1. Discovery of Pyrido[3′,2′:5,6]thiopyrano[4,3-d]pyrimidine-Based Antiproliferative Multikinase Inhibitors
- Author
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Giorgio Amendola, Sabrina Taliani, Sandro Cosconati, Ettore Novellino, Aída Nelly García-Argáez, Elisabetta Barresi, Federico Da Settimo, Stefano Tomassi, Francesca Simorini, Silvia Salerno, Anna Maria Marini, Lisa Dalla Via, Silviasalerno, Elisabettabarresi, AídaNellyGarcía-Argaéz, Sabrinataliani, Francescasimorini, Giorgio, Amendola, Tomassi, S, Sandro, Cosconati, Novellino, Ettore, Federico Da Settimo, Anna Maria Marini, Lisa Dalla Via, Salerno, S., Barresi, E., Garcia-Argaez, A. N., Taliani, S., Simorini, F., Amendola, G., Tomassi, S., Cosconati, S., Novellino, E., Da Settimo, F., Marini, A. M., and Dalla Via, L.
- Subjects
antiproliferative activity ,Pyridothiopyranopyrimidines ,Pyrimidine ,Angiogenesis ,Kinase ,Organic Chemistry ,Pyridothiopyranopyrimidine ,Biochemistry ,Multikinase inhibitor ,Human tumor ,chemistry.chemical_compound ,chemistry ,Cell culture ,KDR kinase ,Drug Discovery ,Cancer cell ,multitargeted kinase inhibitors ,Cancer research ,Tumor growth ,multitargeted kinase inhibitor - Abstract
[Image: see text] Protein kinases dysregulation is extremely common in cancer cells, and the development of new agents able to simultaneously target multiple kinase pathways involved in angiogenesis and tumor growth may offer several advantages in the treatment of cancer. Herein we report the discovery of new pyridothiopyranopyrimidine derivatives (2–4) showing high potencies in VEGFR-2 KDR inhibition as well as antiproliferative effect on a panel of human tumor cell lines. Investigation on the selectivity profile of the representative 2-anilino-substituted compounds 3b, 3i, and 3j revealed a multiplicity of kinase targets that should account for the potent antiproliferative effect produced by these pyridothiopyranopyrimidine derivatives.
- Published
- 2019