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Updated: Jun 11, 2026

Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography
Published on: September 20, 2016
Tricyclic imidazole antagonists of the Neuropeptide S Receptor
B Wesley Trotter1, Kausik K Nanda, Peter J Manley
1Department of Medicinal Chemistry, Merck Research Laboratories, Boston, MA, USA. bwesley_trotter@merck.com
Abstract:
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.
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