1,2,4-triazine-4-amine derivatives

Abstract

According to the invention there is provided a compound of formula A1 which may be useful in the treatment of a condition or disorder ameliorated by the inhibition of the A 1 -A 2b or, particularly, the A 2a receptor wherein the compound of formula A1 has the structure, wherein, A represents Cy 1 or Het A ; Cy 1 represents a 5- to 14-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one, two or three rings, which Cy 1 group is optionally substituted by one or more R 4a substituents; Het A represents a 5- to 14-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more heteroatoms selected from O, S and N, which heterocyclic group may comprise one, two or three rings and which HetA group is optionally substituted by one or more R4b substituents; B represents a Cy 2 or Het B ; Cy 2 represents a 3- to 10-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one or two rings, which Cy 2 group is optionally substituted by one or more R 4c substituents; Het B represents a 3- to 10-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more heteroatoms selected from O, S and N, which heterocyclic group may comprise one or two rings and which Het a group is optionally substituted by one or more R 4d substituents

1 - 17 . (canceled) 
     
     
         18 . A method of treatment of cancer comprising administering an effective amount of a compound to a patient in need of such treatment, wherein the compound is represented by formula A1: 
       
         
           
           
               
               
           
         
         wherein: 
         A represents Cy AA  or Het AA ; 
         Cy AA  represents a 6-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system, which Cy AA  group is substituted, in the 3-position relative to the point of attachment to the triazine ring, with a R 4a  substituent and is optionally substituted by one or more additional R 4a  substituents: 
         Het AA  represents a 6-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more heteroatoms selected from O, S and N, and which Het AA  group is substituted, in the 3-position relative to the point of attachment to the triazine ring, with a R 4b  substituent and is optionally substituted by one or more additional R 4b  substituents: 
         B represents a Cy BB  or Het BB : 
         Cy BB  represents phenyl optionally substituted by one or more R 4c  substituents: 
         Het BB  represents a 6-membered aromatic heterocyclic group which contains one or more N atoms, and which Het BB  group is optionally substituted by one or more R 4d  substituents: 
         R 4a  to R 4d  represent, independently at each occurrence, 
         (a) halo, 
         (b) CN, 
         (c) C 1-12  alkyl, C 1-12 , alkenyl, C 2-6 , alkynyl, which latter three groups are optionally substituted by one or more substituents selected from halo, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl (which latter three groups are optionally substituted by one or more substituents selected from OH, ═O, halo, C 1-4  alkyl and C 1-4  alkoxy), OR 5a , S(O) q R 5b , S(O) 2 N(R 5c )(R 5d ), N(R 5e )S(O) 2 R 5f , N(R 5g )(R 5h ), B 7 —C(G 1 )—B 2 —R 5i , aryl and Het 1 , 
         (d) Cy 3 , which Cy 3  group is optionally substituted by one or more substituents selected from halo, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl (which latter three groups are optionally substituted by one or more substituents selected from OH, ═O, halo, C 1-4  alkyl and C 1-4  alkoxy), OR 6a , S(O) q R 6b , S(O) 2 N(R 6c )(R 6d ), N(R 6e )S(O) 2 R 6f , N(R 6g )(R 6h ), B 3 —C(G 1 )—B 4 —R 6i , aryl and Het 2 , 
         (e) Het a , which Het a  group is optionally substituted by one or more substituents selected from halo, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl (which latter three groups are optionally substituted by one or more substituents selected from OH, ═O, halo, C 1-4  alkyl and C 1-4  alkoxy), OR 7a , S(O) q R 7b , S(O) 2 N(R 7c )(R 7d ), N(R 7e )S(O) 2 R 7f , N(R 7g )(R 7h ), B 5 —C(G 1 )—B 6 —R 7i  aryl and Het 3 , 
         (f) OR 8 , 
         (g) S(O) r R 9a , 
         (h) S(O) 2 N(R 9b )(R c ), 
         (i) N(R 9d )S(O) 2 R 9e , 
         (j) N(R 9f )(R 9g ), 
         (k) B 7 —C(G 1 )—B 8 —R 9h , 
         (l) ═O, 
         (m) ═S, 
         or when two R 4a , R 4b , R 4c  or R 4d  groups are attached to the same carbon atom in a non-aromatic portion of a Cy AA , Het AA , Cy BB  or Het BB  group, they may form, together with the carbon atom to which they are attached, a saturated or unsaturated 3 to 6-membered ring, which ring optionally contains one to three heteroatoms selected from O, S and N, and which ring is optionally substituted by one or more R 9i  substituents: 
         G 1  represents, independently at each occurrence, O, S or NR 5j ; 
         R 8  represents, independently at each occurrence,
 H, 
 Cy 3 , Het a , aryl a , C 1-8  alkyl, C 2-8 , alkenyl, C 2-8  alkynyl, C 3-8  cycloalkyl, which latter seven groups are optionally substituted by one or more substituents selected from halo, —CN, C 3-6  cycloalkyl, aryl, Het 4 , —C(O)OR 10 , —C(O)R 11 , —C(O)N(R N1 )(R N2 ), S(O) r R 9aa , S(O) 2 N(R 9ba )(R 9ca ), N(R 9da )S(O) 2 R 9ea  and N(R 9fa ): 
 
         Cy 3  represents, independently at each occurrence, a 3- to 6-membered aromatic, fully saturated or partially unsaturated carbocyclic ring: 
         Het a  represents, independently at each occurrence, a 3- to 6-membered heterocyclic ring that may be aromatic, fully saturated or partially unsaturated and which contains one or more heteroatoms selected from O, S and N: 
         R 10  and R 11  independently represent 
         (a) H, 
         (b) C 1-6  alkyl optionally substituted by one or more substituents selected from halo, aryl, —N(R N3 )(R N4 ) and —OR a , 
         (c) aryl or 
         (d)C 3-7  cycloalkyl (which group is optionally substituted by one or more substituents selected from OH, ═O, halo, C 1-4  alkyl and C 4-6  alkoxy); 
         B 1  to B 8  independently represent, at each occurrence, a direct bond, O, S or N(R N3 ): each aryl a  independently represents a C 6-14  carbocyclic aromatic group, which group may comprise one, two or three rings: 
         each aryl independently represents a C 6-14  carbocyclic aromatic group, which group may comprise one, two or three rings and may be substituted by one or more substituents selected from
 halo, 
 C 1-6  alkyl, which latter group is optionally substituted by one or more substituents selected from halo, —N(R N-4 ))(R N5 ) and —OR a , and —OR a ; 
 
         Het a  to Het 4  independently represent 4- to 14-membered heterocyclic groups containing one or more heteroatoms selected from O, S and N, which heterocyclic groups may comprise one, two or three rings and may be substituted by one or more substituents selected from
 halo, 
 C 1-6  alkyl, which latter group is optionally substituted by one or more substituents selected from halo, —N(R N6 ))(R N7 ) and —OR a , and —OR a ; 
 
         R N1  to R N7  independently represent
 H, 
 C 1-6  alkyl or C 3-6  cycloalkyl, which latter two groups are optionally substituted by one or more substituents selected from halo and —OR a : 
 
         R a  represents, independently at each occurrence, 
         (a) H; 
         (b)C 1-12 , alkyl, C 2-12 , alkenyl, C 2-12 , alkynyl, C 3-12 , cycloalkyl, C 4-12  cycloalkenyl, which latter five groups are optionally substituted by one or more substituents selected from halo, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6 , alkynyl, C 3-8  cycloalkyl (which latter four groups are optionally substituted by one or more substituents selected from OH, ═O, halo, C 1-4  alkyl and C 1-4  alkoxy), OR 12a , S(O) q R 12b , S(O) 2 N(R 12c )(R 12d ), N(R 12e )S(O) 2 R 12f , N(R 12g )(R 12h ), B 9 —C(G 2 )—B 10 —R 12i , aryl 1  and Het b , and which C 3-12  cycloalkyl or C 4-12 , cycloalkenyl groups may additionally be substituted by ═O, 
         (c) S(O) r R 13a , 
         (d) S(O) 2 N(R 13b ))(R 13c ) or 
         (e) C(O)—B 11 —R 13d ; 
         R 5a  to R 5j , R 6a  to R 6i , R 7a  to R 7i , R 9a  to R 9i , R 9aa  to R 9ga , R 12a  to R 12i  to R 13a  to R 13d  independently represent, at each occurrence, 
         (a) H, 
         (b) C 1-10  alkyl, C 2-10  alkenyl, C 2-10  alkynyl which latter three groups are optionally substituted by one or more substituents selected from halo, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6 , alkynyl, C 3-6  cycloalkyl (which latter three groups are optionally substituted by one or more substituents selected from OH, ═O, halo, C 1-4  alkyl and C 1-4  alkoxy), OR 5aa , S(O) q R 5ab , S(O) 2 N(R 5ac )(R 5ad ), N(R 5ae )S(O) 3 R 5af , N(R 5ag )(R 5ah ), B 12 —C(G 2 )—B 13 —R 5ai , aryl 1  and Het c ; 
         (c) C 3-10  cycloalkyl, or C 4-10 , cycloalkenyl (which latter two groups are optionally substituted by one or more substituents selected from halo, OH, ═O, C 1-6  alkyl and C 1-6  alkoxy), 
         (d) Het d ; 
         G 2  represents, independently at each occurrence, O, S, or NR 5aj ; 
         R 5aa  to R 5aj  independently represent at each occurrence, 
         (a) H, 
         (b) C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl which latter three groups are optionally substituted by one or more substituents selected from halo, nitro, CN, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl (which latter three groups are optionally substituted by one or more substituents selected from OH, ═O, halo, C 1-4  alkyl and C 1-4  alkoxy), 
         (c) C 3-6  cycloalkyl, or C 4-6 , cycloalkenyl (which latter two groups are optionally substituted by one or more substituents selected from halo, OH, ═O, C 1-4  alkyl and C 1-4  alkoxy), 
         (d) Het e , 
         or R 5ag  and R 5ah  may represent, together with the nitrogen atom to which they are attached, a 3- to 10-membered heterocyclic ring that may be aromatic, fully saturated or partially unsaturated and which may additionally contain one or more heteroatoms selected from O, S and N, which heterocyclic ring is optionally substituted by one or more substituents selected from halo, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl (which latter three groups are optionally substituted by one or more substituents selected from OH, ═O, halo, C 1-4  alkyl and C 1-4  alkoxy); 
         B 9  to B 13  independently represent a direct bond, O, S or N(R N8 ); 
         aryl 1  represents, independently at each occurrence, a C 6-10  carbocyclic aromatic group, which group may comprise one or two rings and may be substituted by one or more substituents selected from
 halo, 
 C 1-6  alkyl, which latter group is optionally substituted by one or more substituents selected from halo, —N(R N10 )(R N11 ) and C 1-6  alkoxy (which latter substituent is optionally substituted by one or more halo atoms), and 
 C 1-6  alkoxy (which latter substituent is optionally substituted by one or more halo atoms); 
 
         R N8 , R N10  and R N11  independently represent
 H, 
 C 1-6  alkyl or C 3-6  cycloalkyl, which latter two groups are optionally substituted by one or more halo atoms, 
 
         Het b  represents a 5- or 6-membered that may be aromatic, fully saturated or partially unsaturated and which contains one or more heteroatoms selected from O, S and N, which heterocyclic group may be substituted by one or more substituents selected from halo, ═O and C 1-6  alkyl; 
         Het c  to Het e  independently represent, a 3- to 6-membered heterocyclic ring that may be aromatic, fully saturated or partially unsaturated and which contains one or more heteroatoms selected from O, S and N, which Het c  to Het e  groups are optionally substituted by one or more substituents selected from halo, nitro, CN, C 1-6 , alkyl, C 2-6  alkenyl, C 2-6  alkynyl (which latter three groups are optionally substituted by one or more substituents selected from OH, ═O, halo, C 1-4  alkyl and C 1-4  alkoxy); 
         q and r independently represent at each occurrence 0, 1 or 2; and 
         unless otherwise specified alkyl, alkenyl, alkynyl, cycloalkyl and the alkyl part of alkoxy groups may be substituted by one or more halo atoms: 
         or a pharmaceutically acceptable salt or solvate, or a pharmaceutically functional derivative thereof, provided that the compound is not: 
         (a) 5-(2-chlorophenyl)-6-(3,4-dimethoxyphenyl)-[1,2,4]triazin-3-ylamine; or 
         (b) 5-(2-chlorophenyl)-6-(3,4,5-trimethoxyphenyl)-[1,2,4]triazin-3-ylamine. 
       
     
     
         19 - 32 . (canceled) 
     
     
         33 . The method as claimed in  claim 18 , wherein A represents Cy AA′ , Het AA′ , Het AA″  or Het AA′″ , and Cy AA′  represents a 6-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system, which Cy AA′  group is substituted, in the 3-position relative to the point of attachment to the triazine ring, with a R 4a  substituent and is substituted in the 4-position relative to the point of attachment to the triazine ring, with a OR 8  substituent and is optionally further substituted by one or more additional R 4a  substituents;
 Het AA′  represents a 6-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more heteroatoms selected from O, S and N, and which Het AA′  group is substituted, in the 3-position relative to the point of attachment to the triazine ring, with a R 4b  substituent and is substituted, in the 4-position relative to the point of attachment to the triazine ring, with a OR 8  substituent, and is optionally further substituted by one or more additional R 4b  substituents; 
 Het AA″  represents a 6-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains, in the 4-position relative to the point of attachment to the triazine ring, a N-atom, and which group optionally contains one or more further heteroatoms selected from O, S and N, which Het AA″  group is substituted, in the 3-position relative to the point of attachment to the triazine ring, with a R 4b  substituent and is optionally substituted by one or more additional R 4b  substituents; and 
 Het AA′″  represents a 6-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more heteroatoms selected from O, S and N, which Het AA′″  group is substituted, in the 3-position relative to the point of attachment to the triazine ring, with a R 4b  substituent and is substituted, in the 4-position relative to the point of attachment to the triazine ring, with an oxo (═O) group, and is optionally further substituted by one or more additional R 4b  substituents. 
 
     
     
         34 . The method as claimed in  claim 18 , wherein:
 when A represents Cy A  or Cy AA′ , that 6-membered carbocyclic ring is further substituted, in the 5-position relative to the point of attachment to the triazine ring, with a R 4a  substituent; or   when A represents Het AA  or Het AA′ , Het AA″  or Het AA′″ , that 6-membered heterocyclic ring is further substituted, in the 5-position relative to the point of attachment to the triazine ring, with a R 4b  substituent.   
     
     
         35 . The method as claimed in  claim 18 , wherein,
 (1) R 4a  and R 4b  represent, independently at each occurrence,
 halo, 
 CN, 
 C 1-6  alkyl, C 2-6  alkenyl or C 2-6  alkynyl (which latter groups are optionally substituted by one or more substituents selected from aryl, halo and OR 5a ), 
 Cy 3  optionally substituted by one or more substituents selected from halo, nitro, CN, C 1-3  alkyl (which group is optionally substituted by one or more substituents selected from OH, ═O, halo, C 1-3  alkyl and C 1-3  alkoxy), OR 6a , S(O) q R 6b , S(O) 2 N(R 6c )(R 6d ), N(R 6e )S(O) 2 R 6f , N(R 6g )(R 6h ), B 3 —C(G 1 )—B 4 —R 6i  and aryl, 
 Het a  optionally substituted by one or more substituents selected from halo, nitro, CN, C 1-3  alkyl (which group is optionally substituted by one or more substituents selected from OH, ═O, halo, C 1-3  alkyl and C 1-3  alkoxy), OR 7a , S(O) q R 7b , S(O) 2 N(R 7c )(R 7d ), N(R 7e )S(O) 2 R 7f , N(R 7g )(R 7h ), B 5 —C(G 1 )—B 6 —R 7i  and aryl, 
 OR 8 , 
 S(O) r R 9a , 
 N(R 9f )(R 9g ), 
 B 7 —C(G 1 )—B 8 —R 9h , 
   ═O,   or when two R 4a  or R 4d  groups are attached to the same carbon atom in a non-aromatic Cy 1 , Cy AA , Het A  or Het AA , group, they may form, together with the carbon atom to which they are attached, a saturated or unsaturated 5-membered ring, which ring optionally contains one or two heteroatoms selected from O and N, and which ring is optionally substituted by one or more R 9i  substituents;   (2) R 4c  and R 4b  represent, independently at each occurrence,
 halo 
 CN, 
 C 1-3  alkyl (which latter group is optionally substituted by one or more substituents selected from halo and OR 5a ), 
 OR 8 , 
 N(R 9f )(R 9g ) or 
 B 7 —C(G 1 )—B 8 —R 9h ; and/or 
   (3) G 1  represents, independently at each occurrence, O.   
     
     
         36 . The method as claimed in  claim 18 , wherein:
 (1) R 8  represents, independently at each occurrence,
 H, 
 Cy 3 , Het a , aryl a , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-6  cycloalkyl, which latter seven groups are optionally substituted by one or more substituents selected from halo, —CN, C 3-6  cycloalkyl, aryl, Het 4 , —C(O)OR 10 , —C(O)R 11  and —C(O)N(R N1 )(R N2 ), S(O) r R 9aa , S(O) 2 N(R 9ba )(R 9ca ), N(R 9da )S(O) 2 R 9ea  and N(R 9fa )(R 9ga ); 
   (2) each aryl a  independently represents a C 6-10  carbocyclic aromatic group, which group may comprise one or two rings;   (3) each aryl independently represents a C 6-10  carbocyclic aromatic group, which group may comprise one or two rings and may be substituted by one or more substituents selected from halo,
 C 1-6  alkyl, which latter group is optionally substituted by one or more substituents selected from halo, —N(R N4 )(R N5 ) and —OR a , and 
 —OR a ; 
   (4) R a  represents, independently at each occurrence,
 H, 
 C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-6  cycloalkyl, C 4 -6 cycloalkenyl (which latter five groups are optionally substituted by one or more substituents selected from halo, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3  cycloalkyl (which latter four groups are optionally substituted by one or more substituents selected from OH, ═O, halo, C 1-4  alkyl and C 1-4  alkoxy), OR 12a , S(O) q R 12b , S(O) 2 N(R 12c )(R 12d ), N(R 12e )S(O) 2 R 12f , N(R 12g )(R 12h ), B 9 —C(G 2 )—B 10 —R 12i , aryl 1  and Het b , and which C 3-6  cycloalkyl or C 4-6  cycloalkenyl groups may additionally be substituted by ═O), 
 S(O) r R 13a , 
 S(O) 2 N(R 13b )(R 13c ) or 
 C(O)—B 11 —R 13d ; 
   (5) R 5a  to R 5j , R 6a  to R 6i , R 7a  to R 7i , R 9a  to R 9i , R 9aa  to R 9ga , R 12a  to R 12i  and R 13a  to R 13d  independently represent, at each occurrence,
 H, 
 C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl (which latter three groups are optionally substituted by one or more substituents selected from halo, OH and C 1-4  alkoxy), 
 C 3-6  cycloalkyl or C 4-6  cycloalkenyl (which latter two groups are optionally substituted by one or more substituents selected from halo, OH, ═O, C 1-6  alkyl and C 1-6  alkoxy), Het d ; and/or 
   (6) G 2  represents, independently at each occurrence, O.   
     
     
         37 . The method as claimed in  claim 36 , wherein:
 (1) R 8  represents, independently at each occurrence,
 H, 
 C 1-6  alkyl, which latter group is optionally substituted by one or more substituents selected from halo, —CN, C 3-6  cycloalkyl, aryl, Het 4 , —C(O)OR 10 , —C(O)R 11  and —C(O)N(R N1 )(R N2 ); 
   (2) B 1  to B 8  independently represent a direct bond or N(R N3 );   (3) each aryl independently represents a phenyl group that is optionally substituted by one or more substituents selected from
 halo, 
 C 1-3  alkyl, which latter group is optionally substituted by one or more substituents selected from halo, —N(R N4 )(R N5 ) and —OR a , and 
 —OR a ; 
   (4) R N1  to R N7  independently represent
 H, 
 C 1-3  alkyl or C 3-5  cycloalkyl, which latter two groups are optionally substituted by one or more substituents selected from halo and —OR a ; 
   (5) R a  represents independently at each occurrence,
 H, 
 C 1-3  alkyl, (which latter group is optionally substituted by one or more substituents selected from halo, OH and C 1-4  alkoxy) or 
 C 3-6  cycloalkyl (which latter group is optionally substituted by one or more substituents selected from halo, OH, ═O, C 1-6  alkyl and C 1-4  alkoxy); and/or 
   (6) R 10  and R 11  independently represent
 H, 
 C 1-3  alkyl optionally substituted by one or more substituents selected from halo, aryl, —N(R N3 )(R N4 ) and —OR a , 
 phenyl (which latter group is optionally substituted by one or more substituents selected from OH, halo, C 1-4  alkyl and C 1-4  alkoxy) or 
 C 3-6  cycloalkyl (which latter group is optionally substituted by one or more substituents selected from OH, ═O, halo, C 1-4  alkyl and C 1-4  alkoxy). 
   
     
     
         38 . The method as claimed in  claim 18 , wherein A is a 6-membered Cy 1 , Cy AA , Het A  or Het AA  group that has:
 substituents in the ortho-positions;   a substituent in one or both of the meta-positions; and, optionally   a substituent in the para-position.   
     
     
         39 . The method as claimed in  claim 18 , wherein the compound of formula A1 is represented by a compound of formula Ixd, Iyd or Izd, 
       
         
           
           
               
               
           
         
         respectively, wherein: 
         rr1 represents 0 or 1; 
         rr2 and rr3 independently represent 0 or 1; 
         ss and tt independently represent, at each occurrence 0 or 1, provided that ss and tt do not both represent 0; 
         R 4a′  takes the same definition as R 4a ; 
         R 4b′  takes the same definition as R 4b ; and 
         L 1  and L 2  both represent direct bonds. 
       
     
     
         40 . The method as claimed in  claim 18 , wherein:
 R 4a  and R 4b  represent, independently at each occurrence, cyclopropyl, iodo, bromo, chloro, fluoro, ethyl, methyl, d 3 -methyl, iso-propyl, —C≡CH, phenyl, CF 3 , CHF 2 , CH 2 F, CH 2 CF 3 , CF 2 CF 3 , CN, ═O, OH, OCH(CH 3 ) 2 , OCH 3 , OCH 2 CH 3 , OCH 2 F, OCHF 2 , OCH 2 CF 3 , OCF 3 , (CH 2 ) 3 OH, CH 2 OH or CH 2 OCH 3 , CH(CH 3 )OH, C(CH 3 ) 3 OH, CH 2 CH 2 OH, NH 2 , N(CH 3 ) 2 , N(H)CH 2 CH 3 , N(H)C(O)CH 3 , C(O)CH 3 , C(O)N(CH 3 ) 2 , S(O) 2 CH 3 , S(O)CH 3 , SCH 3 , S(O) 2 CF 3 , azetidine, morpholine or dioxolane.   
     
     
         41 . The method as claimed in  claim 18 , wherein the compound of formula A1 is selected from the list comprising:
 (iii) 6-(3-methoxyphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (v) 6-(5-chloro-2-methoxyphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (vi) 6-(3-chlorophenyl)-5-phenyl-1,2,4-triazin-3-amine;   (xiii) 6-(3-methylpiperidin-1-yl)-5-phenyl-1,2,4-triazin-3-amine;   (xix) 6-(3-chlorophenyl)-5-(2,4-difluorophenyl)-1,2,4-triazin-3-amine;   (xx) 5-phenyl-6-(3,4,5-difluorophenyl)-1,2,4-triazin-3-amine;   (xxi) 6-(2,6-dimethylmorpholin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (xxiii) 6-(3-chlorophenyl)-5-(3-methoxyphenyl)-1,2,4-triazin-3-amine;   (xxiv) 5-phenyl-6-[3-(trifluoromethyl)phenyl]-1,2,4-triazin-3-amine;   (xxv) 6-(3,5-difluorophenyl)-5-phenyl-1,2,4-triazin-3-amine;   (xxvii) 6-[3-fluoro-5-(trifluoromethyl)phenyl]-5-phenyl-1,2,4-triazin-3-amine;   (xxviii) 6-(3,5-dichlorophenyl)-5-phenyl-1,2,4-triazin-3-amine;   (xxix) 6-(5-chloropyridin-3-yl)-5-phenyl-1,2,4-triazin-3-amine;   (xxx) 6-(3-chloro-4-fluorophenyl)-5-phenyl-1,2,4-triazin-3-amine;   (xxxi) 6-(3-fluoro-5-methoxyphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (xxxiv) 6-(3-chlorophenyl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   (xxxv) 6-(3-chloro-5-methoxyphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (xxxviii) 6-(3,3-dimethylpiperidin-1-yl)-5-phenyl-1,2,4-triazin-3-amine;   (xxxix) 6-(3-bromophenyl)-5-phenyl-1,2,4-triazin-3-amine;   (xli) 5-phenyl-6-[3-(trifluoromethyl)piperidin-1-yl]-1,2,4-triazin-3-amine;   (xlv) 6-(3,4-dichlorophenyl)-5-phenyl-1,2,4-triazin-3-amine;   (xlvi) 6-(3-fluorophenyl)-5-phenyl-1,2,4-triazin-3-amine;   (xlviii) 3-(3-amino-5-phenyl-1,2,4-triazin-6-yl)benzonitrile;   (xlix) 6-(3,5-dimethoxyphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (l) 6-(3,5-dimethylphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (li) 6-(3,4-dimethylphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lii) 6-[3-(dimethylamino)phenyl]-5-phenyl-1,2,4-triazin-3-amine;   (liii) N-[3-(3-amino-5-phenyl-1,2,4-triazin-6-yl)phenyl]acetamide;   (liv) N-[3-(3-amino-5-phenyl-1,2,4-triazin-6-yl)phenyl]methanesulfonamide;   (lv) 6-(3-trifluoromethoxyphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lvii) 5-phenyl-6-[3-(propan-2-yl)phenyl]-1,2,4-triazin-3-amine;   (lviii) 6-(3,5-dichlorophenyl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   (lix) 6-(3,5-bis(trifluoromethyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lx) 4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-methoxyphenol;   (lxi) 4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2,6-dimethylphenol;   (lxii) 4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-chlorophenol;   (lxiii) 6-(2-chloropyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (lxiv) 6-(3-(methylsulfonyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxv) 6-(3,5-dichloro-4-methoxyphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxvi) 6-(4-methoxy-3-(trifluoromethyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxvii) 6-(3-chloro-5-(dimethylamino)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxviii) 3-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-5-(trifluoromethyl)benzonitrile;   (lxix) 4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2,6-dimethylbenzonitrile;   (lxx) 6-(3-chloro-5-(trifluoromethyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxi) 6-(3-chloro-5-methylphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxii) 6-(3-(methylthio)-5-(trifluoromethyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxiii) 6-(3-methoxy-5-(trifluoromethyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxiv) 6-(3-ethoxy-5-(trifluoromethyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxv) 6-(3-tert-butyl-5-methylphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxvi) 6-(2-chloro-6-methylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxvii) 4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-chlorobenzonitrile;   (lxxviii) 6-(3-ethylphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxix) 6-(2-methoxy-6-(trifluoromethyl)pyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxx) 6-(3-methyl-5-(trifluoromethoxy)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxxi) 6-(3-(1,3-dioxolan-2-yl)-5-(trifluoromethyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxxii) 5-phenyl-6-(3-(2,2,2-trifluoroethoxy)phenyl)-1,2,4-triazin-3-amine;   (lxxxiii) 6-(3-(methoxymethyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxxiv) 5-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-1-methylpyridin-2(1H)-one;   (lxxxv) 6-(3-methyl-5-(trifluoromethyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxxvi) 6-(2-methoxypyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (lxxxvii) 1-(3-(3-amino-5-phenyl-1,2,4-triazin-6-yl)phenyl)ethanone;   (lxxxix) 6-(4-fluoro-3-(trifluoromethyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (xc) 6-(4-fluoro-3-methylphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (xci) 6-(3-bromo-5-chlorophenyl)-5-phenyl-1,2,4-triazin-3-amine;   (xciii) 5-phenyl-6-m-tolyl-1,2,4-triazin-3-amine;   (xcvi) 6-(2,6-dimethoxypyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (xcvii) 6-(2,6-dimethylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (xcviii) 5-phenyl-6-(2-(trifluoromethyl)pyridin-4-yl)-1,2,4-triazin-3-amine;   (xcix) 6-(2-cyclopropylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (c) 5-phenyl-6-(2,2,6,6-tetramethyl-3,6-dihydro-2H-pyran-4-yl)-1,2,4-triazin-3-amine;   (ci) 6-(5-chloro-2-fluoro-3-methylphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (cii) 6-(2,6-dichloropyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (ciii) 6-(3-bromo-5-(trifluoromethoxy)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (civ) 4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-chloro-6-methoxyphenol;   (cv) 6-(3,5-dichloro-4-ethoxyphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (cvi) 6-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-5-phenyl-1,2,4-triazin-3-amine;   (cvii) 4-(3-amino-5-(3-fluorophenyl)-1,2,4-triazin-6-yl)-2,6-dimethylbenzonitrile;   (cviii) 6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(3-fluorophenyl)-1,2,4-triazin-3-amine;   (cix) 6-(2-chloro-6-methylpyridin-4-yl)-5-(3-fluorophenyl)-1,2,4-triazin-3-amine;   (cx) 4-(3-amino-5-(4-fluorophenyl)-1,2,4-triazin-6-yl)-2,6-dimethylbenzonitrile;   (cxi) 6-(3-chloro-5-propoxyphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (cxii) 6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   (cxiii) 6-(2-chloropyridin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   (cxiv) 6-(2-chloro-6-methylpyridin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   (cxv) 4-(3-amino-5-(4-chlorophenyl)-1,2,4-triazin-6-yl)-2,6-dimethylbenzonitrile;   (cxvi) 6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(4-chlorophenyl)-1,2,4-triazin-3-amine;   (cxvii) 5-(4-chlorophenyl)-6-(2-chloropyridin-4-yl)-1,2,4-triazin-3-amine;   (cxviii) 6-(2-chloro-6-methylpyridin-4-yl)-5-(4-chlorophenyl)-1,2,4-triazin-3-amine;   (cxix) 4-(3-amino-5-(3-chlorophenyl)-1,2,4-triazin-6-yl)-2,6-dimethylbenzonitrile;   (cxx) 6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(3-chlorophenyl)-1,2,4-triazin-3-amine;   (cxxi) 5-(3-chlorophenyl)-6-(2-chloropyridin-4-yl)-1,2,4-triazin-3-amine;   (cxxii) 6-(2-chloro-6-methylpyridin-4-yl)-5-(3-chlorophenyl)-1,2,4-triazin-3-amine;   (cxxiii) 4-(3-amino-6-(3-chloro-5-(trifluoromethyl)phenyl)-1,2,4-triazin-5-yl)benzonitrile;   (cxxiv) 4-(3-amino-6-(2-chloro-6-methylpyridin-4-yl)-1,2,4-triazin-5-yl)benzonitrile;   (cxxv) 4-(3-amino-5-(3-chloro-5-fluorophenyl)-1,2,4-triazin-6-yl)-2,6-dimethylbenzonitrile;   (cxxvi) 5-(3-chloro-5-fluorophenyl)-6-(2-chloro-6-methylpyridin-4-yl)-1,2,4-triazin-3-amine;   (cxxvii) 6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(3-chloro-5-fluorophenyl)-1,2,4-triazin-3-amine;   (cxxviii) 6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(3,5-difluorophenyl)-1,2,4-triazin-3-amine;   (cxxix) 6-(2-chloro-6-methylpyridin-4-yl)-5-(3,5-difluorophenyl)-1,2,4-triazin-3-amine;   (cxxx) 4-(3-amino-5-(3,5-difluorophenyl)-1,2,4-triazin-6-yl)-2,6-dimethylbenzonitrile;   (cxxxi) 4-(3-amino-5-(3-chloro-4-fluorophenyl)-1,2,4-triazin-6-yl)-2,6-dimethylbenzonitrile;   (cxxxii) 5-(3-chloro-4-fluorophenyl)-6-(2-chloro-6-methylpyridin-4-yl)-1,2,4-triazin-3-amine;   (cxxxiii) 5-(3-chloro-4-fluorophenyl)-6-(2-chloropyridin-4-yl)-1,2,4-triazin-3-amine;   (cxxxiv) 5-(3-chloro-4-fluorophenyl)-6-(3-chloro-5-(trifluoromethyl)phenyl)-1,2,4-triazin-3-amine;   (cxxxv) 4-(3-amino-5-(3,4-difluorophenyl)-1,2,4-triazin-6-yl)-2,6-dimethylbenzonitrile;   (cxxxvi) 6-(2-chloro-6-methylpyridin-4-yl)-5-(3,4-difluorophenyl)-1,2,4-triazin-3-amine;   (cxxxvii) 6-(2-chloropyridin-4-yl)-5-(3,4-difluorophenyl)-1,2,4-triazin-3-amine;   (cxxxviii) 6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(3,4-difluorophenyl)-1,2,4-triazin-3-amine;   (cxxxix) 6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(4-(methoxymethyl)phenyl)-1,2,4-triazin-3-amine;   (cxl) 6-(2-chloro-6-methylpyridin-4-yl)-5-(4-(methoxymethyl)phenyl)-1,2,4-triazin-3-amine;   (cxli) 6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   (cxlii) 6-(3-chloro-5-methylphenyl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   (cxlv) 6-(3,5-diisopropylphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (cxlvi) 6-(3-fluoro-5-(2,2,2-trifluoroethoxy)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (cxlvii) N-(4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-(trifluoromethyl)phenyl)acetamide;   (cxlviii) 5-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-fluorobenzonitrile;   (cxlix) 3-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-N,N-dimethylbenzamide;   (cli) 4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-1-methylpyridin-2(1H)-one;   (clii) 6-(3-(morpholin-4-yl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (clvi) 6-(3-(methylsulfinyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (clvii) 4-(3-amino-6-(2-chloropyridin-4-yl)-1,2,4-triazin-5-yl)benzonitrile;   (clviii) 4-(3-amino-5-(4-(methoxymethyl)phenyl)-1,2,4-triazin-6-yl)-2,6-dimethylbenzonitrile;   (clix) 6-(2-chloropyridin-4-yl)-5-(4-(methoxymethyl)phenyl)-1,2,4-triazin-3-amine;   (clxiii) 6-(3-methoxypiperidin-11-yl)-5-phenyl-1,2,4-triazin-3-amine;   (clxiv) 6-(3-ethynylpiperidin-11-yl)-5-phenyl-1,2,4-triazin-3-amine;   (clxv) 6-(2,6-dimethylmorpholin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   (clxvi) 6-(2-ethylmorpholino)-5-phenyl-1,2,4-triazin-3-amine;   (clxvii) 5-phenyl-6-(6-oxa-9-azaspiro[4.5]decan-9-yl)-1,2,4-triazin-3-amine;   (clxviii) 6-(2,2-diethylmorpholino)-5-phenyl-1,2,4-triazin-3-amine;   (clxix) 6-(2,2-dimethylmorpholino)-5-phenyl-1,2,4-triazin-3-amine;   (clxx) (1-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-3-methylpiperidin-3-yl)methanol;   (clxxi) 6-(3-(methoxymethyl)piperidin-1-yl)-5-phenyl-1,2,4-triazin-3-amine;   (clxxii) 1-(1-(3-amino-5-phenyl-1,2,4-triazin-6-yl)piperidin-3-yl)ethanol;   (clxxiii) (1-(3-amino-5-phenyl-1,2,4-triazin-6-yl)piperidin-3-yl)methanol;   (clxxiv) 1-(1-(3-amino-5-phenyl-1,2,4-triazin-6-yl)piperidin-3-yl)ethanone;   (clxxviii) 5-phenyl-6-(3-phenylpiperidin-1-yl)-1,2,4-triazin-3-amine;   (clxxix) (4-(3-amino-5-phenyl-1,2,4-triazin-6-ylmorpholin-2-yl)methanol;   (clxxxi) 2-(1-(3-amino-5-phenyl-1,2,4-triazin-6-yl)piperidin-3-yl)propan-2-ol;   (clxxxiii) 1-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-3-ethylpiperidin-3-ol;   (clxxxiv) 2-(4-(3-amino-5-phenyl-1,2,4-triazin-6-ylmorpholin-2-yl)ethanol;   (clxxxvii) 1-(3-amino-5-phenyl-1,2,4-triazin-6-yl)pyridin-4(1H)-one;   (cxcvii) 1-(3-amino-5-phenyl-1,2,4-triazin-6-yl)pyridazin-4(1H)-one;   (cxcviii) 1-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-3,5-dichloropyridin-4(1H)-one;   (cciii) 3-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-5-chlorophenol;   (cciv) 6-(3-chloro-5-ethenylphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (ccv) 6-(3-chloro-5-cyclopropylphenyl)-5-phenyl-1,2,4-triazin-3-amine;   (ccviii) 5-(3-chloro-5-fluorophenyl)-6-(2-chloropyridin-4-yl)-1,2,4-triazin-3-amine;   (ccix) 6-(2-chloropyridin-4-yl)-5-(3,5-difluorophenyl)-1,2,4-triazin-3-amine;   (ccx) 4-(3-amino-5-(4-(difluoromethoxy)phenyl)-1,2,4-triazin-6-yl)-2,6-dimethylbenzonitrile;   (ccxi) 6-(2-chloro-6-methylpyridin-4-yl)-5-(4-(difluoromethoxy)phenyl)-1,2,4-triazin-3-amine;   (ccxii) 6-(2-chloropyridin-4-yl)-5-(4-(difluoromethoxy)phenyl)-1,2,4-triazin-3-amine;   (ccxiii) 6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(4-(difluoromethoxy)phenyl)-1,2,4-triazin-3-amine;   (ccxiv) 5-(3-amino-5-(3-fluorophenyl)-1,2,4-triazin-6-yl)-2-chlorophenol;   (ccxv) 4-[3-amino-6-(3-chloro-4-hydroxyphenyl)-1,2,4-triazin-5-yl]benzonitrile;   (ccxvi) 3-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-5-(trifluoromethoxy)phenol;   (ccxvii) 5-(3-chloro-5-fluorophenyl)-6-(2,6-dimethylpyridin-4-yl)-1,2,4-triazin-3-amine;   (ccxviii) 5-(3,5-difluorophenyl)-6-(2,6-dimethylpyridin-4-yl)-1,2,4-triazin-3-amine;   (ccxix) 5-(3,4-difluorophenyl)-6-(2,6-dimethylpyridin-4-yl)-1,2,4-triazin-3-amine;   (ccxx) 5-(3-chloro-4-fluorophenyl)-6-(2,6-dimethylpyridin-4-yl)-1,2,4-triazin-3-amine;   (ccxxi) 5-(4-(difluoromethoxy)phenyl)-6-(2,6-dimethylpyridin-4-yl)-1,2,4-triazin-3-amine;   (ccxxii) 6-(2,6-dimethylpyridin-4-yl)-5-(3-fluorophenyl)-1,2,4-triazin-3-amine;   (ccxxiii) 5-(4-chlorophenyl)-6-(2,6-dimethylpyridin-4-yl)-1,2,4-triazin-3-amine;   (ccxxiv) 4-(3-amino-6-(2,6-dimethylpyridin-4-yl)-1,2,4-triazin-5-yl)benzonitrile;   (ccxxv) 5-(3-chlorophenyl)-6-(2,6-dimethylpyridin-4-yl)-1,2,4-triazin-3-amine;   (ccxxvi) 6-(2,6-dimethylpyridin-4-yl)-5-(4-(methoxymethyl)phenyl)-1,2,4-triazin-3-amine;   (ccxxvii) 4-(3-amino-6-(3-chloro-4-hydroxy-5-methoxyphenyl)-1,2,4-triazin-5-yl)benzonitrile;   (ccxxviii) 5-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-chlorophenol;   (ccxxix) 6-(6-chloropyridin-2-yl)-5-phenyl-1,2,4-triazin-3-amine;   (ccxxx) 6-(4-cyclopropylpyridin-2-yl)-5-phenyl-1,2,4-triazin-3-amine;   (ccxxxi) 5-phenyl-6-(6-(trifluoromethyl)pyridin-2-yl)-1,2,4-triazin-3-amine;   (ccxxxii) 5-phenyl-6-(4-(trifluoromethyl)pyridin-2-yl)-1,2,4-triazin-3-amine;   (ccxxxiii) 6-(6-cyclopropylpyridin-2-yl)-5-phenyl-1,2,4-triazin-3-amine;   (ccxxxv) 4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2,6-diiodophenol;   (ccxxxvi) 4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-iodophenol;   (ccxxxvii) 6-(3-methoxy-5-(trifluoromethoxy)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   (ccxxxviii) 4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-(propan-2-yloxy)phenol;   (ccxxxix) 5-(3-fluorophenyl)-6-(2-chloropyridin-4-yl)-1,2,4-triazin-3-amine;   (ccxli) 6-[2-chloro-6-(trifluoromethyl)pyridin-4-yl]-5-(3,4-difluorophenyl)-1,2,4-triazin-3-amine;   (ccxlii) 6-[2-chloro-6-(trifluoromethyl)pyridin-4-yl]-5-(3,5-difluorophenyl)-1,2,4-triazin-3-amine;   (ccxliii) 6-[2-(ethylamino)-6-methylpyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (ccxliv) 6-[2-chloro-6-(trifluoromethyl)pyridin-4-yl]-5-(3-fluorophenyl)-1,2,4-triazin-3-amine;   (ccxlv) 6-[2-chloro-6-(trifluoromethyl)pyridin-4-yl]-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   (ccxlvi) 6-{2-[ethyl(methyl)amino]-6-methylpyridin-4-yl}-5-phenyl-1,2,4-triazin-3-amine;   (ccxlvii) 6-[2-(dimethylamino)-6-methylpyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (ccxlviii) 1-(6-(2,6-d6-dimethylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (ccxlix) 6-[2-d3-methyl-6-(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (ccl) 5-(4-fluorophenyl)-6-[2-d3-methyl-6-(trifluoromethyl)pyridin-4-yl]-1,2,4-triazin-3-amine;   (ccli) 6-(2,6-dimethylpyridin-4-yl)-5-(2-fluorophenyl)-1,2,4-triazin-3-amine;   (cclii) 6-(2-chloro-6-methylpyridin-4-yl)-5-(2-fluorophenyl)-1,2,4-triazin-3-amine;   (ccliii) 6-(2,6-dimethylpyridin-4-yl)-5-(4-methoxyphenyl)-1,2,4-triazin-3-amine;   (ccliv) 6-(2-chloro-6-methylpyridin-4-yl)-5-(4-methoxyphenyl)-1,2,4-triazin-3-amine;   (cclv) 6-[2-(difluoromethyl)-6-methylpyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (cclvi) 6-[2-chloro-6-(difluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (cclvii) 6-[2-chloro-6-(fluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (cclviii) 6-[2-(difluoromethyl)-6-methylpyridin-4-yl]-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   (cclix) 6-[2,6-bis(fluoromethyl)pyridine-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (cclx) 6-[2-(fluoromethyl)-6-methylpyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (cclxi) 6-(2-chloro-6-methylpyridin-4-yl)-5-(2,5-difluorophenyl)-1,2,4-triazin-3-amine;   (cclxii) 6-[2-chloro-6-(tifluoromethyl)pyridin-4-yl]-5-(2-fluorophenyl)-1,2,4-triazin-3-amine;   (cclxiii) 6-[2-chloro-6-(trifluoromethyl)pyridin-4-yl]-5-(2,5-difluorophenyl)-1,2,4-triazin-3-amine;   (cclxiv) 6-[2-cyclopropyl-6-(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (cclxv) 6-[2-ethyl-6-(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (cclxvi) 6-(2-cyclopropyl-6-methylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (cclxvii) 5-(2-fluorophenyl)-6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-1,2,4-triazin-3-amine;   (cclxviii) 5-(3-fluorophenyl)-6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-1,2,4-triazin-3-amine;   (cclxix) 5-(4-fluorophenyl)-6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-1,2,4-triazin-3-amine;   (cclxx) 5-(2,5-difluorophenyl)-6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-1,2,4-triazin-3-amine;   (cclxxi) 5-(3,4-difluorophenyl)-6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-1,2,4-triazin-3-amine;   (cclxxii) 5-(3,5-difluorophenyl)-6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-1,2,4-triazin-3-amine;   (cclxxiii) 6-[2-(azetidin-1-yl)-6-(tifluoromethyl)pyridin-4-yl]-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   (cclxxiv) 6-[2-methyl-6-(morpholin-4-yl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (cclxxv) 6-(2-chloro-6-methylpyridin-4-yl)-5-(4-ethylphenyl)-1,2,4-triazin-3-amine;   (cclxxvi) 5-(2,5-difluorophenyl)-6-(2,6-dimethylpyridin-4-yl)-1,2,4-triazin-3-amine;   (cclxxvii) 6-(2,6-dimethylpyridin-4-yl)-5-(4-methylphenyl)-1,2,4-triazin-3-amine;   (cclxxviii) 6-[2-(difluoromethyl)-6-methylpyridin-4-yl]-5-(3-fluorophenyl)-1,2,4-triazin-3-amine;   (cclxxix) 6-[2-(difluoromethyl)-6-methylpyridin-4-yl]-5-(2-fluorophenyl)-1,2,4-triazin-3-amine;   (cclxxx) 6-(3,5-dichlorophenyl)-5-(pyridin-2-yl)-1,2,4-triazin-3-amine;   (cclxxxi) 6-(3-chloro-5-methylphenyl)-5-(pyridin-2-yl)-1,2,4-triazin-3-amine;   (cclxxxii) 6-[2-chloro-6-(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (cclxxxiii) 6-[2,6-bis(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (cclxxxiv) 6-[3-chloro-5-(trifluoromethyl)phenyl]-5-(pyridin-2-yl)-1,2,4-triazin-3-amine;   (cclxxxv) 6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (cclxxxvi) 6-(3,5-dimethylphenyl)-5-(pyridin-2-yl)-1,2,4-triazin-3-amine;   (cclxxxvii) 6-[2-(dimethylamino)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (cclxxxviii) 6-(2-bromo-6-methylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (cclxxxix) 6-(2,6-dimethyl-1-oxidopyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (ccxc) 4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-6-methylpyridine-2-carbionitrile;   (ccxci) 6-(3,5-dichlorophenyl)-5-(pyridin-3-yl)-1,2,4-triazin-3-amine;   (ccxcii) 6-(3-chloro-5-methylphenyl)-5-(pyridin-3-yl)-1,2,4-triazin-3-amine;   (ccxciii) 6-(3,5-dichlorophenyl)-5-(pyrimidin-2-yl)-1,2,4-triazin-3-amine;   (ccxciv) 6-[3-chloro-5-(trifluoromethyl)phenyl]-5-(pyrimidin-2-yl)-1,2,4-triazin-3-amine;   (ccxcv) 6-[2-bromo-6-(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (ccxcvi) 6-[3-chloro-5-(trifluoromethyl)phenyl]-5-(pyridin-3-yl)-1,2,4-triazin-3-amine;   (ccxcvii) 6-(3-chloro-5-methylphenyl)-5-(pyrimidin-2-yl)-1,2,4-triazin-3-amine;   (ccxcviii) N-[5-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-methoxyphenyl]acetamide;   (ccxcix) N-[5-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-hydroxyphenyl]acetamide;   (ccc) 6-(2-methyl-6-d3-methylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   (ccci) 1-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-3,5-dimethylpyridin-4(1H)-one;   (cccii) 6-[2-(azetidin-1-yl)-6-methylpyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   (ccciii) 6-[2-(azetidin-1-yl)-6-methylpyridin-4-yl]-5-(4-fluorophenyl)-1,2,4-triazin-3-amine; and   (ccciv) 6-[2-(azetidin-1-yl)-6-(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine.   
     
     
         42 . The method as claimed in  claim 18 , wherein the compound of formula A1 is selected from:
 6-(3,5-dichlorophenyl)-5-phenyl-1,2,4-triazin-3-amine;   6-(3,5-bis(trifluoromethyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   6-(2-chloropyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   6-(3-chloro-5-methylphenyl)-5-phenyl-1,2,4-triazin-3-amine;   6-(2-chloro-6-methylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   6-(3-methyl-5-(trifluoromethyl)phenyl)-5-phenyl-1,2,4-triazin-3-amine;   6-(2-methoxypyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   6-(3-bromo-5-chlorophenyl)-5-phenyl-1,2,4-triazin-3-amine;   6-(2,6-dimethylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   5-phenyl-6-(2-(trifluoromethyl)pyridin-4-yl)-1,2,4-triazin-3-amine;   6-(2-cyclopropylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   6-(2,6-dichloropyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(3-fluorophenyl)-1,2,4-triazin-3-amine;   6-(2-chloro-6-methylpyridin-4-yl)-5-(3-fluorophenyl)-1,2,4-triazin-3-amine;   6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(4-chlorophenyl)-1,2,4-triazin-3-amine;   5-(4-chlorophenyl)-6-(2-chloropyridin-4-yl)-1,2,4-triazin-3-amine;   6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(3-chlorophenyl)-1,2,4-triazin-3-amine;   5-(3-chlorophenyl)-6-(2-chloropyridin-4-yl)-1,2,4-triazin-3-amine;   6-(3-chloro-5-(trifluoromethyl)phenyl)-5-(3,5-difluorophenyl)-1,2,4-triazin-3-amine;   5-(3-chloro-4-fluorophenyl)-6-(2-chloropyridin-4-yl)-1,2,4-triazin-3-amine;   6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   6-(3-chloro-5-methylphenyl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   1-(3-amino-5-phenyl-1,2,4-triazin-6-yl)pyridin-4(1H)-one;   3-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-5-(trifluoromethoxy)phenol;   5-(3,5-difluorophenyl)-6-(2,6-dimethylpyridin-4-yl)-1,2,4-triazin-3-amine;   6-(2,6-dimethylpyridin-4-yl)-5-(3-fluorophenyl)-1,2,4-triazin-3-amine;   5-(4-chlorophenyl)-6-(2,6-dimethylpyridin-4-yl)-1,2,4-triazin-3-amine;   4-(3-amino-6-(3-chloro-4-hydroxy-5-methoxyphenyl)-1,2,4-triazin-5-yl)benzonitrile;   6-(4-cyclopropylpyridin-2-yl)-5-phenyl-1,2,4-triazin-3-amine;   4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-iodophenol;   4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-(propan-2-yloxy)phenol;   5-(3-fluorophenyl)-6-(2-chloropyridin-4-yl)-1,2,4-triazin-3-amine;   6-[2-chloro-6-(trifluoromethyl)pyridin-4-yl]-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   6-[2-d3-methyl-6-(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine; 6-(2-chloro-6-methylpyridin-4-yl)-5-(2-fluorophenyl)-1,2,4-triazin-3-amine; 6-[2-chloro-6-(trifluoromethyl)pyridin-4-yl]-5-(2-fluorophenyl)-1,2,4-triazin-3-amine; 6-[2-chloro-6-(trifluoromethyl)pyridin-4-yl]-5-(2,5-difluorophenyl)-1,2,4-triazin-3-amine; 6-(2-cyclopropyl-6-methylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine;   5-(2-fluorophenyl)-6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-1,2,4-triazin-3-amine;   5-(3-fluorophenyl)-6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-1,2,4-triazin-3-amine;   5-(4-fluorophenyl)-6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-1,2,4-triazin-3-amine;   5-(3,5-difluorophenyl)-6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-1,2,4-triazin-3-amine;   6-[2-chloro-6-(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine; 6-[2-bromo-6-(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   6-[2-(azetidin-1-yl)-6-methylpyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2,6-dimethylphenol;   6-(2-chloro-6-methylpyridin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine;   5-(4-fluorophenyl)-6-[2-d3-methyl-6-(trifluoromethyl)pyridin-4-yl]-1,2,4-triazin-3-amine;   6-[2-(difluoromethyl)-6-methylpyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   6-[2-chloro-6-(difluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   6-[2-chloro-6-(fluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   6-[2-(fluoromethyl)-6-methylpyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine;   6-(2-bromo-6-methylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine; and   N-[5-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-hydroxyphenyl]acetamide.   
     
     
         43 . The method as claimed in  claim 18 , wherein the compound is selected from the group comprising:
 6-(2-chloro-6-methylpyridin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine and   6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine, or a pharmaceutically acceptable salt or solvate, or a pharmaceutically functional derivative thereof.   
     
     
         44 . The method as claimed in  claim 18 , wherein:
 B represents a Cy BB  or Het BB  group, which group is either unsubstituted or is substituted by one or more substituents selected from fluoro, CN, OR 8  or C 1-6  alkyl optionally substituted by one or more substituents selected from halo and OR 5a .   
     
     
         45 . The method as claimed in  claim 44 , wherein:
 B represents a Cy BB  or Het BB  group, which group is either unsubstituted or is substituted by fluoro at the 4-position relative to the point of attachment to the triazine ring.   
     
     
         46 . The method as claimed in  claim 18 , wherein: R 4a  does not represent OR 8  in which R 8  represents CH 3 . 
     
     
         47 . The method as claimed in  claim 43 , wherein the compound of formula A1 is 6-[2-methyl-6-(trifluoromethyl)pyridin-4-yl]-5-phenyl-1,2,4-triazin-3-amine, or a pharmaceutically acceptable salt or solvate, or a pharmaceutically functional derivative thereof. 
     
     
         48 . The method as claimed in  claim 18 , wherein the cancer is selected from the group consisting of prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glia cancer, melanoma cancer, pineal gland cancer, and lung cancer. 
     
     
         49 . The method as claimed in  claim 48 , wherein the cancer is selected from the group consisting of rectal cancer, pancreatic cancer, colon cancer, brain cancer, glia cancer, and lung cancer. 
     
     
         50 . A method of treatment of cancer, comprising administering an effective amount of 6-(2-chloro-6-methylpyridin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine, or a pharmaceutically acceptable salt or solvate, or a pharmaceutically functional derivative thereof, to a patient in need of such treatment. 
     
     
         51 . The method as claimed in  claim 50 , wherein the cancer is selected from the group consisting of prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glia cancer, melanoma cancer, pineal gland cancer, and lung cancer. 
     
     
         52 . The method as claimed in  claim 51 , wherein the cancer is selected from the group consisting of rectal cancer, pancreatic cancer, colon cancer, brain cancer, glia cancer, and lung cancer. 
     
     
         53 . A compound, wherein the compound is 6-(2-chloro-6-methylpyridin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine, or a pharmaceutically acceptable salt or solvate, or a pharmaceutically functional derivative thereof.