| abstract |
This invention relates to compounds that inhibit the binding of E-selectin or P-selectin to sialyl-Lewis<x> or sialyl-Lewis<a> presented on a cell surface having the general structure (II), wherein X is selected from the group consisting of -CO2R, -(CH2)nO(CH2)mCO2R, -(CH2)nCO2R, -O(CH2)nCO2R, -CONH(CHR2)nCO2R, -(CH2)nSO3H, -(CH2)nPO3D1D2, and -OH; A1 and A2 are independently selected from the group consisting of hydrogen, halogen, lower alkyl, -OR, -(CH2)nNR(CH2)mCO2R, -NRR, -CN, -N3, and -NO2; and A3 is hydrogen, halogen, lower alkyl, -(CH2)pNH2, -(CH2)pNR(CH2)qCO2R, or -(CH2)pNH(CH2)qCH3; where n and m are independently 1 to 6, p and q are independently 0 to 12, R is lower alkyl or hydrogen, R2 is any functional group that can be derived from an available alpha or beta amino acid, and D1 and D2 are independently hydrogen or methyl, and the pharmaceutically acceptable salts, esters, amides and prodrugs thereof. This invention also relates to methods of inhibiting the binding of E-selectin or P-selectin to sialyl-Lewis<x> or sialyl-Lewis<a> presented on a cell surface using said compounds and to pharmaceutically active compositions comprising compounds that inhibit the binding of E-selectin to sialyl-Lewis<x> and to methods of treatment of septic shock, ARDS, Crohn's disease, chronic inflammatory diseases, such as psoriasis and rheumatoid arthritis, and reperfusion injuries that occur following heart attacks, strokes and organ transplants and to the treatment of cancer. |