title: Design, synthesis and SAR of a series of 2-substituted 4-amino-quinazoline neuropeptide Y Y5 receptor antagonists.
abstract: 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.
authors.affiliation: Novartis Pharma AG, Metabolic and Cardiovascular Diseases, Basel, Switzerland. heinrich.rueeger@pharma.novartis.com
authors.forename: H
authors.initials: H
authors.lastname: Rueeger
authors.forename: P
authors.initials: P
authors.lastname: Rigollier
authors.forename: Y
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Schmidlin
authors.forename: W
authors.initials: W
authors.lastname: Schilling
authors.forename: L
authors.initials: L
authors.lastname: Criscione
authors.forename: S
authors.initials: S
authors.lastname: Whitebread
authors.forename: M
authors.initials: M
authors.lastname: Chiesi
authors.forename: M W
authors.initials: MW
authors.lastname: Walker
authors.forename: D
authors.initials: D
authors.lastname: Dhanoa
authors.forename: I
authors.initials: I
authors.lastname: Islam
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Gluchowski
mesh_terms: 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
chemical_list: D011799:Quinazolines; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor