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ID: ALA1136898

Journal: Bioorg Med Chem Lett

Title: Conformational analysis of N,N-disubstituted-1,4-diazepane orexin receptor antagonists and implications for receptor binding.

Authors: Cox CD, McGaughey GB, Bogusky MJ, Whitman DB, Ball RG, Winrow CJ, Renger JJ, Coleman PJ.

Abstract: NMR spectroscopy, X-ray crystallography, and molecular modeling studies indicate that N,N-disubstituted-1,4-diazepane orexin receptor antagonists exist in an unexpected low-energy conformation that is characterized by an intramolecular pi-stacking interaction and a twist-boat ring conformation. Synthesis and evaluation of a macrocycle that enforces a similar conformation suggest that this geometry mimics the bioactive conformation.

CiteXplore: 19406641

DOI: 10.1016/j.bmcl.2009.04.026