13,14-dihydro-15(R,S)-hydroxy-16,16-difluoro Prostaglandin E1-d4 (Synonyms: 15hydroxy Lubiprostone)

PGE₁ is produced by the metabolism of dihomo-γ-linolenic acid (DGLA) by the cyclooxygenase pathway. PGE₁ inhibits platelet aggregation (IC₅₀ = 40 nM) and increases vasodilation.^1,213,14-dihydro-16,16-difluoro PGE₁ is a biologically active metabolite of PGE₁, inhibiting platelet aggregation with comparable potency to the parent compound.^3,2 The addition of two electron-withdrawing fluorine atoms, which should stabilize the molecule against hydrolytic cleavage, may be expected to delay degradation in vivo.⁴ 13,14-dihydro-15(R,S)-hydroxy-16,16-difluoro PGE₁-3,3',4,4'-d₄) contains four deuterium atoms at the 3, 3', 4, and 4' positions. It is intended for use as an internal standard for the quantification of 13,14-dihydro-15(R,S)-hydroxy-16,16-difluoro Prostaglandin E₁ by GC- or LC-mass spectrometry (MS).

1.Kobzar, G., Mardla, V., JÄrving, I., et al.Antiaggregating potency of E-type prostaglandins in human and rabbit plateletsProceedings of the Estonian Academy of Sciences.Chemistry40179-180(1991) 2.Westwick, J.The effect of pulmonary metabolites of prostaglandins E1, E2 and F2α on ADP-induced aggregation of human and rabbit plateletsBritish Journal of Pharmacology58297P-298P(1976) 3.Peskar, B.A., Cawello, W., Rogatti, W., et al.On the metabolism of prostaglandin E1 administered intravenously to human volunteersJournal of Physiology and Pharmacology42327-331(1991) 4.Hatano, Y., Kohli, J.D., Goldberg, L.I., et al.Vascular relaxing activity and stability studies of 10,10-difluoro-13,14-dehydroprostacyclinProceedings of the National Academy of Sciences of the United States of America77(11)6846-6850(1980)