10215. Prasugrel

Nomenclature

CAS number: 150322-43-3
2-[2-(Acetyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]-1-cyclopropyl-2-(2-fluorophenyl)ethanone; 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine; 5-[(1RS)-2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate; CS-747.
C20H20FNO3S; mol wt 373.44.
C 64.32%, H 5.40%, F 5.09%, N 3.75%, O 12.85%, S 8.59%.

Description and references

Thienopyridine antiplatelet prodrug. Deacetylated in vivo to an inactive, short-lived thiolactone metabolite; further metabolized by hepatic cytochrome P isoenzymes leading to the open ring, thiol-containing active metabolite, R-138727, which binds irreversibly to platelet P2Y12 adenosine diphosphate (ADP) receptors. Prepn: H. Koike et al., CA 2077695; eidem, US 5288726 (1993, 1994 to Sankyo). LC/MS/MS determn of metabolites in plasma: N. A. Farid et al., Rapid Commun. Mass Spectrom. 21, 169 (2007) DOI PubMed. Stereoselective antagonism in receptor-binding and platelet-aggregation assays: M. Hasegawa et al., Thromb. Haemostasis 94, 593 (2005) DOI. In vivo pharmacology: A. Sugidachi et al., Br. J. Pharmacol. 129, 1439 (2000) DOI PubMed. Clinical comparison with clopidogrel: M. Mariani et al., Expert Rev. Cardiovasc. Ther. 7, 17 (2009) DOI PubMed. Review of chemistry, metabolism, and clinical pharmacology: F. Asai et al., Annu. Rep. Sankyo Res. Lab. 51, 1-44 (1999); of clinical experience and therapeutic potential: U. S. Tantry et al., Expert Opin. Invest. Drugs 15, 1627-1633 (2006) DOI PubMed.

Chemical structure

Properties

White to pale yellow crystalline powder containing masses. mp 121-122°. pKa (25°) 5.40±0.05. Log P (n-octanol/phosphate buffer): 3.7 (pH 7). Practically insol in water; becomes slightly sol with decreasing pH. Soly at 20° (mg/ml): benzene >100; chloroform >100; acetone >100; ethyl acetate 82.5; acetonitrile 67.0; methanol 9.01; ethanol 5.91; n-hexane 0.65. Soly at 20° (μg/ml): aq soln 59.8 (pH 3.57), 14.2 (pH 4.85), 4.01 (pH 6.00), 0.15 (pH 7.12).

Derivative

Hydrochloride.

Nomenclature

CAS number: 389574-19-0
LY-640315; Efient (Lilly).
C20H20FNO3S.HCl; mol wt 409.90.
C 58.60%, H 5.16%, F 4.63%, N 3.42%, O 11.71%, S 7.82%, Cl 8.65%.

Derivative

R-138727.

Nomenclature

CAS number: 204204-73-9
(2Z)-2-[1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-mercapto-3-piperidinylidene] acetic acid.
C18H20FNO3S; mol wt 349.42.
C 61.87%, H 5.77%, F 5.44%, N 4.01%, O 13.74%, S 9.18%.

Description and references

Active metabolite. Mixture of four stereoisomers; (4R,1S)-isomer identified as most active.

Therapeutic Category

Antithrombotic.

Keywords

Antithrombotic