Triazole derivatives and their use as tankyrase inhibitors

Abstract

The present invention relates to compounds of general formula (I), tautomers, stereoisomers, N-oxides, pharmaceutically acceptable salts and pro-drug thereof, to processes for their preparation, to pharmaceutical compositions containing such compounds and to their use in therapy: wherein: a dashed line indicates an optional bond; X represents: a 5- or 6-membered, unsaturated heterocyclic group optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from halogen (i.e. F, Cl, Br, I), Calkyl (e.g. Calkyl), Chaloalkyl (e.g. Chaloalkyl), Calkoxy (e.g. Calkoxy), —CN, —NO, —N(R), and —SOR (where each R is independently H or Calkyl, e.g. H or Calkyl); a Ccycloalkyl group optionally substituted by one or more (e.g. 1 or 2) substituents independently selected from Calkyl (preferably Calkyl), Chaloalkyl (e.g. Chaloalkyl), and Calkoxy (e.g. Calkoxy); or an aryl group optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from halogen (i.e. F, Cl, Br, I), Calkyl (e.g. Calkyl), Chaloalkyl (e.g. Chaloalkyl), and Calkoxy (e.g. Calkoxy); Y represents: an aryl or heteroaryl group optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from halogen (i.e. F, Cl, Br, I), Calkyl (e.g. Calkyl), Chaloalkyl (e.g. Chaloalkyl), and Calkoxy (e.g. Calkoxy); a 5- or 6-membered, saturated heterocyclic group optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from Calkyl (preferably Calkyl), Chaloalkyl (e.g. Chaloalkyl), and Calkoxy (e.g. C_alkoxy); or a Ccycloalkyl group optionally substituted by one or more (e.g. 1 or 2) substituents independently selected from Calkyl (preferably Calkyl), Chaloalkyl (e.g. Chaloalkyl), and Calkoxy (e.g. Calkoxy); and Z represents: an aryl group optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from halogen (i.e. F, Cl, Br, I), Calkyl (e.g. Calkyl), Chaloalkyl (e.g. Chaloalkyl), Calkoxy (e.g. Calkoxy), —CN, —NO, —OH, —N(R)(where each Ris independently H or Calkyl, e.g. H or Calkyl), —SOR(where Ris H or Calkyl, e.g. H or C1-3 alkyl), —SON(R)2 (where each Ris independently H or Calkyl, e.g. H or Calkyl), and —C(O)N(R4)2 (where each R4 is independently H or Calkyl, e.g. H or Calkyl, or wherein both R4 groups, together with the intervening nitrogen atom, form a 3 to 6 membered saturated heterocyclic ring); or an unsaturated, 5- to 10-membered mono- or bicyclic heterocyclic group optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from halogen (i.e. F, Cl, Br, I), Calkyl (e.g. Calkyl), Chaloalkyl (e.g. Chaloalkyl), Calkoxy (e.g. Calkoxy), —CN, —NO, —OH, —N(R)(where each Ris independently H or Calkyl, e.g. H or Calkyl), —SOR(where Ris H or Calkyl, e.g. H or Calkyl), —SON(R)(where each Ris independently H or Calkyl, e.g. H or Calkyl), and —C(O)N(R)(where each Ris independently H or Calkyl, e.g. H or Calkyl, or wherein both Rgroups, together with the intervening nitrogen atom, form a 3 to 6 membered saturated heterocyclic ring); with the proviso: that when the compound is other than an N-oxide of formula (I), Z must be substituted by at least one substituent selected from —OH, —N(R), —SON(R)and —C(O)N(R), preferably by at least one substituent selected from —OH, —SON(R)and —C(O)N(R). These compounds find particular use in the treatment and/or prevention of a disease or disorder responsive to inhibition of tankyrase 1 and/or 2, for example a disorder which is mediated by tankyrase 1 and/or 2 such as cancer.