5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4H,5H,6H,7H-thieno[3,2-c]pyridin-2-yl acetate

• ChemBase ID: 4421
• Molecular Formular: C20H20FNO3S
• Molecular Mass: 373.4411032
• Monoisotopic Mass: 373.11479273
• SMILES: CC(=O)Oc1cc2c(CCN(C2)C(C(=O)C2CC2)c2ccccc2F)s1
• Canonical SMILES: CC(=O)Oc1sc2c(c1)CN(CC2)C(c1ccccc1F)C(=O)C1CC1
• InChI: InChI=1S/C20H20FNO3S/c1-12(23)25-18-10-14-11-22(9-8-17(14)26-18)19(20(24)13-6-7-13)15-4-2-3-5-16(15)21/h2-5,10,13,19H,6-9,11H2,1H3
• InChIKey: DTGLZDAWLRGWQN-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4H,5H,6H,7H-thieno[3,2-c]pyridin-2-yl acetate
• IUPAC Traditional name: prasugrel
• Brand Name: Effient; Efient; Prasita
• Synonyms: CS-747; Prasugrel; Effient; Efient; Prasita; Prasugrel(Effient)

Database IDs

• CAS Number: 150322-43-3
• PubChem SID: 160967853; 99443238
• PubChem CID: 6918456

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.248824
• H Acceptors: 3
• H Donor: 0
• LogD (pH = 5.5): 4.0139766
• LogD (pH = 7.4): 4.3019633
• Log P: 4.3072057
• Molar Refractivity: 96.8121 cm^3
• Polarizability: 37.506584 Å^3
• Polar Surface Area: 46.61 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.67
• LOG S: -5.2
• Solubility (Water): 2.37e-03 g/l

PROPERTIES

Safety Information

• Storage Condition: -20°C

Product Information

• Salt Data: Free Base

DETAILS

DrugBank - DB06209

• Drug Groups: approved; investigational
• Description: Prasugrel, a thienopyridine derivative, is a platelet activation and aggregation inhibitor structurally and pharmacologically related to clopidogrel and ticlopidine. Similar to clopidogrel, prasugrel is a prodrug that requires enzymatic transformation in the liver to its active metabolite, R-138727. R-138727 irreversibly binds to P2Y12 type ADP receptors on platelets thereby inhibiting ADP-mediated platelet activation and aggregation. Prasugrel inhibits ADP-mediated platelet aggregation more rapidly, more consistently and to a greater extent (at least 30%) than clopidogrel. The increased potency of prasugrel appears to be due to more efficient conversion to its active metabolite. The relationship, however, between increased platelet aggregation and clinical response has not been determined. Prasugrel carries a higher risk of bleed compared to clopidogrel, which may be a result of its higher potency. Prasugrel was developed by Daiichi Sankyo Co. and is currently marketed in the United States and Canada in cooperation with Eli Lilly and Company for acute coronary syndromes planned for percutaneous coronary intervention (PCI).
• Indication: Indicated in combination with acetylsalicylic acid (ASA) to prevent atherothrombotic events in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI). May be used in patients with unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI) who are to be managed with PCI. Prasugrel is not recommended in patients 75 years of age or greater due to increased risk of fatal and intracranial bleeding.
• Pharmacology: Prasugrel is a member of the thienopyridine class of ADP receptor inhibitors, like ticlopidine (trade name Ticlid) and clopidogrel (trade name Plavix). These agents reduce the aggregation ("clumping") of platelets by irreversibly binding to P2Y12 receptors. Compared to clopidogrel, prasugrel inhibits adenosine diphosphate–induced platelet aggregation more rapidly, more consistently, and to a greater extent than do standard and higher doses of clopidogrel in healthy volunteers and in patients with coronary artery disease, including those undergoing PCI.
• Toxicity: LD50 (rat) 1,000 - 2,000 mg/kg; LD50 (rabbit) > 1,000 mg/kg
• Affected Organisms: Humans and other mammals
• Biotransformation: Prasugrel is not detected in plasma following oral administration. It is rapidly hydrolyzed in the intestine to thiolactone, which is further metabolized to its active metabolite in a single step by cytochrome P450 enzymes in the liver (primarily CYP3A4 and CYP2B6 and to a lesser extent by CYP2C9 and CYP2C19). The active metabolite is further metabolized by S-methylation or cysteine conjugation to two inactive metabolites.; ; Unlike clopidogrel, transformation of prasugrel to its active metabolite does not appear to be affected by cytochrome P450 polymorphisms.
• Absorption: 79% or greater of the dose is absorbed after oral administration. Absorption and metabolism occur rapidly and peak plasma concentrations (C_max) are reached approximately 30 minutes following oral administration. Administration with a high fat, high calorie meal did not affect the AUC of the active metabolite in healthy individuals, but the C_max was decreased by ~49% and the T_max was increased to 0.5 to 1.5 hours. Prasugrel may be administered with or without food.
• Half Life: The active metabolite has an elimination half-life of about 7.4 hours (range 2-15 hours).
• Protein Binding: Approximately 98% of the active metabolite was bound to human serum albumin in a 4% buffered solution.
• Elimination: Approximately 68% of the orally administered dose is excreted in urine and 27% in the feces, as inactive metabolites. The active metabolite is not expected to be removed by dialysis.
• References: Dovlatova NL, Jakubowski JA, Sugidachi A, Heptinstall S: The reversible P2Y(12) antagonist cangrelor influences the ability of the active metabolites of clopidogrel and prasugrel to produce irreversible inhibition of platelet function. J Thromb Haemost. 2008 May 15;. [Pubmed] ; Tagarakis GI: Ticagrelor and Prasugrel: Two Novel, Most-Promising Antiplatelet Agents. Recent Pat Cardiovasc Drug Discov. 2010 Sep 27. [Pubmed]
• External Links: Wikipedia

Selleck Chemicals - S1258

Research Area: Acute coronary syndromes
Biological Activity:
Prasugrel is a novel platelet inhibitor used for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome who are to be managed with PCI. [1]Prasugrel reduces the aggregation ("clumping") of platelets by irreversibly binding to P2Y12 receptors. In rat platelets, prasugrel AM inhibited in vitro platelet aggregation induced by ADP (10 μm) with an IC50 value of 1.8 μm. [2]

REFERENCES

• Dovlatova NL, Jakubowski JA, Sugidachi A, Heptinstall S: The reversible P2Y(12) antagonist cangrelor influences the ability of the active metabolites of clopidogrel and prasugrel to produce irreversible inhibition of platelet function. J Thromb Haemost. 2008 May 15;. Pubmed
• Tagarakis GI: Ticagrelor and Prasugrel: Two Novel, Most-Promising Antiplatelet Agents. Recent Pat Cardiovasc Drug Discov. 2010 Sep 27. Pubmed
• http://en.wikipedia.org/wiki/Prasugrel