1217656-13-7Relevant academic research and scientific papers
Structure-activity relationship and properties optimization of a series of Quinazoline-2,4-diones as inhibitors of the canonical Wnt pathway
Nencini, Arianna,Pratelli, Carmela,Quinn, Joanna M.,Salerno, Massimiliano,Tunici, Patrizia,De Robertis, Alessandra,Valensin, Silvia,Mennillo, Federica,Rossi, Marco,Bakker, Annette,Benicchi, Tiziana,Cappelli, Federico,Turlizzi, Elisa,Nibbio, Martina,Caradonna, Nicola P.,Zanelli, Ugo,Andreini, Matteo,Magnani, Matteo,Varrone, Maurizio
, p. 526 - 545 (2015)
Wnt signaling pathway plays a critical role in numerous cellular processes, including tumor initiation, proliferation, invasion/infiltration, metastasis formation and resistance to chemotherapy. In a drug discovery project aimed at the identification of inhibitors of the canonical Wnt pathway, we selected a series of quinazoline 2,4-diones as starting point for the therapeutic treatment of glioblastoma multiforme. Despite of poor physico-chemical properties of hit compound 1, our medicinal chemistry effort allowed the discovery and characterization of lead compound 33 (SEN461), with improved ADME profile, good bioavailability and active in vitro and in vivo in glioblastoma, gastric and sarcoma tumors.
Discovery of Orally Bioavailable Ligand Efficient Quinazolindiones as Potent and Selective Tankyrases Inhibitors
Qin, Donghui,Lin, Xiaojuan,Liu, Zhi,Chen, Yan,Zhang, Zhiliu,Wu, Chengde,Liu, Linlin,Pan, Yan,Laquerre, Sylvie,Emery, John,Fergusson, Jeff,Roland, Kimberly,Keenan, Rick,Oliff, Allen,Kumar, Sanjay,Cheung, Mui,Su, Dai-Shi
, p. 1005 - 1010 (2021/05/27)
We report herein the discovery of quinazolindiones as potent and selective tankyrase inhibitors. Elucidation of the structure-activity relationship of the lead compound 1g led to truncated analogues that have good potency in cells, pharmacokinetic (PK) properties, and excellent selectivity. Compound 21 exhibited excellent potencies in cells and proliferation studies, good selectivity, in vitro activities, and an excellent PK profile. Compound 21 also inhibited H292 xenograft tumor growth in nude mice. The synthesis, biological, pharmacokinetic, in vivo efficacy studies, and safety profiles of compounds are presented.
QUINAZOLINEDIONES AS TANKYRASE INHIBITORS
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, (2014/01/07)
This invention relates to the use of quinazolinediones for the modulation, notably the inhibition of the activity of tankyrases (TNKS1 and TNKS2). Suitably, the present invention relates to the use of quinazolinediones in the treatment of cancer, fibrosis and other hyperproliferative diseases through this mechanism.
WNT PATHWAY ANTAGONISTS
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, (2011/04/26)
The present invention relates to known and novel compounds of formula (I) as herein described and pharmaceutical compositions thereof. The compounds of formula (I) have inhibitory effect on the Wnt pathway and are therefore useful in the preparation of a medicament, in particular for the treatment of cancer.
