The identification of a series of novel, soluble non-peptidic neuropeptide Y Y2 receptor antagonists

Gillian E Lunniss; Ashley A Barnes; Nick Barton; Matteo Biagetti; Federica Bianchi; Stephen M Blowers; Laura L Caberlotto; Amanda Emmons; Ian P Holmes; Dino Montanari; Roz Norris; Gemma V Puckey; Dewi J Walters; Steve P Watson; John Willis

doi:10.1016/j.bmcl.2010.10.065

The identification of a series of novel, soluble non-peptidic neuropeptide Y Y2 receptor antagonists

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7341-4. doi: 10.1016/j.bmcl.2010.10.065. Epub 2010 Nov 10.

Authors

Gillian E Lunniss¹, Ashley A Barnes, Nick Barton, Matteo Biagetti, Federica Bianchi, Stephen M Blowers, Laura L Caberlotto, Amanda Emmons, Ian P Holmes, Dino Montanari, Roz Norris, Gemma V Puckey, Dewi J Walters, Steve P Watson, John Willis

Affiliation

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

PMID: 21074426
DOI: 10.1016/j.bmcl.2010.10.065

Abstract

The identification and subsequent optimisation of a selective non-peptidic NPY Y2 antagonist series is described. This led to the development of amine 2, a selective, soluble NPY Y2 receptor antagonist with enhanced CNS exposure.

MeSH terms

Amides / chemical synthesis
Amides / chemistry
Amides / pharmacokinetics
Amines / chemical synthesis
Amines / chemistry
Amines / pharmacokinetics
Animals
Central Nervous System / drug effects
Humans
Microsomes, Liver / metabolism
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / pharmacokinetics
Rats
Receptors, Neuropeptide Y / antagonists & inhibitors*
Receptors, Neuropeptide Y / metabolism
Spiro Compounds / chemical synthesis
Spiro Compounds / chemistry*
Spiro Compounds / pharmacokinetics
Structure-Activity Relationship

Substances

Amides
Amines
Pyrimidines
Receptors, Neuropeptide Y
Spiro Compounds
neuropeptide Y2 receptor