Synthesis of a resorcylic acid lactone (RAL) library using fluorous-mixture synthesis and profile of its selectivity against a panel of kinases.
A library of resorcylic acid lactones (RAL) containing a cis-enone moiety targeting kinases bearing a cysteine residue within the ATP-binding pocket was prepared using a fluorous-mixture synthesis and evaluated against a panel of 19 kinases thus providing important structure-activity trends. Two new analogues were then profiled for their selectivity against a panel of 402 kinases providing the broadest evaluation of this pharmacophores' selectivity.
Jogireddy
Rajamalleswaramma
R
Institut de Science et Ingénierie Supramoléculaires (ISIS-UMR 7006), Université de Strasbourg-CNRS, 8 allée Gaspard Monge, 67000 Strasbourg, France.
Dakas
Pierre-Yves
PY
Valot
Gaëlle
G
Barluenga
Sofia
S
Winssinger
Nicolas
N
D000255:Adenosine Triphosphate / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry*; D062385:Hydroxybenzoates / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D010770:Phosphotransferases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship
D062385:Hydroxybenzoates; D007783:Lactones; D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D005461:Fluorine; D000255:Adenosine Triphosphate; D010770:Phosphotransferases