Discovery of potent, orally bioavailable, selective 5-HT1A/B/D receptor antagonists.
5-HT1 receptor antagonists have been discovered with good selectivity over the 5-HT transporter. This is the first report of highly potent, selective ligands for the 5-HT1A/B/D receptors with low intrinsic activity, which represent a useful set of molecules for further understanding the roles of the 5-HT1 receptor subtypes and providing new approaches for the treatment of depression.
Ward
Simon E
SE
Psychiatry Centre of Excellence for Drug Discovery and Molecular Discovery Research, GlaxoSmithKline, Essex, UK. Simon.E.Ward@gsk.com
Eddershaw
Peter J
PJ
Scott
Claire M
CM
Gordon
Laurie J
LJ
Lovell
Peter J
PJ
Moore
Susan H
SH
Smith
Paul W
PW
Starr
Kathryn R
KR
Thewlis
Kevin M
KM
Watson
Jeannette M
JM
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010879:Piperazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists; D013329:Structure-Activity Relationship
D010879:Piperazines; D011804:Quinolines; D011994:Recombinant Proteins; D058829:Serotonin 5-HT1 Receptor Antagonists