Novel benzodifuran analogs as potent 5-HT2A receptor agonists with ocular hypotensive activity

Zixia Feng; Suchismita Mohapatra; Peter G Klimko; Mark R Hellberg; Jesse A May; Curtis Kelly; Gary Williams; Marsha A McLaughlin; Najam A Sharif

doi:10.1016/j.bmcl.2007.03.073

Novel benzodifuran analogs as potent 5-HT2A receptor agonists with ocular hypotensive activity

Bioorg Med Chem Lett. 2007 Jun 1;17(11):2998-3002. doi: 10.1016/j.bmcl.2007.03.073. Epub 2007 Mar 25.

Authors

Zixia Feng¹, Suchismita Mohapatra, Peter G Klimko, Mark R Hellberg, Jesse A May, Curtis Kelly, Gary Williams, Marsha A McLaughlin, Najam A Sharif

Affiliation

¹ Alcon Research, Ltd, Research Chemistry, 6201 South Freeway, Fort Worth, TX 76134, USA.

PMID: 17419053
DOI: 10.1016/j.bmcl.2007.03.073

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%.

MeSH terms

Animals
Antihypertensive Agents / chemical synthesis
Antihypertensive Agents / chemistry*
Antihypertensive Agents / pharmacology*
Benzofurans / chemical synthesis
Benzofurans / chemistry*
Benzofurans / pharmacology*
Macaca fascicularis
Muscle, Smooth, Vascular / cytology
Muscle, Smooth, Vascular / drug effects
Ocular Hypertension*
Rats
Receptor, Serotonin, 5-HT2A / chemistry
Serotonin 5-HT2 Receptor Agonists*
Serotonin Receptor Agonists / chemical synthesis
Serotonin Receptor Agonists / chemistry*
Serotonin Receptor Agonists / pharmacology*
Structure-Activity Relationship

Substances

Antihypertensive Agents
Benzofurans
Receptor, Serotonin, 5-HT2A
Serotonin 5-HT2 Receptor Agonists
Serotonin Receptor Agonists