Abstract
A series of orexin receptor antagonists was synthesized based on a substituted piperidine scaffold. Through traditional medicinal chemistry structure-activity relationships (SAR), installation of various groups at the 3-6-positions of the piperidine led to modest enhancement in receptor selectivity. Compounds were profiled in vivo for plasma and brain levels in order to identify candidates suitable for efficacy in a model of drug addiction.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Animals
-
Antipsychotic Agents / chemical synthesis*
-
Antipsychotic Agents / pharmacokinetics
-
Brain / drug effects
-
Brain / metabolism
-
Humans
-
Liver / drug effects
-
Liver / metabolism
-
Mice
-
Microsomes, Liver / drug effects
-
Microsomes, Liver / metabolism
-
Molecular Structure
-
Orexin Receptors
-
Piperidines / chemical synthesis*
-
Piperidines / pharmacokinetics
-
Rats
-
Receptors, G-Protein-Coupled / antagonists & inhibitors*
-
Receptors, G-Protein-Coupled / metabolism
-
Receptors, Neuropeptide / antagonists & inhibitors*
-
Receptors, Neuropeptide / metabolism
-
Structure-Activity Relationship
-
Substance-Related Disorders / drug therapy
Substances
-
Antipsychotic Agents
-
Orexin Receptors
-
Piperidines
-
Receptors, G-Protein-Coupled
-
Receptors, Neuropeptide