Tricyclic imidazole antagonists of the Neuropeptide S Receptor

Author:

Trotter, B. Wesley  Nanda, Kausik K.  Manley, Peter J.  Uebele, Victor N.  Condra, Cindra L.  Gotter, Anthony L.  Menzel, Karsten  Henault, Martin  Stocco, Rino  Renger, John J.  Hartman, George D.  Bilodeau, Mark T.  

Journal:

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Issue Date:

2010

Abstract(summary):

A new structural class of potent antagonists of the Neuropeptide S Receptor (NPSR) is reported. High-throughput screening identified a tricyclic imidazole antagonist of NPSR, and medicinal chemistry optimization of this structure was undertaken to improve potency against the receptor as well as CNS penetration. Detailed herein are synthetic and medicinal chemistry studies that led to the identification of antagonists 15 and NPSR-PI1, which demonstrate potent in vitro NPSR antagonism and central exposure in vivo. (C) 2010 Elsevier Ltd. All rights reserved.

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