AL-12182, a novel 11-oxa prostaglandin analog with topical ocular hypotensive activity in the monkey.
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.
Selliah
Robert D
RD
Alcon Research, Ltd, Pharmaceutical Products Research, 6201 South Freeway, MS R2-39 Fort Worth, TX 76134, USA.
Hellberg
Mark R
MR
Sharif
Najam A
NA
McLaughlin
Marsha A
MA
Williams
Gary W
GW
Scott
Daniel A
DA
Earnest
David
D
Haggard
Karen S
KS
Dean
W Dennis
WD
Delgado
Pete
P
Gaines
Michael S
MS
Conrow
Raymond E
RE
Klimko
Peter G
PG
D000287:Administration, Topical; D000818:Animals; D002415:Cats; D000882:Haplorhini; D015814:Ocular Hypotension / Q000188:drug therapy*; D011453:Prostaglandins / Q000008:administration & dosage* / Q000737:chemistry*; D011817:Rabbits
D011453:Prostaglandins