Triazine-oxadiazoles

Abstract

The invention relates to new derivatives of formula (I), wherein the substituents are as defined in the specification; to processes for the preparation of such derivatives; pharmaceutical compositions comprising such derivatives; such derivatives as a medicament; such derivatives for the treatment of chronic pain.

1 - 20 . (canceled) 
     
     
         21 . A compound of formula (I) or a pharmaceutically acceptable salts thereof, 
       
         
           
           
               
               
           
         
       
       wherein 
       R 1  is selected from
 hydrogen- 
 halogen- 
 halo-C 1 -C 7 -alkyl-; 
 
       R 2  is selected from
 hydrogen- 
 C 1 -C 7 -alkyl- 
 halo-C 2 -C 7 -alkyl- 
 amino-C 2 -C 7 -alkyl- 
 N—C 1 -C 7 -alkyl-amino-C 2 -C 7 -alkyl- 
 N,N-di-C 1 -C 7 -alkyl-amino-C 2 -C 7 -alkyl- 
 hydroxy-C 2 -C 7 -alkyl- 
 C 1 -C 7 alkoxy-C 2 -C 7 -alkyl- 
 C 3 -C 10 -cycloalkyl-C 1 -C 7 -alkyl- 
 cyano-C 2 -C 7 -alkyl-; 
 
       or 
       R 1  and R 2 , together with the atoms to which they are attached, form a 4-7 membered, saturated or partially saturated heterocyclic ring, which is unsubstituted or substituted by 1-3 substituents selected from
 C 1 -C 7 -alkyl- 
 halo-C 1 -C 7 -alkyl- 
 amino-C 1 -C 7 -alkyl- 
 N—C 1 -C 7 -alkyl-amino-C 1 -C 7 -alkyl- 
 N,N-di-C 1 -C 7 -alkyl-amino-C 1 -C 7 -alkyl- 
 hydroxy-C 1 -C 7 -alkyl- 
 C 1 -C 7 -alkoxy-C 1 -C 7 -alkyl- 
 C 3 -C 10 -cycloalkyl-C 1 -C 7 -alkyl- 
 cyano-C 1 -C 7 -alkyl-; 
 
       R is selected from
 halogen- 
 halo-C 1 -C 7 -alkyl- 
 C 1 -C 7 -alkoxy- 
 cyano- 
 halo-C 1 -C 7 -alkoxy- 
 nitro; 
 —C(O)—O—R′, wherein R′ is selected from hydrogen, C 1 -C 7 -alkyl; C 3 -C 10 -cycloalkyl; C 1 -C 7 -alkoxy; halo-C 1 -C 7 -alkyl aryl; aryl-C 1 -C 7 -alkyl-; heteroaryl; heteroaryl C 1 -C 7 -alkyl-; 
 heterocyclyl; 
 —S(═O) 2 —C 1 -C 7 -alkyl; —S(═O) 2 —C 3 -C 10 -cycloalkyl; —S(═O) 2 —C 1 -C 7 -alkoxy; 
 
       R 3  is selected from 
       (a) -L-Y, wherein
 -L- is selected from a direct bond; —(CH 2 ) p —, —C(O)—, —NR 7 —, —NR 7 —C(O)— or —C(O)—NR 7 —,
 wherein p is selected from 1, 2 or 3 
 R 7  is selected from hydrogen and C 1 -C 7 -alkyl 
 
 Y is selected from cycloalkyl, aryl, heteroraryl, heterocyclyl, spirocyclyl, which are unsubstituted or substituted by 1-3 substituents selected from
 halogen-; 
 C 1 -C 7 -alkyl-; 
 halo-C 1 -C 7 -alkyl-; 
 halo-C 1 -C 7 -alkyl-oxy-C 1 -C 7 -alkyl; halo-C 1 -C 7 -alkyl-oxy-C 1 -C 7 -alkyl-oxy; 
 C 1 -C 7 -alkoxy-; C 1 -C 7 -alkoxy-C 1 -C 7 -alkoxy-; NC—C 1 -C 7 -alkoxy-; 
 C 1 -C 7 -alkoxy-C 1 -C 7 -alkyl-; 
 C 3 -C 10 -cycloalkyl-oxy-C 1 -C 7 -alkyl-; 
 C 3 -C 10 -cycloalkyl-C 1 -C 7 -alkyl-oxy-; 
 C 3 -C 10 -cycloalkyl-oxy-; 
 C 3 -C 10 -cycloalkyl-NR 7′ —C 1 -C 7 -alkyl-, wherein R 7′  is selected from R 7  is selected from hydrogen and C 1 -C 7 -alkyl; 
 C 3 -C 10 -cycloalkyl-C 1 -C 7 -alkoxy-C 1 -C 7 -alkyl-; 
 C 2 -C 7 -alkenyl; halo-C 2 -C 7 -alkenyl; 
 hydroxy-; 
 hydroxy-C 1 -C 7 -alkyl-; 
 halo-C 1 -C 7 -alkyl-oxy-; 
 amino-; 
 N—C 1 -C 7 -alkyl-amino-; 
 N-halo-C 1 -C 7 -alkyl-amino-; 
 N-heterocyclyl-amino-, N—C 3 -C 10 -cycloalkyl-amino-, wherein the heterocyclyl and cycloalkyl are optionally substituted by halo-C 1 -C 7 -alkyl-oxy, C 1 -C 7 -alkyl; C 3 -C 10 -cycloalkyl and C 1 -C 7 -alkoxy; 
 N—C 3 -C 10 -cycloalkyl-C 1 -C 7 -alkyl-amino-; 
 N,N-di-heterocyclyl-amino-, N,N-di-C 3 -C 10 -cycloalkyl-amino- wherein the heterocyclyl and cycloalkyl are optionally substituted by halo-C 1 -C 7 -alkyl-oxy, C 1 -C 7 -alkyl; C 3 -C 10 -cycloalkyl and C 1 -C 7 -alkoxy; 
 cyano-; oxo; 
 C 1 -C 7 -alkoxy-carbonyl-; 
 C 1 -C 7 -alkoxy-C 1 -C 7 -alkoxy-C 1 -C 7 -alkyl-; 
 aryl; aryl-C 1 -C 7 -alkyl-; aryl-oxy; 
 heterocyclyl; 
 heterocyclyl-C 1 -C 7 -alkyl-; heterocyclyl-oxy-; 
 heterocyclyl-oxy-C 1 -C 7 -alkyl-; aryl-oxy-C 1 -C 7 -alkyl-; heteroaryl-oxy-C 1 -C 7 -alkyl-; 
 hydroxy-carbonyl-; 
 —S— halo-C 1 -C 7 -alkyl; —S—C 1 -C 7 -alkyl; —S— aryl; 
 halo-C 1 -C 7 -alkyl-S—C 1 -C 7 -alkyl; C 1 -C 7 -alkyl-S—C 1 -C 7 -alkyl; 
 —S(═O) 2 —C 1 -C 7 -alkyl; —S(═O) 2 — halo-C 1 -C 7 -alkyl; —S(═O) 2 -aryl; —S(═O) 2 -heteroaryl; 
 —S(═O) 2 —NR 4′ R 4 ; —S(═O) 2 -heterocyclyl; 
 halo-C 1 -C 7 -alkyl-S(═O) 2 —C 1 -C 7 -alkyl; C 1 -C 7 -alkyl-S(═O) 2 —C 1 -C 7 -alkyl; 
 —S(═O)—C 1 -C 7 -alkyl; —S(═O)-halo-C 1 -C 7 -alkyl; —S(═O)—C 1 -C 7 -alkoxy; —S(═O)—C 3 -C 10 -cycloalkyl; 
 —C(O)—C 1 -C 7 -alkyl; —C(O)— halo-C 1 -C 7 -alkyl; —C(O)—C 1 -C 7 -alkoxy; —C(O)—C 3 -C 10 -cycloalkyl; 
 —C(O)O—C 1 -C 7 -alkyl; —C(O)O—C 3 -C 10 -cycloalkyl; —C(O)O-halo-C 1 -C 7 -alkyl; —C(O)O—C 1 -C 7 -alkoxy; 
 —C(O)—NR 4′ R 4  or —NHC(O)—R 4 , wherein 
 R 4  is selected from hydrogen, C 1 -C 7 -alkyl, halo-C 1 -C 7 -alky, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkyl-C 1 -C 7 -alkyl and C 1 -C 7 -alkoxy;
 R 4′  is selected from hydrogen; 
 or R 4  and R 4′  together with the nitrogen atom to which they are attached, form a 4-7 membered, saturated or partially saturated monocyclic heterocyclic ring, optionally containing a further heteroatom selected from N, O or S, and wherein said heterocyclic ring is optionally substituted with aryl, aryl-oxy-, C 1 -C 7 -alkyl, halo-C 1 -C 7 -alkyl or C 1 -C 7 -alkoxy, and said aryl is optionally substituted with halogen, halo-C 1 -C 7 -alkyl or C 1 -C 7 -alkoxy. 
 
 
 
       or 
       (b) —C(O)—NR 5′ R 5  or —C(O)—O—R 5 , wherein
 R 5  and R 5′  are selected from hydrogen, C 1 -C 7 -alkyl; C 3 -C 10 -cycloalkyl; C 1 -C 7 -alkoxy; 
 halo-C 1 -C 7 -alkyl aryl; aryl-C 1 -C 7 -alkyl-; aryl; heteroaryl; heteroaryl C 1 -C 7 -alkyl-; 
 heterocyclyl; indane; or R 5  and R 5′  together with the nitrogen atom to which they are attached, form a 4-9 membered, saturated or partially saturated monocyclic or bicyclic heterocyclic ring, optionally containing a further heteroatom selected from N, O or S; 
 wherein said C 3 -C 10 -cycloalkyl; aryl, heteroaryl, heterocyclyl and indane are optionally substituted with 1 to 3 substituents selected from C 1 -C 7 -alkyl, halo-C 1 -C 7 -alkyl, C 1 -C 7 -alkoxy, halo-C 1 -C 7 -alkyl-oxy-, halo-C 1 -C 7 -alkyl-oxy-C 1 -C 7 -alkyl-oxy-C 1 -C 7 -alkyl and hydroxy-C 1 -C 7 -alkyl; 
 
       or 
       (c) —NR 6′ R 6 , wherein
 R 6  is selected from hydrogen, C 1 -C 7 -alkyl, 
 R 6′  is selected from hydrogen, C 1 -C 7 -alkyl, C 1 -C 7 -alkyl carbonyl-; C 3 -C 10 -cycloalkyl; 
 or R 6  and R 6′  together with the nitrogen atom to which they are attached, form a 4-7 membered, saturated or partially saturated monocyclic, or 7-12 membered, saturated or partially saturated bicyclic heterocyclic ring, optionally containing a further heteroatom selected from N, O or S;
 which monocyclic and bicyclic heterocyclic ring is unsubstituted or substituted by 1-3 substituents selected from 
 C 1 -C 7 -alkoxy-, halo-C 1 -C 7 -alkoxy-, halo-C 1 -C 7 -alkoxy-C 1 -C 7 -alkyl-, hydroxy- and C 1 -C 7 -alkoxy-carbonyl-; 
 
 
       (d) —NR 5′ —C(O)—R 5 , wherein
 R 5  is selected from hydrogen, C 1 -C 7 -alkyl; C 3 -C 10 -cycloalkyl; C 1 -C 7 -alkoxy; halo-C 1 -C 7 -alkyl; aryl; aryl-C 1 -C 7 -alkyl-; heteroaryl; heteroaryl-C 1 -C 7 -alkyl-; heterocyclyl; 
 R 5′  is selected from hydrogen, C 1 -C 7 -alkyl; 
 
       m is 0-1; and 
       n is 0-2; 
       R 8  is hydrogen and R 9  is selected from hydrogen, C 1 -C 7 -alkoxy-C 1 -C 7 -alkyl-, C 1 -C 7 -alkyl, C 1 -C 7 -alkoxy and halo-C 1 -C 7 -alkyl; 
       wherein C 1 -C 7 -alkyl, C 1 -C 7 -alkoxy, heterocyclyl, aryl, heteroaryl are optionally substituted by aryl, heteroaryl, heterocyclyl, C 1 -C 7 -alkoxy, halo-C 1 -C 7 -alkyl; OH; 
       with the proviso that 6-[5-(2-furanyl)-1,2,4-oxadiazol-3-yl]-N2-methyl-N2-phenyl-1,3,5-triazine-2,4-diamine and 6-[5-(2-furanyl)-1,2,4-oxadiazol-3-yl]-N,N,N′-methyl-N′-phenyl-1,3,5-triazine-2,4-diamine are excluded. 
     
     
         22 . A compound according to  claim 21  with formula (I) 
       
         
           
           
               
               
           
         
       
       wherein 
       R 1  is selected from
 hydrogen- 
 halogen- 
 C 1 -C 7 -alkyl- 
 halo-C 1 -C 7 -alkyl-; 
 
       R 2  is selected from
 hydrogen- 
 C 1 -C 7 -alkyl- 
 halo-C 2 -C 7 -alkyl- 
 amino-C 2 -C 7 -alkyl- 
 N—C 1 -C 7 -alkyl-amino-C 2 -C 7 -alkyl- 
 N,N-di-C 1 -C 7 -alkyl-amino-C 2 -C 7 -alkyl- 
 hydroxy-C 2 -C 7 -alkyl- 
 C 1 -C 7 -alkoxy-C 2 -C 7 -alkyl- 
 C 3 -C 10 -cycloalkyl-C 1 -C 7 -alkyl- 
 cyano-C 2 -C 7 -alkyl-; 
 
       or 
       R 1  and R 2 , together with the atoms to which they are attached, form a 4-7 membered, saturated or partially saturated heterocyclic ring, which is unsubstituted or substituted by 1-3 substituents selected from
 C 1 -C 7 -alkyl- 
 halo-C 1 -C 7 -alkyl- 
 amino-C 1 -C 7 -alkyl- 
 N—C 1 -C 7 -alkyl-amino-C 1 -C 7 -alkyl- 
 N,N-di-C 1 -C 7 -alkyl-amino-C 1 -C 7 -alkyl- 
 hydroxy-C 1 -C 7 -alkyl- 
 C 1 -C 7 -alkoxy-C 1 -C 7 -alkyl- 
 C 3 -C 10 -cycloalkyl-C 1 -C 7 -alkyl- 
 cyano-C 1 -C 7 -alkyl-; 
 
       R is selected from
 halogen- 
 C 1 -C 7 -alkyl- 
 halo-C 1 -C 7 -alkyl- 
 C 1 -C 7 -alkoxy- 
 cyano- 
 halo-C 1 -C 7 -alkoxy- 
 nitro; 
 
       R 3  is selected from 
       (a) —(CH 2 ) p —Y, wherein
 p is selected from 0, 1, 2 or 3, and 
 Y is selected from aryl, heteoraryl, heterocyclyl, which are unsubstituted or substituted by 1-3 substituents selected from
 halogen- 
 halo-C 1 -C 7 -alkyl- 
 C 1 -C 7 -alkoxy- 
 C 3 -C 10 -cycloalkyl-oxy- 
 hydroxy- 
 halo-C 1 -C 7 -alkyl-oxy- 
 amino- 
 N—C 1 -C 7 -alkyl-amino- 
 N,N-di-C 1 -C 7 -alkyl-amino- 
 cyano- 
 C 1 -C 7 alkoxy-carbonyl- 
 hydroxy-carbonyl- 
 —C(O)—NR 4′ R 4 , wherein
 R 4  is selected from hydrogen, C 1 -C 7 -alkyl; 
 R 4′  is selected from hydrogen, 
 or R 4  and R 4′  together with the nitrogen atom to which they are attached, form a 4-7 membered, saturated or partially saturated monocyclic heterocyclic ring, optionally containing a further heteroatom selected from N, O or S; 
 
 
 
       or 
       (b) —C(O)—NR 5′ R 5  or —C(O)—O—R 5 , wherein
 R 5  is selected from hydrogen, benzyl, indanyl, tetrahydrofuranyl, tetrahydropyranyl, oxiranyl, C 3 -C 10 -cycloalkyl, C 1 -C 7 -alkyl; 
 R 5′  is selected from hydrogen, C 1 -C 7 -alkyl, 
 or R 5  and R 5′  together with the nitrogen atom to which they are attached, form a 4-7 membered, saturated or partially saturated monocyclic or bicyclic heterocyclic ring, optionally containing a further heteroatom selected from N, O or S; 
 
       or 
       (c) —NR 6′ R 6 , wherein
 R 6  is selected from hydrogen, benzyl, C 3 -C 10 -cycloalkyl, 
 R 6′  is selected from hydrogen, C 1 -C 7 -alkyl, C 1 -C 7 -alkyl carbonyl-, 
 or R 6  and R 6′  together with the nitrogen atom to which they are attached, form a 4-7 membered, saturated or partially saturated monocyclic, or 7-12 membered, saturated or partially saturated bicyclic heterocyclic ring, optionally containing a further heteroatom selected from N, O or S; 
 which are unsubstituted or substituted by 1-3 substituents selected from C 1 -C 7 -alkyl- 
 hydroxy- 
 C 1 -C 7 -alkoxy-carbonyl- 
 
       or 
       (d) —NR 5′ —C(O)—R 5 , wherein
 R 5  is selected from C 3 -C 10 -cycloalkyl; 
 R 5′  is selected from hydrogen, C 1 -C 7 -alkyl; 
 
       m is 0-1; and 
       n is 0-1; 
       with the proviso that 6-[5-(2-Furanyl)-1,2,4-oxadiazol-3-yl]-N2-methyl-N2-phenyl-1,3,5-triazine-2,4-diamine is excluded. 
     
     
         23 . A compound according to  claim 21 , 
       wherein 
       R 1  is selected from
 hydrogen- 
 chloro- 
 fluoro- 
 methyl-; 
 
       R 2  is selected from
 hydrogen- 
 C 1 -C 4 -alkyl- 
 halo-C 2 -C 4 -alkyl- 
 N,N-di-C 1 -C 7 -alkyl-amino-C 2 -C 7 -alkyl- 
 hydroxy-C 2 -C 4 -alkyl- 
 C 1 -C 2 -alkoxy-C 2 -C 4 -alkyl- 
 C 3 -C 6 -cycloalkyl-C 1 -C 7 -alkyl-. 
 
     
     
         24 . A compound according to  claim 21 , wherein 
       R 3  is selected from
 —(CH 2 ) p —Y, wherein
 p is selected from 0, 1, 2 or 3, and 
 Y is selected from aryl, heteoraryl, heterocyclyl, which are unsubstituted or substituted by 1-3 substituents selected from
 halogen- 
 C 1 -C 7 -alkyl- 
 halo-C 1 -C 7 -alkyl- 
 C 1 -C 7 -alkoxy- 
 C 3 -C 10 -cycloalkyl-oxy- 
 hydroxy- 
 halo-C 1 -C 7 -alkyl-oxy- 
 amino- 
 N—C 1 -C 7 -alkyl-amino- 
 —S(═O) 2 —C 1 -C 7 -alkyl; —S(═O) 2 — halo-C 1 -C 7 -alkyl; 
 —S(═O)—C 1 -C 7 -alkyl; —S(═O)-halo-C 1 -C 7 -alkyl C 3 -C 10 -cycloalkyl-C 1 -C 7 -alkoxy-C 1 -C 7 -alkyl-; 
 cyano- 
 C 1 -C 7 alkoxy-carbonyl- 
 hydroxy-carbonyl- 
 —C(O)—NR 4′ R 4 , wherein
 R 4  is selected from hydrogen, C 1 -C 7 -alkyl; 
 R 4′  is selected from hydrogen, 
 or R 4  and R 4′  together with the nitrogen atom to which they are attached, form a 4-7 membered, saturated or partially saturated monocyclic heterocyclic ring, optionally containing a further heteroatom selected from N, O or S. 
 
 
 
 
     
     
         25 . A compound according to  claim 21 , wherein 
       R 3  is selected from
 —(CH 2 ) p —Y, wherein
 p is selected from 0, 1, 2 or 3, and 
 Y is selected from aryl, heteoraryl, heterocyclyl, which are unsubstituted or substituted by 1-3 substituents selected from
 halogen- 
 C 1 -C 7 -alkyl- 
 halo-C 1 -C 7 -alkyl- 
 C 1 -C 7 -alkoxy- 
 C 3 -C 10 -cycloalkyl-oxy- 
 hydroxy- 
 halo-C 1 -C 7 -alkyl-oxy- 
 amino- 
 N—C 1 -C 7 -alkyl-amino- 
 N,N-di-C 1 -C 7 -alkyl-amino-C 2 -C 7 -alkyl- 
 cyano- 
 C 1 -C 7 -alkoxy-carbonyl- 
 hydroxy-carbonyl- 
 —C(O)—NR 4′ R 4 , wherein
 R 4  is selected from hydrogen, C 1 -C 7 -alkyl; 
 R 4′  is selected from hydrogen, 
 or R 4  and R 4′  together with the nitrogen atom to which they are attached, form a 4-7 membered, saturated or partially saturated monocyclic heterocyclic ring, optionally containing a further heteroatom selected from N, O or S. 
 
 
 
 
     
     
         26 . A compound according to  claim 21 , wherein 
       m is O. 
     
     
         27 . A compound according to  claim 21 , wherein 
       R 1  is selected from
 hydrogen- 
 fluoro-; 
 
       R 2  is selected from
 hydrogen- 
 C 1 -C 4 -alkyl- 
 halo-C 2 -C 4 -alkyl- 
 N,N-di-C 1 -C 2 -alkyl-amino-C 2 -C 4 -alkyl- 
 hydroxy-C 2 -C 4 -alkyl- 
 C 1 -C 2 -alkoxy-C 2 -C 4 -alkyl- 
 C 3 -C 6 -cycloalkyl-C 1 -C 7 -alkyl-; 
 or 
 
       R 1  and R 2 , together are selected from 
       —CH 2 —CH 2 — or —CH 2 —CH 2 —CH 2 —; 
       R is selected from
 halogen- 
 C 1 -C 4 -alkyl- 
 halo-C 1 -C 4 -alkyl- 
 C 1 -C 4 -alkoxy- 
 cyano-; and 
 
       R 3  is selected from
 —(CH 2 ) p —Y, wherein
 p is selected from 0, 1, 2 or 3, and 
 Y is selected from aryl, heteoraryl, heterocyclyl, which are unsubstituted or substituted by 1-3 substituents selected from
 halogen- 
 halo-C 1 -C 7 -alkyl- 
 C 1 -C 7 -alkoxy- 
 C 3 -C 10 -cycloalkyl-oxy- 
 hydroxy- 
 halo-C 1 -C 7 -alkyl-oxy- 
 amino- 
 N—C 1 -C 7 -alkyl-amino- 
 N,N-di-C 1 -C 7 -alkyl-amino- 
 cyano- 
 C 1 -C 7 -alkoxy-carbonyl- 
 —C(O)—NR 4′ R 4 , wherein
 R 4  is selected from hydrogen, C 1 -C 7 -alkyl; 
 R 4′  is selected from hydrogen, 
 or R 4  and R 4′  together with the nitrogen atom to which they are attached, form a 4-7 membered, saturated or partially saturated monocyclic heterocyclic ring, optionally containing a further heteroatom selected from N, O or S, 
 
 
 
 
       m is 0; and 
       n is 0-1. 
     
     
         28 . A compound according to  claim 21 , wherein 
       R 3  is selected from
 phenyl, furanyl, thiophenyl, pyridyl, thiazolyl, pyrazolyl, isoxazolyl, imidazolyl, pyrrolyl, benzofuranyl, pyrimidinyl, oxazolyl, morpholinyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, dihydrobenzofuranyl which are unsubstituted or substituted by 1-2 substituents selected from
 chloro- 
 bromo- 
 fluoro- 
 methyl- 
 trifluoromethyl- 
 2,2,2-trifluoro-ethyl- 
 2,2,2-trifluoro-ethyl-oxy-methyl- 
 cyclopropyl-methoxy-methyl- 
 —S(═O) 2 -2,2,2-trifluoro-ethyl-; 
 —S(═O) 2 -propyl; 
 —S(═O)-3,3,3-trifluoro-propyl; 
 3,3,3-trifluoro-propyl-oxy-methyl-; 
 methoxy- 
 cyclopentyl-oxy- 
 trifluoromethyl-oxy- 
 2,2,2-trifluoro-ethyl-oxy- 
 amino- 
 cyano- 
 methoxy-carbonyl- 
 —C(O)—NR 4′ R 4 , wherein
 R 4  is selected from hydrogen, methyl; 
 R 4′  is selected from hydrogen, 
 or R 4  and R 4′  together with the nitrogen atom to which they are attached, form morpholinyl, piperidinyl, pyrrolidinyl. 
 
 
 
     
     
         29 . A compound selected from Examples 1 to 517, or a pharmaceutically acceptable salt thereof. 
     
     
         30 . A compound which is selected from
 2-N-methyl-2-N-phenyl-6-(5-{4-[(2,2,2-trifluoroethoxy)methyl]piperidin-1-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamine;   2-N-methyl-2-N-phenyl-6-{5-[1-(propane-2-sulfonyl)piperidin-4-yl]-1,2,4-oxadiazol-3-yl}-1,3,5-triazine-2,4-diamine;   6-(5-{4-[(cyclopropylmethoxy)methyl]piperidin-1-yl}-1,2,4-oxadiazol-3-yl)-2-N-methyl-2-N-phenyl-1,3,5-triazine-2,4-diamine;   2-N-(3-fluorophenyl)-6-[5-(3-fluoropyridin-2-yl)-1,2,4-oxadiazol-3-yl]-1,3,5-triazine-2,4-diamine;   2-N-methyl-2-N-phenyl-6-(5-{6-[2-(2,2,2-trifluoroethoxy)ethoxy]pyridin-3-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamine;   2-N-methyl-2-N-phenyl-6-{5-[(2R)-1-[(2,2,2-trifluoroethane)sulfonyl]pyrrolidin-2-yl]-1,2,4-oxadiazol-3-yl}-1,3,5-triazine-2,4-diamine;   2-N-methyl-2-N-phenyl-6-(5-{6-[(3,3,3-trifluoropropane)sulfinyl]pyridin-3-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamine;   2-N-methyl-2-N-phenyl-6-(5-{4-[(3,3,3-trifluoropropoxy)methyl]piperidin-1-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamine;   2-N-methyl-2-N-phenyl-6-{5-[1-(propane-2-sulfonyl)piperidin-4-yl]-1,2,4-oxadiazol-3-yl}-1,3,5-triazine-2,4-diamine; and   N-Methyl-N-phenyl-6-{5-[6-(2,2,2-trifluoroethoxy)-pyridin-3-yl]-[1,2,4]oxadiazol-3-yl}-[1,3,5]triazine-2,4-diamine;   
       or a pharmaceutically acceptable salt thereof. 
     
     
         31 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to  claim 21  and one or more pharmaceutically acceptable carriers/excipients. 
     
     
         32 . A combination in particular a pharmaceutical combination, comprising a therapeutically effective amount of a compound of formula (I) according to  claim 21 , and one or more therapeutically active agents, particularly pain-relieving agents. 
     
     
         33 . A method for the treatment of chronic pain, comprising the step of administering to a subject a therapeutically effective amount of a compound of formula (I) according to  claim 21 . 
     
     
         34 . A method according to  claim 33  where the disorder or disease is selected from chronic pain, such as positive symptoms of chronic pain e.g. parethesias, dyesthesias, hyperalgesia, allodynia and spontaneous pain as well as negative symptoms e.g. loss of sensation. 
     
     
         35 . A method of modulating Nav 1.7 activity in a subject, comprising the step of administering to a subject a therapeutically effective amount of a compound of formula (I) according to  claim 21 .