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'. Materials & 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. Conclusion: 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.
Financial & competing interests disclosure
This work was supported by Italian Cystic Fibrosis Foundation (Project FFC#5/2010) with the financial support of P Watch – Morellato and Sector Group. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.