ANTITHROMBOTIC DUAL INHIBITORS COMPRISING A BIOTIN LABEL

摘要

51 ANTICOAGULANT ANTITHROMBOTIC DUAL INHIBITORS COMPRISING A 1310TIN LABEL ABSTRACT THE PRESENT INVENTION RELATES COMPOUNDS OF THE FORMULA: OLIGOSACCHARIDE-SPACER-(GPLFB/ILLA ANTAGONIST), WHEREIN THE OLIGOSACCHARIDE IS A NEGATIVELY CHARGED OLIGOSACCHARIDE RESIDUE COMPRISIRI.A FOUR TO TWENTY FIVE MONOSACCHARIDE UNITS, THE CHARGE BEING COMPENSATED BY POSITIVELY CHARGED COUNTERIONS, AND WHEREIN THE OLIGOSACCHARICLE RESIDUE IS DERIVED FROM AN OLIGOSACCHARIDE WHICH HAS (AT-111 MEDIATED) ANTI-XA ACTIVITY PER SE; THE SPACER IS A BOND OR AN ESSENTIALLY PHARMACOLOGICALLY INACTIVE LINKING RESIDUE; THE GPLLB/ILLA ANTAGONIST IS A RESIDUE MIMICKING THE RGD AND/OR K(QA)GD FRAGMENT OF FIBRINOGEN, COMPRISING A CARBOXYLATE MOIETY AND A BASIC MOIETY LOCATED WITHIN THE RESIDUE AT A DISTANCE OF 10-20 A FROM EACH OTHER; OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF OR A PRODRUG OR A SOLVATE THEREOF-, WHEREIN THE COMPOUND OF FORMULA I FIARTHER COMPRISES AT LEAST ONE COVALENT BOND WITH A BIOTIN LABEL OR AN ANALOGUE THEREOF. THE COMPOUNDS OF THE INVENTION HAVE ANTITHROMBOTIC ACTIVITY AND CAN BE USED IN TREATING OR PREVENTING (KROMBOTIC DISMES. THE ANTITHROMBOTIC ACTIVITY OF THE COMPOUND OF THIS INVENTION CAN BE NEUTRALIZED IN CASE OF EMERGENCY UPON ADMINSTRATION OF AVIDIN, STREPTAVIDIN AND ANALOGUES THEREOF HAVING HIGH BIOTIN AFFINITY.