Synthesis and biological evaluation of a triazole-based library of pyrido[2,3-d]pyrimidines as FGFR3 tyrosine kinase inhibitors
Laurent Le CorreUniversité Paris Descartes, UMR 8601-CNRS, 45 rue des Saints-Pères, 75006 Paris, FranceAnne‐Lise GirardUniversité Paris Descartes, UMR 8601-CNRS, 45 rue des Saints-Pères, FranceJ AubertinCNRS UMR144, Institut Curie, 26 rue d'Ulm, FranceFrançois RadvanyiCNRS UMR144, Institut Curie, 26 rue d'Ulm, FranceCatherine Benoist-LasselinUniversité Paris Descartes, INSERM U781, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, FranceAurélie JonquoyUniversité Paris Descartes, INSERM U781, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, FranceEmilie MugnieryUniversité Paris Descartes, INSERM U781, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, FranceLaurence Legeai‐MalletUniversité Paris Descartes, INSERM U781, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, FrancePatricia BuscaUniversité Paris Descartes, UMR 8601-CNRS, 45 rue des Saints-Pères, FranceYves Le MerrerUniversité Paris Descartes, UMR 8601-CNRS, 45 rue des Saints-Pères, France
2010en
ABI
Аннотация
A library of pyrido[2,3-d]pyrimidines was designed as inhibitors of FGFR3 tyrosine kinase allowing possible interactions with an unexploited region of the ATP binding-site. This library was built-up with an efficient step of click-chemistry giving easy access to triazole-based compounds bearing a large panel of substituents. Among the 27 analogues synthesized, more than half exhibited 55-89% inhibition of in vitro FGFR3 kinase activity at 2 microM and one (19g) was able to inhibit auto-phosphorylation of mutant FGFR3-K650M in transfected HEK cells.
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