17-trifluoromethylphenyl-13,14-dihydro trinor Prostaglandin F1α (Synonyms: 17TFMPGF1α)

A number of 17-aryl trinor and 16-aryloxy tetranor prostaglandin F_2α derivatives have been approved for the treatment of glaucoma.^1,2,3 These "ring" prostaglandin (PG) analogs have improved efficacy over the PGs with an n-alkyl lower side chain. 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.⁴ 17-trifluoromethylphenyl-13,14-dihydro trinor PGF_1α (17-TFM-PGF_1α) is a typical "ring" analog reminiscent of the trifluoromethyl-phenoxy ring of Travoprost. The a chain of 17-TFM-PGF_1α is saturated, making this compound a formal member of the one-series PGs. Recent work has shown that in the "ring" series of analogs, this modification has little impact on FP receptor binding.⁵ As an ocular hypotensive agent, it is expected that 17-TFM-PGF_1α would act very much like the free acid of latanoprost.

1.Woodward, D.F., Krauss, A.H.P., Chen, J., et al.The pharmacology of Bimatoprost (LumiganTM)Survey of Ophthalmology45S337-S345(2001) 2.Stjernschantz, J.W.From PGF2α-isopropyl ester to latanoprost: A review of the development of xalatan. The proper lectureInvestigative Ophthalmology & Visual Science42(6)1134-1145(2001) 3.Sorbera, L.A., and CastaÑer, J.TravoprostDrugs Future25(1)41-45(2000) 4.Resul, B., Stjernschantz, J., No, K., et al.Phenyl-substituted prostaglandins: Potent and selective antiglaucoma agentsJournal of Medicinal Chemistry36243-248(1993) 5.deLong, M.A., Amburgey, J., Taylor, C., et al.Synthesis and in vitro evaluation of human FP-receptor selective prostaglandin analoguesBioorganic & Medicinal Chemistry Letters101519-1522(2000)