Selective pancreatic ATP-sensitive potassium channel openers for the treatment of glucose homeostasis disorders

  title={Selective pancreatic ATP-sensitive potassium channel openers for the treatment of glucose homeostasis disorders},
  author={Pascal de Tullio and Philippe Lebrun and Xavier Florence and M. H. Antoine and Pierre Francotte and Bernard Pirotte},
  journal={Drugs of The Future},
Disorders of glucose homeostasis may be associated with severe pathologies such as type 1 and type 2 diabetes, insulinoma, persistent hyperinsulinemic hypoglycemia of infancy (PHHI), polycystic ovary syndrome (PCOS) and/or obesity. Specific activation of the Kir6.2/SUR1 K ATP channel subtype has been shown to be beneficial for the treatment of these pathologies. Starting from diazoxide, a nonselective Kir6.2/SUR1 K ATP channel activator, many research groups have conducted searches in an… Expand
Novel adenosine 5′-triphosphate-sensitive potassium channel ligands: a patent overview (2005 – 2010)
  • S. Rapposelli
  • Biology, Medicine
  • Expert opinion on therapeutic patents
  • 2011
This review summarizes the current understanding of the molecular biology and pharmacology of KATP channels, and the pathological states that result from aberrant expression or function of these proteins, and considers them as valid targets for several pathologies. Expand
KATP channel openers: tissue selectivity of original 3-alkylaminopyrido- and 3-alkylaminobenzothiadiazine 1,1-dioxides.
Radioisotopic, electrophysiological and pharmacological investigations indicate that the marked vasorelaxant properties of the 3-alkylaminobenzothiadiazine 1,1-dioxides are related to the activation of smooth muscle K(ATP) channels. Expand
Modulation of the 6-position of benzopyran derivatives and inhibitory effects on the insulin releasing process.
Structural-activity relationships indicated that the inhibitory effect on the insulin secreting cells was related to the lipophilicity of the molecules and to the size of the substituent located at the 6-position. Expand
2,2-Dimethyl-3,4-dihydro-2H-1,4-benzoxazines as isosteres of 2,2-dimethylchromans acting as inhibitors of insulin release and vascular smooth muscle relaxants.
The findings indicate that the benzoxazine 8e mainly behaved as a calcium entry blocker on vascular smooth muscle cells, while the myorelaxant activity of some 4-arylureido-substituted benzoxazines was more pronounced than that exhibited by their chroman counterparts. Expand
1,4,2-Benzo/pyridodithiazine 1,1-dioxides structurally related to the ATP-sensitive potassium channel openers 1,2,4-Benzo/pyridothiadiazine 1,1-dioxides exert a myorelaxant activity linked to a distinct mechanism of action.
The present work highlights the critical importance of an intracyclic NH group at the 4-position, as well as an exocyclicNH group linked to the 3-position of the benzo- and pyridothiadiazine dioxides, for activity on KATP channels. Expand
4-Phenylureido/thioureido-substituted 2,2-dimethylchroman analogs of cromakalim bearing a bulky 'carbamate' moiety at the 6-position as potent inhibitors of glucose-sensitive insulin secretion.
Radioisotopic, fluorimetric and pharmacological investigations were performed on rat pancreatic islet and rat vascular smooth muscle cells in order to decipher its mechanism of action, and it is suggested that the mechanism ofaction of 14o is rather unspecific. Expand
Influence of the alkylsulfonylamino substituent located at the 6-position of 2,2-dimethylchromans structurally related to cromakalim: from potassium channel openers to calcium entry blockers?
Investigations suggested that R/S-N-3-chlorophenyl-N'-(3,4-dihydro-6-methylsulfonylamino-2,2-dimethyl-2H-1-benzopyran-4-yl)thiourea did not act as a potassium channel opener but rather as a Ca(2+) entry blocker. Expand