Biheteroaryl compounds and uses thereof

Abstract

The present invention provides for compounds of Formula I and embodiments and salts thereof for the treatment of diseases (e.g., neurodegenerative diseases). R 1 , R 2 , R 3 , X 1 , X 2 , A and Cy variable in Formula all have the meaning as defined herein.

The invention claimed is: 
     
       1. Compounds A compound of formula (I) 
       
         
           
           
               
               
           
         
       
       or salts a pharmaceutically acceptable salt thereof wherein
 R 1 , R 2  and R 3  are each independently H, F, Cl, Br, I, CN, C 1-6  alkyl or C 1-6  haloalkyl; 
 X 1  is N or C—R 4 , wherein R 4  is selected from the group consisting of —F, —Cl, —Br, I -(L 1 ) 0-1 -C 1-6  alkyl, —I, CN, -(L 1 ) 0.1 -C 1-6  alkyl, -(L 1 ) 0-1 -C 1-6  haloalkyl, -(L 1 ) 0-1 -C 1-6  heteroalkyl, -(L 2 ) 0-1 -C 3-8  cycloalkyl, -(L 2 ) 0-1 -3 to 7 membered heterocycloalkyl, -(L 2 ) 0-1 -6-10 membered aryl, -(L 2 ) 0-1 -5-10 membered heteroaryl, wherein L 1  is selected from the group consisting of —O—, —N(H)—, —S—, —N(C 1-6 alkyl)-, ═O and —C(═O)—, and L 2  is selected from the group consisting of —O—, —N(H)—, —N(C 1-6  alkyl)-, —S—, ═O —C(═O)—, C 1-4  alkylene, C 1-4  alkenylene, C 1-4  alkynylene, C 1-4  alkoxylene, C 1-4  aminoalkylene, C 1-4  thioalkylene and C 1-4  heteroalkylene, and wherein R 4  is optionally substituted on carbon atoms and heteroatoms with R R4  substituents selected from the group consisting of F, Cl, Br, I, C 1-6  alkyl, C 1-6  haloalkyl, 3-5 membered cycloalkyl, 3-5 membered heterocycloalkyl, C 1-6  alkoxy, C 1-6  alkylamino, C 1-6  dialkylamino, C 1-6  alkylthio, ═O, —NH 2 , —CN, —NO 2  and —SF 5 ; 
 X 2  is N; 
 A is selected from the group consisting of C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  dialkylamino, 3 to 12 membered cycloalkyl, 3 to 12 membered heterocycloalkyl, wherein A is optionally substituted with 1-5 R A  substituents selected from the group consisting of F, Cl, Br, I, —OH, —CN, —NO 2 , —SF 5 , C 1-8  alkyl, C 1-8  haloalkyl, C 1-8  heteroalkyl, -(L A ) 0-1 -3-8 membered cycloalkyl, -(L A ) 0-1 -3-8 membered heterocycloalkyl, -(L A ) 0-1 -5 to 6 membered heteroaryl, -(L A ) 0-1 -C 6  aryl, -(L A ) 0-1 -NR R1a R R1b , -(L A ) 0-1 -OR R1a , -(L A ) 0-1 -SR R1a , -(L A ) 0-1 -N(R R1a )C(═Y 1 )OR R1c , -(L A ) 0-1 -OC(═O)N(R R1a )(R R1b ), -(L A ) 0-1 -N(R R1a )C(═O)N(R R1a )(R R1b ), -(L A ) 0-1 -C(═O)N(R R1a )(R R1b ), -(L A ) 0-1 -N(R R1a )C(═O)R R1b , -(L A ) 0-1 -C(═O)OR R1a , -(L A ) 0-1 -OC(═O)R R1a , -(L A ) 0-1 -P(═O)(OR R1a )(OR R1b ), -(L A ) 0-1 -S(O) 1-2 R R1c , -(L A ) 0-1 -S(O) 1-2 N(R R1a )(R R1b ), -(L A ) 0-1 -N(R R1a )S(O) 1-2 N(R R1a )(R R1b ) and -(L A ) 0-1 -N(R R1a )S(O) 1-2 (R R1c ), wherein L A  is selected from the group consisting of C 1-4  alkylene, C 1-4  heteroalkylene, C 1-4  alkoxylene, C 1-4  aminoalkylene, C 1-4  thioalkylene, C 2-4  alkenylene, and C 2-4  alkynylene; wherein R R1a  and R R1b  are independently selected from the group consisting of hydrogen, C 1-8  alkyl, C 1-8  haloalkyl, 3-8 membered cycloalkyl, phenyl, benzyl, 5 to 6 membered heteroaryl and 3 to 8 membered heterocycloalkyl; R R1c  is selected from the group consisting of C 1-8  alkyl, C 1-8  haloalkyl, 3 to 8 membered cycloalkyl, phenyl, benzyl, 5 to 6 membered heteroaryl and 3 to 7 membered heterocycloalkyl, and wherein R A  is optionally substituted on carbon atoms and heteroatoms with R RA  substituents selected from, F, Cl, Br, I, —NH 2 , —OH, —CN, —NO 2 , ═O, —SF 5 , C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, C 1-4  (halo)alkyl-C(═O)—, C 1-4  (halo)alkyl-S(O) 0-2 —, C 1-4  (halo)alkyl-N(H)S(O) 0-2 —, C 1-4  (halo)alkyl-S(O) 0-2 N(H)—, (halo)alkyl-N(H)—S(O) 0-2 N(H)—, C 1-4  (halo)alkyl-C(═O)N(H)—, C 1-4  (halo)alkyl-N(H)—C(═O)—, ((halo)alkyl) 2 N—C(═O)—, C 1-4  (halo)alkyl-OC(═O)N(H)—, C 1-4  (halo)alkyl-OC(═O)N(H)—, (halo)alkyl-N(H)—C(═O)O—, ((halo)alkyl) 2 N—C(═O)O—, C 1-4  alkylthio, C 1-4  alkylamino and C 1-4  dialkylamino; and 
 Cy is selected from the group consisting of C 1-6  alkyl, C 1-6  haloalkyl, 3 to 12 membered cycloalkyl, 3 to 12 membered heterocycloalkyl, wherein Cy is optionally substituted on carbon or heteroatoms with R Cy  substituents selected from the group consisting of F, Cl, Br, I, —OH, —CN, —NO 2 , —SF 5 , C 1-8  alkyl, C 1-8  haloalkyl, C 1-8  heteroalkyl, -(L Cy ) 0-1 -3-8 membered cycloalkyl, -(L Cy ) 0-1 -3-8 membered heterocycloalkyl, -(L Cy ) 0-1 -5 to 6 membered heteroaryl, -(L Cy ) 0-1 -phenyl, -(L Cy ) 0-1 -NR RCa R RCb , -(L Cy ) 0-1 -OR RCa , -(L Cy ) 0-1 -SR RCa , -(L Cy ) 0-1 -N(R RCa )C(═Y 1 )OR RCc , -(L Cy ) 0-1 -OC(═O)N(R RCa )(R RCb ), -(L Cy ) 0-1 -N(R RCa )C(═O)N(R RCa )(R RCb ), -(L Cy ) 0-1 -C(═O)N(R RCa )(R RCb ), -(L Cy ) 0-1 -N(R RCa )C(═O)R RCb , -(L Cy ) 0-1 -C(═O)OR RCa , -(L Cy ) 0-1 -OC(═O)R RCa , -(L Cy ) 0-1 -P(═O)(OR RCa )(OR RCb ), -(L Cy ) 0-1 -S(O) 1-2 R RCc , -(L Cy ) 0-1 -S(O) 1-2 N(R RCa )(R RCb ), -(L Cy ) 0-1 N(R RCa )S(O) 1-2 N(R Rca )(R RCb ) -(L Cy ) 0-1 N(R RCa )S(O) 1-2 N(R RCa )(R RCb ) and -(L Cy ) 0-1 -N(R RCa )S(O) 1-2 (R RCc ), wherein L Cy  is selected from the group consisting of C 1-4  alkylene, C 1-4  heteroalkylene, C 1-4  alkoxylene, C 1-4  aminoalkylene, C 1-4  thioalkylene, C 2-4  alkenylene, and C 2-4  alkynylene; wherein R RCa  and R RCb  are independently selected from the group consisting of hydrogen, C 1-8  alkyl, C 1-8  haloalkyl, 3-8 membered cycloalkyl, phenyl, benzyl, 5 to 6 membered heteroaryl and 3 to 8 membered heterocycloalkyl; R RCc  is selected from the group consisting of C 1-8  alkyl, C 1-8  haloalkyl, 3 to 8 membered cycloalkyl, phenyl, benzyl, 5 to 6 membered heteroaryl and 3 to 7 membered heterocycloalkyl, and wherein R Cy  is optionally substituted on carbon atoms and heteroatoms with from 1 to 5 R RCy  substitutents substituents selected from, F, Cl, Br, I, —NH 2 , —OH, —CN, —NO 2 , ═O, —SF 5 , C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, C 1-4  (halo)alkyl-C(═O)—, C 1-4  (halo)alkyl-S(O) 0-2 —, C 1-4  (halo)alkyl-N(H)S(O) 0-2 —, C 1-4  (halo)alkyl-S(O) 0-2 N(H)—, (halo)alkyl-N(H)—S(O) 0-2 N(H)—, C 1-4  (halo)alkyl-C(═O)N(H)—, C 1-4  (halo)alkyl-N(H)—C(═O)—, ((halo)alkyl) 2 N—C(═O)—, C 1-4  (halo)alkyl-OC(═O)N(H)—, C 1-4  (halo)alkyl-OC(═O)N(H)—, (halo)alkyl-N(H)—C(═O)O—, ((halo)alkyl) 2 N—C(═O)O—, C 1-4  alkylthio, C 1-4  alkylamino and C 1-4  dialkylamino. 
 
     
     
       2. A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein either A or Cy is a polycyclic carbocycle or polycyclic heterocycle. 
     
     
       3. A compound according to  claim 1 , wherein X 1  is N. 
     
     
       4. A compound according to  claim 1 , wherein X 1  is C—R 4 . 
     
     
       5. A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4  is selected from the group consisting of —F, —Cl, —CN, -(L 2 ) 0-1 -C 3-8  cycloalkyl, -(L 2 ) 0-1 -3 to 7 membered heterocycloalkyl, -(L 1 ) 0-1 -C 1-6  alkyl, -(L 1 ) 0-1 -C 1-6  haloalkyl, -(L 1 ) 0-1 -C 1-6  heteroalkyl, -(L 2 ) 0-1 -6-10 membered aryl and -(L 2 ) 0-1 -5-10 membered heteroaryl, and is optionally substituted. 
     
     
       6. A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4  is selected from the group consisting of —F, —Cl, C 3-8  cycloalkyl, 3 to 7 membered heterocycloalkyl, C 1-6  alkyl, C 1-6  haloalkyl, —(O)—C 3-8  cycloalkyl, —(O)—3 to 7 membered heterocycloalkyl, —(O)—C 1-6  alkyl and —(O)—C 1-6  haloalkyl, and is optionally substituted. 
     
     
       7. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4  is selected from the group consisting of methoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, cyclopropoxy, cyclobutoxy, cyclopentoxy, methyl, monofluoromethyl difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl and cyclopentyl. 
     
     
       8. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4  is selected from the group consisting of (L 2 ) 0-1 -phenyl -(L 2 ) 0-1 -phenyl, -(L 2 ) 0-1 -pyridyl, -(L 2 ) 0-1 -pyrimidinyl, -(L 2 ) 0-1 pyrazinyl, -(L 2 ) 0-1 -pyridazinyl, -(L 2 ) 0-1 -pyrrolyl, -(L 2 ) 0-1 -pyrazolyl, -(L 2 ) 0-1 -imidazolyl, -(L 2 ) 0-1 -thienyl, -(L 2 ) 0-1 -thiazolyl and, -(L 2 ) 0-1 -thiadiazolyl, -(L 2 ) 0-1 -triazoloyl, -(L 2 ) 0-1 -oxazolyl, -(L 2 ) 0-1 -oxadiazolyl, and -(L 2 ) 0-1 -furanyl and is optionally substituted. 
     
     
       9. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4  is selected from the group consisting of -(L 2 ) 0-1 -phenyl and -(L 2 ) 0-1 -pyridinyl, and is optionally substituted. 
     
     
       10. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4  is —OC(H)(CH 3 )-phenyl wherein said phenyl ring is optionally substituted. 
     
     
       11. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2  and R 3  are each independently selected from the group consisting of F, Cl, CN, hydrogen, C 1-4  alkyl and C 1-4  haloalkyl. 
     
     
       12. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2  and R 3  are each hydrogen. 
     
     
       13. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein A and Cy are independently selected from the group consisting of pyrrolidine, piperidine, azetidine, azepane, piperazine, 7-azaspiro[3.5]nonane, 3,6-diazabicyclo[3.2.1]octane, 2-oxa-5-azabicyclo[2.2.1]heptane, 2,7-diazaspiro[3.5]nonane, octahydrocyclopenta[c]pyrrole, 2-azaspiro[3.3]heptane, 2,5-diazaspiro[3.4]octane, 6-azaspiro[2.5]octane, 3-azabicyclo[3.1.0]hexane, 3-oxabicyclo[3.1.0]hexane, morpholine, hexahydro-2H-furo[3,2-c]pyrrole, 2-azabicyclo[2.1.1]hexane, 2,5-diazabicyclo[2.2.1]heptane, 2-aza-tricyclo[3.3.1.1-3,7]decane, 2-azabicyclo[2.1.1]hexane, 9-azabicyclo[4.2.1]nonane, 9-azabicyclo[3.3.1]nonane, cyclobutane, cyclopropane, cyclopentane, 2-Thia-5-aza-bicyclo[2.2.1]heptane 2,2-dioxide, 2-azabicyclo[2.2.1]heptane, tetrahydro-2H-pyran, 8-azabicyclo[3.2.1]octane and 3-oxa-8-azabicyclo[3.2.1]octane, and is optionally substituted. 
     
     
       14. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is selected from the group consisting of pyrrolidine, piperidine, azetidine, azepane, piperazine, cyclopropane, cyclobutane, cyclopentane, 7-azaspiro[3.5]nonane, 3-oxabicyclo[3.1.0]hexane, 3,6-diazabicyclo[3.2.1]octane, 2-oxa-5-azabicyclo[2.2.1]heptane, 2,7-diazaspiro[3.5]nonane, octahydrocyclopenta[c]pyrrole, 2-azaspiro[3.3]heptane, 2,5-diazaspiro[3.4]octane, 6-azaspiro[2.5]octane, 3-azabicyclo[3.1.0]hexane, morpholine, hexahydro-2H-furo[3,2-c]pyrrole and 2-azabicyclo[2.1.1]hexane, and is optionally substituted. 
     
     
       15. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is selected from the group consisting of 2-azabicyclo[2.1.1]hexane, 3-azabicyclo[3.1.0]hexane, 3oxabicyclo[3.1.0]hexane 3-oxabicyclo[3.1.0]hexane, azetidine, pyrrolidine, cyclopropane, cyclobutane, cyclopentane, and is optionally substituted. 
     
     
       16. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is selected from the group consisting of (1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane, (1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptane, (1R,5S)-3-azabicyclo[3.1.0]hexane, (1S,5R)-3-azabicyclo[3.1.0]hexane, 3-oxabicyclo[3.1.0]hexane, (1R,5S)-3-oxabicyclo[3.1.0]hexane, (1S,5R)-3-oxabicyclo[3.1.0]hexane, (1S,4S)-2,5-diazabicyclo[2.2.1]heptane and (1R,4R)-2,5-diazabicyclo[2.2.1]heptane, and is optionally substituted. 
     
     
       17. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein is A is selected from the group consisting of methyl, ethyl, isopropyl, 
       
         
           
           
               
               
           
         
       
     
     
       18. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy is selected from the group consisting of 2,5-diazabicyclo[2.2.1]heptane, piperidine, pyrrolidine, azetidine, 2-aza-tricyclo[3.3.1.1-3,7]decane, 2-oxa-5-azabicyclo[2.2.1]heptane, 3-azabicyclo [3.1.0]hexane, 3-oxabicyclo[3.1.0]hexane, 2-azabicyclo[2.1.1]hexane, 9-azabicyclo[4.2.1]nonane, 9-azabicyclo[3.3.1]nonane, cyclobutane, 2-Thia-5-aza-bicyclo[2.2.1]heptane 2,2-dioxide, 2-azabicyclo[2.2.1]heptane, tetrahydro-2H-pyran, 8-azabicyclo[3.2.1]octane, and 3-oxa-8-azabicyclo[3.2.1]octane, and is optionally substituted. 
     
     
       19. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy is selected from the group consisting of azetidine, (1S ,4S)-2-oxa-5-azabicyclo[2.2.1]heptane, (1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptane, (1R,5S)-3-azabicyclo[3.1.0]hexane, (1S,5R)-3-azabicyclo[3.1.0]hexane, 3-oxabicyclo[3.1.0]hexane, (1R,5S)-3-oxabicyclo[3.1.0]hexane, (1S,5R)-3-oxabicyclo[3.1.0]hexane, (1S,4S)-2,5-diazabicyclo[2.2.1]heptane and (1R,4R)-2,5-diazabicyclo[2.2.1]heptane, and is optionally substituted. 
     
     
       20. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
       21. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is C 1-6  alkyl or C 1-6  dialkylamino, and is optionally substituted. 
     
     
       22. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is methyl or ethyl. 
     
     
       23. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy is C 1-6  alkyl, and is optionally substituted. 
     
     
       24. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is optionally substituted with from 1 to 5 R A  substituents selected from the group consisting of F, Cl, Br, I, —OH, —CN, —NO 2 , —SF 5 , C 1-8  alkyl, C 1-8  haloalkyl, C 1-8  heteroalkyl, -(L A ) 0-1 -3-8 membered cycloalkyl, -(L A ) 0-1 -3-8 membered heterocycloalkyl, -(L A ) 0-1 -5 to 6 membered heteroaryl, and -(L A ) 0-1 -C 6  aryl, wherein L A  is selected from the group consisting of —C(O)—, —C(O)CH 2 —, —OCH 2 —, —CH 2 O—, —CH 2 —, —CH 2 CH 2 —, —CH 2 OCH 2 —, —N(H)CH 2 —, —N(C 1-3  alkyl)CH 2 —, CH 2 N(H)— —CH 2 N(H)—, and —CH 2 N(C 1-3  alkyl)-; wherein said 3-8 membered cycloalkyl is selected from the group consisting of propane, butane, pentane and hexane; wherein said 3 to 8 membered heterocycloalkyl is selected from the group consisting of oxetane, tetrahydrofuran, tetrahydropyran, oxepane, azetidine, pyrrolidine, piperidine and azepane; wherein said 5 to 6 membered heteroaryl is selected from the group consisting of pyrrole, pyrazole, imidazole, thiophene, thiazole, oxazole, trizole triazole, pyridine, pyrimidine, pyrazine, and pyridazine; wherein said C 6  aryl is phenyl; and where in wherein R A  is optionally substituted with from 1 to 5 R RA  substitutents substituents selected from, F, Cl, Br, I, —NH 2 , —OH, —CN, —NO 2 , ═O, —SF 5 , C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, C 1-4  (halo)alkyl-C(═O)—, C 1-4  (halo)alkyl-S(O) 0-2 —, C 1-4  (halo)alkyl-N(H)S(O) 0-2 —, C 1-4  (halo)alkyl-S(O) 0-2 N(H)—, (halo)alkyl-N(H)—S(O) 0-2 N(H)—, C 1-4  (halo)alkyl-C(═O)N(H)—, C 1-4  (halo)alkyl-N(H)—C(═O)—, ((halo)alkyl) 2 N—C(═O)—, C 1-4  (halo)alkyl-OC(═O)N(H)—, C 1-4  (halo)alkyl-OC(═O)N(H)—, (halo)alkyl-N(H)—(═O)O—, ((halo)alkyl) 2 N—C(═O)O—, C 1-4  alkylthio, C 1-4  alkylamino and C 1-4  dialkylamino. 
     
     
       25. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy is optionally substituted with from 1 to 5 R Cy  substituents selected from the group consisting of F, Cl, Br, I, —OH, —CN, —NO 2 , —SF 5 , C 1-8  alkyl, C 1-8  haloalkyl, C 1-8  heteroalkyl, -(L Cy ) 0-1 -3-8 membered cycloalkyl, -(L Cy ) 0-1 -3-8 membered heterocycloalkyl, -(L Cy ) 0-1 -5 to 6 membered heteroaryl, and -(L Cy ) 0-1 -C 6  aryl, wherein L Cy  is selected from the group consisting of —C(O)—, —C(O)CH 2 —, —OCH 2 —, —CH 2 O—, —CH 2 —, —CH 2 CH 2 —, —CH 2 OCH 2 —, —N(H)CH 2 —, —N(C 1-3  alkyl)CH 2 —, CH 2 N(H)—, —CH 2 N(H)—, and —CH 2 N(C 1-3  alkyl)-; wherein said 3-8 membered cycloalkyl is selected from the group consisting of propane, butane, pentane and hexane; wherein said 3 to 8 membered heterocycloalkyl is selected from the group consisting of oxetane, tetrahydrofuran, tetrahydropyran, oxepane, azetidine, pyrrolidine, piperidine and azepane; wherein said 5 to 6 membered heteroaryl is selected from the group consisting of pyrrole, pyrazole, imidazole, thiophene, thiazole, oxazole, trizole triazole, pyridine, pyrimidine, pyrazine, and pyridazine; wherein said C 6  aryl is phenyl; and where in R Cy  is optionally substituted with from 1 to 5 R RCy  substitutents substituents selected from, F, Cl, Br, I, —NH 2 , —OH, —CN, —NO 2 , ═O, —SF 5 , C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, C 1-4  (halo)alkyl-C(═O)—, C 1-4  (halo)alkyl-S(O) 0-2 —, C 1-4  (halo)alkyl-N(H)S(O) 0-2 —, C 1-4  (halo)alkyl-S(O) 0-2 N(H)—, (halo)alkyl-N(H)—S(O) 0-2 N(H)—, C 1-4  (halo)alkyl-C(═O)N(H)—, C 1-4  (halo)alkyl-N(H)—(═O)—, ((halo)alkyl) 2 N—C(═O)—, C 1-4  (halo)alkyl-OC(═O)N(H)—, C 1-4  (halo)alkyl-OC(═O)N(H)—, (halo)alkyl-N(H)—(═O)O—, ((halo)alkyl) 2 N—C(═O)O—, C 1-4  alkylthio, C 1-4  alkylamino and C 1-4  dialkylamino. 
     
     
       26. A compound of claim of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy is optionally substituted with 1 to 5 R Cy  substituents selected from the group consisting of F, Cl, Br, I, CN, OH, 2,3-difluorophen-1-yl-C(═O)—, 4-fluorophen-1-yl-C(═O)—, 3-fluorophen-1-yl-C(═O)—, 3,5-difluorophen-1-yl-C(═O)—, 3-fluoro-4-methyl-phen-1-yl-C(═O)—, 2,5-difluorophen-1-yl-C(═O)—, oxetane, oxetan-3-yl, thiazole, thiazol-2-yl, —CH 3 CH 2 C(═O)—, CH 3 C(═O)—, CF 3 CH 2 —, (HO)C(CH 3 ) 2 CH 2 —, CH 3 OCH 2 CH 2 —, CH 3 OC(CH 3 ) 2 C(═O)—, CH 3 OCH 2 C(═O)—, isopropyl, ethyl and methyl. 
     
     
       27. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is optionally substituted with 1 to 5 R A  substituents selected from the group consisting of F, Cl, Br, I, CN, CH 3 O—, CH 3 , cyclopropylmethyl, CF 3  and butyl. 
     
     
       28. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the subformula consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
       29. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the subformula consisting of 
       
         
           
           
               
               
           
         
       
     
     
       30. A compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the subformula consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       wherein R Cy  if present replaces a hydrogen atom attached to a carbon or nitrogen atom of the Cy ring. 
     
     
       31. A compound of  claim 1  selected from the group consisting of:
 [3-[6-[2-amino-4-(trifluoromethyl)pyrimidin-5-yl]-2-methyl-pyrimidin-4-yl]pyrrolidin-1-yl]-phenyl-methanone; 
 [3-[6-(2-aminopyrimidin-5-yl)-2-methyl-pyrimidin-4-yl]-1-piperidyl]-phenyl-methanone; 
 [3-[6-[2-amino-4-(trifluoromethyl)pyrimidin-5-yl]-2-methyl-pyrimidin-4-yl]-1-piperidyl]-phenyl-methanone; 
 [3-[6-(2-aminopyrimidin-5-yl)-2-methyl-pyrimidin-4-yl]pyrrolidin-1-yl]-phenyl-methanone 
 6-((1R,3R,5R,7R)-2-azaadamantan-2-yl)-2-(2-azabicyclo[2.1.1]hexan-2-yl)-[4,5′-bipyrimidin]-2′-amine; 
 3-(difluoromethoxy)-5-[2-(3,3-difluoropyrrolidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyridin-2-amine; 
 5-[2-(3,3-difluoro-1-piperidyl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(4-fluoro-1-piperidyl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 1-[(1R,5S)-6-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-cyclopropyl-pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]propan-1-one; 
 1-[(1R,5S)-6-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-cyclopropyl-pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]ethanone; 
 1-[(1S,4S)-5-[6-[6-amino-5-(trifluoromethyl)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]ethanone; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 1-[(1R,5S)-6-[6-[6-amino-5-(trifluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; 
 1-[(1R,5S)-6-[6-[6-amino-5-(trifluoromethyl)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; 
 [6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; 
 1-[(1R,5S)-6-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; 
 1-[(1R,5S)-6-[6-[6-amino-5-(trifluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]ethanone; 
 5-[2-(3,3-difluoro-1-piperidyl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(4-fluoro-1-piperidyl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 1-[(1R,5S)-6-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-cyclopropyl-pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]propan-1-one; 
 1-[(1R,5S)-6-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-cyclopropyl-pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]ethanone; 
 1-[(1S,4S)-5-[6-[6-amino-5-(trifluoromethyl)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]ethanone; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 1-[(1R,5S)-6-[6-[6-amino-5-(trifluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; 
 1-[(1R,5S)-6-[6-[6-amino-5-(trifluoromethyl)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; 
 [6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; 
 1-[(1R,5S)-6-[6-[6-amino-5-(trifluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo-[3.1.0]hexane-3-yl]ethanone; 
 1-[(1R,5S)-6-[6-[6-amino-5-(trifluoromethyl)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3yl]-ethanone; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(trifluoromethoxy)pyridin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(trifluoromethyl)pyridin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]pyrimidin-2-amine;  
 5-[2-cyclopropyl-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-(trifluoromethoxy)pyridin-2-amine; 
 5-[2-(3-methoxyazetidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3,3-dimethylazetidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-(5-((1R,5S,6s)-3-oxabicyclo[3.1.0]hexan-6-yl)-1-isopropyl-1H-pyrazol-3-yl)-3-fluoro-1H-pyrrolo[2,3-b]pyridine; 
 5-[2-(2-azabicyclo[2.1.1]hexan-2-yl)-6-[(1S,4S)-5-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 1-[(1S,4S)-5-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]-2-methoxy-2-methyl-propan-1-one; 
 [6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]-2-methoxy-ethanone; 
 1-[(1S,4S)-5-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]-2-methoxy-ethanone; 
 3-(difluoromethoxy)-5-[2-[(3R,4S)-3,4-difluoropyrrolidin-1-yl]-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyridin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-(3-azabicyclo[2.1.1]hexan-4-yl)pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(azetidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 3-(difluoromethoxy)-5-[2-(3-fluoroazetidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyridin-2-amine; 
 5-[2,6-bis[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3,3-difluoroazetidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octan-3-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-2-isopropyl-2,5-diazabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-5-ethyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-2-(oxetan-3-yl)-2,5-diazabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(3S,4R)-3,4-difluoropyrrolidin-1-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 1-[(1S,4S)-5-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]ethanone; 
 1-[3-[6-(2-aminopyrimidin-5-yl)-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-8-azabicyclo[3.2.1]octan-8-yl]ethanone; 
 5-[2-(2-fluoro-7-azaspiro[3.5]nonan-7-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-[(1R,5S)-3-methyl-3,6-diazabicyclo[3.2.1]octan-6-yl]-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(4,4-difluoroazepan-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(4-cyclobutylpiperazin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(2-methyl-2,7-diazaspiro[3.5]nonan-7-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 4-(2-aminopyrimidin-5-yl)-N,N-diethyl-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-2-amine; 
 5-[2-(4-methylpip erazin- 1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-2-(1-piperidyl)pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(azetidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-[(3aS,6aR)-5,5-difluoro-1,3,3a,4,6,6a-hexahydrocyclopenta[c]pyrrol-2-yl]-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-2-pyrrolidin-1-yl-pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3,3-difluoroazetidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(7,7-difluoro-2-azaspiro[3.3]heptan-2-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-[(3aR,6aS)-4,4-difluoro-1,3,3a,5,6,6a-hexahydrocyclopenta[c]pyrrol-2-yl]-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(5-methyl-2,5-diazaspiro[3.4]octan-2-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(6-azaspiro[2.5]octan-6-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[8-(oxetan-3-yl)-8-azabicyclo[3.2.1]octan-3-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 1-[6-[6-(2-aminopyrimidin-5-yl)-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]ethanone; 
 1-[(1S,4S)-2-[6-(2-aminopyrimidin-5-yl)-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-5-yl]-2-methyl-propan-2-ol; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-5-(2-methoxyethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[3.1.0]hexan-3-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 1-[6-[6-(2-aminopyrimidin-5-yl)-2-cyclopropyl-pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]ethanone; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-(9-azabicyclo[3.3.1]nonan-9-yl)pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-[(3S,4R)-3,4-difluoropyrrolidin-1-yl]-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3,3-difluoropyrrolidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-fluoroazetidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(4-cyclopropylpiperazin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-[(1R,4R)-5,5-difluoro-2-azabicyclo[2.2.1]heptan-2-yl]-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-2-[4-(trifluoromethyl)-1-piperidyl]pyrimidin-4-yl]pyrimidin-2-amine; 
 1-[2-(2-aminopyrimidin-5-yl)-6-(3-azabicyclo[2.1.1]hexan-3-yl)-4-pyridyl]cyclobutanecarbonitrile; 
 1-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]cyclobutanecarbonitrile; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-cyclopropyl-pyridin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-isopropoxy-pyridin-2-amine; 
 5-[2-cyclopropyl-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-(8-azabicyclo[3.2.1]octan-3-yl)pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-[4-(cyclopropylmethyl)piperazin-1-yl]-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[6-(3-azabicyclo[2.1.1]hexan-3-yl)-4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-2-pyridyl]-3-(difluoromethoxy)pyridin-2-amine; 
 5-[6-(3-azabicyclo[2.1.1]hexan-3-yl)-2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[3.1.0]hexan-3-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 1-[(1S,4S)-5-[6-(2-aminopyrimidin-5-yl)-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]ethanone; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-2,2-dioxo-2-thia-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-5-(2,2,2-trifluoroethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-(8-azabicyclo[3.2.1]octan-8-yl)pyrimidin-4-yl]pyrimidin-2-amine; 
 1-[6-(2-aminopyrimidin-5-yl)-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]cyclobutanecarbonitrile; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-5-fluoro-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[3-(oxetan-3-yl)-3-azabicyclo[3.2.1]octan-8-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-(trifluoromethoxy)pyridin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-(2,5-diazabicyclo[2.2.1]heptan-2-yl)pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-(3-azabicyclo[3.2.1]octan-8-yl)pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[6-[(1R,4S)-3-azabicyclo[2.2.1]heptan-3-yl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 5-[6-[(1R,4S)-3-azabicyclo[2.2.1]heptan-3-yl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-cyclopropyl-6[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 8-[6-(2-aminopyrimidin-5-yl)-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-methyl-8-azabicyclo[3.2.1]octan-3-ol; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-(2,6-dimethylmorpholin-4-yl)pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2,6-bis(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 2-amino-5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyridine-3-carbonitrile; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-chloro-pyridin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-(trifluoromethyl)pyridin-2-amine; 
 8-[6-(2-aminopyrimidin-5-yl)-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-8-azabicyclo[3.2.1]octan-3-ol; 
 5-[6-(3-azabicyclo[2.1.1]hexan-3-yl)-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-2-pyridyl]pyrimidin-2-amine; 
 5-[4,6-bis(3-azabicyclo[2.1.1]hexan-3-yl)-2-pyridyl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[6-(3-azabicyclo[2.1.1]hexan-3-yl)-4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-2-pyridyl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-(2,2-dimethylmorpholin-4-yl)pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[2-(2-methylpyrrolidin-1-yl)-6-tetrahydropyran-4-yl-pyrimidin-4-yl]pyrimidin-2-amine; 
 5-[6-(3-methoxyazetidin- 1-yl)-4-[1-(oxetan-3-yl)-4-piperidyl]-2-pyridyl]-3-(trifluoromethyl)pyridin-2-amine; 
 5-[6-(3-fluoroazetidin-1-yl)-4-[1-(oxetan-3-yl)-4-piperidyl]-2-pyridyl]-3-(trifluoromethyl)pyridin-2-amine; 
 3-chloro-5-[6-(3-fluoroazetidin- 1-yl)-4-[1-(oxetan-3-yl)-4-piperidyl]-2-pyridyl]pyridin-2-amine; 
 5-[6-(3-fluoroazetidin-1-yl)-4-[1-(oxetan-3-yl)-4-piperidyl]-2-pyridyl]pyrimidin-2-amine; 
 5-(2,6-dimorpholinopyrimidin-4-yl)pyrimidin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(2-methoxyethyl)-3-azabicyclo [3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 1-[(1R,5S)-6-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]ethanone; 
 1-[(1R,5S)-6-[6-(2-aminopyrimidin-5-yl)-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(trifluoromethyl)pyridin-2-amine; 
 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(trifluoromethoxy)pyridin-2-amine; 
 5-[2-cyclopropyl-6-[(1R,5S)-3-(oxetan-3-yl)-3azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridine-2-amine; 
 5-[2-cyclopropyl-6-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 5-[2-cyclopropyl-6-[(1R,5S)-3-(2,2,2-trifluoroethyl)-3azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridine-2amine; 
 5-[2-cyclopropyl-6-[(1R,5S)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 5-[2-cyclopropyl-6-[(1R,5S)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; 
 1-[(1R,5S)-6-[6-[6-amino 5-(difluromethoxy)-3-pyridyl]-2-cyclopropyl-pyrmidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; 
 1-[(1R,5S)-6-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-cyclopropyl-pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; 
 1-[(1R,5S)-6-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]propan-1one; 
 1-[(1R,5S)-6-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]propan-1-one; 
 3-(difluoromethoxy)-5-[2-[(3S)-3-fluoropyrrolodin-1-yl]-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5yl]pyrimidin-4-yl]pyridin-2-amine; 
 3-(difluoromethoxy)-5-[2-[(3S)-3-fluoropyrrolidin-1-yl]-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyridin-2-amine; 
 3-(difluoromethoxy)-5-[2-3-methoxypyrrolidin-1-yl)-6-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)pyrimidin-4-yl]pyridin-2-amine; 
 5-[2-(2-azaspiro[3.3]heptan-2-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-(difluoromethoxy)-pyridin-2-amine; 
 5-[2-(2,3,3a,4,6,6a-hexahydrofuro[2,3-c]pyrrol-5yl)-6-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)pyrimidin-4-yl]-3-(difluoromethoxy)pyridine-2-amine; 
 5-[2-(2,3,3a,4,6,6a-hexahydrofuro[2,3-c]pyrrol-5-yl)-6-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; and 
 3-(difluoromethoxy)-5-[2-(3-methoxy-3-methyl-azetidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyridin-2-amine; and 
 6-cyclopropyl-5′-(difluoromethoxy)-4-(1-(oxetan-3-yl)azetidin-3-yl)-[2,3′-bipyridin]-6′-amine 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
       32. A pharmaceutical composition comprising a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
       33. A compound of  claim 1  which is 3-(difluoromethoxy)-5-[2-(3,3-difluoropyrrolidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4]pyridin-2-amine wherein is 3-(difluoromethoxy)-5-[2-(3,3-difluoropyrrolidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyridin-2-amine; or a pharmaceutically acceptable salt thereof. 
     
     
       34. A compound of  claim 1  which is 1-[(1R,5S)-6-[6-[6-amino-5-(trifluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo [3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; or a pharmaceutically acceptable salt thereof. 
     
     
       35. A compound of  claim 1  which is 1-[(1R,5S)-6-[6-[6-amino-5-(trifluoromethyl)-3-pyridyl]-2-(3-azabicyclo [2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; or a pharmaceutically acceptable salt thereof. 
     
     
       36. A compound of  claim 1  which is [6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol which is 1-[(1R,5S)-6-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)-pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; or a pharmaceutically acceptable salt thereof. 
     
     
       37. A compound of  claim 1  which is 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(trifluoromethyl)pyridin-2-amine; or a pharmaceutically acceptable salt thereof. 
     
     
       38. A compound of  claim 1  which is 1-[(1S,4S)-5-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]-2-methoxy-2-methyl-propan-1-one; or a pharmaceutically acceptable salt thereof. 
     
     
       39. A compound of  claim 1  which is [6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]-2-methoxy-ethanone which is 1-[(1S,4S)-5-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]-2-methoxy-ethanone; or a pharmaceutically acceptable salt thereof. 
     
     
       40. A compound of  claim 1  which is 3-(difluoromethoxy)-5-[2-[(3R,4S)-3,4-difluoropyrrolidin-1-yl]-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyridin-2-amine; or a pharmaceutically acceptable salt thereof. 
     
     
       41. A compound of  claim 1  which is 1-[(1S,4S)-5-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]ethanone; or a pharmaceutically acceptable salt thereof. 
     
     
       42. A compound of  claim 1  which is 5-[2-(3-azabicyclo[3.1.0]hexan-3-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; or a pharmaceutically acceptable salt thereof. 
     
     
       43. A compound of  claim 1  which is 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; or a pharmaceutically acceptable salt thereof. 
     
     
       44. A compound of  claim 1  which is 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-isopropoxy-pyridin-2-amine; or a pharmaceutically acceptable salt thereof. 
     
     
       45. A compound of  claim 1  which is 5-[2-cyclopropyl-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; or a pharmaceutically acceptable salt thereof. 
     
     
       46. A compound of  claim 1  which is 5-[6-[(1R,4S)-3-azabicyclo[2.2.1]heptan-3-yl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; or a pharmaceutically acceptable salt thereof. 
     
     
       47. A compound of  claim 1  which is 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; or a pharmaceutically acceptable salt thereof. 
     
     
       48. A compound of  claim 1  which is 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; or a pharmaceutically acceptable salt thereof. 
     
     
       49. A compound of  claim 1  which is 1-[(1R,5S)-6-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]ethanone; or a pharmaceutically acceptable salt thereof. 
     
     
       50. A compound of  claim 1  which is 1-[(1R,5S)-6-[6-(2-aminopyrimidin-5-yl)-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol. 
     
     
       51. A compound of  claim 1  which is 5-[2-(3-azabicyclo[2.1.1]hexan-3-yl)-6-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; or a pharmaceutically acceptable salt thereof. 
     
     
       52. A compound of  claim 1  which is 5-[2-cyclopropyl-6-[(1R,5S)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrimidin-4-yl]-3-(difluoromethoxy)pyridin-2-amine; or a pharmaceutically acceptable salt thereof. 
     
     
       53. A compound of  claim 1  which is 1-[(1R,5S)-6-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-cyclopropyl-pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-methyl-propan-2-ol; or a pharmaceutically acceptable salt thereof. 
     
     
       54. A compound of  claim 1  which is 1-[(1R,5S)-6-[6-[6-amino-5-(difluoromethoxy)-3-pyridyl]-2-(3-azabicyclo[2.1.1]hexan-3-yl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-3-yl]propan-1-one; or a pharmaceutically acceptable salt thereof. 
     
     
       55. A compound of  claim 1  which is 3-(difluoromethoxy)-5-[2-[(3S)-3-fluoropyrrolidin-1-yl]-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyridin-2-amine; or a pharmaceutically acceptable salt thereof. 
     
     
       56. A compound selected from the group consisting of: