Ticagrelor

Base Information

• Chemical Name: Ticagrelor
• CAS No.: 274693-27-5
• Molecular Formula: C23H28F2N6O4S
• Molecular Weight: 522.576
• Hs Code.: 29335990
• European Community (EC) Number: 619-540-9
• UNII: GLH0314RVC
• DSSTox Substance ID: DTXSID901009337
• Nikkaji Number: J1.905.358J
• Wikipedia: Ticagrelor
• Wikidata: Q420542
• NCI Thesaurus Code: C76404
• RXCUI: 1116632
• Pharos Ligand ID: 2AXUW7HYJT92
• Metabolomics Workbench ID: 43727
• ChEMBL ID: CHEMBL398435
• Mol file: 274693-27-5.mol

Synonyms:3-(7-((2-(3,4-difluorophenyl)cyclopropyl)amino)-5-(propylthio)-3H-(1-3)-triazolo(4,5-d)pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol;AZD 6140;AZD-6140;AZD6140;Brilinta;Brilique;Ticagrelor

Chemical Property of Ticagrelor

Chemical Property:

• Appearance/Colour: white powder
• Refractive Index: 1.744
• Boiling Point: 777.551 °C at 760 mmHg
• PKA: 13.26±0.70(Predicted)
• Flash Point: 424.048 °C
• PSA: 163.74000
• Density: 1.676 g/cm³
• LogP: 2.08670
• Storage Temp.: Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
• Solubility.: Methanol (Slightly)
• XLogP3: 2
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 12
• Rotatable Bond Count: 10
• Exact Mass: 522.18608089
• Heavy Atom Count: 36
• Complexity: 736

Purity/Quality:

99.0% ^*data from raw suppliers

Ticagrelor ^*data from reagent suppliers

Safty Information:

• Safety Statements: 24/25

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antithrombotic Agents
• Canonical SMILES: CCCSC1=NC(=C2C(=N1)N(N=N2)C3CC(C(C3O)O)OCCO)NC4CC4C5=CC(=C(C=C5)F)F
• Isomeric 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
• Recent ClinicalTrials: Comparison of Anti-coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis
• Recent EU Clinical Trials: Ischemic and bleeding outcomes after angiolite stent implantation and an abbreviated dual antiplatelet therapy. A 2x2 factorial, all-comer, multicenter, randomized controlled trial: Angiodapt.
• Recent NIPH Clinical Trials: A pilot study investigating change of platelet function during interruption of P2Y12 inhibitor
• Description: Ticagrelor is a reversible antagonist of the platelet purinergic P2Y12 receptor (Ki = 14 nM; IC50 = 1.8 μM), which is the main receptor responsible for ADP-induced platelet aggregation. It functions by directly changing the conformation of the P2Y12 receptor to inhibit ADP binding. Formulations containing ticagrelor have been used to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome. In December 2010, the P2Y12 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 P2Y12 receptors. The action of ADP binding to the P2Y12 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 P2Y12 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) .
• Uses: Ticagrelor, the first reversible oral P2Y12 receptor antagonist, provides faster, greater, and more consistent ADP-receptor inhibition than Clopidogrel. Used in the treatment of acute coronary syndromes (ACS) Ticagrelor is the first reversibly binding oral P2Y12 receptor antagonist, also inhibits CYP2C9 and 4-hydroxylation with IC50 of 10.5 μM and 8.2 μM respectively Ticagrelor, the first reversible oral P2Y12 receptor antagonist, provides faster, greater, and more consistent ADP-receptor inhibition than Clopidogrel. Used in the treatment of acute coronary syndromes (ACS).
• 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.
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration possibly increased by clarithromycin - avoid; concentration possibly increased by erythromycin; concentration reduced by rifampicin. Anticoagulants: concentration of dabigatran increased. Antifungals: concentration increased by ketoconazole - avoid. Antivirals: concentration possibly increased by atazanavir and ritonavir - avoid. Cardiac glycosides: concentration of digoxin increased. Ciclosporin: possibly increases ciclosporin concentration. Ergot alkaloids: concentration of ergot alkaloids possibly increased. Lipid-regulating drugs: concentration of simvastatin increased - increased risk of toxicity.

Technology Process of Ticagrelor

There total 288 articles about Ticagrelor which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 97.1%

[3aR-[3aα,4α,6α,(1R,2S),6aα]]-2-[6-[[[7-(2-(3,4-difluorophenyl)cyclopropyl)]amino-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]tetrahydro-2,2-dimethyl-4H-cyclopenteno-1,3-dioxolan-4-yl]oxy]ethanol (274693-26-4) → ticagrelor (274693-27-5,2096989-55-6,2096989-56-7)

Guidance literature:

With hydrogenchloride; In methanol; at -3 - 20 ℃; for 3h; Large scale;

Reference yield: 97.0%

N-((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)-3-((3aS,4R,6S,6aR)-2,2-dimethyl-6-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-5-(propylthio)-3H-[1,2,3]triazol[4,5-d]pyrimidin-7-amine → ticagrelor (274693-27-5,2096989-55-6,2096989-56-7)

Guidance literature:

With hydrogenchloride; In methanol; water; at 0 - 20 ℃; for 4.5h;

Reference yield: 96.0%

(1R,2S)-2-(3,4-difluorophenyl)cyclopropanamine (1006614-49-8,220352-38-5,1459719-81-3) + 9-[(1’R,2’S,3’S,4’S)-2’,3’-dihydroxyl-4'-hydroxyethoxycyclopenta-1'-yl]-9H-2-thiopropyl-6-chloro-8-azepine (1354945-69-9) → ticagrelor (274693-27-5,2096989-55-6,2096989-56-7)

Guidance literature:

With triethylamine; In tetrahydrofuran; at 20 ℃; for 2h;

upstream raw materials:

[3aR-[3aα,4α,6α,(1R,2S),6aα]]-2-[6-[[[7-(2-(3,4-difluorophenyl)cyclopropyl)]amino-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]tetrahydro-2,2-dimethyl-4H-cyclopenteno-1,3-dioxolan-4-yl]oxy]ethanol

4,6-dihydroxy-2-(propylsulfanyl)pyrimidine

4,6-dihydroxy-5-nitro-2-(propylthio)pyrimidine

(1R,2S)-2-(3,4-difluorophenyl)cyclopropanamine

Refernces

• 1、 -. "Production process of ticagrelor fine product". Paragraph 0020; 0025-0026; 0027; 0032-0033; 0034; 0039-0040. . Retrieved 2020/12/09.
• 2、 -. "Method for preparing ticagrelor". . . Retrieved 2020/12/09.