Ciba-geigy Corporation

Isis Pharmaceuticals, Inc.

Gerhard Baschang

Albert Hartmann

Jaroslav Stanek

Lajos Tarcsay

Oskar Wacker

Alfred Sallmann

Alberto Rossi

Alex Sele

Felix M Dietrich

Roland Gisler

Phillip Dan Cook

Bruno Fechtig

Bruno Kamber

Bohumir Lukas

Alfred Sallman

Peter Wirz

Bohumir Lucas

Hans Hirt

Bruno Baehler

Jean M Tronchet

Oligonucleotide surrogates comprising a plurality of cyclobutyl moieties covalently joined by linking moieties are prepared and used as antisense diagnostics, therapeutics and research reagents. Methods of synthesis and use of both the oligonucleotide surrogates and intermediates thereof are disclosed.

Cyclobutyl oligonucleotide surrogates

Oligonucleotide surrogates comprising a plurality of cyclobutyl moieties covalently joined by linking moieties are prepared and used as antisense diagnostics and research reagents. Methods of synthesis and use of both the oligonucleotide surrogates and intermediates thereof are disclosed.

Salts of aminosulfonic acid derivatives of formula I ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are each independently of the others an aliphatic hydrocarbon radical having from 7 to 21 carbon atoms,

Aminosulfonic acid derivatives and processes for their preparation

The L-arginine salt of N-(D)-{[2-(2,6-dichlorophenylamino}phenyl]acetyl]aspartic acid, represented by the formula ##STR1## in which AmH .sym. represents the cation derived from L-arginine Am of the formula ##STR2## and its hydrates exhibit and excellent water-solubility and a physiologically favorable pH value and also a pleasant taste in aqueous solutions and are therefore excellently suitable for enternal and parenteral forms of administration. It is manufactured by reacting L-arginine with D-{[2-(2,6-dichlorophenylamino)phenyl]-acetyl}aspartic acid.

Novel Guanidinium aspartates

Cephalin derivatives of the formula I ##STR1## in which R.sup.1 and R.sup.2 each represents, independently of the other, hydrogen or lower alkyl, R.sup.3 represents hydrogen, lower alkoxycarbonyl, carbamoyl or free or protected carboxy, R.sup.4 represents hydrogen or an aliphatic, aromatic, aromatic-aliphatic or cycloaliphatic radical, W represents hydrogen and Z represents a 1,2-dihydroxyethyl, 2-hydroxyethyl or hydroxymethyl group in which at least one hydroxy group is esterified by an aliphatic C.sub.6-30 -carboxylic acid or etherified by an aliphatic C.sub.6-30 -alcohol and in which the other hydroxy group, if present, is free, esterified by an aliphatic C.sub.2-30 -carboxylic acid or etherified by an aliphatic C.sub.1-30 -alcohol, or W represents hydroxymethyl or a hydroxymethyl group that is esterified by an aliphatic C.sub.6-30 -alcohol and Z represents a hydroxymethyl group that is esterified by an aliphatic C.sub.6-30 -carboxylic acid or etherified by an aliphatic C.sub.6-30 -alcohol, and their salts are suitable for the prophylaxis and treatment of virus infections in warm-blooded animals.

Phosphorus compounds, processes for their manufacture, and their use

Mono- and di-saccharidyl derivatives that are linked via a bridge member to a cephalin derivative, of the formula I, and processes for their manufacture are described. ##STR1## In the formula, R.sup.1 represents (a) aldohexosyl, (b) D-aldohexosyl that is glycosidically linked in the 4- or the 6-position to D-aldohexosyl, (c) aldopentosyl, (d) 6-deoxyaldohexosyl or (e) 2-acetylamino-2-deoxy-D-aldohexosyl, it being possible for free hydroxy groups present in the radicals mentioned under (a) to (e) above to be peracetylated, X represents oxygen or sulphur, Y represents alkylene having up to 10 carbon atoms in which from 1 to 3 non-terminal methylene groups may be replaced by oxygen, by carbonylimino or by carbonyloxy, R.sup.2 represents hydrogen, carboxy, lower alkoxycarbonyl, benzyloxycarbonyl or carbamoyl, R.sup.3 represents hydrogen and R.sup.4 represents a 1,2-dihydroxy-ethyl, 2-hydroxy-ethyl or hydroxymethyl group in which at least one hydroxy group is esterified by an unsubstituted aliphatic C.sub.10-24 -carboxylic acid and in which the other hydroxy group, if present, is free or esterified by an aliphatic C.sub.2-24 -carboxylic acid, or R.sup.3 and R.sup.4 each represents a hydroxymethyl group esterified by an unsubstituted aliphatic C.sub.10-24 -carboxylic acid. These compounds can be used as medicaments, for example for the prophylaxis and therapy of virus infections.

Saccharide derivatives and processes for their manufacture

Described are phosphatidyl compounds of the formula I ##STR1## in which R.sup.1 represents C.sub.3-14 -alkanoyl, benzoyl, the acyl radical of an .alpha.-aminocarboxylic acid that is other than glycine, L-alanine and derivatives thereof having a substituted amino group, and of which the .alpha.-amino group may be substituted by lower alkanoyl, lower alkoxycarbonyl or by benzyloxycarbonyl, or the acyl radical of a .beta.-aminocarboxylic acid or an .alpha.- or .beta.-hydroxycarboxylic acid,

Phosphatidyl compounds, processes for their manufacture, and their use

There are described sugar derivatives of the formula I ##STR1## that have immuno-stimulating action and that contain as inventive element at least one radical A.sup.1 or A.sup.2. These radicals A.sup.1 and A.sup.2, which may be constituents of the radicals R.sup.1, R.sup.2, R.sup.4, R.sup.6, R.sup.9, R.sup.10 or R.sup.12 according to formula I, are defined as follows:

Acylated sugar derivatives, processes for their manufacture, and their

The invention relates to lipopeptides of the formula I, ##STR1## in which each of R.sub.a.sup.1 and R.sub.b.sup.1, independently of the other, represents an aliphatic or cycloaliphatic-aliphatic hydrocarbon radical having from 7 to 21 carbon atoms that is optionally substituted by oxygen functions, or

Novel peptide derivatives

The invention relates to novel antigen derivatives comprising an antigen and at least one muramylpeptide covalently bonded thereto, if appropriate via a spacer, to pharmaceutical preparations which contain such compounds and to their use as a vaccine. The novel antigen derivatives produce a pronounced increase in the immuno-response to the antigen, and in particular also a cell-medicated immunity under clinically acceptable conditions of administration.

Antigen derivatives and processes for their preparation

The compounds of the formula I ##STR1## in which each of R.sup.1, R.sup.4 and R.sup.6, independently of the others, represents hydrogen or lower alkanoyl, R.sup.2 represents C.sub.1-4 -alkyl, hydroxymethyl or phenyl, R.sup.3 represents hydrogen or methyl, R.sup.5 represents hydrogen or C.sub.1-3 -alkyl, R.sup.7 represents C.sub.1-3 -alkyl that is unsubstituted or substituted by hydroxy, mercapto or methylthio, R.sup.8 represents hydrogen or lower alkyl, X represents oxygen or the group NH, Y represents C.sub.1-4 -alkylidene, and each of R.sup.9 and R.sup.10, independently of the other, represents C.sub.11-17 -alkyl or C.sub.11-17 -alkenyl, and their salts, have an immunostimulating activeity.

Muramyl peptides and processes for their manufacture

The invention relates to novel antigen derivatives comprising an antigen and at least one muramyl-peptide covalently bonded thereto, if appropriate via a spacer, to pharmaceutical preparations which contain such compounds and to their use as a vaccine. The novel antigen derivatives produce a pronounced increase in the immuno-response to the antigen, and in particular also a cell-medicated immunity under clinically acceptable conditions of administration.

The present invention relates to new lipopeptides and in particular to compounds of either of the formulae ##STR1## wherein R.sub.1 and R.sub.2 each represent a saturated or unsaturated aliphatic or mixed aliphatic-cycloaliphatic hydrocarbon radical which has 11-21 C atoms and which is also optionally substituted by oxygen functions, R.sub.3 represents hydrogen or the radical R.sub.1 --CO--O--CH.sub.2 --, where R.sub.1 has the same meaning, R.sub.1 ' is a saturated or unsaturated aliphatic hydrocarbon radical of at least 9 C atoms, which is optionally substituted at one of the C atoms non adjacent to the sulfur atom by a free hydroxyl group or a hydroxyl group esterified with a monobasic carboxylic acid and which is optionally interrupted in the C atoms chain by one or more oxygen atoms, and which hydrocarbon is optionally substituted by a maximum of 2 cycloaliphatic hydrocarbon radicals having 5-8 ring C atoms, or R.sub.1 ' is the radical --CO--R.sub.1 ', wherein R.sub.1 ' represents a saturated or unsaturated aliphatic or mixed aliphatic-cycloaliphatic hydrocarbon radical of 11-21 C-atoms and which is optionally interrupted in the C atoms chain by oxygen atoms, and X represents an amino acid with free esterified or amidated carboxyl group, or an amino acid sequence of 2-10 aliphatic amino acids, the terminal carboxyl group of which is free or in the ester or amide form, the amino acids being naturals ones in the case of compounds of formula (1).

Peptide derivatives

There are described hexopyranose compounds of the formula I and salts thereof having immunomodulatory action, which can be used, for example, in the form of pharmaceutical preparations, and also together with antibiotics, and processes for their manufacture. ##STR1## The variables are as described in the disclosure. The invention relates to the above-mentioned compounds as immunomodulators, especially as immunostimulants, their use as pharmacologically active substances, especially their use as immunomodulators, particularly as immunostimulants, and their use for the manufacture of pharmaceutical preparations, and to pharmaceutical preparations containing these compounds.

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Bettingen, Switzerland

Gerhard Baschang