oil; nonaqueous vehicles, for example, fractionated coconut oil, almond oil, peanut oil and the like; or antiseptics, for example, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, or sorbic acid. Further, these preparations for oral use may contain, if necessary, preservatives, stabilizers and the like additives.

In case where the present active ingredients are administered in the form of non-oral suppository, they may be formulated according to the ordinary method using oleophilic substrates such as cacao oil or Witepsol (registered Trade Mark) or may be used in the form of rectum capsule obtained by wrapping a mixture of polyethylene glycol, sesame oil, peanut oil, germ oil, fractionated coconut oil and the like in a gelatin sheet. The rectum capsule may be coated, if necessary, with waxy materials.

When the present active ingredients are used in the form of injection, they may be formulated into preparations of oil solution, emulsified solution or aqueous solution, and they may contain commonly used emulsifiers, 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%, preferably 5 to 50%.

The procedure of formulating the present active ingredients into various preparations is illustrated below with reference to pharmaceutical examples.

Pharmaceutical Example 1 Hard capsule preparations for oral use A mixture of 25 g of N-(3-decaprenylaminopropyl)diethanolamine and 7.5 g of polyoxyethylene castor oil in acetone was mixed with 25 g of silicic anhydride. After evaporation of the acetone, the mixture was mixed further with 5 g of calcium carboxymethylcellulose, 5 g of corn starch, 7.5 g of hydroxypropylcellulose and 20 g of microcrystalline cellulose, and 30 ml of water was added thereto and kneaded to give a granular mass. The mass was pelletized by means of a pelletizer (ECK pelletizer of Fuji Paudal Co., Japan) equipped with No. 24 mesh (B.S.) screen to obtain granules. The granules were dried to less than 5% moisture content and screened with No. 1 6 mesh (B.S.) screen.The screened granules were capsuled 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 preparation for oral use A homogeneous solution was prepared by mixing 50 g of N-(3-decaprenylaminopropyl)diethanolamine with 130 g of polyethylene glycol (Macrogol 400). Separately, a gelatin solution was prepared which contained 93 g of gelatin, 1 9 g of glycerin, 10 g of D-sorbitol, 0.4 g of ethyl phydroxybenzoate, 0.2 g of propyl p-hydroxybenzoate 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 1 80 mg.

Pharmaceutical Example 3 Injections A mixture of 5 g of N-solanesyl-N'-(3,4-dimethoxybenzyl)ethylenediamine dihydrochloride, 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 1-amino-3-solanesylamino-2-propanol dihydrochloride, 5.0 g of Nikkol HCO-60 (a trade name) (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

1. A compound of formula

CH3 I HCH2-C=CH-CH2#NH-(AlkyIene)-Y wherein n is 9 or 10, (Alkylene) is an alkylene chain of 2 or more carbon atoms, optionally substituted by hydroxy, and Y is NH2, diethanolamino or benzylamino which is optionally nucleically substituted, or an acid addition salt thereof.

2. A compound according to claim 1 wherein (Alkylene) is an alkylene chain of 2 or 3 carbon atoms.

3. A compound according to claim 1 or 2 wherein Y as benzylamino is nucleically substituted by one or more methoxy groups.

4. N-(3-decaprenylaminopropyl)diethanolamine.

5. N-solanesyl-N'-(3,4-dimethoxybenzyl)ethylenediamine dihydrochloride.

6. 1 -amino-3-solanesylamino-2-propanol dihydrochloride.

7. 1 -(3,4-dimethoxybenzylamino)-3-solanesylamino-2-propanol.

8. A process of preparing a compound as claimed in claim 1 which comprises allowing a compound of formula

wherein n is as defined in claim 1, in the form of the corresponding halide or arylsulfonic acid ester, to react with a compound of formula H2N-(Alkylene)-Y (III) wherein (Alkylene) and Y are as defined in claim 1, and optionally converting the product to an acid addition salt thereof.

9. A process of preparing a compound as claimed in claim 1 wherein Y is optionally substituted benzylamino, which comprises allowing a compound of formula

CH3 H+CH2C=CHCH24"NH(Alkylene)Y wherein n and (Alkylene) are as defined in claim 1 and Y is NH2, to react in the presence of a base with a compound of formula R'COX wherein R' is unsubstituted or substituted phenyl and X is a halogen, subsequently reducing the product, and optionally converting it to an acid addition salt thereof.

1 0. A process according to claim 8 substantially as hereinbefore described with reference to any one of Preparative Examples 1-3.

11. A process according to claim 9 substantially as hereinbefore described with reference to Preparative Example 2 or 4.

1 2. A pharmaceutical composition comprising an active ingredient a compound as claimed in any one of claims 1 to 7 and a carrier or diluent.

13. A composition according to claim 12 substantially as hereinbefore described with reference to any one of the Pharmaceutical Examples.

14. A compound according to claim 1 for use in a method of therapy practised on the human or animal body.

1 5. A compound according to claim 1 for use as an anti-viral agent.