4 - (2-butylamino) - 2, 7-dimethyl-8- (2-methyl-6-methoxypyrid-3-yl) pyrazolo- [1,5-A] - 1,3,5-triazine, its enantiomers and pharmaceutically acceptable salts as corticotropin releasing factor receptor ligands

Abstract

Corticotropin releasing factor (CRF) antagonists of Formula (I): and its use in treating anxiety, depression, and other psychiatric, neurological disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress.

What is claimed is:  
     
         1 . A compound of Formula (I):  
       
         
           
           
               
               
           
         
       
       isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, pharmaceutically acceptable prodrugs thereof, or pharmaceutically acceptable salt forms.  
     
     
         2 . A compound of  claim 1 , pharmaceutically acceptable prodrugs thereof, or pharmaceutically acceptable salt forms thereof, wherein said compound is 4-((R)-2-butylamino)2,7-dimethyl-8-(2-methyl-6-methoxypyrid-3-yl) [1,5-a]-pyrazolo-1,3,5-triazine.  
     
     
         3 . A compound of  claim 1 , pharmaceutically acceptable prodrugs thereof, or pharmaceutically acceptable salt forms thereof, wherein said compound is substantially free of its (S) stereoisomer.  
     
     
         4 . A compound of  claim 1 , wherein said compound is 4-(2-butylamino)2,7-dimethyl-8-(2-methyl-6-methoxypyrid-3-yl) [1,5-a]-pyrazolo-1,3,5-triazine.  
     
     
         5 . A compound of  claim 1 , wherein said compound is 4-((R)-2-butylamino)2,7-dimethyl-8-(2-methyl-6-methoxypyrid-3-yl) [1,5-a]-pyrazolo-1,3,5-triazine.  
     
     
         6 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of  claim 1 .  
     
     
         7 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of  claim 5 .  
     
     
         8 . A method of antagonizing a CRF receptor in a mammal, comprising administering to the mammal, a therapeutically effective amount of a compound as claimed in  claim 1 .  
     
     
         9 . A method of treating a disorder manifesting hypersecretion of CRF in a warm-blooded animal, comprising administering to the animal a therapeutically effective amount of a compound as claimed in  claim 1 .  
     
     
         10 . A method for the treatment of a disorder, the treatment of which can be effected or facilitated by antagonizing CRF, comprising administering to the mammal a therapeutically effective amount of a compound of  claim 1 .  
     
     
         11 . A method of antagonizing a CRF receptor in a mammal, comprising administering to the mammal, a therapeutically effective amount of a compound as claimed in  claim 5 .  
     
     
         12 . A method of treating anxiety or depression in mammals, comprising administering to the mammal a therapeutically effective amount of a compound of  claim 1 .  
     
     
         13 . A method of treating anxiety or depression in mammals, comprising administering to the mammal a therapeutically effective amount of a compound of  claim 5 .  
     
     
         14 . A method for screening for ligands for CRF receptors, which method comprises: 
 a) carrying out a competitive binding assay with a CRF receptor, a compound according to  claim 1  which is labelled with a detectable label, and a candidate ligand; and    b) determining the ability of said candidate ligand to displace said labelled compound.    
     
     
         15 . A method for detecting CRF receptors in tissue comprising: 
 a) contacting a compound of  claim 1 , which is labelled with a detectable label, with a tissue, under conditions that permit binding of the compound to the tissue; and    b) detecting the labelled compound bound to the tissue.    
     
     
         16 . A method of inhibiting the binding of CRF to a CRF-1 receptor, comprising contacting a compound of  claim 1  with a solution comprising cells expressing the CRF1 receptor, wherein the compound is present in the solution at a concentration sufficient to inhibit the binding of CRF to the CRF-1 receptor.  
     
     
         17 . An article of manufacture comprising: 
 a) a packaging material;    b) a compound of  claim 1;  and    c) a label or package insert contained within said packaging material idicating that said compound is effective for treating anxiety or depression.