Identification of potent and selective VEGFR receptor tyrosine kinase inhibitors having new amide isostere headgroups

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 3, 2010, Pages 848-852

  Gaudette, Frédéric ^a   Raeppel, Stéphane ^a   Nguyen, Hannah ^a   Beaulieu, Normand ^a   Beaulieu, Carole ^a   Dupont, Isabelle ^a   Macleod, A Robert ^a   Besterman, Jeffrey M ^a   Vaisburg, Arkadii ^a  

^a METHYLGENE INC   (Canada)

Author keywords

Amide isostere; Angiogenesis; c Met; RTK inhibitors; VEGFR2 KDR

Indexed keywords

AMIDE; PROTEIN TYROSINE KINASE INHIBITOR; SCATTER FACTOR RECEPTOR; VASCULOTROPIN RECEPTOR 2; PROTEIN KINASE INHIBITOR; VASCULOTROPIN RECEPTOR;

ARTICLE; CELL PROLIFERATION; DRUG IDENTIFICATION; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; IN VITRO STUDY; ANTAGONISTS AND INHIBITORS; CHEMISTRY; COCULTURE; COMPARATIVE STUDY; DRUG EFFECTS; ENDOTHELIUM CELL; ENZYMOLOGY; FIBROBLAST; METABOLISM; STRUCTURE ACTIVITY RELATION;

AMIDES; COCULTURE TECHNIQUES; ENDOTHELIAL CELLS; FIBROBLASTS; HUMANS; PROTEIN KINASE INHIBITORS; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; STRUCTURE-ACTIVITY RELATIONSHIP; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 74049094480     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.12.099     Document Type: Article

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32. 50s were calculated in a four parameters equation curve plotting inhibition (%).
33. 50 curves using a 4-parameter fit model. These curves were calculated using GraFit 5.0 software.
34. Compound 8 showed no significant inhibitory activity (<50%) when tested at 0.1 μM against a representative panel of human kinases: ALK, Bmx, CHK1, cKit, c-Raf, EphB4, FAK, GSK3β, Haspin, IKKβ, JAK2, JAK3, LIMK1, MEK1, PDK1, PI3Kb, Pim-1, PKBα, Ret.