Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1996-06-25
1999-05-18
Wilson, James O.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 2, 514 23, 514 25, 514 43, 514885, 536 41, 536 172, 536 173, 536 174, 536 177, 536 185, 536 186, 536 187, 536 53, 536116, 536122, 536123, A61K31/70
Patent
active
059050713
DESCRIPTION:
BRIEF SUMMARY
The invention relates to (2-anmioacylamino-2-deoxy-glycosyl)-amides which are substituted on the nitrogen atom, to processes for their preparation, and their use in medicaments.
It is known that glycosylamides of aldopyranoses or of amino sugars are able to intensify the endogenous immune response (DE-A 32 13 650). It is also known that (2-amino-2-deoxy-glycosyl)-amides substituted with amino acids can bring about an increase both in the specific and in the nonspecific immune response (DE-A 35 21 994).
Now, the present invention relates to (2-aminoacylamino-2-deoxy-glycosyl)-amides which are substituted on the nitrogen atom of the amino acid, of the general formula (I) ##STR2## in which R.sup.1 represents straight-chain or branched, saturated or unsaturated alkyl having up to 25 carbon atoms, allyl having up to 25 carbon atoms, 1-hydroxy-ethyl, mercapto-methyl, 2-methylthio-ethyl, 3-amino-propyl, 3-ureido-propyl, 3-guanidyl-propyl, 4amino-butyl, carboxy-methyl, carbamoyl-methyl, 2-carboxy-ethyl, 2-carbamoyl-ethyl, benzyl, 4-hydroxy-benzyl, 3-indolyl-methyl or 4-imidazolyl-methyl, different from it, peptide chemistry (cf. A Hubbuch, Kontakte (Darmstadt) 1979, 14; E. E. Bullesbach, Kontakte (Darmstadt) 1980, 23), different.
The compounds according to the invention have a plurality of asymmetric carbon atoms. They can therefore exist in different stereochemical forms. The invention relates both to the individual isomers and to mix thereof.
Preferred compounds of the general formula (I) are those in which radical having 10 to 20 carbon atoms, radical having 10 to 20 carbon atoms, 1-hydroxy-ethyl, mercapto-methyl, 2-methylthio-ethyl, 3-amino-propyl, 3-ureido-propyl, 3-guanidyl-propyl, 4-amino-butyl, carboxy-methyl, carbamoyl-methyl, 2-carboxy-ethyl, 2-carbamoyl-ethyl, benzyl, 4hydroxy-benzyl, 3-indolyl-methyl or 4-imidazolyl-methyl, different from it, trifluoroacetyl, methoxycarbonyl, tert-butyloxycarbonyl, allyloxycarbonyl, trichloroethoxycarbonyl, benzyloxycarbonyl or fluorenylmethoxycarbonyl, different.
In addition, two processes have been found for the preparation of the compounds of the general formula (I) according to the invention. The two processes differ in the sequence and in the structural units with which the peptide linkages can be linked.
In the first process (A), N-(2-aminoacylamino-2-deoxy-hexopyranosyl)-N-alkyl-carboxamides of the formula (II) ##STR3## in which R.sup.1, R.sup.2 and R.sup.3 have the meaning given above the general formula (III) ##STR4## in which R.sup.4 has the meaning given above, the nitrogen atom of amino acids, which can be eliminated again selectively to give the peptide linkage, and peptide chemistry, for the activation of amino acids, different, with one another in such a way that an amide linkage is formed and compounds of the general formula (I) are obtained.
In a second reaction step, the N-terminal protecting group R.sup.5 in the compounds of the formula (I) is eliminated to give the compounds of the general formula (I) having a free amino group.
The starting compounds of the general formula (II) are known and can be prepared by the methods described in DE 3521994 (Le A 23620).
The derivatives of the di- or tripeptides of the general formula (III) are likewise known in principle.
Examples of suitable protecting groups R.sup.6 for the amino function in compounds of the formula (III) are acyl groups such as trifluoroacetyl or trichloroacetyl, o-nitrophenylsulphenyl, 2,4-dinitrophenylsulphenyl or optionally substituted lower alkoxycarbonyl, for example methoxycarbonyl, tert-butyloxycarbonyl, benzyloxycatbonyl, p-methoxybenzyloxycarbonyl, fluorenylmethoxycarbonyl or 2,2,2-trichloroethoxycarbonyl.
Preferred amino-protecting groups R.sup.6 are the tert-butyloxycarbonyl group or the benzyloxycarbonyl group.
The linkage of the 2-aminoacylamino-2-deoxy-glycosylamides of the general formula (II) with the N-substituted amino acids, di- or tripeptides of the general formula (III) can be accomplished by conventional methods of Chemistry! (Houben-Weyl) (E. Muller, ed.) Volume XV/I
REFERENCES:
patent: 4308376 (1981-12-01), Lemieux et al.
patent: 4362720 (1982-12-01), Lemieux et al.
patent: 4683222 (1987-07-01), Stradler et al.
patent: 4855283 (1989-08-01), Lockhoff et al.
O. Lockhoff et al., Angewandte Chemie International Ed. Eng. vol. 30,pp.1611-1620 (1991).
A. Hubbuch, Kontakte, No. 3, pp. 19-22 (1979).
E.E. Bullesbach, Kontakte, No. 1,pp. 23-35 (1980).
E.Wunsch, in. "Methoden Der Organischen Chemie (Houben-Wegl)", E. Muller, ed., vol. XV/1 and XV/II, 4th ed., thiene Veilog, Stuffgart (1974).
Brunner Helmut
Lockhoff Oswald
Mielke Burkhard
Schaller Klaus
Bayer Aktiengesellschaft
Wilson James O.
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