HYDROPHOBIC POLYAMINE AMIDES AS POTENT LIPOPOLYSACCHARIDE SEQUESTRANTS

摘要

Lysine-spermine conjugates with a long-chain aliphatic (CSUB12/SUB-CSUB20/SUB) substituent at RSUB1 /SUBbind and neutralize bacterial lipopolysaccharides. These compounds reduce lethality in a murine model of lipopolysaccharide-induced shock, and may serve as novel leads for developing novel anti-lipopolysaccharide agents for the therapy of Gram-negative sepsis. These compounds are represented by the formula: wherein X is O or H, H; R is a hydrophobic CSUB12/SUB-CSUB20 /SUBchain and Y is -NHSUB2 /SUBor -H; and pharmaceutically acceptable salts thereof and prodrugs thereof.