Design and synthesis of orally-active and selective azaindane 5HT2c agonist for the treatment of obesity

Based on our original pyrazine hit, CP-0809101, novel conformationally-restricted 5HT2c receptor agonists with 2-piperazin-azaindane scaffold were designed. Synthesis and structure–activity relationship (SAR) studies are described with emphasis on optimization of the selectivity against 5HT2a and 5HT2b receptors with excellent 2c potency. Orally-active and selective compounds were identified with dose–responsive in vivo efficacy in our pre-clinical food intake model.

Graphical abstractA series of novel conformationally-restricted 5HT2c receptor agonists with 2-piperazin-azaindane scaffold were designed. Orally-active compounds were identified with excellent functional selectivity against 5HT2a and 5HT2b receptors and with excellent 2c potency.Figure optionsDownload full-size imageDownload as PowerPoint slide