The discovery of GSK221149A: a potent and selective oxytocin antagonist

John Liddle; Michael J Allen; Alan D Borthwick; David P Brooks; David E Davies; Richard M Edwards; Anne M Exall; Chris Hamlett; Wendy R Irving; Andrew M Mason; Gerald P McCafferty; Fabrizio Nerozzi; Simon Peace; Joanne Philp; Derek Pollard; Mark A Pullen; Shaila S Shabbir; Steve L Sollis; Timothy D Westfall; Pat M Woollard; Charlene Wu; Deirdre M B Hickey

doi:10.1016/j.bmcl.2007.11.008

The discovery of GSK221149A: a potent and selective oxytocin antagonist

Bioorg Med Chem Lett. 2008 Jan 1;18(1):90-4. doi: 10.1016/j.bmcl.2007.11.008. Epub 2007 Nov 6.

Affiliation

¹ Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, UK. [email protected]

PMID: 18032036
DOI: 10.1016/j.bmcl.2007.11.008

Abstract

Optimisation of a series of oxazole diketopiperazines has led to the discovery of a very potent and selective oxytocin antagonist GSK221149A. GSK221149A has been shown to inhibit oxytocin-induced uterine contractions in the anaesthetised rat.

MeSH terms

Animals
Female
Humans
Kinetics
Oxytocin / antagonists & inhibitors*
Oxytocin / metabolism
Piperazines / chemistry*
Piperazines / pharmacokinetics
Piperazines / pharmacology*
Rats
Rats, Sprague-Dawley
Receptors, Oxytocin / metabolism
Structure-Activity Relationship
Uterine Contraction / drug effects

Substances

GSK221149A
Piperazines
Receptors, Oxytocin
Oxytocin