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.
Cole DC,
Stock JR,
Lennox WJ,
Bernotas RC,
Ellingboe JW,
Boikess S,
Coupet J,
Smith DL,
Leung L,
Zhang GM,
Feng X,
Kelly MF,
Galante R,
Huang P,
Dawson LA,
Marquis K,
Rosenzweig-Lipson S,
Beyer CE,
Schechter LE.
Chemical and Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, New York 10965, USA. coledc@wyeth.com
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.
PMID: 17948978 [PubMed - indexed for MEDLINE]