8-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones: dual-acting 5-HT1 receptor antagonists and serotonin reuptake inhibitors--part II.
8-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones have been identified as highly potent 5-HT(1A/B/D) receptor antagonists with and without additional SerT activity and a high degree of selectivity over hERG potassium channels. Modulation of the different target activities gave compounds with a range of profiles suitable for further in vivo characterization.
Bromidge
Steven M
SM
Neurosciences CEDD, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, UK. twatanabe@bikaken.or.jp
Bertani
Barbara
B
Borriello
Manuela
M
Bozzoli
Andrea
A
Faedo
Stefania
S
Gianotti
Massimo
M
Gordon
Laurie J
LJ
Hill
Matthew
M
Zucchelli
Valeria
V
Watson
Jeannette M
JM
Zonzini
Laura
L
D000818:Animals; D048588:Benzoxazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
D048588:Benzoxazines; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D010879:Piperazines; D044263:Receptors, Serotonin, 5-HT1; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C000606913:KCNH2 protein, human