Identification of a potent and selective 5-HT1B receptor antagonist.
An SAR study around the mixed 5-HT1ABD receptor antagonist SB-272183 found that introduction of cis-2,6-dimethyl substitution onto the piperazine ring was a key structural change, which imparted a combination of both excellent selectivity over the 5-HT1A and 5-HT1D receptors and low intrinsic activity. This led to the identification of the selective 5-HT1B receptor antagonist SB-616234.
Wyman
Paul A
PA
Psychiatry CEDD, New Frontiers Science Park, GlaxoSmithKline, Third Avenue, Harlow, Essex CM19 5AW, UK. paul.wyman@gsk.com
Marshall
Howard R
HR
Flynn
Sean T
ST
King
Ron J
RJ
Thompson
Mervyn
M
Smith
Paul W
PW
Hadley
Michael S
MS
Price
Gary W
GW
Scott
Claire M
CM
Dawson
Lee A
LA
D000818:Animals; D006801:Humans; D008024:Ligands; D008862:Microsomes, Liver; D051381:Rats; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D008024:Ligands; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists