Bicyclic piperazinylbenzenesulphonamides are potent and selective 5-HT6 receptor antagonists.
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.
Bromidge
Steven M
SM
Department of Psychiatry, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, CM19 5AW, Essex, UK.
Clarke
Stephen E
SE
King
Frank D
FD
Lovell
Peter J
PJ
Newman
Helen
H
Riley
Graham
G
Routledge
Carol
C
Serafinowska
Halina T
HT
Smith
Douglas R
DR
Thomas
David R
DR
D015195:Drug Design; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides