TICAGRELOR Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
In December 2010, the P2Y
12 receptor antagonist ticagrelor (also
known as AZD6140) was approved in Europe for the treatment of acute
coronary syndrome (ACS), a condition that covers several clinical symptoms
with the potential to cause acute myocardial ischemia (MI).
ADP binds to two purinergic receptors, the P2Y1 and P2Y
12 receptors. The
action of ADP binding to the P2Y
12 receptor results in activation of the GP
Ⅱb/Ⅲa (integrin) receptor.GP Ⅱb/Ⅲa initiates and prolongs platelet aggregation,
which in turn results in the cross-linking of platelets through fibrin
and finally thrombus formation. Inhibition of ADP stimulation of the P2Y
12
receptor has been found to be an effective strategy for managing the atherothrombotic
events associated with ACS and potentially resulting from
percutaneous coronary intervention (PCI, stent implantation) .
Chemische Eigenschaften
White Solid
History
Ticagrelor, developed by AstraZeneca, originated from observations of the structure of the endogenous P2Y12 receptor antagonist adenosine triphosphate (ATP), ultimately leading to the synthesis of a non-thienopyridine, reversibly binding P2Y12 receptor antagonist. The chemical discovery of ticagrelor can be traced back to international patent application WO00/34283-A1, while detailed chemical and pharmacological studies of it as an orally active P2Y12 receptor antagonist (initially codenamed AZD6140) were published by B. Springthorpe and his team in 2007. A milestone in its drug development was the PLATO (Platelet Inhibition and Patient Outcomes) clinical trial, led by Lars Wallentin, which recruited over 18,000 patients with acute coronary syndrome (ACS) to compare the efficacy and safety of ticagrelor with clopidogrel. The results of the PLATO trial, published in *The New England Journal of Medicine* on August 30, 2009, confirmed that ticagrelor was superior to clopidogrel in reducing the composite endpoint of cardiovascular death, myocardial infarction, or stroke, without increasing the overall risk of major bleeding. Based on this crucial evidence, ticagrelor (brand name Brilinta/Brilique) received approval from the European Medicines Agency (EMA) in 2010 and from the U.S. Food and Drug Administration (FDA) on July 20, 2011, marking its official entry into clinical use and becoming an important option in the field of dual antiplatelet therapy.
Definition
ChEBI: A triazolopyrimidine that is an adenosine isostere; the cyclopentane ring is similar to ribose and the nitrogen-rich [1,2,3]triazolo[4,5-d]pyrimidine moiety resembles the nucleobase adenine. A platelet aggregation inhibitor which is used for p
evention of thromboembolic events in patients with acute coronary syndrome.
Clinical Use
Ticagrelor, discovered and developed by AstraZeneca, is a platelet
adenosine diphosphate (ADP) P2Y12 (P2T) reversible receptor
antagonist approved in the E.U. in 2010 and launched in Germany
and the UK in 2011 for the treatment of patients with acute coronary
syndromes (ACS). It was approved in the U.S. and Canada in
2011 following successful clinical trial results in patients with
ACS which showed it to be superior to preexisting drugs for reducing death due to vascular causes. Ticagrelor is an oral drug
indicated for use in combination with acetylsalicylic acid (aspirin)
for the prevention of atherothrombotic events in adult patients
with ACS (unstable angina, non-ST elevation myocardial infarction
(NSTEMI), or ST elevation myocardial infarction (STEMI)). Unlike
its competitors prasugrel and clopidogrel, which require bioactivation,
ticagrelor is not a prodrug and does not require in vivo activation.
It has a rapid onset of action, relatively rapid reversibility,
greater potency, and exhibits consistency in platelet inhibition.
Following dosing, ticagrelor reaches Cmax in about 1.5 h, with formation
of a major metabolite with equipotent intrinsic activity to
the parent compound.
TICAGRELOR Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
2-[[(3aS,4R,6S,6aR)-4-[7-[[(1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]-2,2-dimethyl-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]oxy]ethanol
