Design and discovery of 3-aryl-5-substituted-isoquinolin-1-ones as potent tankyrase inhibitors was written by 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.. And the article was included in MedChemComm in 2015.Product Details of 37812-51-4 This article mentions the following:
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 antagonize oncogenic WNT signalling. To identify chem. inhibitors of tankyrase we carried out an in silico small mol. screen using a set of ‘PARP-binding’ pharmacophores together with a generated (liganded) tankyrase homol. 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 optimization followed by cell-based studies in WNT-dependent tumor cells, as well as co-crystallization 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. In the experiment, the researchers used many compounds, for example, 4-(Morpholinomethyl)benzonitrile (cas: 37812-51-4Product Details of 37812-51-4).
4-(Morpholinomethyl)benzonitrile (cas: 37812-51-4) belongs to nitriles. Nitrile compounds can be prepared by the incorporation of a cyanide source through C–C bond formation or by dehydration of primary carboxamides. Industrially, the main methods for producing nitriles are ammoxidation and hydrocyanation. Both routes are green in the sense that they do not generate stoichiometric amounts of salts.Product Details of 37812-51-4
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts