Novel benzodifuran analogs as potent 5-HT2A receptor agonists with ocular hypotensive activity.
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%.
Feng
Zixia
Z
Alcon Research, Ltd, Research Chemistry, 6201 South Freeway, Fort Worth, TX 76134, USA.
Mohapatra
Suchismita
S
Klimko
Peter G
PG
Hellberg
Mark R
MR
May
Jesse A
JA
Kelly
Curtis
C
Williams
Gary
G
McLaughlin
Marsha A
MA
Sharif
Najam A
NA
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
D000959:Antihypertensive Agents; D001572:Benzofurans; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists