title: 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.affiliation: Alcon Research, Ltd, Pharmaceutical Products Research, 6201 South Freeway, MS R2-39 Fort Worth, TX 76134, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Selliah
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hellberg
authors.forename: Najam A
authors.initials: NA
authors.lastname: Sharif
authors.forename: Marsha A
authors.initials: MA
authors.lastname: McLaughlin
authors.forename: Gary W
authors.initials: GW
authors.lastname: Williams
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Scott
authors.forename: David
authors.initials: D
authors.lastname: Earnest
authors.forename: Karen S
authors.initials: KS
authors.lastname: Haggard
authors.forename: W Dennis
authors.initials: WD
authors.lastname: Dean
authors.forename: Pete
authors.initials: P
authors.lastname: Delgado
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gaines
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Conrow
authors.forename: Peter G
authors.initials: PG
authors.lastname: Klimko
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002415:Cats; D000882:Haplorhini; D015814:Ocular Hypotension / Q000188:drug therapy*; D011453:Prostaglandins / Q000008:administration & dosage* / Q000737:chemistry*; D011817:Rabbits
chemical_list: D011453:Prostaglandins