Novel Pyrimidinyl-DiazoSpiro Compounds

Abstract

The invention relates to spiro derivatives, to the use of said derivatives in treating diseases and conditions mediated by modulation of voltage-gated sodium channels, to compositions containing said derivatives and processes for their preparation.

What is claimed is: 
     
         1 .- 18 . (canceled) 
     
     
         19 . A method for treating a disease or condition mediated by modulation of voltage-gated sodium channels, comprising administering to the patient an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof 
       
         
           
           
               
               
           
         
       
       wherein:
 Ring A represents a phenyl ring, a 5- or 6-membered aromatic heterocyclic ring or a 5- to 12-membered aromatic or non-aromatic bicyclic heterocyclic group; 
 n represents an integer selected from 0 to 4; 
 each R 1  independently represents C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, —Z—C 3-6  cycloalkyl, halogen, haloC 1-6  alkyl, C 1-6  alkoxy, haloC 1-6  alkoxy, —Z-phenyl, —Z-Het, —CN, —CONR 6 R 7 , —NR 6 R 7 , —Z—C 1-3  alkyl, wherein said Het group represents a 5- or 6-membered aromatic heterocyclic ring or a 4- to 7-membered non-aromatic heterocyclic ring, wherein said phenyl or Het group of R 1  may be optionally substituted by one or more (e.g. 1, 2 or 3) R 8  groups and wherein n represents an integer greater than 1, said R 1  groups represent no more than one —Z-phenyl or one —Z-Het group; 
 Z represents a bond or a linker selected from —O—, —CH 2 —, —CH 2 —O— or —O—CH 2 —; 
 R 6  and R 7  independently represent hydrogen or C 1-6  alkyl or R 6  and R 7  together with the nitrogen atom to which they are attached join to form a 4- to 7-membered nitrogen containing non-aromatic heterocyclic ring; 
 R 8  represents C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, halogen, haloC 1-6 alkyl, C 1-6  alkoxy, haloC 1-6 alkoxy, —CN or —NR 6 R 7 ; 
 m represents an integer selected from 0 to 2; 
 each R 2  independently represents C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, halogen, haloC 1-6 alkyl, C 1-6  alkoxy, haloC 1-6 alkoxy, —CN or —NR 7 R 8 ; 
 R 3  represents hydrogen or C 1-6  alkyl; 
 R 4  represents hydrogen or C 1-6  alkyl; 
 p represents an integer from 0 to 3; 
 each R 5  independently represents C 1-3  alkyl or fluoro; 
 Y represents —CH 2 — or —(CH 2 ) 2 —; 
 q represents an integer selected from 0 to 2; and 
 R 9  represents C 1-3  alkyl. 
 
     
     
         20 . The method of  claim 19 , wherein the compound of formula (I) is other than 7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one. 
     
     
         21 . The method of  claim 19 , wherein q represents 0. 
     
     
         22 . The method of  claim 19 , wherein Ring A represents a phenyl ring. 
     
     
         23 . The method of  claim 19 , wherein n represents an integer selected from 1 or 2. 
     
     
         24 . The method of  claim 19 , wherein R 1  independently represents halogen, haloC 1-6  alkyl, C 1-6  alkoxy or haloC 1-6  alkoxy. 
     
     
         25 . The method of  claim 19 , wherein m represents an integer selected from 0 or 1. 
     
     
         26 . The method of  claim 19 , wherein R 2  represents C 1-6  alkyl. 
     
     
         27 . The method of  claim 19 , wherein R 3  represents hydrogen. 
     
     
         28 . The method of  claim 19 , wherein R 4  represents hydrogen or methyl. 
     
     
         29 . The method of  claim 19 , wherein p represents 0. 
     
     
         30 . The method of  claim 19 , wherein Y represents CH 2 . 
     
     
         31 . A method for treating a disease or condition mediated by modulation of voltage-gated sodium channels, comprising administering to the patient an effective amount of a pharmaceutical composition comprising a compound of formula (I) as defined in  claim 19 , or a pharmaceutically acceptable salt thereof, with one or more pharmaceutically acceptable carrier(s), diluents(s) and/or excipient(s). 
     
     
         32 . A method for treating a disease or condition mediated by modulation of voltage-gated sodium channels, comprising administering to the patient an effective amount of a compound selected from:
 (2R,5S)-7-Methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-7-Methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-7-Methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5R)-7-Methyl-2-[4-[4-(trifluoromethyl)-phenyl]-pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5R)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1, 7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5 S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,6S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-1,8-diazaspiro[4.5]decan-7-one;   (2S,6S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-1,8-diazaspiro[4.5]decan-7-one;   (2R,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5 S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5S)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5R)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6 one;   (2S,5S)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5R)-2-[4-(4-Isopropoxyphenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-2-[4-(4-Isopropoxyphenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-2-[4-(4-Isopropoxyphenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-2-[4-(4-Isopropoxyphenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5S)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5R)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-2-[4-[2-Fluoro-5-(trifluoromethoxy)phenyl]-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5S)-2-[4-[2-Fluoro-5-(trifluoromethoxy)phenyl]-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5R)-2-[4-[2-Fluoro-5-(trifluoromethoxy)phenyl]-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-2-[4-[2-Fluoro-5-(trifluoromethoxy)phenyl]-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5S)-7-Methyl-2-[4-methyl-6-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-7-Methyl-2-[4-methyl-6-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2R,6R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-1,8-diazaspiro[4.5]decan-7-one;   (2S,6R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-1,8-diazaspiro[4.5]decan-7-one;   (2R,5S)-2-[4-Methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1, 7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-2-[4-Methyl-6-[4-(trifluoromethyl)phenyl]-pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-2-[4-Methyl-6-[4-(trifluoromethyl)-phenyl]-pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5R)-2-[4-Methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5S)-8,8-Dimethyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-8,8-Dimethyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-8,8-Dimethyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one; and   (2R,5R)-8,8-Dimethyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one   
       or a pharmaceutically acceptable salt thereof. 
     
     
         33 . A method for treating a disease or condition mediated by modulation of voltage-gated sodium channels, comprising administering to the patient an effective amount of a pharmaceutical composition comprising a compound of  claim 32 , or a pharmaceutically acceptable salt thereof, with one or more pharmaceutically acceptable carrier(s), diluents(s) and/or excipient(s). 
     
     
         34 . A method for treating a disease or condition mediated by modulation of voltage-gated sodium channels, comprising administering to the patient an effective amount of a hydrochloride selected from:
 (2R,5S)-7-Methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-7-Methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-7-Methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5R)-7-Methyl-2-[4-[4-(trifluoromethyl)-phenyl]-pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5R)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1, 7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5 S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,6S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-1,8-diazaspiro[4.5]decan-7-one hydrochloride;   (2S,6S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-1,8-diazaspiro[4.5]decan-7-one hydrochloride;   (2R,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5 S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5S)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5R)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6 one hydrochloride;   (2S,5S)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5R)-2-[4-(4-Isopropoxyphenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-2-[4-(4-Isopropoxyphenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-2-[4-(4-Isopropoxyphenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-2-[4-(4-Isopropoxyphenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5S)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5R)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-2-[4-[2-Fluoro-5-(trifluoromethoxy)phenyl]-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5S)-2-[4-[2-Fluoro-5-(trifluoromethoxy)phenyl]-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5R)-2-[4-[2-Fluoro-5-(trifluoromethoxy)phenyl]-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-2-[4-[2-Fluoro-5-(trifluoromethoxy)phenyl]-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5S)-7-Methyl-2-[4-methyl-6-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-7-Methyl-2-[4-methyl-6-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,6R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-,8-diazaspiro[4.5]decan-7-one hydrochloride;   (2S,6R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-1,8-diazaspiro[4.5]decan-7-one hydrochloride;   (2R,5S)-2-[4-Methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-2-[4-Methyl-6-[4-(trifluoromethyl)phenyl]-pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-2-[4-Methyl-6-[4-(trifluoromethyl)-phenyl]-pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5R)-2-[4-Methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5S)-8,8-Dimethyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-8,8-Dimethyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-8,8-Dimethyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride; and   (2R,5R)-8,8-Dimethyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1, 7-diazaspiro[4.4]nonan-6-one hydrochloride.   
     
     
         35 . A method for treating a disease or condition mediated by modulation of voltage-gated sodium channels, comprising administering to the patient an effective amount of a pharmaceutical composition comprising a hydrochloride of  claim 34  with one or more pharmaceutically acceptable carrier(s), diluents(s) and/or excipient(s). 
     
     
         36 . A method for treating a disease or condition mediated by modulation of voltage-gated sodium channels, comprising administering to the patient an effective amount of a compound selected from:
 (2R,5S)-7-Methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-7-Methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-7-Methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5R)-7-Methyl-2-[4-[4-(trifluoromethyl)-phenyl]-pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5R)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1, 7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5 S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,6S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-1,8-diazaspiro[4.5]decan-7-one;   (2S,6S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-1,8-diazaspiro[4.5]decan-7-one;   (2R,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5 S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5S)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5S)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2S,5R)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;   (2R,5R)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one; and   (2S,5S)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one   
       or a pharmaceutically acceptable salt thereof. 
     
     
         37 . A method for treating a disease or condition mediated by modulation of voltage-gated sodium channels, comprising administering to the patient an effective amount of a pharmaceutical composition comprising a compound of  claim 36 , or a pharmaceutically acceptable salt thereof, with one or more pharmaceutically acceptable carrier(s), diluents(s) and/or excipient(s). 
     
     
         38 . A method for treating a disease or condition mediated by modulation of voltage-gated sodium channels, comprising administering to the patient an effective amount of a hydrochloride selected from:
 (2R,5S)-7-Methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-7-Methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-7-Methyl-2-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5R)-7-Methyl-2-[4-[4-(trifluoromethyl)-phenyl]-pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5R)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5 S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,6S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-1,8-diazaspiro[4.5]decan-7-one hydrochloride;   (2S,6S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-1,8-diazaspiro[4.5]decan-7-one hydrochloride;   (2R,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5 S)-2-[4-(5-Ethoxy-2-fluoro-phenyl)pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5S)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5S)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2S,5R)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-,7-diazaspiro[4.4]nonan-6-one hydrochloride;   (2R,5R)-7-Methyl-2-[4-[3-(trifluoromethoxy)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride; and   (2S,5S)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one hydrochloride.   
     
     
         39 . A method for treating a disease or condition mediated by modulation of voltage-gated sodium channels, comprising administering to the patient an effective amount of a pharmaceutical composition comprising a hydrochloride of  claim 38  with one or more pharmaceutically acceptable carrier(s), diluents(s) and/or excipient(s).