7-Sulfonamido-3-benzazepines as potent and selective 5-HT2C receptor agonists: hit-to-lead optimization.
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.
Fish
Paul V
PV
Discovery Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent CT13 9NJ, UK.
Brown
Alan D
AD
Evrard
Edel
E
Roberts
Lee R
LR
D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D041701:Swiss 3T3 Cells
D001552:Benzazepines; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D013449:Sulfonamides