Analogs of JHU75528, a PET ligand for imaging of cerebral cannabinoid receptors (CB1): development of ligands with optimized lipophilicity and binding affinity.
Article Details
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Fan H, Kotsikorou E, Hoffman AF, Ravert HT, Holt D, Hurst DP, Lupica CR, Reggio PH, Dannals RF, Horti AG
Analogs of JHU75528, a PET ligand for imaging of cerebral cannabinoid receptors (CB1): development of ligands with optimized lipophilicity and binding affinity.
Eur J Med Chem. 2009 Feb;44(2):593-608. doi: 10.1016/j.ejmech.2008.03.040. Epub 2008 Apr 18.
- PubMed ID
- 18511157 [ View in PubMed]
- Abstract
Cyano analogs of Rimonabant with high binding affinity for the cerebral cannabinoid receptor (CB1) and with optimized lipophilicity have been synthesized as potential positron emission tomography (PET) ligands. The best ligands of the series are optimal targets for the future radiolabeling with PET isotopes and in vivo evaluation as radioligands with enhanced properties for PET imaging of CB1 receptors in human subjects. Extracellular electrophysiological recordings in rodent brain slices demonstrated that JHU75528, 4, the lead compound of the new series, has functional CB antagonist properties that are consistent with its structural relationship to Rimonabant. Molecular modeling analysis revealed an important role of the binding of the cyano group with the CB1 binding pocket.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Rimonabant Cannabinoid receptor 1 Ki (nM) 40 N/A N/A Details