22362-50-1Relevant academic research and scientific papers
Investigation of new 2-aryl substituted Benzothiopyrano[4,3-d[pyrimidines as kinase inhibitors targeting vascular endothelial growth factor receptor 2
Salerno, Silvia,Marini, Anna Maria,Fornaciari, Giacomo,Simorini, Francesca,La Motta, Concettina,Taliani, Sabrina,Sartini, Stefania,Da Settimo, Federico,Garciá-Argaéz, Aída Nelly,Gia, Ornella,Cosconati, Sandro,Novellino, Ettore,D'Ocon, Pilar,Fioravanti, Anna,Orlandi, Paola,Bocci, Guido,Dalla Via, Lisa
, p. 29 - 43 (2015)
Vascular Endothelial Growth Factor (VEGF) pathway has emerged as one of the most important positive modulators of Angiogenesis, a central process implicated in tumour growth and metastatic dissemination. This led to the design and development of anti-VEGF monoclonal antibodies and small-molecule ATP-competitive VEGFR-inhibitors. In this study, we describe the synthesis and the biological evaluation of novel 2-aryl substituted benzothiopyrano-fused pyrimidines 1a-i, 2a-i and 3a-i. The ability of the compounds to target the VEGF pathway was determined in vitro exploiting the compounds' antiproliferative efficacy against HUVEC cells. The VEGFR-2 inhibition was confirmed by enzymatic assays on recombinant human kinase insert domain receptor (KDR), by cell-based phospho-VEGFR-2 inhibition assays, and by ex vivo rat aortic ring tests. The selectivity profile of the best performing derivatives belonging to series 2 was further explored combining modeling studies and additional assays in a panel of human cell lines and other kinases.
