DERIVATIVES OF 17-PHENYL-18,19,20-TRINORPROSTAGLANDIN F2-ALPHA ISOPROPYL ESTER - POTENTIAL ANTIGLAUCOMA AGENTS

The 15R and 15S epimers of a series of phenyl substituted analogs of 1 7-phenyl-18,19,20-trinorprostaglandin F-2 alpha isopropyl ester [(15S) -3] have been synthesized. The intraocular pressure (IOP) lowering eff ects and potential side effects of these novel derivatives have been s tudied in cats and rabbits. In addition, the effects of selected analo gues on IOP have been studied in monkeys. Furthermore, we have hydroly zed some of the isopropyl esters and assessed the ability of the resul ting carboxylic acids to contract the cat iris sphincter muscle in vit ro. In general, the 15S-derivatives were more active than the 15R-epim ers. Derivatives substituted with an acetyl group in the benzene ring appeared to have a better side effect profile as compared to(15S)-3. F urthermore, substitution with an aromatic moiety had a dramatic effect on the activity in that the resulting compounds reduced IOP in cats b ut had little effect on the pupil diameter. Thus, the activity profile of (15S)-3 may be changed by the introduction of substituents in the benzene ring.