Cyclic amines

Abstract

The present invention is directed to novel cyclic amines which inhibit the P2X7 receptor.

1 - 22 . (canceled) 
     
     
         23 . A method of treating seizures and seizure-associated neurodegenerative pathology in epilepsy caused by P2X7 receptor activation comprising administering a therapeutically P2X7 inhibiting effective amount of at least one compound of formula I: 
       
         
           
           
               
               
           
         
         wherein R 1  is pyrimidyl optionally substituted with one or more C 1-6  alkyl, halogen, hydroxy, C 1-4 fluoroalkyl, C 3-6 Cycloalkyl, C 1-6 alkoxy, C 1-6 fluoroalkoxy, cyano or —S0 2 R 7 ; 
         wherein R 2a  and R 2b  combine with the nitrogen to which they are attached to form piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, pyrrolo, imidazo, azetidinyl, 6 to 10 membered spiro(heterocyclyl), homomorpholinyl, homopiperidinyl or homopiperazinyl each of which is optionally substituted with one or more C 1-6  alkyl, C 1-6  alkenyl, C 3-6 -cycloalkyl, C 1-6  alkoxy, oxo, —NR 5 R 6  or fluorines; 
         wherein R 3  is halogen, C 1-4 fluoroalkyl, cyano, cyclopropyl, C 1-4 alkyloxy, C 1-4 fluoroalkyloxy, —S0 2 R 7 —NR 5 R 6  or C 1-6 alkyl; 
         wherein R 4  is halogen, C 1-6 alkyl, C 1-4 fluoroalkyl, cyano, —SO 2 R 7 , —NR 5 R 6 , C 1-6 alkoxy, C 1-4 fluoroalkoxy or C 3-6 -cycloalkyl; 
         wherein R 5  and R 6  independently of each other are hydrogen or C 1-6 alkyl; 
         wherein R 7  is C 1-6 alkyl, C 3-6 cycloalkyl, C 1-4 fluoroalkyl; and 
         wherein n is 0-3; 
         or a pharmaceutically acceptable salt of said compound. 
       
     
     
         24 . The compound of claim  1 , wherein R 2a  and R 2b  combine with the nitrogen to which they are attached to form optionally substituted piperazinyl. 
     
     
         25 . The compound of claim  1 , wherein R 2a  and R 2b  combine with the nitrogen to which they are attached to form optionally substituted piperidinyl. 
     
     
         26 . The compound of claim  1 , wherein R 2a  and R 2b  combine with the nitrogen to which they are attached to form optionally substituted morpholinyl. 
     
     
         27 . The compound of claim  1 , wherein R 2a  and R 2b  combine with the nitrogen to which they are attached to form optionally substituted pyrrolidinyl. 
     
     
         28 . The compound of claim  1 , wherein R 2a  and R 2b  combine with the nitrogen to which they are attached to form optionally substituted pyrrolo. 
     
     
         29 . The compound of claim  1 , wherein R 2a  and R 2b  combine with the nitrogen to which they are attached to form optionally substituted imidazo. 
     
     
         30 . The compound of claim  1 , wherein R 2a  and R 2b  combine with the nitrogen to which they are attached to form optionally substituted 6 to 10 membered spiro(heterocyclyl). 
     
     
         31 . The compound of claim  1 , wherein R 2a  and R 2b  combine with the nitrogen to which they are attached to form optionally substituted homomorpholinyl. 
     
     
         32 . The compound of claim  1 , wherein R 2a  and R 2b  combine with the nitrogen to which they are attached to form optionally substituted homopiperidinyl. 
     
     
         33 . The compound of claim  1 , wherein R 2a  and R 2b  combine with the nitrogen to which they are attached to form optionally substituted homopiperazinyl. 
     
     
         34 . The compound of claim  1 , wherein R 2a  and R 2b  combine with the nitrogen to which they are attached to form optionally substituted azetidinyl. 
     
     
         35 . The compound of claim  1 , wherein R 3  is chlorine, methyl or trifluoromethyl. 
     
     
         36 . The compound of claim  1 , wherein n is 0. 
     
     
         37 . The compound of claim  1 , wherein n is 1. 
     
     
         38 . The compound of claim  1 , wherein n is 2. 
     
     
         39 . The compound of claim  1 , wherein R 4  is fluorine, chlorine, C 1-3  alkyl, C 1-4 fluoroalkyl, cyano, C 1-3  alkoxy or C 1-4 fluoroalkoxy. 
     
     
         40 . The compound of claim  1 , wherein said compound is 2-chloro-N-[2-morpholino-2-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl]benzamide. 
     
     
         41 . The compound of claim  1 , wherein said compound is (−)2-chloro-N-[2-morpholino-2-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl]benzamide. 
     
     
         42 . The compound of claim  1 , wherein said compound is (+)2-chloro-N-[2-morpholino-2-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl]benzamide.