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

  • Bioorg Med Chem Lett. 2008 Jul 15;18(14):3844-7. doi: 10.1016/j.bmcl.2008.06.064.
Chul Min Park  1 ,  So Young Kim ,  Woo Kyu Park ,  No Sang Park ,  Churl Min Seong
Affiliations
  • 1. Center for Medicinal Chemistry, Drug Discovery Division, Korea Research Institute of Chemical Technology, 100 Chang-dong, Yuseong-gu, Daejeon 305-606, South Korea.
PMID: 18602261 DOI: 10.1016/j.bmcl.2008.06.064
Abstract

A novel series of 1H-indole-3-carboxylic acid pyridine-3-ylamides were synthesized and identified to show high affinity and selectivity for 5-HT(2C) receptor. Among them, 1H-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.