Tafluprost (free acid)

A number of 17-phenyl trinor PGF2.alpha. derivatives have been approved for the treatment of glaucoma.{8941,8322,8839,9311} 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.{9736} Alternatively, it was recently reported that analogs incorporating a 15-deoxy-15,15-difluoro modification also had a favorable ophthalmic activity profile.{12141} Tafluprost is a 2-series, 16-phenoxy analog of PGF2.alpha. with the 15,15-difluoro substitution. Tafluprost (free acid) is a very potent FP receptor agonist, with a Ki of 0.4 nM.{12141} The ester prodrug forms of tafluprost are also potent ocular hypotensives in monkeys.