7-Sulfonamido-3-benzazepines as potent and selective 5-HT2C receptor agonists: hit-to-lead optimization

Paul V Fish; Alan D Brown; Edel Evrard; Lee R Roberts

doi:10.1016/j.bmcl.2009.02.071

7-Sulfonamido-3-benzazepines as potent and selective 5-HT2C receptor agonists: hit-to-lead optimization

Bioorg Med Chem Lett. 2009 Apr 1;19(7):1871-5. doi: 10.1016/j.bmcl.2009.02.071. Epub 2009 Feb 21.

Authors

Paul V Fish¹, Alan D Brown, Edel Evrard, Lee R Roberts

Affiliation

¹ Discovery Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent CT13 9NJ, UK.

PMID: 19269173
DOI: 10.1016/j.bmcl.2009.02.071

Abstract

New 7-sulfonamido-3-benzazepines 3 are disclosed as 5-HT(2C) receptor agonists. Appropriate substitution of the amino group (R(1)R(2)N-) gave compounds that were potent 5-HT(2C) agonists with minimal activation of the 5-HT(2A) and 5-HT(2B) receptors. Furthermore, representative examples had excellent in vitro ADME properties and good selectivity over ion channel activity.

MeSH terms

Animals
Benzazepines / chemical synthesis*
Benzazepines / chemistry
Benzazepines / pharmacokinetics*
Humans
Mice
Receptor, Serotonin, 5-HT2C / metabolism
Serotonin 5-HT2 Receptor Agonists*
Structure-Activity Relationship
Sulfonamides / chemical synthesis*
Sulfonamides / chemistry
Sulfonamides / pharmacokinetics*
Swiss 3T3 Cells

Substances

Benzazepines
Receptor, Serotonin, 5-HT2C
Serotonin 5-HT2 Receptor Agonists
Sulfonamides