Discovery of Novel Aminopyrimidines as Selective EP2 Receptor Antagonists
EP2 is a G-protein coupled receptor that is activated by prostaglandin E2 (PGE2). Signaling through the EP2 receptor has been shown to play a key role in various processes involved in diseases such as immune disorders or cancer. A new class of selective EP2 antagonists with an attractive in vitro and in vivo profile has been identified. The amide bond in the original screening hit is replaced by various alternatives. The introduction of an aminopyrimidine scaffold results in excellent potency. Improvement of physicochemical and ADME properties is achieved by incorporation of a carboxylic acid moiety, resulting in lead compound 29 exhibiting drug-like properties.
Authors
- Christoph Boss (ORCID: https://orcid.org/0000-0001-8838-8190)
- Ruben de Kanter (ORCID: https://orcid.org/0000-0001-7503-9776)
- Olivier Corminboeuf (ORCID: https://orcid.org/0000-0003-2728-3699)
- Isabelle Lyothier
- Lorenza Wyder
- Hervé Siendt
- Carmela Gnerre
- Sébastien Jeay (ORCID: https://orcid.org/0000-0001-7476-3340)
- Heinz Fretz
- Julien Pothier
- Dominique S. Meyer (ORCID: https://orcid.org/0000-0001-8673-0511)
- Thierry Sifferlen (ORCID: https://orcid.org/0009-0004-8073-9434)
- Stefan Diethelm (ORCID: https://orcid.org/0009-0002-4681-6892)
- Davide Pozzi (ORCID: https://orcid.org/0000-0001-6436-0556)
- François Lehembre
Institutions
- Idorsia (Switzerland) (CH)
- Actelion (Switzerland) (CH)
Publication Details
- Journal
- ChemMedChem
- Published
- 2025-04-07
- DOI
- https://doi.org/10.1002/cmdc.202500119
- Citations
- 2
- Primary Topic
- Inflammatory mediators and NSAID effects
- Type
- article
- Field-Weighted Citation Impact
- 2.79