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.
Authors
- Bo Lindmark (ORCID: https://orcid.org/0000-0002-4708-8797)
- Anneli Nordqvist (ORCID: https://orcid.org/0000-0001-5829-3836)
- Kenneth L. Granberg (ORCID: https://orcid.org/0000-0003-3655-741X)
- Anna Aagaard (ORCID: https://orcid.org/0000-0002-2901-8496)
- K. A. P. Edman (ORCID: https://orcid.org/0000-0002-2560-2388)
- Zhong-Qing Yuan
- Lena William‐Olsson (ORCID: https://orcid.org/0000-0002-2604-2183)
- Ida Ivarsson
- Krister Bamberg (ORCID: https://orcid.org/0000-0002-0538-6083)
- Yoseph Atilaw (ORCID: https://orcid.org/0000-0003-2899-9912)
- Anders Hogner (ORCID: https://orcid.org/0000-0003-3823-4534)
- Stefan Tångefjord (ORCID: https://orcid.org/0000-0002-3846-6637)
- Marléne Fredenwall
- Louise Barlind
- Henrik Sørensen (ORCID: https://orcid.org/0000-0003-4032-1282)
- Jan Lindberg
- Eva Hansson
- Gavin O'Mahony
- Maria Johansson
- Dongmei Liu
Institutions
- Pharmaron (United Kingdom) (GB)
- AstraZeneca (Finland) (FI)
- AstraZeneca (Sweden) (SE)
Publication Details
- Journal
- ChemMedChem
- Published
- 2026-04-30
- DOI
- https://doi.org/10.1002/cmdc.202501047
- Primary Topic
- Hormonal Regulation and Hypertension
- Type
- article
- Field-Weighted Citation Impact
- 0.00