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ID: ALA1141720

Journal: Bioorg Med Chem

Title: A study of the structure-activity relationship of GABA(A)-benzodiazepine receptor bivalent ligands by conformational analysis with low temperature NMR and X-ray analysis.

Authors: Han D, Holger Försterling F, Li X, Deschamps JR, Parrish D, Cao H, Rallapalli S, Clayton T, Teng Y, Majumder S, Sankar S, Roth BL, Sieghart W, Furtmuller R, Rowlett JK, Weed MR, Cook JM.

Abstract: The stable conformations of GABA(A)-benzodiazepine receptor bivalent ligands were determined by low temperature NMR spectroscopy and confirmed by single crystal X-ray analysis. The stable conformations in solution correlated well with those in the solid state. The linear conformation was important for these dimers to access the binding site and exhibit potent in vitro affinity and was illustrated for alpha5 subtype selective ligands. Bivalent ligands with an oxygen-containing linker folded back upon themselves both in solution and the solid state. Dimers which are folded do not bind to Bz receptors.

CiteXplore: 18790643

DOI: 10.1016/j.bmc.2008.08.072