121425-19-2Relevant articles and documents
Design and discovery of 3-aryl-5-substituted-isoquinolin-1-ones as potent tankyrase inhibitors
Elliott, Richard J. R.,Jarvis, Ashley,Rajasekaran, Mohan B.,Menon, Malini,Bowers, Leandra,Boffey, Ray,Bayford, Melanie,Firth-Clark, Stuart,Key, Rebekah,Aqil, Rehan,Kirton, Stewart B.,Niculescu-Duvaz, Dan,Fish, Laura,Lopes, Filipa,McLeary, Robert,Trindade, Ines,Vendrell, Elisenda,Munkonge, Felix,Porter, Rod,Perrior, Trevor,Springer, Caroline,Oliver, Antony W.,Pearl, Laurence H.,Ashworth, Alan,Lord, Christopher J.
supporting information, p. 1687 - 1692 (2015/09/21)
The tankyrase proteins (TNKS, TNKS2), members of the PARP superfamily of enzymes, are attractive anti-cancer drug targets, particularly as inhibition of their catalytic activity has been shown to antagonise oncogenic WNT signalling. To identify chemical inhibitors of tankyrase we carried out an in silico small molecule screen using a set of 'PARP-binding' pharmacophores together with a generated (liganded) tankyrase homology model. This approach identified a structurally diverse set of ~1000 compounds for further study. Subsequent in vitro screening of recombinant tankyrase protein identified a subset of 59 confirmed inhibitors. Early optimisation followed by cell-based studies in WNT-dependent tumour cells, as well as co-crystallisation studies, identified a novel class of 3-aryl-5-substituted isoquinolin-1-ones, such as 21, that exhibit potent inhibition of tankyrase activity as well as growth inhibition of colorectal cancer cells.
A practical in situ generation of the schwartz reagent. reduction of tertiary amides to aldehydes and hydrozirconation
Zhao, Yigang,Snieckus, Victor
supporting information, p. 390 - 393 (2014/04/03)
A new, highly efficient in situ protocol (Cp2ZrCl2/LiAlH(OBu-t)3) is described for the generation of the Schwartz reagent which provides a convenient method for the amide to aldehyde reduction and the regioselective hydrozirconation-iodination of alkynes and alkenes. Highlighted are chemoselective reductions of benzamides derived by directed ortho metalation (DoM) chemistry, allowing the synthesis of valuable 1,2,3-substituted benzaldehydes. The single-step, three-component process proceeds in a very short reaction time, shows excellent functional group compatibility, and uses inexpensive and long-storage stable reducing reagents.