Novel Tetrahydronaphalene Antagonists to the Thromboxane A2 (TP) Receptor

Abstract

The present invention relates to TP receptor antagonists, which have the ability to bind to TP receptor and optionally cross the blood brain barrier. The invention also provides compositions and methods for treating a disorder wherein activation of TP receptor is detrimental.

What is claimed is: 
     
         1 . A composition comprising a TP receptor antagonist, wherein said antagonist comprises the chemical structures set forth in  FIG. 12A , a salt thereof, a prodrug thereof, and combinations thereof. 
     
     
         2 . The composition of  claim 1 , wherein said antagonist binds to a TP receptor or a TP-like receptor. 
     
     
         3 . The composition of  claim 1 , wherein said antagonist inhibits activation of a TP receptor or a TP-like receptor. 
     
     
         4 . The composition of  claim 1 , wherein said antagonist is able to cross the blood brain barrier of a mammal. 
     
     
         5 . The composition of  claim 1 , wherein said antagonist is not able to cross the blood brain barrier of a mammal. 
     
     
         6 . The composition of  claim 1 , wherein said antagonist is selected from the group consisting of CNDR-51418, CNDR-51281, CNDR-51354 and CNDR-51414. 
     
     
         7 . A method of treating a disorder associated with activation of a TP receptor in a mammal in need thereof, said method comprising administering to said mammal a therapeutically effective amount of a compound, wherein said compound comprises a TP receptor antagonist, wherein said antagonist comprises the chemical structures set forth in  FIG. 12A , a salt thereof, a prodrug thereof, and combinations thereof. 
     
     
         8 . The method of  claim 7 , wherein said antagonist is able to cross the blood brain barrier of said mammal. 
     
     
         9 . The method of  claim 7 , wherein said antagonist is not able to cross the blood brain barrier of said mammal. 
     
     
         10 . The method of  claim 7 , wherein said mammal is a human. 
     
     
         11 . The method of  claim 7 , wherein said disorder associated with activation of a TP receptor is a neurodegenerative disorder. 
     
     
         12 . The method of  claim 11 , wherein said neurodegenerative disorder is Alzheimer's disease. 
     
     
         13 . The method of  claim 7 , wherein said compound is administered to the mammal orally, parenterally, intravascularly, intranasally, or intrabronchially. 
     
     
         14 . The method of  claim 7 , wherein said compound substantially modulates central nervous system function of said mammal. 
     
     
         15 . The method of  claim 7 , wherein said compound inhibits activation of a TP receptor on a cell of the central nervous system such that said cell does not mediate said disorder, wherein said inhibition of TP receptor is mediated by contacting a TP receptor on said cell of the central nervous system with an effective amount of a TP antagonist. 
     
     
         16 . The method of  claim 15 , wherein said TP antagonist binds to a TP receptor or a TP-like receptor. 
     
     
         17 . The method of  claim 7 , wherein said compound is administered in combination with a second therapeutic agent, wherein said therapeutic agent is an anti-amyloid medicament. 
     
     
         18 . The method of  claim 17 , wherein said second therapeutic agent is administered simultaneously, prior to, or after administration of said compound.