Discovery of N1-(6-Chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl)tryptamine as a Potent, Selective, and Orally Active 5-HT6 Receptor Agonist

• Published in: Journal of medicinal chemistry Vol. 50; no. 23; pp. 5535 - 5538
• Main Authors: Cole, Derek C, Stock, Joseph R, Lennox, William J, Bernotas, Ronald C, Ellingboe, John W, Boikess, Steve, Coupet, Joseph, Smith, Deborah L, Leung, Louis, Zhang, Guo-Ming, Feng, Xidong, Kelly, Michael F, Galante, Rocco, Huang, Pingzhong, Dawson, Lee A, Marquis, Karen, Rosenzweig-Lipson, Sharon, Beyer, Chad E, Schechter, Lee E
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 15.11.2007
• Subjects: Biological and medical sciences; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Serotoninergic system; Obsessive compulsive disorder; Agonist; Intraperitoneal administration; Tryptamine; Rat; Anxiety disorder; 5-HT6 serotonin receptor; Selectivity; Chlorine Organic compounds; Imidazothiazole derivatives; Dog; Polydipsia; Fissipedia; Carnivora; Stability; Sulfonamide; Rodentia; Oral administration; In vitro; Biological activity; In vivo; Vertebrata; Mammalia; Animal; Biogenic amine; Indole derivatives; Pharmacokinetics; Primary amine
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm070521y

N 1-Arylsulfonyltryptamines have been identified as 5-HT6 receptor ligands. In particular, N 1-(6-chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl)tryptamine (11q) is a high affinity, potent full agonist (5-HT6 K i = 2 nM, EC50 = 6.5 nM, E max = 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.