A review.The C-1 carboxylic acid has been considered as an essential pharmacophoric group for ligand binding to the FP-receptor.Replacement of the C-1 carboxylic acids with a variety of uncharged C-1 substituents was studied.A diverse series of neutrally charged C1-analogs was synthesized and it was determined that this replacement provided compounds that do not bind to the classical FP-receptor or any other known prostanoid receptors.Two compounds, AGN-190910 (PGF2Fa 1-OH) and AGN-191129, exhibited interesting pharmacol.Unlike 17-Ph PGF2Fa, AGN-191129 potently lowered intraocular pressure (IOP) in rabbits.This result coupled with the lack of affinity of AGN-191129 for any recombinant PG receptors suggests that the effect of rabbit IOP cannot be predicted by activity at the FP receptor.The unique pharmacol. of AGN-191129 is apparent in both in vitro and in vivo biol. systems.