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

Abstract

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.

• Authors: Robert D Selliah, Mark R Hellberg, Najam A Sharif, Marsha A McLaughlin, Gary W Williams, Daniel A Scott, David Earnest, Karen S Haggard, W Dennis Dean, Pete Delgado, Michael S Gaines, Raymond E Conrow, Peter G Klimko
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 14 Issue 17 Pg. 4525-8 (Sep 06 2004) ISSN: 0960-894X [Print] England
• PMID: 15357985 (Publication Type: Journal Article)

Chemical References

• Prostaglandins

Topics

• Administration, Topical
• Animals
• Cats
• Haplorhini
• Ocular Hypotension (drug therapy)
• Prostaglandins (administration & dosage, chemistry)
• Rabbits