title: Novel benzodifuran analogs as potent 5-HT2A receptor agonists with ocular hypotensive activity.
abstract: A series of 8-substituted benzodifuran analogs was prepared and evaluated for 5-HT(2A) receptor binding and activation. Several compounds containing ether and ester functionality were found to be potent agonists. Topical ocular administration of 5, 18, and 25 effectively reduced intra-ocular pressure in the hypertensive cynomolgus monkey eye in the range of 25-37%.
authors.affiliation: Alcon Research, Ltd, Research Chemistry, 6201 South Freeway, Fort Worth, TX 76134, USA.
authors.forename: Zixia
authors.initials: Z
authors.lastname: Feng
authors.forename: Suchismita
authors.initials: S
authors.lastname: Mohapatra
authors.forename: Peter G
authors.initials: PG
authors.lastname: Klimko
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hellberg
authors.forename: Jesse A
authors.initials: JA
authors.lastname: May
authors.forename: Curtis
authors.initials: C
authors.lastname: Kelly
authors.forename: Gary
authors.initials: G
authors.lastname: Williams
authors.forename: Marsha A
authors.initials: MA
authors.lastname: McLaughlin
authors.forename: Najam A
authors.initials: NA
authors.lastname: Sharif
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008252:Macaca fascicularis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D009798:Ocular Hypertension; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000737:chemistry; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000959:Antihypertensive Agents; D001572:Benzofurans; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists