US RE35,706 EGranted

Lipophila derivatives of muramylpeptides having properties of activating macrophages and compositions containing them

AssigneeVacsyn S.A.

InventorsNigel Phillips, Fran.cedilla.oise Audibert, Jean-Marie Bernard, Louis Chedid, Pierre Lefrancier, Michel Level, Monique Parant

Life of this patent

Estimating the term…

patentgrep

Loading patent…

Abstract

The invention relates to muramyleptide derivatives resulting essentially from the conjugation or the coupling, as the case may require, through an arm, between a muramylpeptide and a group containing two atoms contiguous with one another to each of which is attached a lipophile chain comprising from 8 to 100 carbon atoms, preferably from 14 to 24 carbon atoms. The derivatives according to the invention are endowed with remarkable stimulating properties with respect to the activation of macrophages, of which they amplify the tumoricidal properties.

A muramylpeptide of the formula:

##STR6## wherein:
R.sub.1 is --H or --CH.sub.3 ;
R.sub.2 is --NH.sub.2, --OH or --OD, with D being a hydrocarbon group of 1 to 10 carbon atoms;
R.sub.11 is ..--H or a phenylamino groups.!. --OH ;
R.sub.14 is --H or an acyl group of 1 to 4 carbon atoms;
X is an aminoacyl residue which is selected from the group consisting of alanyl, valyl, isoleucyl, norleucyl, leucyl, seryl, threonyl, prolyl, glutaminyl, asparaginyl, methionyl, tryptophanyl, phenylalanyl, tyrosyl and glycycl and which may be N-substituted by a lower alkyl group;
Y is --NH.sub.2, --OH, --OD or a ..--OCH.sub.2 --CHO(R.sub.3)CH.sub.2 O(R.sub.4).!. --OCH.sub.2 --CH(OR.sub.3)CH.sub.2 O(R.sub.4) lipophile group in which a hydrogen on a methylene in its glyceryl group may be replaced by a lower alkyl group;
R.sub.3 and R.sub.4 being identical or different and being individually an acyl or alkyl group of 8 to 100 carbon atoms and D is as defined above ;
Z is --NH.sub.2, --OH, --OD or a ..--CO--CHO(R.sub.3)CH.sub.2 O(R.sub.4).!. --OCO--CH(OR.sub.3)CH.sub.2 O(R.sub.4) , lipophile group in which a hydrogen on a methylene in its glyceryl group may be replaced by a lower alkyl group;
Y or Z or both being a lipophile group and D is as defined above ;
..W is --O-- or, when Z is a lipophile group, --NH--;
and.!.
A ..and B are.!. is either a direct linkage..s.!. or a bridging arm..s.!. which ..are identical or different and which.!. comprise s ..individually.!. one to three aminoacyl residues, themselves identical or different from one another, said aminoacyl residues being selected from the group consisting of alanyl, valyl, isoleucyl, norleucyl, leucyl, seryl, threonyl, prolyl, glutaminyl, asparaginyl, methionyl, tryptophanyl, phenylalanyl, tyrosyl and glycyl and which may be N-substituted by a lower alkyl group, or a --NH--(CH.sub.2).sub.2 --O-- group;
a hydrogen on a methylene in a glutamyl group of said muramylpeptide being replaceable by a lower alkyl group.

11 more elements

Abstract

Claims22