Synthesis and structure-activity relationship of N-(3-azabicyclo[3.1.0]hex-6-ylmethyl)-5-(2-pyridinyl)-1,3-thiazol-2-amines derivatives as NPY Y5 antagonists

Matteo Biagetti; Colin Philip Leslie; Angelica Mazzali; Catia Seri; Domenica Antonia Pizzi; Jonathan Bentley; Thorsten Genski; Romano Di Fabio; Laura Zonzini; Laura Caberlotto

doi:10.1016/j.bmcl.2010.06.140

Synthesis and structure-activity relationship of N-(3-azabicyclo[3.1.0]hex-6-ylmethyl)-5-(2-pyridinyl)-1,3-thiazol-2-amines derivatives as NPY Y5 antagonists

Bioorg Med Chem Lett. 2010 Aug 15;20(16):4741-4. doi: 10.1016/j.bmcl.2010.06.140. Epub 2010 Jul 1.

Authors

Matteo Biagetti¹, Colin Philip Leslie, Angelica Mazzali, Catia Seri, Domenica Antonia Pizzi, Jonathan Bentley, Thorsten Genski, Romano Di Fabio, Laura Zonzini, Laura Caberlotto

Affiliation

¹ GlaxoSmithKline, Neurosciences Centre of Excellence for Drug Discovery, Medicines Research Centre, Verona, Italy. matteo.2.biagetti@gsk.com

PMID: 20630754
DOI: 10.1016/j.bmcl.2010.06.140

Abstract

A novel class of small molecule NPY Y5 antagonists based around an azabicyclo[3.1.0]hexane scaffold was identified through modification of a screening hit. Structure-activity relationships and efforts undertaken to achieve a favourable pharmacokinetic profile in rat are described.

MeSH terms

Amines / chemical synthesis
Amines / chemistry*
Amines / pharmacokinetics
Animals
Azabicyclo Compounds / chemistry*
Cell Line
Humans
Rats
Receptors, Neuropeptide Y / antagonists & inhibitors*
Receptors, Neuropeptide Y / metabolism
Stereoisomerism
Structure-Activity Relationship

Substances

Amines
Azabicyclo Compounds
Receptors, Neuropeptide Y
neuropeptide Y5 receptor