公开(公告)号：WO2019243822A1

公开(公告)日：2019-12-26

申请号：PCT/GB2019/051728

申请日：2019-06-19

Applicant: OSLO UNIVERSITETSSYKEHUS HF ,  FORSCHINGSVERBUND BERLIN E.V ,  UNIVERSITY OF OULU ,  GOLDING, Louise

Inventor： KRAUSS, Stefan ,  NAZARE, Marc ,  ANUMALA, Upendra Rao ,  LEHTIO, Lari ,  WAALER, Jo ,  WEGERT, Anita ,  LEENDERS, Ruben Gerardus George

IPC: C07D401/14 ,  C07D405/14 ,  A61K31/4196 ,  C07D401/04 ,  C07D403/04 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  A61P35/00

Abstract: The present invention relates to compounds of formula (I), tautomers, stereoisomers, pharmaceutically acceptable salts and pro-drugs 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, C1, 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, C1, 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 , -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); 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, C1, 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). 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.