title: Synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK inhibitors with anti-angiogenic activity.
abstract: We report herein the synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK (focal adhesion kinase) inhibitors and the evaluation of their anti-angiogenic activity on HUVEC cells. Generally, the effects of these compounds on endothelial cells could be correlated with their kinase inhibitory activity. The most efficient compounds displayed inhibition of viability against HUVEC cells in the micromolar range, as observed with TAE-226, which was designed by Novartis Pharma AG. X-ray crystallographic analysis of the co-crystal structure for compound 34 revealed that the mode of interaction with the FAK kinase domain is highly similar to that observed in the complex of TAE-226.
authors.affiliation: Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR8601, CNRS, Université Paris Descartes, PRES Sorbonne Paris Cité, UFR Biomédicale, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Dao
authors.forename: Rafika
authors.initials: R
authors.lastname: Jarray
authors.forename: Johanne
authors.initials: J
authors.lastname: Le Coq
authors.forename: Daniel
authors.initials: D
authors.lastname: Lietha
authors.forename: Ali
authors.initials: A
authors.lastname: Loukaci
authors.forename: Yves
authors.initials: Y
authors.lastname: Lepelletier
authors.forename: Réda
authors.initials: R
authors.lastname: Hadj-Slimane
authors.forename: Christiane
authors.initials: C
authors.lastname: Garbay
authors.forename: Françoise
authors.initials: F
authors.lastname: Raynaud
authors.forename: Huixiong
authors.initials: H
authors.lastname: Chen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D042783:Endothelial Cells / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D009025:Morpholines; C524632:TAE226; D014227:Triazines; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: Anti-angiogenic activity; Diarylamino-1,3,5-triazines; FAK inhibitors; Synthesis; X-ray structure