Abstract
The stable conformations of GABAA-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 α5 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.
Original language | English (US) |
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Pages (from-to) | 8853-8862 |
Number of pages | 10 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 16 |
Issue number | 19 |
DOIs | |
State | Published - Oct 1 2008 |
Externally published | Yes |
Keywords
- Benzodiazepines
- Conformation
- GABA
- NMR
ASJC Scopus subject areas
- Drug Discovery
- Molecular Medicine
- Molecular Biology
- Biochemistry
- Clinical Biochemistry
- Pharmaceutical Science
- Organic Chemistry