Tafluprost

A number of 17-phenyl trinor Prostaglandin F_2α derivatives have been approved for the treatment of glaucoma.^1,2,3,4 Of these, the ones wherein the 13,14-double bond has been hydrogenated retain relatively good potency, but show a significantly reduced incidence of local irritant side effects.⁵ Alternatively, it was recently reported that analogs incorporating a 15-deoxy-15,15-difluoro modification also had a favorable ophthalmic activity profile.⁶ Tafluprost is a 2-series, 16-phenoxy analog of PGF_2α with the 15,15-difluoro substitution. Tafluprost free acid is a very potent FP receptor agonist, with a K_i of 0.4 nM.⁶ The ester prodrug forms of tafluprost are also potent ocular hypotensives in monkeys.

1.Woodward, D.F., Krauss, A.H., Chen, J., et al.The pharmacology of bimatoprost (LumiganTM)Surv. Ophthalmol.45(Suppl 4)S337-S345(2001) 2.Abramovitz, M., Adam, M., Boie, Y., et al.The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogsBiochim. Biophys. Acta1483(2)285-293(2000) 3.Sorbera, L.A., and Casta?er, J.TravoprostDrugs Future25(1)41-45(2000) 4.Maxey, K.M., Johnson, J., and LaBrecque, J.The hydrolysis of bimatoprost in corneal tissue generates a potent prostanoid FP receptor agonistSurv. Ophthalmol.47(Suppl 1)S34-S40(2002) 5.Resul, B., Stjernschantz, J., No, K., et al.Phenyl-substituted prostaglandins: Potent and selective antiglaucoma agentsJ. Med. Chem.36243-248(1993) 6.Nakajima, T., Matsugi, T., Goto, W., et al.New fluoroprostaglandin F2α derivatives with prostanoid FP-receptor agonistic activity as potent ocular-hypotensive agentsBiol. Pharm. Bull.26(12)1691-1695(2003)