Discovery and SAR of 4-amino-2-biarylbutylurea MCH 1 receptor antagonists through solid-phase parallel synthesis.
-4-Amino-2-arylbutylbenzamides such as 1 were identified as micromolar MCH 1 receptor (MCH1R) antagonists via screening using a scintillation proximity assay based on [125I]-MCH binding to recombinant, human MCH1R. Subsequent lead optimization efforts using solid-phase parallel synthesis resulted in the defined structure-activity relationships and the identification of 4-amino-2-biarylbutylureas, such as 11g, as potent single digit nanomolar MCH1R antagonists.
Guo
Tao
T
Pharmacopeia Drug Discovery, Inc., P.O. Box 5350, Princeton, NJ 08543-5350, USA. tguo@pharmacop.com
Hunter
Rachael C
RC
Gu
Huizhong
H
Rokosz
Laura L
LL
Stauffer
Tara M
TM
Hobbs
Doug W
DW
D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015394:Molecular Structure; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*
C103263:MCHR1 protein, human; D017481:Receptors, Somatostatin; D014508:Urea