2. Academic Validation
  3. Discovery of Pyrido[3',2':5,6]thiopyrano[4,3- d]pyrimidine-Based Antiproliferative Multikinase Inhibitors

Discovery of Pyrido[3',2':5,6]thiopyrano[4,3- d]pyrimidine-Based Antiproliferative Multikinase Inhibitors

  • ACS Med Chem Lett. 2019 Jan 17;10(4):457-462. doi: 10.1021/acsmedchemlett.8b00499.
Silvia Salerno 1,  Elisabetta Barresi 1,  Aída Nelly García-Argáez 2,  Sabrina Taliani 1,  Francesca Simorini 1,  Giorgio Amendola 3,  Stefano Tomassi 3,  Sandro Cosconati 3,  Ettore Novellino 4,  Federico Da Settimo 1,  Anna Maria Marini 1,  Lisa Dalla Via 2
Affiliations

Affiliations

  • 1 Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
  • 2 Dipartimento di Scienze del Farmaco, Università di Padova, Via Marzolo 5, 35131 Padova, Italy.
  • 3 DiSTABiF, Università della Campania Luigi Vanvitelli, Via Vivaldi 43, 81100 Caserta, Italy.
  • 4 Dipartimento di Farmacia, Università di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
PMID: 30996779 DOI: 10.1021/acsmedchemlett.8b00499
Abstract

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 VEGFR2/KDR/Flk-1 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.

Figures