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ID: ALA1800075

Journal: Bioorg Med Chem Lett

Title: Tricyclic imidazole antagonists of the Neuropeptide S Receptor.

Authors: Trotter BW, Nanda KK, Manley PJ, Uebele VN, Condra CL, Gotter AL, Menzel K, Henault M, Stocco R, Renger JJ, Hartman GD, Bilodeau MT.

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.

CiteXplore: 20615693

DOI: 10.1016/j.bmcl.2010.04.016