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

Chul Min Park; So Young Kim; Woo Kyu Park; No Sang Park; Churl Min Seong

doi:10.1016/j.bmcl.2008.06.064

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. Epub 2008 Jun 21.

Authors

Chul Min Park¹, So Young Kim, Woo Kyu Park, No Sang Park, Churl Min Seong

Affiliation

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.

MeSH terms

Amines / chemical synthesis*
Amines / chemistry
Animals
CHO Cells
Carboxylic Acids / chemistry
Chemistry, Pharmaceutical / methods
Cricetinae
Cricetulus
Drug Design
Humans
Indoles / chemical synthesis*
Indoles / pharmacology
Inhibitory Concentration 50
Models, Chemical
Pyridines / chemical synthesis*
Pyridines / pharmacology
Receptor, Serotonin, 5-HT2C / metabolism
Serotonin 5-HT2 Receptor Antagonists*
Structure-Activity Relationship
Sulfonamides / chemistry
Technology, Pharmaceutical / methods

Substances

1H-indole-3-carboxylic acid pyridine-3-ylamide
Amines
Carboxylic Acids
Indoles
Pyridines
Receptor, Serotonin, 5-HT2C
Serotonin 5-HT2 Receptor Antagonists
Sulfonamides