Discovery of potent and selective small molecule NPY Y5 receptor antagonists.
The discovery of a new class of sulfonamide NPY Y5 receptor antagonists is described. Optimization of this series led to the identification of compounds with high affinity for the hY5 subtype and excellent selectivity over the other NPY receptor subtypes. The SAR for this series was examined and a model for understanding the ligand-receptor interactions was developed.
Islam
Imadul
I
Synaptic Pharmaceutical Corporation, 215 College Road, Paramus, NJ 07652. USA.
Dhanoa
Dale
D
Finn
John
J
Du
Ping
P
Walker
Mary W
MW
Salon
John A
JA
Zhang
Jack
J
Gluchowski
Charles
C
D000818:Animals; D019556:COS Cells; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D011869:Radioligand Assay; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D008565:Membrane Proteins; D017476:Receptors, Neuropeptide Y; D013449:Sulfonamides; C100568:neuropeptide Y5 receptor; D006639:Histidine