Coumarins are a large class of naturally occurring phenolic substances consisting in fused benzene and α-pyrone rings (benzo-α-pyrones). Coumarins are extremely variable in structure, due to different types of substituents in their scaffold, which can influence their biological activity. Coumarin-derivatives possessing a 4-hydroxyl group have been therapeutically used for their orally anticoagulant activity (e.g. warfarin). Nevertheless, being vitamin K antagonists, coumarins have a delayed onset and offset of action and several interactions with many drugs and food. In opposite, heparin, which is a polysulfated polysaccharide, has a short onset and offset of action, due to an effective mechanism of action, but is only active by parenteral route. As a result, it is important to develop effective orally active antithrombotic agents. In this work, a hybridization strategy was planned joining a coumarin scaffold with a heparin-like sugar sulfated moiety. With this approach it is expected to mimetize the sulfated polysaccharide anticoagulants, while adding some hydrophobic character to the resulting molecule to achieve oral bioavailability.

Five persulfated triazole and non-triazole linked coumarin glucosides were obtained by microwave irradiation with triethylamine-sulfur trioxide adduct, and their structure elucidation was established by IR and NMR for the first time. A purification procedure involving dialysis with a cellulose membrane was successfully applied to remove water soluble impurities. The anticoagulant activity was measured by the classical clotting times - activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The most active compound exhibited an APTT₂ of 22×10^-5 M. In the future, oral bioavailability of this innovative coumarin hybrid will be evaluated.