Ticagrelor (Brilinta) and Dabigatran Etexilate (Pradaxa): P2Y₁₂ Platelet Inhibitors as Anticoagulants

Anticoagulants mainly come from two classes of anticoagulation mechanism: the direct thrombin inhibitors (DTIs) and the platelet aggregation inhibitors. This chapter describes the direct thrombin inhibitor, dabigatran etexilate, and P2Y112 platelet inhibitor, ticagrelor, used as anticoagulants. It discusses general information, the discovery, and the chemical process of these two representative drugs. For the chemical process of dabigatran etexilate, the main task is to determine the order and the method of the chemical assembly of four chemical fragments. Boehringer Ingelheim has presented four strategies as the chemical process route for dabigatran etexilate in their patents from 1998 to 2012. Since the discovery of ticagrelor in 2007, a number of patents have been published with various improvements made for the preparation of the drug, especially for the large-scale synthesis. The large-scale preparation proceeds via a convergent strategy involving the coupling of three key intermediates.