The binding and mechanism of a positive allosteric modulator of Kv3 channels.

Small-molecule modulators of diverse voltage-gated K (Kv) channels may help treat a wide range of neurological disorders. However, developing effective modulators requires understanding of their mechanism of action. We apply an orthogonal approach to elucidate the mechanism of action of an imidazolidinedione derivative (AUT5), a highly selective positive allosteric modulator of Kv3.

A direct fixation of CO for isotopic labelling of hydantoins using iodine-phosphine charge transfer complexes.

Herein, we report a method for the isotopic labelling of hydantoins directly from CO by means of trimethyl-λ-phosphine diiodide mediated carbonyl insertion. The method is suitable for C-labelling of diverse substrates and was implementated for C-labelling in PET-imaging facilities for the synthesis of radiotracers. Isolated yields of 90% and radiochemical yields of 89% were achieved for hydantoin containing drug candidates in formulation within 30 min with high molar activity (>400 MBq nmol).