Discovery of N1-(6-chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl)tryptamine as a potent, selective, and orally active 5-HT(6) receptor agonist

  • J Med Chem. 2007 Nov 15;50(23):5535-8. doi: 10.1021/jm070521y.
Derek C Cole  1 ,  Joseph R Stock ,  William J Lennox ,  Ronald C Bernotas ,  John W Ellingboe ,  Steve Boikess ,  Joseph Coupet ,  Deborah L Smith ,  Louis Leung ,  Guo-Ming Zhang ,  Xidong Feng ,  Michael F Kelly ,  Rocco Galante ,  Pingzhong Huang ,  Lee A Dawson ,  Karen Marquis ,  Sharon Rosenzweig-Lipson ,  Chad E Beyer ,  Lee E Schechter
Affiliations
  • 1. Chemical and Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, New York 10965, USA. [email protected]
PMID: 17948978 DOI: 10.1021/jm070521y
Abstract

N1-Arylsulfonyltryptamines have been identified as 5-HT6 receptor ligands. In particular, N1-(6-chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl)tryptamine (11q) is a high affinity, potent full agonist (5-HT6 Ki = 2 nM, EC50 = 6.5 nM, Emax = 95.5%). Compound 11q is selective in a panel of over 40 receptors and ion channels, has good pharmacokinetic profile, has been shown to increase GABA levels in the rat frontal cortex, and is active in the schedule-induced polydipsia model for obsessive compulsive disorders.