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
Beck H, Mesch S, Zimmermann S, Vakalopoulos A, Lehmann L, Gericke KM, Süßmeier F, Baerfacker L, Hillisch A, Meier K, Tersteegen A, Buchmüller A, Gerdes C, Dietze-Torres J, Kersten E, Partikel K, Bröhl A, Levilain G, Heitmeier S, Pfaff N, Follmann M
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.
Journal of medicinal chemistry, 2025-06-28