AL-12182, a novel 11-oxa prostaglandin analog with topical ocular hypotensive activity in the monkey

Graphic A series of 11-oxa prostaglandin analogs was evaluated for FP receptor binding and activation. Several compounds having aryloxy-terminated lower chains were found to be potent agonists. Topical ocular dosing of AL- 12182, the isopropyl ester prodrug of the potent agonist 13, lowered intraocular pressure in the monkey by 40% accompanied by minimal conjunctival hyperemia in the rabbit. AL- 12182 was synthesized on multigram scale starting with d-sorbitol.