Synthesis and biological evaluation of ...
Document type :
Article dans une revue scientifique
PMID :
Permalink :
Title :
Synthesis and biological evaluation of di-aryl urea derivatives as c-Kit inhibitors
Author(s) :
Ravez, Severine [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Institut de Chimie Pharmaceutique Albert Lespagnol [ICPAL]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Arsenlis, Stephane [Auteur]
Institut de Chimie Pharmaceutique Albert Lespagnol [ICPAL]
Barczyk, Amelie [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Dupont, Anthony [Auteur]
Institut de Chimie Pharmaceutique Albert Lespagnol [ICPAL]
Frederick, Raphael [Auteur]
Université Catholique de Louvain = Catholic University of Louvain [UCL]
Hesse, Stephanie [Auteur]
Université de Lorraine [UL]
Kirsch, Gilbert [Auteur]
Structure et Réactivité des Systèmes Moléculaires Complexes [SRSMC]
Depreux, Patrick [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - EA 7365
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Goossens, Laurence [Auteur]
495476|||Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Institut de Chimie Pharmaceutique Albert Lespagnol [ICPAL]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Arsenlis, Stephane [Auteur]
Institut de Chimie Pharmaceutique Albert Lespagnol [ICPAL]
Barczyk, Amelie [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Dupont, Anthony [Auteur]
Institut de Chimie Pharmaceutique Albert Lespagnol [ICPAL]
Frederick, Raphael [Auteur]
Université Catholique de Louvain = Catholic University of Louvain [UCL]
Hesse, Stephanie [Auteur]
Université de Lorraine [UL]
Kirsch, Gilbert [Auteur]
Structure et Réactivité des Systèmes Moléculaires Complexes [SRSMC]
Depreux, Patrick [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - EA 7365
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Goossens, Laurence [Auteur]
495476|||Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Journal title :
Bioorganic & Medicinal Chemistry Letters
Abbreviated title :
Bioorg. Med. Chem.
Volume number :
23
Pages :
7340-7347
Publication date :
2015
ISSN :
0960-894X
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
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. ...
Show more >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.Show less >
Show more >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.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
CHU Lille
Inserm
CHU Lille
Inserm
Collections :
Research team(s) :
Modélisation biopharmaceutique et pharmacocinétique
Submission date :
2019-02-26T17:11:48Z
2022-01-12T11:55:12Z
2022-01-12T11:55:12Z