Structure-activity relationship of a series of diaminoalkyl substituted benzimidazole as neuropeptide Y Y1 receptor antagonists.
A series of benzimidazoles (4) was synthesized and evaluated in vitro as potent and selective NPY Y1 receptor antagonists. Substitution of the piperidine nitrogen of 4 with appropriate R groups resulted in compounds with more than 80-fold higher affinity at the Y receptor compared to the parent compound 5 (R = H). The most potent benzimidazole in this series was 21 (Ki = 0.052 nM).
Zarrinmayeh
H
H
Eli Lilly and Company, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Zimmerman
D M
DM
Cantrell
B E
BE
Schober
D A
DA
Bruns
R F
RF
Gackenheimer
S L
SL
Ornstein
P L
PL
Hipskind
P A
PA
Britton
T C
TC
Gehlert
D R
DR
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D009479:Neuropeptides / Q000187:drug effects / Q000235:genetics; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014162:Transfection
D001562:Benzimidazoles; D009479:Neuropeptides; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C031000:benzimidazole; D000262:Adenylyl Cyclases