1532-47-4Relevant academic research and scientific papers
Design and synthesis of spirocyclic ligands of glucocorticoid receptors
Badarau, Eduard,Robert, Frédéric,Massip, Stéphane,Jakob, Florian,Lucas, Simon,Frormann, Sven,Ghosez, Léon
, p. 5119 - 5128 (2018/03/07)
Spirocyclic indazoles were designed as potential ligands for the glucocorticoid receptors (GRs). A short and efficient synthetic sequence was developed allowing the preparation of pure diastereomeric spirocyclic analogs of fluorocortivazol. Our studies also revealed a new application of Burgess reagent leading to a ring expansion. The structures and conformations of several key intermediates and products were confirmed by single crystal X-ray diffraction analysis. Conformational assignments were also supported by DFT calculations. As a proof of concept we tested the affinity of diastereomeric compounds 13b and 14b for the GRs. Rewardingly, it was found that 14b showed a promising IC50 of 27 nM.
