Pyrazine compounds as phosphodiesterase 10 inhibitors

Abstract

Pyrazine compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein m, n, p, R 1 , R 2 , R 3 , R 4 , X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , Y and Z are defined in the specification, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

1 . A method of treating conditions that may be treated with PDE10 inhibitors comprising the step of administering to a subject a therapeutically effective amount of a compound of formula I: 
       
         
           
           
               
               
           
         
         or any pharmaceutically-acceptable salt thereof, wherein: 
         Each of X 1 , X 2 , X 3 , X 4 , and X 5  is independently N or C; wherein no more than two of X 1 , X 2 , X 3  and X 4  are N; 
         Each of X 6 , X 7 , X 9 , and X 10  is independently N or C; each of X 8  and X 11  is C; wherein no more than three of X 6 , X 7 , X 9 , and X 10  are N; 
         Y is NH, NR S , CH(OH), C(═O), —CR a R b , or CF 2 ; or alternatively Y and R 3  form a 5- to 6-membered ring fused to the ring containing both said Y and R 3 ; 
         Z is NH, NR 6 , S, SO, SO 2 , O, or C; wherein Z is only C when X 5  is N; 
         m is 0, 1, 2, 3 or 4; 
         n is 0, 1 or 2; 
         p is 0, 1 or 2; 
         R 1  is selected from the group consisting of 
         (a) H, F, Cl, Br, I, C 1-8 alk, C 1-4 haloalk, —OR a , —NR a R a , —N(R a )C(═O)R b , —C(═O)NR a R a , —C(═O)R d , —C(═O)—O—R a , —OR c , —NR a R c , —N(R c )C(═O)R b , —N(R a )C(═O)R c , —C(═O)NR a R b , or —C(═O)NR a R c ; 
         (b) a saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered monocyclic ring or a saturated, partially-saturated or unsaturated 8-, 9-, 10-, 11-, or 12-membered bicyclic ring, wherein each said ring contains 0, 1, 2, 3, or 4 N atoms and 0, 1, or 2 atoms selected from O and S, and wherein each said ring is substituted by 0, 1, 2 or 3 groups selected from F, Cl, Br, C 1-6 alk, C 1-4 haloalk, —OR a , —OC 1-4 haloalk, CN, —C(═O)R b , —C(═O)OR a , —C(═O)NR a R a , —C(═NR a )NR a R a , —OC(═O)R b , —OC(═O)NR a R a , —OC 2-6 alkNR a R a , —OC 2-6 alkOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —NR a R c , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkNR a R a , —NR a C 2-6 alkOR a , —C 1-6 alkNR a R a , —C 1-6 alkOR a , —C 1-6 alkN(R a )C(═O)R b , —C 1-6 alkOC(═O)R b , —C 1-6 alkC(═O)NR a R a , —C 1-6 alkC(═O)OR a , R 7 , R 8  and oxo; 
         (c) group -L-R 7 , wherein L is CH 2 , NH, N(C 1-4 alk), —C(═O)NR a R a (C 1-4 alk), O, S, S═O, or S(═O) 2 ; or 
         (d) C 1-6 alk substituted by 0, 1, 2 or 3 groups selected from F, Cl, Br, C 1-6 alk, C 1-4 haloalk, —OR a , —OC 1-4 haloalk, CN, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OC(═O)R b , —OC(═O)NR a R a , —OC 2-6 alkNR a R a , —OC 2-6 alkOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkNR a R a , —NR a C 2-6 alkOR a , —C 1-6 alkNR a R a , —C 1-6 alkOR a , R 8  and oxo; 
         R 2  is, independently in each instance, F, Cl, Br, CN, OH, OC 1-4 alk, C 1-4 alk or C 1-4 haloalk; 
         R 3  is, independently in each instance, F, Cl, Br, CN, OH, OC 1-4 alk, C 1-4 alk, C 1-4 haloalk, or —NR a C 1-4 alk; 
         R 4  is independently in each instance, F, Cl, CH 3 , CN, CF 3 , CHF 2 , CH 2 F, OR a , or NR a R a ; 
         R 5  is C 1-8 alk, C 1-4 haloalk, —C(═O)R b , or R c ; 
         R 6  is C 1-8 alk, C 1-4 haloalk, —C(═O)R b , or R c ; 
         R 7  is a saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered monocyclic or 8-, 9-, 10-, 11-, or 12-membered bicyclic ring containing 0, 1, 2 or 3 N atoms and 0 or 1 atoms selected from O and S, which is substituted by 0, 1, 2 or 3 groups selected from F, Cl, Br, C 1-6 alk, C 1-4 haloalk, —OR a , —OC 1-4 haloalk, CN, —C(═O)R b , —C(═O)OR a , —C(═O)NR a R a , —C(═NR a )NR a R a , —OC(═O)R b , —OC(═O)NR a R a , —OC 2-6 alkNR a R a , —OC 2-6 alkOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkNR a R a , —NR a C 2-6 alkOR a , —C 1-6 alkNR a R a , —C 1-6 alkOR a , —C 1-6 alkN(R a )C(═O)R b , —C 1-6 alkOC(═O)R b , —C 1-6 alkC(═O)NR a R a , —C 1-6 alkC(═O)OR a , R 8  and oxo; 
         R 8  is a C 1-6 alk substituted by 0, 1, 2 or 3 groups selected from F, Cl, Br, C 1-6 alk, C 1-4 haloalk, —OR a , —OC 1-4 haloalk, CN, —C(═O)R b , —C(═O)OR a , —C(═O)NR a R a , —C(═NR a )NR a R a , —OC(═O)R b , —OC(═O)NR a R a , —OC 2-6 alkNR a R a , —OC 2-6 alkOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkNR a R a , —NR a C 2-6 alkOR a , —C 1-6 alkNR a R a , —C 1-6 alkOR a , —C 1-6 alkN(R a )C(═O)R b , —C 1-6 alkOC(═O)R b , —C 1-6 alkC(═O)NR a R a , —C 1-6 alkC(═O)OR a  and oxo; 
         R a  is independently, at each instance, H or R b ; 
         R b  is independently, at each instance, phenyl, benzyl, or C 1-6 alk, wherein said phenyl, benzyl, and C 1-6 alk are being substituted by 0, 1, 2 or 3 substituents selected from halo, C 1-4 alk, C 1-3 haloalk, —OH, —OC 1-4 alk, —NH 2 , —NHC 1-4 alk, —OC(═O)C 1-4 alk, or —N(C 1-4 alk)C 1-4 alk; 
         R c  is a C 0-4 alk-linked saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered monocyclic; or 8-, 9-, 10-, 11-, or 12-membered bicyclic ring containing 0, 1, 2 or 3 N atoms and 0 or 1 atom selected from O and S, wherein said C 0-4 alk and said ring moiety may be substituted by 0, 1, 2 or 3 groups selected from F, Cl, Br, C 1-6 alk, C 1-4 haloalk, R 7 , —OR a , —OC 1-4 haloalk, CN, —C(═O)R b , —C(═O)OR a , —C(═O)NR a R a , —C(═NR a )NR a R a , —OC(═O)R b , —OC(═O)NR a R a , —OC 2-6 alkNR a R a , —OC 2-6 alkOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkNR a R a , —NR a C 2-6 alkOR a , —C 1-6 alkNR a R a , —C 1-6 alkOR a , —C 1-6 alkN(R a )C(═O)R b , —C 1-6 alkOC(═O)R b , —C 1-6 alkC(═O)NR a R a , —C 1-6 alkC(═O)OR a  and oxo; and 
         R d  is a nitrogen-linked saturated, partially-saturated, or unsaturated 5-, 6- or 7-membered ring heterocycle containing the linking nitrogen and 0, 1 or 2 additional nitrogen atoms and containing 0 or 1 sulfur or oxygen atom, the heterocycle being substituted by 0, 1, 2 or 3 substituents selected from oxo, halo, C 1-4 alk, C 1-3 haloalk, —OC 1-4 alk, —NH 2 , —NHC 1-4 alk, and —N(C 1-4 alk)C 1-4 alk. 
       
     
     
         2 . The method of  claim 1  wherein said condition is selected from the group consisting of psychoses, Parkinson's disease, dementias, obsessive compulsive disorder, tardive dyskinesia, choreas, depression, mood disorders, impulsivity, drug addiction, attention deficit/hyperactivity disorder (ADHD), depression with parkinsonian states, personality changes with caudate or putamen disease, dementia and mania with caudate and pallidal diseases, and compulsions with pallidal disease. 
     
     
         3 . The method of  claim 1  wherein said condition is selected from the group consisting of obesity, schizophrenia, Huntington's disease, bipolar disorder, and obsessive-compulsive disorder. 
     
     
         4 . A method of treating conditions that may be treated with PDE10 inhibitors comprising the step of administering to a subject a therapeutically effective amount of a compound of formula II: 
       
         
           
           
               
               
           
         
       
       or any pharmaceutically-acceptable salt thereof, wherein:
 Z is NH, NR 6 , S or O; 
 m is 0, 1, 2, 3 or 4; 
 n is 0, 1 or 2; 
 p is 0, 1 or 2; 
 y is 0, 1, 2, 3 or 4; 
 X 1  is N or C; 
 X 5  is N or C; 
 Ring A is a carbon-linked-saturated, carbon-linked-partially-saturated, or carbon-linked-unsaturated 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered carbocycle ring containing 0, 1 or 2 N atoms and containing 0 or 1 S or O atom; or a nitrogen-linked-saturated, nitrogen-linked-partially-saturated, or nitrogen-linked-unsaturated 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered ring heterocycle containing the linking nitrogen and 0, 1 or 2 additional N atoms and containing 0 or 1 S or O atom; 
 R 2  is, independently in each instance, F, Cl, Br, CN, OH, OC 1-4 alk, C 1-4 alk or C 1-4 haloalk; 
 R 3  is, independently in each instance, F, Cl, Br, CN, OH, OC 1-4 alk, C 1-4 alk, C 1-4 haloalk, or —NR a C 1-4 alk; 
 R 4  is independently in each instance, F, Cl, CH 3 , CN, CF 3 , CHF 2 , CH 2 F, OR a , or NR a R a ; 
 R 5  is C 1-8 alk, C 1-4 haloalk, —C(═O)R b , or R c ; 
 R 6  is C 1-8 alk, C 1-4 haloalk, —C(═O)R b , or R c ; 
 R 7  is a saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered monocyclic or 8-, 9-, 10-, 11-, or 12-membered bicyclic ring containing 0, 1, 2, 3, or 4 N atoms and 0 or 1 atoms selected from O and S, which is substituted by 0, 1, 2 or 3 groups selected from F, Cl, Br, C 1-6 alk, C 1-4 haloalk, —OR a , —OC 1-4 haloalk, CN, —C(═O)R b , —C(═O)OR a , —C(═O)NR a R a , —C(═NR a )NR a R a , —OC(═O)R b , —OC(═O)NR a R a , —OC 2-6 alkNR a R a , —OC 2-6 alkOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkNR a R a , NR a C 2-6 alkOR a , —C 1-6 alkNR a R a , —C 1-6 alkOR a , —C 1-6 alkN(R a )C(═O)R b , —C 1-6 alkOC(═O)R b , —C 1-6 alkC(═O)NR a R a , —C 1-6 alkC(═O)OR a , R 8  and oxo; 
 R 8  is a C 1-6 alk substituted by 0, 1, 2 or 3 groups selected from F, Cl, Br, C 1-6 alk, C 1-4 haloalk, —OR a , —OC 1-4 haloalk, CN, —C(═O)R b , —C(═O)OR a , —C(═O)NR a R a , —C(═NR a )NR a R a , —OC(═O)R b , —OC(═O)NR a R a , —OC 2-6 alkNR a R a , —OC 2-6 alkOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkNR a R a , —NR a C 2-6 alkOR a , —C 1-6 alkNR a R a , —C 1-6 alkOR a , —C 1-6 alkN(R a )C(═O)R b , —C 1-6 alkOC(═O)R b , —C 1-6 alkC(═O)NR a R a , —C 1-6 alkC(═O)OR a  and oxo; 
 R 9  is independently selected from the group consisting of H, F, Cl, Br, C 1-6 alk, C 1-4 haloalk, —OR a , —OC 1-4 haloalk, CN, —C(═O)R b , —C(═O)OR a , —C(═O)NR a R a , —C(═NR a )NR a R a , —OC(═O)R b , —OC(═O)NR a R a , —OC 2-6 alkNR a R a , —OC 2-6 alkOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —NR a R c , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkNR a R a , —NR a C 2-6 alkOR a , —C 1-6 alkNR a R a , —C 1-6 alkOR a , —C 1-6 alkN(R a )C(═O)R b , —C 1-6 alkOC(═O)R b , —C 1-6 alkC(═O)NR a R a , —C 1-6 alkC(═O)OR a , R 7 , R 8  and oxo; 
 R a  is independently, at each instance, H or R b ; 
 R b  is independently, at each instance, phenyl, benzyl or C 1-6 alk, the phenyl, benzyl and C 1-6 alk being substituted by 0, 1, 2 or 3 substituents selected from halo, C 1-4 alk, C 1-3 haloalk, —OH, —OC 1-4 alk, —NH 2 , —NHC 1-4 alk, —OC(═O)C 1-4 alk, or —N(C 1-4 alk)C 1-4 alk; and 
 R c  is a C 0-4 alk-linked saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered monocyclic or 8-, 9-, 10-, 11-, or 12-membered bicyclic ring containing 0, 1, 2 or 3 N atoms and 0 or 1 atom selected from O and S, which is substituted by 0, 1, 2 or 3 groups selected from F, Cl, Br, C 1-6 alk, C 1-4 haloalk, R 7 , —OR a , —OC 1-4 haloalk, CN, —C(═O)R b , —C(═O)OR a , —C(═O)NR a R a , —C(═NR a )NR a R a , —OC(═O)R b , —OC(═O)NR a R a , —OC 2-6 alkNR a R a , —OC 2-6 alkOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkNR a R a , —NR a C 2-6 alkOR a , —C 1-6 alkNR a R a , —C 1-6 alkOR a , —C 1-6 alkN(R a )C(═O)R b , —C 1-6 alkOC(═O)R b , —C 1-6 alkC(═O)NR a R a , —C 1-6 alkC(═O)OR a  and oxo. 
 
     
     
         5 . The method of  claim 4  wherein said condition is selected from the group consisting of psychoses, Parkinson's disease, dementias, obsessive compulsive disorder, tardive dyskinesia, choreas, depression, mood disorders, impulsivity, drug addiction, attention deficit/hyperactivity disorder (ADHD), depression with parkinsonian states, personality changes with caudate or putamen disease, dementia and mania with caudate and pallidal diseases, and compulsions with pallidal disease. 
     
     
         6 . The method of  claim 4  wherein said condition is selected from the group consisting of obesity, schizophrenia, Huntington's disease, bipolar disorder, and obsessive-compulsive disorder. 
     
     
         7 . A method of treating conditions that may be treated with PDE10 inhibitors comprising the step of administering to a subject a therapeutically effective amount of a compound of formula III: 
       
         
           
           
               
               
           
         
       
       or any pharmaceutically-acceptable salt thereof, wherein:
 Z is NH, NR 6 , S or O; 
 m is 0, 1, 2, 3 or 4; 
 n is 0, 1 or 2; 
 p is 0, 1 or 2; 
 y is 0, 1, 2, 3 or 4; 
 X 1  is N or C; 
 X 5  is N or C; 
 Ring A is a carbon-linked-saturated, carbon-linked-partially-saturated, or carbon-linked-unsaturated 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered carbocycle ring containing 0, 1 or 2 N atoms and containing 0 or 1 S or O atom; or a nitrogen-linked-saturated, nitrogen-linked-partially-saturated, or nitrogen-linked-unsaturated 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered ring heterocycle containing the linking nitrogen and 0, 1 or 2 additional N atoms and containing 0 or 1 S or O atom; 
 R 2  is, independently in each instance, F, Cl, Br, CN, OH, OC 1-4 alk, C 1-4 alk or C 1-4 haloalk; 
 R 3  is, independently in each instance, F, Cl, Br, CN, OH, OC 1-4 alk, C 1-4 alk or C 1-4 haloalk; 
 R 4  is independently in each instance, F, Cl, CH 3 , CN, CF 3 , CHF 2 , CH 2 F, OR a , or NR a R a ; 
 R 5  is C 1-8 alk, C 1-4 haloalk, —C(═O)R b , or R c ; 
 R 6  is C 1-8 alk, C 1-4 haloalk, —C(═O)R b , or R c ; 
 R 7  is a saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered monocyclic or 8-, 9-, 10-, 11-, or 12-membered bicyclic ring containing 0, 1, 2, 3, or 4 N atoms and 0 or 1 atoms selected from O and S, which is substituted by 0, 1, 2 or 3 groups selected from F, Cl, Br, C 1-6 alk, C 1-4 haloalk, —OR a , —OC 1-4 haloalk, CN, —C(═O)R b , —C(═O)OR a , —C(═O)NR a R a , —C(═NR a )NR a R a , —OC(═O)R b , —OC(═O)NR a R a , —OC 2-6 alkNR a R a , —OC 2-6 alkOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkNR a R a , —NR a C 2-6 alkOR a , —C 1-6 alkNR a R a , —C 1-6 alkOR a , —C 1-6 alkN(R a )C(═O)R b , —C 1-6 alkOC(═O)R b , —C 1-6 alkC(═O)NR a R a , —C 1-6 alkC(═O)OR a , R 8  and oxo; 
 R 8  is a C 1-6 alk substituted by 0, 1, 2 or 3 groups selected from F, Cl, Br, C 1-6 alk, C 1-4 haloalk, —OR a , —OC 1-4 haloalk, CN, —C(═O)R b , —C(═O)OR a , —C(═O)NR a R a , —C(═NR a )NR a R a , —OC(═O)R b , —OC(═O)NR a R a , —OC 2-6 alkNR a R a , —OC 2-6 alkOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkNR a R a , —NR a C 2-6 alkOR a , —C 1-6 alkNR a R a , —C 1-6 alkOR a , —C 1-6 alkN(R a )C(═O)R b , —C 1-6 alkOC(═O)R b , —C 1-6 alkC(═O)NR a R a , —C 1-6 alkC(═O)OR a  and oxo; 
 R 9  is independently selected from the group consisting of H, F, Cl, Br, C 1-6 alk, C 1-4 haloalk, —OR a , —OC 1-4 haloalk, CN, —C(═O)R b , —C(═O)OR a , —C(═O)NR a R a , —C(═NR a )NR a R a , —OC(═O)R b , —OC(═O)NR a R a , —OC 2-6 alkNR a R a , —OC 2-6 alkOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —NR a R c , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkNR a R a , —NR a C 2-6 alkOR a , —C 1-6 alkNR a R a , —C 1-6 alkOR a , —C 1-6 alkN(R a )C(═O)R b , —C 1-6 alkOC(═O)R b , —C 1-6 alkC(═O)NR a R a , —C 1-6 alkC(═O)OR a , R 7 , R 8  and oxo; 
 R a  is independently, at each instance, H or R b ; 
 R b  is independently, at each instance, phenyl, benzyl or C 1-6 alk, the phenyl, benzyl and C 1-6 alk being substituted by 0, 1, 2 or 3 substituents selected from halo, C 1-4 alk, C 1-3 haloalk, —OH, —OC 1-4 alk, —NH 2 , —NHC 1-4 alk, —OC(═O)C 1-4 alk, or —N(C 1-4 alk)C 1-4 alk; 
 R c  is a C 0-4 alk-linked saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered monocyclic or 8-, 9-, 10-, 11-, or 12-membered bicyclic ring containing 0, 1, 2 or 3 N atoms and 0 or 1 atom selected from O and S, which is substituted by 0, 1, 2 or 3 groups selected from F, Cl, Br, C 1-6 alk, C 1-4 haloalk, R 7 , —OR a , —OC 1-4 haloalk, CN, —C(═O)R b , —C(═O)OR a , —C(═O)NR a R a , —C(═NR a )NR a R a , —OC(═O)R b , —OC(═O)NR a R a , —OC 2-6 alkNR a R a , —OC 2-6 alkOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkNR a R a , —NR a C 2-6 alkOR a , —C 1-6 alkNR a R a , —C 1-6 alkOR a , —C 1-6 alkN(R a )C(═O)R b , —C 1-6 alkOC(═O)R b , —C 1-6 alkC(═O)NR a R a , —C 1-6 alkC(═O)OR a  and oxo. 
 
     
     
         8 . The method of  claim 7  wherein said condition is selected from the group consisting of psychoses, Parkinson's disease, dementias, obsessive compulsive disorder, tardive dyskinesia, choreas, depression, mood disorders, impulsivity, drug addiction, attention deficit/hyperactivity disorder (ADHD), depression with parkinsonian states, personality changes with caudate or putamen disease, dementia and mania with caudate and pallidal diseases, and compulsions with pallidal disease. 
     
     
         9 . The method of  claim 7  wherein said condition is selected from the group consisting of obesity, schizophrenia, Huntington's disease, bipolar disorder, and obsessive-compulsive disorder. 
     
     
         10 . The method as in any one of  claims 1 ,  4 , and  7 , in which said compound of formula I, II, or III, is selected from the group consisting of:
 (1H-Benzo[d]imidazol-2-yl)(4-(3-morpholinopyrazin-2-yloxy)phenyl)methanone;   (S)-(1H-benzo[d]imidazol-2-yl)(4-(3-(4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)piperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-chloropyrazin-2-yloxy)phenyl)methanone;   [4-(3-Chloro-pyrazin-2-yloxy)-phenyl]-(6-fluoro-1H-benzoimidazol-2-yl)-methanone;   (1-Methyl-1H-benzo[d]imidazol-2-yl)(4-(3-morpholinopyrazin-2-yloxy)phenyl)-methanone;   (1-Isopropyl-1H-benzo[d]imidazol-2-yl)(4-(3-morpholinopyrazin-2-yloxy)phenyl)-methanone;   4-(3-(4-((1H-benzo[d]imidazol-2-yl)difluoromethyl)phenoxy)pyrazin-2-yl)morpholine   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-(2-hydroxypropan-2-yl)piperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-hydroxypiperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(3-hydroxypiperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-methoxypiperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(pyrrolidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(piperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (R)-(1H-benzo[d]imidazol-2-yl)(4-(3-(2-(methoxymethyl)pyrrolidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2,6-dimethylmorpholino)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-methylpiperazin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperazin-1-yl)ethanone;   1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidine-4-carbonitrile;   (1H-benzo[d]imidazol-2-yl)(4-(3-(tetrahydro-2H-pyran-4-ylamino)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(tetrahydro-2H-pyran-3-ylamino)pyrazin-2-yloxy)phenyl)methanone;   (4-(3-(1,4-oxazepan-4-yl)pyrazin-2-yloxy)phenyl)(1H-benzo[d]imidazol-2-yl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-(methoxymethyl)piperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-4-one;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-(trifluoromethyl)piperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-(2-hydroxyethyl)piperazin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   ethyl 2-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperazin-1-yl)acetate;   (1H-benzo[d]imidazol-2-yl)(4-(3-(6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-methoxypiperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   8-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)-2-methyl-2,8-diazaspiro[4.5]decan-1-one;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-morpholinopiperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(3-hydroxypyrrolidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)-1-methylpiperazin-2-one;   (S)-(1H-benzo[d]imidazol-2-yl)(4-(3-(2-(hydroxymethyl)pyrrolidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (S)-(1H-benzo[d]imidazol-2-yl)(4-(3-(3-(hydroxymethyl)pyrrolidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(3-methyl-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)pyrazin-2-yloxy)phenyl)methanone;   (R)-(1H-benzo[d]imidazol-2-yl)(4-(3-(3-(hydroxymethyl)pyrrolidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (S)-(1H-benzo[d]imidazol-2-yl)(4-(3-(2-(methoxymethyl)pyrrolidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-(2-hydroxyethyl)piperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidine-3-carbonitrile;   1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)pyrrolidine-3-carbonitrile;   ethyl 1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidine-4-carboxylate;   methyl 1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)pyrrolidine-3-carboxylate;   ethyl 1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidine-3-carboxylate;   (1H-benzo[d]imidazol-2-yl)(4-(3-(3-(3-methyl-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (S)-(1H-benzo[d]imidazol-2-yl)(4-(3-(3-hydroxypyrrolidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-(1-hydroxyethyl)piperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidine-4-carboxylic acid;   (1H-benzo[d]imidazol-2-yl)(4-(3-(3-(2-hydroxyethyl)piperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-(hydroxymethyl)piperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(3-(2-hydroxypropan-2-yl)piperidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)-6-methylpiperazin-2-one;   (1H-imidazo[4,5-b]pyridin-2-yl)(4-(3-morpholinopyrazin-2-yloxy)phenyl)methanone;   (4-(3-chloropyrazin-2-yloxy)phenyl)(1H-imidazo[4,5-b]pyridin-2-yl)methanone;   (4-(3-chloropyrazin-2-yloxy)phenyl)(7-fluoro-1H-benzo[d]imidazol-2-yl)methanone;   (4-(3-chloropyrazin-2-yloxy)phenyl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(3-hydroxyazetidin-1-yl)pyrazin-2-yloxy)phenyl)methanone;   (S)—N-(4-(3-(2-(Methoxymethyl)pyrrolidin-1-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(Tetrahydro-2H-pyran-3-ylamino)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   (S)-2-(1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)pyrrolidin-2-yl)propan-2-ol;   1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)-4-methylpiperidin-4-ol;   Benzo[d]thiazol-2-yl(4-(3-morpholinopyrazin-2-yloxy)phenyl)methanone;   N-(4-(3-Chloropyrazin-2-yloxy)phenyl)-6-fluorobenzo[d]thiazol-2-amine;   N-(4-(3-morpholinopyrazin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine;   5-fluoro-N-(4-(3-morpholinopyrazin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine;   N-(4-(3-morpholinopyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   2-(1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-4-yl)propan-2-ol;   1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-4-ol;   N-(4-(3-(pyrrolidin-1-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-3-ol;   1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidine-4-carbonitrile;   1-(4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperazin-1-yl)ethanone;   N-(4-(3-(4-methylpiperazin-1-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   2-(1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-4-yl)-1,1,1-trifluoropropan-2-ol;   N-(4-(3-(2,6-dimethylmorpholino)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-((3-(1,1-dioxido-4-thiomorpholinyl)-2-pyrazinyl)oxy)phenyl)-1,3-benzothiazol-2-amine;   (S)-(1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)pyrrolidin-2-yl)methanol;   N-(4-(3-(azetidin-1-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)azetidine-3-carboxylic acid;   2-(4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperazin-1-yl)ethanol;   N-(4-(3-(6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidine-4-carboxamide;   N-(4-(3-(2-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   methyl 1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)azetidine-3-carboxylate;   1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)pyrrolidine-3-carbonitrile;   (R)-(1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)pyrrolidin-3-yl)methanol;   2-(1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-4-yl)ethanol;   N-(4-(3-(4-(methoxymethyl)piperidin-1-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(3-(methoxymethyl)pyrrolidin-1-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   (1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-4-yl)methanol;   4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperazin-2-one;   4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)-1-isopropylpiperazin-2-one;   N-(4-(3-(4-methoxypiperidin-1-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)azetidine-3-carbonitrile;   4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)-6-methylpiperazin-2-one;   1-(1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-4-yl)ethanol;   methyl 1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)pyrrolidine-3-carboxylate;   (1-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-2-yl)methanol;   N-(4-(3-(3-(methoxymethyl)piperidin-1-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-chloropyrazin-2-yloxy)phenyl)-7-fluorobenzo[d]thiazol-2-amine;   N-(4-(3-chloropyrazin-2-yloxy)phenyl)-6-fluorobenzo[d]thiazol-2-amine;   N-(4-(3-chloropyrazin-2-yloxy)phenyl)-5-fluorobenzo[d]thiazol-2-amine;   N-(4-(3-chloropyrazin-2-yloxy)-2-fluorophenyl)benzo[d]thiazol-2-amine;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-(trifluoromethyl)pyridin-4-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-(4-methoxybenzyloxy)pyridin-3-yl)pyrazin-2-yloxy)phenyl)methanone;   3-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)pyridin-2(1H)-one;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-methylpyridin-4-yl)pyrazin-2-yloxy)phenyl)methanone;   4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)benzonitrile;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-methylpyridin-3-yl)pyrazin-2-yloxy)phenyl)methanone;   (1-methyl-1H-benzo[d]imidazol-2-yl)(4-(3-(2-methylpyridin-3-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2,6-dimethoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(3-methoxypyridin-4-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-methoxyphenyl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-methoxyquinolin-3-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(5-fluoro-2-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)methanone;   (5-fluoro-1H-benzo[d]imidazol-2-yl)(4-(3-(2-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(5-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)methanone;   (4-(3-(2-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-methoxypyridin-4-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(6-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(pyridin-3-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(pyridin-4-yl)pyrazin-2-yloxy)phenyl)methanone;   3-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)benzonitrile;   methyl 4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)benzoate;   4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)benzoic acid;   (1H-benzo[d]imidazol-2-yl)(4-(3-(3-methoxyphenyl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(quinolin-4-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(quinolin-5-yl)pyrazin-2-yloxy)phenyl)methanone;   (4-(3-(3,6-dihydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)(1H-imidazo[4,5-b]pyridin-2-yl)methanone;   2-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)-4,4-dimethylcyclohex-2-enone;   1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone;   (1-(2-fluoroethyl)-1H-benzo[d]imidazol-2-yl)(4-(3-(2-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)methanone;   N-(4-(3-(2-methylpyridin-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   3-(3-(4-(benzo[d]thiazol-2-ylamino)-3-fluorophenoxy)pyrazin-2-yl)cyclohex-2-enone;   3-(3-(4-(benzo[d]thiazol-2-ylamino)-3-fluorophenoxy)pyrazin-2-yl)cyclohex-2-enol;   N-(4-(3-(6-morpholinopyridin-3-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(4-morpholinophenyl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(6-methylpyridin-3-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   5-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)picolinonitrile   N-(4-(3-(pyrimidin-5-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(2-methoxypyrimidin-5-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(6-chloropyridin-3-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   (5-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)pyridin-2-yl)methanol;   N-(4-(3-(quinolin-5-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(pyridin-3-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(3-methoxypyridin-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(3-methoxyphenyl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   7-fluoro-N-(4-(3-(2-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(2-methoxypyridin-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   6-fluoro-N-(4-(3-(2-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   5-fluoro-N-(4-(3-(2-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(2-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(5-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(2-fluoro-4-(3-(2-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(2-fluoro-4-(3-(2-fluoropyridin-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   tert-butyl 4-(3-(4-(benzo[d]thiazol-2-ylamino)-3-fluorophenoxy)pyrazin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate;   (1H-benzo[d]imidazol-2-yl)(4-(3-methoxypyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-isopropoxypyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-isobutoxypyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(cyclopropylmethoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2,2,2-trifluoroethoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-methoxyethoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(pyridin-2-ylmethoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-phenoxypyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(pyridin-3-yloxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(but-2-ynyloxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-(4-methylthiazol-5-yl)ethoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-((tetrahydrofuran-3-yl)methoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-morpholinoethoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-(pyrrolidin-1-yl)ethoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-(dimethylamino)ethoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-(1-methylpyrrolidin-2-yl)ethoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(pyridin-4-ylmethoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-(pyridin-2-yl)ethoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(3-(pyridin-3-yl)propoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(pyridin-3-ylmethoxy)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-propoxypyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-imidazo[4,5-b]pyridin-2-yl)(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)methanone;   (6-fluoro-1H-benzo[d]imidazol-2-yl)(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)methanone;   (1-methyl-1H-benzo[d]imidazol-2-yl)(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)methanone;   (6-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)methanone;   (5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)methanone;   1H-benzimidazol-2-yl(4-((3-(tetrahydro-2H-pyran-3-yl)-2-pyrazinyl)oxy)-phenyl)methanone;   1H-Benzimidazol-2-yl(4-((3-(4-methoxy-1-cyclohexen-1-yl)-2-pyrazinyl) oxy)phenyl)methanone;   1H-benzimidazol-2-yl(4-((3-(cis-4-hydroxycyclohexyl)-2-pyrazinyl)oxy)phenyl)methanone; and 1H-benzimidazol-2-yl(4-((3-(trans-4-hydroxycyclohexyl)-2-pyrazinyl)oxy)phenyl)methanone;   cis-(1H-benzo[d]imidazol-2-yl)(4-(3-(3-hydroxycyclohexyl)pyrazin-2-yloxy)phenyl)methanone;   trans-(1H-benzo[d]imidazol-2-yl)(4-(3-(3-hydroxycyclohexyl)pyrazin-2-yloxy)phenyl)methanone;   cis-3-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)cyclohexanol;   trans-3-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)cyclohexanol;   N-(4-(3-(Tetrahydro-2H-pyran-3-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   3-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)cyclohexanone;   4-(2-(4-(1H-Benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)cyclohexanone;   (1H-Benzo[d]imidazol-2-yl)(4-(3-((1s,4s)-4-hydroxy-4-methylcyclohexyl)pyridin-2-yloxy)phenyl)methanone;   (1H-Benzo[d]imidazol-2-yl)(4-(3-((1r,4r)-4-hydroxy-4-methylcyclohexyl)pyridin-2-yloxy)phenyl)methanone;   (1H-Benzo[d]imidazol-2-yl)(4-(3-(oxepan-4-yl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4,4-difluorocyclohex-1-enyl)pyrazin-2-yloxy)phenyl)methanone;   4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)tetrahydro-2H-pyran-4-carbonitrile;   N-methyl-N-(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)tetrahydro-2H-pyran-4-ol;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-fluorotetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)methanone;   N-(4-(3-(4-fluorotetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   1-tert-butyl 4-methyl 4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidine-1,4-dicarboxylate;   tert-butyl 4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)-4-(hydroxymethyl)piperidine-1-carboxylate;   N-(4-(3-(Tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine;   N-(4-(3-(Tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   7-Methoxy-N-(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine;   3-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)cyclohexanone;   4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)tetrahydro-2H-pyran-4-carbonitrile;   methyl 4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)tetrahydro-2H-pyran-4-carboxylate;   (1H-benzo[d]imidazol-2-yl)(4-(3-(4-hydroxytetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)methanone;   6-fluoro-N-(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(2-fluoro-4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(2-fluoro-4-(pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   7-fluoro-N-(4-(pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   5-fluoro-N-(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   5-fluoro-N-(4-(pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   (1H-benzo[d]imidazol-2-yl)(4-(3-cyclopentylpyrazin-2-yloxy)phenyl)methanone;   N-(4-(3-(tetrahydrofuran-3-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   1H-benzo[d]imidazole-2-yl(4-(3-(tetrahydro-2H-thiopyran-4-yl)pyrazin-2-yloxy)phenyl)methanone;   N-(4-(3-cyclopentylpyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone;   1-(4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(1-(2-fluoroethyl)piperidin-4-yl)pyrazin-2-yloxy)phenyl)methanone;   methyl 4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidine-1-carboxylate;   1-(4-(3-(4-((1H-benzo[d]imidazol-2-yl)(hydroxy)methyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-(2-methoxypyridin-3-yl)pyrazin-2-yloxy)phenyl)methanol;   (1H-benzo[d]imidazol-2-yl)(4-(3-(piperidin-4-yl)pyrazin-2-yloxy)phenyl)methanone;   1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)perdeuteroethanone;   1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-methoxyethanone;   1-(4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-methoxyethanone;   1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-fluoropropan-1-one;   1-(4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-fluoropropan-1-one;   N-(4-(3-(1-(2-fluoroethyl)piperidin-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   N-(4-(3-(1-methylpiperidin-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine;   1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)-1-oxopropan-2-yl acetate;   1-(4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-hydroxypropan-1-one;   1-(3-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)pyrrolidin-1-yl)ethanone;   1-(3-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)pyrrolidin-1-yl)ethanone;   1-(4-(3-(4-(1-methyl-1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone;   2-methoxy-1-(4-(3-(4-(1-methyl-1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone;   2-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-oxoethyl acetate;   1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-(dimethylamino)ethanone;   1-(4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-(dimethylamino)ethanone;   3-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)-3-oxopropanenitrile;   1-(4-(3-(4-(benzo[d]thiazol-2-ylamino)-2-fluorophenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone;   1-(4-(3-(6-(benzo[d]thiazol-2-ylamino)pyridin-3-yloxy)pyrazin-2-yl)piperidin-1-yl)ethanone;   1-(3-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)azetidin-1-yl)ethanone;   1-(3-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone;   4-(3-(4-(1H-Benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)-1-methyl-5,6-dihydropyridin-2(1H)-one;   4-(3-(4-(1H-Benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)-1-methylpiperidin-2-one;   3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)-N-phenethylpyrazine-2-carboxamide;   3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)-N-(4-(trifluoromethyl)phenethyl)pyrazine-2-carboxamide;   (S)-3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)-N-(1-methoxypropan-2-yl)pyrazine-2-carboxamide;   3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)-N-(2-(pyridin-2-yl)ethyl)pyrazine-2-carboxamide;   3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)-N-(2-hydroxyethyl)pyrazine-2-carboxamide;   3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)-N-(1-(pyridin-2-yl)propan-2-yl)pyrazine-2-carboxamide;   3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)-N-(1-benzylcyclopropyl)pyrazine-2-carboxamide;   (R)-1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)pyrrolidine-3-carbonitrile;   (S)-1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)pyrrolidine-3-carbonitrile;   (R)-ethyl 1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidine-3-carboxylate;   (S)-ethyl 1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidine-3-carboxylate;   (S)-methyl 1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)pyrrolidine-3-carboxylate;   (R)-methyl 1-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)pyrrolidine-3-carboxylate;   (R)-4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)-6-methylpiperazin-2-one;   (S)-4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)-6-methylpiperazin-2-one;   (1H-benzo[d]imidazol-2-yl)(4-(3-((1R,3S)-3-hydroxycyclohexyl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-((1S,3R)-3-hydroxycyclohexyl)pyrazin-2-yloxy)phenyl)methanone;   (1S,3R)-3-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)cyclohexanol;   (1R,3S)-3-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)cyclohexanol;   (1H-benzo[d]imidazol-2-yl)(4-(3-((1S,3S)-3-hydroxycyclohexyl)pyrazin-2-yloxy)phenyl)methanone;   (1H-benzo[d]imidazol-2-yl)(4-(3-((1R,3R)-3-hydroxycyclohexyl)pyrazin-2-yloxy)phenyl)methanone;   (1S,3S)-3-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)cyclohexanol;   (1R,3R)-3-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)cyclohexanol;   (R)-1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-fluoropropan-1-one;   (S)-1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-fluoropropan-1-one;   (R)-1-(4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-fluoropropan-1-one;   (S)-1-(4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-fluoropropan-1-one;   (R)-3-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)cyclohexanone;   (S)-3-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)cyclohexanone; or   any pharmaceutically-acceptable salt thereof.