title: Novel small molecule epithelial sodium channel inhibitors as potential therapeutics in cystic fibrosis - a patent evaluation.
abstract: Novel molecular platforms for epithelial sodium channel (ENaC) modulators are claimed in the following six patents: WO2012035158(A1); WO2009074575(A2); WO2011028740(A1); WO2009150137(A2); WO2011079087(A1); WO2008135557(A1). These ENaC inhibitors may be used in blocking transepithelial sodium and consequently water absorption across airway epithelia. This may result in airway rehydration and enhanced mucociliary clearance in patients with cystic fibrosis (CF) lung disease. All inhibitors resemble the classical ENaC blocker amiloride but follow different strategies to increase structural diversity in a sterically tolerant region. These substitutions can be modified to i) enhance potency of ENaC inhibition; ii) reduce epithelial permeability; and iii) broaden applicability in order to be used as potential drugs for CF therapy. Most of the claims and patent data are supported by the currently available literature. The patents deliver a solid chemical basis for a variety of chemical modifications of the ENaC inhibitor amiloride. These modifications may result in the development of a novel, applicable ENaC inhibitors which may have lasting effects on diseased airways and may achieve airway rehydration and enhanced mucociliary clearance in CF lung disease.
authors: University of Munich, Department of Chemistry and Center for Integrated Protein Science , Butenandtstraße 5 - 13 (F4.086), 81377 Munich , Germany.
authors: Matthias
authors: M
authors: Schoenberger
authors: Mike
authors: M
authors: Althaus
mesh_terms: D000584:Amiloride / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003550:Cystic Fibrosis / Q000188:drug therapy*; D062686:Epithelial Sodium Channel Blockers / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D009079:Mucociliary Clearance; D010330:Patents as Topic; D054852:Small Molecule Libraries; D014867:Water / Q000378:metabolism
chemical_list: D062686:Epithelial Sodium Channel Blockers; D054852:Small Molecule Libraries; D014867:Water; D000584:Amiloride