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

Abstract A novel series of 1 H -indole-3-carboxylic acid pyridine-3-ylamides were synthesized and identified to show high affinity and selectivity for 5-HT 2C receptor. Among them, 1 H -indole-3-carboxylic acid[6-(2-chloro-pyridin-3-yloxy)-pyridin-3-yl]-amide ( 15k ) exhibits the highest affinity (IC 50  = 0.5 nM) with an excellent selectivity (>2000 times) over other serotonin (5-HT 1A , 5-HT 2A , and 5-HT 6 ) and dopamine (D 2 –D 4 ) receptors.