Cycloalkyl[b][1,4]benzodiazepinoindoles are agonists at the human 5-HT2C receptor.
Evaluation of selected compounds from our Corporate Compound Library in a human 5-HT(2C) receptor binding assay led to the discovery of WAY-629, a cyclohexyl[b][1,4]benzodiazepinoindole (K(i) 56 nM, E(max) 90%), which is selective for the 5-HT(2C) receptor versus other serotonin receptor subtypes, and dopamine, histamine, adrenergic, and muscarinic receptors. In addition, WAY-629 was active in vivo in a rat model of feeding behavior. An SAR study based on WAY-629 led to compound 11 (K(i) 13 nM, E(max) 102%).
Sabb
Annmarie L
AL
Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543-8000, USA. sabba@wyeth.com
Vogel
Robert L
RL
Welmaker
Gregory S
GS
Sabalski
Joan E
JE
Coupet
Joseph
J
Dunlop
John
J
Rosenzweig-Lipson
Sharon
S
Harrison
Boyd
B
D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D007211:Indoles; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; D001569:Benzodiazepines