ORALS

This work contributes to the chemistry of chromones. Chromone is a privileged scaffold for drug discovery.[1] Variety of useful properties of naturally occurring chromones encourage to expect interesting types of biological activity in newly synthetized chromone derivatives.[2] However, structural modification of chromone scaffold is not a trivial task because of the instability of their γ-pyrone cycle. Which methods could be applied to modify the chromone moiety? We answer this question by presentation of rapid and effective three-step domino reaction, which delivers a wide library of novel substituted chromenopyrrolones.[3,4] Application of a chemiluminescent assay demonstrates ability of isolated chromenopyrrolones to inhibit mammalian tissue nonspecific alkaline phosphatase in micromolar range of concentrations.[4] This kind of biological activity was not reported for chromone derivatives to date. Elevated levels of the given enzyme causes pathological hypercalcification disorders in soft tissues in the body. Potently chromenopyrrolone inhibitors of alkaline phosphatase can find application as therapeutic agents in treatment of atherosclerotic lesions.

References:
[1] – R. Musiol, Expert Opinion on Drug Discovery 12 (2017) 583.
[2] – J. Reis, A. Gaspar, N. Milhazes, F. Borges, J. Med. Chem. 60 (2017) 7941.
[3] – T. A. N. Tien, M. Miliutina, R. Radolko; R. Thom, T. T. Dang, P. Ehlers, P. Langer, Tetrahydron 104 (2022) 132608.
[4] – M. Miliutina, Y. Ivon, Y. Slobodianiuk, S. A. Ejaz, J. Iqbal, A. Villinger, V. O. Iaroshenko, P. Langer, Chem. Heterocycl. Comp. 55 (2019) 465.