Satigrel (previously known as E5510) was developed as an antithrombotic agent. Satigrel antagonized platelet activation by inhibiting phospholipase C and/or A2, which results in suppression of both phosphatidylinositol breakdown and arachidonic acid release from phospholipids, as well as by inhibiting cyclooxygenase. Satigrel was studied in patients with intermittent claudication due to arteriosclerosis obliterans, where the drug improved the cutaneous circulation and symptoms of patients. In addition, the therapeutic effect of satigrel was studied on biopsy-proven chronic rejection after kidney transplantation. Also was shown that the drug had a clinical benefit over aspirin for the treatment of transient ischemic attacks. However, all these studied were apparently discontinued.

Clocoumarol is a synthetic antagonist of vitamin K, developed in the 1970s. Clocoumarol exhibits strong anticoagulant properties in rat and rabbit.

Tucaresol, a substituted benzaldehyde, was being developed by Glaxo Wellcome for the prevention of sickle cell disease. Tucaresol was designed to interact with haemoglobin to increase oxygen affinity and has been shown to inhibit sickling in vitro. Tucaresol is also a low-molecular-weight compound that enhances co-stimulatory signaling to CD4 cells. Immune induction is dependent on transient covalent bonding (Schiff base formation) between carbonyls and amines expressed on antigen presenting cell (APC) and T-cell surfaces. Tucaresol substitutes for the natural donor of carbonyl groups to mimic the transient bonding that is essential for T-cell activation. In preliminary studies, tucaresol has been shown to stimulate HIV-specific cytotoxic T lymphocyte responses and generation of naive T cells via thymopoiesis in patients receiving ART who have suppressed viremia. Tucaresol appears to specifically increase type 1 cytokine production. Tucaresol has been used in trials studying the treatment of HIV infections. However, the development of tucaresol for HIV, Hepatitis B and sickle cell diseas treatment has been discontinued.

Nafazatrom [BAY G 6575] is a leukotriene synthesis inhibitor that was being developed by Bayer in Germany. It is a pyrazolinone derivative with potential antimetastatic activities. Nafazatrom, originally developed as an antithrombotic agent, inhibits the key prostaglandin catabolic enzyme, 15-hydroxyprostaglandin dehydrogenase, which prolongs the biological half-life of prostacyclin (prostaglandin I2; PGI2) and prevents intravascular coagulation. Nafazatrom, in the micromolar range, inhibits the metabolism of PGs (prostaglandins) by 15-OH PGDH in a dose-dependent manner. The IC50 for inhibition of 15-OH PGDH was estimated to be 18.5 uM when [3H]PGF2 alpha was used as substrate. This agent also serves as a reducing cofactor with the hydroperoxidase moiety of cyclooxygenase and accelerates the conversion of arachidonic acid into precursors of PGI2. An elevated level of PGI2 prevents aggregation of platelets; subsequently it decreases the formation of tumor cell-platelet aggregates as well as their sequestration in blood vessels, which is an important initiating step in the development of metastasis. Nafazatrom may have had potential as an antithrombotic, anti-ischaemic and antiasthmatic agent. However, the development of nafazatrom was discontinued.

Pamicogrel is a cyclooxygenase inhibitor with platelet anti-aggregatory properties which is under development by Kanebo for chronic arterial occlusion. It also has potential in both prophylaxis and treatment of ischemic brain injury. An NDA was submitted in Japan in April 1997. The effects of the drug on platelet aggregation were originally disclosed in EP-00159677, while the later European patent, EP-00560136, claims its use in brain dysfunction induced by hypoxia arising from disturbance of cerebral circulation, such as cerebral hemorrhage or cerebral infarction.

Hydrobentizide is a diuretic.

PAI-749 is a small molecule inhibitor of PAI-1 with proven antithrombotic efficacy in several preclinical models. PAI-1 inactivation by PAI-749 using purified components can result from a dual mechanism of action. First, PAI-749 binds directly to PAI-1, blocks PAI-1 from accessing the active site of tPA, and abrogates formation of the SDS-stable tPA/PAI-1 complex. Second, binding of PAI-749 to PAI-1 renders PAI-1 vulnerable to plasmin-mediated proteolytic degradation. Despite its efficacy in a purified human system and in preclinical models of thrombosis, the ex vivo clinical study suggests that PAI-749 does not affect thrombus formation or fibrinolysis in a range of established human plasma and whole blood-based systems.

Dacopafant (R-enantiomer RP 55778, racemate RP 48740) is an antagonist fo a platelet-activating factor and an inhibitor of TNH-alpha synthesis. It was developed by Rhone-Poulenc Rorer (France, now Aventis). In vitro, treatment of HIV-1 infected monocyte-derived macrophages with dacopafant resulted in a significant decrease in TNF-alpha levels and viral production. RP 48740 inhibited [3H]PAF platelet binding with IC50 of 2.3 uM and antagonized PAF-induced platelet activation with IC50 of 16 uM. In a clinical trial on human volunteers, RP 48740 was well tolerated and inhibited ex vivo platelet aggregation by as much as 79% 6 hr after administration.

Sumetizide is a sulfonamide derivative belonging to the class of the thiazide diuretics with anti-hypertensive activity. Sumetizide was patented by Richard Hurmer and Jean Vernin but never marketed.

Terbogrel, an agent having two pharmacodynamic actions, namely inhibition of thromboxane A2 synthase and antagonism of the thromboxane A2 receptor. The antithrombotic effect of terbogrel was dose-dependent and was associated with enhanced prostacyclin production. The drug was studied for the treatment of peripheral vascular disorders, pulmonary hypertension, and thrombosis. Terbogrel participated in phase II clinical trial to investigate its safety and efficacy in patients with primary pulmonary hypertension, however, this study was discontinued due to terbogrel’s induction of leg pain.