Ticagrelor
[CAS 274693-27-5]

Identification

• Classification: API >> Blood system medication >> Anticoagulant and antiplatelet drugs
• Name: Ticagrelor
• Synonyms: AR-C 126532XX; AZD 6140; (1S,2S,3R,5S)-3-[7-[[(1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-1,2-cyclopentanediol
• Molecular Formula: C₂₃H₂₈F₂N₆O₄S
• Molecular Weight: 522.57
• CAS Registry Number: 274693-27-5
• EC Number: 619-540-9
• SMILES: CCCSC1=NC(=C2C(=N1)N(N=N2)[C@@H]3C[C@@H]([C@H]([C@H]3O)O)OCCO)N[C@@H]4C[C@H]4C5=CC(=C(C=C5)F)F

Properties

• Density: 1.7$+/-$0.1 g/cm³ Calc.^*
• Boiling point: 777.6$+/-$70.0 $degree$C 760 mmHg (Calc.)^*
• Flash point: 424.0$+/-$35.7 $degree$C (Calc.)^*
• Solubility: DMSO 105 mg/m, Water $lessThan$1 mg/ml (Expl.)
• Index of refraction: 1.744 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Specific target organ toxicity - repeated exposure	STOT RE	2	H373

Discovery and Applications

Ticagrelor is an oral antiplatelet drug used to reduce the risk of thrombotic cardiovascular events such as myocardial infarction and stroke. It belongs to the class of P2Y₁₂ receptor antagonists and is used primarily in patients with acute coronary syndromes and in those with a history of coronary artery disease.

The development of ticagrelor was driven by the need for more effective and rapidly acting platelet aggregation inhibitors compared with earlier agents such as clopidogrel. Clopidogrel is a prodrug that requires metabolic activation and exhibits variable patient response due to genetic differences in metabolic enzymes. Ticagrelor was designed as a direct-acting, reversible inhibitor of the platelet P2Y₁₂ receptor, providing more consistent pharmacological effects.

The P2Y₁₂ receptor is an adenosine diphosphate (ADP) receptor located on the surface of platelets. When activated by ADP, it promotes platelet aggregation through activation of the glycoprotein IIb/IIIa complex, which facilitates fibrinogen binding and clot formation. Ticagrelor binds reversibly to the P2Y₁₂ receptor at a site distinct from the ADP binding site, preventing receptor activation and thereby inhibiting platelet aggregation.

Structurally, ticagrelor is not a thienopyridine like clopidogrel and prasugrel, but rather a cyclopentyltriazolopyrimidine derivative. This non-thienopyridine structure allows it to act directly without metabolic activation. Its molecular design was optimized to achieve high affinity for the P2Y₁₂ receptor while maintaining reversibility, which contributes to its relatively rapid onset and offset of action.

Ticagrelor was developed through a medicinal chemistry program aimed at improving antiplatelet therapy outcomes in acute coronary syndromes. Preclinical and clinical studies demonstrated that it provides more potent and consistent platelet inhibition compared with clopidogrel. It also has a faster onset of action due to its direct activity and does not require hepatic bioactivation via CYP2C19, reducing variability in patient response.

In addition to P2Y₁₂ receptor inhibition, ticagrelor has been shown to inhibit equilibrative nucleoside transporter 1 (ENT1), leading to increased extracellular adenosine levels. Adenosine has vasodilatory, anti-inflammatory, and cardioprotective effects, which may contribute to some of ticagrelor’s clinical benefits, although the primary antiplatelet effect is mediated through P2Y₁₂ inhibition.

Clinically, ticagrelor is used in combination with low-dose aspirin as part of dual antiplatelet therapy in patients with acute coronary syndrome and in those undergoing percutaneous coronary intervention. It is also used for secondary prevention of cardiovascular events in selected high-risk patients. Its use is guided by the need to balance antithrombotic efficacy with bleeding risk.

Ticagrelor is administered orally and has relatively rapid absorption. It is metabolized in the liver primarily by CYP3A4 to an active metabolite that contributes to its overall pharmacological effect. Both the parent drug and metabolite are active, and the drug exhibits reversible binding to its target, allowing platelet function to recover within a few days after discontinuation.

Adverse effects of ticagrelor include bleeding, dyspnea, and, in some cases, bradyarrhythmias. The increased bleeding risk is a direct consequence of its antiplatelet activity. Dyspnea is thought to be related in part to adenosine-mediated effects due to ENT1 inhibition.

Overall, ticagrelor is a direct-acting, reversible P2Y₁₂ receptor antagonist developed to improve the consistency and effectiveness of antiplatelet therapy. Its discovery reflects advances in cardiovascular pharmacology aimed at reducing thrombotic risk in patients with coronary artery disease while overcoming limitations of earlier prodrug-based therapies.

References

2026. Early vascular healing after neXt-generation drug-eluting stent implantation in Patients with non-ST elevation acute Coronary syndrome: a randomized optical coherence Tomography imaging study (EXPECT). The International Journal of Cardiovascular Imaging.
DOI: 10.1007/s10554-024-03258-w

2026. CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) in 2026. Cardiovascular Intervention and Therapeutics.
DOI: 10.1007/s12928-026-01247-5

2026. Half-dose ticagrelor versus clopidogrel dual antiplatelet therapy in flow diverter-treated intracranial aneurysms: analysis of platelet reactivity and perioperative safety outcomes. Acta Neurochirurgica.
DOI: 10.1007/s00701-026-06805-7