Cycloalkyl[b][1,4]benzodiazepinoindoles are agonists at the human 5-HT2C receptor

Abstract 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%).