Ligand-based design, in silico ADME-Tox filtering, synthesis and biological evaluation to discover new soluble 1,4-DHP-based CFTR activators

Sonja Visentin, Giuseppe Ermondi, Claudio Medana, Nicoletta Pedemonte, Luis Galietta, Giulia Caron

Research output: Contribution to journalArticle

Abstract

The altered gating of the mutant CFTR chloride channel cystic fibrosis (CF) may be corrected by small molecules called potentiators. We present a molecular scale simulation system for the discovery of ΔF508-CFTR soluble potentiators. Results report the design, ADME-Tox prediction, synthesis, solubility determination and in vitro biological evaluation of two 1,4-dihydropyridines (DHPs). Compound 1 shows a promising ADME-Tox profile and good potency.

Original languageEnglish
Pages (from-to)188-194
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume55
DOIs
Publication statusPublished - Sep 2012

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Keywords

  • 3D-QSAR
  • ADME-Tox
  • CFTR potentiators
  • DHP
  • GRIND
  • VolSurf+

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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