Synthesis and structure–activity relationship of 1H-indole-3-carboxylic acid pyridine-3-ylamides: A novel series of 5-HT2C receptor antagonists

A novel series of 1H-indole-3-carboxylic acid pyridine-3-ylamides were synthesized and identified to show high affinity and selectivity for 5-HT2C receptor. Among them, 1H-indole-3-carboxylic acid[6-(2-chloro-pyridin-3-yloxy)-pyridin-3-yl]-amide (15k) exhibits the highest affinity (IC50 = 0.5 nM) with an excellent selectivity (>2000 times) over other serotonin (5-HT1A, 5-HT2A, and 5-HT6) and dopamine (D2–D4) receptors.

The synthesis and biological evaluation of a series of 1H-indole-3-carboxylic acid pyridine-3-ylamides 5-HT2C receptor antagonists are described.Figure optionsDownload as PowerPoint slide