Factor IXa is a plasma serine protease involved in the regulation of blood coagulation. While blood coagulation is a necessary and important part of the regulation of an organism's homeostasis, abnormal blood coagulation can also have deleterious effects. For instance, thrombosis is the formation or presence of a blood clot inside a blood vessel or cavity of the heart. Such a blood clot can lodge in a blood vessel blocking circulation and inducing a heart attack or stroke. Thromboembolic disorders are the largest cause of mortality and disability in the industrialized world.
Blood coagulation involves three distinct phases: initiation, priming and propagation.1,2,3 Initiation involves binding of tissue factor (TF) to activated factor VII, a circulating coagulation factor. Blood, in general is not exposed to TF which is a transmembrane protein expressed on extravascular cells. Vascular injury causes the TF-bearing cells to be exposed to blood, and initiates the coagulation process.1
The TF/VIIa complex activates factors IX and X.1,4 Factor IXa is relatively unstable in plasma and diffuses toward activated platelets. Factor Xa on the other hand, is unstable in plasma and is rapidly inhibited by TF pathway inhibitor and antithrombin III.1,5,6 Factor Xa binds factor Va on the surface of TF-bearing cells.1.7 In turn, the Xa/Va complex generates a small but sufficient amount of thrombin to cause platelet activation.1,8,9 
Thrombin activates platelets and coagulation factors in the priming phase.1,2 Thrombin binds and cleaves platelet protease-activated receptors (PAR1 and PAR4), triggering a signaling cascade that catalyzes platelet activation and release of factor V from platelet α granules. Thrombin also activates factors V, VIII, and XI.1 
It is during the propagation phase that thrombin generation is maximized on the surface of platelets. The primed, activated platelets bind the IXa/VIIIa “tenase” complex. Additional IXa is generated by factor XIa on the platelet surface.10 The IXa/VIIIa complex, in physical proximity to Va, recruits factor X to the platelet surface for activation. The Xa/Va complex on the platelet surface is protected from TF pathway inhibitor and antithrombin III.11,12 
Enzymology studies have shown that activation of factor X by IXa/VIIIa is nearly 50× more efficient than activation by factor VIIa/TF.13 The platelet Xa/Va complex generates a “burst” of thrombin, resulting in a stable fibrin-platelet clot.1 
The cell-based model of coagulation highlights the importance of the IXa/VIIIa complex in clot formation. Factor IXa therefore represents an excellent target for anticoagulant therapy.1 There is a need for effective inhibitors of factor IXa in order to treat or prevent thromboembolic disorders.
Vijaykumar et al., Biorganic & Medicinal Chemistry Letters (2006), 16 (10), 2796-2799, discloses hydroxy pyrazole based factor IXa inhibitors.