Design, synthesis and biological evaluation of new classes of thieno[3,2-d]pyrimidinone and thieno[1,2,3]triazine as inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2)

  • Eur J Med Chem. 2013 May:63:765-81. doi: 10.1016/j.ejmech.2013.03.022.
Enrico Perspicace  1 ,  Valérie Jouan-Hureaux ,  Rino Ragno ,  Flavio Ballante ,  Stefania Sartini ,  Concettina La Motta ,  Federico Da Settimo ,  Binbin Chen ,  Gilbert Kirsch ,  Serge Schneider ,  Béatrice Faivre ,  Stéphanie Hesse
Affiliations
  • 1. Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, UMR CNRS 7565 SRSMC, Institut Jean Barriol, FR CNRS 2843, Université de Lorraine, 1 Boulevard Arago, 57070 Metz, France.
PMID: 23583911 DOI: 10.1016/j.ejmech.2013.03.022
Abstract

Driven by a multidisciplinary approach combination (Structure-Based (SB) Three-Dimensional Quantitative Structure-Activity Relationships (3-D QSAR), molecular modeling, organic chemistry and various biological evaluations) here is reported the disclosure of new thienopyrimidines 1-3 as inhibitors of KDR activity and human umbilical vein endothelial cell (HUVEC) proliferation. More specifically, compound 2f represents a new lead compound that inhibits VEGFR-2 and HUVEC at μM concentration. Moreover by the mean of an endothelial cell tube formation in vitro model 2f tartaric acid salt proved to block angiogenesis of HUVEC at μM level.

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