Discovery and SAR of biaryl piperidine MCH1 receptor antagonists through solid-phase encoded combinatorial synthesis.
An encoded combinatorial library based on aryl and biaryl piperidine scaffolds was designed and synthesized. Screening of this library resulted in the discovery of high-nanomolar biaryl piperidine-based MCH1 receptor antagonists. Follow-up optimization using a parallel synthesis provided potent, single digit nanomolar antagonists.
Guo
Tao
T
Pharmacopeia Drug Discovery, Inc., P.O. Box 5350, Princeton, NJ 08543-5350, USA. tguo@pharmacop.com
Shao
Yuefei
Y
Qian
Gang
G
Rokosz
Laura L
LL
Stauffer
Tara M
TM
Hunter
Rachael C
RC
Babu
Suresh D
SD
Gu
Huizhong
H
Hobbs
Doug W
DW
D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
C103263:MCHR1 protein, human; D010880:Piperidines; D017481:Receptors, Somatostatin