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

Bioorg Med Chem Lett. 2004 May 17;14(10):2603-7. doi: 10.1016/j.bmcl.2004.02.100.

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%).

MeSH terms

  • Animals
  • Benzodiazepines / chemical synthesis
  • Benzodiazepines / pharmacology
  • Feeding Behavior / drug effects
  • Humans
  • Indoles / chemical synthesis
  • Indoles / pharmacology*
  • Rats
  • Serotonin 5-HT2 Receptor Agonists*
  • Serotonin Receptor Agonists / chemical synthesis*
  • Serotonin Receptor Agonists / pharmacology
  • Structure-Activity Relationship

Substances

  • Indoles
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin Receptor Agonists
  • Benzodiazepines