Eur J Med Chem 2021 Aug 28;226:113797. Epub 2021 Aug 28.
Department of Drug Design and Optimization (DDOP), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany; Department of Pharmacy, Saarland University, Campus E8.1, 66123, Saarbrücken, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 66123, Saarbrücken, Germany. Electronic address:
A short and divergent route towards new derivatives of 2-(trifluoromethyl)pyridines as potent inverse agonists of the bacterial target PqsR against Pseudomonas aeruginosa (PA) infections is described. This Gram-negative pathogen causes severe nosocomial infections and common antibiotic treatment options are rendered ineffective due to resistance issues. Based on an earlier identified optimized hit, we conducted derivatization and rigidification attempts employing two central building blocks. Read More