Vorapaxar
Grundinformationen
- CAS
618385-01-6- Standard-SMILES
CCOC(=O)N[C@@H]1CC[C@@H]2[C@@H](C1)C[C@H]1C(=O)O[C@H](C)[C@H]1[C@H]2/C=C/c1ccc(-c2cccc(F)c2)cn1- InChIKey
ZBGXUVOIWDMMJE-QHNZEKIYSA-N- Summenformel
- C29H33FN2O4
- Durchschnittliche Molmasse
- 492,6 g/mol
- Monoisotopische Masse
- 492,2424357
Überblick
Vorapaxar is a carbamate ester that is the ethyl ester of [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethynyl}-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl]carbamic acid. A protease-activated receptor-1 antagonist used (as its sulfate salt) for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease. It has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke and urgent coronary revascularisation. It has a role as a cardiovascular drug, a platelet aggregation inhibitor and a protease-activated receptor-1 antagonist. It is a carbamate ester, a lactone, a member of pyridines, an organofluorine compound and a naphthofuran. It is a conjugate base of a vorapaxar(1+).
Namen und Bezeichner
- Bevorzugter Name
- Vorapaxar
- IUPAC
- ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]carbamate
- Englischer Name
- Vorapaxar
- Summenformel
- C29H33FN2O4
- Molmasse
- 492.58
Namen und Synonyme
Vorapaxar618385-01-6SCH-530348SCH530348ZCE93644N2CHEBI:82702DTXSID201009336ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(1E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethenyl]-1-methyl-3-oxo-dodecahydronaphtho[2,3-c]furan-6-yl]carbamatevorapaxarumethyl N-((1R,3aR,4aR,6R,8aR,9S,9aS)-9-((1E)-2-(5-(3-fluorophenyl)pyridin-2-yl)ethenyl)-1-methyl-3-oxo-dodecahydronaphtho(2,3-c)furan-6-yl)carbamateethyl N-((3R,3aS,4S,4aR,7R,8aR,9aR)-4-((E)-2-(5-(3-fluorophenyl)pyridin-2-yl)ethenyl)-3-methyl-1-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-3H-naphtho(6,7-c)furan-7-yl)carbamateethyl N-[(3R,3aS,4S,4aR,7R,8aR,9aR)-4-[(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethenyl]-3-methyl-1-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-3H-naphtho[6,7-c]furan-7-yl]carbamate
Weitere Namen anzeigen
MK-5348Vorapaxar (SCH 530348)[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(1E)-2-[5-(3-Fluorophenyl)-2-pyridinyl]ethenyl]dodecahydro-1-methyl-3-oxonaphtho[2,3-c]furan-6-yl]-carbamic acid ethyl esterCS-2015
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- 5,3
- Polarare Oberfläche (TPSA)
- 77,5 Ų
- H-Brücken-Donoren
- 1
- H-Brücken-Akzeptoren
- 6
- Frei drehbare Bindungen
- 6
- Schwere Atome
- 36
- Formalladung
- 0
- Komplexität
- 821
Experimentelle und physikochemische Eigenschaften
Drugs
Pharmaceuticals -> Listed in ZINC15
Pharmaceuticals -> Blood and blood forming organs -> Antithrombotic agents
Physikochemische Eigenschaften
- Siedepunkt
- 676 · 676.0±55.0 °C(Predicted)
- Dichte
- 1.24 · 1.24±0.1 g/cm3(Predicted)
- storage temp.
- -20 ° · Store at -20° C
- Löslichkeit
- 24.65 mg/mL · ≥24.65 mg/mL in DMSO; insoluble in H2O; ≥10.64 mg/mL in EtOH with ultrasonic
- Aggregatzustand
- solid
- pka
- 12.49 · 12.49±0.60(Predicted)
- Farbe
- White to off-white
- InChIKey
- ZBGXUVOIWDMMJE-QHNZEKIYSA-N
- SMILES
- C(OCC)(=O)N[C@@H]1CC[C@]2([H])[C@@]([H])(C1)C[C@@]1([H])C(=O)O[C@H](C)[C@@]1([H])[C@H]2/C=C/C1=NC=C(C2=CC=CC(F)=C2)C=C1
Sicherheit und Regulatorisches
GHS-Klassifizierung
GHS Classification
Warning
H371 (66.7%): May cause damage to organs [Warning Specific target organ toxicity, single exposure]
P260, P264, P270, P273, P308+P316, P319, P391, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 3 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Gefahrenhinweise
Hazard Classes and CategoriesSTOT SE 2 (66.7%)
Toxikologische Informationen
Hepatotoxicity
Vorapaxar is associated with a low rate of serum enzyme elevations during therapy that was similar to the rate that occurred with placebo or comparator therapies. In a large controlled trial in over 10,000 patients monitored over a 2 year period, ALT elevations above 5 times the upper limit of normal occurred in 1% of vorapaxar vs 1.4% of placebo patients. In pooled analyses of laboratory studies from more than 39,000 patients receiving vorapaxar or placebo, GGT was the only liver test that was abnormal in a higher proportion of patients receiving vorapaxar (3.8%) than placebo (3.3%), and there were no reports of liver related serious adverse events or clinically apparent liver injury. Thus, liver injury from vorapaxar must be rare, if it occurs at all.
Sicherheitsdaten
- wgk
- WGK 3
- Speicherklasse
- 11 - Combustible Solids
- Hazard Classifications
- Aquatic Acute 1Aquatic Chronic 1
Chemie und Industrie
Pharmakologische Informationen
ATC Code
B - Blood and blood forming organs
QB - Blood and blood forming organs
Protein BindingVorapaxar is extensively bound (>99%) to human plasma proteins, such as human serum albumin.
Mechanism of Action
Vorapaxar inhibits platelet aggregation through the reversible antagonism of protease-activated receptor 1 (PAR-1), also known as thrombin receptor. PARs are a family of G-protein coupled receptors highly expressed on platelets and activated by serine protease activity of thrombin to mediate thrombotic response. By blocking PAR-1 activating, vorapaxar inhibits thrombin-induced platelet aggregation and thrombin receptor agonist peptide (TRAP)-induced platelet aggregation. Vorapaxar does not inhibit platelet aggregation induced by other agonists such as adenosine diphosphate (ADP), collagen or a thromboxane mimetic.
Biological Half-LifeVorapaxar has an effective half life of 3-4 days and an apparent terminal half life of 8 days.
Metabolism/MetabolitesVorapaxar is metabolized to its major circulating metabolite, M20, and its predominant metabolite excreted into feces, M19, by CYP3A4 and CYP 2J2.
FDA Pharmacological Classification
ZCE93644N2
VORAPAXAR
Established Pharmacologic Class [EPC] - Protease-activated Receptor-1 Antagonist
Mechanisms of Action [MoA] - Protease-activated Receptor-1 Antagonists
Vorapaxar is a Protease-activated Receptor-1 Antagonist. The mechanism of action of vorapaxar is as a Protease-activated Receptor-1 Antagonist.
MeSH Pharmacological Classification
Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.
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