Design, synthesis and SAR of a series of 2-substituted 4-amino-quinazoline neuropeptide Y Y5 receptor antagonists.
The design of a novel series of NPY-Y5 receptor antagonists is described. Key elements for the design were the identification of weak Y5 hits from a Y1 program, results from a combinatorial approach and database mining. This led to the discovery of the quinazoline 4 and the aryl-sulphonamide moiety as major components of the pharmacophore for Y5 affinity. The synthesis and SAR towards CGP71683A is described.
Rueeger
H
H
Novartis Pharma AG, Metabolic and Cardiovascular Diseases, Basel, Switzerland. heinrich.rueeger@pharma.novartis.com
Rigollier
P
P
Yamaguchi
Y
Y
Schmidlin
T
T
Schilling
W
W
Criscione
L
L
Whitebread
S
S
Chiesi
M
M
Walker
M W
MW
Dhanoa
D
D
Islam
I
I
Zhang
J
J
Gluchowski
C
C
D015195:Drug Design; D008958:Models, Molecular; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D011799:Quinazolines; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor