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.
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.
Biagetti
Matteo
M
GlaxoSmithKline, Neurosciences Centre of Excellence for Drug Discovery, Medicines Research Centre, Verona, Italy. matteo.2.biagetti@gsk.com
Leslie
Colin Philip
CP
Mazzali
Angelica
A
Seri
Catia
C
Pizzi
Domenica Antonia
DA
Bentley
Jonathan
J
Genski
Thorsten
T
Di Fabio
Romano
R
Zonzini
Laura
L
Caberlotto
Laura
L
D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D053961:Azabicyclo Compounds / Q000737:chemistry*; D002460:Cell Line; D006801:Humans; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000588:Amines; D053961:Azabicyclo Compounds; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor