Axially Chiral Cannabinols: A New Platform for Cannabinoid-Inspired Drug Discovery |
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Authors: | Dr Primali V Navaratne Dr Jenny L Wilkerson Kavindri D Ranasinghe Evgeniya Semenova Jasmine S Felix Dr Ion Ghiviriga Prof Adrian Roitberg Prof Lance R McMahon Prof Alexander J Grenning |
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Affiliation: | 1. Department of Chemistry, University of Florida, Gainesville, FL, 32611 USA;2. Department of Pharmacodynamics, University of Florida, Gainesville, FL, 32611 USA |
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Abstract: | Phytocannabinoids (and synthetic analogs thereof) are gaining significant attention as promising leads in modern medicine. Considering this, new directions for the design of phytocannabinoid-inspired molecules is of immediate interest. In this regard, we have hypothesized that axially-chiral-cannabinols (ax-CBNs), unnatural and unknown isomers of cannabinol (CBN) may be valuable scaffolds for cannabinoid-inspired drug discovery. There are two main factors directing our interest to these scaffolds: (a) ax-CBNs would have ground-state three-dimensionality; ligand-receptor interactions can be more significant with complimentary 3D-topology, and (b) ax-CBNs at their core structure are biaryl molecules, generally attractive platforms for pharmaceutical development due to their ease of functionalization and stability. Herein we report a synthesis of ax-CBNs, examine physical properties experimentally and computationally, and perform a comparative analysis of ax-CBN and THC in mice behavioral studies. |
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Keywords: | cannabinoids cannabinol atropisomerism axial chirality total synthesis |
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