6-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones: dual-acting 5-HT1 receptor antagonists and serotonin reuptake inhibitors.
Investigation of a series 6-[2-(4-aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones has led to the discovery of potent 5-HT(1A/1B/1D) receptor antagonists with and without additional SerT affinity. 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 CM19 5AW, UK. steve.bromidge@gsk.com
Bertani
Barbara
B
Borriello
Manuela
M
Faedo
Stefania
S
Gordon
Laurie J
LJ
Granci
Enrica
E
Hill
Matthew
M
Marshall
Howard R
HR
Stasi
Luigi P
LP
Zucchelli
Valeria
V
Merlo
Giancarlo
G
Vesentini
Alessia
A
Watson
Jeannette M
JM
Zonzini
Laura
L
D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008956:Models, Chemical; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*
D000928:Antidepressive Agents; D001583:Benzoxazoles; D000077489:Piperazine; D010879:Piperazines; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors