title: The search for a common structural moiety among selected pharmacological correctors of the mutant CFTR chloride channel.
abstract: BACKGROUND
  The F508del mutation impairs the trafficking of CFTR from endoplasmic reticulum to plasma membrane and is responsible of a severe form of cystic fibrosis. Trafficking can be improved by small organic molecules called 'correctors'.
  
  
  METHODS
  By different synthetic ways, we prepared 4-chloroanisole and 2-(4-chloroanisol-2-yl)aminothiazole derivatives. Such compounds were ineffective as correctors but we could find a sign of activity in an intermediate. In the meantime, we found a common pharmacophoric moiety present in four known correctors.
  
  
  RESULTS
  Following this structural indication, we synthesized a small set of new molecules endowed with a significant, even if not great, F508del-CFTR rescue activity.
  
  
  CONCLUSIONS
  The cited structural feature seems interesting in the search of new correctors. To corroborate this observation, later on we found a new pyrazine derivative (Novartis) endowed with a potent activity as corrector and having the cited common design.
authors.affiliation: Department of Pharmacy, University of Genova, Viale Benedetto XV, 3 - 16132 Genova, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Nieddu
authors.forename: Benedetta
authors.initials: B
authors.lastname: Pollarolo
authors.forename: Marco T
authors.initials: MT
authors.lastname: Mazzei
authors.forename: Maria
authors.initials: M
authors.lastname: Anzaldi
authors.forename: Silvia
authors.initials: S
authors.lastname: Schenone
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Pedemonte
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pesce
authors.forename: Luis J V
authors.initials: LJ
authors.lastname: Galietta
authors.forename: Mauro
authors.initials: M
authors.lastname: Mazzei
mesh_terms: D000840:Anisoles / Q000737:chemistry; D003550:Cystic Fibrosis / Q000188:drug therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D010879:Piperazines / Q000737:chemistry; D011687:Purines / Q000737:chemistry; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000737:chemistry; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D000840:Anisoles; D010879:Piperazines; D011687:Purines; D011719:Pyrazines; D013449:Sulfonamides; D013844:Thiazoles; D014665:Vasodilator Agents; C551392:4-chloroanisole; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000068677:Sildenafil Citrate