SIALYL LEWIS-X ANALOGUES AS INHIBITORS OF CELLULAR ADHESION

摘要

The inventive compounds are analogues of sialyl Lex that inhibit cellular adhesion between a selectin and cells that express sialyl Lex on their surfaces, and their synthetic intermediates. An inventive compound has structure A, IMAGE A wherein Z is hydrogen, C1-C6 acyl or IMAGE Y is C(O), SO2, HNC(O), OC(O) or SC(O); R1 is an aryl, a substituted aryl or a phenyl C1-C3 alkylene group, wherein an aryl group has one five- or six-membered aromatic ring, a fused five/six-membered aromatic ring, or two fused six-membered aromatic rings, which rings are hydrocarbyl, monooxahydrocarbyl, monothiahydrocarbyl, monoazahydrocarbyl or diazahydrocarbyl rings, and a substituted aryl group is an aryl group having a halo, trifluoromethyl, nitro, C1-C18 alkyl, C1-C18 alkoxy, amino, mono-C1-C18 alkylamino, di-C1-C18 alkylamino, benzylamino, C1-C18 alkylbenzylamino, C1-C18 thioalkyl or C1-C18 alkyl carboxamido substituent, or R1 Y is allyloxycarbonyl or chloroacetyl; R2 is hydrogen, C1-C18 straight chain, branched chain or cyclic hydrocarbyl, C1-C6 alkyl C1-C5 alkylene omega -carboxylate, omega -tri(C1-C4 alkyl/phenyl)silyl C2-C4 alkylene, monosaccharide or disaccharide, or OR2 together form a C1-C18 straight chain, branched chain or cyclic hydrocarbyl carbamate; R3 is hydrogen or C1-C6 acyl; R4 is hydrogen, C1-C6 alkyl or benzyl; R5 is hydrogen, benzyl, methoxybenzyl, dimethoxybenzyl or C1-C6 acyl; R7 is methyl or hydroxymethyl; and X is C1-C6 acyloxy, C2-C6 hydroxylacyloxy, hydroxy, halo or azido.