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US 5,885,968 AGranted
Triantennary cluster glycosides, their preparation and use
AssigneesRijksuniversiteit te Leiden, Nederlandse Hartstichting
InventorsEricus Anna Leonardus Biessen, Theodorus Josephus Cornelis van Berkel, Jacobus Hubertus van Boom
Life of this patent
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Abstract
Triantennary cluster glycoside, wherein each glycoside residue is attached to the branching point of the cluster by a spacer of a long, flexible, hydrophilic chain comprising at least 4 atoms in the chain. The glyciside spacer preferably comprises at least two hydrophilic groups. Use of the triantennary cluster glycoside in pharmaceutical preparations, for instance hypolipidemic medicines.
Claims23
Triantennary cluster glycoside having the formula 1:
- GO--X.sup.1 --!.sub.3 A--X.sup.2 --Z (2)
- wherein GO is a glycoside residue selected from the group consisting of monosaccharides and disaccarides;
- where X.sup.1 is a long, flexible, hydrophilic spacer having about 4 atoms to about 15 atoms and having the formula:
- --HG-Alk-!.sub.e --
- wherein HG is a hydrophilic group, wherein Alk is a branched or straight C.sub.1 -C.sub.4 alkylene group, and wherein e is from 1-8, and wherein the Alk is arranged between two hydrophilic groups;
- wherein A is a branching point of the cluster which is a carbon atom or a sugar group;
- wherein X.sup.2 is an end group spacer of a chain length having about 4 atoms to about 12 atoms;
- and
- wherein Z is an end group selected from the group consisting of a protected reactive group, a lipophilic group, a drug residue and a drug carrier residue, excluding a tetrakis-O-(3-carboxy-propionyl)pentaerythritol tetrakis-(1,2,3,4-tetra-O-benzyl-.alpha.-D-glucopyranosid-6-yl)tetraester, and a tetrakis-O-(3-carboxy-propionyl)pentaerythritol tetrakis-(.alpha.-D-glucopyranosid-6-yl)tetraester.
6 more elements
Method of preparing a triantennary cluster glycoside of formula 5:
- GO--(CHR.sup.1).sub.n O--CHR.sup.2).sub.p !.sub.r OCH.sub.2 O(CHR.sup.3).sub.q --!.sub.3 C--X.sup.2 --Z (5)
- wherein GO-- is a glycoside residue selected from the group consisting of monosaccharides and disaccharides;
- wherein X.sup.2 is an end spacer having about 4 atoms to about 12 atoms;
- wherein Z is an end group selected from the group consisting of an optionally protected reactive group, a lipophilic group, a drug residue and a drug carrier residue, excluding tetrakis-O-(3-carboxy-propionyl)pentaerythritol tetrakis-(1,2,3,4-tetra-O-benzyl-.alpha.-D-glucopyranosid-6-yl)tetraester or a tetrakis-O-(3-carboxy-propionyl)pentaerythritol tetrakis-(.alpha.-D-glucopyranosid-6-yl)tetraester, wherein R.sup.1 -R.sup.3 is a hydrogen atom, and an alkyl group having 1-4 carbon atoms;
- wherein p and q is an integer from 1-4;
- and
- wherein n and r is an integer from 0-6;
- said method of preparing said triantennary cluster glycoside having the step of:
- reacting a compound having the formula 6:
- G'O--(CHR.sup.1)nO(CHR.sup.2).sub.p !.sub.r OH (6)
- wherein G'O-- is a residue of a protected glycoside selected from the group consisting of monosaccharides and disaccharides,
- with a compound having the formula 7:
- CH.sub.3 SCH.sub.2 O(CHR.sup.3).sub.q --!.sub.3 C--X.sup.2 --Z'(7)
- wherein Z' is the end group Z or another group to be replaced by the end group Z;
- and wherein if the group Z' is another group to be replaced by the end group Z, then group Z' is replaced by said end group Z, and wherein G'O is deprotected to obtain a compound having the residue GO.
12 more elements
Method of preparing a triantennary cluster glycoside of formula 8:
- GO--(CHR.sup.1).sub.n O(CHR.sup.2).sub.p !.sub.r OCH.sub.2 O(CHR.sup.3).sub.q --!.sub.3 C--NH--X.sup.3 --Z (8)
- wherein GO-- is a glycoside residue selected from the group consisting of monosaccharides and disaccharides;
- wherein X.sup.3 is an end group spacer about 4 atoms to about 12 atoms;
- wherein Z is an end group selected from the group consisting of an optionally protected reactive group, a lipophilic group, a drug residue and a drug carrier residue, excluding a tetrakis-O-(3-carboxy-propionyl)pentaerythritol tetrakis-(1,2,3,4-tetra-O-benzyl-.alpha.-D-glucopyranosid-6-yl)tetraester, and a tetrakis-O-(3-carboxy-propionyl)pentaerythritol tetrakis-(.alpha.-D-glucopyranosid-6-yl)tetraester;
- wherein R.sup.1 -R.sup.3 is a hydrogen atom or an alkyl group having 1-4 carbon atoms;
- wherein n, p and q is an integer from 1-6;
- and
- wherein r is an integer from 0-6;
- said method of preparing said triantennary glycoside having the step of:
- reacting formula 6:
- G'O--(CHR.sup.1).sub.n O(CHR.sup.2).sub.p !.sub.r OH (6)
- wherein G'O-- is a residue of a protected glycoside selected from the group consisting of monosaccharides and disaccharides,
- with a compound of formula 9:
- CH.sub.3 SCH.sub.2 O(CHR.sup.3).sub.q --!.sub.3 C--NHQ (9)
- wherein Q is an amino-protecting group, thereby resulting in a compound having a free amino group for subsequent attachment of --X.sup.3 --Z to said free amino group to form a --NH--X.sup.3 --Z group, and wherein in the glycoside residue G'O is deprotected to obtain the glycoside residue GO.
12 more elements
Dependencies are inferred from the claim text.