17-trifluoromethylphenyl-13,14-dihydro trinor Prostaglandin F1α

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.

17-Trifluoromethylphenyl-13,14-dihydro trinor prostaglandin F1α (Compound 8) is a saturated prostaglandin analogue. 17-Trifluoromethylphenyl-13,14-dihydro trinor prostaglandin F1α has good affinity and receptor selectivity for human prostaglandin F receptor (hFP receptor) witn an EC50 of 85 nM[1].

ChEBI: 17-trifluoromethylphenyl-13,14-dihydro trinor Prostaglandin F1alpha is a prostanoid.

1. Woodward, D.F., Krauss, A.H., Chen, J., et al. The pharmacology of bimatoprost (Lumigan) Surv. Ophthalmol. 45(Suppl 4),S337-S345(2001).
2. Stjernschantz, J.W. From PGF_2α-isopropyl ester to latanoprost: A review of the development of xalatan. The proper lecture Invest. Ophthalmol. Vis. Sci. 42(6),1134-1145(2001).
3. Sorbera, L.A., and Castaer, J. Travoprost Drugs Future 25(1),41-45(2000).
4. Resul, B., Stjernschantz, J., No, K., et al. Phenyl-substituted prostaglandins: Potent and selective antiglaucoma agents J. Med. Chem. 36,243-248(1993).
5. deLong, M.A., Amburgey, J., Taylor, C., et al. Synthesis and in vitro evaluation of human FP-receptor selective prostaglandin analogues Bioorg. Med. Chem. Lett. 10,1519-1522(2000).