Prasugrel hydrochloride
[CAS# 389574-19-0]

Identification

• Classification: API >> Circulatory system medication
• Name: Prasugrel hydrochloride
• Synonyms: 2-[2-(Acetyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]-1-cyclopropyl-2-(2-fluorophenyl)ethanone hydrochloride
• Molecular Formula: C₂₀H₂₀FNO₃S.HCl
• Molecular Weight: 409.90
• CAS Registry Number: 389574-19-0
• EC Number: 627-126-4
• SMILES: CC(=O)OC1=CC2=C(S1)CCN(C2)C(C3=CC=CC=C3F)C(=O)C4CC4.Cl

Properties

• Solubility: water:>30 mg/mL, DMSO: >25 mg/mL (Expl.)

Safety Data

• Hazard Symbols: GHS07;GHS08;GHS09 Danger
• Risk Statements: H302-H319-H372-H373-H411
• Safety Statements: P260-P264-P264+P265-P270-P273-P280-P301+P317-P305+P351+P338-P319-P330-P337+P317-P391-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Specific target organ toxicity - repeated exposure	STOT RE	2	H373

Discovery and Applications

Prasugrel hydrochloride is a third-generation thienopyridine antiplatelet agent used to prevent thrombotic cardiovascular events, including myocardial infarction and stroke. Structurally, it is a prodrug that undergoes rapid hepatic biotransformation to its active metabolite, which irreversibly inhibits the P2Y₁₂ receptor on platelets. This receptor antagonism prevents adenosine diphosphate (ADP)-mediated platelet aggregation, reducing the risk of clot formation in patients with acute coronary syndrome or undergoing percutaneous coronary intervention.

The development of prasugrel hydrochloride arose from the need for more consistent and potent platelet inhibition compared to earlier thienopyridines such as clopidogrel. Unlike clopidogrel, which is metabolized via a two-step CYP450-dependent pathway with variable activation among individuals, prasugrel undergoes rapid hydrolysis by esterases followed by a single CYP-mediated oxidation step. This pharmacokinetic profile allows for faster and more predictable generation of the active metabolite, leading to more consistent platelet inhibition across patient populations.

Chemically, prasugrel hydrochloride consists of a thienopyridine core substituted with a cyclopropylcarbonyl group and an acetoxy ester moiety. The hydrochloride form enhances the compound's stability and solubility, facilitating oral formulation. In clinical preparations, it is administered orally, and after absorption, it is converted to its active metabolite within the liver. The irreversible binding to the P2Y₁₂ receptor ensures sustained platelet inhibition for the lifespan of affected platelets, approximately 7–10 days.

In addition to its primary use in cardiovascular medicine, prasugrel hydrochloride has been the subject of studies investigating its pharmacogenomic advantages over clopidogrel. Genetic polymorphisms in CYP2C19, which affect clopidogrel activation, have less impact on prasugrel efficacy, making it a suitable option for patients with reduced or absent CYP2C19 activity. Its predictable pharmacodynamics allow for standardized dosing without the need for routine platelet function monitoring, although patient-specific factors such as body weight, age, and bleeding risk must still be considered.

The synthesis of prasugrel hydrochloride involves stereoselective formation of the chiral thienopyridine derivative, followed by esterification and formation of the hydrochloride salt. Control of stereochemistry is critical, as the active metabolite requires specific stereoconfiguration for optimal P2Y₁₂ receptor binding. The compound’s formulation as a hydrochloride salt improves both the handling during manufacturing and the bioavailability upon oral administration.

Prasugrel hydrochloride is widely used in clinical practice for the prevention of arterial thrombosis, particularly in patients undergoing percutaneous coronary intervention with stent placement. Its consistent and potent platelet inhibition has demonstrated a reduction in major cardiovascular events compared to older thienopyridines, though with a concomitant increase in bleeding risk, necessitating careful patient selection. The compound is also employed in research to study platelet function, thrombotic mechanisms, and the development of novel antiplatelet therapies.

Overall, prasugrel hydrochloride represents a significant advancement in antiplatelet therapy, combining a thienopyridine scaffold with optimized pharmacokinetics and pharmacodynamics. Its role as a prodrug activated to a potent irreversible P2Y₁₂ receptor inhibitor underpins its clinical efficacy and positions it as a key agent in cardiovascular disease management.