title: Recent developments in the chemistry of potassium channel activators: the cromakalim analogs.
abstract: Potassium channels play a crucial role in controlling the cell membrane potential. Among the different varieties of K(+) channels, the ATP-sensitive potassium channels (K(ATP) channels) have been characterized in numerous cell types, such as skeletal and smooth muscle cells, endocrine cells, cardiac cells and central neurons. Several molecules are known to activate K(ATP) channels and have been named "potassium channel openers" (PCOs). Such compounds may have a wide therapeutic potential and a few drugs are currently used as antihypertensive agents. Different chemical series of PCOs have been explored. This heterogeneous group of organic compounds comprises the benzopyran series including potent vasorelaxant drugs, such as cromakalim. The latter compound, a typical example of potassium channel opener, exerts its biological effect by activating K(ATP) channels. This review presents recent developments in the chemistry of cromakalim analoges and reports chemical aspects governing their potency and tissue selectivity.
authors.affiliation: Centre Interfacultaire de Recherche en Pharmacochimie des substances naturelles et synthétiques, Laboratoire de Chimie Pharmaceutique, Université de Liège, 1, Avenue de l'Hôpital, B-4000 Liège, Belgium. Sophie.Sebille@ulg.ac.be
authors.forename: S
authors.initials: S
authors.lastname: Sebille
authors.forename: P
authors.initials: P
authors.lastname: De Tullio
authors.forename: S
authors.initials: S
authors.lastname: Boverie
authors.forename: M H
authors.initials: MH
authors.lastname: Antoine
authors.forename: P
authors.initials: P
authors.lastname: Lebrun
authors.forename: B
authors.initials: B
authors.lastname: Pirotte
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects; D019806:Cromakalim / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects; D015221:Potassium Channels / Q000819:agonists* / Q000187:drug effects; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim