168080-76-0Relevant articles and documents
Facile Synthesis of Alkylidene Phthalides by Rhodium-Catalyzed Domino C?H Acylation/Annulation of Benzamides with Aliphatic Carboxylic Acids
Liu, Sien,He, Bangyue,Li, Hongyi,Zhang, Xiaofeng,Shang, Yaping,Su, Weiping
supporting information, p. 15628 - 15633 (2021/10/05)
The Rh-catalyzed ortho-C(sp2)?H functionalization of 8-aminoquinoline-derived benzamides with aliphatic acyl fluorides generated in situ from the corresponding acids has been developed. This reaction initiated with 8-aminoquinoline-directed ortho-C(sp2)?H acylation, which was accompanied by subsequent intramolecular nucleophilic acyl substitution of amide group to produce alkylidene phthalides This approach exhibits high stereo-selectivity for Z-isomer products, and tolerates a variety of functional groups as well as aliphatic carboxylic acids with diverse structural scaffolds.
Rhodium-Catalyzed Alkylation of C?H Bonds in Aromatic Amides with Non-activated 1-Alkenes: The Possible Generation of Carbene Intermediates from Alkenes
Yamaguchi, Takuma,Natsui, Satoko,Shibata, Kaname,Yamazaki, Ken,Rej, Supriya,Ano, Yusuke,Chatani, Naoto
supporting information, p. 6915 - 6919 (2019/05/10)
The alkylation of C?H bonds (hydroarylation) in aromatic amides with non-activated 1-alkenes using a rhodium catalyst and assisted by an 8-aminoquinoline directing group is reported. The addition of a carboxylic acid is crucial for the success of this reaction. The results of deuterium-labeling experiments indicate that one of deuterium atoms in the alkene is missing, suggesting that the reaction does not proceed through the commonly accepted mechanism for C?H alkylation reactions. Instead the reaction is proposed to proceed through a carbene mechanism. The carbene mechanism is also supported by preliminary DFT calculations.
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.
