Bivalent sialyl X saccharides

A compound of the formula ##STR22## wherein R is selected from the group consisting of ##STR23## R.sup.1 is selected from the group consisting of hydrogen, a C.sub.1 -C.sub.18 straight chain, branched chain or cyclic hydrocarbyl, a C.sub.1 -C.sub.6 alkyl C.sub.1 -C.sub.5 alkylene .omega.-carboxylate and an .omega.-tri(C.sub.1 -C.sub.4 alkyl/phenyl)silyl C.sub.2 -C.sub.4 alkylene group, or OR.sup.1 together form a C.sub.1 -C.sub.18 straight chain, branched chain or cyclic hydrocarbyl carbamate;

• Y is selected from the group consisting of C(O), SO.sub.2, HNC(O), OC(O) and SC(O);
• R.sup.2 is selected from the group consisting of a C.sub.1 -C.sub.18 aliphatic, an aryl, a substituted aryl and a phenyl C.sub.1 -C.sub.3 alkylene group, wherein said aryl group has one six-membered aromatic ring or two fused six-membered aromatic rings, which ring or rings are hydrocarbyl, monoazahydrocarbyl, or diazahydrocarbyl rings, and said substituted aryl group is a before-mentioned aryl group having a substituent selected from the group consisting of halo, trifluoromethyl, nitro, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, amino, mono-C.sub.1 -C.sub.6 alkylamino, di-C.sub.1 -C.sub.6 alkylamino, benzylamino and C.sub.1 -C.sub.6 alkylbenzylamino;
• R.sup.3 is methyl or hydroxymethyl;
• X is selected from the group consisting of hydroxyl, C.sub.1 -C.sub.6 acyloxy, C.sub.2 -C.sub.6 hydroxylacyloxy, halo and azido;
• Z.sup.1 and Z.sup.2 are .alpha.-L-fucosyl or hydrogen (H), but at least one of Z.sup.1 and Z.sup.2 is .alpha.-L-fucosyl;
• and
• M is a proton (H.sup.+) or a pharmaceutically acceptable cation.

A pharmaceutical composition comprising an amount of a bivalent sialyl Lewis X saccharide sufficient to inhibit the binding of cells that express sialyl Le X on their surfaces to selectin, said bivalent sialyl Lewis X saccharide being dissolved or dispersed in a pharmaceutically acceptable diluent and having the structure ##STR32## wherein R is a directly linked bivalent monosaccharide unit;

• Y is selected from the group consisting of C(O), SO.sub.2, HNC(O), OC(O) and SC(O);
• R.sup.2 is selected from the group consisting of a C.sub.1 -C.sub.6 aliphatic, an aryl, a substituted aryl and a phenyl C.sub.1 -C.sub.3 alkylene group, wherein said aryl group has one six-membered aromatic ring or two fused six-membered aromatic rings, which ring or rings are hydrocarbyl, monoazahydrocarbyl, or diazahydrocarbyl rings, and said substituted aryl group is a before-mentioned aryl group having a substituent selected from the group consisting of halo, trifluoromethyl, nitro, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, amino, mono-C.sub.1 -C.sub.6 alkylamino, di-C.sub.1 -C.sub.6 alkylamino, benzylamino and C.sub.1 -C.sub.6 alkylbenzylamino;
• R.sup.3 is methyl or hydroxymethyl;
• X is selected from the group consisting of hydroxyl, C.sub.1 -C.sub.6 acyloxy, C.sub.2 -C.sub.6 hydroxylacyloxy, halo and azido;
• Z.sup.1 and Z.sup.2 are .alpha.-L-fucosyl or hydrogen (H), out at least one of Z.sup.1 and Z.sup.2 is .alpha.-L-fucosyl;
• and
• M is a proton (H.sup.+) or a pharmaceutically acceptable cation.

A process for inhibiting adhesion between selectin and cells that express sialyl Le X on their surfaces that comprises admixing selectin, and cells that express sialyl Le X on their surfaces in an aqueous medium with an adhesion-inhibiting amount of a bivalent SLe.sup.x saccharide compound having the formula ##STR34## wherein R is a directly linked divalent monosaccharide unit;

• Y is selected from the group consisting of C(O), SO.sub.2, HNC(O), OC(O) and SC(O);
• R.sup.2 is selected from the group consisting of a C.sub.1 -C.sub.18 aliphatic, an aryl, a substituted aryl and a phenyl C.sub.1 -C.sub.3 alkylene group, wherein said aryl group has one six-membered aromatic ring or two fused six-membered aromatic rings, which ring or rings are hydrocarbyl, monoazahydrocarbyl, or diazahydrocarbyl rings, and said substituted aryl group is a before-mentioned aryl group having a substituent selected from the group consisting of halo, trifluoromethyl, nitro, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, amino, mono-C.sub.1 -C.sub.6 alkylamino, di-C.sub.1 -C.sub.6 alkylamino, benzylamino and C.sub.1 -C.sub.6 alkylbenzylamino;
• R.sup.3 is methyl or hydroxymethyl;
• X is selected from the group consisting of hydroxyl, C.sub.1 -C.sub.6 acyloxy, C.sub.2 -C.sub.6 hydroxylacyloxy, halo and azido;
• Z.sup.1 and Z.sup.2 are .alpha.-L-fucosyl or hydrogen (H), but at least one of Z.sup.1 and Z.sup.2 is .alpha.-L-fucosyl;
• and
• M is a proton (H.sup.+) or a pharmaceutically acceptable cation.