From Cromakalim to Different Structural Classes of KATP Channel Openers

Violetta      Cecchetti; Oriana      Tabarrini; Stefano      Sabatini

doi:10.2174/156802606777323683

Abstract

ATP-Sensitive potassium channel openers (KATPCOs) are a group of compounds with a broad spectrum of potential therapeutic applications, as they constitute efficient tools for dampening cell excitability. Interest in the KATPCOs was triggered in the early 1980s by the discovery of the benzopyran-based structure cromakalim (CRK), which is a powerful smooth muscle relaxant. CRK can be considered the archetype of KATPCOs and is by far the most mimicked structure. In many structure-activity studies various substitutions have been made at the different positions of the benzopyran ring permitting the optimal activity to be correlated with a specific set of structural characteristics and stereochemical features of the molecule. Thus, many potent benzopyran derivatives have been identified. The benzopyran nucleus itself has also been modified in both the aromatic ring and in the pyran moiety. The intention of this review is to bring together all the different structural classes of KATPCOs arising from the replacement of CRK benzopyran-based structure with various ring systems; design, structure-activity relationship, and synthesis will be given.

Keywords: KATP channels, cromakalim analogues, thienopyrans, pyranopyridines, benzoxepines, indanes, benzothiopyrans, quinolines, naphthalenes, benzoxazines