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

= 8.4. X-ray crystallography of a protein-ligand complex structure with an l-alanine based compound revealed an internal hydrogen bond imposing a cyclic conformation on the acylurea, which in turn formed a bidentate hydrogen bond interaction with the side chain of Asn770, a key polar interaction site in MR for endogenous as well as synthetic ligands. Further lead generation efforts identified two compounds with suitable in vivo PK properties allowing assessment of their effect on acute urinary electrolyte excretion.