Bicyclic piperazinylbenzenesulphonamides are potent and selective 5-HT6 receptor antagonists

Steven M Bromidge; Stephen E Clarke; Frank D King; Peter J Lovell; Helen Newman; Graham Riley; Carol Routledge; Halina T Serafinowska; Douglas R Smith; David R Thomas

doi:10.1016/s0960-894x(02)00172-5

Bicyclic piperazinylbenzenesulphonamides are potent and selective 5-HT6 receptor antagonists

Bioorg Med Chem Lett. 2002 May 20;12(10):1357-60. doi: 10.1016/s0960-894x(02)00172-5.

Authors

Steven M Bromidge¹, Stephen E Clarke, Frank D King, Peter J Lovell, Helen Newman, Graham Riley, Carol Routledge, Halina T Serafinowska, Douglas R Smith, David R Thomas

Affiliation

¹ Department of Psychiatry, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, CM19 5AW, Essex, UK.

PMID: 11992776
DOI: 10.1016/s0960-894x(02)00172-5

Abstract

The synthesis of novel 3-(octahydropyrido[1,2-a]pyrazin-2-yl)- and 3-(hexahydropyrrolo[1,2-a]pyrazin-2-yl)phenyl-2-benzo[b]thiophene sulphonamide derivatives 3, (S)-4 and (R)-4 is described. The compounds show high affinity for the 5-HT6 receptor, excellent selectivity against a range of other receptors and good brain penetration.

MeSH terms

Drug Design
Kinetics
Models, Molecular
Molecular Conformation
Piperazines / chemical synthesis*
Piperazines / pharmacology
Receptors, Serotonin / drug effects
Receptors, Serotonin / metabolism*
Serotonin Antagonists / chemical synthesis*
Serotonin Antagonists / pharmacology
Structure-Activity Relationship
Sulfonamides / chemical synthesis*
Sulfonamides / pharmacology

Substances

Piperazines
Receptors, Serotonin
Serotonin Antagonists
Sulfonamides