[New activators of potassium channels: design, pharmacology and therapeutic perspectives]

Potassium channels (K+ channels) constitute the most diverse group of ionic channels. One of them, the ATP-sensitive K+ channel (KATP channel), was identified in numerous tissues (smooth muscle, pancreatic B-cells, central nervous system,...). This channel is of particular interest for us since we have developed various pharmacological models for the study of new potassium channel openers. Among those, diazoxide (a benzothiadiazine dioxide) is an interesting reference compound since its biological activity was observed with comparable intensity on the vascular tissue (smooth muscle) as well as on the pancreatic tissue (endocrine tissue). One of our aims was the preparation of original pyridinic analogues of diazoxide (pyridothiadiazinedioxides) and their evaluation as potassium channel openers in order to show a tissue selectivity different from that of diazoxide. Indeed, therapeutic perspectives of potassium channel openers will depend upon the discovery of new classes of compounds exhibiting an effective tissue selectivity.