Facile prepartion of unstable metabolic intermediates; Epoxide(s) of pyrazolo[1,5-a]pyridine derivatives by the cytochrome P-450 chemical model.

Overcoming Fungal Echinocandin Resistance through Inhibition of the Non-essential Stress Kinase Yck2

“…In parallel, the poor metabolic stability of the scaffold clearly needs to be corrected. Previous work with GW and related pyrazolopyridine compounds defined the core heterocycle as a key liability due to P450-driven oxidative metabolism (Nagatsu et al, 1989;Cheung et al, 2008). Unfortunately, our initial efforts to directly address the oxidation of the pyrazolopyridine heterocycle were unsuccessful in improving the metabolic stability of GW.…”