Benzodiazepine derivatives for imaging thrombi
AssigneesDiatide, Inc., Genentech, Inc.
InventorsRichard T. Dean, John Lister-James, Michael C. Venuti, Todd C. Somers
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Abstract
The invention provides compounds comprising glycoprotein IIb/IIIa receptor-binding benzodiazepine derivatives covalently linked to metal ion chelators. The compounds of the invention may be labeled with a radionuclide such as 99mTc and used to image thrombi.
Claims25
A compound comprising a glycoprotein IIb/IIIa receptor binding benzodiazepine moiety covalently linked to a metal ion chelator, wherein the compound has an IC50 for inhibition of human platelet aggregation of less than about 1 μM, as measured in a standard inhibition of platelet aggregation assay.
A compound having a formula:
- wherein M is a metal ion chelator.
A pharmaceutical composition comprising 1-[(carboxyglycyl-glycyl-glycyl-cysteinamide)methyl]-4-(2-carboxyethyl)-7-[(4-amidinophenyl)methyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione trifluoroacetate, in combination with a pharmaceutically acceptable carrier or diluent.
A scintigraphic imaging agent comprising a γ-emitting radionuclide and a compound comprising a glycoprotein IIb/IIIa receptor binding benzodiazepine covalently linked to a metal ion chelating moiety, wherein the compound has an IC50 for inhibition of human platelet aggregation of less than about 1 μM, as measured in a standard inhibition of platelet aggregation assay.
A complex of a γ-emitting radionuclide and a compound comprising a glycoprotein IIb/IIIa receptor binding benzodiazepine covalently linked to a metal ion chelating moiety, wherein the compound has an IC50 for inhibition of human platelet aggregation of less than about 1 μM, as measured in a standard inhibition of platelet aggregation assay.
A 99mTc chelate of a compound comprising a glycoprotein IIb/IIIa receptor binding benzodiazepine covalently linked to a metal ion chelating moiety, wherein:
- a) the compound has an IC50 for inhibition of human platelet aggregation of less than about 1 μM, as measured in a standard inhibition of platelet aggregation assay;
- and
- b) the chelate contains at least one sulfur ligand bound to 99mTc.
A kit comprising a sealed vial containing:
- a) a predetermined quantity of 1-[(carboxyglycyl-glycyl-glycyl-cysteinamide)methyl]-4-(2-carboxyethyl)-7-[(4-amidinophenyl)methyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione trifluoroacetate;
- and
- b) a reducing agent.
Dependencies are inferred from the claim text.