Selective calcium channel antagonists

Abstract

The present invention relates to compositions and methods for the treatment and/or prevention of neurodegenerative disorders, e.g., Parkinson's disease (PD). In particular, the present invention provides compositions comprising selective antagonists of calcium ion channels (e.g., Cav1.3-type ion channels), and methods of use thereof to treat or prevent neurodegenerative disorders.

What is claimed is: 
     
         1 . A method of selectively inhibiting a Cav1.3-calcium ion channel, comprising contacting said Cav1.3-calcium ion channel with a compound of the formula: 
       
         
           
           
               
               
           
         
         wherein R1 comprises a cycloalkane or bicycloalkane, and R2 comprises a substituted aryl ring group. 
       
     
     
         2 . The method of  claim 1 , wherein R1 comprises cyclohexane, cyclopentane, or bicyclo[2.2.1]heptanes (norbornane). 
     
     
         3 . The method of  claim 1 , wherein R 2  comprises a substituted phenyl group. 
     
     
         4 . The method of  claim 4 , wherein said phenyl group comprises a single non-hydrogen substituent selected from the group consisting of: F, Cl, Br, CF 3 , CO 2 H, CN, NO 2 , MeO, and Me. 
     
     
         5 . The method of  claim 1 , wherein said compound has formula: 
       
         
           
           
               
               
           
         
       
       or derivatives thereof. 
     
     
         6 . The method of  claim 1 , wherein said compound has the formula: 
       
         
           
           
               
               
           
         
       
       or derivatives thereof. 
     
     
         7 . The method of  claim 1 , wherein said compound has the formula: 
       
         
           
           
               
               
           
         
       
       or derivatives thereof. 
     
     
         8 . The method of  claim 1 , wherein said compound has the formula: 
       
         
           
           
               
               
           
         
       
       or derivatives thereof. 
     
     
         9 . The method of  claim 1 , wherein said compound has the formula: 
       
         
           
           
               
               
           
         
       
       or derivatives thereof. 
     
     
         10 . The method of  claim 1 , wherein said compound has the formula: 
       
         
           
           
               
               
           
         
       
       or derivatives thereof. 
     
     
         11 . The method of  claim 1 , wherein said compound has the formula: 
       
         
           
           
               
               
           
         
       
       or derivatives thereof. 
     
     
         12 . A method of treating and/or preventing a neurodegenerative disorder comprising administering to a subject a Cav1.3-selective calcium ion channel antagonist of the formula: 
       
         
           
           
               
               
           
         
       
       wherein R1 comprises a cycloalkane or bicycloalkane, and R2 comprises a substituted aryl ring group. 
     
     
         13 . The method of  claim 12 , wherein said neurodegenerative disorder comprises Parkinson's disease. 
     
     
         14 . The method of  claim 12 , wherein said neurodegenerative disorder comprises Alzheimer's disease. 
     
     
         15 . The method of  claim 12 , wherein said subject suffers from a neurodegenerative disorder. 
     
     
         16 . The method of  claim 12 , wherein said subject has one or more risk factors for a neurodegenerative disorder. 
     
     
         17 . The method of  claim 16 , wherein said risk factors for a neurodegenerative disorder comprise: increased age, genetic polymorphisms linked to neurodegenerative disorders, environmental factors, gender, education, endocrine conditions, oxidative stress, inflammation, stroke, hypertension, diabetes, smoking, head trauma, depression, infection, tumors, vitamin deficiencies, immune and metabolic conditions, and chemical exposure. 
     
     
         18 . The method of  claim 12 , wherein R1 comprises cyclohexane, cyclopentane, or bicyclo[2.2.1]heptanes (norbornane). 
     
     
         19 . The method of  claim 12 , wherein R2 comprises a substituted phenyl group. 
     
     
         20 . A pharmaceutical composition comprising a Cav1.3-selective calcium ion channel antagonist of the formula: 
       
         
           
           
               
               
           
         
       
       wherein R1 comprises a cycloalkane or bicycloalkane, and R2 comprises a substituted aryl ring group. In some embodiments, R1 comprises cyclohexane, cyclopentane, or bicyclo[2.2.1]heptanes (norbornane). In some embodiments, R2 comprises a substituted phenyl group. In some embodiments, the phenyl group comprises a single non-hydrogen substituent selected from the group consisting of: F, Cl, Br, CF 3 , CO 2 H, CN, NO 2 , MeO, and Me.