Patent WO-2022008896-A1 (WO)
Title: Triazole derivatives and their use as tankyrase inhibitors.
Inventor: KRAUSS STEFAN
IPC: C07D401/14
Filed: 2021-07-06
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), C 1-6  alkyl (e.g. C 1-3  alkyl), C 1-6  haloalkyl (e.g. C 1-3  haloalkyl), C 1-6  alkoxy (e.g. C 1-3  alkoxy), -CN, -NO 2 , -N(R) 2 , and -SO 2 R (where each R is independently H or C 1-6  alkyl, e.g. H or C 1-3  alkyl); a C 3-5  cycloalkyl group optionally substituted by one or more (e.g. 1 or 2) substituents independently selected from C 1-6  alkyl (preferably C 1-3  alkyl), C 1-6  haloalkyl (e.g. C 1-3  haloalkyl), and C 1-6  alkoxy (e.g. C 1-3  alkoxy); 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), C 1-6  alkyl (e.g. C 1-3  alkyl), C 1-6  haloalkyl (e.g. C 1-3  haloalkyl), and C 1-6  alkoxy (e.g. C 1-3  alkoxy); 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), C 1-6  alkyl (e.g. C 1-3  alkyl), C 1-6  haloalkyl (e.g. C 1-3  haloalkyl), and C 1-6  alkoxy (e.g. C 1-3  alkoxy); a 5- or 6-membered, saturated heterocyclic group optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from C 1-6  alkyl (preferably C 1-3  alkyl), C 1-6  haloalkyl (e.g. C 1-3  haloalkyl), and C 1-6  alkoxy (e.g. C 1-3  alkoxy); or a C 3-6  cycloalkyl group optionally substituted by one or more (e.g. 1 or 2) substituents independently selected from C 1-6  alkyl (preferably C 1-3  alkyl), C 1-6  haloalkyl (e.g. C 1-3  haloalkyl), and C 1-6  alkoxy (e.g. C 1-3  alkoxy); 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), C 1-6  alkyl (e.g. C 1-3  alkyl), C 1-6  haloalkyl (e.g. C 1-3  haloalkyl), C 1-6  alkoxy (e.g. C 1-3  alkoxy), -CN, -NO 2 , -OH, -N(R' ) 2  (where each R 1  is independently H or C 1-6  alkyl, e.g. H or C 1-3  alkyl), -SO 2 R 2  (where R 2  is H or C 1-6  alkyl, e.g. H or C1-3 alkyl), -SO 2 N(R 3 )2 (where each R 3  is independently H or C 1-6  alkyl, e.g. H or C 1-3  alkyl), and -C(0)N(R4)2 (where each R4 is independently H or C 1-6  alkyl, e.g. H or C 1-3  alkyl, 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), C 1-6  alkyl (e.g. C 1-3  alkyl), C 1-6  haloalkyl (e.g. C 1-3  haloalkyl), C 1-6  alkoxy (e.g. C 1-3  alkoxy), -CN, -NO 2 , -OH, -N(R') 2  (where each R 1  is independently H or C 1-6  alkyl, e.g. H or C 1-3  alkyl), -SO 2 R 2  (where R 2  is H or C 1-6  alkyl, e.g. H or C 1-3  alkyl), -SO 2 N(R 3 ) 2  (where each R 3  is independently H or C 1-6  alkyl, e.g. H or C 1-3  alkyl), and -C(O)N(R 4 ) 2  (where each R 4  is independently H or C 1-6  alkyl, e.g. H or C 1-3  alkyl, or wherein both R 4  groups, 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 3 ) 2 , -SO 2 N(R 3 ) 2  and -C(O)N(R 4 ) 2 , preferably by at least one substituent selected from -OH, -SO 2 N(R 3 ) 2  and -C(O)N(R 4 ) 2 . 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.