Method of treatment using substituted pyrazolo[1,5-a] pyrimidine compounds

Abstract

Compounds useful in the synthesis of compounds for treating pain, cancer, inflammation, neurodegenarative disease or Typanosoma cruzi infection in a mammal.

What is claimed is: 
     
         1 . A compound having the general formula I 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is H or (1-6C alkyl); 
 R 2  is NR b R c , (1-4C)alkyl, (1-4C)fluoroalkyl, CF 3 , (1-4C)hydroxyalkyl, -(1-4C alkyl)hetAr 1 , -(1-4C alkyl)NH 2 , -(1-4C alkyl)NH(1-4C alkyl), -(1-4C alkyl)N(1-4C alkyl) 2 , hetAr 2 , hetCyc 1 , hetCyc 2 , phenyl which is optionally substituted with NHSO 2 (1-4C alkyl), or (3-6C)cycloalkyl which is optionally substituted with (1-4C alkyl), CN, OH, OMe, NH 2 , NHMe, N(CH 3 ) 2 , F, CF 3 , CO 2 (1-4C alkyl), CO 2 H, C(═O)NR e R f  or C(═O)OR g ; 
 R b  is H or (1-6C alkyl); 
 R c  is H, (1-4C)alkyl, (1-4C)hydroxyalkyl, hetAr 3 , or phenyl, wherein said phenyl is optionally substituted with one or more substituents independently selected from halogen, CN, CF 3  and —O(1-4C alkyl), 
 or NR b R c  forms a 4 membered heterocyclic ring having a ring nitrogen atom, wherein said heterocyclic ring is optionally substituted with one or more substituents independently selected from halogen, OH, (1-4C alkyl), (1-4 C)alkoxy, —OC(═O)(1-4C alkyl), NH 2 , —NHC(═O)O(1-4C alkyl) and (1-4C)hydroxyalkyl, 
 or NR b R c  forms a 5-6 membered heterocyclic ring having a ring heteroatom which is nitrogen and optionally having a second ring heteroatom or group selected from N, O and SO 2 , wherein the heterocyclic ring is optionally substituted with one or more substituents independently selected from OH, halogen, CF 3 , (1-4C)alkyl, CO 2 (1-4C alkyl), CO 2 H, NH 2 , NHC(═O)O(1-4C alkyl) and oxo, 
 or NR b R c  forms a 7-8 membered bridged heterocyclic ring having a ring nitrogen atom and optionally having a second ring heteroatom selected from N and O, wherein said ring is optionally substituted with CO 2 (1-4C alkyl); 
 hetAr 1  is a 5-membered heteroaryl ring having 1-3 ring nitrogen atoms; 
 hetAr 2  is 5-6 membered heteroaryl ring having at least one nitrogen ring atom and optionally having a second ring heteroatom independently selected from N and S, wherein said heteroaryl ring is optionally substituted with one or more substituents independently selected from (1-4C alkyl), halogen, -(1-4 C)alkoxy and NH(1-4C alkyl); 
 hetCyc 1  is a carbon-linked 4-6 membered azacyclic ring optionally substituted with one or more substituents independently selected from (1-4C alkyl), and CO 2 (1-4C alkyl); 
 hetCyc 2  is a pyridinone or pyridazinone ring which is optionally substituted with a substituent selected from (1-4C)alkyl; 
 hetAr 3  is a 5-6 membered heteroaryl ring having 1-2 ring heteroatoms independently selected from N and O and optionally substituted with one or more substituents independently selected from (1-4C)alkyl; 
 R e  is H or (1-4C)alkyl; 
 R f  is H, (1-4C)alkyl, or (3-6C)cycloalkyl; 
 or NR e R f  forms a 4-6-membered azacyclic ring optionally having an additional ring heteroatom selected from N and O, wherein the azacyclic ring is optionally substituted with OH; 
 R g  is H or (1-6C)alkyl; 
 Y is (i) phenyl optionally substituted with one or more substituents independently selected from halogen, (1-4C)alkoxy, CF 3  and CHF 2 , or (ii) a 5-6 membered heteroaryl ring having a ring heteroatom selected from N and S, wherein said heteroaryl ring is optionally substituted with one or more halogen atoms; 
 X is null, —CH 2 —, CH 2 CH 2 —, —CH 2 O—, or —CH 2 NR d —; 
 R d  is H or (1-4C alkyl); 
 R 3  is H or (1-4C alkyl); 
 each R 4  is independently selected from halogen, (1-4C)alkyl, OH, (1-4 C)alkoxy, NH 2 , NH(1-4C alkyl) and CH 2 OH; and 
 n is 0, 1, 2, 3, 4, 5 or 6.