Synthesis and biological evaluation of di-aryl urea derivatives as c-Kit inhibitors - Université de Lorraine Accéder directement au contenu
Article Dans Une Revue Bioorganic and Medicinal Chemistry Année : 2015

Synthesis and biological evaluation of di-aryl urea derivatives as c-Kit inhibitors

Résumé

Inhibition of receptor tyrosine kinases (RTKs) continued to be a successful approach for the treatment of many types of human cancers and many potent small molecules kinase inhibitors have been discovered the last decade. In the present study, we describe the synthesis of thienopyrimidine derivatives and their pharmacological evaluation against nine kinases (EGFR, PDGFR-ss, c-Kit, c-Met, Src, Raf, VEGFR-1, -2 and -3). Most of the synthesized compounds showed from moderate to potent activities against c-Kit with IC50 values in the nanomolar range. Among them, 4-anilino(urea) thienopyrimidine analogs showed selectivity and potent c-Kit inhibition with IC50 values less than 6 nM. Docking simulation was performed for the most promising compound 9 into the c-Kit active site to determine the potential binding mode. This study reveal that the 4-anilino(urea) thienopyrimidine is an interesting scaffold to design novel potent and selective c-Kit inhibitors which may make promising candidates for cancers where c-Kit receptors are overexpressed.

Domaines

Chimie
Fichier non déposé

Dates et versions

hal-01495970 , version 1 (27-03-2017)

Identifiants

Citer

Séverine Ravez, Stephane Arsenlis, Amelie Barczyk, Anthony Dupont, Raphael Frederick, et al.. Synthesis and biological evaluation of di-aryl urea derivatives as c-Kit inhibitors. Bioorganic and Medicinal Chemistry, 2015, 23 (22), pp.7340-7347. ⟨10.1016/j.bmc.2015.10.035⟩. ⟨hal-01495970⟩
95 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More