Identification of a potent and selective oxytocin antagonist, from screening a fully encoded differential release combinatorial chemical library

B Evans; A Pipe; L Clark; M Banks

doi:10.1016/s0960-894x(01)00201-3

Identification of a potent and selective oxytocin antagonist, from screening a fully encoded differential release combinatorial chemical library

Bioorg Med Chem Lett. 2001 May 21;11(10):1297-300. doi: 10.1016/s0960-894x(01)00201-3.

Authors

B Evans¹, A Pipe, L Clark, M Banks

Affiliation

¹ Department of Lead Discovery, GlaxoSmithKline Medicines Research Centre, Stevenage, Herts, UK. be0897@gsk.com

PMID: 11392541
DOI: 10.1016/s0960-894x(01)00201-3

Abstract

A library of 1,296 1,4-benzodiazepines was prepared on 160 microM Tentagel beads. Compounds are attached to the beads using orthogonally cleavable linkers. The library was first screened as pools of 30 beads where 50% of the material is released and screened. GW405212X, a selective oxytocin antagonist, was identified by picking single beads from active pools.

MeSH terms

Animals
Benzodiazepines / chemical synthesis
Benzodiazepines / pharmacology
CHO Cells
Combinatorial Chemistry Techniques*
Cricetinae
Drug Evaluation, Preclinical / methods
Humans
Inhibitory Concentration 50
Oxytocin / antagonists & inhibitors*
Peptide Library
Receptors, Oxytocin / metabolism
Structure-Activity Relationship
Transfection

Substances

Peptide Library
Receptors, Oxytocin
Benzodiazepines
Oxytocin