The identification and optimisation of novel and selective diamide neuropeptide Y Y2 receptor antagonists.
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.
Lunniss
Gillian E
GE
GlaxoSmithKline, Neurosciences Centre of Excellence for Drug Discovery, New Frontiers Science Park, Harlow, UK.
Barnes
Ashley A
AA
Barton
Nick
N
Biagetti
Matteo
M
Bianchi
Federica
F
Blowers
Stephen M
SM
Caberlotto
Laura
L
Emmons
Amanda
A
Holmes
Ian P
IP
Montanari
Dino
D
Norris
Ros
R
Walters
Dewi J
DJ
Watson
Steve P
SP
D000577:Amides / Q000737:chemistry*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D002625:Chemistry, Organic / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000577:Amides; D001552:Benzazepines; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D001120:Arginine; C403256:BIIE 0246