2. Academic Validation
  3. Discovery of BAY 3389934 Hydrochloride: A Potent and Selective Small-Molecule Dual Factor IIa/Xa Inhibitor with Short Half-Life for the Acute Treatment of Sepsis-Induced Coagulopathy

Discovery of BAY 3389934 Hydrochloride: A Potent and Selective Small-Molecule Dual Factor IIa/Xa Inhibitor with Short Half-Life for the Acute Treatment of Sepsis-Induced Coagulopathy

  • J Med Chem. 2025 Jun 26;68(12):12687-12707. doi: 10.1021/acs.jmedchem.5c00538.
Hartmut Beck 1,  Stefanie Mesch 2,  Stefanie Zimmermann 1,  Alexandros Vakalopoulos 1,  Lutz Lehmann 1,  Kersten Matthias Gericke 1,  Frank Süßmeier 1,  Lars Baerfacker 1,  Alexander Hillisch 3,  Katharina Meier 1,  Adrian Tersteegen 1,  Anja Buchmüller 1,  Christoph Gerdes 1,  Julia Dietze-Torres 1,  Elisabeth Kersten 1,  Katrin Partikel 1,  Andreas Bröhl 1,  Guillaume Levilain 4,  Stefan Heitmeier 1,  Nils Pfaff 1,  Markus Follmann 1
Affiliations

Affiliations

  • 1 Bayer AG, Pharmaceuticals, Research & Development, 42113 Wuppertal, Germany.
  • 2 F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
  • 3 UCB BioSciences GmbH, 40789 Monheim, Germany.
  • 4 Sanofi, 45 Chemin de Météline, 04200 Sisteron, France.
PMID: 40498640 DOI: 10.1021/acs.jmedchem.5c00538
Abstract

Sepsis-induced coagulopathy (SIC) is a severe and frequent complication of sepsis, which is associated with high mortality in patients. So far, attempts have failed to establish a global standard of care in this difficult-to-treat indication. Anticoagulation with a dual inhibitor of the coagulation factors IIa (FIIa, Thrombin) and Xa (FXa) has the potential to improve the treatment of life-threatening acute coagulation disorders, such as SIC. Herein, we describe the discovery of BAY 3389934 hydrochloride (31), a potent and highly selective, direct dual FIIa/Xa inhibitor, with high solubility suited for i.v. application. This small molecule acts as a metabolically soft active pharmaceutical ingredient (API) due to a labile carboxylic ester group, which is responsible for the desired short pharmacokinetic and pharmacological half-life (t1/2), resulting in a high controllability of the pharmacological action.

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