The Discovery of Vorapaxar (SCH 530348), a Thrombin Receptor (Protease Activated Receptor-1) Antagonist with Potent Antiplatelet Effects - Accounts in Drug Discovery Case Studies in Medicinal Chemistry - page 29

Table 2.2 Major marketed antiplatelet agents and candidates in advanced
stage of development.
Generic name or code
name Brand name Formulation Status

Cyclooxygenase inhibitor
Acetylsalicylic acid Aspirin Oral launched

ADP antagonists
Ticlopidine Ticlid Oral launched

Clopidogrel Plavix Oral launched

Prasugrel Eent Oral launched

Ticagrelor (AZD6140) Brilinta Oral P-III

Glycoprotein IIb/IIIa antagonists
Abciximab Reopro iv launched

Eptifibatide Integrilin Iv launched

Tirofiban Aggrastat iv launched

Thrombin receptor (PAR-1) antagonists
Vorapaxar (SCH 530348) Oral P-III

E5555 Oral P-II

Phosphodiesterase-III Inhibitors
Cilostazol

Pletal Oral launched

Adenosine Reuptake Inhibitors
Dipyridamole Persantine, Oral launched

Aggrenox (in combina-
tion with aspirin)

Oral launched

2.3 Antiplatelet Agents
Antiplatelet agents have been the mainstay of treatment for ACS over the past
40 years, and exhibit well-established benefits in preventing coronary throm-
bosis and myocardial infarction in patients with ACS. Results of a meta-ana-
lysis of 145 clinical studies reported a 25% reduction of cardiovascular events
in high-risk patients treated with antiplatelet therapy. 33 Another meta-analysis
of 109 clinical trials has concluded that antiplatelet medications were able to
reduce transient ischemic attacks and strokes by 22%, reduce coronary artery
disease by 29%, and reduce peripheral artery disease by 23%. 34 Table 2.2
summarizes the major antiplatelet agents available commercially and promising
compounds in late stage development.

2.4 Thrombin Receptor (Protease-activated Receptor-
1) Antagonists as Promising Antiplatelet Agents
with Improved Safety Margin
As mentioned before, thrombin plays a dual procoagulant and proaggregatory
role in the context of hemostasis (see Figure 2.1). The platelet activation of
thrombin is mediated by specific cell-surface receptors known as protease-activated