The University of North Carolina at Chapel Hill

Inspire Pharmaceuticals, Inc.

Gillian M Olins

Benjamin R Yerxa

James G Douglass, Iii

José L Boyer

Sammy Ray Shaver

Krzysztof Bednarski

This invention is directed to a method of preventing or treating diseases or conditions associated with platelet aggregation. The method is also directed to a method of treating thrombosis. The method comprises administering to a subject a pharmaceutical composition comprising a therapeutic effective amount of P2Yreceptor antagonist compound, wherein said amount is effective to bind the P2Yreceptors on platelets and inhibit ADP-induced platelet aggregation. The P2Yreceptor antagonist compounds useful for this invention include mononucleoside 5'-monophosphates, mononucleoside polyphosphates, and dinucleoside polyphosphates of general Formula I, or salts thereof. The present invention also provides novel compounds of mononucleoside 5&#x2032;-monophosphates, mononucleoside polyphosphates, and dinucleoside polyphosphates. The present invention further provides pharmaceutical formulations comprising mononucleoside 5&#x2032;-monophosphates, mononucleoside polyphosphates, or dinucleoside polyphosphates.

Composition and method for inhibiting platelet aggregation

This invention is directed to a method of preventing or treating diseases or conditions associated with platelet aggregation. The method is also directed to a method of treating thrombosis. The method comprises administering to a subject a pharmaceutical composition comprising a therapeutically effective amount of P2Yreceptor antagonist compound, wherein said amount is effective to bind the P2Yreceptors on platelets and inhibit ADP-induced platelet aggregation. The P2Yreceptor antagonist compounds useful for this invention include mononucleoside polyphosphates and dinucleoside polyphosphates of general Formula I, or salts thereof The present invention also provides compositions comprising mononucleoside polyphosphates and dinucleoside polyphosphates according to Formula Ia and Ib.

The present invention provides novel compounds of dinucleotide polyphosphates and the method of preventing or treating diseases or conditions associated with platelet aggregation. The method comprises administering systemically to a patient a pharmaceutical comprising a purinergic P2receptor antagonist, in an amount effective to elevate its extracellular concentration to bind to P2receptors and inhibit P2receptor-mediated platelet aggregation. Methods of systemic administration include injection by intravenous, intramuscular, intrasternal and intravitreal routes, infusion, transdermal administration, oral administration, rectal administration and intra-operative instillation.

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Cary, NC, United States of America

Gillian M Olins