IE55793B1

IE55793B1 - Use of sugar derivatives for the prophylaxis and treatment of virus infections

Info

Publication number: IE55793B1
Application number: IE1728/83A
Authority: IE
Original assignee: Ciba Geigy Ag
Priority date: 1982-07-23
Filing date: 1983-07-22
Publication date: 1991-01-16
Also published as: ZA835360B; IL69294A0; NZ205000A; DE3326163A1; IT8348734A0; BE897359A; SG77989G; EP0102319A1; IT1168778B; IL69294A; AU566879B2; HK79890A; AU1721983A; EP0102319B1; IE831728L; JPS5933297A

Abstract

1. A pharmaceutical composition for enteral or parenteral application, which composition contains, as sole active ingredient, an effective amount, but less than 1 % by weight, of a compound of the formula I see diagramm : EP0102319,P31,F1 in which the sugar moiety is derived from (D)-galactose, (D)-mannose or (D)-glucose, which compound has at an asymmetrically substituted C(-R**3) atom the (D)-configuration, at an asymmetrically substituted C(-R**6) atom the (L)-configuration and at an asymmetrically substituted C(-R**8) atom the (D)-configuration, and in which compound each of X**1 and X**2 independently to the other represents a group of the formula -O- or -N(R**14)-, R**14 representing hydrogen or lower alkyl, each of R**1, R**2, R**12 and R**13 independently represents a radical of the formula Ia -(Z**1-Y**1-X**3)n -A**1 in which n represents 0 or 1, Z**1 represents carbonyl or thiocarbonyl, Y**1 represents unsubstituted or substituted alkylene which may be interrupted by iminocarbonyl or oxycarbonyl, X**3 represents a group of the formula -O- or -N(R**14)-, wherein R**14 has the meaning given above, and A**1 represents a radical of the formula Ib see diagramm : EP0102319,P31,F2 in which R**15 represents an aliphatic or cycloaliphatic radical having at least 7 carbon atoms, or A**1 represents a group of the formula Ic see diagramm : EP0102319,P31,F3 in which R**16 represents hydrogen and R**17 represents 2-hydroxyethyl or 1,2-dihydroxyethyl, wherein at least one hydroxy group is esterified or etherified by a radical having at least 7 carbon atoms, or in which each or R**16 and R**17 independently of the other represents esterified or etherified hydroxymethyl, the esterifying or etherifying radicals having at least 7 carbon atoms, or each of R**1, R**2, R**12 and R**13 independently represents hydrogen, acyl other than a radical of the formula Ia in which n represents 1, or aliphatically substituted silyl, each of R**3, R**4, R**5, R**7 and R**8 independently represents hydrogen or lower alkyl, R**6 represents hydrogen or lower alkyl that is unsubstituted or substituted by a group of the formula Id -E-(Z**2-Y**2-X**4)m -A**2 in which m represents 0 or 1, E represents a group of the formula -O-, -S- or -N(R**14), R**14 having the meaning given above, Z**2 represents carbonyl or thiocarbonyl, Y**2 represents unsubstituted or substituted alkylene which may be interrupted by iminocarbonyl or oxycarbonyl, X**4 represents a group of the formula -O- or -N(R**14)-, having the meaning given above, and A**2 represents a radical of the formula Ib or lc ; or by free or etherified hydroxy or mercapto, by esterified hydroxy or mercapto other than a group of the formula Id, by free amino or substituted amino other than a group of the formula Id, by free, esterified or amidated carboxy, by cycloalkyl, by carbocyclic aryl or by nitrogen-containing heteroaryl having 5 or 6 ring members in the heterocyclic ring, or R**5 and R**6 together represent unsubstituted 1,3- or 1,4-lower alkylene, each of R**9 and R**11 independently of the other represents a radical of the formula Ie -X**5-Y**3-X**6-A**3 in which X**5 represents a group of the formula -O-, -S- or -N(R**14)-, and X**6 represents a group of the formula -O- or -N(R**14)-, in each case R**14 having the meaning given above, Y**3 represents unsubstituted or substituted alkylene which may be interrupted by iminocarbonyl or oxycarbonyl, and A**3 represents a radical of the formula Id or lc, or free hydroxy or mercapto, etherified hydroxy or mercapto other than a radical of the formula Ie, or free amino or substituted amino other than a radical of the formula Ie, and represents hydrogen or free, esterified or amidated carboxy, with the proviso that radicals qualified by the term "lower" contain up to and including 7 carbon atoms and that the compounds of the formula I have at least one radical A**1, A**2 or A**3 and/or a pharmaceutically acceptable salt thereof, together with a pharmaceutical carrier.

Description

The present invention relates to the use of hexopyranose derivatives, containing a phosphoryl residue and in the 3-position of the sugar moiety a peptidic side chain, for the manufacture of pharmaceutical compositions which are to .be used for the prophylaxis and therapy of diseases caused by viruses, as well as to pharmaceutical compositions containing less than 1 % by weight of such a hexopyranose derivative.

The above-mentioned hexopyranose compounds of the formula I 70 and the salts thereof as well as the manufacture thereof are described in the European patent applications with the publication numbers*0025 495, 0027 258 and 0056 992 which are in . the name of the Applicants of the present invention, and the last-mentioned application was not published until after the priority date of the present application. The use of the phosphoryl muramylpeptides per se for the manufacture of pharmaceutical compositions for the prophylaxis and therapy . of infections caused by viruses is neither described in nor made obvious by the above-mentioned applications.

The penultimate paragraph on page 13 of the above-mentioned application 0025 495 relates only to the use as an adjuvant in admixture with vaccines.

The above-mentioned applications 0025 495 and 0027 258 describe also pharmaceutical compositions which, however, contain about 10 % to about 95 % of an active ingredient. In the above-men tioned application 0056 992 pharmaceutical compositions containing about 1 % to about XOO %, especially about 5 % to about 50 %, of an active ingredient are described.

The task according to the invention was the preparation of pharmaceutical compositions outstandingly suitable for the prophylaxis and therapy of infections caused by viruses in warm-blood animals. lo According to the present application the solution of this task resides in the finding that hexopyranose compounds of the formula I, R13—ΧΟΗ r12-o~> (ΐ) / V-R2 I 4 C-R* C—NII ό 0=C-R9 R10 O I I β N—CH— CH2— CH— C— R in which the sugar moiety is derived from (D)-galactose, (D)-mannose or (D)-glucose, which compound has at an asym3 metrically substituted C(-R ) atom the (D)-configuration, at an asymmetrically substituted C(-R^) atom the (L)-confi8 guration and at an asymmetrically substituted C(-R ) atom the (D)-configuration, and tn which compound each of X1 and 2 X r independently of the other, represents a group of the formula -O- or each of R1, R2, R12 and R15, K(R^)-, r!4 representing hydrogen or lower alkylf Independently of one another, represents a radical of the formula Ia -( X~)n-A (Ia) in which £ represents 0 or 1, represents carbonyl or thiocarbonyl, represents unsubstituted or substituted alkylene which may be interrupted by Iminocarbonyl or oxyx carbonyl, X represents a group of the formula -0or -R(R^)-, wherein R^ has the meaning given above, and A^ represents a radical of the formula lb, II -P-O-R db) OH in which R represents an aliphatic or cycloaliphatic radical having at least 7 carbon atoms, or A^" represents a group of the formula Ic, v O R II I -Ρ - Ο - CH 1 'Χ7 OH RA (Ic) in which iP*® represents hydrogen and R represents 2-hydroxyethyl or 1,2-dihydroxyethyl, wherein at least one hydroxy group is esterified or etherified by a radical having at least 7 carbon atoms, or in which each of fil® and R1*7, independently of the other, represents esterified or etherified hydroxymethyl, the esterifying or etherifying radicals having at .least 7 carbon atoms, or 2 T9 19 each of R , R , R and R , independently of one another, represents hydrogen, acyl other than a radical of the formula Ia in which n represents 1, or aliphatically substituted silyl. each of r\ r\ r\ & R' and R , Independently of one another, represents hydrogen or lower alkyl, . represents hydrogen or lower alkyl that is unsubstituted or substituted by a group of the formula Id, w -β-(ζ2-Y2-X4 )m-A2 (Id) * in which jj represents 0 or 1, E represents a group of the formula -0*. -3- or -41(1.^)-, having the to meaning given above, Z represents carbonyl or thiocarbonyl, X2 represents unsubstituted or substituted alkylene 15 which may be interrupted by iminocarbonyl or oxy* carbonyl, X* represents a group of the formula -0or -H(R14)-, R34 having 2o the meaning given above, and A represents a radical of the formula lb or Io; or by free or etherified hydroxy or mercapto, 25 by esterified hydroxy or mercapto other than a group of the formula Id, by free amino or substituted amino other than a 30 group of the formula Id, by free, esterified or ‘ amidated carboxy, by cycloalkyl, by carbocyclio aryl ΟΓ and Β6 Q 11 each of Br and fi , or by nitrogen-containing heteroaryl having 5 or 6 ring members in the heterocyclic ring» together represent unsubetituted or substituted lt 3- or 1,4-lower alkylene, independently of the other, represents a radical of the formula Is, -x5-y3-x6-A3 (le) in which represents a group of the formula -0-, —S— or —fi(fi^)—, and X® represents a group of the formula -0- or -fi(fi^)-, in each case fi^ having the meaning given above, T? represents unsubatituted or substituted alkylene which may be interrupted by iminocarbonyl or oxycarbonyl, and A? represents a radical of the formula Ib or Ic, or free hydroxy or mercapto, etherified hydroxy or mercapto other than a radical of the formula Ie, or free amino or substituted amino other than a radical of the formula Ie, and represents hydrogen or free» esterified or amidated carboxy, with the proviso that radicals qualified by the term lower contain up to and including 7 carbon atoms and that the cons1 2 pounds of the formula I have at least one radical A , A or 3 A , and pharmaceutically acceptable salts of such compounds are suitable for the manufacture of pharmaceutical compositions to be used for the prophylaxis and (preferably) treatment of virus infections in warm-blooded animals, especially and including humans. 4.

By contrast with the treatment of bacterial infections, agents available for the prophylaxis and treatment of virus infections are few and inadequate so that to overcome viral diseases it is in almost all cases necessary that the organism itself has adequate powers of defence· In accordance with the invention It has surprisingly been found that the above-mentioned hexopyranose compounds of the formula I and their pharmaceutically acceptable salts are excellently suitable both for the prophylaxis and treatment of virus infections, as demonstrated, for example, by animal experiments such as those illustrated in the Examples. In these animal experiments animals, such as mice or guinea pigs, are infected by a vide variety of types of virus in a dose that is lethal for all or the large majority of untreated (control) animals, for example ^gQ_goe ***& the course of the infection -is observed in the untreated control animals compared with animals that are treated before, at the same time as, or after the infection, with one of the above-mentioned hexopyranose compounds or a salt thereof.

These experiments demonstrate that the antiviral action of the above-mentioned hexopyranose compounds of the formula I and their salts is not achieved by any hitherto known antiviral substance of any structure.

It is especially remarkable that a prophylactic effect is produced when hexopyranose compounds of the formula I are administered from just a few days up to a few, for example four, weeks before Infection* and a therapeutic effect still occurs on administration several days, for example 1 week, after infection.

. Remarkable and hitherto unprecedented le also the broad viral spectrum against which the above-mentioned compounds are effective· The hexopyranose compounds of the formula I can be used especially for the prophylaxis and treatment of diseases caused by the viruses specified in detail hereinafter [for nomenclature cf. J.L. Melnick, Prog. med. Tirol. 26, 214-232 (I960) and 28, 208-221 (1982)]: DMA viruses with cubic symmetry and naked nucleocapsid, DMA viruses with enveloped virion and also RMA viruses with cubic, and those with helical, synmetry of the capsid.

Preferably, the compounds of the formula I are used in the case of DMA viruses with enveloped virion and cubic symmetry of the capsid, in the case of RMA viruses with cubic symmetry of the capsid and naked virion, and in the ease of RMA viruses with helical symmetry of the capsid, in which the nucleocapsid casing is located at the surface membrane, but also In the base of A&enovirldae, Poxvlridae and Corona30 viridae, such as, especially, human coronaviruses.

The compounds of the formula I are uaed especially in the case of Herpet ovir idae, Picoraavirldae and myxoviruses, but also in the case of mastadenoviruses, such as, especially, human adenoviruses, in the case of Chordopoxvirlnae, such as, chiefly, orthopoxviruses, such as, especially, for example, vaccinal viruses, in the case of Reoviridae, chiefly (especially human) rotaviruses, and also in the case of Caliciviridae and Rhabdovir idae, such as, especially, vesiculoviruses in humans as well as horses, cows and pigs.

The conpounds of the formula I are mainly used in the case of Alphaherpesvirinae like Varicellaviruses, * for example human varicellazoster viruses, rhinoviruses, cardioviruses and Orthanyxoviridae, but also in the case of Betaherpesvirinae, such as, especially, human * cytomegaloviruses, in the case of aphthoviruses, especially aphthoviruses of cloven-hoofed animals, such as, chiefly, cows, and in the case of Paramyxoviridae, such as, especially, pneumoviruses, for exanple respiratory syncytial viruses in humans, and such as, in . addition, morbilliviruaes or paramyxoviruses, such as parainfluenza viruses, for exanple human parainfluenza viruses, including Sendai viruses, as well as in the case of arboviruses or vesiculoviruses, for exanple vesicular stomatitis viruses.

Above all the conpounds of the formula I are used for sinplex viruses, for exanple human herpes sinplex viruses of types 1 and 2, and in the case of human encephalomyocarditis viruses, influenza viruses, such as mainly influenza A and influenza B viruses, and most especially in the case of the viruses mentioned in the Exanples.

The hexopyranose conpounds of the formula X can be used in accordance with the invention by administering than enterally or parenterally, especially to30 gether with suitable adjuncts or carriers. Preferably they are applied to the mucous membrane, for exanple intranasally, rectally, vaginally or to the conjunctiva of the eye, or orally. The antiviral effect occurs, however, also if administered in other ways, for exaiple subcutaneously, intravenously, intramuscularly or if applied to the skin. * 1 The dosage of the active ingredient depends, inter alia, on the species of the warm-blooded animal , the defensive condition of the organism, the mode of administration and the nature of the virus* There is no especially pronounced relationship between dosage and action.

For prophylaxis, a single dose of from approximately 0*01 mg to approximately 25 mg, preferably from 0.05 to 7 mg, for example 0*5 mg, of active ingredient is administered to a warm-blooded animal of approximately 70 kg body weight, for example a hua;n. The prophylactic effect of this dose lasts for several weeks. If required, tor example at times of increased risk of infection, the administration of this dose can be repeated.

The therapeutic dose for warm-blooded animals of approximately 70 kg body weight is between 0.1 mg and 50 mg, preferably between 1 and 10 mg, for example 5 mg, especially when administered orally* The dosage in the case of topical, especially intranasal, administration is lower by up to a factor of 10* If required, the administration of the hexopyranose compounds of the formula I oan be repeated until there is an Improvement in the disease. Normally, however, one administration is adequate* The hexopyranose compounds of the formula I are used in accordance with the invention in the form of pharmaceutical preparations that contain a pharmacologically active amount of the active ingredient together with pharmaceutically acceptable carriers that are suitable for enteral, for example oral, or parenteral, administration and may be inorganic or organic, solid or liquid* For example, tablets or gelatin capsules that contain the active ingredient together with diluente, for example lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and/or glycerin, and/or lubricants, for example siliceous earth, talc, stearic acid or salts thereof, such as magnesium or calcium stearate, and/or polyethylene glycol, are used. Tablets may likewise contain binders, for example magnesium aluminium silicate, starches, such , as corn, wheat or rice starch, gelatin, methyl cellulose, sodium carboxymethyl cellulose and/or polyvinylpyrrolidone and, if desired, disintegrators, a for example starches, agar, alginic acid or a salt lo thereof, such as sodium alginate, and/or effervescing mixtures, or adsorbents, colouring substances, flavouring substances and sweeteners· Furthermore, the pharmacologically active compounds of the present invention can be used in the form of parenterally administrable preparations, for example infusion solutions. Such solutions are preferably isotonic aqueous solutions or suspensions, and these, for example in the case of lyophilised preparations that · contain the active ingredient alone or together with a carrier, for example mannitol, can be prepared before use. The pharmaceutical preparations may be sterilised and/or contain adjuncts, for example preservatives, stabilisers, wetting agents and/or emulsifiers, solubilisers, saltsfbr regulating the osmotic pressure and/or buffers# The pharmaceutical preparations in question are produced in a manner known per se. for example by means of conventional mixing, granulating, confectioning, dissolving or lyophilising processes, and contain from approximately 0.001 % up to approxi30 mately 95 % of active ingredient, an active ingredient content of lees than 1 % being suitable especially for preparations that are to be topically administered· Pharmaceutical preparations for enteral or parenteral administration that contain an effective · amount, but less than 1% by weight, of a hexopyranose compound of the formula I or a salt thereof together with a pharmaceutical carrier, are novel and the invention relates also to these.

The invention relates especially to pharmaceutical . 5 preparations containing a hexopyranose compound of the formula X that is mentioned below as being preferred for the use in accordance with the invention· The following forms of administration, which have not been prior-published, of hexopyranose compounds IO of the formula X are especially suitable for the use in accordance with the invention: creams, ointments, pastes or a gel with an active ingredient content of from 0.001 % up to, but exclusive of, 1 % by weight, principally of from 0.001 % to 0.9 %, especially from 0.01 % to 0.1 %, for example 0.05 %, for example ointments for intranasal administration, vaginal or rectal suppositories or lipsticks, aqueous solutions having an active ingredient content of from 0.001 % by weight up to, but exclusive of, 1 % by weight, principally 2o from 0.001 % to 0.9 %, especially from 0.05 % to 0.5 %, for example 0.1 %, preferably isotonic, sterile and physiologically tolerable solutions, for example eye drops, preferably in disposable, micro-containers, or sprays for use in the mouth* or pharyngeal cavity, or tablets or capsules having an active ingredient content of from 0.1 up to, but exclusive of, 1 % by weight, for example 0.9 The pharmaceutical preparations described in the Examples are especially suitable.

Creams are oil-in-water emulsions that contain more than 50 % of water. There are used as oily base substances especially fatty alcohols, for example lauryl, cetyl or stearyl alcohol, fatty acids, for example palmitic or stearic acid, liquid to solid waxes, for example isopropyl myristate, wool wax or beeswax. and/or hydrocarbons, for example petroleum jelly (petrolatum) or paraffin oil· There come into consideration as emulsifiers surface-active substances having predominantly hydrophilic properties, such as corresponding non-ionic emulsifiers, for example fatty acid esters of polyalcohols or ethylene oxide adducts thereof, such as polyglycerin fatty acid esters or polyoxyethylene sorbitan fatty acid esters (Tweens^ , also polyoxyethylene fatty alcohol ethers or fatty acid esters, or corresponding ionic emulsifiers, such as alkali metal salts of fatty alcohol sulphates, for example eodium lauryl sulphate, eodium cetyl sulphate or sodium stearyl sulphate, which are usually used in the presence of fatty alcohols, for example cetyl alcohol or stearyl alcohol· Additives to the aqueous phase are, inter alia· agents that reduce the drying out of creams, for example polyalcohols, such as glycerin, sorbitol, propylene glycol and/or polyethylene glycols, and also preservatives and perfumes.

Ointments are water-in-oil emulsions that contain up to 70 %, preferably from approximately 20 % to approximately 50 ¢, of water or aqueous phase· There come into consideration as fatty phase especially hydrocarbons, for example petroleum jelly, paraffin oil and/or hard paraffine, which, in order to improve the water-binding ability, preferably contain suitable hydroxy compounds, such as fatty alcohols or esters thereof, for example cetyl alcohol or wool wax alcohols, or vool wax. Emulsifiers are corresponding lipophilic substances, such as sorbitan fatty acid esters (Spans), for example sorbitan oleate and/or sorbitan isostearate· Additives to the aqueous phase are, for example, humectants, such as polyalcohols, for example glycerin, propylene glycol, sorbitol and/or polyethylene glycol, as well as preservatives and perfumes.

Fatty ointments are anhydrous and contain as the base substance especially hydrocarbons, for example paraffin, petroleum jelly and/or liquid paraffins, also natural or partially synthetic fats, for example coconut fatty acid triglyceride, or preferably hardened oils, for example hydrogenated peanut or castor oil, and fatty acid partial esters of glycerin, for example glycerin mono- and di-stearate, as well as, for example, the fatty alcohols that increase water-ab1O sorbing ability, emulsifiers and/or additives mentioned in connection with the ointments.

Bastes are creams and ointments with secretionabsorbing powder constituents» such as metal oxides, for example titanium oxide or zinc oxide, and also talc and/or aluminium silicates, the purpose of which is to bind any moisture or secretions present.

Foams are administered from pressurised containers and are liquid oil-in-water emulsions in aerosol form, halogenated hydrocarbons, such as chlorofluoro20 lower alkanes, for example dichlorddifluoromethane and dichlorotetrafluoroethane, being used as propellants. There are used as oily phase, inter alia, hydrocarbons, for example paraffin oil, fatty alcohols, for example cetyl alcohol, fatty acid esters, for example isopro25 pyl myristate, and/or other waxes. There are used as emulsifiers, inter alia, mixtures of those having predominantly hydrophilic properties, such as polyoxyethylene sorbitan fatty acid esters (Tweens (Trade Hark]), and those having predominantly lipophilic pro30 perties, such as sorbitan fatty acid esters (Spans [Trade Hark]). In addition there are the customary additives» such as preservatives.

Tinctures and solutions usually have an aqueous/ ethanolic base substance to which there are added, later alia, polyalcohols, for example glycerin, gly16 cols and/or polyethylene glycol, as humectants for reducing evaporation, and fat-restoring substances, such as fatty acid eeters vlth low polyethylene glycols, that is to say lipophilic substances soluble in aqueous mixture as a replacement for the fatty substances removed from the skin by the ethanol, and, if necessary, other adjuncts and additives.

The manufacture of the topically administrable pharmaceutical preparations is carried out in a manner io known per se. for example by dissolving or suspending the active ingredient in the base substance, or in a portion thereof, if necessary. When processing the active ingredient in the form of a solution, it is usually dissolved in one of the two phases before emul15 sification; when processing in the form of a suspension it is mixed with a portion of the base substance after emulsification and then added to the remainder of the formulation.

The above terms used for the definition of the compounds of the formula I have, within the scope of this application, preferably the following meanings: Acyl, for example as r\ R^, and is especially the acyl radical of an organic carboxylic acid, especially an aliphatic, but also a cycloali25 phatic, cycloaliphatic-aliphatic, aromatic or araliphatic carboxylic acid, which may have, for example, up to 90 carbon atoms.

Aliphatic carboxylic acids are, inter alia, alkanecarboxylio acids that are unsubstituted or sub30 stituted, for example, by hydroxy or etherifled or esterified hydroxy, such as lower alkoxy or lower alkanoyloxy, or by unsubstituted or substituted amino, such as lower alkylamino, di-lower alkylamino or acylamino, for example alkanoylamino, and corresponding alkene- or alkyne-carboxylic acids that may have one or more double or triple bonds. These acids may contain, 7 ο for example, up to 90 carbon atoms, R as the radical of an dliphatic carboxylic acid, in the case when X1 represents a group of the formula preferably representing the acyl radical of an unsubstituted or hydroxy-substituted lower alkanecarboxylic acid.

Cycloaliphatic carboxylic acids may be monocyclic or polycyclic and as a cycloaliphatic radical contain monocyclic or polycyclic cycloalkyl that is unsubstituted or is substituted, for example by hydroxy, and corresponding cyoloalkenyl.

In cycloaliphatic-aliphatic radicals, the cycloaliphatic moiety and the aliphatic moiety have the meanings given above; such radicals are especially monocyclic or polycyclic cycloalkyl-lower alkyl* Aromatic and araliphatic carboxylic acids are, inter alia* benzoic or phenyl-lower alkanecarboxylic acids that are unsubstituted or substituted, for example by lower alkyl, hydroxy, lower alkoxy or halogen* Aliphatically substituted silyl is e.g. tri-lower alkylsilyl.

Substituents of alkylene, which Is represented by the radicals Υ1, Y2 and y\ are, inter alia, hydroxy, esterified or etherified hydroxy, such as acyloxy, for example lower alkanoyloxy, or lower alkoxy, amino or substituted amino, such as lower alkylamino, di-lower alkylamino or acylamino, for example lower alkanoylamino· In an alkylene radical that is interrupted by iminocarbonyl or oxycarbonyl, there may be one or more, for example two, such groups and these may be present as groups of the formula -N(R^)-C(=O)- or -0-0(=0)-, and as groups of the formula -0(=0)-^(^1^). or -0(=0)-0-, and R^ has the meaning given above and preferably represents hydrogen. An alkylene radical formed by the groups R^ and R® and having 3 or 4 carbon atoms in the chain may be substituted, for example by hydroxy, which may be acylated, for example by a group of the formula Ia· Δη aliphatic radical having at least 7 carbon · atoms that is the group R1^ or etherlfies a hydroxy yg 17 group in a radical R or R is especially a corresponding unsubstituted or substituted alkyl radical « but may also represent a corresponding unsaturated io radical, such as an unsubstituted or substituted alkenyl radical having one or more double bonds, such radicals having, for example, from 7 up to and including 90 carbon atoms, preferably from 7 up to and including 30 carbon atoms· Substituents of such aliphatic radicals are, for example, hydroxy, etherified or esterified hydroxy, such as lower alkoxy or lower alkanoyloxy and/or unsubstituted or substituted amino, such as lower alkylamino, di-lower alkylamino or alkanoylamino· Δ corresponding cycloaliphatic radical that is the group R1^ or a radical etherifying a hydroxy group 16 17 in a radical R or R is especially monocyclic or polycyclic cycloalkyl, or also corresponding cycloalkenyl, which may contain one or more double bonds· Such radicals contain at least 7> and preferably from to 30, carbon atoms, and may, in addition, bs substituted, for example by hydroxy, etherified or esterified hydroxy, such as lower alkoxy or lower alkanoyloxy, or by unsubstituted or substituted amino, such as lower alkylamino, di-lower alkylamino or alkanoylamino.

Etherified hydroxy or substituted amino as a radical R^ or Ru is, for example, lower alkoxy, or, for example, lower alkylamino, in which lower alkyl may be substituted. · Δ radical esterifying a hydroxy group in a radical y g 17 R or R is especially an acyl radical of an organic carboxylic acid, especially of one of the above-mentioned aliphatic and cycloaliphatic, cycloaliphaticaliphatic, aromatic or araliphatic, carboxylic acids, preferably having from 7 to 90 carbon atoms· Etherified hydroxy or mercapto or esterified hydroxy or mercapto other than a radical of the formula Id as substituent of lower alkyl Εθ is, for example, lower alkoxy, acyloxy, such as alkanoyloxy, wherein, alkanoyl contains up to 90, for example from 7 to 30, carbon atoms and may optionally be substituted, for example by hydroxy, or is halogen, lover alkylthio or acyl thio, such as alkanoyl thio, wherein alkanoyl contains up to 90, for example from 7 to 30, carbon atoms· Substituted amino other than a radical of the formula • g Id as substituent of a lower alkyl group H is, for example,, lower alkylamino, guanylamino or acylamino, such as alkanoylamino, wherein alkanoyl may contain up to 90, for example up to 30, carbon atoms· Esterified carboxy as substituent of a lower alkyl radical Εθ is preferably carboxy esterified by an aliphatic radical, such as alkyl having up to 30 carbon atoms, that is to say, for example, corresponding alkoxycarbonyl, whilst corresponding amidated carboxy, is, for example, aminocarbonyl or lower alkylaminocarbonyl, wherein lower alkyl may be substituted, for example by carboxy, alkoxyearbonyl or aminocarbonyl· Esterified or amidated carboxy in a radical Εθ may also be a radical of the formula O -C E—( Y2 X4 )m A2 (Ida) m especially phenyl that is unsubstituted or substituted, for example by lower alkyl, hydroxy or etherifled or esterified hydroxy, such as lower alkoxy, or halogen, whilst nitrogen-containing heteroaryl having 5 or 6 ring members in the heterocyclic ring as corresponding substituent of Is monocyclic or bicyclic heteroaryl containing one or two nitrogen atoms as ring members· Etherifled mercapto as radical or is es< pecially lower alkylthio, whilst in a lower alkylamino stituted, for example by carboxy, lower alkoxycarbonyl or aminocarbonyl· * or N-lower alkylcarbamoyl, wherein lower alkyl may be substituted, for example by carboxy, lower alkoxycarbonyl or aminocarbonyl.

In the context of the present description, the general terse used above have the following meanings, radicals and compounds that are termed lower* containing up to and Including 7, preferably up to and including 4, carbon atoms: Alkyl is, for example, lower alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tributyl* sec.-butyl or tert.-butyl, also n-pentyl, neopentyl, n-hexyl or n-heptyl, or higher alkyl* such as straightchain or branched octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, nonadecyl or heneicosyl, and also higher alkyl of the triacontyl, tetracontyl, pentacontyl, hexacontyl, heptacontyl, octacontyl or nonacontyl series.

Lower alkoxy is, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert·butoxy.

Alkanoyloxy Is lover or higher alkanoyloxy, lower alkanoyloxy being, for example, formyloxy, acetoxy, propionyloxy or butyryloxy, whilst higher alkanoyloxy is, • 5 for example, lauroyloxy, myristinoyloxy, palmitoyloxy, stearoyloxy or behenoyloxy· Alkanoyloxy substituted by hydroxy, for example higher alkanoyloxy, is, inter • alia* mycoloyloxy.

Lower alkylamino is, for example, methylamino, lo ethylamino, n-propylamino or isopropylamino. Di-lower alkylamino is, for example, dimethylamino, dlethylamino or di-isopropylamino· Alkanoylamino is lower alkanoylamino, for example formylamino, acetylamino or proplonylamino, or higher alkanoylamino, for example lauroylamino, palmitoylamino, stearoylamino or behenoylamino.

An alkanecarboxylic acid is, for example, a lower alkanecarboxylic acid, such as acetic acid, propionic acid, butyric acid or oaprolc acid, or a higher alkane20 carboxylic acid, such as lauric acid, myrlstic acid, palmitift acid, stearic acid or behenic acid, whilst, for example, an alkanoic acid substituted by hydroxy may be, inter alia, mycollc acid· Alkene* and alkyne-carboxylic acids are, inter alia» lower alkene- and lower alkyne-carboxylic acids, such as acrylic acid, crotonic acid or tetrollc acid, or higher alkene- and higher alkyne-carboxylic acids, such as undecylenlc acid, oleic acid or elaidic acid· The acyl radical of a lower alkanecarboxylic acid, which is the group It in the c&ae when X represents the radical of the formula -N(R^)-, is especially acetyl or hydroxyacetyl, and propionyl· Cycloalkyl is, for example, cyclopentyl, cyclo• hexyl or adamant yl, whilst cycloalkenyl may be, for example, 1-cyclohexenyl, and cycloalkyl-lower alkyl may be, for example, 3-cholanylmethyl or the acyl radical of cholanio acid· Phenyl-lower alkanecarboxylic acids are, for example, phenylacetic acid or phenylpropionic acid, which may be substituted, for example as stated. « Halogen is preferably halogen having an atomic number of up to 35 and represents especially chlorine, but also fluorine or bromine· « Tri-lower alkylsilyl is especially trimethylsllyl· Alkylene is straight-chain or branched and is especially lower alkylene, for example methylene, ethylene, 1,2-propylene, 1,3-propylene or 1,6-hexylene, but also higher alkylene, such as 1,11-undecylene.

Alkenyl is lower alkenyl, for example allyl or methallyl, or higher alkenyl, for example decenyl.

Lower alkylthio is, for example, methylthio or ethylthio.

In an alkanoyl thio radical, the alkanoyl radical represents lower alkanoyl, for example acetyl, propionyl, butyryl or hexanoyl, but may also represent higher alkanoyl, for example lauroyl, myristinoyl, palmitoyl, stearoyl or behenoyl· Alkoxycarbonyl is lower alkoxycarbonyl, for example methoxycarbonyl, ethoxycarbonyl or tert.-butoxycarbonyl, or higher alkoxycarbonyl, for example dodecyloxy carbonyl, tetradecyloxycarbonyl, hexadecyloxycarbonyl or henelcosyloxycarbonyl· Lower alkylaminocarbonyl is, for example, methylaminocarbonyl or ethylaminocarbonyl, also carboxy-, lower alkoxycarbonyl- or carbamoyl-lower alkylaminocarbonyl, such as carboxyme thylamino carbonyl, 1-oarboxyethylaminocarbonyl, methoxycarbonylmethylaminocarbonyl or carbamoylmethylaminocarboziyl· Nitrogen-containing heteroaryl having 5 or 6 ring . · members in the heterocyclic ring is, for example, imidazolyl, such as 4-imidazoiyl, or indolyl, such aa 3-indolyl.

The hexopyranose compounds of the formula 1 may be in the form of isomeric mixtures or pure isomers.

The optionally substituted 1-hydroxy group of the formula -0-R^ may have the a- or the β-οοηflguration; the novel compounds of the formula I may, however, also be in the form of a mixture of the l-«and Ι-β-lsomers. in the compounds of the formula 1, the proton bonded to phosphorus via an oxygen atom can readily be replaced by a cation, that is to say, the compounds form salts. In this case, the compounds of the formula 1 may be ln salt form or in the form of a mixture of il 4 the free compounds and their salts. These are especially metal or ammonium salts, such as alkali metal and alkaline earth metal salts, for example sodium, potassium, magnesium or calcium salts, and ammonium salts, or salts with suitable organic amines, such as lower alkylamines, for example triethylamine. Compounds of the formula I having basic groupe, for example amino groups, are in the form of internal salts but, when there are more basic than acidic groups in a molecule XO of the formula 1, they may also form acid addition salts with external acids, such as salts with inorganic acids, such as mineral acids, for example hydrochloric, sulphuric or phosphoric acid, or organic carboxylic or sulphonic acids, for example acetic, maleic, fumaric, tartaric, citric, methanesulphonic or 4-toluenesulphonic acid. Only the pharmaceutically acceptable, non-toxic salts are used therapeutically.

The present invention relates especially to the use of: (a) compounds of the formula X in which X3, and X3 have the meanings given above, R^ represents a radical of the formula la in which η, Ζ1, Υ1, X3 and A1 have the meanings given above, each of R3, R3,3 and R3*3, independent25 ly of one another, represents hydrogen, acyl other than a radical, of the formula Ia in which n represents 1, or aliphatically substituted silyl, R3, R4, r\ r\ R® and R^° have the meanings given above, R® represents hydrogen or lower alkyl that is unsubstituted or substituted by free or etherified hydroxy or mercapto, by esterified hydroxy or mercapto other than a corresponding group of the formula Id or by free amino or substituted amino other than a corresponding group of the formula Id, by free, io esterified or amidated carboxy, by cycloalkyl, by carbocyclic aryl or by nitrogen-containing heteroaryl having 5 or 6 ring members in the heterocyclic ring, or and Εθ together represent unaubstituted or substituted 1,3- or 1,4-lower alkylene, and in which each q IT. of R and fi , independently of the other, represents free hydroxy or mercapto, etherified hydroxy or mercapto other than a radical of the formula Ie, or free amino or substituted amino other than a radical of the formula Ie, it being possible for free functional groups to be in protected form, and of pharmaceutically acceptable salts of such compounds; (b) compounds of the formula I in which Xx and X have the meanings given above, E represents a radical of the formula Ia in which £, z\ I3*, X^ and A1 have the meanings given above, each of e\ R3·2 and independently of one another, represents hydrogen, acyl other than a radical of the formula Ia in which n represents 1, or aliphatically substituted silyl, 4 5 7 8 XO R , R , R , R , R and R have the meanings given above, R6 represents hydrogen or lower alkyl that is unsubstituted or substituted by free or etherified hydroxy or mercapto, by esterified hydroxy or mercapto other than a corresponding group of the formula Id, by free amino or substituted amino other than a corresponding group of the formula Id, by free, esterified or amidated carboxy, by cycloalkyl, 2β by carbocycllc aryl or hy nitrogen-containing heteroaryl having 5 or 6 ring members in the heterocyclic ring, or S? and R® together represent unsubstituted or substituted 1,3- or 1,4-lower alkylene, and in which q m . each of R and R , independently of the other, represents free hydroxy or mercapto, etherified hydroxy or mercapto other than a radical of the formula Ie, or free amino or substituted amino other than a radical of the formula Ie, it being possible for free functional groups to be in protected form, and of pharmaceutically acceptable salts of such compounds; (c) compounds of the formula I in which X1 and X2 have the meanings given above, R^ represents a radical of the formula Ia in which £, Ζ1, I1, !? and A1 have the meanings given above, each of r\ R2 and R12, independently of one another, represents hydrogen, acyl other than a radical of the formula Ia in which £ represents 1, or aliphatically substituted silyl R8 and R10 R3, R4 have the meanings given above, R® represents hydrogen or lower alkyl that is unsubstituted or substituted by free or etherified hydroxy or mercapto, by esterified hydroxy or mercapto other than a corresponding group of the formula Id, by free amino or substituted amino other than a corresponding group of the formula Id, by free, esterified or amidated carboxy, by cycloalkyl, by carbocycllc aryl or by nitrogen-containing heteroaryl having 5 or 6 ring members in the heterocyclic ring, or R^ and R® together represent unsubstituted or substituted lower alkylene having 3 or 4 carbon atoms in the chain, and in which each of R7 and R , independently of the other, represents free hydroxy or mercapto, etherified hydroxy or mercapto other than a radical of the formula Ie, or free amino or substituted amino other than a radical of the formula £e, it being possible for free functional groupe to be in protected form, and of pharmaceutically acceptable salts of such compounds; or (d) conpounds of the formula I in which X1 and X2 have the meanings given above, each of R1, R2, R12 and R13, independently of one another, represents hydrogen, acyl other than a radical of the formula la in which n repre3 *" 4 5 sents 1, or aliphatically substituted silyl, R , R , R , R7, R8 and R10 have the meanings given above, R8 represents lower alkyl substituted by a radical of the formula Id, in *9 9 A O which m, Ε, Ζ , Y , X and A have the meanings given above, or R8 represents lower alkyl substituted by a group of the formula Ida in which m, Ε, Y2, x^ and A2 have the mean*** 9 11 ings given above, and in which each of R and R , independently of the other, represents free hydroxy or mercapto, etherified hydroxy or mercapto other than a radical of the formula Ie, or free amino or substituted amino other than a radical of the formula Ie, 2o it being possible for free functional groups to be in protected form, and of pharmaceutically acceptable salts of such compounds, and to novel pharmaceutical pre-, parationa containing these conpounds.

The invention includes especially the use of D-galac25 to-, D-manno- or particularly D-glucopyranose 2 compounds of the formula I, in which X and X have 2 12 13 the meanings given above, each of R , R , R and R , independently of one another, represents hydrogen, the acyl radical of an aliphatic, cycloaliphatic, aromatic or ataliphatic carboxylic acid, especially of an alkanecarboxylic acid having up to 90 carbon atoms, that is unsubstituted or substituted, for exanple by hydroxy, amino and/or alkanoylamino, such as higher alkanoylamino, a tri-lower alkylsilyl group or a I radical of the formula la in which £ and X^ have the meanings given above, Z1 represents thiocarbonyl or, preferably, carbonyl, represents lower alkylene which may be interrupted by iminocarbonyl or oxycarbonyl, and A1 represents a radical of the formula lb 1*5 or Ic, ln which Br represents an aliphatic, radical having at least 7 carbon atoms, R1® represents hydrogen and a17 represents 2-hydroxyethyl or 1,2-dihydroxyethyl, in which at least one hydroxy group is etherifled by an aliphatic radical having at least 7 and up to 90 carbon atoms or is esterified by a corresponding yg n j aliphatic acyl radical, or each of R and R , independently of the other, represents hydroxymethyl etherifled by an aliphatic radical having at least 7 ' and up to 90 carbon atoms or esterified by a corresponding aliphatic acyl radical, R^, R4, R? and R8 have the meanings given above, R^ represents hydrogen or lower alkyl which is unsubstituted or substituted by a radical of the formula Id ln which £, B and X4 2 have the meanings given above, Z represents thio-, carbonyl or, especially, carbonyl, I2 represents lower alkylene which may be interrupted by iainocarbonyl or oxycarbonyl, and A^ represents a radical of the formula lb or Ic in which R1^ represents an aliphatic radical having at least 7. carbon atoms, a16 represents hydrogen and R1? represents 2-hydroxyethyl or 1,2i dihydroxy ethyl, in which at least one hydroxy group —is esterified by an aliphatic radical having at least and up to 90 carbon, atoms or by a corresponding ali16 17 phasic acyl radical, or each of R and R , independently of the other, represents hydroxymethyl etherified by an aliphatic radical having at least 7 and up to 90 carbon atoms or esterified by a corresponding . aliphatic acyl radical, or R^ represents lower alkyl substituted by hydroxy or mercapto, by hydroxy or mercapto etherified by an aliphatic radical containing up to 90 carbon atoms, by hydroxy or mercapto that ia esterified by an aliphatic acyl radical containing up to 90 carbon atoms and is other than the group of the formula Id, by amino, by amino that is substituted by an acyl radical containing up to 90 carbon atoms and is other than a radical of the formula Id, by free carboxy, by lower alkoxycarbonyl, by carbamoyl, by lower alkylaminocarbonyl, by carboxy-lower alkylaminocarbonyl or by amidated carboxyl of the formula Ida, by phenyl that is unaubstituted or substituted by hydroxy, lower alkoxy or halogen, or'by imidazolyl or indolyl, or and r together represent 1,3- or 1,4-lower q τι alkylene, each of R and R , independently of the other, represents hydroxy, lower alkoxy, amino, lower alkylamino, carboxy-lower alkylamino, or a radical of the formula Ie, in which J? and have the meanings •i given above, Y represents lower alkylene which may be interrupted by iminocarbonyl or oxycarbonyl, and represents a radical of the formula lb or Ic, In which R^5 represents an aliphatic radical having at least 7 carbon atoms, R represents hydrogen and R ' represents 2-hydroxyethyl or 1,2-dihydroxyethyl, in which at least one hydroxy group is etherified by an aliphatic radical having at least 7 and up to 90 carbon atoms or is esterified by a corresponding aliphatic acyl radical, or each of H16 and R1?, independently of the other, represents hydroxymethyl etherified by an aliphatic radical having at least 7 and up to 90 carbon atoms or esterified by a corresponding aliphatic acyl radical, and represents hydrogen, carboxy, lower alkoxycarbonyl, carbamoyl, lower alkylaminocarbonyl or carboxy-lower alkylaminooarbonyl, it being possible for free functional groups to be in protected form, with the proviso that the compounds of the formula I have at least one radical A1, A2 or A5, and of pharmaceutically acceptable salts of such compounds, and to novel pharmaceutical preparations containing these compounds.

The invention relates especially to (e) the use of the D-galacto-, D-manno- or especially D-glucopyranose compounds of the formula I mentioned under (a), (b), (c) and (d) in which one, several or all of the * radicals X^ X2, R1, R2, R5, R4, R5, R6, R7, R8, R9, rIO, Β?-3·, R12 and R^ have the meanings given in the preceding paragraphs, and of pharmaceutically acceptable salts of such compounds· The invention relates more especially to (f) the use of D-glucopyranose compounds of the formula If r13-O. a CH, l/' R12-l· R^-CH 3 \ ,/ 1 la c—κ—c—CII h *7 H O R O ft >O-Rt O«C-R, I a -N—CH—CH. H (If) H ii •CH2-C-R^ in which R. represents hydrogen, lower alkanoyl or a a 1 group of the formula Ia in which £ represents 1, Z represents carbonyl, T1 represents lower alkylene which may he interrupted hy iminocarbonyl, X^ represents a group of the formula -0- or -39H-, and A^ represents a radical of the formula Ih or Xc, in which R ' represents an alkyl radical having from 7 to 30 carbon atoms that is unsubstituted or substituted hy hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, R16 17 represents hydrogen and R ' represents 2-hydroxyethyl or 1,2-dihydroxyethyl, the hydroxy groups in a radical R3*? being etherified by an alkyl radical having from 7 to 30 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 lo carbon atoms or being esterified hy an alkanoyl radical having from 7 to 90 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or each of R and R independently of the other, represents hydroxymethyl in which the hydroxy group is etherified by an alkyl radical having from 7 to 30 carbon atoms that is unaubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms or is esterified by an al kanoyl radical having from 7 to 90 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, represents lower alkanoyl, hydroxylower alkanoyl, benzoyl or a group of the formula Ia, in which £, Ζ3*, T3*, X^ and A3' have the meanings given above, R£ represents hydrogen or lower alkanoyl, represents hydrogen, alkanoyl or hydroxyalkanoyl having up to 90 carbon atoms, alkanoylaminoalkanoyl having up to 30 carbon atoms or a group of the formula Ia In which £, Z3*, T3', X^ and A3* have the meanings given above, and R? represent hydrogen or methyl, Βθ represents hydrogen or lower alkyl that is unsubstituted or substituted by free hydroxy or mercapto, lower alkoxy, lower alkylthio, alkanoyloxy or hydroxyalkanoyloxy having up to 90 carbon atoms, phenyl, imidazo35 lyl, indolyl or hy a group of the formula Id, in which £ represents 1, E represents a group of the formula 2 2 -0- or -3-, Z represents carbonyl, Y represents lover alkylene which may be interrupted by iminocarbonyl, X4 represents a group of the formula -0-, and A2 represents a radical of the formula lb or Ic, in which R1^ represents an alkyl radical having from 7 to 30 carbon Λ atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, 17 R represents hydrogen and & represents 2-hydroxy- * ethyl or 1,2-dihydroxyethyl, the hydroxy groups in a radical R ' being etherified by an alkyl radical having from 7 to 30 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms or being esterified by an alkanoyl radical having from 7 to 90 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or 16 17 each of R and R , independently of the other, represents hydroxymethyl In which the hydroxy group is etherified by an alkyl radical having from 7 to 30 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or is esterified by an alkanoyl radical having from 7 to 90 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, and each of the radicals Q 11 fi^ and R^ , independently of the other, represents hydroxy, lower alkoxy, amino, lover alkylamino, carboxy-lower alkylamino or a radical of the formula Ie R in which X-* represents a group of the formula -0- or -MH-, Y5 represents lower alkylene which may be interrupted by iminocarbonyl, X® represents a group of the formula -0-, and A~ represents a radical of the IB formulalb or Ic, in which R represents an alkyl radical having from 7 to 30 carbon atoms that is un- * substituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, R3*® represents hydrogen and R represents 2-hydroxyethyl or 1,2-dihydroxyethyl, the hydroxy groupe in a radical R^? being etherifled by an alkyl radical having from 7 to 30 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or being esterified by an alkanoyl radical having from 7 to 90 carbon atoms that is unsubs tituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or each of 10 and R3·?, independently of the other, represents hydroxymethyl in which the hydroxy group is etherifled by an alkyl radical having from 7 to 30 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or is esterified by an alkanoyl radical having from 7 to carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 q carbon atoms, Rf preferably represents one of the amino ii a groups and R^ preferably represents hydroxy, with the proviso that the compounds have at least one, and preferably only one, radical A , A or Ay, and of pharmaceutically acceptable salts thereof, and to novel pharmaceutical preparations containing these compounds.

The invention relates especially to (g) the use of the D-glucopyranose compounds of the formula 1 mentioned under (a), (b), (c) and (d) in which X1 represents a 2 group of the formula -NH-, X represents a group of the formula -0-, R4, R^, R® and R1® represent hydrogen, and R1, R2, R3, R6, R7, R9, R11, R12 and R13 have the meanings given in the foregoing section for the radicals Rj, R2, H3, R®, R7, R9, rJ1, rJ2 and h£3, respectively, and of pharmaceutically acceptable salts thereof· The invention relates chiefly to h) the use of compounds of the formula 1 in which X1 represents a group of the formula -H(R^)-, R1^ representing hydrogen or O^-alkyl, X represents oxygen, It represents hydrogen, lower alkanoyl, or a group of the formula la in which a represents 0 or 1, 21 represents carbonyl, 7^ represents lower alkylene which may be interrupted by iminocarbonyl, X^ represents oxygen and A3* represents 15 a radical of the formula lb or le in which R represents an alkyl or alkenyl radical having from 7 to 30 carbon atoms that Is unsubstituted or substituted by io hydroxy, amino and/or alkanoylamino having up to 22 17 carbon atoms, R represents hydrogen and R represents 2-hydroxyethyl or 1,2-dihydroxyethyl, at least one hydroxy group in a radical R being etherified by an alkyl or alkenyl radical having from 7 to 30 carbon J 5 atoms, or being esterified by an alkanoyl or alkenoyl radical having from 7 to 30 carbon atoms, or each of R and R ', independently of the other, represents hydroxymethyl in which the hydroxy group is etherified by an alkyl or alkenyl radical having from 7 to 30 2o carbon atoms, or is esterified by an alkanoyl or o alkenoyl radical having from 7 to 30 carbon atoms, R represents lower alkanoyl, hydroxy-lower alkanoyl, benzoyl or, independently of r\ R^2 and R1^, a group of the formula Ia as defined hereinbefore, each of r\ r\ R^, R? and R®, independently of one another, represents hydrogen, methyl or ethyl, R^ represents hydrogen, or lower alkyl that is unsubstituted or substituted by free hydroxy, free mercapto, lower alkoxy, lower alkylthio, alkanoyloxy having from 2 to 30 carbon atoms, alkenoyl oxy having from 6 to 30 carbon atoms, phenyl, 4-hydroxyphenyl, or by a group of the formula Id in which m represents 0 or 1, E represents oxygen or sulphur, 22 represents carbonyl, 72 represents lower alkylene that is unsubstituted or substituted by phenyl and may be interrupted by iminocarbonyl, X^ represents 13 oxygen and A , independently of A and A , represents a radical of the formula lb or Ic as defined hereino 11 before in this Specification, each of fr and R , independently of the other, represents hydroxy, lower alkoxy, amino, lower alkylamino, carboxy-lower alkylamino, lower alkoxycarbonyl-lower alkylamino, carbamoyl-lower alkylamino, or a radical of . the formula Ie in which X^ represents oxygen or RH, Y^ represents lower alkylene which may be interrupted by iminocarbong 3 1 lo yl, % represents oxygen and A-\ independently of Δ and A, represents a radical of the formula lb or Ic as defined hereinbefore in this Specification, R10 represents hydrogen, R represents hydrogen, lower alkanoyl or the same radical as R^\ and R1^ represents hydrogen, or alkanoyl or alkenoyl each having up to 30 carbon 2 atoms or, independently of R and R , a radical of the formula la as defined hereinbefore in this-Specif ication, with the proviso that the compounds contain at least one, and at most two, radicals selected from 12 3 the group A , A and A·7, and the use of pharmaceutically acceptable salts of these compounds· The invention relates especially to 1) the use of compounds of the formula I in which X1, represents the 2 1 group RH, X represents oxygen, R represents hydrogen 2 or lower alkanoyl, R represents lower alkanoyl, benzoyl or a group of the formula la in which £ represents 0 or 1, represents carbonyl, Y^ represents lower alkylene whioh may be interrupted by one or two iminocarbonyl groups, X^ represents oxygen, and A1 3o represents a radical of the formula lb or Ic in which R y represents an alkyl radical having from 7 to 22 16 1 7 carbon atoms, R represents hydrogen, and R ' represents 1,2-dihydroxyethyl in which each of the hydroxy groupe, independently of the other, is esterified by an alkanoyl or alkenoyl radical having from 10 to 22 carbon atoms, R^ represents hydrogen or methyl, R4, R , R' and R each represents hydrogen, R represents hydrogen, or lower alkyl that is unsubstituted or substituted by free hydroxy, alkanoyloxy having from to 22 carbon atoms, alkenoyloxy having from 6 to 22 . carbon atoms, phenyl or by a group of the formula Id in which £ represents 0 or 1, £ represents oxygen, Z 2 represents carbonyl, 7 represents lower alkylene that « is unsubstituted or substituted by phenyl and may be interrupted by iminocarbonyl, X4 represents oxygen and 1 5 A , independently of A and kr, represents a radical of the above-defined formula lb or Ic, each of R^ and R^3*, independently of the other, represents hydroxy, lower alkoxy, amino, lower alkylamino, e-carboxy-lower alkylamino*, α-lower alkoxycarbonyl-lower alkylamino, «-carbamoyl-lower alkylamino, or a radical of the formula Ie in which X^ represents the group NH, 7^ represents lower alkylene which may be interrupted by one or two iminocarbonyl groups, X^ represents oxygen *5 12 and k't independently of k and A , represents a radical of the formula lb or Ic defined hereinbefore, R3*8 τ ? represents hydrogen, R represents hydrogen, lower 1*3 13 alkanoyl or the same radical aa R , and R ' represents hydrogen, alkanoyl having from 2 to 22 carbon atoms, alkenoyl having from 6 to 22 carbon atoms or, indepen2 dently of R , a radical of the formula la as defined hereinbefore, and the use of pharmaceutically acceptable salts of these compounds.

The invention relates most especially to j) the use of compounds of the formula I in which I?- repre2 1 sente the group NH, X represents oxygen, R represents 2 hydrogen or C2_^-alkanoyl, R represents C^-alkanoyl or a group of the formula Ia in which £ represents 0 or 1, Z1 represents carbonyl, T1 represents lower alkylene which may be interrupted by one or tvo iminocarbonyl 1· groups, Hr represente oxygen, and A represents a 1C radical of the formula Xb or lc in which R represents an unbranched alkyl radical having from 12 to 18 carbon atoms, a16 represents hydrogen and R^7 represents 1,25 dipalmitoyloxyethyl or 2-oleoyloxy-l-palmitoyloxyethyl, R3 represents hydrogen or methyl, R , R’, R8 and each represents hydrogen, R® represents methyl, ethyl or isopropyl, each of which is unsubstituted or substituted by a radical of the formula Id IO in which m represents 0 or 1, £ represents oxygen, Z represents carbonyl, Y2 represents lower alkylene that is unsubstituted or substituted by phenyl and may be interrupted by one or two iminocarbonyl groups, X4 13 represents oxygen and A , independently of A and A^, represents a radical of the formula Ib or lc defined q ll hereinbefore, R represents amino, R represents c hydroxy or a radical of the formula Ie in which X 3 represents the group RH, Y-' represents lower alkylene which may be interrupted by one or two iminocarbonyl groups, X® represente oxygen and a\ independently of 1 2 A and A , represents a radical of the formula Ib or 12 Ic defined hereinbefore, R represents hydrogen, 13 acetyl or the same radical as R , and R represents 2 hydrogen, acetyl or, independently of R , a radical of the formula Ia as defined hereinhefore, and the use of pharmaceutically acceptable salts of these compounds.

The invention relates principally to k) the use of the above-mentioned compounds of the formula I in 12 3 which the radicals A , A and A , if present, represent radical of the formula Ic, and the use of pharmaceutically acceptable salts thereof.

The Invention relates especially to l) the use of the above-mentioned compounds of the formula I that carry only one phorphoryl substituent, that is in the 11 9 radical R or R , and the use of pharmaceutically acceptable salts thereof.

The Invention relates most especially to m) the use of the compounds of the formula 1 mentioned above under i) or k) that contain as the sugar moiety a derivative of D-glucose and that, in the case of asymmetric substitution, have at the C-R^ the (p)-configuration, at the C-Κθ the (L)-configuration, and at the C-N-Ηθ the (D)-configuration, and that carry (only) one phorphoryl substituent, that is in the radical R7 or R » wherein, in this phorphoryl substituent of the formula le, the radical A7 represents a radical of the formula lc, which is defined according to h) or j), and the use of pharmaceutically acceptable salts thereof.

The invention relates preferably to the use of compounds of the formula 1 that have at an asymmetrically substituted C(-H^)-atom the (D)-configuration, at an asymmetrically substituted C(-R^)-atom the (L)-confi figuration, and at the C(-N-R )-atom the (D) -configuration, and in which the sugar moiety is derived from (D)-glucose, Xx represents the group NH, X* represents oxygen, Η1, Β4, Β5, Β7, Β8, Β10, B12 and B13 each ό represents hydrogen, R represents Cn --alkyl or phenyl, R -represents hydrogen or C^-alkyl, R represents hydrogen, C^^-alkyl optionally substituted by hydroxy, methoxy, mercapto, methylmercapto or by halogen, phenyl or phenylmethyl each optionally substituted by hydroxy, methoxy or halogen, or heterocyclyl or heterocyclylmethyl each containing one or two aza atoms and having ring members, or R^ and Ηθ together represent triq methylene, one of the radicals R7 and Rx represents a radical of the formula Ie in which X^ represents the group NH or oxygen, represents C2_^-alkylene or a radical of the formula -u2-coo-U3 or H 3 -U-C-NH-U 3 9 *4 In which each of U. and U , independently of the other, represents C^^-alkylene that is unaubstituted or substituted by C^^-alkyl optionally substituted by hydroxy, lower alkoxy, mercapto or by lower alkylmer5 capto, or by phenyl or phenyl-lower alkyl each of which is optionally substituted by hydroxy, methoxy or halogen, or by heterocyclyl or heterocyclyl-(Clej-alkyl) each containing one or two aza atoms and having 5 or 6 ring members, X represents oxygen, and br represents a radical of the formula Ic in which R1^ represents hydrogen and R ' represents a 1,2-dihydroxyethyl or 2-hydroxyethyl group in each of which at least one of the hydroxy groups is esterified by an aliphatic C^6-20-carboxylic acid that is optionally singly or doubly unsaturated, or i3 etherified by an aliphatic ^12-18-^0°1101 is optionally singly or doubly unsaturated, and the other of the radicals R^ and represents hydroxy, lower alkoxy, amino, lower alkylamino or aminocarbonyl-lower alkylamino, and the use of pharmaceutically acceptable salts of such compounds· The invention relates most preferably to the use of compounds of the formula I that have at an asymmetrically substituted C(-R^)-atom the (D)-configuration, at an asymmetrically substituted C(-E^)-atom the (L)-configuration and at the C.(-U-R8)-atom the (D)configuration, and in which the sugar moiety is derived from (D)-glucose, X1 represents the group UH, X2 represents oxygen, R1, R^, R^, fi8, R10, R12 and R1^ each o represents hydrogen, R represents lower alkyl or phenyl, each of R^ and r\ independently of the other, represents hydrogen or methyl, R6 represents C, ,q ii X—4 alkyl, R represents amino and R represents a radical of the formula . II ι (—NH—u -C )r-NH-CH2-CH2-O-P-O-CH2 in which £ represents 0 or 1, U3, of the formula OH CH-O-Ra1 b CH2-Q-R represents a radical H-C CH.

CH-CH. Γ3 -CH(L) CHV CH-CH.

» ' -CH— Γ2 -CH— (L) or CH\2 CH-CH.

-CH— (L) a h and each of R and R , independently of the other, represents the acyl radical of a saturated aliphatic carboxylic acid having from 12 to 22 carbon atoms or of an unsubstituted aliphatic carboxylic acid having from 12 to 22 carbon atoms and containing one or two double bonds, and the use of pharmaceutically acceptable salts of such compounds* The invention relates above all to the use In accordance with the invention of the following compounds : the sodium salt of B^acetylmuramyl-L-alanyl-D-ieoglutamine-2- (1,2-dipalmitoyl—sn-glycero-4-hydroxyphosphoryloxy)-ethylamide, the sodium salt of N-acetyldesmethylmuramyl-L-alanyl-2"isoglutamine-2-( 1,2-dipalmit oyl-englyoero-3-hydroxyphosphoryloxy)-ethylamide, the sodium salt of N-aeetyldesmethylmuramyl-L-alanyl-g-isoglutamine-2-(l-palmitoyl-2-oleoyl-en-glycero-3*hydroxyphosphoryloxy)-ethylamide, the sodium salt of Nacetyldeamethylmaraayl-Ij-alanyl-D-iBoglutaminyl-Lalanine-2-( 1,2-dipalmitoyl^sn-glycero-3-hydroxyphosphoryloxy)-ethylamlde, N-acetylmuramyl-L-alanyl-Disoglutaminyl-L-alanine-2-(3-palmitoyl-rac-glycero-1hydroxyphosphoryloxy)-ethylaaide, the sodium salt of N-acetylmuramyl—I^-aminobtttyryl-g-ieoglutaminyl-Lalanine-2-(l ,2-dipalaitoyl-sn-glyoero-3-hydroxyphosphoryloxy)-ethylamide, the sodium salt of N-benzoylwuramyl-L-alaayl-D-isoglutaminyl-Ii-alanine-2-(l ,2dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy)-ethylamide, N-acetylmaramyl-L-alanyl-D-isoglutaminyl-L-alanine-2(tetradecyloxyfaydroxyphosphoryloxy )-ethylamide, H-acetylmnfaayl-If-alaxiyl-D-isogluteminyl-V-alanine-2(hexadecyloxyfaydroxyphosphoryloxy)-ethylamide, the sodium salt of N-acetylinaramyl-L-a-aminobutyryl-D-ieoglutaminylL-alanlne-2-[ (3R)-hydroxy-(2S)-pal>itoylamino-4toctadecenyloxyhydroxyphosphoryloxy]-ethylamidef the sodium salt of N-acetylmuramyl-L-a-aminobutyryl-Disoglutaminyl-Ir~alaaine-2-[ (3R)-hydroxy-{ 2S)-palmltoylaminooctadecyloxyhydroxyphosphoryloxy]-ethylamide f the sodium salt of N-acetylmiiramyl-I^alanyl-D-ieoglutaminylIf-alaaine-2- (cholest—5-en-3 β-oxyhydroxyphosphoryloxy ]ethylamide, the sodium salt of N-acetylmuramyl-L-O-£(B[2-( 1 -palmitoyl-2-oleoyl-en-glycero-3"hydroxyphosphoryloxy)-ethyl]-succittamoyl)-glyeylJ-aeryl-D-isoglutaalne, the sodium salt of H-acetylnormuramyl-L-O~(l,2-dipalmitoyl-rac-glycero-3-hydroxyphosphcryl)-seryl-J)isoglutamine, the sodium salt of N-acetyl-6-O-([l,2dipalmitoyl-rac-glycero-3-hydroxyphos phoryloxy ]5 acetyl)-norrauramyl-L-danyl-D-isoglutamine , the sodium salt of N-acetyl-6-0-(l, 2-dipalmitoyl-racglycero-3-hydroxyphoephoryloxy)-normuraayl-L-alanylD-isoglutamine» the sodium salt of N-[N-[2-(l,2d ipalmi toyl-sn-glycero) -3-hydroxyphos phoryloxy ]lo ethyl^-succinamoylmuramyl-Ij-alanyl-D-isoglutaraine, the sodium salt of H-acetyl-6-0-[H~[ 2-(1,2-dipalmit oyl-sn-glyc ero-3-hydroxy phosphoryloxy) -ethyl ] succinamoyl^ -muramyl-L-o-aminobutyryl-D-isoglutamine, the sodium salt of R-acetylnormuramyl-L-O-[N-[2-tetra15 decyloxybydroxyphosphoryloxy)-ethyl]-succinamoyl3 seryl-D-isoglutamine, the sodium salt of H-acetylmuramyl-L-O- [[R-(l-palmitoyl-2-oleoyl-sn-glycero-3'" hydroxy phosphoryloxy ) -ethyl ] -succ inamoy 1-L-pheny lalanylj -seryl-D-isoglutamine, the sodium salt of R-acetyl20 muramyl-L-O- (hexadecy loxyhydroxyphosphoryl) -seryl-Disoglutamine and the sodium salt of N-acetylmuramylL-0-(l, 2-dipalraitoyl-3-sn-glyeerohydroxyphosphoryl )seryl-D-isoglutamine.

The invention relates especially to the use of the compounds of the formula 1 described in the Examples, and of the pharmaceutically acceptable salts thereof, and above all to the use of H-acetylmuramylL-alanyl-D-isoglutaminyl-^-alanine-2-( 1,2-dipalmitoylsn-glycero-3-hydroxyphosphoryloxy ) -ethylamide, espe30 daily the sodium salt of this compound, referred to hereinafter as compound I· The following Examples illustrate the invention but do not limit the invention in any way.

Example 1: Groups of 30» 40 or 50 female MF-2f SPF mice each 5 having a body weight of 14-16 g, or of 12-14 g in the case of tests with herpes simplex 1 viruses» are infected intranasally, under light anaesthesia using a mixture of equal parts of ether» ethanol and chloroform» with lethal doses (approximately number of IO plaque-forming units [PFU] see Table 1) of the under- mentioned virus strains in the form of 0.05 ml in each case of a suspension of the viruses.

At the time indicated below (days) in relation to the day of infection, 10 or 20 of these mice are administered once (single dose) the quantities indicated in Table 1 of the active ingredient, the sodium salt of N-acetylmuramyl-^-alanyl-D^isoglutaminyl-t^-alanine-2- (1,2-dipalmitoyl-sn-gLycero-3hydroxyphosphoryloxy)-ethylamide (compound I), in 0.05 ml or 0.1 ml of phosphate-buffered salt solution (PBS) or in 0.2 ml of a 0.05 % by weight solution of sodium carboxymethylcellulose in double-distilled water, by means of intranasal, intravenous or oral administration respectively, in the manner indicated in Table 1.

The remainder of the above-mentioned mice, that is 20 or 30, serve as the control, that is to say they either receive no treatment or are given a placebo.

The intranasal administration of compound I is 30 effected under light anaesthesia using a mixture of equal parts of diethyl ether, ethanol and chloroform.

Table 1 Virus [PFU] Mode of administration Time of administration [days] - : before infection + : after infection Perceni in dep< [mg/kg statist 500 ;age of sndence. 1 Lical si 1OO mice sv on the gnifica 20 trviving quantxt ince XP< IO 20 day y of ac = 0.05, 1‘rs afte :tive i ’"p-O 0.1 r infection ng red lent .Ol (Vierfelder test) O » control Influenza A/ Victoria/3/75 (H3N2) (mouse adapted) [2xlO3-lxlO4 PFU] 1 intravenous -7 80** 90** 30 20 -5 80« 80« 30 -1 80« ao« 7OX 0 90« 1OO« 70* - +1 90« 7OX 60 intranasal -14 60 7O(X> 8OX 40 -7 ioo« 100** 80X oral ! +3 70« 90** 80« 15 1 +7 1OO« ioo« 70« »u Table 1: (continuation) Virus [PFU] Mode of administration Time of administration [days] - : before infection + : after infection Percentage of mice surviving 20 days after infection in dependence on tbe quantity of active ingredient [mg/kg] statistical significance P£ 0.05, 500 100 Influenza ft/ intravenous 66' USS (H1N1 (mouse* adapted) [3x10^-1x10' PFU J XX 50' xx.

PX0.01 (Vierfelder test) 0.1 control XX +2 +6 100' XX xx XX xx XX Influenza A/ Texas/1/7 7( H^Nj (mouse-adapted) [2x10°-lxio1 PFU] intranasal xx 40' (X) 1OO oral +7 (x) XX XX Continuation of Table 1 Virus [PFU] Mode of administration Application time Percent 500 age aur\ 1OO 'Ivors 20 10 1 0.1 0 Influenza B / Hong Kona/5/72 [3xlOS-lxlO6 PPU] intravenous -7 9OX 70 70 42 -5 90* 100" 8O(X) -2 loo** 9OX lOO** -1 loo** 9OX 8Oix) o 100" 1OO** 9OX +1 80*χϊ 8Ο*ΧΪ 60 +2 lOO** 70 9OX +6 lOO™ 8O*x) 70 intranasal -7 100" 60 8OX 30 oral +3 50x 5OX 15 +7 80** 90** 5OX Influenza B / Ann Arbor (Ms·Lu.25.Russ) (mouse-adapted) [lxlo1 PFU] intranasal -14 50X 20 20 O -7 80*" 5OX 20 j oral 43 ICO** 90^ so** I ! 1 15 , 1 1 +7 lOO** i 80** 80** 1 Continuation of Table 1 Virus [PFU] Mode of administration Application time Percentage survivors 500 100 20 10 1 0.1 0 Encephalomyo- carditis [lxloLixio2 PFU] oral o eox lOO** 60 +2 60 80* 90** 30 +4 lOO** 7Otx^ 90** Heroes Simplex l/TUP [2xlO4 PFU] intranasal -7 70X 6OX -_X 60 20 Heroes Simolex l/virtpe intranasal -7 90X 100X 70 40 [2xlO3 PFU] Ml· The course of some of the above-described infections over a period of time is illustrated in Figures 1 and 2. * The great superiority of the phosphoryl compounds of the formula 1 over muramyl peptides, such as N-acetylmuramyl-Ir-alanyl-D^glutamine-n-butyl ester * (compound II) is demonstrated, for example, by the fact that in the case of the above-mentioned tests carried out for comparison purposes, on oral administration of mg of the latter compound on day +7 all the mice die from infection with Influenza A/Texas/1/77, whilst on administration of the same quantity of the phosphorylmuramyl peptide compound I at the same time, as can be seen in the Table, 65 % of the mice survive the infection.

Furthermore, on intranasal administration of 1 mg/kg of compound II on day -7 it is not possible to detect any kind of protective action in the case of infection with Influenza A/Texas/1/77, whilst on administration of the same quantity of compound I at the same time 90 % of the mice survive the infection.

It is also not possible to detect any kind of protective action on intranasal administration of 10 mg/kg of compound II on day -7 in the case of intranasal infection with Herpesvirus hominis 1/TUP, as can be seen from Figure 3.

Example 2 The number indicated in the following Table of female albino guinea pigs of the Pirbright strain <150— 180 g body weight) are infected intravaginally with λ/IO4 PFU (plaque-forming units) of Herpesvirus hominis 2/Angelotti, cultivated in HEL (human χ V* embryonal lungs) cells, as described in B. Lukas et al,. Arch. ges. Virusforsch. 44, 153—155 (1974).

At the time indicated in the following Table (the XO time difference in days in relation to the day of infection, - [minus] indicating a time before infection) the number N of guinea pigs indicated in Table 2 are treated intravaginally with a single dose of in each case 0.1 ml of a gel containing the concentration of comppund I indicated in Table 2.

The gel without active ingredient has the following composition: 2.25 ft sodium carboxymethylcellulose (Hercules, USA) 2o 10 ft glycerine made up to 100 ft with bi-distilled water.

The effect of the treatment can be seen in Table 2.

The symptoms occurring in untreated animals are 25 described in B. Lukas et al., Arch. Virol. 49, 1-11 (1975).

Table 2 Effect on local synqptoras in the topical chemotherapy of Herpes genitalis in guinea pigs (statistical significance XP< 0.05, <.0.01 in the Fisher test) Active ingredient concent rat ion w Treatment time [daya] N Animals [%] with regression of symptoms of > 66% on day Symptom-free animals [%] on day 10 12 14 21 34 7 10 12 14 1.0 -7 14 29 79« 71« 93« 21 57X 86« 86X 100X 0.1 -7 14 21 57x 86** 1OO« 43x 64« 86« 86** 1OO« 1.0 +4 14 79« 79« 86« 93« 36 64« 79** 86« 1OO« 0.1 +4 13 62« es** 1OO« 93** 70** 77« 85« 1OO« loo** o (placebo) +4 14 o 0 o O O 0 o 0 0 control (untreated) 20 0 0 0 O 0 o o _ o 20 Of o Example 3: Eye drops Compositions compound 1 0.10 mg boric acid 30.00 mg sodium tetraborate. 0. 10 mg benzalkonium chloride 0.20 mg water for injection to make up to 1.00 ml Preparation: The boric acid, sodium tetraborate and IO benzalkonium chloride are dissolved while stirring at room temperature under aseptic conditions in a portion of' the above-mentioned quantity of water for injection. CGP 19835 is then dissolved in the resulting solution, and water for injection is added to make up to the final volume of 1.0 ml.

The solution, or a portion or a multiple thereof, is filtered through a membrane filter and introduced into cleaned containers. Suitable containers are, for example: - flexible plastics containers (5 ml or 10 ml) having a dropping attachment, - glass containers (5 ml or 10 ml) having a glass of plastics dropping pipette and an elastomeric pipette filler, or - plastics single-dose pipettes (contents 1 - 2 drops).

I Example 4: Non-aqueous single dose for nasal administration.

♦ Composition: compound I 0.03 mg * Miglyol 812 to make up to 30.00 mg Preparation: 0.03 mg of compound I is dissolved under aseptic conditions in 29.97 mg of Miglyol 812.

This solution is introduced into a commercially IO available single-dose nasal applicator, for example an applicator according to US Patent No. 3 739 951, which is attached to an aerosol-container before use.

Example 5: Nose drops: Composition: I II compound I 0.15 mg 0.10 mg thiomersal 0.02 mg - sodium monohydrogen phosphate.2h20 0. 30 mg 0.30 mg sodium dihydrogen phosphate· 121^0 10 · 10 mg 10.10 mg benzalkonium chloride - 0.10 mg disodium salt of ethylenediaminetetraacetic acid (EDTA) 0.50 mg 0.50 mg sodium chloride 3.70 mg 4.50 mg demineralised water 988.30 mg 987.60 mg pH value: 5.0 i 0.3 5.0 ± 0. lowering of freezing point At - 0.5I°C - 0.56°C Preparation: While stirring at room temperature, the sodium dihydrogen phosphate, disodium monohydrogen phosphate, sodium chloride, thlomersal and the disodium salt of EDTA are dissolved in a portion of the above-mentioned quantity of demineralised water Compound I is then dissolved in this solution and the whole is supplemented with the remaining demineralised water.

The solution, or a portion or a multiple thereof, is filtered through a membrane filter and introduced into cleaned containers.

Suitable containers are, for example: a) glass or plastics containers (5 ml or 10 ml) having a glass or plastics pipette with an elastomeric pipette filler b) compressible plastics bottles having a central tube and a plastics spraying head • c) single-dose plastics containers (contents 2-3 drops), or * glass or plastics bottles that are provided with a standardised pumpable dosing spray made of plastics (no propellant).

Example 6: Gel Composition: compound I 0.01 9 glycerine 85 ft 10.00 9 methyl paraben 0.12 9 propyl paraben 0.03 9 sodium carboxymethylcellulose (high viscosity) 2.50 9 demineralised water 87.34 9 Preparation: The methyl paraben and propyl paraben are dissolved in a portion of the hot demineralised water.

The sodium carboxymethylcellulose is then incorporated into the resulting solution while stirring vigorously, while stirring, the glutinous product is allowed to swell. After cooling, the glycerine and a solution of the active ingredient, compound 1, in the remaining water are then added to this product. » Example 7: Cream Compositions f/5 compound 1 0.10 9 sorbitan monostearate 0.60 9 cetyl alcohol 3.00 9 isopropyl palmitate 2.00 g methyl paraben 0.12 g paraffin oil, viscous 10.00 g PEG (20)-sorbitan monostearate 4.40 g propyl paraben 0.03 g JO % solution of crystalline sorbitol 6.00 9 in demineralised water stearic acid 9.00 g demineralised water 64.67 g · Preparation: The fatty phase, comprising sorbitan monostearate, cetyl alcohol, stearic acid, PEG (20)-sorbitan monostearate, isopropyl palmitate and paraffin oil, is . melted. The methyl paraben and propyl paraben are then 20 dissolved in a portion of the hot demineralised water.

The sorbitol solution is added to the aqueous phase. While stirring, the aqueous phase is then added at . approximately 75°C to the fatty phase. The cream base is then allowed to cool while stirring. A solution of the active ingredient, compound I, in the remaining water is then added to the cream base at approximately 40°C.

Example 8: Nasal ointment Compositions compound 1 0.03 g paraffin oil, viscous 20.00 g white petroleum jelly 30.00 g wool fat, anhydrous 40.00 g demineralised water 19.97 g Pr epara t ions The fatty phase, comprising paraffin oil, petroleum jelly and wool fat, is melted. The aqueous solution of the active ingredient is incorporated into the fatty phase at approximately 50°C.

·# Example 9: Skin ointment Composition compound 1 0.25 g sorbitan sesquioleate 10.00 g white beeswax 5.00 g cetyl alcohol 2.50 g methyl paraben 0. 15 g paraffin oil, viscous 20.00 g propyl paraben 0.02 g stearyl alcohol 2.50 g white petroleum jelly 40.00 g demineralised water 19.58 g Preparation: The fatty phase, comprising sorbitan sesquioleate, white beeswax, cetyl alcohol, paraffin oil, stearyl alcohol and white petroleum jelly is melted. The methyl paraben and propyl paraben are then dissolved in the main quantity of the water at elevated temperature.

• The aqueous phase is incorporated into the fatty phase at approximately 80°C. A solution of the active ingredient, compound I, in the remaining water is added • to the resulting ointment base at approximately 40°C.

Example 10; Lipstick Composition; compound 1 1.00 g polyethylene glycol having an average molecular weight of 400 15.00 g polyethylene glycol having an average molcular weight of 1000 83.00 g polyethylene glycol having an average molecular weight of 4000 1.00 g Preparation: The active ingredient is finely dispersed in the molten polyethylene glycols. The viscous melt is poured into suitable lipstick cases and left to harden.

- Example Us Preparation of compound I A solution of 1.5 mmol of N-acetylmuramyl-L-alanylD-isoglutaminyl-L-alanine-N-hydroxysuccinimide ester in 5 ml of dimethyl acetamide is added dropwise to a solution of 1 mmol of 2-(1,2-dipalmitoyl-sn-glycero-3hydroxyphosphoryloxy)-ethylamide and 3.5 mmol of N' ethyImorpholine in 25 ml of chloroform:methanol:water » 65:25:4. After stirring for 8 hours at room temperature the reaction is complete. 130 ml of water are added to the reaction mixture. Chloroform and portions of the methanol are distilled off under reduced pressure. The aqueous solution is filtered through a millipore filter made of Teflon (pore size 5 um). The filtrate is dialysed, while stirring, in an Amicon ultrafiltration cell through an Amicon YM 10 membrane in a diafiltration process firstly against water (400 ml), then against 0.1M sodium phosphate buffer - 0.1M NaCl, pH 7 (200 ml), and subsequently against water (850 ml). The internal dialysate is filtered through a millipore filter, pore size 0.45 um, and freeze-dried, yielding the sodium salt of N-acetyl15 muramyl-L-alanyl-D-isoglutaininyl-I^-alanine-2- (1,2dipalraitoyl-sn-glycero-3-hydroxyphosphoryloxy)ethylamide hydrate.

I Example 12: Groups of 20 female Tif:MF-2f (SPF) mice each having a body weight of 14-16 g are infected intravenously, under light anaesthesia using a mixture of equal parts of diethyl ether, ethanol and chloroform, with 2 χ 103 PFU vaccinal virus IHD in the form of in each case 0.1 ml of a suspension of the virus in beef heart infusion broth. of these mice from each of the above-mentioned groups are treated on the fourth or sixth day after infection, that is to say on day +4 or +6 (administration day), with a single oral administration of 1 mg/kg of compound I in 0.2 ml of a 0.05 % by weight aqueous solution of sodium carboxymethylcellulose.

The remaining 10 mice from each of the abovementioned groups serve as the controls and receive a 9 placebo.

On the seventh, ninth, tenth and twelfth day after infection the number of tail lesions in the mice is determined, this being carried out substantially as described by J.J. Boyle, R.F. Haff and R.C. Stewart in Antimicrobial Agents and Chemotherapy, 536-539 (1966), and it should be noted that the first tail lesions can be identified only on the sixth or seventh day. The results can be seen in Table 3: Table 3s Day of administration Number of tail lesions (mean + standard deviation) on day +7 +9 +1O +12 +4 0.9+0.7* 0.9+0.9* 0.9+1.4* O.2+0.4* +6 1.1+1.4* 0.9+1.6* 0. 3+0.7* 0.5+1.0* control 4.3+1.9 4.3+1.9 5.9+1.9 4.6+1.8 * statistical significance P< 0.01 (Student's T-test) Example 13: Groups of 50 - 54 female albino guinea pigs of the Pirbright strain (150—180 g body weight) are infected intravaginally with 1 χ 103 PFU of the neurotropic virus strain Herpes simplex 2/MS in a manner analogous to Example 2. In the case of the Alabama strain, on the third day after infection 15 to 18 of these guinea pigs are administered orally a single dose, as indicated in Figure 4, of compound I in 0.2 XO ini of a 0.005 % by weight aqueous solution of sodium carboxymethylcellulose. In the case of the MS strain, . on the seventh day before infection 17 to 19 of the above-mentioned guinea pigs, under light anaesthesia using a mixture of equal parts of diethyl ether, X5 ethanol and chloroform, are administered intranasally a single dose, as indicated in Figure 5, of compound 1 in 0.2 ml of a 0.005 % by weight aqueous solution of sodium carboxymethylcellulose.

The control groups each comprise 35 animals and 2o. receive no treatment (Fig. 4) or are given a placebo (Fig. 5). The results are shown in Figures 4 and 5, respectively.

Example 14: Groups of 30 or 34 female Tif:MF 2f (SPF) mice 25 each having a body weight of 14-16 g are infected intranasally under light anaesthesia with from 10 to 50 PFU of Parainfluenza Virus 1 (Sendai)/52 (mouseadapted, stored at -70°C in the form of a mouse-lung suspension in ampoules). For the above-mentioned 30 anaesthesia there is used a mixture of equal parts of diethyl ether, alcohol and chloroform.

At the time indicated in Figures 6 and 7, 10 (in the case of Fig. 6) and 14 (in the case of Fig. 7) of these mice are administered once the quantities indicated in the Figures of compound I in 0.2 ml of 0.005 % by weight sodium carboxymethylcellulose in double-distilled water in the manner indicated in the , Figures, in the case of intranasal administration of the active ingredient before infection under anaesthesia using a mixture of equal parts of diethyl ,, ether, alcohol and chloroform and in the case of intranasal administration of the active ingredient after infection under anaesthesia using Nembutal (0.5 IO mg/mouse, intraperitoneal), followed after 20-25 minutes by intranasal administration by drip of 0.02 ml of 1 % aqueous clnchocaine hydrochloride solution.

The remaining 20 mice from each of the above-mentioned groups serve as the control. The control animals either receive no treatment or are given a placebo.

The action of compound 1 can be seen from Figures 6 and 7.

Example 15: Groups of 30 female Tif:HF-2f (SPF) mice having a body weight of 14-16 g are infected intranasally under light anaesthesia, using a mixture of equal parts by volume of diethyl ether, ethanol and chloroform, with lethal doses (approximately LDgQ_g0) of the virus strains indicated in Table 4. At the time shown in Table 4 [days in relation to the day of infection] 10 of these mice in each case are administered once (single dose) with the quantity, the active ingredient, n . and in the manner of administration, all as indicated in Table 4.

The active ingredients are: * the sodium salt of N-acetyl-6-0-{[N-2-(1,2-dipalmitoylsn-glycero-3-hydroxyphosphoryloxy)-ethyl]-succinamoyl^normuramyl-L-alanyl-D-isoglutaraine (III), · ί·3 the sodium salt of N-propionyldesmethylmuramyl-Lalanyl-D-isoglutarainyl-L-alanine-2-(1,2-dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy)ethylamide (IV), 5 the sodium salt of N-acetyl-1,4,6-0-triacetylmuramyl-L^alanyl-D^isoglutaminyl-L-alanine-2(1,2-dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy)ethylamide (V), the sodium salt of N-acetylmuramyl-L-alanyl10 D-isoglutamine-2-(1,2-dipalmitoyl-sn-glycero-3hydroxyphosphoryloxy)-ethylamide (VI), and the sodium salt of N-acetylmuramyl-L-alanylD-isoglutaminyl-y-oxymethylcarbonyl-2-(1,2dipaImitoyl-sn-glycero-3-hydroxyphosphoryloxy)15 ethylamide (VII)· The remaining 20 mice in each group serve as the control, that is to say instead of the active ingredient they receive a placebo (0.005 % by weight of . sodium carboxymethylcellulose in double-distilled 2o water).

The results of the test are shown in Table 4.

Table 4 Active ingredient Virus Mode of administration Time of administration Percentage of mice surviving 23 days after infection in dependence upon the quantity of active ingredient [mg/kg] 1OO 10 1 0.1 0 (placebo) III Influenza A/Texaa/1/77 3n2) oral +7 60 60 60 30 IV Influenza A/Texaa/1/77 (h3»2) oral +7 60 30 V Influenza A/Texas/1/77 (h3n2) oral +7 50 40 15 VI Influenza A/Texas/1/77 (h3n25 oral +7 60 60 80 15 VII Influenza A/Texas/1/77 (h3n2) oral +7 60 40 15 Example 16: Manufacture of 1000 tablets containing 0.5 ft of active ingredient Composition for 1000 tablets: compound I 0.5 g lactose, ground 43.0 g corn starch 52.0 g Pharmacoat 603® (hydroxypropyl- 3.0 g methylcellulose containing 28-30 % methoxy groups, supplied by Shinetsu Chemical Company, Tokyo, Japan) Aerosil® (colloidal silica, supplied 1.0 g by oegussa, Frankfurt, Federal Republic of Germany) magnesium stearate 0.5 g Preparation: Compound 1 and )5 g of lactose are premixed. The resulting premix is mixed with 28 g of lactose and 47 g of corn starch. Using the resulting mixture and an aqueous solution of the Pharmacoat a composition suit20 able for granulation is prepared and is granulated, dried and ground. 5 g of corn starch, the Aerosil and magnesium stearate are mixed in and the whole is pressed to form 1000 tablets each weighing 100 mg.

The compacts can be provided with a coating that is resistant to gastric juices in a manner known per se.

Example 17: Active ingredient in the form of a dry lyophilised substance 0.5 mg of compound I and 500 mg of mannitol GO (pyrogen-free) are dissolved in water for injection and sterile-filtered through a membrane filter. The sterile-filtered solution is introduced under aseptic conditions into a sterilised glass ampoule or into a glass phial and freeze-dried. After lyophilisation the ampoule is sealed or the phial is sealed with a rubberelastomeric seal and aluminium cap.

Example 18; Single-dose pipette with nose drops A 0.05 % solution of compound 1 in 1,2-propylene glycol, benzyl alcohol or ethanol or in a mixture of 1,2-propylene glycol and polyethylene glycol having an average molecular weight of 300 is prepared.

The solution is filtered and introduced into single-dose pipettes made of deformable plastics. The single-dose pipettes contain the quantity of nose drops required for one application, that is to say they each contain 0.1 ml of the above solution.

Claims

1. · A pharmaceutical composition for enteral or parenteral application, which composition contains, aa sole active ingredient, an effective amount, but less than 1 Z by weight, of a compound of the 5 formula X in which the sugar moiety la derived from (D)-galactose, (D)-mannooo or (D)-glucose, which compound has at an asymmetrically substituted 3 C(-R ) atom the (D)-configuratlon, at an asymmetrically substituted IO C(-R^) atom the (L) -configuration and at an asymmetrically substig tuted C(-R ) atom the (D)-conflguratlon, and in which compound 1 2 ~ each of X and X independently of the other represents a group of the formula -0- or -N(R 14 )-, R 14 representing 12 12 13 hydrogen or lower alkyl, each of R , R , R and R 15 independently represents a radical of the formula la -(•zW-X^n-A 1 (Ia) in which n represents 0 or 1, Z 1 represents carbonyl or thiocarbonyl, Y 1 represents unsubstituted or substituted alkylene which may be interrupted by iminocarbonyl or oxycarbonyl, X represents a group of the formula -0- or 14 14 -N(R )-, wherein R has the meaning given above, and A represents a radical of the formula Ib P-O-R OH in which represents radical having at least group of the formula Ic (Ib) an aliphatic or cycloaliphatic 7 carbon atoms, or A^ represents a 0 R 16 Π I -P-O-CH 1 *17 OH R ' in which R^® represents (Ic) hydrogen and R^ 7 represents 2. -hydroxyethyl or 1,2-dihydroxyethyl, wherein at least onq hydroxy group is esterified or etherified by a radical having at least 7 carbon atoms, or In which each of R 1 ® and r!7 independently of the other represents esterified or etherified hydroxymethyl, the esterifying or etherifying 1 2 radicals having at least 7 carbon atoms, or each of R , R , 12 13 R . and R independently represents hydrogen, acyl other than a radical of the formula Ia in which n represents 1, or aliphatically substituted silyl, each of R^, R 4 R 5 , R 7 8 6 and R° independently represents hydrogen or lower alkyl, R° represents hydrogen or lower alkyl that is unsubstituted or substituted by a group of the formula Id 2 2 A 7 -Ε-(Ζ Ζ -Υ-χ\-Α Ζ (Id) in which m represents 0 or 1, E represents a group of the formula -0-, -S- or -N(R^ 4 )-, R^ 4 having the meaning given 2 ‘2 above, Z represents carbonyl or thiocarbonyl, Y represents unsubstituted or substituted alkylene which may 4 be interrupted by iminocarbonyl or oxycarbonyl, X 14 14 represents a group of the formula -0- or -N(R )-, R 2 5 having the meaning given above, and A represents a radical . of the formula lb or Ic; pr by free or etherified hydroxy or mercapto, by esterified hydroxy or mercapto other than a group of* the formula Id, by free amino or substituted amino other than a group of the formula Id, by free, IQ esterified or amidated carboxy, by cycloalkyl, by carbocyclic aryl or by nitrogen-containing heteroaryl having 5 or 6 ring members in the heterocyclic ring, or R 5 and R^ together represent unsubstituted or substituted 1,3- or 9 11 1,4-lower alkylene, each of R and R independently of 15 the other represents a radical of the formula Ie -X 5 -Y 3 -X 6 -A 3 (Ie) in which X^ represents a group of the formula -0-, -S- or and Χθ represents a group of the formula -0- or -N(rI^)-, in each case R^ having the meaning given abovej 3 20 Ύ represents unsubstituted or substituted alkylene which may.be interrupted by iminocarbonyl or oxycarbonyl, and A represents a radical of the formula lb or Ic, or free hydroxy pr mercapto, etherified hydroxy or mercapto other than a radical of the formula Ie, or free amino or 25 substituted amino other than a radical of the formula le, . and represents hydrogen or free, esterified or amidated carboxy, with the proviso that radicals qualified by the term ’’lower 11 contain up to and including 7 carbon atoms and that the compounds of the formula I have at least one 30 radical A , A or A and/or a pharmaceutically acceptable salt thereof, together with a pharmaceutical carrier.

2. A composition according to claim 1, which contains a . 1 2 12 compound of the formula 1. in which each or R , R , R and R independently represents hydrogen, the acyl radical of an aliphatic, cycloaliphatic, aromatic or araliphatic carboxylic acid having up to 90 carbon * atoms, tri-lower alkylsilyl, or a radical of the formula Ia in which ri and X 3 have the meanings given in claim 1, represents carbonyl, Y^ represents lower ( alkylene which may be interrupted by iminocarbonyl or oxycarbonyl, and A^ represents a radical of the formula lb or Ic in which represents an aliphatic 1 β radical having at least 7 carbon atoms, R represents hydrogen and represents 2-hydroxyethyl or 1,2dihydroxyethyl, in which at least one hydroxy group is etherified by an aliphatic radical having at least 7 and up to 90 carbon atoms or is esterified by a corresponding aliphatic acyl radical, or each of and R?\ independently of the other, represents hydroxymethyl etherified by an aliphatic radical having at least 7 and up to 90 carbon atoms or esterified by a corresponding aliphatic acyl radical, R 6 represents hydrogen or lower alkyl that is unsubsituted or substituted by a radical of the formula Id in which m, E and have the meanings given in claim 1, Z 2 represents carbonyl, Y represents lower alkylene which may be Interrupted by iminocarbonyl or oxycarbonyl, and A 2 represents a radical of the formula lb or Ic in which R^ 5 represents an aliphatic radical having at least 7 carbon atoms, R^ represents hydrogen and R 1 ? represents 2-hydroxyethyl or 1,2-dihydroxyethyl, in which at least one hydroxy group is esterified by an aliphatic radical having at least 7 and up to 90 carbon atoms or by a corresponding aliphatic acyl radical, or each of R ie and R 17 , independently of the other, represents hydroxymethyl esterified by an aliphatic acyl radical haying at least 7 and up to 90 carbon atoms, or R 6 represents lower alkyl substituted by hydroxy or 5 mercapto, by hydroxy or mercapto etherified by an aliphatic radical containing up to 90 carbon atoms, by hydroxy or mercapto that is esterified by an aliphatic acyl radical containing up to 90 carbon atoms and is other than the group of the formula Id, by amino, by IO amino that is substituted by an acyl radical containing up to 90 carbon atoms and is other than a radical of the formula Id, by free carboxy, by lower alkoxycarbonyl, by carbamoyl, by lower alkylaminocarbonyl, by carboxy-lower alkylaminocarbonyl or by amidated carboxyl of the 1.5 formula II 2 4 2 -C-E-(Y 2 4 2 in which m, Ε, Υ , X and Λ have the meanings given in claim 1, by phenyl that is unsubstituted or substituted . by hydroxy, lower alkoxy or halogen, or by imidazolyl or 2o indolyl, or R^ and R® together represent 1,3- or 1,4lower alkylene, each of R^ and R^\ independently of the other, represents hydroxy, lower alkoxy, amino, lower alkylamino, carboxy-lower alkylamino, or a radical of the formula Ie, in which X$ and X 6 have the 25 meanings given in claim 1, Y 3 represents lower alkylene which may be interrupted by iminocarbonyl or oxycarbonyl, and A^ represents a radical of the formula lb or Ic, in which R^ represents an aliphatic radical having at least 7 carbon atoms, represents 30 hydrogen and R 17 represents '2-hydroxyethyl or 1,2dihydroxyethyl, in which at least one hydroxy group is etherified by an aliphatic radical having at least 7 and up to 90 carbon atoms or is esterified by a corresponding aliphatic acyl radical, or each of R 16 and R^ 7 , independently of the other, represents hydroxymethyl etherified by an aliphatic radical having at least 7 and up to 90 carbon atoms or esterified by a 5 corresponding aliphatic acyl radical, and R 10 represents hydrogen, carboxy, lower alkoxycarbonyl, carbamoyl, lower alkylaminocarbonyl or carboxy-lower alkylaminocarbonyl, with the proviso that the compounds * of the formula I have atleast one radical A 1 , A 2 or A 3 , Lq and/or a pharmaceutically acceptable salt thereof.

3. Λ composition according to claim 1 which contains a compound of the formula I, wherein represents the group NH and 2 1 X. represents oxygen, R represents hydrogen, lower alkanoyl, or a group of the formula Ia in which 15 represents 1, Z^ represents carbonyl, Y^ represents lower alkylene which may be interrupted by iminocarbonyl, represents a group of the formula -0- or -NH-, and A^ represents a radical of the formula lb or Ic in which r15 represents an alkyl radical having from 7 to 2o 3.0 carbon atoms that is unsubstituted or substituted by hydroxy., amino and/or alkanoylamino having up to 30 carbon atoms, R^ represents hydrogen and K^ 7 represents 2-hydr0xyethyl or 1,2-dihydroxyethyl, wherein each of the hydroxy groups in a radical R^ 7 , independ25 ently of the other, is etherified by an alkyl radical having from 7 to 30 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or is esterified by an alkanoyl radical having from 7 to 90 30 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or each of R^ and R^ 7 , independently of the other, represents hydroxymethyl in which the hydroxy group is etherified by an alkyl radical having from 7 'to 30 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or is esterif'ied by an 5 alkanoyl radical having from 7 to 90 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, R represents lower alkanoyl, hydroxy-lower alkanoyl, benzoyl, or a group of the formula Ia in which ii, z\ χθ ' X 3 and have the meanings given hereinbefore in this claim, R^ 2 represents hydrogen or lower alkanoyl, R 13 represents hydrogen, alkanoyl or hydroxyalkanoyl having up to 90 carbon atoms, alkanoylaminoalkanoyl having up to 30 carbon atoms, or a group of the formula X5 la in which ri, z\ X 3 and have the meanings given hereinbefore in this claim, R 3 and R 7 .each represents hydrogen or methyl, R 4 , R 5 , R® and R 10 each represents hydrogen, R® represents hydrogen, lower alkyl that is unsubstituted or substituted by free hydroxy or 2q mercapto, lower alkoxy, lower alkylthio, alkanoyloxy or hydroxyalkanoyloxy having up to 90 carbon atoms, or by phenyl, imidazolyl or indolyi, or by a group of the formula Id in which m represents 1, E represents a ο group of the formula -O- or -S-, Z represents carbonyl, 25 Y 2 represents lower alkylene which may be interrupted by iminocarbonyl, represents a group of the formula -0-, and A 2 represents a radical of the formula lb or Ic in which represents an alkyl radical having from 7 to 30 carbon atoms that is unsubstituted or 3q substituted by hydroxy, amino and/or alkanoylamino haying up to 30. carbon atoms, R^ represents hydrogen, and R 17 represents 2-hydroxyethyl or 1,2-dihydroxyethyl, wherein each of the hydroxy groups in a radical R^ 7 , independently of the other, is etherified by an 35 alkyl radical having from 7 to 30 carbon atoms that is Λ 7 4 unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or is esterified by an alkanoyl radical having from 7 to 90 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or each of R 1 ^ and R 17 , independently of the other, represents hydroxymethyl in which the hydroxy group is etherified by an alkyl radical having from 7 to 30 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or is esterified by an alkanoyl radical having from 7 to 90 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, and each of the radicals R 9 and R^\ independently of the other, represents hydroxy, lower alkoxy, amino, lower alkylamino, carboxy-lower alkylamino, or a radical of the formula Io in which represents a group of the formula -0- oc -Nil-, Y 3 represents lower alkylene which may be interrupted by iminocarbonyl, X^ represents a group of the formula -0- and Λ 3 represents a radical of the formula Ib or Lc in which R?5 represents an alkyl radical having from 7 to 30 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, R^ represents hydrogen and R 33 represents 2-hydroxyethyl or 1,2-dihydroxyethyl, wherein each of the hydroxy groups in a radical R 17 , independently of the other, is etherified by an alkyl radical having from 7 to 30 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or is esterified by an alkanoyl radical having from 7 to 90 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or each of R 3 ® and R^ 7 , independently of the*other, represents hydroxymethyl in which the hydroxy group is etherified by an alkyl radical having from 7 to 30 carbon atoms that is unsubstituted or 5 substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, or is esterified by an alkanoyl radical having from 7 to 90 carbon atoms that is unsubstituted or substituted by hydroxy, amino and/or alkanoylamino having up to 30 carbon atoms, with the 10 proviso that the compounds contain at least one radical selected from the group A 1 , A 2 and A 3 , and/or a pharmaceutically acceptable salt thereof.

4. A composition according to claim 1 which contains a compound of the formula 1, wherein 15 . χΐ represents a group of the formula -N(R 14 )-, R 14 representing hydrogen or Cj -4 -alkyl, ·? 1 X represents oxygen, R represents hydrogen, lower alkanoyl, or a group of the formula T.a in which ri reposonts 0 or 1, represents carbonyl, Y^ 20 represents lower alkylene which may be interrupted by imihocarbonyl, X 3 represents oxygen, and A^ represents a radical of the formula lb or Ic in which R^ represents an alkyl or alkenyl radical having from 7 to 30 carbon atoms that is unsubstituted or substituted by 25 hydroxy, amino and/or alkanoylamino having up to 22 carbon atoms, R^ represents hydrogen and R 17 represents 2-hydroxyethyl or 1,2-dihydroxyethyl, at least one hydroxy group in a radical R 17 being etherified by an alkyl or alkenyl radical having from 7 30 to 30 carbon atoms, or being, esterified by an alkanoyl or alkenoyl radical having from 7 to'30 carbon atoms, or each of R 16 and R 17 , independently of the other, . represents hydroxymethyl in which the hydroxy group is etherified by an alkyl or alkenyl radical having from 7 to 30 carbon atoms, or is esterified by an alkanoyl or * 2 alkenoyl radical having from 7 to 30 carbon atoms, R represents lower alkanoyl, hydroxy-lower alkanoyl, benzoyl or, independently of r\ R^ 2 and R^ 3 , a group of 5. The formula Ia as defined hereinbefore in this claim, each of R 3 , R 4 , R 5 , R 7 and R 8 independently represents hydrogen, methyl or ethyl, R® represents hydrogen, or lower alkyl that is unsubstituted or substituted by free hydroxy, free mercapto, IO lower alkoxy, lower alkylthio, alkanoyloxy having from 2 to 30 carbon atoms, alkenoyloxy having from 6 to 30 carbon atoms, phenyl, 4-hydroxyphenyl, or by a group of the formula Id in which m represents 0 or 1, E represents oxygen or sulphur, Ζ Λ represents carbonyl, Y 15 represents lower alkylene that is unsubstituted or substituted by phenyl and may be interrupted by iminocarbonyl, X 4 represents oxygen and A 2 , independently of A^ and A 3 , represents a radical of the formula lb or Ic as defined hereinbefore in this q ii 20 claim, each of R and R, independently of the other, represents hydroxy, lower alkoxy, amino, lower alkylamino, carboxy-lower alkylamino, lower alkoxycarbonyl-lower alkylamino, carbamoyl-lower alkylamino, or a radical of the formula Ie in which X 5 25 represents oxygen or NH, Y 3 represents lower alkylene which may be interrupted by iminocarbonyl, X® represents oxygen and A 3 , independently of A^ and A 2 , represents a radical of the formula lb or Ic as defined hereinbefore in this claim, R^® represents 30 hydrogen, r' 2 represents hydrogen, lower alkanoyl or the same radical as R^ 3 , and R^ 3 represents hydrogen, or alkanoyl or alkenoyl each having up to 30 carbon atoms or, independently of R^ and R 2 , a radical of the formula Ia as defined hereinbefore in 35 this claim, with the proviso that the compounds contain at least one, and at most two, radical selected from the 12 3 group A , A and A , and/or a pharmaceutically acceptable salt thereof.

5. A composition according to claim 4, which 3 contains a compound of the formula I, 1 2 wherein X represents the group NH, X represents oxygen, represents hydrogen or lower alkanoyl, represents lower alkanoyl, benzoyl or a group of the formula Ia in which in represents 0 or 1, IO Z^ represents carbonyl, Y^ represents lower alkylene which may be interrrupted by one or two iminocarbonyl groups, X^ represents oxygen, and represents a radical of the formula lb or Ic in which R^ represents an alkyl radical having from 7 to 22 carbon atoms, R 16 15 represents hydrogen, and R^ 7 represents 1,2-dihydroxyethyl in which each of the hydroxy groups, independently of the other, is esterified by an alkanoyl or alkenoyl radical having From 10 to 22 carbon atoms, R 3 represents hydrogen or methyl, R^, R 5 , R 7 and R® each 20 represents hydrogen, R® represents hydrogen, or lower alkyl that is unsubstituted or substituted by free hydroxy, alkanoyloxy having from 2 to 22 carbon atoms, alkenoyloxy having from 6 to 22 carbon atoms, phenyl or by a group of the formula Id in which m represents 0 or 25 1, E represents oxygen, Z 7 represents carbonyl, Y^ represents lower alkylene that is unsubstituted or substituted by phenyl and may be interrupted by iminocarbonyl, X^ represents oxygen and A^, independently of A and A, represents a radical of the above-defined 50 formula lb or Ic, each of R 9 and R^, independently of the other, represents hydroxy, lower alkoxy, amino, lower alkylamino, α-carboxy-lower alkylamino, ot-lower alkoxycarbonyl-lower alkylamino, a-carbamoyl-lower alkylamino, or a radical of the formula Ie in which X 5 35 represents the group NH, Y 3 represents lower alkylene which may be interrupted by one or two iminocarbonyl groups, X® represents oxygen and A 3 , independently of A^- and A 2 , represents a radical of the formula lb or Ic defined hereinbefore, represents hydrogen, R^ 2 5 represents hydrogen, lower alkanoyl or the same radical as R 13 , and R 13 represents hydrogen, alkanoyl having from 2 to 22 carbon atoms, alkenoyl having from 6 to 22 caibon atoms or, independently of R 2 , a radical of the formula Ia as defined hereinbefore, and/or 10 a pharmaceutically acceptable salt thereof.

6. A composition according to claim 5, which contains a compound of the formula I, 1 2 wherein X represents the group NH, X represents oxygen, R^ represents hydrogen or C 2 _4 alkanoyl, R represents G 2 _4-alkanoyl or a group of the formula Ia in which r\ represents 0 or 1, represents carbonyl, Y 1 represents lower alkylene which may be interrupted by one or two iminocarbonyl groups, X 3 represents oxygen, and A^ represents a radical of the formula lb or Ic in which represents an unbranched alkyl radical having from 12 to 18 carbon atoms, R^ 6 represents hydrogen and R^ 7 represents 1,2-dipalmitoyloxyethyl or 2-oleoyloxy-1-palmitoyloxyethyl, R 3 represents hydrogen or methyl, r\ r\ r 7 f r® and each represents hydrogen, r6 represents methyl, ethyl or isopropyl, each of which is unsubstituted or substituted by a retdical of the formula Id in which m represents 0 or 1, E represents oxygen, Z 2 represents carbonyl, Y 2 represents lower alkylene that is unsubstituted or substituted by phenyl and may be interrupted by one or two intinocarbonyl groups, represents oxygen and A 2 , independently of A^ and A 3 , represents a radical of the formula lb or Ic defined hereinbefore, R^ represents amino, R^ represents hydroxy or a radical of the formula ie in which X 5 represents the group NH, Y 3 represents lower alkylene which may be interrupted by one or two irainocarbonyl groups, X® represents oxygen and A 3 , independently of A^ and A 2 , represents a radical of the formula lb or Ic defined hereinbefore, R^ 2 represents hydrogen, acetyl or the same radical as R^ 3 , and R^ 3 represents hydrogen, acetyl or, independently of R 2 , a radical of the formula Ia as defined hereinbefore, and/or a pharmaceutically acceptable salt thereof.

7. A composition according to any one of claims 1 to 6 which contains a compound of formula I, in which the 12 3 radicals A ,, A and A , if present, represent a radical of the formula Ic, and/or a pharmaceutically acceptable salt thereof.

8. A composition according to any one of claims 1 to 7 which contains a compound of formula I, in which the sugar moiety is derived from (D)-galactose or (D)-mannose, and/or a pharmaceutically acceptable salt thereof.

9. A composition according to any one of claims 1 to 7 which contains a compound of formula I, in which the sugar moiety is derived from (D)-glucose, and/or a pharmaceutically acceptable salt thereof.

10. A composition according to any one of claims 1 to 9 which contains a compound of formula I that carries only 13 one phosphoryl substituent, namely in the radical R , and/or a pharmaceutically acceptable salt thereof.

11. A composition according to any one of claims 1 to 9 which contains a compound of formula 1 thaL carries only 6 one phosphoryl substituent,, namely in the radical R and/or a pharmaceutically acceptable salt thereof.

12. A composition according to any one of claims 1 to 9 which contains a compound of formula I that carries only one phosphoryl substituent, namely in the radical R^ 1 , f and/or a pharmaceutically acceptable salt thereof.

13. A composition according to claim 1 which contains N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanine-2(1,2-dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy )ethylamide and/or a pharmaceutically acceptable salt thereof.

14. Λ composition according to any one of claims 1 to 13 which contains a pharmaceutically acceptable salt of a compound of the formula I.

15. A composition according to claim 14 which contains a sodium salt of a compound of the formula I.

16. A compost ion according to claim 1 which contains a compound of formula I that has at an asymmetrically substituted C(-R 3 )-atom the (Ώ)-configuration, at an asymmetrically substituted C(-R^)-atom the (L)-configurfi ation, and at the C(-N-R°)-atom the (θ)configuration, and in which the sugar moiety is derived from (D)glucose, X^ represents the group NH, X 2 represents oxygen, R 1 , R 4 , R 5 , R 7 , R®, R 10 , R 12 and R 13 each represents hydrogen, R 2 represents C-j_ 3 -alkyl or phenyl, R 3 represents hydrogen or C^ -3 -alkyl, R® represents · hydrogen, C^j-alkyl optionally substituted by hydroxy, methoxy, mercapto, methylmercapto or by halogen, phenyl βί or phenylmethyl each optionally substituted by hydroxy, methoxy or halogen, or heterocyclyl or heterocyclylmethyl each containing one or two aza atoms and having 5 ring members, or R 9 and R® together represent trimethylene, 5 one of the radicals R 9 and represents a radical of the formula le in which X^ represents the group NH or oxygen, Y 3 represents C 2 _ 3 -alkylene or a radical of the formula 2 3 2 Π 3 -ϋ -COO-U - or -U -C-NH-U -, 10 in which each of and U 3 , independently of the other, represents C^^-alkylene that is unsubstituted or substituted by Cj^-alkyl optionally substituted by hydroxy, lower alkoxy, mercapto or by lower alkylmercapto, or by phenyl or phenyl-lower alkyl each of 35 which is optionally substituted by hydroxy, methoxy or halogen, or by heterocyclyl or heterocyclyl-(C-|_-j_alkyl) each containing one or two aza atoms and having 5 or 6 ring members, X® represents oxygen, and A 3 represents a radical of the formula Ic in which represents 20 hydrogen and R 17 represents a 1,2-dihydroxyethyl or 2-hydroxyethyl group in which at last one of the.hydroxy groups is esterified by an aliphatic Cj 6 _ 2 o-carboxylic acid that is optionally singly or doubly unsaturated, or is etherified by an aliphatic C^2-ig“ a lkohol that is 25 optionally singly or doubly unsaturated, and the other of the radicals R 9 and R^ represents hydroxy, lower alkoxy, amino, lower alkylamino or aminocarbonyl-lower alkylamino, and/or a pharmaceutically acceptable salt . thereof.

17. A composition according to claim 1 which contains a compound of the formula I that has at an asymmetrically substituted C(-R 3 )-atom the (D)-configuration, at an asymmetrically 5 substituted C(-R 6 )-atora the (L)-configuration and at the C(-N-R®)-atom the (D)-configuration, and in which the sugar moiety is derived from (D)-glucose, X^ 2 14 represents the group NH, X represents oxygen, R , R , r\ R 8 , R 10 , r^ 2 and R^ each represents hydrogen, R 2 0 represents lower alkyl or phenyl, each of R 3 and r\ independently of the other, represents hydrogen or methyl, R 6 represents C^-alkyl, R 9 represents 1 1 ammo and R represents a radical of the formula 0 0 (-NH-U 1 -(5) r -NH-CH 2 -CH 2 -O-P-O-CH 2 OH CH-O-R I b CH 2 “O-R 15 in which .r represents 0 or 1, iP represents a radical of the formula CH. V c: CH-CH. CH. \ 2 l 3 CH-CH_ I 3 CH-CH I 1 -CH- , 1 —CH— 1 -CH- or 1 -CH- (L) (L) (L) (D and each of R a and R u , independently of the other, represents the acyl radical of a saturated aliphatic carboxylic acid having from 12 to 22 carbon atoms or of an unsubstituted aliphatic carboxylic acid having from 5 12 to 22 carbon atoms and containing one or two double bonds, and/or a pharmaceutically acceptable salt thereof.

18. A pharmaceutical composition for topical application according to any one of claims 1 to 19 that contains from 0.001 % up to, but exclusive of, 1 % of active ingredient.

19. Eye drops according to claim 18.

20. Aqueous nose drops according to claim 18.

21. - Anhydrous nose drops according to claim 18.

22. Gel according to claim 18.

23. Cream according to claim 18.

24. Nasal ointment according to claim 18.

25. Skin ointment according to claim 18.

26. - Lipstick according to claim 18.

27. A pharmaceutical composition according, to any one of claims 1 to 17 for oral administration in the form of 20 tablets or capsules with an .active ingredient content of 0.1 to 0.9 % by weight.

28. A pharmaceutical composition according to any one of claims 1 to 17 in dosage unit form having an active ingredient content of 0.1 to 1 mg per dosage unit.

29. A pharmaceutical composition according to any one of 5 claims 1 to 28 for administration to warm-blooded animals for the prophylaxis or therapy of diseases caused by viruses.

30.. Use of a compound of the formula 1 as defined in any one of claims 1 to 17, or of a pharmaceutically acceptable 10 salt thereof, for the preparation of medicaments for administration to warm-blooded animals for the prophylaxis or therapy of diseases caused by viruses.

31. -. Use according to claim 30 for the prophylaxis or therapy of diseases caused by influenza or Herpes simplex 15 viruses.

32. Use according to claim 30 for the prophylaxis or therapy of diseases caused by encephalomyocarditis, vaccinia or para-influenza viruses.

33. A pharmaceutical composition according to claim 1, substantially as hereinbefore described and exemplified.