Discovery of the first potent, selective 5-hydroxytryptamine1D receptor antagonist

Simon E Ward; Frank P Harrington; Laurie J Gordon; Susanna C Hopley; Claire M Scott; Jeannette M Watson

doi:10.1021/jm049039v

Discovery of the first potent, selective 5-hydroxytryptamine1D receptor antagonist

J Med Chem. 2005 May 19;48(10):3478-80. doi: 10.1021/jm049039v.

Authors

Simon E Ward¹, Frank P Harrington, Laurie J Gordon, Susanna C Hopley, Claire M Scott, Jeannette M Watson

Affiliation

¹ Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, U.K. Simon.E.Ward@gsk.com

PMID: 15887956
DOI: 10.1021/jm049039v

Abstract

A series of 5-(piperidinylethyloxy)quinoline 5-hydroxytryptamine(1D) (5-HT(1D)) receptor antagonists have been discovered from elaboration of the series of dual 5-hydroxytryptamine(1)-selective serotonin reuptake inhibitors (5HT(1)-SSRIs) reported previously. This is the first report of highly potent, selective antagonists for the 5-HT(1D) receptor, which represents an extremely useful set of pharmacological tools for further understanding the roles of the 5-HT(1) receptor subtypes.

MeSH terms

Animals
Binding, Competitive
CHO Cells
Cerebral Cortex / drug effects
Cerebral Cortex / metabolism
Cricetinae
Cricetulus
In Vitro Techniques
Piperazines / chemical synthesis*
Piperazines / chemistry
Piperazines / pharmacology
Quinolines / chemical synthesis*
Quinolines / chemistry
Quinolines / pharmacology
Radioligand Assay
Rats
Selective Serotonin Reuptake Inhibitors / chemical synthesis
Selective Serotonin Reuptake Inhibitors / chemistry
Selective Serotonin Reuptake Inhibitors / pharmacology
Serotonin 5-HT1 Receptor Agonists
Serotonin 5-HT1 Receptor Antagonists*
Structure-Activity Relationship

Substances

Piperazines
Quinolines
Serotonin 5-HT1 Receptor Agonists
Serotonin 5-HT1 Receptor Antagonists
Serotonin Uptake Inhibitors