Prasugrel
[CAS# 150322-43-3]

Identification

• Classification: API >> Blood system medication >> Anticoagulant and antiplatelet drugs
• Name: Prasugrel
• Synonyms: 2-[2-(Acetyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]-1-cyclopropyl-2-(2-fluorophenyl)ethanone
• Molecular Formula: C₂₀H₂₀FNO₃S
• Molecular Weight: 373.44
• CAS Registry Number: 150322-43-3
• EC Number: 801-962-1
• SMILES: CC(=O)OC1=CC2=C(S1)CCN(C2)C(C3=CC=CC=C3F)C(=O)C4CC4

Properties

• Solubility: DMSO: > 10 mM (Expl.)
• Density: 1.347 g/mL

Safety Data

• Hazard Symbols: GHS07;GHS08;GHS09 Danger
• Risk Statements: H302-H370-H373-H411
• Safety Statements: P260-P264-P270-P273-P301+P317-P308+P316-P319-P321-P330-P391-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Specific target organ toxicity - single exposure	STOT SE	1	H370

Discovery and Applications

Prasugrel is a third-generation thienopyridine antiplatelet agent that functions as a prodrug, requiring metabolic activation to exert its therapeutic effects. It was developed to address limitations associated with earlier thienopyridines, such as clopidogrel, including variability in patient response and delayed onset of action. Prasugrel contains a dihydrothieno[3,2-c]pyridine core and a chiral center at the 5-position, which is critical for its pharmacological activity.

The discovery of prasugrel emerged from medicinal chemistry programs aimed at improving platelet inhibition in patients at risk of thrombotic events, particularly those undergoing percutaneous coronary intervention. Its design focused on generating a more efficient metabolic activation pathway while maintaining selectivity for the platelet P2Y₁₂ receptor. Unlike clopidogrel, prasugrel is hydrolyzed by esterases to an intermediate thiolactone, which is then rapidly oxidized by cytochrome P450 enzymes to the active metabolite. This dual-step activation reduces interindividual variability and results in a more predictable antiplatelet effect.

Prasugrel selectively and irreversibly binds to the P2Y₁₂ receptor on platelets, inhibiting adenosine diphosphate (ADP)-mediated platelet aggregation. This action prevents thrombus formation in patients with acute coronary syndromes and reduces the risk of stent thrombosis after coronary interventions. Clinical studies have demonstrated that prasugrel provides faster, more consistent, and more potent platelet inhibition compared to clopidogrel, making it a preferred choice in certain high-risk patient populations.

The synthesis of prasugrel involves the preparation of the thienopyridine core, followed by the introduction of a chiral center through selective esterification and functionalization of the side chain. The active metabolite contains a thiol group essential for covalent binding to the P2Y₁₂ receptor. The prodrug form, used in oral administration, ensures stability and bioavailability before enzymatic conversion in vivo.

In addition to its primary use as an antiplatelet therapy, prasugrel has contributed to research on the pharmacogenomics of platelet inhibition. Studies comparing prasugrel with clopidogrel have highlighted the impact of genetic polymorphisms in cytochrome P450 enzymes on drug metabolism and efficacy. Prasugrel’s more efficient activation pathway minimizes the influence of such genetic variability, providing clinicians with a more reliable therapeutic profile.

The clinical adoption of prasugrel has significantly influenced treatment guidelines for acute coronary syndromes, emphasizing rapid and potent platelet inhibition in patients undergoing stent placement. Its pharmacological properties, combined with predictable pharmacokinetics, have improved outcomes in interventional cardiology and have provided a valuable tool for preventing adverse thrombotic events.

Beyond its therapeutic application, prasugrel has served as a model compound in drug development, demonstrating the value of prodrug strategies, stereochemistry control, and selective receptor targeting in optimizing pharmacodynamic response. Research continues on developing next-generation antiplatelet agents inspired by the pharmacological principles established by prasugrel, aiming to further improve efficacy and safety in cardiovascular medicine.