University of Oulu

Forschungsverbund Berlin E.v.

Oslo Universitetssykehus Hf

Lari Lehtiö

Anita Wegert

Ruben Gerardus George Leenders

Marc Nazare

Jo Waaler

Stefan Krauss

Bernhard Lüscher

Harikanth Venkannagari

Patricia Verheugd

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, Cl, Br, I), Calkyl (e.g. Calkyl), Chaloalkyl (e.g. Chaloalkyl), Calkoxy (e.g. Calkoxy), —CN, —NO, —N(R)2, 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. Calkoxy); 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, —N(R), and —SOR (where each R is independently H or Calkyl, e.g. H or Calkyl); 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, —N(R), and —SOR (where each R is independently H or Calkyl, e.g. H or Calkyl). 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.

1,2,4-triazole derivatives as tankyrase inhibitors

It is an aim of the present invention to provide inhibitors of human diphtheria toxin-like ADP-ribosyltransferases, such as ARTD10, for use as a medicine. It is another aim of the invention to provide compounds for use as human mono-ADP-ribosyltransferase (mARTD) inhibitors in vitro. In the present invention, it has been discovered that human ARTD10, which belongs to an enzyme family linked to cancer biology, can be specifically inhibited by the benzamide comprising compounds disclosed in the invention, such as 4,4'-oxydibenzamide.

Compounds for use in the treatment of cancer

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Oulu, Finland

Lari Lehtiö