# US 4,574,058 A · Antigen derivatives and processes for their preparation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 4,574,058 A - Document ID: US4574058A - Status: Granted - Kind: A - Application number: 06/477,281 - Filed: 1983-03-21 - Granted: 1986-03-04 - Earliest claimed: 1978-02-24 - Assignees: Ciba-Geigy Corporation - Inventors: Gerhard Baschang; Felix M. Dietrich; Roland Gisler; Albert Hartmann; Jaroslav Stanek; Lajos Tarcsay - Web page: https://patentgrep.com/patent/US4574058A ## CPC - C07H 9/04: Cyclic acetals - A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) - A61K 39/385: Haptens or antigens, bound to carriers - C07H 23/00: Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12 (esters with inorganic acids C07H11/00) - C07K 9/005: {containing within the molecule the substructure [IMAGE cpc-sch-C07K-1009.gif] with m, n > 0 and m+n > 0, A, B, D, E being heteroatoms; X being a bond or a chain, e.g. muramylpeptides} - A61K 2039/55583: {Polysaccharides} - A61K 2039/6062: {Muramyl peptides} - Y10S 530/807: Hapten conjugated with peptide or protein - C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS ## Abstract 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. ## Claims ### Claim 1 A muramyl-peptide of the general formula ##STR10## in which X is a carbonyl group, R.sub.1, R.sub.4 and R.sub.6 are tri-lower alkyl-silyl, R.sub.2 is unsubstituted or substituted alkyl or carbocyclic aryl, R.sub.3 is hydrogen or alkyl, R.sub.7 and R.sub.13 are hydrogen or lower alkyl, R.sub.8 is hydrogen, lower alkyl, free, esterified or etherified hydroxy-lower alkyl, free, esterified or etherified mercapto-lower alkyl, free or acylated amino-lower alkyl, cycloalkyl having 5 or 6 carbon atoms, cycloalkyl-lower alkyl, of which the cycloalkyl radical contains 5 or 6 carbon atoms, unsubstituted or substituted aryl or aralkyl, nitrogen-containing heterocyclyl or heterocyclyl-lower alkyl, R.sub.7 and R.sub.8 together can also be alkylene having 3 or 4 carbon atoms, R.sub.9 is hydrogen or lower alkyl, the radicals R.sub.10 and R.sub.12 independently of one another are a carboxyl radical which may or may not be esterified or amidised, and R.sub.11 is hydrogen or a carboxyl radical which may or may not be esterified or amidised. ### Claim 2 (depends on 1) A compound according to claim 1 in which R.sub.2 represents alkyl having 1 to 18 carbon atoms which is unsubstituted or substituted by hydroxy, lower alkoxy, lower alkanoyloxy, halogen, mercapto, lower alkylmercapto, lower alkanoylmercapto, carboxy, lower alkoxycarbonyl and/or carbamoyl, or represents phenyl which is unsubstituted or substituted by lower alkyl, hydroxy, lower alkoxy, lower alkanoyl, lower alkylenedioxy, halogen and/or trifluoromethyl, R.sub.3, R.sub.7, R.sub.9 and R.sub.13 are independently of one another hydrogen or lower alkyl, R.sub.8 is hydrogen, lower alkyl which is unsubstituted or substituted by hydroxy, lower alkoxy, lower alkanoyloxy, mercapto, lower alkylmercapto, lower alkanoylmercapto, amino, lower alkanoylamino, carbamoylamino or cycloalkyl having 5 or 6 carbon atoms, or represents cycloalkyl having 5 or 6 carbon atoms, phenyl or phenyl-lower alkyl, in which the phenyl radicals are unsubstituted or substituted as defined above, or heterocyclyl or heterocyclyl-lower alkyl wherein the heterocyclyl radicals are 5- or 6-membered, contain one or two nitrogen atoms in the ring and may or may not contain a fused phenyl radical, R.sub.7 and R.sub. 8 together can also represent alkylene having 3 or 4 carbon atoms, R.sub.10 and R.sub.12 independently of one another represent carboxyl, lower alkoxycarbonyl, tri-lower alkylsilyloxycarbonyl or carbamoyl which is unsubstituted or mono- or disubstituted at the nitrogen atom by unsubstituted or carboxy- or carbamoyl-substituted lower alkyl or by phenyl, benzyl, tetramethylene or pentamethylene or R.sub.11 represents, independently, the same groups as R.sub.10 and R.sub.12 or hydrogen. ### Claim 3 (depends on 1) A compound according to claim 1 wherein R.sub.13 represents hydrogen. ### Claim 4 (depends on 2) A compound according to claim 2 wherein R.sub.3, R.sub.7, and R.sub.13 are hydrogen, and R.sub.2 is lower alkyl which is unsubstituted or substituted by hydroxyl or lower alkoxy, or is phenyl which is unsubstituted or substituted by hydroxy, lower alkoxy, lower alkyl or halogen. ### Claim 5 (depends on 2) A compound according to claim 2 wherein R.sub.7 and R.sub.13 are hydrogen, R.sub.2 is lower alkyl which is unsubstituted or substituted by hydroxyl or lower alkoxy or is phenyl which is unsubstituted or substituted by hydroxyl, lower alkoxy, lower alkyl or halogen, and R.sub.3 is methyl. ### Claim 6 (depends on 2) a compound according to claim 2 wherein R.sub.7, R.sub.9 and R.sub.13 are hydrogen, R.sub.2 is lower alkyl which is unsubstituted or substituted by hydroxyl or methoxy or is phenyl which is unsubstituted or substituted by hydroxyl, methoxy, methyl, ethyl or halogen, R.sub.3 is hydrogen or methyl, R.sub.8 is benzyl, p-hydroxybenzyl, phenyl or lower alkyl which is unsubstituted or substituted or lower alkylmercapto or hydroxy, and R.sub.10 and R.sub.12 are, independently, carboxyl, lower alkoxycarbonyl or carbamoyl and R.sub.11 represents, independently, the same groups as R.sub.10 and R.sub.12 or hydrogen. ### Claim 7 (depends on 2) A compound according to claim 2 wherein R.sub.13 is hydrogen, R.sub.2 is lower alkyl which is unsubstituted or substitured by hydroxyl or methoxy or is phenyl which is unsubstituted or substituted by hydroxyl, methoxy, methyl, ethyl or halogen, R.sub.3 and R.sub.9 are hydrogen or methyl, R.sub.8 is methyl, ethyl, n-propyl, i-propyl, 2-methyl-propyl, methylmercaptomethyl, hydroxymethyl, hydroxyethyl, phenyl, benzyl or p-hydroxybenzyl and R.sub.10 and R.sub.12 are carboxyl, lower alkoxycarbonyl or carbamoyl and R.sub.11 represents the same groups as R.sub.10 and R.sub.12 or hydrogen. ### Claim 8 (depends on 2) A compound according to claim 2 wherein R.sub.7 and R.sub.8 together are propylene or butylene. ### Claim 9 (depends on 2) A compound according to claim 2 wherein R.sub.11 is hydrogen. ### Claim 10 (depends on 2) A compound according to claim 2 wherein R.sub.11 and R.sub.13 are hydrogen, R.sub.2 is methyl, ethyl or phenyl, R.sub.3 is hydrogen or methyl, R.sub.7 is hydrogen, methyl, ethyl or n-propyl, R.sub.8 is methyl, ethyl or isopropyl, R.sub.9 is hydrogen or methyl, R.sub.10 is carboxyl, carbamoyl, N-(carbamoylmethyl)-carbamoyl or N-(1-carboxyethyl)-carbamoyl and R.sub.12 is carboxy or N-(1-carboxy-ethyl)-carbamoyl. ### Claim 11 (depends on 1) A compound according to claim 1, which is 2-acetamido-3-O-{[L-1-(D-1-carbamoyl-3-trimethylsilyloxycarbonyl-propyl)-c arbamoyl-ethyl]-carbamoyl-methyl}-2-deoxy-1,4,6-O-tris-trimethylsilyl-D-glu cose. ### Claim 12 (depends on 1) A compound according to claim 1, which is 2-benzamido-3-O-{[L-1-(D-1-carbamoyl-3-trimethylsilyloxycarbonylpropyl)-ca rbamoyl-ethyl]-carbamoyl-methyl}-2-deoxy-1,4,6-O-tris-trimethylsilyl-D-gluc ose. ### Claim 13 (depends on 2) A compound according to claim 2, wherein R.sub.1, R.sub.4 and R.sub.6 each represent trimethylsilyl. ### Claim 14 (depends on 6) A compound according to claim 6, wherein R.sub.1, R.sub.4 and R.sub.6 each represent trimethylsilyl. ### Claim 15 (depends on 7) A compound according to claim 7, wherein R.sub.1, R.sub.4 and R.sub.6 each represent trimethylsilyl.