ABSTRACT
Potassium channels comprise the most diverse group of ion channels so far investigated. Amongst these, the A TP sensitive K channels (KATP channels) have been the most studied. During the last ten years compounds have been discovered which can activate or block these KATP channels. In particular K channel activators (KCAs) have been found, along with many other activities, to be smooth muscle relaxants with their main utility in hypertension and bronchodilatation. There are at least seven classes of activators (Edwards and Weston, 1990) of which the main four are shown in Figure 3.1. The benzopyrans, typified by cromakalim (CRK, shown as its (-) 3S, 4R-enantiomer levcromakalim (LCRK)), have been the class most thoroughly explored with more than thirty companies claiming patents. In comparison there have been few reports of structural modifications in the other classes of KCAs. This chapter covers the syntheses and structure-activity relationships (SARs) of the pyridine classes of KCAs: the thioformamides, cyanoguanidines and organic nitrates together with their hybrid molecules.
