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

  • Bioorg Med Chem Lett. 2004 Sep 6;14(17):4525-8. doi: 10.1016/j.bmcl.2004.06.037.
Robert D Selliah  1 ,  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
Affiliations
  • 1. Alcon Research, Ltd, Pharmaceutical Products Research, 6201 South Freeway, MS R2-39 Fort Worth, TX 76134, USA.
PMID: 15357985 DOI: 10.1016/j.bmcl.2004.06.037
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.