The identification and optimisation of novel and selective diamide neuropeptide Y Y2 receptor antagonists

Gillian E Lunniss; Ashley A Barnes; Nick Barton; Matteo Biagetti; Federica Bianchi; Stephen M Blowers; Laura Caberlotto; Amanda Emmons; Ian P Holmes; Dino Montanari; Ros Norris; Dewi J Walters; Steve P Watson

doi:10.1016/j.bmcl.2009.06.035

The identification and optimisation of novel and selective diamide neuropeptide Y Y2 receptor antagonists

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4022-5. doi: 10.1016/j.bmcl.2009.06.035. Epub 2009 Jun 13.

Authors

Gillian E Lunniss¹, Ashley A Barnes, Nick Barton, Matteo Biagetti, Federica Bianchi, Stephen M Blowers, Laura Caberlotto, Amanda Emmons, Ian P Holmes, Dino Montanari, Ros Norris, Dewi J Walters, Steve P Watson

Affiliation

¹ GlaxoSmithKline, Neurosciences Centre of Excellence for Drug Discovery, New Frontiers Science Park, Harlow, UK.

PMID: 19581086
DOI: 10.1016/j.bmcl.2009.06.035

Abstract

A novel small molecule NPY Y2 antagonist (3) identified from high throughput screening is described. A subsequent SAR study and optimisation programme based around this molecule is also described, leading to the identification of potent and soluble pyridyl analogue 36.

MeSH terms

Amides / chemistry*
Animals
Arginine / analogs & derivatives*
Arginine / pharmacology
Benzazepines / pharmacology*
Chemistry, Organic / methods
Chemistry, Pharmaceutical / methods
Drug Design
Humans
Inhibitory Concentration 50
Models, Chemical
Peptide Fragments / chemistry
Protein Binding
Rats
Receptors, Neuropeptide Y / antagonists & inhibitors*
Receptors, Neuropeptide Y / chemistry*
Structure-Activity Relationship

Substances

Amides
Benzazepines
Peptide Fragments
Receptors, Neuropeptide Y
neuropeptide Y2 receptor
Arginine
BIIE 0246