2-aminopyrimidine modulators of the histamine h4 receptor

Abstract

2-Aminopyrimidine compounds are described, which are useful as H 4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H 4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritus.

1 . A chemical entity selected from compounds of Formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is:
 a) a C 1-6 alkyl group, optionally substituted with —OH, —OC 1-4 alkyl, —CF 3 , or —O— (monocyclic cycloalkyl); 
 b) a benzyl, —CH 2 -(monocyclic heteroaryl), or phenethyl group, each optionally substituted with halo; 
 c) a monocyclic cycloalkyl, —(CH 2 ) 0-1 -tetrahydrofuranyl, or —(CH 2 ) 0-1 -tetrahydropyranyl group, each optionally fused to a phenyl ring, and each optionally substituted with C 1-4 alkyl or phenyl; or 
 d) an adamantyl group; 
 
         R 2  is H, F, methyl, or methoxy; 
         or R 1  and R 2  taken together form —(CH 2 ) 3-5 — or —(CH 2 ) 2 OCH 2 —; and —N(R 3 )R 4  is one of the following acyclic, monocyclic, spirocyclic, bridged, or fused ring systems: 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           where q is 0 or 1; 
           R 3  and R 4  are taken together as defined by the structure of each one of such moieties; 
           R a  is H or OH; 
           R b  and R c  are each independently H or C 1-3 alkyl; and 
           each R d  substitutent is methyl or two R d  substituents taken together form a methylene or ethylene bridge; 
         
         provided that when R 1  is methyl, then —N(R 3 )R 4  is selected from said spirocyclic, bridged, and fused ring systems; 
         and pharmaceutically acceptable salts of compounds of Formula (I), pharmaceutically acceptable prodrugs of compounds of Formula (I), and pharmaceutically active metabolites of Formula (I). 
       
     
     
         2 . A chemical entity as in  claim 1 , wherein R 1  is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, methoxymethyl, ethoxymethyl, isopropoxymethyl, tert-butoxymethyl, 3,3,3-trifluoropropyl, cyclopropoxymethyl, benzyl, 4-chlorobenzyl, thiophen-2-ylmethyl, thiophen-3-ylmethyl, pyridin-4-ylmethyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 2-phenyl-cyclopropyl, indan-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl, 4-methyl-tetrahydro-pyran-4-yl, 2,3-dihydro-benzofuran-2-yl, tetrahydrofuran-2-ylmethyl, or adamantyl. 
     
     
         3 . A chemical entity as in  claim 1 , wherein R 1  is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. 
     
     
         4 . A chemical entity as in  claim 1 , wherein R 2  is H. 
     
     
         5 . A chemical entity as in  claim 1 , wherein R 1  and R 2  taken together form —(CH 2 ) 4 —. 
     
     
         6 . A chemical entity as in  claim 1 , wherein R 1  and R 2  taken together form —(CH 2 ) 2 OCH 2 —. 
     
     
         7 . A chemical entity as in  claim 1 , wherein —N(R 3 )R 4  is: 
       
         
           
           
               
               
           
         
       
     
     
         8 . A chemical entity as in  claim 1 , wherein —N(R 3 )R 4  is: 
       
         
           
           
               
               
           
         
       
     
     
         9 . A chemical entity as in  claim 1 , wherein —N(R 3 )R 4  is: 
       
         
           
           
               
               
           
         
       
     
     
         10 . A chemical entity as in  claim 1 , wherein —N(R 3 )R 4  is: 
       
         
           
           
               
               
           
         
       
     
     
         11 . A chemical entity as in  claim 1 , wherein —N(R 3 )R 4  is: 
       
         
           
           
               
               
           
         
       
     
     
         12 . A chemical entity as in  claim 1 , wherein —N(R 3 )R 4  is: 
       
         
           
           
               
               
           
         
       
     
     
         13 . A chemical entity as in  claim 1 , wherein —N(R 3 )R 4  is: 
       
         
           
           
               
               
           
         
       
     
     
         14 . A chemical entity as in  claim 1 , wherein R a  is H. 
     
     
         15 . A chemical entity as in  claim 1 , wherein R b  and R c  are each independently H or methyl. 
     
     
         16 . A chemical entity selected from the group consisting of:
 4-Cyclopentyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-piperidin-1-yl)-6-cyclopentyl-pyrimidin-2-ylamine;   (R)-4-Cyclopentyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   trans-1-(2-Amino-6-cyclopentyl-pyrimidin-4-yl)-4-methylamino-pyrrolidin-3-ol;   4-Cyclopentyl-6-(cis-hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Isopropyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-piperidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;   (S)-4-(3-Amino-piperidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;   (R)-4-Isopropyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;   trans-1-(2-Amino-6-isopropyl-pyrimidin-4-yl)-4-methylamino-pyrrolidin-3-ol;   (S,S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-6-isopropyl-pyrimidin-2-ylamine;   (R,R)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-6-isopropyl-pyrimidin-2-ylamine;   4-(cis-Hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-6-isopropyl-pyrimidin-2-ylamine;   (R,R)-4-(Hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-6-isopropyl-pyrimidin-2-ylamine;   4-Isopropyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-Isopropyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   (R,R)-4-Isopropyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   (R)-4-Methyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Methyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4,5-Dimethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4,5-Dimethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-5,6-dimethyl-pyrimidin-2-ylamine;   (R)-4,5-Dimethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-(cis-Hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-5,6-dimethyl-pyrimidin-2-ylamine;   4,5-Dimethyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4,5-Dimethyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   (S,S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-5,6-dimethyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-ethyl-pyrimidin-2-ylamine;   (R)-4-Ethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R,R)-(4-Ethyl-6-hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-pyrimidin-2-ylamine;   4-Ethyl-6-(cis-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   (R,R)-(4-Ethyl-6-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Cyclopropyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-(4-Cyclopropyl-6-3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Cyclopropyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Cyclobutyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-Cyclobutyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-piperidin-1-yl)-6-cyclobutyl-pyrimidin-2-ylamine;   (R)-4-Cyclobutyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Cyclobutyl-6-(cis-hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-pyrimidin-2-ylamine;   4-Cyclobutyl-6-(cis-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-Cyclobutyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-Cyclobutyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   (R,R)-(4-Cyclobutyl-6-cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Cyclohexyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-(4-Cyclohexyl-6-3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Cyclohexyl-6-(cis-hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-pyrimidin-2-ylamine;   (R,R)-4-Cyclohexyl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Piperazin-1-yl-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   4-Piperazin-1-yl-6-(tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-(tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   (R,R)-4-(Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-6-(tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   4-Benzyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-Benzyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-Benzyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R,R)-4-Benzyl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   4-(4-Piperazin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   (R,R)-4-(Hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   4-(cis-Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   (R,R)-4-(Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   (S,S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6,7-dihydro-5H-cyclopentapyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopentapyrimidin-2-ylamine;   4-tert-Butyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-tert-Butyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-4-tert-Butyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R,R)-4-tert-Butyl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-cyclopentyl-pyrimidin-2-ylamine;   (R,R)-4-Cyclopentyl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   (R,R)-4-Cyclopentyl-6-(hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(cis-1,7-diaza-spiro[4.4]non-7-yl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-cyclopentyl-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(trans-hexahydro-pyrrolo[3,4-b][1,4]oxazin-6-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(cis-hexahydro-pyrrolo[3,4-b][1,4]oxazin-6-yl)-pyrimidin-2-ylamine;   (2-Amino-ethyl)-6-isopropyl-pyrimidine-2,4-diamine;   4-(3-Amino-azetidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;   4-(1,7-Diaza-spiro[4.4]non-7-yl)-6-isopropyl-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-isopropyl-N 4 -methyl-pyrimidine-2,4-diamine;   4-(cis-Hexahydro-pyrrolo[3,4-b][1,4]oxazin-6-yl)-6-isopropyl-pyrimidin-2-ylamine;   4-(trans-Hexahydro-pyrrolo[3,4-b][1,4]oxazin-6-yl)-6-isopropyl-pyrimidin-2-ylamine;   4-Isopropyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   (R,R)-4-(Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   4-Piperazin-1-yl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   4-Butyl-5-methoxy-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-Butyl-6-[1,4]diazepan-1-yl-5-methoxy-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-butyl-5-methoxy-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-butyl-5-methoxy-pyrimidin-2-ylamine;   (S)-4-(3-Amino-pyrrolidin-1-yl)-6-butyl-5-methoxy-pyrimidin-2-ylamine;   (R)-4-Butyl-5-methoxy-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (S)-4-Butyl-5-methoxy-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Butyl-5-methoxy-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-butyl-5-methoxy-N 4 -methyl-pyrimidine-2,4-diamine;   N 4 -(2-Amino-ethyl)-6-butyl-5-methoxy-pyrimidine-2,4-diamine;   4-(3-Amino-azetidin-1-yl)-6-cyclopentyl-5-methoxy-pyrimidin-2-ylamine;   4-Cyclopentyl-6-[1,4]diazepan-1-yl-5-methoxy-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-cyclopentyl-5-methoxy-pyrimidin-2-ylamine;   (S)-4-Cyclopentyl-5-methoxy-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-cyclopentyl-5-methoxy-N 4 -methyl-pyrimidine-2,4-diamine;   N 4 -(2-Amino-ethyl)-6-cyclopentyl-5-methoxy-pyrimidine-2,4-diamine;   4-[1,4]Diazepan-1-yl-6-methoxymethyl-pyrimidin-2-ylamine;   (S)-4-(3-Amino-pyrrolidin-1-yl)-6-methoxymethyl-pyrimidin-2-ylamine;   (S)-4-Methoxymethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Cyclopropyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-Cyclopropyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-cyclopropyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-cyclopropyl-pyrimidin-2-ylamine;   4-Cyclopropyl-6-(cis-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   (S)-4-Isopropyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (S)-4-(3-Amino-pyrrolidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-tert-butyl-pyrimidin-2-ylamine;   4-tert-Butyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   (S)-4-(3-Amino-pyrrolidin-1-yl)-6-tert-butyl-pyrimidin-2-ylamine;   (S)-4-tert-Butyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-tert-butyl-N 4 -methyl-pyrimidine-2,4-diamine;   4-tert-Butyl-6-(cis-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-tert-butyl-pyrimidin-2-ylamine;   4-tert-Butyl-6-(3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-butyl-pyrimidin-2-ylamine;   4-Butyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-4-Butyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-butyl-N 4 -methyl-pyrimidine-2,4-diamine;   4-Butyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   Butyl-6-(cis-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-Butyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Butyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-Butyl-6-(3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-propyl-pyrimidin-2-ylamine;   4-(cis-5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-6-propyl-pyrimidin-2-ylamine;   4-Isobutyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-Isobutyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-4-Isobutyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-isobutyl-pyrimidin-2-ylamine;   (S)-4-Ethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-Adamantan-1-yl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Adamantan-1-yl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-tetrahydro-pyran-4-yl)-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-(4-methyl-tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(4-methyl-tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   4-(trans-2-Phenyl-cyclopropyl)-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-(trans-2-phenyl-cyclopropyl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-(trans-2-phenyl-cyclopropyl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-(trans-2-phenyl-cyclopropyl)-pyrimidine-2,4-diamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(trans-2-phenyl-cyclopropyl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-indan-2-yl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-indan-2-yl-pyrimidin-2-ylamine;   4-Indan-2-yl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-4-Indan-2-yl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Indan-2-yl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-benzyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-benzyl-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-indan-2-yl-pyrimidine-2,4-diamine;   (R)-4-(2,3-Dihydro-benzofuran-2-yl)-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-(cis-Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-6-(4-methyl-tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   4-(2,3-Dihydro-benzofuran-2-yl)-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-(2,3-dihydro-benzofuran-2-yl)-pyrimidin-2-ylamine;   4-(cis-Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-6-indan-2-yl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-(4-methyl-tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-(tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-(tetrahydro-pyran-4-yl)-pyrimidine-2,4-diamine;   N 4 -(2-Amino-ethyl)-N 4 -methyl-6-(tetrahydro-pyran-4-yl)-pyrimidine-2,4-diamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-phenethyl-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-phenethyl-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-phenethyl-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-(3,3,3-trifluoro-propyl)-pyrimidin-2-ylamine;   4-Piperazin-1-yl-6-(3,3,3-trifluoro-propyl)-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(3,3,3-trifluoro-propyl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-(3,3,3-trifluoro-propyl)-pyrimidin-2-ylamine;   4-Cyclopentyl-5-methoxy-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-5-methoxy-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-4-Cyclopentyl-5-methoxy-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R,R)-4-Cyclopentyl-5-methoxy-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-N 4 -methyl-6-(tetrahydro-furan-3-yl)-pyrimidine-2,4-diamine;   4-(cis-Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   4-[1,4]Diazepan-1-yl-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   (−)-4-Piperazin-1-yl-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   (+)-4-Piperazin-1-yl-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-(tetrahydro-furan-3-yl)-pyrimidine-2,4-diamine;   N 4 -(3-Amino-propyl)-6-(tetrahydro-furan-3-yl)-pyrimidine-2,4-diamine;   N 4 -Methyl-N 4 -(2-methylamino-ethyl)-6-(tetrahydro-furan-3-yl)-pyrimidine-2,4-diamine;   N 4 -(2-Methylamino-ethyl)-6-(tetrahydro-furan-3-yl)-pyrimidine-2,4-diamine;   5-Fluoro-4-methyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   5-Fluoro-4-methyl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   5-Fluoro-4-methyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-5-Fluoro-4-methyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-5-fluoro-6,N 4 -dimethyl-pyrimidine-2,4-diamine;   4-Piperazin-1-yl-6-pyridin-4-ylmethyl-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-pyridin-4-ylmethyl-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-pyridin-4-ylmethyl-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-thiophen-3-ylmethyl-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-thiophen-3-ylmethyl-pyrimidin-2-ylamine;   4-Piperazin-1-yl-6-thiophen-3-ylmethyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-thiophen-3-ylmethyl-pyrimidin-2-ylamine;   4-(cis-Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-6-thiophen-3-ylmethyl-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-thiophen-3-ylmethyl-pyrimidine-2,4-diamine;   4-(4-Methyl-piperazin-1-yl)-6-thiophen-2-ylmethyl-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-thiophen-2-ylmethyl-pyrimidin-2-ylamine;   4-Piperazin-1-yl-6-thiophen-2-ylmethyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-thiophen-2-ylmethyl-pyrimidin-2-ylamine;   4-(cis-Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-6-thiophen-2-ylmethyl-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-thiophen-2-ylmethyl-pyrimidine-2,4-diamine;   N 4 -(2-Amino-ethyl)-6-methoxymethyl-pyrimidine-2,4-diamine;   4-(3-Amino-azetidin-1-yl)-6-methoxymethyl-pyrimidin-2-ylamine;   (R)-4-Methoxymethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-methoxymethyl-pyrimidin-2-ylamine;   4-Methoxymethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-Methoxymethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-piperidin-1-yl)-6-methoxymethyl-pyrimidin-2-ylamine;   (R,R)-4-Methoxymethyl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-(tetrahydro-furan-2-ylmethyl)-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(tetrahydro-furan-2-ylmethyl)-pyrimidin-2-ylamine;   4-(cis-5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-6-(tetrahydro-furan-2-ylmethyl)-pyrimidin-2-ylamine;   4-Piperazin-1-yl-6-(tetrahydro-furan-2-ylmethyl)-pyrimidin-2-ylamine;   4-(cis-Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-6-(tetrahydro-furan-2-ylmethyl)-pyrimidin-2-ylamine;   4-(4-Chloro-benzyl)-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-(4-Chloro-benzyl)-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-4-(4-Chloro-benzyl)-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-(4-chloro-benzyl)-pyrimidin-2-ylamine;   4-(4-Chloro-benzyl)-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-(4-Chloro-benzyl)-6-(cis-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-(4-chloro-benzyl)-N 4 -methyl-pyrimidine-2,4-diamine;   4-Ethoxymethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-Ethoxymethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-Ethoxymethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-Ethoxymethyl-6-(3-amino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   Isopropoxymethyl-6-((R)-3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Isopropoxymethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-Isopropoxymethyl-6-(3-amino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Isopropoxymethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-Phenethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-phenethyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-(tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-benzyl-N 4 -methyl-pyrimidine-2,4-diamine;   4-Indan-2-yl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   4-(cis-5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(2-phenyl-cyclopropyl)-pyrimidin-2-ylamine (diastereomer 1);   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(2-phenyl-cyclopropyl)-pyrimidin-2-ylamine (diastereomer 2);   4-Cyclopentyl-6-(cis-1,7-diaza-spiro[4.4]non-7-yl)-pyrimidin-2-ylamine (enantiomer 1);   4-Cyclopentyl-6-(cis-1,7-diaza-spiro[4.4]non-7-yl)-pyrimidin-2-ylamine (enantiomer 2);   (R)-4-Isopropoxymethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-isopropoxymethyl-pyrimidin-2-ylamine;   4-Isopropoxymethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-Isopropoxymethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-isopropoxymethyl-pyrimidin-2-ylamine;   4-Isopropoxymethyl-6-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   (R)-4-Cyclopropoxymethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-cyclopropoxymethyl-pyrimidin-2-ylamine;   4-Cyclopropoxymethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-Cyclopropoxymethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-cyclopropoxymethyl-pyrimidin-2-ylamine;   4-Cyclopropoxymethyl-6-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   (R)-4-tert-Butoxymethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-tert-butoxymethyl-pyrimidin-2-ylamine;   4-tert-Butoxymethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-tert-Butoxymethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-tert-butoxymethyl-pyrimidin-2-ylamine;   4-tert-Butoxymethyl-6-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   4-Ethyl-6-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   4-(8-Methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-6-propyl-pyrimidin-2-ylamine;   4-Isopropyl-6-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   and pharmaceutically acceptable salts thereof.   
     
     
         17 . A pharmaceutical composition for treating a disease, disorder, or medical condition mediated by histamine H 4  receptor activity, comprising an effective amount of at least one chemical entity selected from compounds of Formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is:
 a) a C 1-6 alkyl group, optionally substituted with —OH, —OC 1-4 alkyl, —CF 3 , or —O— (monocyclic cycloalkyl); 
 b) a benzyl, —CH 2 — (monocyclic heteroaryl), or phenethyl group, each optionally substituted with halo; 
 c) a monocyclic cycloalkyl, —(CH 2 ) 0-1 -tetrahydrofuranyl, or —(CH 2 ) 0-1 -tetrahydropyranyl group, each optionally fused to a phenyl ring, and each optionally substituted with C 1-4 alkyl or phenyl; or 
 d) an adamantyl group; 
 
         R 2  is H, F, methyl, or methoxy; 
         or R 1  and R 2  taken together form —(CH 2 ) 3-5 — or —(CH 2 ) 2 OCH 2 —; and 
         —N(R 3 )R 4  is one of the following acyclic, monocyclic, spirocyclic, bridged, or fused ring systems: 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           where q is 0 or 1; 
           R 3  and R 4  are taken together as defined by the structure of each one of such moieties; 
           R a  is H or OH; 
           R b  and R c  are each independently H or C 1-3 alkyl; and 
           each R d  substitutent is methyl or two R d  substituents taken together form a methylene or ethylene bridge; 
         
         provided that when R 1  is methyl, then —N(R 3 )R 4  is selected from said spirocyclic, bridged, and fused ring systems; 
         and pharmaceutically acceptable salts of compounds of Formula (I), pharmaceutically acceptable prodrugs of compounds of Formula (I), and pharmaceutically active metabolites of compounds of Formula (I). 
       
     
     
         18 . A pharmaceutical composition as in  claim 17 , wherein said chemical entity is selected from the group consisting of:
 4-Cyclopentyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-piperidin-1-yl)-6-cyclopentyl-pyrimidin-2-ylamine;   (R)-4-Cyclopentyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   trans-1-(2-Amino-6-cyclopentyl-pyrimidin-4-yl)-4-methylamino-pyrrolidin-3-ol;   4-Cyclopentyl-6-(cis-hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Isopropyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-piperidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;   (S)-4-(3-Amino-piperidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;   (R)-4-Isopropyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;   trans-1-(2-Amino-6-isopropyl-pyrimidin-4-yl)-4-methylamino-pyrrolidin-3-ol;   (S,S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-6-isopropyl-pyrimidin-2-ylamine;   (R,R)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-6-isopropyl-pyrimidin-2-ylamine;   4-(cis-Hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-6-isopropyl-pyrimidin-2-ylamine;   (R,R)-4-(Hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-6-isopropyl-pyrimidin-2-ylamine;   4-Isopropyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-Isopropyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   (R,R)-4-Isopropyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   (R)-4-Methyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Methyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4,5-Dimethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4,5-Dimethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-5,6-dimethyl-pyrimidin-2-ylamine;   (R)-4,5-Dimethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-(cis-Hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-5,6-dimethyl-pyrimidin-2-ylamine;   4,5-Dimethyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4,5-Dimethyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   (S,S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-5,6-dimethyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-ethyl-pyrimidin-2-ylamine;   (R)-4-Ethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R,R)-(4-Ethyl-6-hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-pyrimidin-2-ylamine;   4-Ethyl-6-(cis-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   (R,R)-(4-Ethyl-6-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Cyclopropyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-(4-Cyclopropyl-6-3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Cyclopropyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Cyclobutyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-Cyclobutyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-piperidin-1-yl)-6-cyclobutyl-pyrimidin-2-ylamine;   (R)-4-Cyclobutyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Cyclobutyl-6-(cis-hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-pyrimidin-2-ylamine;   4-Cyclobutyl-6-(cis-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-Cyclobutyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-Cyclobutyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   (R,R)-(4-Cyclobutyl-6-cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Cyclohexyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-(4-Cyclohexyl-6-3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Cyclohexyl-6-(cis-hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-pyrimidin-2-ylamine;   (R,R)-4-Cyclohexyl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Piperazin-1-yl-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   4-Piperazin-1-yl-6-(tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-(tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   (R,R)-4-(Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-6-(tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   4-Benzyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-Benzyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-Benzyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R,R)-4-Benzyl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   4-(4-Piperazin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   (R,R)-4-(Hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   4-(cis-Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   (R,R)-4-(Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   (S,S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6,7-dihydro-5H-cyclopentapyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopentapyrimidin-2-ylamine;   4-tert-Butyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-tert-Butyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-4-tert-Butyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R,R)-4-tert-Butyl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-cyclopentyl-pyrimidin-2-ylamine;   (R,R)-4-Cyclopentyl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   (R,R)-4-Cyclopentyl-6-(hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(cis-1,7-diaza-spiro[4.4]non-7-yl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-cyclopentyl-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(trans-hexahydro-pyrrolo[3,4-b][1,4]oxazin-6-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(cis-hexahydro-pyrrolo[3,4-b][1,4]oxazin-6-yl)-pyrimidin-2-ylamine;   (2-Amino-ethyl)-6-isopropyl-pyrimidine-2,4-diamine;   4-(3-Amino-azetidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;   4-(1,7-Diaza-spiro[4.4]non-7-yl)-6-isopropyl-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-isopropyl-N 4 -methyl-pyrimidine-2,4-diamine;   4-(cis-Hexahydro-pyrrolo[3,4-b][1,4]oxazin-6-yl)-6-isopropyl-pyrimidin-2-ylamine;   4-(trans-Hexahydro-pyrrolo[3,4-b][1,4]oxazin-6-yl)-6-isopropyl-pyrimidin-2-ylamine;   4-Isopropyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   (R,R)-4-(Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   4-Piperazin-1-yl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   4-Butyl-5-methoxy-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-Butyl-6-[1,4]diazepan-1-yl-5-methoxy-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-butyl-5-methoxy-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-butyl-5-methoxy-pyrimidin-2-ylamine;   (S)-4-(3-Amino-pyrrolidin-1-yl)-6-butyl-5-methoxy-pyrimidin-2-ylamine;   (R)-4-Butyl-5-methoxy-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (S)-4-Butyl-5-methoxy-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Butyl-5-methoxy-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-butyl-5-methoxy-N 4 -methyl-pyrimidine-2,4-diamine;   N 4 -(2-Amino-ethyl)-6-butyl-5-methoxy-pyrimidine-2,4-diamine;   4-(3-Amino-azetidin-1-yl)-6-cyclopentyl-5-methoxy-pyrimidin-2-ylamine;   4-Cyclopentyl-6-[1,4]diazepan-1-yl-5-methoxy-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-cyclopentyl-5-methoxy-pyrimidin-2-ylamine;   (S)-4-Cyclopentyl-5-methoxy-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-cyclopentyl-5-methoxy-N 4 -methyl-pyrimidine-2,4-diamine;   N 4 -(2-Amino-ethyl)-6-cyclopentyl-5-methoxy-pyrimidine-2,4-diamine;   4-[1,4]Diazepan-1-yl-6-methoxymethyl-pyrimidin-2-ylamine;   (S)-4-(3-Amino-pyrrolidin-1-yl)-6-methoxymethyl-pyrimidin-2-ylamine;   (S)-4-Methoxymethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Cyclopropyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-Cyclopropyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-cyclopropyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-cyclopropyl-pyrimidin-2-ylamine;   4-Cyclopropyl-6-(cis-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   (S)-4-Isopropyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (S)-4-(3-Amino-pyrrolidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-tert-butyl-pyrimidin-2-ylamine;   4-tert-Butyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   (S)-4-(3-Amino-pyrrolidin-1-yl)-6-tert-butyl-pyrimidin-2-ylamine;   (S)-4-tert-Butyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-tert-butyl-N 4 -methyl-pyrimidine-2,4-diamine;   4-tert-Butyl-6-(cis-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-tert-butyl-pyrimidin-2-ylamine;   4-tert-Butyl-6-(3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-butyl-pyrimidin-2-ylamine;   4-Butyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-4-Butyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-butyl-N 4 -methyl-pyrimidine-2,4-diamine;   4-Butyl-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   Butyl-6-(cis-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-Butyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-Butyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-Butyl-6-(3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-propyl-pyrimidin-2-ylamine;   4-(cis-5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-6-propyl-pyrimidin-2-ylamine;   4-Isobutyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-Isobutyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-4-Isobutyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-isobutyl-pyrimidin-2-ylamine;   (S)-4-Ethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-Adamantan-1-yl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Adamantan-1-yl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-tetrahydro-pyran-4-yl)-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-(4-methyl-tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(4-methyl-tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   4-(trans-2-Phenyl-cyclopropyl)-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-(trans-2-phenyl-cyclopropyl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-(trans-2-phenyl-cyclopropyl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-(trans-2-phenyl-cyclopropyl)-pyrimidine-2,4-diamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(trans-2-phenyl-cyclopropyl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-indan-2-yl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-indan-2-yl-pyrimidin-2-ylamine;   4-Indan-2-yl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   (R)-4-Indan-2-yl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Indan-2-yl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-benzyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-benzyl-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-indan-2-yl-pyrimidine-2,4-diamine;   (R)-4-(2,3-Dihydro-benzofuran-2-yl)-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-(cis-Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-6-(4-methyl-tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   4-(2,3-Dihydro-benzofuran-2-yl)-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-(2,3-dihydro-benzofuran-2-yl)-pyrimidin-2-ylamine;   4-(cis-Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-6-indan-2-yl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-(4-methyl-tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-(tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-(tetrahydro-pyran-4-yl)-pyrimidine-2,4-diamine;   N 4 -(2-Amino-ethyl)-N 4 -methyl-6-(tetrahydro-pyran-4-yl)-pyrimidine-2,4-diamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-phenethyl-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-phenethyl-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-phenethyl-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-(3,3,3-trifluoro-propyl)-pyrimidin-2-ylamine;   4-Piperazin-1-yl-6-(3,3,3-trifluoro-propyl)-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(3,3,3-trifluoro-propyl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-(3,3,3-trifluoro-propyl)-pyrimidin-2-ylamine;   4-Cyclopentyl-5-methoxy-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-5-methoxy-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-4-Cyclopentyl-5-methoxy-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R,R)-4-Cyclopentyl-5-methoxy-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-N 4 -methyl-6-(tetrahydro-furan-3-yl)-pyrimidine-2,4-diamine;   4-(cis-Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   4-[1,4]Diazepan-1-yl-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   (−)-4-Piperazin-1-yl-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   (+)-4-Piperazin-1-yl-6-(tetrahydro-furan-3-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-(tetrahydro-furan-3-yl)-pyrimidine-2,4-diamine;   N 4 -(3-Amino-propyl)-6-(tetrahydro-furan-3-yl)-pyrimidine-2,4-diamine;   N 4 -Methyl-N 4 -(2-methylamino-ethyl)-6-(tetrahydro-furan-3-yl)-pyrimidine-2,4-diamine;   N 4 -(2-Methylamino-ethyl)-6-(tetrahydro-furan-3-yl)-pyrimidine-2,4-diamine;   5-Fluoro-4-methyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   5-Fluoro-4-methyl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   5-Fluoro-4-methyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-5-Fluoro-4-methyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-5-fluoro-6,N 4 -dimethyl-pyrimidine-2,4-diamine;   4-Piperazin-1-yl-6-pyridin-4-ylmethyl-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-pyridin-4-ylmethyl-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-pyridin-4-ylmethyl-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-thiophen-3-ylmethyl-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-thiophen-3-ylmethyl-pyrimidin-2-ylamine;   4-Piperazin-1-yl-6-thiophen-3-ylmethyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-thiophen-3-ylmethyl-pyrimidin-2-ylamine;   4-(cis-Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-6-thiophen-3-ylmethyl-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-thiophen-3-ylmethyl-pyrimidine-2,4-diamine;   4-(4-Methyl-piperazin-1-yl)-6-thiophen-2-ylmethyl-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-thiophen-2-ylmethyl-pyrimidin-2-ylamine;   4-Piperazin-1-yl-6-thiophen-2-ylmethyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-thiophen-2-ylmethyl-pyrimidin-2-ylamine;   4-(cis-Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-6-thiophen-2-ylmethyl-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-thiophen-2-ylmethyl-pyrimidine-2,4-diamine;   N 4 -(2-Amino-ethyl)-6-methoxymethyl-pyrimidine-2,4-diamine;   4-(3-Amino-azetidin-1-yl)-6-methoxymethyl-pyrimidin-2-ylamine;   (R)-4-Methoxymethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-methoxymethyl-pyrimidin-2-ylamine;   4-Methoxymethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-Methoxymethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-piperidin-1-yl)-6-methoxymethyl-pyrimidin-2-ylamine;   (R,R)-4-Methoxymethyl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-(4-Methyl-piperazin-1-yl)-6-(tetrahydro-furan-2-ylmethyl)-pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(tetrahydro-furan-2-ylmethyl)-pyrimidin-2-ylamine;   4-(cis-5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-6-(tetrahydro-furan-2-ylmethyl)-pyrimidin-2-ylamine;   4-Piperazin-1-yl-6-(tetrahydro-furan-2-ylmethyl)-pyrimidin-2-ylamine;   4-(cis-Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-6-(tetrahydro-furan-2-ylmethyl)-pyrimidin-2-ylamine;   4-(4-Chloro-benzyl)-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-(4-Chloro-benzyl)-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-4-(4-Chloro-benzyl)-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-(4-chloro-benzyl)-pyrimidin-2-ylamine;   4-(4-Chloro-benzyl)-6-(cis-5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   4-(4-Chloro-benzyl)-6-(cis-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-(4-chloro-benzyl)-N 4 -methyl-pyrimidine-2,4-diamine;   4-Ethoxymethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-Ethoxymethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-Ethoxymethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-Ethoxymethyl-6-(3-amino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   Isopropoxymethyl-6-((R)-3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Isopropoxymethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   (R)-Isopropoxymethyl-6-(3-amino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   4-Isopropoxymethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-Phenethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-phenethyl-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-(tetrahydro-pyran-4-yl)-pyrimidin-2-ylamine;   N 4 -(2-Amino-ethyl)-6-benzyl-N 4 -methyl-pyrimidine-2,4-diamine;   4-Indan-2-yl-6-(octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;   4-(cis-5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-ylamine;   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(2-phenyl-cyclopropyl)-pyrimidin-2-ylamine (diastereomer 1);   (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6-(2-phenyl-cyclopropyl)-pyrimidin-2-ylamine (diastereomer 2);   4-Cyclopentyl-6-(cis-1,7-diaza-spiro[4.4]non-7-yl)-pyrimidin-2-ylamine (enantiomer 1);   4-Cyclopentyl-6-(cis-1,7-diaza-spiro[4.4]non-7-yl)-pyrimidin-2-ylamine (enantiomer 2);   (R)-4-Isopropoxymethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-isopropoxymethyl-pyrimidin-2-ylamine;   4-Isopropoxymethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-Isopropoxymethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-isopropoxymethyl-pyrimidin-2-ylamine;   4-Isopropoxymethyl-6-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   (R)-4-Cyclopropoxymethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-cyclopropoxymethyl-pyrimidin-2-ylamine;   4-Cyclopropoxymethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-Cyclopropoxymethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-cyclopropoxymethyl-pyrimidin-2-ylamine;   4-Cyclopropoxymethyl-6-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   (R)-4-tert-Butoxymethyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;   (R)-4-(3-Amino-pyrrolidin-1-yl)-6-tert-butoxymethyl-pyrimidin-2-ylamine;   4-tert-Butoxymethyl-6-piperazin-1-yl-pyrimidin-2-ylamine;   4-tert-Butoxymethyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;   4-(3-Amino-azetidin-1-yl)-6-tert-butoxymethyl-pyrimidin-2-ylamine;   4-tert-Butoxymethyl-6-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   4-Ethyl-6-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   4-(8-Methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-6-propyl-pyrimidin-2-ylamine;   4-Isopropyl-6-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   4-Cyclopentyl-6-(8-methyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-ylamine;   and pharmaceutically acceptable salts thereof.