Design and synthesis of 13,14-dihydro prostaglandin F-1 alpha analogues aspotent and selective ligands for the human FP receptor

The in vitro evaluation of a new class of potential bone anabolic agents fo r the treatment of osteoporosis is described. These compounds are potent an d selective ligands for the human prostaglandin F receptor (hFP receptor). The compounds lack the olefin unsaturation required for potency in the natu ral ligand PGF(2 alpha) yet retain binding affinity for the hFP receptor in the nanomolar to micromolar range. Removal of the alkenes also results in a better selectivity ratio for the hFP receptor over the other prostaglandi n receptors tested. A rationale for the selectivity differences of various analogues, based on ligand docking experiments to a putative hFP receptor m odel, is also described.