Mineralocorticoid Receptor Antagonists With an Acylurea as a Key Polar Interaction Motif.

Key Points

• This research aims to explore acylurea interactions with the mineralocorticoid receptor and their effects on electrolyte excretion.
• Utilized X-ray crystallography to analyze protein-ligand complex structure.
• Investigated internal hydrogen bonds and cyclic conformation effects on acylurea.
• Conducted lead generation to identify compounds with suitable pharmacokinetic properties.
• Two compounds with favorable in vivo pharmacokinetics were identified.
• These compounds showed significant effects on acute urinary electrolyte excretion.
• Hydrogen bonding interactions were confirmed to be critical for ligand binding.