11 -fluoro 15 -hydroxy PGF2 analogs as FP receptor antagonists

The FP prostaglandin receptor belongs to a family of prostaglandin receptors, all of which have seven-transmembrane domains and couple to specific G-proteins. When activated by the binding of a specific ligand (a prostaglandin belonging to one of several defined classes of prostaglandins) the G-proteins transmit and amplify within the cell a signal to their preferred prostaglandin receptors on the surface of the cell membrane. (Coleman et al., 46:205-229 (94)). Ligand-induced activation of the FP prostaglandin receptor is believed to involve activation of the enzyme phospholipase C (mediated by specific G-proteins), resulting in rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate in the cell membrane. The products of this hydrolysis are inositol 1,4,5-trisphosphate (IP ) and diacylglycerol (DAG), which act as second messengers inside the cell. (Coleman et al., 46:205-229 (1994); Berridge, 361:315-325 (1993); Davis et al., 4,5- (USA) 84:3728-3732 (1987); Nakao et al., 3 3 155:257-264 (1993); and Griffin et al., 3 3 281: 845-854 (1997)). IP mobilizes Ca++ from intracellular stores and DAG activates protein kinase C. Together these second messengers activate various enzymes and other proteins to produce the final biological responses. The latter may involve tissue contraction, hormone release, fluid secretion, or initiation of an inflammatory response. Methods and compositions for the antagonism of FP receptor-mediated biological responses are disclosed.