# US 4,391,800 A · Immunologically active peptidyl disaccharides and methods of preparation

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- Number: US 4,391,800 A
- Document ID: US4391800A
- Status: Granted
- Kind: A
- Application number: 06/033,597
- Filed: 1979-04-27
- Granted: 1983-07-05
- Earliest claimed: 1979-04-27
- Assignees: Merck & Co., Inc.
- Inventors: Philippe L. Durette; Tsung-Ying Shen
- Web page: https://patentgrep.com/patent/US4391800A

## CPC

- 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}
- A61P 31/04: Antibacterial agents
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

2-Amino-2-deoxy-.beta.-D-glucopyranosyl-(1-4)-2-amino-2-deoxy-D-glucoses of the general structural formula: ##STR1## wherein R.sub.1 is hydrogen, alkyl (1-7C), substituted alkyl (1-7C), phenyl, substituted phenyl, benzyl, or substituted benzyl; R.sub.2 is alkyl, substituted alky, phenyl, or substituted phenyl and each R.sub.2 may be the same group or a different group; R.sub.3 is H or ##STR2## wherein R.sub.8 is H or lower alkyl (1-10C), and provided at least one of R.sub.3 is not H, R.sub.9 is H, or R.sub.9 -R.sub.10 together is --CH.sub.2 --CH.sub.2 --CH.sub.2 --; R.sub.10 is H, alkyl (L-7C), hydroxymethyl, mercaptomethyl, benzyl, or substituted benzyl; R.sub.11 and R.sub.12 each is carboxyl, esterified carboxyl (1-7C), amidated carboxyl, or mono- or di-alkyl- (1-3C) amidated carboxyl; R.sub.4 and R.sub.5 are the same or different and are H, aliphatic or aromatic acyl (2-21C) or substituted acyl (2-21C); when R.sub.8 is lower alkyl, the stereochemistry at asymmetric center I can be either D or L; when R.sub.10 is not H, the stereochemistry at asymmetric center II is L; the stereochemistry at asymmetric center III is D. These compounds possess immunostimulatory properties.

## Claims

### Claim 1

A 2-amino-2-deoxy-.beta.-D-glucopyranosyl-(1.fwdarw.4)-2-amino-2-deoxy-D-glu cose of the general structural formula: ##STR14## wherein R.sub.1 is hydrogen, alkyl (1-7C), substituted alkyl (1-7C) wherein the substituent is hydroxy, mercapto, alkoxy of 1-3 carbons, alkyl mercapto of 1-3 carbons, hydroxy or mercapto esterified by an acid of 1-4 carbon atoms, F, Cl, Br, carboxyl, or carboxyl functionally modified by esterification with an alcohol of 1-3 carbons or by amidation, phenyl, substituted phenyl wherein the substituent is an alkyl group of 1-3 carbons, hydroxy, mercapto, hydroxy or mercapto etherified by an alkyl group of 1-3 carbons, hydroxy or mercapto esterified by an acid of 1-4 carbons, alkyldioxy (1-4C), cycloalkyldioxy (5-7C), amino or trifluoromethyl, benzyl, or substituted benzyl wherein the substituent is an alkyl group of 1-3 carbons, hydroxy, mercapto, hydroxy or mercapto etherified by an alkyl group of 1-3 carbon atoms, hydroxy or mercapto esterified by an acid of 1-4 carbons, alkyldioxy (1-4C), cycloalkyldioxy (5-7C), amino or trifluoromethyl;
R.sub.2 is alkyl (1-7C), substituted alkyl (1-7C) wherein the substituent is hydroxy, mercapto, alkoxy of 1-3 carbons, alkylmercapto of 1-3 carbons, hydroxy or mercapto esterified by an acid of 1-4 carbon atoms, F, Cl, Br, carboxyl, or carboxyl functionally modified by esterification with an alcohol of 1-3 carbons or by amidation, phenyl, or substituted phenyl wherein the substituent is an alkyl group of 1-3 carbons, hydroxy, mercapto, hydroxy or mercapto etherified by an alkyl group of 1-3 carbon atoms, hydroxy or mercapto esterified by an acid of 1-4 carbons, alkyldioxy (1-4C), cycloalkyldioxy (5-7C), amino or trifluoromethyl and each R.sub.2 may be the same group or a different group;
R.sub.3 and R'.sub.3 are H or ##STR15## wherein R.sub.8 is H or lower alkyl (1-10C), and provided at least one of R.sub.3 and R'.sub.3 is not H;
R.sub.9 is H, or R.sub.9 -R.sub.10 together is --CH.sub.2 CH.sub.2 CH.sub.2 --;
R.sub.10 is H, alkyl (1-7C) hydroxymethyl, mercaptomethyl, benzyl, or substituted benzyl wherein the substituent is an alkyl group of 1-3 carbon atoms, hydroxy, mercapto, hydroxy or mercapto etherified by an alkyl group of 1-3 carbons, hydroxy or mercapto esterified by an acid of 1-4 carbons, alkyldioxy (1-4C), cycloalkyldioxy (5-7C), amino or trifluoromethyl;
R.sub.11 and R.sub.12 each are independently carboxyl, esterified carboxyl (1-7C), amidated carboxyl, or mono- or di-alkyl (1-7C) amidated carboxyl;
R.sub.4, R.sub.5 and R'.sub.5 are the same or different and are H, aliphatic or aromatic acyl (2-21C) or substituted acyl (2-21C) wherein the substituent is halogen, alkyl (1-3C), alkoxy (1-3C), trifluoromethyl, hydroxy, alkanoyloxy (1-3C),
provided when R.sub.8 is loweralkyl, the stereo chemistry at asymmetric center I can be either D or L; and when R.sub.10 is not H, the stereochemistry at asymmetric center II is L; the stereochemistry at asymmetric center III is D;
provided further when R.sub.1, R.sub.5, R'.sub.3, R.sub.4, and R'.sub.5 are each H and each R.sub.2 is CH.sub.3, R.sub.3 is not H.sub.3 CCHCOR.sub.13 wherein R.sub.13 is a dipeptide.

### Claim 2 (depends on 1)

A compound of claim 1 wherein R.sub.2 is methyl.

### Claim 3 (depends on 1)

A compound of claim 1 wherein R.sub.1 and R.sub.5 are hydrogen, and R.sub.4 and R'.sub.5 are hydrogen or acetyl.

### Claim 4 (depends on 1)

A compound of claim 1 wherein R.sub.3 and R'.sub.3 are H or ##STR16##

### Claim 5 (depends on 2)

A compound of claim 2 wherein R.sub.1, R.sub.3, R.sub.4, R'.sub.5 and R.sub.5 are hydrogen and R'.sub.3 is ##STR17##

### Claim 6 (depends on 2)

A compound of claim 2 wherein R.sub.1 and R.sub.3 and R.sub.5 are hydrogen, R.sub.4 and R'.sub.5 are acetyl and R'.sub.3 is ##STR18##

### Claim 7 (depends on 2)

A compound of claim 2 wherein R.sub.1 R'.sub.3, R.sub.4, R'.sub.5 and R.sub.5 are hydrogen and R.sub.3 is ##STR19##

### Claim 8 (depends on 1)

A compound of claim 1 wherein R.sub.1 is H, alkyl of 1-3 carbons, benzyl, phenyl or phenyl p-substituted by alkyl (1-3C), amino, F, Cl, Br, hydroxy or trifluoromethyl; R.sub.2 is alkyl of 1-3 carbons, or phenyl, or phenyl p-substituted by alkyl (1-3C), amino, F, Cl, Br, hydroxy or trifluoromethyl; R.sub.3 is H, R.sub.4 and R.sub.5 are H, alkanoyl of 2-21 carbons, benzoyl or naphthoyl; R.sub.10 is H, alkyl or 1-4 carbons, hydroxymethyl, mercaptomethyl, benzyl or p-hydroxybenzyl; R.sub.9 and R.sub.10 together are --CH.sub.2 CH.sub.2 CH.sub.2 --; and R.sub.11 and R.sub.12 are carboxyl, carboxyl esterified by an alcohol of 1-4 carbons, carboxamide, or monoalkyl or dialkyl substituted carboxamide wherein the alkyl group has from 1-3 carbons.

### Claim 9

Compounds of the formula ##STR20## wherein Ac is a residue of an aliphatic carboxylic acid having at least 3 carbon atoms; and R is a dipeptide.

### Claim 10 (depends on 1)

A composition having immunostimulatory properties comprising a compound of claim 1 in an amount effective to produce an immunostimulatory effect and a pharmaceutically acceptable carrier.

### Claim 11 (depends on 1)

An antibacterial composition comprising a compound of claim 1 in an amount effective to produce an antibacterial effect and a physiologically acceptable medium.

### Claim 12 (depends on 10)

A composition of claim 10 in aqueous formulation.

### Claim 13 (depends on 10)

A composition of claim 10 in oil formulation.